ORCID Profile
0000-0002-1253-6393
Current Organisations
Western Sydney Local Health District
,
University of Sydney
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Publisher: Wiley
Date: 04-04-2012
DOI: 10.1111/J.1742-6723.2012.01550.X
Abstract: Access block (AB) and hospital overcrowding adversely affect ED functionality. ED throughput measures have been described in the literature with positive impacts on key performance indicators (KPIs)--time to first seen, did-not-wait rates, off-stretcher times for ambulances and ED length of stay figures. In this study, we aimed to assess the impact of a new model of care, the Senior Streaming Assessment Further Evaluation after Triage (SAFE-T) zone concept on ED performance indicators and statistical outcomes. We implemented a model of care at our tertiary hospital ED amalgamating multiple ED throughput interventions. These interventions included dynamic transition waiting room concept, early senior ED physician assessment and decision-making, early streaming, acute-care bed quarantining and ED short stay and observation units. The principal intervention was the SAFE-T zone. End-point data were compared for similar periods (77 days) of 2010 and 2011 with and without the new model of care. In total, 11 408 and 11 845 patients were included in the study periods pre- and post-intervention, respectively. Time to physician KPI improved from 72.5% to 84.1%. Did-not-wait rates dropped from 10.7% to 9.6% (P= 0.02) and off-stretcher times for ambulances KPI improved from 74.5% to 79.5% (P < 0.001). ED length of stay dropped most significantly for Australasian Triage Scale categories 3 and 4 (14.3% and 11.8%, P-values <0.001). These results were achieved despite worsened AB and hospital bed-occupancy rates during the intervention period (+3.9% and +6.7%). The SAFE-T zone model of care involving multiple ED throughput measures achieved improvements in ED performance despite AB and hospital overcrowding.
Publisher: Springer Science and Business Media LLC
Date: 21-11-2013
DOI: 10.1007/S10840-012-9750-X
Abstract: Return electrode burns occur occasionally in cardiac radiofrequency ablation and more frequently in tumor radiofrequency ablation. A return electrode incorporating a thermochromic liquid crystal (TLC) layer, which changes color with temperature, has been shown in sheep studies to accurately indicate underlying skin temperature. We aimed to validate the accuracy of TLC-coated return electrodes in indicating skin temperature in the clinical setting of cardiac radiofrequency ablation. The top layer of a standard return electrode was replaced with TLC. Fluoro-optic thermometer (FOT) probes were laid on the skin side of the return electrode, which was then placed on the left lateral mid-thigh of 18 patients (mean age = 61 ± 12 years, 12 men) undergoing cardiac radiofrequency ablation. Return electrode photographs were taken when FOT temperature exceeded 35 °C. TLC color changes, observed in 11 patients, were converted to temperature and compared with FOT temperature. TLC temperature correlated well with FOT temperature (Pearson's coefficient = 0.97 ± 0.03). Bland-Altman analysis showed good agreement (mean temperature difference = -0.04 ± 0.08 °C, upper limit of agreement = 0.11 ± 0.005 °C, lower limit of agreement = -0.19 ± 0.005 °C). The maximum FOT temperature recorded was 39.6 °C. There was no thermal injury at the return electrode site on any patients, when assessed immediately after and the day following the procedure. TLC-coated return electrodes accurately indicate underlying skin temperature in cardiac radiofrequency ablation and may help prevent burns. This technology might be essential in high energy radiofrequency ablation.
Publisher: Elsevier BV
Date: 1995
Publisher: American Association for Cancer Research (AACR)
Date: 09-2008
DOI: 10.1158/1078-0432.CCR-08-0606
Abstract: Purpose: The human ABCB1 gene encodes P-glycoprotein, which transports a broad range of anticancer drugs, including paclitaxel. Although the functional consequences of ABCB1 polymorphisms have been the subject of numerous studies, few have assessed the association with clinical outcome. Experimental Design: We assessed the association between the 2677G& T/A, 3435C& T, and 1236C& T ABCB1 polymorphisms and progression-free and overall survival in 309 patients from the Australian Ovarian Cancer Study treated with paclitaxel/carboplatin and subsequently tested significant observations in an independent validation set. Results: Women who carried the minor T/A alleles at the 2677G& T/A polymorphism were significantly less likely to relapse following treatment compared with homozygote GG carriers (PLog-rank = 0.001) in the Australian Ovarian Cancer Study cohort. Subgroup analyses showed that this effect was limited to cases with residual disease ≤1 cm (PLog-rank = 0.0004), not for those with residual disease & cm (PLog-rank = 0.3). This effect was not confirmed in an independent validation set of carboplatin aclitaxel-treated patients (n = 278) using a higher residual disease cut point (≤2 cm). However, analysis of the unrestricted data set expanded to include docetaxel-treated patients (n = 914) did support an effect of the 2677T/A allele in patients with no macroscopic residual disease (hazard ratio, 0.70 95% confidence interval, 0.46-1.04 Pone-sided = 0.039). Conclusion: Our findings indicate that there is an effect of the 2677G& T/A polymorphism on progression-free survival in ovarian cancer patients who are treated with a taxane/carboplatin, which is dependent on the extent of residual disease, with a better prognosis for patients with the 2677T/A allele and minimal residual disease.
Publisher: Public Library of Science (PLoS)
Date: 31-10-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2013
Publisher: Elsevier BV
Date: 12-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-03-2020
DOI: 10.1097/DSS.0000000000002376
Abstract: As the availability of Mohs micrographic surgery (MMS) continues to expand in Australia and incidence of keratinocyte cancer increases in adolescents and young adults, there has been rising interest in the use of MMS in this population. This study aimed to evaluate the characteristics of MMS cases in patients younger than 40 years. A review was performed of all MMS cases in patients younger than 40 years at the time of their surgery from 2012 to 2017 at the Skin and Cancer Foundation Australia, with comparison to a control group, aged older than 40 years. Patient, tumor and management characteristics were analyzed. Four hundred ninety-three cases were eligible. Study and control groups differed significantly regarding gender ( p .001), tumor pathology ( p .001), anatomic site of tumor ( p .001), Mohs surgery stages ( p = .039), defect size ( p .001), and repair method ( p .001). Retrospective study at a single institution. Mohs micrographic surgery cases in patients younger than 40 years exhibit unique patient and tumor characteristics influencing choice of repair method.
Publisher: Wiley
Date: 31-05-2019
DOI: 10.1111/ENE.13981
Abstract: Ischaemic stroke frequently has a cardioembolic (CE) source. Clinical and echocardiographic parameters associated with CE stroke were evaluated. In all, 93 consecutive ischaemic stroke patients who underwent a transthoracic echocardiogram were retrospectively analysed strokes were classified by TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Echocardiographic parameters related to CE stroke, including left atrial volumes and function, were compared to 73 healthy controls. Of 93 patients (mean age 66.1 years, 56% male), nine (10%) had large artery atherosclerosis, 38 (41%) CE stroke, two (2%) small vessel disease, two (2%) other and 42 (45%) undetermined aetiology. Left atrial (LA) maximum volumes (LAVI Left atrial enlargement with reduced LA function was associated with CE stroke and LAFI was the best independent predictor. LA parameters were also altered in the undetermined aetiology group, suggesting an underlying LA myopathy in this subset.
Publisher: Oxford University Press (OUP)
Date: 05-11-2008
DOI: 10.1093/JNCI/DJN345
Abstract: X chromosome inactivation, which silences gene expression from one of the two X chromosomes in females, is usually random. Skewed X inactivation has been implicated in both the expression and the suppression of X-linked disease phenotypes and has been reported to occur more frequently in breast and ovarian cancer patients, including BRCA1 or BRCA2 mutation carriers, than in control subjects. We assessed the pattern of X chromosome inactivation using methylation-specific polymerase chain reaction lification of the exon 1 microsatellite region of the X-linked androgen receptor (AR) gene in DNA from blood s les obtained from control subjects without a personal history of breast or ovarian cancer (n = 735), ovarian cancer patients (n = 313), familial breast cancer patients who did not carry mutations in BRCA1 or BRCA2 (n = 235), and affected and unaffected carriers of mutations in BRCA1 (n = 260) or BRCA2 (n = 63). We defined the pattern of X chromosome inactivation as skewed when the same X chromosome was active in at least 90% of cells. The association between skewed X inactivation and disease and/or BRCA mutation status was assessed by logistic regression analysis. The association between skewed X inactivation and age at cancer diagnosis was assessed by Cox proportional hazards regression analysis. All statistical tests were two-sided. The age-adjusted frequency of skewed X inactivation was not statistically significantly higher in ovarian cancer or familial breast cancer case subjects compared with control subjects. Skewed X inactivation was higher in BRCA1 mutation carriers than in control subjects (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.1 to 6.2 P = .02), particularly among unaffected women (OR = 6.1, 95% CI = 1.5 to 31.8 P = .005). Among BRCA1 mutation carriers, those with skewed X inactivation were older at diagnosis of breast or ovarian cancer than those without skewed X inactivation (hazard ratio [HR] of breast or ovarian cancer = 0.37, 95% CI = 0.14 to 0.95 P = .04). Among BRCA2 mutation carriers, skewed X inactivation also occurred more frequently in unaffected carriers than in those diagnosed with breast or ovarian cancer (OR = 5.2, 95% CI = 0.5 to 28.9 P = .08) and was associated with delayed age at onset (HR = 0.59, 95% CI = 0.37 to 0.94 P = .03). Skewed X inactivation occurs at an increased frequency in BRCA1 (and possibly BRCA2) mutation carriers compared with control subjects and is associated with a statistically significant increase in age at diagnosis of breast and ovarian cancer.
Publisher: Wiley
Date: 12-02-2010
DOI: 10.1111/J.1753-6405.1983.TB00064.X
Abstract: We present an investigation of the photochemistry of aluminum nanoparticles (Al NPs) capped with poly(methyl methacrylate) (PMMA). Powder X-ray diffraction and Fourier transform infrared spectroscopy with total attenuated reflection confirm the presence of crystalline aluminum cores and the PMMA cap and allow us to confirm the latter's photodegradation upon exposure to UV light. The PMMA-Al NPs were also characterized by differential scanning calorimetry coupled with thermogravimetric analysis to study the thermal profiles for polymer combustion and metal oxidation exotherms. Transmission electron microscopy confirms that the Al NPs, around 36 nm in diameter, are embedded in the PMMA matrix. Following UV irradiation, the PMMA-Al NPs react considerably faster with alkaline solutions, compared with unphotolyzed s les. Photoactivation of the nanocomposite induces partial decomposition of the PMMA capping layer, exposing the underlying reactive metal cores to the surrounding environment and accelerating its redox reactivity. Photolysis times of 1, 6, 24, and 52 h were investigated to establish a minimum UV exposure time for the activation of the PMMA-Al NPs toward hydrolytic hydrogen gas generation.
Publisher: Wiley
Date: 06-1999
DOI: 10.1111/J.1445-5994.1999.TB00710.X
Abstract: Older patients with cirrhosis due to hepatitis C are at risk of developing hepatocellular carcinoma (HCC), but additional risk factors may vary between countries. In the present study, we sought to identify additional risk factors for HCC among a cohort of Australian patients with chronic hepatitis C. Case-control study of patients with advanced fibrosis stage hepatitis C who developed HCC during five-year follow up at a referral liver clinic. Cases were compared to twice the number of age-matched patients with chronic hepatitis C of similar fibrotic severity who did not develop HCC over a similar interval, using conditional logistic regression analysis (CLRA) and multivariate analysis. The main outcome measures were demographic and disease-related variables at first presentation in relation to the development of HCC. HCC developed in 17 cases, an annual incidence among those considered to be at risk of 2%. The duration of follow up since first assessment was comparable among the cases and 34 selected age-matched controls (4.1 and 5.2 years respectively, p=0.5). Cases were more often male (p=0.03), born in Asia (p=0.05), and had poorer liver function as indicated by serum albumin concentration (p=0.02). Anti-hepatitis B core-antibody (anti-HBc) was detected in 59% (ten/17) of cases, compared to 21% (seven/34) of the controls (p=0.01). No patient with a sustained response to interferon developed HCC during follow up. There were no significant differences in the mode of HCV transmission, HCV genotype, alcohol exposure, serum bilirubin level or prothrombin time between the cases and the controls. Although the data set was small, multivariate CLR analysis identified serum albumin < or = 35 g/L and anti-HBc positivity to be independent risk factors for development of HCC. Among older Australian patients (over the age of 40 years) with advanced fibrosis stage hepatitis C, the annual incidence of HCC is about 2%. Those who have low serum albumin and evidence of previous exposure to hepatitis B virus (anti-HBc positivity) appear to have the highest risk of developing HCC during follow up, but males and those born in Asia could also be at increased risk.
Publisher: Public Library of Science (PLoS)
Date: 08-01-2010
Publisher: The American Association of Immunologists
Date: 11-2008
DOI: 10.4049/JIMMUNOL.181.9.6604
Abstract: In human recurrent cutaneous herpes simplex, there is a sequential infiltrate of CD4 and then CD8 lymphocytes into lesions. CD4 lymphocytes are the major producers of the key cytokine IFN-γ in lesions. They recognize mainly structural proteins and especially glycoproteins D and B (gD and gB) when restimulated in vitro. Recent human vaccine trials using recombinant gD showed partial protection of HSV seronegative women against genital herpes disease and also, in placebo recipients, showed protection by prior HSV1 infection. In this study, we have defined immunodominant peptide epitopes recognized by 8 HSV1+ and/or 16 HSV2+ patients using 51Cr-release cytotoxicity and IFN-γ ELISPOT assays. Using a set of 39 overlapping 20-mer peptides, more than six immunodominant epitopes were defined in gD2 (two to six peptide epitopes were recognized for each subject). Further fine mapping of these responses for 4 of the 20-mers, using a panel of 9 internal 12-mers for each 20-mers, combined with MHC II typing and also direct in vitro binding assay of these peptides to in idual DR molecules, showed more than one epitope per 20-mers and promiscuous binding of in idual 20-mers and 12-mers to multiple DR types. All four 20-mer peptides were cross-recognized by both HSV1+/HSV2− and HSV1−/HSV2+ subjects, but the sites of recognition differed within the 20-mers where their sequences were ergent. This work provides a basis for CD4 lymphocyte cross-recognition of gD2 and possibly cross-protection observed in previous clinical studies and in vaccine trials.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.GIE.2022.02.022
Abstract: The risk of cancer in large nonpedunculated colorectal polyps ≥20 mm (LNPCPs) in the rectum relative to the remainder of the colon is unknown. We aimed to describe differences between rectal and colonic LNPCPs to better inform treatment decisions. Patients with LNPCPs referred to tertiary centers for endoscopic resection within a prospective, multicenter, observational cohort were evaluated. Data recorded were participant demographics, LNPCP location, morphology, resection modality, and histopathologic data. Multiple logistic regression analysis was used to identify those variables independently associated with rectal versus nonrectal location in the colon. Patients with LNPCPs referred for endoscopic resection between July 2008 and July 2021 were included. Rectal LNPCPs (n = 618) were larger (median size, 40 mm vs 30 mm P < .001) and more likely to be granular (79% vs 50%, P < .001) with a nodular component (53% vs 17%, P < .001) compared with nonrectal LNPCPs (n = 2787). Rectal LNPCPs were more likely to have tubulovillous histopathology (72% vs 47%, P < .001) and contain cancer (15% vs 6%, P < .001). After adjusting for the other features independently associated with location, cancer was more common in the rectum compared with the colon (odds ratio, 1.77 95% confidence interval, 1.25-2.53). This study suggests that compared with LNPCPs in the rest of the colon, rectal LNPCPs are more likely to be larger and contain more advanced pathology. These findings have implications for curative endoscopic resection techniques particularly where early cancer is present. (Clinical trial registration numbers: NCT01368289 and NCT02000141.).
Publisher: Oxford University Press (OUP)
Date: 02-2007
Abstract: To investigate the mechanisms via which lung volume related caudal tracheal traction decreases upper airway collapsibility. Acute physiological study. 20 male, supine, anesthetised, tracheostomised, spontaneously breathing, NZ white rabbits fitted with a sealed face mask. N/A. Upper airway extraluminal tissue pressure (ETP) was measured in the lateral (ETPlat) and anterior (ETPant) pharyngeal walls (pressure transducer tipped catheters). Graded traction was applied to the isolated upper airway (n = 17, 0-140 g). Subsequently, inflation and deflation was performed (with and without traction, 48 g, n = 13) with measurement of intraluminal pressure. Upper airway transmural pressure (PTM) was calculated (at closure and reopening) for both ETP sites (PTMlat and PTMant, respectively). A traction force of 144 g decreased ETPlat from 2.6 +/- 0.7 cm H2O (mean +/- SEM) to 2.1 +/- 0.7 cm H2O and ETPant from 1.1 +/- 0.4 cm H2O to 0.8 +/- 0.4 cm H2O (both P < 0.001). Increasing traction decreased closing and reopening pressures by 1.4 +/- 0.2 cm H2O for 48 g of traction (n = 13, P < 0.0001). In addition, 48 g of traction decreased ETPlat (at closure and reopening) by 0.2 +/- 0.05 cm H2O (P < 0.0001), and decreased ETPant by 0.5 +/- 0.1 cm H2O at closing pressure and 0.8 +/- 0.1 cm H2O at reopening (both p < 0.0001). Thus, for 48 g of traction, PTMlat (at closure and reopening) fell by 1.1 +/- 0.2 cm H2O and PTMant (reopening only) fell by 0.9 +/- 0.3 cm H2O (all P < 0.0001). Since tracheal traction decreased PTMlat and PTMant by a greater amount than ETPlat and ETPant, we conclude that the decrease in upper airway collapsibility mediated by lung volume related caudal tracheal traction is partially explained by reductions in ETP.
Publisher: Elsevier BV
Date: 11-2021
Publisher: AMPCo
Date: 08-2007
Publisher: Baishideng Publishing Group Inc.
Date: 2013
Publisher: Elsevier BV
Date: 07-1990
DOI: 10.1016/0016-5085(90)91225-U
Abstract: The effects of cimetidine maintenance therapy on the socioeconomic life of patients with peptic ulcers in the 3 years after healing and the extent to which treatment was cost-effective were studied. Three hundred eleven patients with healed ulcers (184 gastric, 127 duodenal) were studied for periods of up to 3 years 261 patients (152 gastric ulcer, 109 duodenal ulcer) completed the 3-year follow-up. Cimetidine (400 mg at night) was compared with placebo in a double-blind, randomized prospective study. Intention-to-treat analysis was used. In the placebo group, the major costs of ulcer disease in gastric ulcer patients were attributable to endoscopic procedures and absenteeism in duodenal ulcer patients, the major costs were endoscopic procedures, absenteeism, and surgery. Cimetidine was cost-effective in both gastric ulcer and duodenal ulcer patients in the first 2 years after healing. Over the 3-year period it was also cost-effective, but no benefit was seen in the third year.
Publisher: Elsevier BV
Date: 2014
Abstract: Cardiac toxicity an uncommon but serious side-effect of some fluoropyrimides. Cardiac toxicity from raltitrexed is rarely reported. With this background, we initiated this study to investigate the incidence of cardiac events in patients who had switched to raltitrexed following cardiac toxicity from fluoropyrimidines (5-fluorouracil or capecitabine). Pharmacy records were used to identify patients receiving raltitrexed from January 2004 till March 2012. Medical records were then reviewed to confirm the use of raltitrexed after cardiac toxicity from 5-fluorouracil or capecitabine. The primary end point was the rate of further cardiac events after commencing raltitrexed. Forty-two patients were identified and the majority had colorectal cancer. Prior regimens included 5-fluorouracil ± leucovorin, capecitabine alone, FOLFOX, FOLFIRI, epirubicin/cisplatin/5-fluorouracil, and capecitabine/oxaliplatin. Seven patients (17%) had bolus 5-fluorouracil regimens, 26 patients (62%) had infusion 5-fluorouracil regimens, and 9 patients (21%) had capecitabine alone or in combination. Angina was the most common cardiac toxicity from 5-fluorouracil or capecitabine and usually occurred in the first or the second cycle. Four patients after their first cardiac event continued with the same 5-fluorouracil or capecitabine regimen with the addition of nitrates and calcium antagonists but still had further cardiac events. After changing to raltitrexed, either as a single agent or a continuing combination regimen, no patients experienced further cardiac toxicity. Raltitrexed is associated with no significant cardiac toxicity in patients who have experienced prior cardiac toxicity from 5-fluorouracil or capecitabine. Raltitrexed, alone or in combination with oxaliplatin or irinotecan, provides a safe option in terms of cardiac toxicity for such patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2006
Publisher: Wiley
Date: 10-1992
DOI: 10.1111/J.1440-1746.1992.TB01029.X
Abstract: Direct comparisons of ulcer perforation rates and trends between countries have not been made in the past. Data on hospital admissions for perforated peptic ulcer during 1 January 1979 to 31 December 1985 were collected in Hong Kong (5868 perforations) and New South Wales, Australia (1669 perforations). Age and sex specific rates per 100,000 population were calculated. In Hong Kong, annual duodenal ulcer and gastric ulcer perforation rates were 13-16 and under two per 100,000 population respectively. In New South Wales, the corresponding rates were between three and four and under two per 100,000 population, respectively. The male:female ratios for duodenal ulcer perforation were consistently about 5:1 in Hong Kong and 2:1 in New South Wales, and for gastric ulcer perforation about 2:1 and 1:1, respectively. The incidence of perforation increased with age, and there was a statistically significant rise, over time, in duodenal but not gastric ulcer perforation rates in persons aged over 60 years in New South Wales similar trends were seen in Hong Kong. Thus duodenal ulcer perforation occurs five times more commonly in Hong Kong than in New South Wales and this is largely accountable for by the higher rates of duodenal ulcer perforation in Chinese than in Australian males. Such geographical differences can best be explained by the occurrence of multiple aetiological mechanisms in ulcer perforation. Furthermore, there appears to be an increased susceptibility and an appreciable rising trend for duodenal ulcer perforation to occur in the elderly.
Publisher: Springer Science and Business Media LLC
Date: 07-03-2011
Publisher: Elsevier BV
Date: 06-1994
DOI: 10.1016/0167-5273(94)90054-X
Abstract: Sustained ventricular tachyarrhythmias unrelated to coronary artery disease are uncommon. Currently there are no clear guidelines to aid selection of the most appropriate treatment strategy. Therefore, factors potentially predictive of arrhythmia recurrence and death and the ability of the electrophysiologic study to predict treatment outcome in patients with spontaneous sustained ventricular tachyarrhythmias unrelated to coronary artery disease were examined in 41 medically treated patients followed for a median of 25 (range 1-76) months. Examined factors were: syncope associated with the spontaneous arrhythmia, the morphology and cycle length of the presenting arrhythmia, underlying ventricular function, cardiac pathology, and the results of drug assessment at electrophysiologic study. Random variability in the ease of arrhythmia induction at electrophysiologic study was measured for the group as a whole and was allowed for in prediction of an effective drug response. The 95% confidence intervals for variability in the ease of repeat arrhythmia induction at the same study were < or = 1 extrastimulus and for variability in the ease of repeat arrhythmia inductions at different studies were < or = 2 extrastimuli. Poisson regression models were used for data analysis. Arrhythmia recurrence was most likely in: (1) patients on treatment not predicted to be anti-arrhythmic at electrophysiologic study (2) patients whose treatment was not assessable at electrophysiologic study because the arrhythmia was not reliably inducible (3) patients with impaired ventricular function and (4) re-entered patients whose arrhythmia had recurred on previously allocated therapy. The risk of arrhythmia recurrence decreased with time from hospital assessment. All five deaths occurred in patients with impaired ventricular function. drug efficacy should be tested at electrophysiologic study in patients with reproducibly inducible clinical arrhythmias. Treatment not proven to be anti-arrhythmic at electrophysiologic study is usually ineffective. Patients with ventricular dysfunction are at highest risk of death from arrhythmia recurrence and should be considered for an implantable defibrillator, arrhythmia surgery, or heart transplantation if drug treatment is not predicted to be effective or is not assessable at electrophysiologic study.
Publisher: Springer Science and Business Media LLC
Date: 11-10-2019
DOI: 10.1007/S40519-017-0443-4
Abstract: Obesity is a major public health burden. Outpatient clinics are an essential resource for in iduals with obesity to access advice for weight loss management. The aim of this study was to compare anthropometric and weight loss outcomes between participants receiving general dietary (GD) advice, and those on a very low energy diet (VLED) under non-trial conditions. Data from 276 adults with obesity attending a multidisciplinary weight management clinic were analysed. Changes in anthropometry, body composition, and blood pressure (BP) over 12 months were analysed using linear mixed-effects models. Males on the GD demonstrated statistically greater reductions in body weight (BW), BMI, percent fat mass (FM), systolic BP, waist and hip circumference (p < 0.01). Changes in males on a VLED did not reach significance. Females showed statistically significant reductions in BW, BMI, waist and hip circumference regardless of dietary intervention (p < 0.01) those on the GD significantly reduced percent FM (p < 0.001). Females on a VLED had statistically greater reductions in BW, BMI and systolic BP compared to those on the GD. No effect of exercise physiologist was observed in this study. Participants prescribed a GD attended for significantly longer than those on a VLED (p < 0.05), irrespective of gender. At 12 months, 14.3 and 4.5% of males and females on a VLED were still attending, compared to 10.6 and 4.5% on the GD. In this retrospective study, females in both dietary intervention groups achieved significant changes across multiple measures. Only men receiving GD advice demonstrated significant changes. Level II-2.
Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.AMJCARD.2005.10.040
Abstract: Patients are generally advised to return to full normal activities, including work, 6 to 8 weeks after acute myocardial infarction (AMI). We assessed the outcomes of early return to normal activities, including work at 2 weeks, after AMI in patients who were stratified to be at a low risk for future cardiac events. Patients were considered for randomization before discharge if they had no angina, had left ventricular ejection fraction >40%, a negative result from a symptom-limited exercise stress test for ischemia ( 7 METs. Patients with left ventricular ejection fraction <40% were included only if they did not have inducible ventricular tachycardia at electrophysiologic studies. Seventy-two patients were randomized to return to normal activities at 2 weeks and 70 patients to undergo standard cardiac rehabilitation and return to normal activities at 6 weeks after AMI. There were no deaths or heart failure in either group. There was no significant difference in the incidence of reinfarction, revascularization, left ventricular function, lipids, body mass index, smoking, or exercise test results at 6 months. In conclusion, return to full normal activities, including work at 2 weeks, after AMI appears to be safe in patients who are stratified to a low-risk group. This should have significant medical and socioeconomic implications.
Publisher: Wiley
Date: 1982
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2004
Publisher: Wiley
Date: 20-02-2008
DOI: 10.1111/J.1445-5994.2007.01525.X
Abstract: The aim of the study was to investigate: (i) familial scleroderma (FS) risk factors, (ii) subtype concordance and (iii) relationship between dates (DSO) and ages (ASO) at scleroderma onset. Forty-seven cases (23 families 25 FS pairs) were identified. Scleroderma disease onset was defined by (i) Raynaud's onset, (ii) first symptom onset (1SxO), (iii) second symptom onset (2SxO) and (iv) scleroderma diagnosis (SDx). Female : male and limited : diffuse (L : D) ratios were 8.4:1 and 3.3:1. The Raynaud's onset - SDx interval was longer in limited disease (L : D = 14.6:3.1 years P = 0.01). Raynaud's first occurred in 36% women > or =50 years. The median differences in ASO between affected family members were 10-12 years. Disease subtype concordance exceeded discordance (16:9 clusters (P = 0.32) 16:7 families (P = 0.17)). The observed/expected LL : LD : DD ratios were 14: 8:1/11:7:1 (P = 0.66). FS affected 34% (95% confidence interval 19-50) sister-sister and 44% (95% confidence interval 27-75) mother-daughter pairs. The second family member's SDx was made at the same (9%) or a younger age (80%) than the first family member. In 14 LL disease families ASO was closer between sisters than mothers-daughters (P = 0.07). There was a trend towards closer ages - than dates - at Raynaud's and 1SxO in scleroderma-affected family members (P = 0.054) and closer dates - than ages - at 2SxO (P = 0.02) and SDx. FS showed female predominance, relatively late onset Raynaud's, subtype ratios similar to idiopathic scleroderma and earlier SDx in younger family members. Familial L scleroderma has a longer prediagnostic latency than familial D scleroderma. FS is likely under-ascertained. In LL scleroderma, Raynaud's/1SxO is possibly more genetically determined and 2SxO/SDx more environmentally determined.
Publisher: Wiley
Date: 2011
Publisher: Georg Thieme Verlag KG
Date: 26-05-2011
Abstract: Endoscopic mucosal resection (EMR) for large colonic laterally spreading tumors (LSTs) is a safe, efficacious, and cost-effective treatment. The most common serious complication is delayed bleeding, which reduces these advantages, but consensus guidelines for large-polyp EMR do not exist. Data from two large prospective intention-to-treat studies of EMR for colonic LSTs 20 mm or greater in size were analyzed. Data collection was comprehensive, and included patient and lesion characteristics. EMR technique and cessation of anticoagulant and antiplatelet therapy was standardized. Clinically significant delayed bleeding was defined as that requiring hospital admission. EMR was performed on 302 lesions in 288 patients. There was clinically significant delayed bleeding in 21 cases (7 %). Ten underwent colonoscopy. One required angiography. One required surgery after perforation following hemostatic clip placement. There were no deaths. Risk factors for bleeding on multivariate analysis were right colon location [adjusted odds ratio (OR) 4.4, P = 0.01], use of aspirin (OR 6.3, P = 0.005), and age (OR per decade of age 1.70). All bleeds occurred before aspirin was restarted. Patient characteristics, including ASA grade and co-morbidity type, were not predictive. Despite requiring more complex EMR, larger lesion size ( P = 0.2), multiple excisions rather than en bloc resection ( P = 0.1), polyp morphology ( P = 0.2), and previous attempts ( P = 0.5), were not associated with increased risk. Proximal lesion location is a highly significant risk for clinically significant delayed bleeding following colonic EMR, and this knowledge could form the basis of a targeted therapeutic trial. Recent aspirin use also increases bleeding risk--specific consensus guidelines in this area are required for colonic EMR.
Publisher: Wiley
Date: 02-04-2015
DOI: 10.1002/CA.22532
Abstract: The cardiac axis in a structurally normal heart is influenced by a number of factors. We investigated the anatomical and electrical cardiac axes in middle-aged in iduals without structural heart disease and compared this with age-matched obese and older in iduals without structural heart disease. A retrospective study of controls included those between 30 and 60 years old with a normal body mass index (BMI), who were then compared with obese in iduals between 30 and 60 years old and with in iduals more than 60 years old with a normal BMI. The anatomical cardiac axis was determined along the long axis by cardiac computed tomography (CT) and correlated with the electrical cardiac axis on a surface electrocardiogram (ECG) in the frontal plane. A total of 124 patients were included. In the controls (n = 59), the mean CT axis was 38.1° ± 7.8° whilst the mean ECG axis was 51.8° ± 26.6°, Pearson r value 0.12 (P = 0.365). In the obese (n = 36), the mean CT axis was 25.1° ± 6.2° whilst the mean ECG axis was 20.1° ± 23.9°, Pearson r value 0.05 (P = 0.808). In the older group (n = 29), the mean CT axis was 34.4° ± 9.1° whilst the mean ECG axis was 34.4° ± 30.3°, Pearson r value 0.26 (P = 0.209). Obese in iduals have a more leftward rotation of both axes than age-matched normals (P <0.0001), which could be secondary to elevation of the diaphragm. Older in iduals have a more leftward rotation only of their electrical cardiac axis (P = 0.01), which could be a normal variant or reflect underlying conduction disturbances in this age group.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2012
DOI: 10.1161/CIRCEP.111.970293
Abstract: Electric isolation of the pulmonary veins and posterior left atrium with a single ring of radiofrequency lesions (single-ring isolation [SRI]) may result in fewer atrial fibrillation (AF) recurrences than wide antral pulmonary vein isolation (wide antral isolation [WAI]) by abolishing extravenous AF triggers. The effect of mitral isthmus line (MIL) ablation on outcomes after SRI has not previously been assessed. We randomly assigned 220 consecutive patients (58±10 years old 82% men) with highly symptomatic AF (61% paroxysmal, 39% persistent/longstanding persistent) to undergo either SRI or WAI. Half of each cohort was also randomly allocated to have left lateral MIL ablation (2×2 factorial study design). Patients were followed clinically and with 7-day Holter studies for arrhythmia recurrences. The primary end points were recurrence of AF and organized atrial tachyarrhythmias. AF-free survival at 2 years was better after SRI (74% [95% CI, 65%–82%]) than WAI (61% [51%–70%] P =0.031). Organized atrial tachyarrhythmia–free survival was similar after SRI and WAI (67% [57%–75%] ersus 64% [54%–72%], respectively, at 2 years P =0.988). MIL ablation resulted in better 2-year organized atrial tachyarrhythmia–free survival (71% [62%–79%] versus 60% [50%–69%] P =0.07), which approached statistical significance. Survival free of any atrial arrhythmia after one procedure was not significantly affected by isolation technique or MIL ablation. SRI resulted in fewer AF recurrences compared with WAI on long-term follow-up but did not reduce the recurrence of all atrial arrhythmias. MIL ablation may reduce organized atrial tachyarrhythmia recurrences. www.anzctr.org.au ACTRN12606000467538.
Publisher: Wiley
Date: 23-09-2019
DOI: 10.1111/AJD.12933
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/S0016-5107(04)02468-X
Abstract: Bile leak is a recognized complication of cholecystectomy. Endoscopic intervention is widely accepted as a treatment for this complication, but the optimal form is not well defined. An ERCP database was reviewed retrospectively to identify all cases of bile leak related to cholecystectomy. Patient records and endoscopy reports were reviewed, and structured telephone interviews were conducted to collect data. A total of 100 patients (61 women, 39 men mean age, 53 [17] years) with suspected postcholecystectomy bile leak were referred for ERCP. Cholecystectomy was commenced laparoscopically in 83 patients (with an open conversion rate of 30%). The most common symptoms were pain (n = 62) and fever (n = 37). Cholangiography was obtained in 96 patients. A leak was identified in 80/96 patients, the most common site being the cystic-duct stump (48), followed by ducts of Luschka (15), the T-tube site (7), and other sites (10). Treatment included stent insertion alone (40), sphincterotomy alone (18), combination stent/sphincterotomy (31), none (6), and other (1). Three patients with major bile-duct injuries were excluded from the analysis. Endoscopic therapy was unsuccessful in 7 patients (6 in the sphincterotomy alone group p = 0.001). Four patients underwent surgery subsequent to ERCP to control the leak. All 4 were in the sphincterotomy alone group ( p = 0.001). Post-ERCP pancreatitis developed in 4 patients (3 mild, 1 moderate). The optimal endoscopic intervention for postcholecystectomy bile leak should include temporary insertion of a biliary stent.
Publisher: BMJ
Date: 31-03-2021
DOI: 10.1136/EMERMED-2020-209751
Abstract: ABG s les are often obtained in trauma patients to assess shock severity. Venous blood gas (VBG) s ling, which is less invasive, has been widely used to assess other forms of shock. The study aim was to determine the agreement between VBG and ABG measurements in trauma. Patients were enrolled at an Australian trauma centre between October 2016 and October 2018. Bland-Altman limits of agreement (LOA) between paired blood gas s les taken min apart were used to quantify the extent of agreement. The impact of using only VBG measurements was considered using an a priori plan. Cases where venous s ling failed to detect ‘concerning levels’ were flagged using evidence-based cut-offs: pH ≤7.2, base deficit (BD) ≤−6, bicarbonate and lactate ≥4. Case summaries of these patients were assessed by independent trauma clinicians as to whether an ABG would change expected management. During the study period 176 major trauma patients had valid paired blood gas s les available for analysis. The median time difference between paired measurements was 11 min (IQR 6–17). There was a predominance of men (81.8%) and blunt trauma (92.0%). Median Injury Severity Score was 13 (range 1–75) and inpatient mortality was 6.3%. Mean difference (ABG−VBG) and LOA between paired arterial and venous measurements were 0.036 (LOA −0.048 to 0.120) for pH, −1.27 mmol/L (LOA −4.35 to 1.81) for BD, −0.64 mmol/L (LOA −1.86 to 0.57) for lactate and −1.97 mmol/L (LOA −5.49 to 1.55) for bicarbonate. Independent assessment of the VBG ‘false negative’ cases (n=20) suggested an ABG would change circulatory management in two cases. In trauma patients VBG and ABG parameters displayed suboptimal agreement. However, in cases flagged as VBG ‘false negative’ independent review indicated that the availability of an ABG was unlikely to change management.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.BBMT.2015.06.006
Abstract: We compared outcomes for 2 retrospective cohorts of patients undergoing reduced-intensity conditioning (RIC) therapy transplants using haploidentical related donors and post-transplant prophylaxis against graft-versus-host disease (GVHD) with high-dose cyclophosphamide, tacrolimus, and mycophenolate. The first cohort of 13 was transplanted with bone marrow (BM) as the stem cell source, whereas the second cohort of 23 used peripheral blood stem cells (PBSCs) mobilized with granulocyte colony-stimulating factor. The BM cohort received a single 60-mg/kg dose of cyclophosphamide on day +3, whereas the PBSC cohort received 2 doses on days +3 and +4. Patients in the first cohort were slightly older and had a higher proportion of acute myeloid leukemia, but there were no differences in the distribution of Disease Risk Index scores between the 2 groups. Patients in the PBSC group received double the number of CD34(+) cells in the stem cell graft. Times to neutrophil and platelet recovery were not different between the 2 groups. Three patients, all in the PBSC group, failed to engraft but recovered with autologous hemopoiesis and survived. The 6-month cumulative incidences of acute GVHD were 55.1% for BM and 48.5% for PBSCs (P = .651), whereas 24-month cumulative rates for chronic GHVD were 28.6% for BM and 32.3% for PBSCs (P = .685). Only 2 patients, both in the BM group, died of nonrelapse causes, both of second cancers. The 2-year cumulative incidences of relapse were 43.9% for BM and 23.5% for PBSCs (P = .286). Overall survival at 2 years was significantly better for PBSC patients (P = .028), at 83.4% versus 52.7% for BM. Relapse-free and event-free survival did not differ significantly between BM and PBSC groups. In this retrospective analysis, we conclude that the use of PBSCs for haploidentical RIC transplants is a feasible strategy, with equivalent rates of acute and chronic GVHD and risk of relapse and low nonrelapse mortality compared with BM.
Publisher: American Medical Association (AMA)
Date: 04-09-2018
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/798963
Abstract: Aim . The primary objective of the study was to assess the iodine nutritional status, and its effect on thyroid function, of pregnant women in a private obstetrical practice in Sydney. Methods . It was a cross-sectional study undertaken between November 2007 and March 2009. Blood s les were taken from 367 women at their first antenatal visit between 7 and 11 weeks gestation for measurement of thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels and spot urine s les for urinary iodine excretion were taken at the same time as blood collection. Results . The median urinary iodine concentration (UIC) for all women was 81 μ g/l (interquartile range 41–169 μ g/l). 71.9% of the women exhibited a UIC of μ g/l. 26% of the women had a UIC μ g/l, and 12% had a UIC μ g/l. The only detectable influences on UIC were daily milk intake and pregnancy supplements. There was no statistically significant association between UIC and thyroid function and no evidence for an effect of iodine intake on thyroid function. Conclusions . There is a high prevalence of mild to moderate iodine deficiency in women in Western Sydney but no evidence for a significant adverse effect on thyroid function. The 6.5% prevalence of subclinical hypothyroidism is unlikely to be due to iodine deficiency.
Publisher: Elsevier BV
Date: 08-2000
Abstract: The Sydney Olympic and Paralympic Games will be held in September-October 2000, which is early to mid-spring in the southern hemisphere. Pollen-sensitive athletes may encounter problems with allergic symptoms triggered by pollen exposure, thus compromising their ability to attain peak performance. We sought to monitor pollen levels at the major Olympic venues to provide information for allergic athletes and their team doctors in order to adequately prepare them for Olympic competition. We performed aerobiologic monitoring of the major Olympic venues to provide a profile of the most prevalent pollen species appearing during the spring. In the second part of this study, we surveyed a population of elite Australian athletes from Olympic sports to ascertain the prevalence of allergic rhinoconjunctivitis, to investigate the major allergens involved in sensitization, and to conduct a pilot study to assess the effect of allergic rhinoconjunctivitis on quality of life. The pollen counts obtained at the 3 major sites were high over the period of Olympic competition. Tree pollens appeared from July, and grasses appeared from early September and peaked in the second week of October, the beginning of Paralympic competition. A relatively small number of pollen varieties comprise the majority of the total pollen count. Two hundred fourteen athletes (61% male mean age, 21 +/- 16 years) representing 12 Olympic sports participated in the study. Fifty-six percent gave a symptom history consistent with allergic rhinoconjunctivitis, 41% had symptoms of allergic rhinoconjunctivitis and a positive test response to any one allergen, and 29% had seasonal allergic rhinoconjunctivitis (a positive history and at least one positive skin prick test response to a seasonal allergen). Athletes from aquatic sports were more likely to have symptoms than those from other sports. Symptom scores were higher and quality of life ratings were poorer in allergic compared with nonallergic athletes over the spring period. Olympic team managers and medical officers need to adequately prepare Olympic athletes for the possibility of exposure to high pollen levels in the weeks leading up to this most important sporting event. Symptoms of pollen sensitivity, such as rhinoconjunctivitis and exacerbation of asthma, could be devastating to athletes expecting peak performance. Potential Olympic athletes should be screened for the possibility of pollen allergy and have medical programs with permitted medication tailored to meet their needs. This may involve preventative therapy with medication, such as intranasal corticosteroid sprays or immunotherapy programs, if symptoms are particularly severe. The newer nonsedating antihistamines are the treatment of choice for acute intermittent symptoms. Appropriate management will ensure that the allergic athlete will safely perform to maximum ability with permitted medication during the Spring 2000 Olympic Games in Sydney.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.YEBEH.2015.03.016
Abstract: A primary brain tumor (PBT) is often a fatal disease of the nervous system and has a serious impact on health-related quality of life (HRQOL). Presence of epilepsy and adverse reactions from tumor and epilepsy treatments may cause additional decline in HRQOL. We aimed to study the impact of epileptic seizures on cognition, mood, and HRQOL in patients with brain tumor-related epilepsy. Patients were grouped on an ordinal scale according to epilepsy burden from none to severe based on the presence of epileptic seizures and seizure frequency: L1, no epilepsy L2, with epilepsy, seizure-free in the last 6 months with antiepileptic drugs and L3, with epilepsy, at least one seizure in the last 6 months with AEDs. Health-related quality of life was measured by Functional Assessment of Cancer Therapy-Brain (FACT-Br) and Quality of Life in Epilepsy-31 (QOLIE-31) tools, cognition by the Montreal Cognitive Assessment (MoCA) tool and Frontal Assessment Battery (FAB), mood by the Hospital Anxiety and Depression Scale (HADS), activities of daily living (ADLs) by the Barthel Index (BI), and performance status by the Karnofsky Performance Status (KPS) scale in patients with primary brain tumors at least one month following neurosurgery with or without radiotherapy and chemotherapy. Eighty-one patients with a diagnosis of primary brain tumors were recruited. Sixty-eight percent of patients were diagnosed with primary brain tumor-related epilepsy, 50.61% patients had cognitive impairment, 33% had abnormal scores in the anxiety scale, and 34% had abnormal scores in the depression scale. There were no statistically significant differences in these scores among L1, L2, and L3 groups. There were statistically significant differences in duration of disease and KPS and BI scores between L1 and L3 groups. The L3 group has significantly longer duration of disease and scored low in both the BI and KPS scale when compared to the L1 group. All patients with primary brain tumors scored significantly low in FACT-Br 'physical well-being' (PWB) and 'emotional well-being' (EWB) and high in 'social well-being' (SWB) when compared to healthy controls. When scores of each group were in idually compared to healthy controls, the L3 group showed the lowest scores in PWB, EWB, and 'functional well-being'. In SWB, L1 and L2 groups showed statistically significantly high scores when compared to normative data. The QOLIE-31 applied to groups with epilepsy showed statistically significantly lower scores in the L3 group when compared to the L2 group in 'cognitive' and 'social functioning' domains. On multivariate analysis, both poor performance status and frequency of seizures were found to be independent risk factors for poor HRQOL when FACT-Br mean scores were compared. Level of seizures was found to be an independent risk factor for poor HRQOL when QOLIE-31 scores were compared between L2 and L3 groups. Presence of brain tumors could be attributed to cognitive impairment irrespective of the presence of epilepsy in our cohort. High seizure burden is an independent risk factor for poor HRQOL in patients with primary brain tumors. The QOLIE-31 is a more sensitive tool than the FACT-Br because of the presence of a seizure-related questionnaire.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1999
Publisher: Bentham Science Publishers Ltd.
Date: 11-2011
DOI: 10.2174/156720111797635478
Abstract: To examine the clinical and histological outcomes following intra-articular injection of an immunomodulatory peptide (CP) during an acute attack of adjuvant induced arthritis in rats. Arthritis in rats was induced by injecting 0.1 mL of Mycobacterium Tuberculosis (MTB 10mg/ml) intra-dermally at the base of the tail. After the onset of arthritis, affected ankle joints were injected with either 20 μl of water, dexamethasone (4 mg/ml), cyclosporine (0.38 mg equivalent to 3mg/kg in humans), CP (60 mg/ml 12.5 mg/ml 6.25 mg/ml 3.125 mg/ml) or a CP analogue (CPD 6.25mg/ml). There were a minimum of 5 rats/group and intra-articular injection was given on two separate occasions following the onset of arthritis. Rat weight, paw thickness, paw-width, ankle width and arthritic joint count were measured. Affected joints were X-rayed and joint tissue taken for histology. Rats given dexamethasone and cyclosporine had a significant improvement in clinical outcomes compared to the control group. CP at the highest dose was significantly better compared to the water group and the clinical effects were dose dependent. Histology of the joints showed severe inflammation and destruction in the water treated group with minimal inflammatory effects in the dexamethasone and cyclosporine group. Joints injected with cyclosporine were characterized by extensive fibrosis. The joints from CP treated rats showed mild to moderate inflammation with histological features somewhere between the cyclosporine and water injected groups. This study demonstrates that CP given intra-articularly has antiarthritic effects and raises new possibilities for treatment.
Publisher: Wiley
Date: 1979
Publisher: Wiley
Date: 06-1980
Publisher: Wiley
Date: 05-2004
Publisher: BMJ
Date: 2007
Publisher: Wiley
Date: 09-1998
DOI: 10.1111/J.1440-1746.1998.TB00761.X
Abstract: The aim of this study was to determine the distribution of hepatitis C virus (HCV) genotypes in Australian patients with hepatitis C and to identify factors associated with particular genotypes. Serum isolates of HCV-RNA were genotyped using a commercial oligonucleotide hybridization (line probe) assay. Relationships between demographic factors, mode of HCV transmission and HCV genotype were assessed by logistic regression analysis. Among 463 patients with hepatitis C, 425 tested positive for HCV-RNA and a single HCV genotype was identified in 420 cases. The patients' places of birth were Australia or New Zealand (62%), Asia (13%), Europe (12%), Mediterranean (6%), Middle East (6%) and other countries (< 1%). The most common genotypes were type 1 (52%) or type 3 (32%) type 2 (9.3%), type 4 (5.5%) and type 6 (1.7%) were less common. Patients with genotype 1b were older (48 +/- 13 years, P< 0.001) and patients with genotype 3 were younger than the remaining patients (37 +/- 11 years vs 42 +/- 12 years, P< 0.001). Among type 1 isolates, 1b was more common for patients born outside Australia compared with those born in Australia (50% vs 13%, P 95% of Australian-born patients, but in only 33% of Asian or Mediterranean-born patients. Logistic regression analysis indicated that region of birth and risk factor (intravenous drug use or not) would allow 98% of type 4 cases and 76% of type 1b cases to be identified correctly. In summary, region of birth, patterns of migration over time and risk factors for transmission of HCV interact to determine the distribution of HCV genotypes in a multi-racial community like Australia.
Publisher: Wiley
Date: 19-11-2020
DOI: 10.1111/ECHO.14922
Publisher: AMPCo
Date: 04-2011
DOI: 10.5694/J.1326-5377.2011.TB03000.X
Abstract: To test the hypothesis that lower 25-hydroxyvitamin D (25[OH]D) levels in late pregnancy are associated with poorer glucose control in gestational diabetes mellitus (GDM). Retrospective cross-sectional study, in a GDM clinic at a tertiary referral centre. Women attending the GDM clinic at Westmead Hospital from 1 February 2007 to 1 February 2008, excluding those with prepregnancy glucose intolerance. Levels of glycated haemoglobin (HbA(1c)) and 25(OH)D measured during the third trimester maternal age, ethnicity, body mass index (BMI) and occupational status and results of oral glucose tolerance testing (OGTT). 147 women with a mean gestational age of 35 ± 2 weeks were included, of whom 41% had insufficient or deficient levels of 25(OH)D (≤ 50 nmol/L). Ethnicity, occupational status and season significantly influenced 25(OH)D levels (P < 0.01 for all) but BMI did not. 25(OH)D levels were inversely associated with fasting and 2-hour blood glucose levels during OGTT (Spearman r = - 0.16 P = 0.05 for both) and with log[HbA(1c)] (Spearman r = - 0.32 P < 0.001). BMI and insulin doses were also associated with HbA(1c) levels. Multivariable analysis identified 25(OH)D and blood glucose levels during the OGTT as independent predictors of HbA(1c) levels. Lower 25(OH)D levels are independently associated with poorer glycaemic control. Future randomised trials are needed to determine whether vitamin D plays a role in glycaemic control in GDM. Regardless, maternal vitamin D insufficiency has adverse effects including neonatal hypocalcaemia and rickets. The 41% prevalence of inadequate 25(OH)D levels in the women in our study is unacceptably high. We propose routine 25(OH)D testing of all pregnant women at screening for GDM or earlier, and treatment of women who are found to be deficient.
Publisher: Wiley
Date: 13-10-2006
DOI: 10.1111/J.1445-5994.2006.01169.X
Abstract: Pulmonary hypertension, when advanced, markedly limits exercise capacity, activities of daily living and quality of life (QoL). No measure of QoL has yet been validated for the assessment of pulmonary hypertension. The aim of the study was to compare the validity of the Minnesota Living with Heart Failure (MLwHF) questionnaire, the Short Form-36 (SF-36) questionnaire and the Australian Quality of Life (AQoL) measure for assessing pulmonary hypertension treatment. Eighty-three patients were enrolled in three studies of pulmonary hypertension treatment (treprostinil, bosentan and sildenafil). They were assessed at baseline and 3 months with the MLwHF questionnaire. Treprostinil and bosentan groups also had 6 and 12 months' data. Twenty-one patients in the sildenafil trial completed concurrently, the SF-36 and AQoL measures at baseline and 3 months. QoL scores were correlated with the 6-min walk test distance, New York Heart Association functional class and right heart catheter-derived haemodynamic parameters of the disease for all matching time points and for changes in scores and clinical measurements over time. The MLwHF and SF-36 scores correlated well with the 6-min walk test distance and New York Heart Association functional class, but did not correlate with haemodynamic measurements. MLwHF and SF-36 scores also correlated with the rate of change of the 6-min walk test distance and New York Heart Association functional class over time. The MLwHF questionnaire and SF-36 are useful tools for the assessment of QoL in pulmonary hypertension and may be useful in the ongoing evaluation of QoL in the treatment and study of pulmonary hypertension.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Springer Science and Business Media LLC
Date: 04-2005
Publisher: Wiley
Date: 08-2010
DOI: 10.1111/J.1528-1167.2010.02552.X
Abstract: This study aims to map the temporal and extratemporal 18-fluorodeoxyglucose positron emission tomography (FDG-PET)-defined hypometabolism in mesial temporal lobe epilepsy (MTLE). We hypothesize that quantitative analysis will reveal extensive extratemporal glucose hypometabolism (EH), that the EH is related to seizure propagation beyond the temporal lobe, hypometabolism restricted to one temporal lobe predicts a good outcome following surgery, and EH predicts a poor outcome. Sixty-four patients were studied who had undergone temporal lobectomy for intractable MTLE and had at least 2 years of postoperative follow-up. Spatial preprocessing and statistical analysis on preoperative interictal FDG-PET using statistical parametric mapping (SPM 2) identified significant regions of hypometabolism compared to normal controls. The predictors of outcome were determined by univariable and multiple logistic regression analyses. EH was common and widespread, occurring most frequently in the ipsilateral insula and frontal lobe. The extent of EH was not significantly associated with age of onset or the duration of epilepsy. Presence of secondarily generalized tonic--clonic seizures (SGTCS) was associated with a larger extent of remote hypometabolism (RH, p < 0.005). Multiple logistic regression analysis identified the extent of RH and the age at surgery as independent predictors of seizure outcome. Our results indicate that RH in MTLE is associated with a poorer surgical outcome, especially if seen in the contralateral hemisphere. The extent of RH relates to SGTCS but not to duration of epilepsy.
Publisher: AMPCo
Date: 11-1993
Publisher: American Physiological Society
Date: 11-2007
DOI: 10.1152/JAPPLPHYSIOL.01413.2006
Abstract: Snoring-associated vibration energy transmission from the upper airway to the carotid artery has been hypothesized as a potential atherosclerotic plaque initiating/rupturing event that may provide a pathogenic mechanism linking snoring and embolic stroke. We examined transmission of oscillatory pressure waves from the pharyngeal lumen to the common carotid artery wall and lumen in seven male, anesthetized, spontaneously breathing New Zealand White rabbits. Airflow was monitored via a pneumotachograph inserted in series in the intact trachea. Fifteen 20-s runs of, separately, 40-, 60-, and 90-Hz oscillatory pressure waves [pressure litude in the trachea (Ptr ), litude 2–20 cmH 2 O] were generated by a loudspeaker driven by a sine wave generator and lifier and superimposed on tidal breathing via the cranial tracheal connector. Pressure transducer-tipped catheters measured pressure litudes in the tissues adjacent to the common carotid artery bifurcation (Pcti ) and within the lumen (carotid sinus Pcs ). Data were analyzed using power spectrum analysis and linear mixed-effects statistical modeling. Both the frequency (f) and litude of the injected pressure wave influenced Pcti and Pcs , in that ln Pcti = 1.2(Ptr ) + 0.02(f) − 5.2, and ln Pcs = 0.6(Ptr ) + 0.02(f) − 4.9 (both P 0.05). Across all frequencies tested, transfer of oscillatory pressure across the carotid artery wall was associated with an litude gain, as expressed by a Pcs -to-Pcti ratio of 1.8 ± 0.3 ( n = 6). Our findings confirm transmission of oscillatory pressure waves from the upper airway lumen to the peripharyngeal tissues and across the carotid artery wall to the lumen. Further studies are required to establish the role of this incident energy in the pathogenesis of carotid artery vascular disease.
Publisher: Wiley
Date: 1996
DOI: 10.1111/J.1440-1746.1996.TB00007.X
Abstract: Drug metabolism is usually impaired in malnourished patients with decompensated cirrhosis, but the separate influence of clinicopathological variables, including nutritional status, on the expression of hepatic cytochrome P450 proteins has not been well characterized. We determined the hepatic content of CYP1A2, CYP2C8/10, CYP2E1 and CYP3A proteins in 71 subjects, 21 with histologically normal livers and 50 with chronic liver disease, and then tested for potential relationships between patient variables and in idual CYP proteins by multivariate linear regression analysis. Variables analysed included nutritional status (determined by experienced clinicians), serum albumin and bilirubin concentrations, prothrombin time, the grade of ascites and hepatic encephalopathy, and the Child-Pugh score. Impaired nutrition and cachexia were associated with reductions of CYP2C8/10 levels of approximately 19 and 39%, respectively, relative to cases in which nutrition was replete. Similarly, CYP2E1 protein was reduced by approximately 13 and 26%, according to the apparent severity of nutritional impairment. In contrast, nutritional status did not contribute to variability in expression of CYP1A2 or CYP3A proteins. Of the clinicopathological variables analysed, only serum bilirubin was shown to have an independent influence on CYP protein content. Thus, elevated serum bilirubin concentrations were associated with significant declines in the contents of CYP1A2 and CYP2C8/10 but not CYP3A or CYP2E1. The mechanisms for the effects of nutritional status and serum bilirubin concentration on the levels of CYP proteins are unclear, but could be mediated by factors such as cytokines, dietary composition and alterations in the level of serum bile acids. Knowledge of the influence of clinicopathological factors and nutritional status on CYP expression should lead to more rational drug prescribing in patients with hepatic disease.
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.HLC.2008.06.005
Abstract: The purpose of this study was to evaluate the outcome of cardiac surgery at Allamanda Hospital which is a small private hospital carrying out less than 100 operations per year. Data on patients undergoing cardiac surgery since 2002 were prospectively entered into a database. An analysis of this data is presented and compared with national and international benchmarks for results from larger national and international cardiac surgery units. From October 2002 to March 2007, there were 360 patients who underwent cardiac surgery in a small private cardiothoracic surgical unit (average of 80 patients per year). The average logistic EuroSCORE, Cleveland Clinic and Parsonnet Scores for the patients were 13%, 5.7 and 13.4, respectively. The mean logistic EuroSCORE observed in this study of 13% was substantially higher than those of other published series and institutions. The Allamanda results were compared with those from the European database (EuroSCORE), the STS and the Victorian National Cardiac Surgery Database. The overall observed mortality at Allamanda of 7.5% was lower than predicted by the mean logistic EuroSCORE of 13%. In comparison with the Victorian database, there was no significant difference in mortality for low-risk (additive EuroSCORE 0-3) and medium-risk (4-6) groups. Patients in the high-risk group with additive EuroSCOREs>or=7 were similarly ided into categories of three additive EuroSCOREs. There was no significant difference in any of the categories in the high-risk group. There was a greater proportion of high-risk (additive EuroSCORE>or=7) patients in the Allamanda series (P<0.0001). Patients in the Allamanda series were older (mean age 70.1) than the other published series (P<0.0001). The mean logistic EuroSCORE for the mortality group was 35.9+/-29.4% (6.4-65.3%). Low volume cardiac surgery can be undertaken safely in a small Australian private cardiothoracic unit with acceptable results. The trend towards improved outcomes for high-risk patients in larger institutions suggests that such patients undergoing elective procedures should be given the option of doing so in a larger centre. Ongoing quality assurance programs are equally important for large and small cardiac surgical units with participation in a national or international cardiac surgery database.
Publisher: Wiley
Date: 02-09-2010
DOI: 10.1002/GCC.20816
Abstract: The heterogeneity of multiple case breast cancer families that do not carry mutations in BRCA1 or BRCA2 (non-BRCA1/2 families) poses a challenge to the identification of breast cancer susceptibility genes. The aim of this study was to determine whether intrafamilial concordance in breast cancer pathology could identify subgroups of non-BRCA1/2 families with consistent genotypic features. Invasive breast cancers were reviewed from 84 in iduals belonging to 30 multiple-case families BRCA1 (n = 9), BRCA2 (n = 10), and non-BRCA1/2 (n = 11). Hierarchical cluster analysis based on histopathology and age at first diagnosis was then used to specify three subgroups designated Clusters 1-3. The genomic features of non-BRCA1/2 families were examined by genome wide linkage and FGFR2 SNP genotyping, according to whether they showed cluster-concordant or cluster-mixed familial pathology. The majority of pathogenic BRCA1 mutation carriers (80%) fell into a single cluster. In contrast pathogenic BRCA2 mutation carriers were distributed across all three clusters and within families, cluster groups were also generally mixed. Most non-BRCA1/2 mutation carriers belonged to Cluster 3 (71%). Genome wide linkage data from five non-BRCA1/2 Cluster 3-concordant families were compared with four mixed cluster non-BRCA1/2 families. This revealed a number of distinct linkage peaks, including some regions previously associated with breast cancer susceptibility. The distribution of low risk alleles in FGFR2 was not different between these two subgroups (P = 0.237). The pattern of breast cancer pathology concordance amongst family members may assist the investigation of breast cancer susceptibility in multiple case families.
Publisher: Elsevier BV
Date: 07-1996
Publisher: Wiley
Date: 04-2009
DOI: 10.1111/J.1445-5994.2009.01800.X
Abstract: The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment. A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18-year period. The primary outcome was time to cessation of MTX. Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity-related discontinuation occurred in 93 patients (11.8%) and due to non-adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57-0.96 P = 0.014) patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42-0.74 P < 0.001). Being of the male sex aged more than 60 years and having a non-RA diagnosis predisposed to stopping MTX earlier. MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re-evaluate and revise the current monitoring guidelines.
Publisher: Elsevier BV
Date: 08-2007
DOI: 10.1016/J.HLC.2007.02.085
Abstract: Prediction of the location of culprit lesions responsible for ST-segment elevation myocardial infarctions may allow for prevention of these events by safe and easily deliverable local therapies. A retrospective analysis of coronary movement was performed on coronary angiograms of patients who subsequently represented with ST-segment elevation myocardial infarction treated by primary or rescue angioplasty at a single institution. Twenty patients were identified. The stretch-compression type of coronary artery movement (CAM) was a statistically significant independent predictor of the segment containing the culprit lesion (odds ratio 6.10, p-value 0.005). The stretch-compression type of coronary artery movement is an independent predictor of the location of culprit lesions responsible for ST-segment elevation myocardial infarctions.
Publisher: American College of Physicians
Date: 21-02-2006
DOI: 10.7326/0003-4819-144-4-200602210-00005
Abstract: Clinically important rapid bone loss occurs within 3 to 6 months after liver transplantation and may be associated with osteoporotic fractures. To determine whether bisphosphonate treatment with zoledronic acid reduces transplant-related bone loss more than placebo in adults having liver transplantation for chronic liver disease. 12-month randomized, double-blind, placebo-controlled trial. 2 large liver transplantation centers in Australia. 62 adults having liver transplantation for chronic liver disease. Infusions of zoledronic acid, 4 mg (n = 32), or saline (n = 30) were given within 7 days of transplantation and again at months 1, 3, 6, and 9 after transplantation. All patients received supplementation with calcium carbonate, 600 mg/d, and ergocalciferol, 1000 U/d. The primary outcome was bone mineral density (BMD) measured by dual x-ray absorptiometry before transplantation and 3, 6, and 12 months later. Secondary outcomes included bone turnover markers that were measured before transplantation and 1, 3, 6, 9, and 12 months later. There were statistically significant interactions between treatment effects and time for BMD measurements at the lumbar spine (P = 0.002), femoral neck (P = 0.001), and total hip (P < 0.001). Differences in acute bone loss 3 months after transplantation favored zoledronic acid over placebo. Differences between groups in percentage change from baseline adjusted for baseline weight and serum parathyroid hormone (PTH) level were 4.0% (95% CI, 1.1% to 7.0%) for the lumbar spine, 4.7% (CI, 1.9% to 7.6%) for the femoral neck, and 3.8% (CI, 1.7% to 6.0%) for the total hip. At 12 months after transplantation, the difference in percentage change from baseline between the 2 groups adjusted for baseline weight and serum PTH level was 1.1% (CI, -2.1% to 4.4%) for the lumbar spine, 2.7% (CI, 0.0% to 5.4%) for the femoral neck, and 2.4% (CI, 0.1% to 4.7%) for the total hip. Treatment with zoledronic acid induced temporary secondary hyperparathyroidism and postinfusion hypocalcemia statistically significantly more often than did placebo. The trial was not powered to assess fractures, and 10 of 62 (16%) patients were not included in adjusted analyses because of missing weight or serum PTH measurements. Treatment with zoledronic acid can prevent bone loss within the first year after liver transplantation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1991
DOI: 10.1097/00004836-199110000-00006
Abstract: Dyspepsia patterns during the course of duodenal ulcer (DU) were examined in terms of the number of consecutive months that patients experienced dyspepsia either intermittently or continuously, or were dyspepsia-free. The patients (n = 224) were community-based. After ulcer healing, they were evaluated every 3 months for less than or equal to 7 years. Antiulcer agents were prescribed at the physicians' discretion. We analyzed the data on a patient-month basis using a 2-state Markov chain model. The fitted mean number of consecutive months with dyspepsia and the number of months dyspepsia-free were, respectively, 1.7 and 14 in patients on antiulcer agents, and 1.5 and 9 in patients not taking them. On average, patients experienced dyspepsia during 15% of months studied if they were on antiulcer agents, and during 20% of months if not. Regardless of antiulcer therapy, dyspepsia periods were lengthened by age, especially greater than 60 years male sex widowhood/ orce/separation increasing acetaminophen use and increasing length of time since initial onset of ulcerlike dyspepsia. Dyspepsia-free periods were lengthened by age greater than 70 years, and shortened by widowhood/ orce/separation and increasing cigarette consumption. These results suggest that dyspepsia occurs for less than or equal to 20% of the time in DU patients on about a yearly basis. The least dyspepsia may be expected in patients neither widowed, orced, nor separated, in whom length of time since the initial onset of ulcerlike dyspepsia does not exceed 7 years, and who neither smoke nor use analgesics regularly.
Publisher: AMPCo
Date: 06-2008
DOI: 10.5694/J.1326-5377.2008.TB01831.X
Abstract: To document the population iodine nutritional status in Australian schoolchildren. Cross-sectional survey of schoolchildren aged 8-10 years, based on a one-stage random cluster s le drawn from all Year 4 school classes in government and non-government schools in the five mainland Australian states of New South Wales, Victoria, South Australia, Western Australia and Queensland. The study was conducted between July 2003 and December 2004. 1709 students from 88 schools (881 boys and 828 girls), representing 85% of the estimated target number of students. The class participation rate was 65%. (i) Urinary iodine excretion (UIE) levels (compared with the criteria for the severity of iodine deficiency of the World Health Organization/International Council for the Control of Iodine Deficiency Disorders: iodine replete, UIE > or = 100 microg/L mild iodine deficiency, UIE 50-99 microg/L moderate iodine deficiency, UIE 20-49 microg/L severe iodine deficiency, UIE < 20 microg/L) (ii) Thyroid volumes measured by ultrasound (compared with new international reference values). Overall, children in mainland Australia are borderline iodine deficient, with a national median UIE of 104 microg/L. On a state basis, NSW and Victorian children are mildly iodine deficient, with median UIE levels of 89 microg/L and 73.5 microg/L, respectively. South Australian children are borderline iodine deficient, with a median UIE of 101 microg/L. Both Queensland and Western Australian children are iodine sufficient, with median UIE levels of 136.5 microg/L and 142.5 microg/L, respectively. Thyroid volumes in Australian schoolchildren are marginally increased compared with international normative data obtained from children living in iodine sufficient countries. There was no significant association between UIE and thyroid volume. Our results confirm the existence of inadequate iodine intake in the Australian population, and we call for the urgent implementation of mandatory iodisation of all edible salt in Australia.
Publisher: Bioscientifica
Date: 31-03-2008
DOI: 10.1677/JME-07-0149
Abstract: Epithelial ovarian cancer, the leading cause of death from gynecological malignancy in Western countries, is thought to arise from the ovarian surface epithelium (OSE). It has been postulated that the constant rounds of proliferation and repair following ovulation contributes to neoplastic transformation. However, there is little information on the genes and pathways which are involved in the normal functions of the ovarian epithelium, in particular genes that are hormone responsive and those central to functions such as proliferation and apoptosis during ovulation. We used laser microdissection and cDNA microarrays to profile gene expression specifically in mouse ovarian epithelial cells, first compared with other ovarian cells, and secondly between ovarian epithelium collected at different physiological stages. We identified over 1000 transcripts that were consistently more highly expressed in the ovarian epithelium compared with remaining ovarian cell types, including genes involved in cell growth, transcription, and cell adhesion. At the various physiological stages examined, the highest number of regulated genes was found during the estrous cycle, specifically on the evening of proestrus, coincident with the ovulatory surge of hormones and just prior to ovulation. The expression of several selected genes, identified by the microarray analysis, including Villin 2, Keratin 8 , Arginine-rich mutated in epithelial tumors , and Tumor-associated calcium signal transducer 1 , was validated by independent methods. The identification of genes expressed and regulated in the OSE, and characterization of the pathways involved, will contribute to a more detailed understanding of the ovarian epithelium transcriptome and ultimately lead to a better understanding of the aberrations leading to malignant transformation in the ovarian epithelium.
Publisher: Elsevier BV
Date: 06-1995
DOI: 10.1016/0167-5273(95)93682-I
Abstract: Analysis of the surface ECG can predict the locations of pacing foci but is of limited value for locating arrhythmogenic substrates causing ventricular tachycardia because of the effects of myocardial infarction, ischaemia, and bundle branch block on ventricular activation. To determine whether analysis of the initial 60 ms segment of the surface QRS improves the accuracy of the ECG for predicting ventricular tachycardia origin we correlated the locations of 37 arrhythmogenic areas present in 20 patients with the 3D vectors of the ventricular tachycardias generated by each respective area. The 3D vector of each ventricular tachycardia morphology was calculated from the integrals of the initial 60 ms of the surface vectorcardiogram and from the entire QRS recorded in each lead of the Frank orthogonal lead vectorcardiogram. Sixty eight-morphologies of ventricular tachycardia were mapped using simultaneous recordings from 60 catheter electrodes. Ventricular tachycardias with 3D vectors directed inferiorly and posteriorly or superiorly and anteriorly were more likely to originate from the septum, P = 0.04, whereas tachycardias directed superiorly and to the right were more likely to originate from the inferior wall and the cardiac apex, P = 0.001. However, the same arrhythmogenic area could generate multiple ventricular tachycardias with different 3D vectors. In addition, ventricular tachycardias with similar 3D vectors were generated by arrhythmogenic areas in the septal, apical and inferior walls. The variances of the mean 3D vectors of ventricular tachycardias originating from each of 12 different cardiac regions were no different when based on the initial 60 ms of the surface QRS than on the entire surface QRS. Analysis of the surface ECG provides only an approximate guide to the locations of arrhythmogenic areas generating ventricular tachycardia even when analysis is restricted to the initial forces in the surface QRS. Therefore, detailed mapping is needed to accurately determine the number and location of arrhythmogenic areas.
Publisher: Springer Science and Business Media LLC
Date: 16-05-2018
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JTCVS.2013.12.064
Abstract: To identify predictors of early and late outcomes of cardiac surgery in patients with chronic kidney disease. Patients (n=545) with serum creatinine≥200 μmol/L or renal dialysis were identified from databases maintained by the largest Sydney cardiothoracic surgical units with data consistent with the Australian and New Zealand Society of Cardiothoracic Surgeons data definitions. The patient data were matched against the National Dialysis Database and the New South Wales Register of Births, Deaths, and Marriages. Statistical analysis was used to identify predictors of early and late outcomes. The Kaplan-Meier estimate of 1-, 5-, and 10-year survival for all patients was 78%, 56%, and 36%, respectively. The outcomes were similar after coronary bypass surgery and valve replacement and were also similar for dialysis and nondialysis patients. The odds ratios for the significant independent predictors of outcomes were, for perioperative death, age (1.4 per decade), emergency surgery (7.0), redo surgery (3.8), left ventricular impairment (moderate, 2.7 severe, 4.4) for new early postoperative dialysis, estimated glomerular filtration rate<20 mL/min (3.8), emergency surgery (2.7), tricuspid valve surgery (4.4) for new permanent dialysis within 6 months of surgery, serum estimated glomerular filtration rate<20 mL/min (odds ratio, 4.6). The hazard ratio for the independent predictors of late death in those alive 6 months after surgery was 1.4 per decade for age and 1.4 for moderate or severe left ventricular impairment. Left ventricular impairment is a risk factor for perioperative and late death in patients with kidney disease. After cardiac surgery, preoperative dialysis-dependent and dialysis-free patients had similar long-term outcomes.
Publisher: Elsevier BV
Date: 09-1991
DOI: 10.1016/0002-9149(91)90354-N
Abstract: Accurate anatomic localization of accessory pathways during preoperative electrophysiologic study and during operative mapping depends on a knowledge of the dimensions of the posterior septal space and the left free wall. These dimensions were therefore studied in 48 human cadaver hearts. Mean distance from the coronary sinus orifice to the left margin of the posterior septal space was 2.3 +/- 0.4 cm and mean length of the left free wall was 5.0 +/- 1.0 cm. The posterior septal space at the level of the valve anuli extended a mean of 3.4 +/- 0.5 cm around the epicardium. The width of the posterior septum measured in the coronary sinus was related to heart weight and a combination of body weight and patient age (p less than 0.05). The probability of an accessory pathway being located in the left free wall or the posterior septum during catheter mapping was calculated for various distances from the coronary sinus orifice for adults of different ages and body weights. In adults, accessory pathways located in the proximal 1.5 cm of the coronary sinus are almost always in the posterior septum. Those located between 1.5 and 3 cm from the coronary sinus orifice may be in either the left free wall or the posterior septum, and those located greater than 3 cm from the coronary sinus orifice are almost invariably in the left free wall.
Publisher: Wiley
Date: 26-10-2006
DOI: 10.1111/J.1365-2559.2006.02538.X
Abstract: Germline variants in the ataxia telangiectasia mutated (ATM) gene have been implicated in increased breast cancer risk. The aim of this study was to determine whether the histopathology of breast cancers occurring in ATM variant carriers is distinctive or resembles the described BRCA1 mutation-associated phenotype. The histopathological features of breast cancers occurring in ATM variant carriers from multiple-case breast cancer families were compared with matched controls. The test group included 21 cases of in situ and/or invasive cancer from carriers of either the IVS10-6T-->G, 2424V-->G or 1420L-->F ATM variants in the absence of BRCA1 or BRCA2 mutations. An additional four invasive cancers from carriers of a pathogenic BRCA1 mutation in the context of a familial ATM variant were also examined. The histopathology of breast cancers in ATM variant-only carriers was not significantly different from controls and known features of BRCA1 mutation-associated cancer were rarely seen. In contrast, these features were prominent in the small group of cases with a pathogenic BRCA1 mutation. Breast cancer occurring in carriers of ATM variants is not associated with distinctive histopathological features and does not resemble the tumour phenotype commonly observed in BRCA1 mutation carriers.
Publisher: BMJ
Date: 19-01-2016
DOI: 10.1136/GUTJNL-2015-310249
Abstract: Endoscopic mucosal resection (EMR) is effective for large laterally spreading flat and sessile lesions (LSLs). Sessile serrated adenomas olyps (SSA/Ps) are linked to the relative failure of colonoscopy to prevent proximal colorectal cancer. We aimed to examine the technical success, adverse events and recurrence following EMR for large SSA/Ps in comparison with large conventional adenomas. Over 74 months till August 2014, prospective multicentre data of LSLs ≥20 mm were analysed. A standardised dye-based conventional EMR technique followed by scheduled surveillance colonoscopy was used. From a total of 2000 lesions, 323 SSA/Ps in 246 patients and 1527 adenomas in 1425 patients were included for analysis. Technical success for EMR was superior in SSA/Ps compared with adenomas (99.1% vs 94.5%, p<0.001). Significant bleeding and perforation were similar in both cohorts. The cumulative recurrence rates for adenomas after 6, 12, 18 and 24 months were 16.1%, 20.4%, 23.4% and 28.4%, respectively. For SSA/Ps, they were 6.3% at 6 months and 7.0% from 12 months onwards (p<0.001). Following multivariable adjustment, the HR of recurrence for adenomas versus SSA/Ps was 1.7 (95% CI 0.9 to 3.0, p=0.097). Subgroup analysis by lesion size revealed an eightfold increased risk of recurrence for 20-25 mm adenomas versus SSA/Ps, but no significantly different risk between lesion types in larger lesion groups. Recurrence after EMR of 20-25 mm LSLs is significantly less frequent in SSA/Ps compared with adenomatous lesions. SSA/Ps can be more effectively removed than adenomatous LSLs with equivalent safety. Ensuring complete initial resection is imperative for avoiding recurrence. ClinicalTrials.gov NCT01368289.
Publisher: Elsevier BV
Date: 02-2022
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.GIE.2009.09.024
Abstract: In the absence of precut needle-knife sphincterotomy (NKS), failure of biliary cannulation may occur in up to 10% of cases. There are few prospective evaluations of the safety and efficacy of NKS, and studies of its early use in difficult cannulation have been inconclusive. Whether precut NKS after failure of primary biliary cannulation is independently associated with post-ERCP pancreatitis (PEP) remains controversial. To examine the relationship between NKS and PEP. Analysis of prospectively collected data from two randomized trials of ERCP techniques, with PEP as the primary endpoint measure. Tertiary-care academic medical center. This study involved 732 patients from two successive, prospective, randomized trials of naïve papilla cannulation between November 2001 and April 2006. Patients with pancreatic or ullary cancer were excluded. Naïve papilla cannulation, NKS, primary guidewire versus contrast-assisted cannulation, and glyceryl trinitrate patch versus placebo. PEP and procedure-related complications. NKS was performed in 94 of 732 patients (12.8%) and was successful in achieving bile duct access in 80 of 94 patients (85%). Cannulation success in the entire group was 717 of 732 patients (97.7%). The overall frequency of PEP following NKS was 14.9% (14 of 94 patients) compared with 6.1% (39 of 638 patients) without NKS (P < .001). The incidence of PEP increased with an increasing number of attempts at cannulating the papilla. Pancreatic stents were inserted in 22 patients, 5 of whom developed pancreatitis. In multivariate analysis, independent predictors of PEP were as follow: female sex (odds ratio [OR] = 3.5, P = .028), suspected sphincter of Oddi dysfunction (SOD) (OR = 9.7, P /=15 attempts at papilla cannulation (OR = 9.4, P = .013). NKS was not an independent predictor of PEP. There were no perforations, no major bleeding, and no cases of severe pancreatitis in the NKS group. Nonrandomized for NKS intervention. The number of attempts at cannulating the papilla is independently associated with PEP, and the risk increases with an increasing number of attempts. NKS is not an independent predictor of PEP.
Publisher: American Dental Society of Anesthesiology (ADSA)
Date: 2011
DOI: 10.2344/09-00001.1
Abstract: The death of a patient under sedation in New South Wales, Australia, in 2002 has again raised the question of the safety of dental sedation. This study sought answers to 2 questions: Can safe oxygen saturation levels (≥94%) be consistently maintained by a single operator/sedationist? Does the additional use of propofol, in subanesthetic doses, increase the risk of exposure to hypoxemia? Three thousand five hundred cases generated between 1996 and 2006 were randomly examined and ided into 2 subcohorts: 1750 patients were sedated with midazolam and fentanyl, and 1750 patients received propofol, in subanesthetic increments, in addition to midazolam and fentanyl. Initial sedation was established using midazolam and fentanyl in both subcohorts. The second subcohort received propofol during times of noxious stimulation. Patient exposure to 2 or more oxygen desaturations below 94% was uncommon. The variables that were significantly associated with low saturations were age, gender, and weight. Neither the dose of midazolam nor the additional use of propofol was a significant risk factor. ASA classification (I or II) was not a determinant of risk. The data, within the limitations of the study, showed that a single operator/sedationist, supported by a well-trained team of nurses, can consistently maintain safe oxygen saturation levels. The additional use of propofol did not increase exposure to hypoxemia.
Publisher: Springer Science and Business Media LLC
Date: 28-08-2018
DOI: 10.1007/S40519-018-0566-2
Abstract: Excessive gestational weight gain is associated with detrimental outcomes to both the mother and baby. Currently, the best approach to prevent excessive gestational weight gain in overweight and obese women is undetermined. The present study aimed to evaluate the effectiveness of a group-based outpatient dietary intervention in pregnancy to reduce excessive gestational weight gain. In this retrospective study, overweight and obese pregnant women who attended a single 90-min group education session were compared to women who received standard care alone. Total gestational weight gain, maternal and neonatal outcomes were compared between the intervention and control groups. Data were analysed using Student t, Mann-Whitney and Chi-squared tests as appropriate. A 24-h dietary recall was analysed and compared to the Australian National Nutrition Survey. A significant reduction in gestational weight gain was observed with this intervention (P = 0.010), as well as in the rate of small for gestational age births (P = 0.043). Those who attended the intervention had saturated fat and sodium intake levels that exceeded recommendations. Intake of pregnancy-specific micronutrients including folate, calcium and iron were poor from diet alone. A low-intensity antenatal dietary intervention may be effective in reducing excessive gestational weight gain, although multi-disciplinary interventions yield the best success. Further research is required to identify the optimal modality and frequency to limit excessive gestational weight gain. Dietary interventions tailored to ethnicity should also be explored. Level II, controlled trial without randomization.
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.HLC.2007.02.098
Abstract: Linear and endoventricular techniques of left ventricular (LV) reconstruction often utilise prosthetic material for epicardial reinforcement or endocardial patch. We report a technique of LV aneurysm repair using absorbable suture without prosthetic material. Between November 1999 and August 2004, 55 patients underwent linear LV reconstruction, for ischaemic cardiomyopathy, using only continuous 3/0 polydioxanone suture. Survival, functional class and echocardiographic outcomes are reported. Fifty-two patients (mean age 64+/-10 years) were studied. There was no perioperative mortality and the Kaplan-Meier survival at five years was 81%. Fifty-one patients underwent postoperative follow up (mean 28 months) with echocardiography (mean 20 months). There were no recurrent aneurysms. The postoperative LV eccentricity index (EI) was 0.72 (CI 0.48-0.9). Mean LV ejection fraction increased from 0.33+/-0.09 preoperatively to 0.41+/-0.15 at late follow up (mean within patient change 0.08+/-0.15, p=0.003). Mean symptom class improved from 3.3+/-0.8 to 1.6+/-0.7 (mean within patient improvement 1.6+/-1.0, p<0.001). Mitral regurgitation of grade 2/4 was identified in six patients and grade 3/4 in one patient. Linear repair with absorbable suture material and without prosthetic material may be safely undertaken with good early and mid-term results.
Publisher: Canadian Science Publishing
Date: 09-2008
DOI: 10.1139/F08-101
Abstract: Abalone surveys worldwide measure relative stock abundance. However, important advantages accrue if er surveys measure absolute numbers or biomass per square metre. Principally, absolute biomass permits quota setting from a single survey using a decision table. Although relative abundance surveys have permanently fixed s ling protocols and locations, absolute abundance survey designs can be improved with technology over time. Furthermore, surveys can be directed to areas of principal management focus, and absolute survey population numbers by length with confidence intervals provide informative model input. We propose and test a transect survey design to estimate and map absolute density and biomass of abalone or other sedentary invertebrates. Divers count and measure all abalone within 1 m of a 100 m, boat-deployed leaded rope line. Semi-systematic transect locations provide spatially representative s ling inside bounded survey regions and geostatistical data for contour maps of abalone density and mean size. The effectiveness of the design for estimating change in population size under harvesting and for locating areas of fishable density was tested by a fish-down experiment, using surveys run before and after commercial harvest. The leaded-line survey design estimates of population change and spatial distribution showed agreement with the fish-down experimental harvest.
Publisher: AMPCo
Date: 11-2000
Publisher: Elsevier BV
Date: 06-2012
Abstract: In an ageing population, a greater proportion of geriatric patients will be considered for systemic chemotherapy. Colorectal cancer (CRC) is a common malignancy and will be a major health issue in geriatrics. We used the MAX population to investigate whether age affected the improved outcome found in CRC when bevacizumab is added to capecitabine chemotherapy. MAX, a three arm study of Capecitabine (C) versus CBevacizumab (CB) versus CBMitomycin C (CBM), found an improvement in progression-free survival (PFS), with addition of B [+/- mitomycin C (MMC)] to C. This analysis assesses the effect of adding B (+/- MMC) to C on PFS, overall survival (OS), response rate (RR), toxicity and dose intensity in geriatric patients (age ≥ 75 years). Ninety-nine patients (21%) were aged 75-86 years. Baseline characteristics were well balanced. Eighty-eight per cent commenced C at the lower optional dose of 2000 mg/m(2)/day days 1-14, q21 (61% for 90% in all patients. There were no major differences in toxicity patterns between age cohorts. Addition of B to C significantly improved PFS in this geriatric population, with similar benefits to those aged <75 years. Treatment was well tolerated with no signal of increased toxicity (including thromboembolism) when compared with those aged <75 years.
Publisher: Informa UK Limited
Date: 06-2016
DOI: 10.1080/21678421.2016.1188961
Abstract: Riluzole is an established therapy for amyotrophic lateral sclerosis (ALS), although its effects are modest, prolonging survival by three months on average. While the neuroprotective effects of riluzole appear to be mediated by inhibition of glutaminergic transmission and antagonization of Na
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-1993
DOI: 10.1097/00004836-199306000-00019
Abstract: Gastric and duodenal ulcer (GU,DU) mortality in Western countries has varied over time by age and sex. Temporal variation raises the question of whether these ulcers have an environmental etiology. Using death certificate data, we investigated peptic ulcer mortality time trends from 1971 to 1987 in Sydney, Australia, and whether ulcer mortality and overall mortality in Sydney were similar with regard to time trends and associations with demographic and environmental factors. In men in all age groups and in women age or = 70, GU mortality remained constant and DU mortality increased. Average age at ulcer death increased: from 1971 to 1987, ulcer deaths at age > or = 70 rose from 52 to 80% of all ulcer deaths. In men who died at age 30-54, GU and DU mortality decreased relative to overall mortality. In women who died at age > or = 55, DU mortality increased relative to overall mortality. Compared with overall mortality, the ulcer mortality rate was affected more adversely by lower social class and lack of the marriage tie, and smoking rates tended to correlate more strongly with GU mortality. The greater-than-expected decrease in GU and DU mortality in younger men and the increase in DU mortality in elderly women suggest important changes in as yet unidentified environmental risk factors for ulcer mortality within the young adult male and elderly female general populations.
Publisher: Wiley
Date: 06-2020
DOI: 10.1111/IMJ.14416
Abstract: Cardioembolism (CE) contributes to a large proportion of ischaemic stroke. To evaluate the demographic and clinical profile of CE stroke in Western Sydney. A retrospective analysis of ischaemic stroke patients presenting to Westmead Hospital (January-October 2016) was performed. Strokes were classified by TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria into different categories. Clinical and demographic data were collected on all stroke patients, and differences between CE and other stroke causes were identified. Two hundred and twenty-eight consecutive patients (70.9 years 53% male) were identified. By TOAST criteria, 21 (9%) had large-artery atherosclerosis, 94 (41%) CE, 10 (5%) small-vessel disease, 2 (1%) other aetiology and 101 (44%) undetermined aetiology. A significant proportion of CE stroke patients had cardiovascular risk factors including hypertension (66%), hypercholesterolaemia (50%), diabetes (26%) and ischaemic heart disease (28%). The majority (81%) of patients with CE had atrial flutter/flutter. CE stroke, compared with other types of stroke, was more common in females (56 vs 41%, P = 0.022) and patients with CE stroke were more likely to have previous cerebral ischaemia (34 vs 21%, P = 0.026), suggesting increased recurrence in this group. Of the patients with atrial flutter/flutter (n = 56), the majority (87%) had a high CHA Cardioembolic stroke remains a significant burden in Western Sydney, and it is likely that a significant proportion may be preventable, as evidenced by the substantial presence of modifiable cardiovascular risk factors, and inadequate anticoagulation of patients with atrial arrhythmias.
Publisher: BMJ
Date: 10-11-2020
DOI: 10.1136/GUTJNL-2020-321753
Abstract: Large (≥20 mm) sessile serrated lesions (L-SSL) are premalignant lesions that require endoscopic removal. Endoscopic mucosal resection (EMR) is the existing standard of care but carries some risk of adverse events including clinically significant post-EMR bleeding and deep mural injury (DMI). The respective risk-effectiveness ratio of piecemeal cold snare polypectomy (p-CSP) in L-SSL management is not fully known. Consecutive patients referred for L-SSL management were treated by p-CSP from April 2016 to January 2020 or by conventional EMR in the preceding period between July 2008 and March 2016 at four Australian tertiary centres. Surveillance colonoscopies were conducted at 6 months (SC1) and 18 months (SC2). Outcomes on technical success, adverse events and recurrence were documented prospectively and then compared retrospectively between the subsequent time periods. A total of 562 L-SSL in 474 patients were evaluated of which 156 L-SSL in 121 patients were treated by p-CSP and 406 L-SSL in 353 patients by EMR. Technical success was equal in both periods (100.0% (n=156) vs 99.0% (n=402)). No adverse events occurred in p-CSP, whereas delayed bleeding and DMI were encountered in 5.1% (n=18) and 3.4% (n=12) of L-SSL treated by EMR, respectively. Recurrence rates following p-CSP were similar to EMR at 4.3% (n=4) versus 4.6% (n=14) and 2.0% (n=1) versus 1.2% (n=3) for surveillance colonoscopy (SC)1 and SC2, respectively. In a historical comparison on the endoscopic management of L-SSL, p-CSP is technically equally efficacious to EMR but virtually eliminates the risk of delayed bleeding and perforation. p-CSP should therefore be considered as the new standard of care for L-SSL treatment.
Publisher: Wiley
Date: 03-1996
DOI: 10.1111/J.1365-2893.1996.TB00086.X
Abstract: Virus and host factors have both been linked to the response to interferon treatment among patients with chronic hepatitis C but their relative importance and potential interactions are unclear. Hepatitis C virus genotype and level of viraemia were determined in pretreatment sera from 65 Australian patients treated with interferon-alpha 2b (IFN-alpha 2b), 3 MU tiw for 6 months. Hepatitis C viraemia was quantitated by a competitive reverse transcription-polymerase chain reaction (RT-PCR) method and genotype was determined by a line probe assay. By univariate analysis, there were positive associations between initial (short-term) responses to IFN treatment and younger age (P = 0.004), absence of cirrhosis (P = 0.01), and injecting drug use as risk factor for infection (P = 0.05) but not gender, duration of infection, or level of viraemia. Genotype appeared to be important (P = 0.06) but failed to reach statistical significance. By multivariate analysis, absence of cirrhosis was the only significant independent predictor of treatment response (P = 0.01). Among initial responders, the factors associated with long-term response were the pretreatment HCV RNA titre and the duration of infection. There was a close association between viral genotype, but not viral load, and the severity of liver disease. An interplay of factors determines the outcome of a 6-month course of interferon treatment for hepatitis C. Severity of liver disease, but not the viral load, is the most crucial determinant of initial response to interferon, and histological severity appeared to be influenced by the viral genotype. The level of hepatitis C virus (HCV) viraemia and the duration of infection are independent determinants of long-term response by affecting the relapse rate after interferon treatment.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2000
Abstract: To identify variables that are independent predictors of adverse outcomes in chronic hepatitis C, we analyzed a cohort of 455 patients followed for a median of 4.7 years. Associations were sought between demographic and behavioral factors, hepatitis C virus (HCV) genotype, liver histology and liver tests at entry, and development of liver complications, hepatocellular carcinoma (HCC), hepatic transplantation and liver-related death. Independent predictors were identified by multivariate analysis. The following were associated with a significantly higher rate of liver complications: age birth in Asia, Europe, Mediterranean region, or Egypt transmission by blood transfusion or sporadic cases HCV genotypes 1b and 4 (compared with 1/1a) fibrosis stage 3 or 4 (cirrhosis) serum albumin bilirubin prothrombin time and alpha-fetoprotein. However, the only independent predictors of liver-related complications were sporadic transmission (P <.001), advanced fibrosis (P =.004), and low albumin (P <.001). The corresponding independent risk factors for HCC were male gender (P =. 07), sporadic transmission (P <.001), and albumin (P <.001) bilirubin (P =.02) was an additional predictor of transplantation or liver-related death. It is concluded that only patients with advanced hepatic fibrosis or cirrhosis, are at risk of developing hepatic complications of chronic hepatitis C during 5-year follow-up. Among such patients, abnormalities in serum albumin, bilirubin, or prothrombin time indicate a high probability of complications. Patients without definite risk factors for HCV (sporadic cases) are at higher risk of complications, possibly because of interaction between older age, duration of infection, country of birth, and HCV genotypes 1b and 4.
Publisher: American Society of Hematology
Date: 02-05-2013
DOI: 10.1182/BLOOD-2012-08-448977
Abstract: Infusion of CMV-specific T cells early posttransplant does not increase acute or chronic graft-versus-host disease. CMV-specific T cells early posttransplant reduce the need for pharmacotherapy without increased rates of CMV-related organ damage.
Publisher: American Diabetes Association
Date: 07-2003
DOI: 10.2337/DIACARE.26.7.2005
Abstract: OBJECTIVE—Women who have had gestational diabetes mellitus (GDM) have a high risk of subsequently developing diabetes. However, the contribution of GDM toward the total population of people with diabetes, or its population health impact, has not been examined. Therefore, the aim of this study is to determine the population health significance of GDM by estimating the proportion of cases of diabetes in women that would have been preceded by a pregnancy complicated by GDM. RESEARCH DESIGN AND METHODS—A MEDLINE search was conducted to identify controlled follow-up studies of women with GDM. Meta-analysis of these studies, using the Mantel-Haenszel method for pooling relative risks (RRs), provided an overall RR for the development of diabetes in women with GDM versus control women who had been pregnant without GDM. Recent large studies examining the prevalence of GDM were also reviewed. This enabled the calculation of the population-attributable risk (PAR) for these populations. In this case, the PAR represents the proportion of cases of diabetes among parous women that were associated with previous GDM. RESULTS—From six controlled follow-up studies, the overall RR for developing diabetes after GDM was calculated to be 6.0 (95% CI 4.1–8.8). Applying this to the studies of GDM prevalence, the PAR for GDM ranged from 0.10 to 0.31 (i.e., 10–31% of parous women with diabetes would have experienced a GDM pregnancy earlier). CONCLUSIONS—In some populations, women who have had GDM comprise a substantial proportion of subjects who ultimately develop diabetes. Effective measures to prevent women with GDM from progressing to frank diabetes could therefore have a significant population health impact.
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1080/00313020802035899
Abstract: In recent years histopathology has made an important contribution to the study of familial breast cancer, largely on the basis of the distinctive cancer phenotype commonly identified in BRCA1-mutation carriers. The aim of this study was to identify this phenotype amongst index cases from families in the kConFab familial breast cancer resource with no known pathogenic mutation ('BRCAX' families). The histopathology of breast cancer from 180 in iduals was reviewed: 132 members of in idual BRCAX families, 26 BRCA1 and 15 BRCA2 mutation carriers and seven mutation negative in iduals from families with a known pathogenic mutation. BRCAX breast cancers were a heterogeneous group with 25.8% grade 1, 37.9% grade 2 and 36.4% grade 3. Overall, 45/180 (25%) cases were designated 'BRCA1-phenotype' including 22/132 (16.7%) BRCAX cases, 18/26 (69.2%) BRCA1 and 5/15 (33.3%) BRCA2 mutation carriers. For BRCAX cases, a BRCA1 phenotype designation was negatively correlated with age. Characteristic breast cancer pathology is not diagnostic of a germline BRCA1 mutation, but it does indicate a pathogenic mechanism that occurs with increased frequency in BRCA1 mutation carriers. In BRCAX families, BRCA1 tumour phenotype may signal the presence of an unidentified BRCA1 mutation. However, this finding must be interpreted with regard to limits of the association between histopathology and genotype, and the importance of clinical context.
Publisher: Cambridge University Press (CUP)
Date: 18-12-2015
DOI: 10.1017/ICE.2014.26
Abstract: No previous studies of methicillin-resistant Staphylococcus aureus (MRSA) epidemiology in adult intensive care units (ICUs) have assessed the utility of rapid, highly discriminatory strain typing in the investigation of transmission events. Observational. A 22-bed medical-surgical adult ICU. Those admissions MRSA-positive on initial screening and all admissions hours in duration were excluded, leaving a cohort of 653 patients (median age, 61 years APACHE-II, 19). We conducted this study of MRSA transmission over 1 year (August 1, 2011 to July 31, 2012) using a multiplex PCR-based reverse line blot (mPCR/RLB) assay to genotype isolates from surveillance swabs obtained at admission and twice weekly during ICU stays. MRSA prevalence and incidence rates were calculated and transmission events were identified using strain matching. Colonization pressure was calculated daily by summation of all MRSA cases. Of 1,030 admissions to ICU during the study period, 349 patients were excluded. MRSA acquisition occurred during 31 of 681 (4.6%) remaining admissions 19 of 31(61%) acquisitions were genotype-confirmed, including 7 (37%) due to the most commonly transmitted strain. Moving averages of MRSA patient numbers on the days prior to a documented event were used in a Poisson regression model. A significant association was found between transmission and colonization pressure when the average absolute colonization pressure on the previous day was ≥3 (χ 2 =7.41, P =0.01). mPCR/RLB characterizes MRSA isolates within a clinically useful time frame for identification of single-source clusters within the ICU. High MRSA colonization pressure (≥3 MRSA-positive patients) on a given day is associated with an increased likelihood of a transmission event. Infect Control Hosp Epidemiol 2014 (0):1–9
Publisher: Springer Science and Business Media LLC
Date: 2000
Abstract: We assessed a large number of adults (368 from Australia and 494 from Japan) with de novo acute myeloid leukemia (AML) to define the biological differences between the two populations. In this study, AML was classified using the French-American-British (FAB) criteria into seven groups (M1-M7). M2 was more common in Japan than in Australia, whereas M4 occurred more frequently in Australia than in Japan. Other FAB subtypes were evenly distributed. Cytogenetically, Japanese M2 displayed a higher frequency of t(8 ) than Australian (33.1% vs 15.3%, P < 0.05). The t(15 ), inv/del(16), 11q23 aberrations and 5/7/8 abnormalities were seen at similar frequencies. Immunophenotypically, Japanese M4/M5 more frequently displayed CD13 and CD14 than Australian, whereas the stem cell markers, CD34 and HLA-DR were observed at a relatively higher rate in Australian M3 than in Japanese M3. The B cell antigen, CD19 was more frequently seen in Japanese M2 than in Australian M2, but found more often in Australian M5 than in Japanese M5. In both populations, a close relationship was observed between the expression of CD19 and t(8 ). These findings suggest different biological characteristics of AML between the two populations, the main differences being generated by a higher frequency of t(8 ) chromosomal abnormality in Japanese AML. Leukemia(2000) 14, 163-168.
Publisher: SAGE Publications
Date: 09-2011
DOI: 10.3109/00048674.2011.595685
Abstract: Background: Personality disorder comorbidity has been extensively studied in young adult populations, to a lesser extent in elderly populations, and not at all in an Australian population. This study examines PD comorbidity over the life span 18-100. Aim: The object of this study was to examine the interactions of comorbid personality disorder and age on outcome of Axis I disorders. Method: A total of 238 consecutive consenting eligible psychiatric inpatients were assessed on admission, prior to discharge, and after 6 and 12 months as regards symptoms, function, well-being, relapse and readmission rates and social supports. Outcomes were compared for young (18–40 years old), middle-aged (41–64) and old (65+) patients. Results: Patients improved over time symptomatically and functionally. Across all age groups patients with comorbid personality disorder had worse outcomes than those without, but improved though never to the same extent. Personality disorder was associated with increased rates of relapse and readmission in the whole s le and in the older group, but not increased length of stay. Severity of personality disorder was associated with poorer outcome. Conclusion: Personality disorder adversely affects outcomes, particularly for younger (and older) patients with psychiatric disorders independently of diagnosis and other factors.
Publisher: Wiley
Date: 09-1992
DOI: 10.5694/J.1326-5377.1992.TB137246.X
Abstract: To determine the annual incidence of admissions for paracetamol overdosage in the years 1985 to 1990, morbidity and mortality rates, predictors of poor prognosis and the most appropriate use of N-acetylcysteine (NAC). A retrospective review of case records of all patients with a discharge diagnosis of paracetamol overdosage. A 900-bed tertiary referral teaching hospital in western Sydney with a busy accident and emergency department. 306 patient records were reviewed and details of the overdose and admission were recorded. NAC infusion in patients with possible paracetamol hepatotoxicity. Blood paracetamol levels elevated alanine aminotransferase levels prolonged prothrombin time severe liver injury and NAC side effects. Annual admission rate was constant at circa 55 per annum. Female to male ratio was 2:1. Predictors of liver injury included paracetamol dose over 10 g, presentation more than 10 hours after the overdose and chronic ingestion of more than 80 g alcohol per day. There were no deaths. Fifty-five patients (18%) had toxic paracetamol levels, 51% received treatment with NAC, including 40% of those with non-toxic levels, and 11% of those treated with NAC experienced side effects. Paracetamol overdosage continues to be a significant cause of hospital admissions in western Sydney. Severe hepatic damage occurs infrequently and the prognosis for liver injury, when it occurs, is good. Treatment with NAC should be reserved for patients with definite indications for the drug.
Publisher: BMJ
Date: 2018
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 12-02-2010
DOI: 10.1111/J.1753-6405.1992.TB00073.X
Abstract: Simple indicators such as education, income, occupation, and employment status are often used to adjust for social class in studies of morbidity or mortality. The effect of social class on such outcomes can be different for men and women. In population-based studies, residential area may be the only means of assessing social class. This study investigated sex differences in the association between mortality between 1979 and 1983 and several area indices of social class--percentage with a degree, percentage professional, percentage blue collar, percentage unemployed, percentage with annual income greater than $40,000, and the composite indicator constructed by the Australian Bureau of Statistics. Thirty-seven Sydney statistical local areas were ranked for men and women separately according to the indicators and standardised mortality ratios. Correlations between the indicators and mortality were all negative and stronger for men than for women. The composite indicator and percentage unemployed correlated most strongly with mortality. There was a moderate correlation between the remaining indicators and mortality for men, but only a weak correlation for women. The results suggest that the use of simple area indicators may be inadequate to classify the social class of women, and that the unemployment rate in those over 35 years of age may be a reasonable alternative to the composite indicator for the purpose of social class adjustment in mortality studies.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Elsevier BV
Date: 08-2011
Abstract: Bevacizumab is an antiangiogenic mAb with efficacy against several cancers, but it is associated with risk of arterial thromboembolism (ATE). Further data are needed to determine the safety of bevacizumab. We recorded grade 3, 4, or 5 ATE events and other data (including age, baseline cardiovascular risk factors, history of ATE, and aspirin use) from 471 patients with metastatic colorectal cancer in the MAX (Mitomycin, Avastin, Xeloda) trial of capecitabine monotherapy versus capecitabine with bevacizumab with or without mitomycin C. Bevacizumab-treated patients had 12 grade 3, 4, or 5 ATEs (3.8% incidence). ATEs occurred in 2.1% of patients >65 years, 5% of those with a history of ATE, and 5% of those with cardiac risk factors. Age, history of ATE, or vascular risk factors did not increase risk. Aspirin users had a higher incidence than nonusers (8.9% versus 2.7%) but had higher rates of vascular risk factors. Bevacizumab was associated with a modestly higher risk of ATE, but safety was not significantly worse in older patients or patients with a history of ATE or vascular risk factors. The effect of aspirin in preventing ATE in patients receiving bevacizumab could not be determined from this study.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2012
Publisher: Wiley
Date: 14-12-2019
DOI: 10.1002/CCD.28038
Publisher: Wiley
Date: 2011
Publisher: Wiley
Date: 03-10-2018
DOI: 10.1002/DC.24021
Abstract: The cytomorphological features in the distinction between phyllodes tumour (PT) and fibroadenoma (FA) on fine needle aspiration biopsy (FNAB) remains challenging because of the biphasic nature of these lesions and the rarity of PT. FNAB smears of histologically confirmed PT (N = 26) and FA (N = 78) cases were retrieved from a retrospective database interrogation from the Department of Cytology/Tissue Pathology, ICPMR Pathology West (Cerner Millennium) in Westmead Hospital. For each case, two smears were selected, de-identified and independently reviewed by four observers comprising two cytologists and two cytopathologists. Cytological parameters examined included detailed evaluation of smear cellularity, epithelial and stromal components as well as the smear background. The cytological features of moderate to marked stromal cellularity and stromal nuclear atypia were more evident in PT than in FA, identified by three out of four observers. The epithelial characteristics, presence of macrophages, multinucleated giant cells and blood vessels showed no statistically significant differences in the distinction between the two lesions. The results of this study indicate that in all of the cytological features assessed for PT and FA, no single cytological feature was found to be statistically significant in identifying PT across all observers. This reflects the overlap of cytological features seen in these lesions. FNAB cytology cannot reliably distinguish FA and PT.
Publisher: Springer Science and Business Media LLC
Date: 06-03-2021
DOI: 10.1186/S12913-021-06203-Y
Abstract: While multidisciplinary teams (MDTs) are now considered an essential part of cancer care decision-making, how they perform varies widely. The authors hypothesised that a comprehensive, multipronged improvement program, and associated annual member survey, could strengthen MDT performance across a whole cancer service. The study comprised the introduction of a structured program, the Tumour Program Strengthening Initiative (TPSI) linked with an annual survey of member’s perceptions of their performance. Three iterations of the survey have been completed (2017, 2018 and 2019). Generalised estimating equations (GEEs) were used to test for a difference in the proportion of positive survey responses between 2017 and 2019 adjusted for team clustering. Twelve teams participated in TPSI. One hundred twenty-nine, 118 and 146 members completed the survey in 2017, 2018 and 2019, respectively. Of the 17 questions that were asked in all three years, nine showed significant improvement and, of these, five were highly significant. Documenting consensus, developing Terms of Reference (TORs), establishing referral criteria and referring to clinical practice guidelines showed most improvement. Questions related to patient considerations, professional development and quality improvement (QI) activities showed no significant change. TPSI resulted in sustained and significant improvement. The MDT survey not only allowed MDT members to identify their strengths and weaknesses but also provided insights for management to flag priority areas for further support. Overall program improvement reflected the strengthening of the weakest teams as well as further improvement in highly performing MDTs. Importantly, the initiative has the potential to achieve behaviour change amongst clinicians.
Publisher: Wiley
Date: 10-07-2018
DOI: 10.1111/JOSH.12647
Abstract: School-level socioeconomic status (SES) influences on adolescents' lifestyle behaviors is understudied. We examined how school-level SES and sex influence adolescents' health-related lifestyle behaviors and intentions. Grade 8 students aged 13-14 years completed an online questionnaire regarding their sociodemographic characteristics, dietary behaviors, physical activity participation and recreational screen-time, and intentions regarding these behaviors. School-level SES, based on an Index of Community Socio-Educational Advantage (ICSEA), was categorized as low or high. Generalized estimating equations estimated in idual-level summary statistics, adjusted for clustering. Students (N = 2538 response rate = 79%) from 23 high schools (low ICSEA = 16) participated. Compared with low ICSEA students, high ICSEA students were more likely to report eating breakfast daily (OR 1.9 [95% CI 1.5, 2.4]), not drinking sugar-sweetened beverages (SSBs) daily (2.9 [1.9, 4.3]), and were more likely to have intentions to eat breakfast (1.8 [1.3, 2.3]) and ≥ 5 vegetable serves (1.2 [1.0, 1.5]) daily. Boys were more likely than girls to meet recommendations for breakfast eating, vegetable intake, moderate-to-vigorous physical activity and screen-time, but boys were less likely to meet recommendations regarding SSB intake. Students from low ICSEA schools would benefit from additional support to improve dietary-related behaviors and intentions. More research is required to identify what targeted approaches will address sex differences in adolescents' lifestyle behaviors.
Publisher: Elsevier BV
Date: 08-2003
DOI: 10.1016/S0003-4975(03)00511-3
Abstract: The right phrenic nerve is at risk of injury during high mobilization of the right internal mammary artery (RIMA). The incidence and implications of this injury have not been previously defined. Prospectively collected data on all patients who underwent RIMA harvesting between January 1995 and February 2002 were analyzed. Thirty-one patients with right phrenic nerve injury were identified and the medical charts reviewed. Phrenic nerve injury was diagnosed when a postoperative chest roentgenogram showed the right hemidiaphragm to be two or more intercostal spaces higher than the left, or transection of the nerve was seen intraoperatively. Investigations included fluoroscopy and spirometry in upright and supine positions. Diaphragm plication was offered for symptom control. Subsequent follow-up was undertaken to determine the incidence of spontaneous recovery of diaphragm function and the benefits of diaphragm plication. Seven hundred and eighty-three patients underwent high mobilization of the RIMA with proximal detachment for use as a free graft. Thirty-one patients with right hemidiaphragm dysfunction were identified in the postoperative period providing an injury incidence of 4% (confidence interval, 2.6% to 5.3%). Of these, 12 patients underwent diaphragm plication (4 early and 8 late), 14 patients achieved spontaneous recovery, and 5 patients were lost to follow-up. The supine to upright forced vital capacity ratios at the time of phrenic nerve dysfunction, after diaphragm plication, and after spontaneous recovery were 0.79, 0.90, and 0.96 respectively. The incidence of phrenic nerve injury associated with high RIMA harvesting was 4% but spontaneous recovery may be anticipated in two thirds (14 of 22) of patients in whom the injury is identified postoperatively. High RIMA harvesting should be used with caution in patients with preoperative pulmonary dysfunction in whom phrenic nerve injury would be poorly tolerated.
Publisher: Cold Spring Harbor Laboratory
Date: 11-12-2020
DOI: 10.1101/2020.12.10.419176
Abstract: While loss of BRCA1 promoter methylation has been shown to cause PARP inhibitor (PARPi) resistance in high-grade serous ovarian carcinoma (HGSC), the impacts of RAD51C methylation (me RAD51C ) remain unresolved. In this study, three PARPi-responsive HGSC patient-derived xenografts (PDX) with RAD51C gene silencing and homologous recombination deficiency were found to have either homogeneous or heterogeneous patterns of me RAD51C . PDX could lose me RAD51C following PARPi treatment (rucaparib/niraparib), where a single unmethylated RAD51C copy was sufficient to drive PARPi-resistance. Genomic profiling revealed this resistance was acquired independently in two distinct PDX lineages. Furthermore, we describe a patient s le where 1/3 RAD51C gene copies lost methylation following neoadjuvant chemotherapy. We show me RAD51C is a positive predictive biomarker for PARPi response and should be screened for routinely in patients. However, methylation loss in a single gene copy is sufficient to cause PARPi resistance and should be carefully assessed in previously treated patients considering PARPi therapy.
Publisher: Elsevier BV
Date: 03-2018
Publisher: Oxford University Press (OUP)
Date: 07-2023
Abstract: This study assessed associations of minimum final extrastimulus coupling interval utilized within electrophysiology study (EPS) after myocardial infarction (MI) and possible site of origin of induced ventricular tachycardia (VT) with long-term occurrence of spontaneous ventricular tachyarrhythmia and long-term survival. This prospective study recruited consecutive patients with left ventricular ejection fraction (LVEF) ≤ 40% who underwent EPS days 3–5 after MI between 2004 and 2017. Positive EPS was defined as sustained monomorphic VT cycle length ≥200 ms for ≥10 s or shorter duration if haemodynamic compromise occurred. Each of the four extrastimuli was shortened by 10 ms at a time, until it failed to capture the ventricle (ventricular refractoriness) or induced ventricular tachyarrhythmia. Outcomes included spontaneous ventricular tachyarrhythmia occurrence and all-cause mortality. Shorter coupling interval length of final extrastimulus that induced VT was associated with higher risk of spontaneous ventricular tachyarrhythmia (P & 0.001). Significantly higher rates of spontaneous ventricular tachyarrhythmia (65.2% vs. 23.2% P & 0.001) were observed for final coupling interval at EPS & ms vs. & ms. Right bundle branch block (RBBB) morphology of induced VT, with possible site of origin from the left ventricle, was associated with all-cause mortality [hazard ratio (HR) 3.2, P = 0.044] and a composite of spontaneous ventricular tachyarrhythmia recurrence or mortality (HR 1.8, P = 0.043). Ventricular tachycardia induced with shorter coupling intervals was associated with higher risk of spontaneous ventricular tachyarrhythymia on follow-up, indicating that the final extrastimulus coupling interval at EPS early after MI should be determined by ventricular refractoriness. Induced VT with possible origin from left ventricle was associated with increased risk of spontaneous ventricular tachyarrhythmia recurrence or death.
Publisher: Elsevier BV
Date: 08-1995
DOI: 10.1016/0006-2952(95)00192-3
Abstract: Multivariate linear regression analysis was used to examine the influence of age, gender and environmental variables on the hepatic content of cytochromes P450 (CYP, P450) 1A2, 2C, 2E1 and 3A in 71 subjects 21 with histologically normal livers and 50 with chronic liver disease. There was a clear negative association between age and total P450 content, NADPH-cytochrome c reductase activity and levels of 2E1 and 3A proteins. 1A2 and 2C proteins were unaltered with advancing age. Gender did not influence the expression of any of the CYP proteins. Cigarette smoking was associated with enhanced levels of 1A2, but effects of drug ingestion and alcohol consumption were not apparent in this study, probably because of case selection. It is concluded that age but not gender is a constitutional factor that influences the hepatic content of cytochrome P450 and selected CYP proteins.
Publisher: Wiley
Date: 29-03-2009
DOI: 10.1111/J.1440-1843.2009.01510.X
Abstract: While recent meta-analyses suggest that OSA elevates daytime blood pressure (BP), most studies have included patients with mild hypertension, so CPAP treatment has only reduced BP by 2-3 mm Hg. To determine the strength of the OSA-BP relationship, this study examined the effect of CPAP in a cohort where severe OSA and under-treated hypertension coexist. Baseline demographic and sleep study data were recorded in 221 consecutive patients referred for sleep studies in Samoa. OSA was treated with CPAP and BP recorded for 6-7 months in 180 patients. A subgroup of 64 patients, representative of the entire group, but with regular follow-up, is also described. OSA was diagnosed in 218/221 patients of those who commenced CPAP, 180 returned for follow-up at least once within 7 months. Following CPAP, BP decreased by 7.1/5.9 mm Hg at 1 month and 12.9/10.5 mm Hg at 6 months (n = 180, P < 0.0001). In the 64 patients with regular follow-up, those with the highest baseline BP had the greatest fall in BP with CPAP BP in the hypertensive subgroup (32/64) decreased 21.5/13.1 mm Hg at 6 months (P < 0.0001). Hypertensive OSA patients can exhibit large falls in BP with CPAP at 1 month, with further significant reductions at 3 and 6 months. Overall, the fall in BP was proportional to the initial elevation of the BP with many patients achieving normal BP at 6 months.
Publisher: Elsevier BV
Date: 12-2003
DOI: 10.1053/J.GASTRO.2003.08.032
Abstract: Chronic hepatitis C virus infection is associated with an increased prevalence of type 2 diabetes. We hypothesized that virus-induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection. In 260 hepatitis C virus-infected subjects, we examined the relationship between histological findings and anthropometric and biochemical data, including insulin resistance determined by the homeostasis model assessment (HOMA-IR). We also compared fasting serum insulin, C peptide, and HOMA-IR levels between the subset of 121 hepatitis C virus patients with stage 0 or 1 hepatic fibrosis and 137 healthy volunteers matched by sex, body mass index, and waist-hip ratio. Hepatitis C virus-infected subjects with stage 0 or 1 hepatic fibrosis had higher levels of insulin, C peptide, and HOMA-IR (all P < or = 0.01) compared with matched healthy controls. In the 250 hepatitis C virus patients (fibrosis stage 0 to 4), viral genotype and portal, but not lobular, inflammation were univariate predictors of HOMA-IR. By multiple linear regression analysis, independent predictors of HOMA-IR included body mass index (P < 0.001), previous failed antiviral treatment (P < 0.001), portal inflammatory grade (P < 0.001), and genotype 3 status (P = 0.01). Genotype 3 had significantly lower HOMA-IR than other genotypes (which were comparable when adjusted for effects of the remaining independent predictors). HOMA-IR was an independent predictor for the degree of fibrosis (P < 0.001) and the rate of fibrosis progression (P = 0.03). Hepatitis C virus may induce insulin resistance irrespective of the severity of liver disease, and this effect seems to be genotype specific. Further, our findings support the hypothesis that insulin resistance may contribute to fibrotic progression in chronic hepatitis C virus infection.
Publisher: Informa UK Limited
Date: 1978
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1016/J.SLEEP.2004.08.004
Abstract: Obstructive sleep apnea (OSA) is associated with intermittent hypoxia and cognitive decrements. As the hippoc us is particularly susceptible to hypoxia, we hypothesized that it may show biochemical abnormalities, and they may relate to apnea severity. Eight males with OSA and five age-matched controls underwent neurocognitive testing before and after polysomnography and proton magnetic resonance spectra were obtained from the left hippoc al area of all subjects. In the left hippoc al area, N-acetyl-containing/creatine-containing compounds was significantly increased in OSA (P=0.04). Inspection of these compounds with respect to the water resonance indicated that this was most likely due to a decrease in creatine-containing compounds rather than any change in N-acetyl-containing compounds. Lower levels of hippoc al creatine-containing compounds were correlated with worse OSA severity and neurocognitive performance. We suggest the changes in creatine levels in the hippoc al area represent adjustments to brain bioenergetics, similar to those seen in ischemic preconditioning, and may reflect the different susceptibility of these tissues to hypoxic damage in OSA.
Publisher: Springer Science and Business Media LLC
Date: 2009
DOI: 10.1007/S00701-008-0171-7
Abstract: Intracranial electrode monitoring is still required in epilepsy surgery however, it is associated with significant morbidity. To identify risk factors associated with complications during invasive intracranial EEG monitoring. Retrospective study of all patients undergoing invasive monitoring at Westmead between 1988-2004. From detailed chart reviews, the following variables were recorded: duration of intracranial monitoring, the site of grid implantation, number of grids and electrodes, seizure frequency, postoperative complications and seizure outcome. Seventy-one patients (median age: 24 years) underwent subdural electrode implantation 62% had extratemporal lobe epilepsy and 46% were non-lesional. Of the 58 monitored patients who had cortical resections, 45 had good seizure outcomes. Complications related to subdural electrode implantation included transient complications requiring no treatment (12.7%), transient complications requiring treatment (9.9%) and two deaths (2.8%). Specific complications included subdural haemorrhage, transient neurological deficit, infarction and osteomyelitis. The two deaths occurred within 48 h of implantation were related to raised intracranial pressure (one venous infarction, one unexplained). Complications were associated with maximal size of grid (p < 0.001), greater number of electrodes (p < 0.001), electrode density per cortical surface implanted (p < 0.001), right central surface implantation (p = 0.003) and left central surface implantation (p = 0.013). Multiple logistic regression identified larger size grids and right central surface implantation as independent predictors of complications. There are significant complications during intracranial EEG evaluations but the majority of these are transient. We found a relationship between the size of the electrode arrays and the incidence of complications. The results of this study have been used to modify our implantation and monitoring protocols.
Publisher: Oxford University Press (OUP)
Date: 06-08-2008
DOI: 10.1016/J.EUJE.2007.06.002
Abstract: This study evaluates a simple echocardiographic rhythm independent expression of left atrial (LA) function, 'the left atrial function index' (LAFI). Quantitation of LA function is challenging and often established parameters including peak A are limited to sinus rhythm (SR). We hypothesized that atrial function could be characterized independent of rhythm by combining analogues of LA volume, reservoir function and LV stroke volume. Seventy-two patients with chronic atrial fibrillation (CAF) were followed for six months post cardioversion (CV). Thirty-seven age matched healthy subjects were controls. The LAFI = LAEF x LVOT-VTI/LAESVI (LAEF = LA emptying fraction, LAESVI = maximal LA volume indexed to BSA, LVOT-VTI = outflow tract velocity time integral). The LAFI pre-CV in the CAF group was depressed vs controls (0.10 +/- 0.05 vs 0.54 +/- 0.17 P = 0.0001). Post-CV, LAFI was lower in persistent AF than in those restored to SR (AF vs SR: 0.08 +/- 0.03 vs 0.15 +/- 0.08 P = 0.0001), improved progressively in SR and was unchanged when AF persisted. The LAFI, a simple, rhythm independent expression of atrial function, appears sensitive to differences between in iduals in AF and those restored to SR and justifies clinical and investigative applications.
Publisher: BMJ
Date: 27-07-2016
DOI: 10.1136/GUTJNL-2015-309848
Abstract: Perforation is the most serious complication associated with endoscopic mucosal resection (EMR). We propose a new classification for the appearance and integrity of the muscularis propria (MP) after EMR including various extents of deep mural injury (DMI). Risk factors for these injuries were analysed. Endoscopic images and histological specimens of consecutive patients undergoing EMR of colonic laterally spreading lesions ≥20 mm at a large Australian tertiary referral endoscopy unit were retrospectively analysed using our new DMI classification system. DMI was graded according to MP injury (I/II intact MP without/with fibrosis, III target sign, IV/V obvious transmural perforation without/with contamination). Histological specimens were examined for included MP and patient outcomes were recorded. All type III-V DMI signs were clipped if possible, types I and II DMI were clipped at the endoscopists' discretion. EMR was performed in 911 lesions (mean size 37 mm) in 802 patients (male sex 51.4%, mean age 67 years). DMI signs were identified in 83 patients (10.3%). Type III-V DMI was identified in 24 patients (3.0%) clipping was successfully performed in all patients. A clinically significant perforation occurred in two patients (0.2%). Only one of the 59 type I/II cases experienced a delayed perforation. 85.5% of patients with DMI were discharged on the same day, all without sequelae. On multivariable analysis, type III-V DMI was associated with transverse colon location (OR 3.55, p=0.028), en bloc resection (OR 3.84, p=0.005) and high-grade dysplasia or submucosal invasive cancer (OR 2.97, p 0.014). In this retrospective analysis, use of the new classification and management with clips appeared to be a safe approach. Advanced DMI types (III-V) occurred in 3.0% of patients and were associated with identifiable risk factors. Further prospective clinical studies should use this new classification. NCT01368289 results.
Publisher: Wiley
Date: 05-1992
DOI: 10.1111/J.1360-0443.1992.TB02714.X
Abstract: The aim of this study was to evaluate the assessment policies of a regional unit established to process requests for entry to several long-term methadone maintenance programmes. The factors which led staff to reject an applicants request for methadone maintenance were retrospectively analysed from assessment records. Analysis indicated that the decision to reject applicants had been based on the judgement that they were not physically dependent on opioids other factors favouring rejection included less involvement in crime, youth, and short duration of drug use. Eighty-four applicants who had either been rejected (n = 58) or failed to complete the assessment (n = 26) were followed. At follow-up, more than half of the subjects had entered methadone programmes, usually after a long delay. Four subjects had achieved a degree of stable abstinence. The remainder were continuing to use illicit drugs, or were in treatment or prison. Four subjects had died. We conclude that: (1) our criteria for excluding people from treatment were based on the perceived need to keep non-addicted people from maintenance treatment and (2) such a policy in practice served to prolong the applicants' illicit drug use and delay their entry to treatment.
Publisher: Public Library of Science (PLoS)
Date: 22-04-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-01-2019
DOI: 10.1212/WNL.0000000000006876
Abstract: The aim of the study was to assess the utility of a novel amyotrophic lateral sclerosis (ALS) diagnostic index (ALSDI). A prospective multicenter study was undertaken on patients presenting with suspected ALS. The reference standard (Awaji criteria) was applied to all patients at recruitment. Patients were randomly assigned to a training (75%) and a test (25%) cohort. The ALSDI was developed in the training cohort and its diagnostic utility was subsequently assessed in the test cohort. A total of 407 patients were recruited, with 305 patients subsequently diagnosed with ALS and 102 with a non-ALS mimicking disorder. The ALSDI reliably differentiated ALS from neuromuscular disorders in the training cohort (area under the curve 0.92, 95% confidence interval 0.89–0.95), with ALSDI ≥4 exhibiting 81.6% sensitivity, 89.6% specificity, and 83.5% diagnostic accuracy. The ALSDI diagnostic utility was confirmed in the test cohort (area under the curve 0.90, 95% confidence interval 0.84–0.97), with ALSDI ≥4 exhibiting 83.3% sensitivity, 84% specificity, and 83.5% diagnostic accuracy. In addition, the diagnostic utility of the ALSDI was confirmed in patients who were Awaji negative at recruitment and in those exhibiting a predominantly lower motor neuron phenotype. The ALSDI reliably differentiates ALS from mimicking disorders at an early stage in the disease process. This study provides Class I evidence that for patients with suspected ALS, the ALSDI distinguished ALS from neuromuscular mimicking disorders.
Publisher: Oxford University Press (OUP)
Date: 03-1999
Abstract: To compare the efficacy of sotalol versus amiodarone for long-term treatment of ventricular tachyarrhythmias. Patients (n=75) with spontaneous, sustained ventricular tachyarrhythmias secondary to remote myocardial infarction were studied. After intravenous electrophysiological testing, both sotalol and amiodarone were predicted to be ineffective in 50 (67%) patients. Five patients were excluded. Forty-five patients were randomized to receive sotalol (n=22) or amiodarone (n=23) for maintenance therapy. The primary outcome variable was the time to first recurrence of sustained ventricular tachyarrhythmia. At 36 months. 75% of those allocated sotalol remained free of ventricular tachyarrhythmia compared with 38% of those allocated amiodarone (P=0.05). On multivariate analysis the risk of recurrence of ventricular tachyarrhythmia for patients on amiodarone was 5.9 times higher (P=0.008) than that for patients on sotalol. Sotalol is superior to amiodarone for long-term treatment of ventricular tachyarrhythmia secondary to coronary artery disease when both drugs have been predicted to be ineffective at intravenous electrophysiological testing. Randomized trials in larger numbers of patients with ventricular tachyarrhythmia need to be performed comparing the two agents directly.
Publisher: Elsevier BV
Date: 08-2013
Publisher: Wiley
Date: 23-03-2016
DOI: 10.1111/AJO.12462
Abstract: Hypothyroidism in pregnancy is associated with adverse obstetrical events and neurodevelopmental disorders in infants. The prevalence of thyroid dysfunction during pregnancy in Australia is not well documented, and universal screening remains questionable. To assess the prevalence of thyroid dysfunction and positive thyroid antibodies and review the indications for universal screening of thyroid function in pregnancy. The prospective observational study was undertaken between 2009 and 2014. Thyroid-stimulating hormone (TSH), free thyroxine (FT4) levels, thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb) were measured in 1069 women at booking-in. One hundred and three women, (9.6%), exhibited subclinical hypothyroidism, with TSH levels >2.5mIU/l. Eighty-seven women (8.1%) had TSH levels > 2.5 and ≤5 mIU/l. Of these, 41.4% (36 patients) were positive for TPOAb. Twelve women (1.5%) had a TSH >5 and ≤10 mIU/l with 66.7% (8 patients) positive for TPOAb. Four patients (0.4%) had a TSH level >10 mIU/l with 50% (2 patients) positive for TPOAb. Positive thyroid antibodies were detected in 258 patients (24.13%). Although statistically significant, the rank correlations between TSH and TPOAb (r = 0.08, P = 0.023) and TgAb (r = -0.081, P = 0.021) were weak. Similarly, weak rank correlations were observed between TSH and age (r = -0.095), parity (r = -0.081) and weight (r = 0.089). A high prevalence of subclinical hypothyroidism and positive thyroid antibodies exists in this cohort, as well as unsuspected chemical hypothyroidism, providing a strong case for universal screening with TSH and the consideration of thyroid antibody testing of all Australian pregnant women.
Publisher: American Medical Association (AMA)
Date: 20-06-2011
DOI: 10.1001/ARCHDERMATOL.2011.133
Abstract: To determine whether certain patient demographics are associated with poorer specificity for the diagnosis of melanoma in nevi undergoing short-term sequential digital dermoscopic imaging. Retrospective cohort study performed from April 1, 1998, through May 31, 2007. Sydney Melanoma Diagnostic Centre, a tertiary referral institution. A total of 2497 benign melanocytic lesions in 1765 patients undergoing short-term sequential digital dermoscopic imaging during 2.5 to 4.5 months (42.3% male mean [SD] age, 40 [14] years age range, 1-86 years). Proportion of changed nevi as a function of age, sex, lesion diameter, and anatomical site. The only variable significantly associated with nevus change was age group (P = .002). When compared with the middle-aged (aged 36-50 years) group, the odds of change were significantly increased in the child and adolescent (aged 0-18 years: odds ratio, 2.60 95% confidence interval, 1.30-5.22), young adult (aged 19-35 years: 1.50 1.04-2.17), and elderly (> 65 years old: 2.04 1.04-3.99) age groups. Within the changed benign lesions, a significant association was observed between histologic subtype and age group (P = .01). The proportion of changed lesions of the banal nevi type decreased and the proportion of the dysplastic nevi type increased with age. In the elderly group, 75.9% of changed lesions were of the dysplastic nevi type compared with 35.7% in the youngest group. A poorer specificity is observed for the diagnosis of melanoma for nevi undergoing short-term sequential digital dermoscopic imaging in children and adolescents (75.7%) and elderly patients (77.9%) compared with other patients (84.6%).
Publisher: Oxford University Press (OUP)
Date: 12-02-2018
DOI: 10.1093/IJE/DYY013
Abstract: We propose methods to determine the minimum number of subjects remaining at risk after which Kaplan-Meier survival plots for time-to-event outcomes should be curtailed, as, once the number remaining at risk drops below this minimum, the survival estimates are no longer meaningful in the context of the investigation. The size of the decrease of the Kaplan-Meier survival estimate S(t) at time t if one extra event should occur is considered in two ways. In the first approach, the investigator sets a maximum acceptable absolute decrease in S(t) should one extra event occur. In the second, a minimum acceptable number of subjects still at risk is calculated by comparing the size of the decrease in S(t) if an extra event should occur with the variability of the survival estimate had all subjects been followed to that time (confidence interval approach). We recommend calculating both limits for the number still at risk and then making an informed choice in the context of the particular investigation. We explore further how the amount of information actually available can assist in considering issues of data maturity for studies whose outcome of interest is a survival percentage at a particular time point. We illustrate the approaches with a number of published studies having differing s le sizes and censoring issues. In particular, one study was the subject of some controversy regarding how far in time the Kaplan-Meier plot should be extended. The proposed methods allow for limits to be calculated simply using the output provided by most statistical packages.
Publisher: Elsevier BV
Date: 08-2020
Publisher: American Medical Association (AMA)
Date: 12-2015
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1053/J.GASTRO.2018.10.003
Abstract: Colorectal cancer (CRC) can be prevented by colonoscopy and polypectomy. Endoscopic mucosal resection (EMR) is performed to remove large laterally spreading colonic lesions that have a high risk of progression to CRC. Endoscopically invisible micro-adenomas at the margins of the EMR site might contribute to adenoma recurrence, which occurs in 15% to 30% of patients who undergo surveillance. We aimed to determine the efficacy of adjuvant thermal ablation of the EMR mucosal defect margin in reducing polyp recurrence. We performed a prospective study of 390 patients with large laterally spreading colonic lesions (≥ 20 mm, n = 416) referred for EMR at 4 tertiary centers in Australia. After complete lesion excision by EMR, lesions were randomly assigned to thermal ablation of the post-EMR mucosal defect margin (n = 210) or no additional treatment (controls, n = 206). We performed surveillance colonoscopies with standardized photo documentation and biopsies of the scar after 5 to 6 months. Patient, procedure, and lesion characteristics were similar between the groups. The primary endpoint was detection of lesion recurrence at first surveillance colonoscopy. A significantly lower proportion of patients who received thermal ablation of the post-EMR mucosal defect margin had evidence of recurrence at first surveillance colonoscopy (10/192, 5.2%) than controls (37/176, 21.0%) (P < .001). The relative risk of recurrence in the thermal ablation group was 0.25 compared with the control group (95% confidence interval 0.13-0.48). Rates of adverse events were similar between the groups. In a multicenter randomized trial, thermal ablation of the post-EMR mucosal defect margin significantly reduced polyp recurrence at first surveillance colonoscopy, compared with no additional treatment. Routine implementation of this simple and safe technique could increase the utility of EMR, decrease surveillance burdens, and reduce morbidity and mortality from CRC. ClinicalTrials.gov no: NCT01789749.
Publisher: Informa UK Limited
Date: 1991
DOI: 10.3109/00365529109037016
Abstract: The purpose of this study was to investigate whether any specific causes of death were more frequent than expected in an Australian group of 305 gastric ulcer patients (131 men, 174 women) who had died in New South Wales between 1 January 1974 and 31 December 1983. The distribution of causes of death among the ulcer population deaths was compared with that among the New South Wales population deaths, after adjusting for sex, 5-year age group, and time period of death (1974-1978, 1979-1983). Causes of death were ascertained from death certificates. Deaths due to peptic ulcer, liver cirrhosis, and diffuse pulmonary disease were more frequent than expected (p less than 0.05). The associations found with these other diseases accord with those found in previous surveys on causes of death in gastric ulcer patients and in studies of living gastric ulcer populations. Overall, the combined evidence suggests that liver cirrhosis and diffuse pulmonary disease are associated with gastric ulcer.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2019
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.JAAD.2019.06.035
Abstract: The treatment response to new immunotherapy in advanced melanoma patients remains varied between in iduals. Immune-related cutaneous side effects might have prognostic value. To determine whether development of ≥1 of the 3 immune-mediated cutaneous events (eczema, lichenoid reaction, or vitiligo-like depigmentation) is associated with improved progression-free survival. A cohort study of adults with stage IIIC-IV melanoma treated with pembrolizumab or nivolumab during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. Treatment response was based on iRECIST version 1.1. In total, 82 patients of an average age of 59.9 years were included. Median follow-up was 40.7 months 33 patients had ≥1 target skin reaction. Skin reactions developed in one-third of in iduals by 6 months. At any given time, the instantaneous risk of disease progression and death was lower for in iduals who had ≥1 cutaneous adverse event (CAE) develop. Compared with in iduals with no CAE, the hazard ratio for disease progression and death for in iduals who had ≥1 CAE develop was 0.46 (95% confidence interval 0.23-0.91 P = .025) by the time-dependent Cox proportional hazards model. Single-center study. This study demonstrates an association between the development of ≥1 of 3 CAEs and improved progression-free survival in this cohort of patients.
Publisher: Elsevier BV
Date: 2010
DOI: 10.3109/00313020903434355
Abstract: Columnar cell lesions (CCLs) of the breast have been increasingly recognised in biopsies taken to investigate mammographic screen detected microcalcification. The aim of this study was to identify distinct CCL subtypes by systematic analysis of histopathology. Hierarchical cluster analysis was performed based on the profile of histopathological features in 102 screen detected CCLs. Features assessed included nuclear morphology, acinar dilatation, epithelial cell hyperplasia, cell crowding, apical snout formation and intraluminal secretion. The stability of this classification was tested in an independent cohort of 32 cases. The histopathology of screen detected CCLs was extremely variable. Hierarchical cluster analysis identified two subclasses: Class 1 (34/102, 33%) characterised by absence of nuclear atypia and less pronounced hyperplasia and Class 2 (68/102, 67%) that were generally more atypical. Ki-67 scores were significantly lower for Class 1 CCLs (p < 0.001). In the independent cohort of 32 cases, Class 1 cases were clearly distinguished from Class 2, indicating that these were stable phenotypes amongst screen detected CCLs. The histopathological features of CCLs diagnosed at screening are extremely heterogeneous. Using a systematic approach, we have devised a broad classification system that delineates a category of less atypical CCLs that could form a basis for future studies.
Publisher: BMJ
Date: 08-01-2014
DOI: 10.1136/JCLINPATH-2013-201793
Abstract: To evaluate the utility of Ki67 as a prognostic marker in a series of patients with node-negative breast cancer untreated with adjuvant systemic therapy. The cohort consisted of 203 cases treated with breast conserving surgery and radiation only median follow-up was 183 months (range 156-277 months). An immunohistochemical panel of oestrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK)5/6 and Ki67 and human epidermal growth factor 2 in situ hybridization (HER2-ISH) was performed on the tumour s les. Ki67 scores were evaluable in 193/203 patients (95.1%). The primary outcome was breast cancer specific survival (BCSS). Of the cohort, 29 (14.2%) died of breast cancer. A cut off of 10% separated tumours into a 'Ki67-low' (n=70) or 'Ki67-high' group (n=123). The breast cancer specific survival was 97.1% and 77.6% for Ki67-low and Ki67-high groups, respectively. Univariate analysis showed that in this lymph node-negative cohort, the predictors for BCSS were tumour size, Ki67, LVI, age and histological grade 3. Multivariable analysis showed that Ki67 index and lymphovascular space invasion were independent predictors of breast cancer death. To examine the utility of Ki67 in assignment of immunohistochemically molecular subtypes, cases were assigned into Luminal A (ER-positive, HER2-negative, Ki67 ≤14%), Luminal B (ER-positive, HER2-negative, Ki67 >14%) and triple negative (ER/PR-negative and HER2-negative, any Ki67). The 15-year breast cancer specific survival was 91.7%, 79.4% and 75.8%, respectively. A statistically significant difference in breast cancer specific survival is seen in groups defined using Ki67 and receptor status, whereas histological grading was not a significant predictor of survival. Ki67 immunostaining provides prognostic information beyond traditionally assessed clinicopathological variables.
Publisher: JSTOR
Date: 03-1982
DOI: 10.2307/2530295
Publisher: Elsevier BV
Date: 05-2005
DOI: 10.1016/J.CLINPH.2004.12.001
Abstract: To examine response decrement of the recently reported inspiratory skin conductance response (SCR) [Lim CL, Seto-Poon M, Clouston PD, Morris JG. Sudomotor nerve conduction velocity and central processing time of the skin conductance response. Clin Neurophysiol 2003 :2172-80]. Twelve healthy adult volunteers performed 3 tasks (A) a control task of maintaining tidal breathing and then two randomized tasks, (B) a deep inspiration to a target oral pressure and (C) tapping with a finger. Each task was performed 30 times on cue every 20s in 3 runs with 5 min of rest between runs. The SCR, oral pressure, airflow, inspired volume and cue signal were recorded continuously and analysed offline. SCR litude was logarithmically transformed and then statistically analysed, using a linear mixed effects model, as a function of run number, trial number and absolute error between target and actual oral pressures. Inspiratory efforts elicited exponentially decreasing SCR litude with increasing trial number during each run (P < 0.0001). After adjusting for trial number, the mean SCR litude of the second and the third run were, respectively, 24.2 (95% CI (0.175, 0.336), P < 0.001) and 14.4% (95% CI (0.104, 0.200), P < 0.001) of the first run litude. Volitional deep inspiration reliably activates an SCR that exhibits response decrement with repetition, which may be habituation. The volitional inspiratory SCR may assist in the assessment of sympathetic autonomic status in patients with peripheral afferent neuropathy.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2017
Publisher: Wiley
Date: 10-2003
DOI: 10.1046/J.1460-9592.2003.00305.X
Abstract: Transmural recordings using plunge needle electrodes are useful in mapping ventricular tachyarrhythmia, but they interfere with activation sequences or damage the myocardium. This study evaluated the effects of insertion of 66 transmural needles on myocardial activation, structure, and function. Epicardial maps were performed at thoracotomy using a 40-electrode plaque in five mongrel dogs. Sixty-six transmural plunge needles were introduced into the anterior aspect of the septum and left ventricle. Transmural maps of unipolar electrograms were recorded every 15 minutes via 124 electrodes over a 2-hour period. Epicardial maps were repeated after the needles were removed. All recordings were performed during sinus rhythm and ventricular pacing at 300- and 200-ms cycle lengths. Gated heart pool studies were performed preoperatively and 2 weeks after thoracotomy. Programmed ventricular stimulation was performed 2 weeks after thoracotomy. In total, 15,996 electrograms were analyzed. Maximum negative dV/dt of each electrogram and the activation time at each electrode did not change significantly over the 2 hours of needle insertion. After removal of the needles, epicardial maps were unchanged compared to before needle insertion. Mean left ventricular ejection fraction 2 weeks after needle insertion was 59% versus 58% before needle insertion (P=0.9). No dogs had inducible ventricular tachycardia. Histology showed contraction bands of 0.8-mm diameter adjacent to the needle tracks but no scarring. Insertion of 66 closely spaced plunge needles did not distort epicardial or transmural maps. Multiple needles did not result in myocardial scarring, left ventricular dysfunction, or predispose to ventricular tachycardia.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2014
DOI: 10.1038/SREP04669
Publisher: SLACK, Inc.
Date: 2004
DOI: 10.3928/1081-597X-20040101-03
Abstract: ABSTRACT PURPOSE: To assess vision in patients with myopia and myopic astigmatism before and after refractive surgery. METHODS: A prospective controlled study of visual quality amongst myopes and astigmatic myopes. Focus groups, ophthalmic surgeons, and questionnaire experts devised a Subjective Vision Questionnaire (SVQ), modified after a pilot trial. Participants were administered the SVQ before clinical evaluation. Items answered by over 95%, with factor loadings .55 were included. Test-retest reliability was assessed by repeat testing. Factor analysis identified groups of questions measuring particular dimensions of data. RESULTS: Sixty-seven items were answered by 128 patients and reduced to 24 items in a final questionnaire. Factor analysis identified six types of questions within the questionnaire, the most important of which was related to driving. CONCLUSION: The simplicity, low cost, and psychometric properties of the Subjective Vision Questionnaire support its use clinically and in research. [J Refract Surg 2004 :10-19]
Publisher: BMJ
Date: 11-1999
DOI: 10.1136/FN.81.3.F162
Abstract: To examine the role of Ureaplasma urealyticum colonisation or infection in neonatal lung disease. Endotracheal aspirates from ventilated infants less than 28 weeks of gestation were cultured for U urealyticum and outcomes compared in infants with positive and negative cultures. U urealyticum was isolated from aspirates of 39 of 143 (27%) infants. Respiratory distress syndrome (RDS) occurred significantly less often in colonised, than in non-colonised infants (p=0.002). Multivariate logistic regression analysis showed that in singleton infants, ureaplasma colonisation was the only independent (negative) predictor of RDS (OR 0.36 p=0. 02). Both gestational age (OR 0.46 p=0.006) and isolation of U urealyticum (OR 3.0 p=0.05) were independent predictors of chronic lung disease (CLD), as defined by requirement for supplemental oxygen at 36 weeks of gestational age. Multiple gestation was also a major independent predictor of RDS and CLD. Colonisation or infection with ureaplasma apparently protects premature infants against the development of RDS (suggesting intrauterine infection). However, in singleton infants, it predisposes to development of CLD, independently of gestational age. Treatment of affected infants after birth is unlikely to significantly improve the outcome and methods are required to identify and treat the women with intrauterine ureaplasmal infection, before preterm delivery occurs.
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 28-09-2018
DOI: 10.1038/S41467-018-05564-Z
Abstract: Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2 -mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1 -methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1- methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2012
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.LEUKRES.2006.03.009
Abstract: The tumor protein D52 gene or protein is frequently overexpressed in several carcinomas, and has been identified as a B cell differentiation marker. D52-like genes are also differentially expressed in particular haematological malignancies, where transcript or protein levels may reflect cellular proliferative or differentiative status. We used RT-PCR to analyse the expression of three D52-like genes in bone marrow at the time of ALL or AML diagnosis in children. Whereas D53 transcripts were undetectable in all s les, D52 and D54 transcripts were frequently detected in ALL and AML, where they were frequently co-expressed. While D52 and D54 transcripts were detected in T-ALL and pre-B ALL at comparable frequencies, D52 was less frequently detected in ALL bone marrow with hyperdiploid karyotypes, compared with s les with normal karyotypes. We also found that total RNA yields significantly differed according to D52 and D54 expression status, and that bone marrow freezer storage time (up to 945 days) differed significantly according to D52 expression status. These results indicate that D52-like genes are not ubiquitously expressed in leukemic bone marrow in children, and that RNA s le parameters may influence measures of gene expression more than commonly appreciated.
Publisher: AMPCo
Date: 02-2006
Publisher: The Endocrine Society
Date: 03-2006
DOI: 10.1210/JC.2005-1862
Abstract: The identification of mutations in genes encoding peptides of succinate dehydrogenase (SDH) in pheochromocytoma araganglioma syndromes has necessitated clear elucidation of genotype-phenotype associations. Our objective was to determine genotype-phenotype associations in a cohort of patients with pheochromocytoma araganglioma syndromes and succinate dehydrogenase subunit B (SDHB) or subunit D (SDHD) mutations. The International SDH Consortium studied 116 in iduals (83 affected and 33 clinically unaffected) from 62 families with pheochromocytoma araganglioma syndromes and SDHB or SDHD mutations. Clinical data were collected between August 2003 and September 2004 from tertiary referral centers in Australia, France, New Zealand, Germany, United States, Canada, and Scotland. Data were collected on patients with pheochromocytomas and/or paragangliomas with respect to onset of disease, diagnosis, genetic testing, surgery, pathology, and disease progression. Clinical features were evaluated for evidence of genotype-phenotype associations, and penetrance was determined. SDHB mutation carriers were more likely than SDHD mutation carriers to develop extraadrenal pheochromocytomas and malignant disease, whereas SDHD mutation carriers had a greater propensity to develop head and neck paragangliomas and multiple tumors. For the index cases, there was no difference between 43 SDHB and 19 SDHD mutation carriers in the time to first diagnosis (34 vs. 28 yr, respectively P = 0.3). However, when all mutation carriers were included (n = 112), the estimated age-related penetrance was different for SDHB vs. SDHD mutation carriers (P = 0.008). For clinical follow-up, features of SDHB mutation-associated disease include a later age of onset, extraadrenal (abdominal or thoracic) tumors, and a higher rate of malignancy. In contrast, SDHD mutation carriers, in addition to head and neck paragangliomas, should be observed for multifocal tumors, infrequent malignancy, and the possibility of extraadrenal pheochromocytoma.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2002
DOI: 10.1097/00042752-200209000-00007
Abstract: To assess change in symptoms, quality of life (QOL), and performance ability before, during, and after treatment with budesonide in a group of Olympic and Paralympic athletes with seasonal allergic rhinoconjunctivitis (SAR/C). Because budesonide has already been proven to be an effective and well-tolerated treatment of SAR/C(1), an open-label treatment format was used. The study was community-based with participating athletes preparing for Olympic competition. Olympic and Paralympic athletes were screened for the presence of SAR/C using history and positive skin test results for pollen allergens. All were offered treatment with intranasal budesonide, applied to each nostril, once daily for eight weeks. Symptom and medication diaries were completed before treatment and after 4 and 8 weeks of treatment. Similarly, Quality of Life (QOL) was measured with the Rhinoconjunctivitis Quality of Life Questionnaire. As a secondary outcome measure, the ability to train and compete was assessed using a performance diary. Of the 236 athletes eligible for the study, 145 (61%) agreed to participate. Forty-six percent of the athletes who were dispensed treatment did not return questionnaires. For those returning questionnaires, scores between baseline (week 0) and weeks 4 and 8 were calculated for total symptoms, QOL, and performance scores. There were statistically significant improvements in symptoms, QOL, and performance scores in athletes who used intranasal budesonide. SAR/C is a common condition and has demonstrable negative effects on athletes. Better education of coaches and athletes is necessary to ensure that the condition is correctly diagnosed and treated, with safe, effective, permitted medication.
Publisher: Wiley
Date: 30-04-2004
Publisher: Wiley
Date: 02-1992
DOI: 10.1111/J.1360-0443.1992.TB02699.X
Abstract: The impact of different approaches to methadone maintenance on the level of crime committed by heroin addicts was examined in a cohort of addicts entering methadone treatment. The cohort comprises three groups: 72 subjects (group 1) who were approved for treatment and referred to a long-term programme which tolerated continued illicit drug use in treatment 159 subjects (group 2) who were referred to an abstinence orientated programme from which clients who continued to use heroin were expelled and 84 subjects who were rejected as unsuitable or failed to complete the assessment process. Official records of convictions were used to calculate conviction rates in the pre- and post-assessment periods. Differences between groups in conviction rates for drug and property crimes were analysed using Poisson regression. Three variables--age, sex and age of first criminal conviction--were significant predictors of conviction rates and all analyses controlled for these variables. Most of the rejected subjects entered treatment during the study period and it was, therefore, not possible to interpret differences between treated and untreated subjects. Among those who entered treatment, property offence rates actually rose, due to a significant increase in conviction rates in group 2. Subjects in group 1 were retained significantly longer in treatment than those in group 2. Among those who remained in treatment less than 12 months, most offences occurred after leaving treatment. When conviction rates were adjusted for time spent in treatment, the differences between the clinics disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: SAGE Publications
Date: 06-2003
DOI: 10.1177/021849230301100213
Abstract: Statistical analysis of data collected prospectively from all patients undergoing surgery under cardiopulmonary bypass from September 1994 to November 1998 (group 1) was performed to identify preoperative risk factors for reopening for bleeding. Multiple logistic regression analysis of 19 preoperative variables was carried out with reoperation for bleeding as the endpoint. The protocol for intraoperative use of aprotinin was then changed to include high-risk patients. Data collected from all subsequent patients from May 1999 to March 2002 (group 2) were analyzed. Subgroup analyses on primary isolated coronary artery surgery were also performed. Data were obtained from 1,946 patients aged 22 to 88 years (mean, 62.5 years). Older age, severe left ventricular impairment, redo surgery, and chronic renal failure were the independent predictors of reopening for bleeding in group 1. There were no independent predictors of reopening in group 2. Older age and chronic renal failure were the predictors of reexploration for bleeding in patients undergoing primary isolated coronary artery grafting. Prophylactic measures to prevent excessive bleeding should be used in elderly patients and those with severe left ventricular impairment, redo surgery, and chronic renal failure.
Publisher: Springer Science and Business Media LLC
Date: 03-01-2021
Publisher: Springer Science and Business Media LLC
Date: 12-02-2020
Publisher: Elsevier BV
Date: 08-2004
Publisher: Wiley
Date: 12-2008
DOI: 10.1002/J.2055-2335.2008.TB00386.X
Abstract: Few studies have investigated the incidence and management of adverse drug reactions that occur during home parenteral therapy. To determine the incidence, characteristics and risk factors for adverse drug reactions associated with home parenteral therapy to evaluate the management of these reactions and to determine the ideal contents of an anaphylaxis kit. 673 consecutive patients starting home parenteral therapy were recruited from the Sydney West Area Health Service (June 2002 to November 2004). Data were collected on patient characteristics diagnosis known drug allergies concurrent medications drug dose and frequency duration of treatment and adverse drug reactions, their management and outcomes. 714 treatment courses were administered to 673 patients. Commonly treated conditions were cellulitis (313 courses 44%), orthopaedic infections (73 courses 10%) and wound infections (63 courses 8.8%). Frequently prescribed drugs were cephazolin (376 courses 50%), ceftriaxone (149 courses 20%) and vancomycin (52 courses 7.1%). Adverse drug reactions occurred in 38 (5.3%) courses, of which 5 were ranked as serious or life‐threatening. Adverse drug reactions included skin reactions in 18 (2.5%) courses, abdominal symptoms in 8 (1.1%) courses, and vascular symptoms in 5 (0.7%) courses. Risk factors included concurrent beta‐blocker use, which was associated with an adverse drug reaction in 9 out of 54 courses (OR 4.4 95%CI 1.9–9.7 p = 0.0003). There was a low incidence of adverse drug reactions with home parenteral therapy, with a small risk of serious reactions. Patients taking concurrent beta‐blockers may be at greater risk of adverse drug reactions when treated with parenteral drugs. Patients need to be screened for documented allergies, regularly monitored, and an anaphylaxis kit containing adrenaline and glucagon made available.
Publisher: Oxford University Press (OUP)
Date: 22-05-2013
DOI: 10.1093/CID/CIT341
Abstract: We describe antifungal therapy and management of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least 12 months. Patient data from culture-confirmed cases (2000-2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months. Clinical, laboratory, and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution inflammatory syndrome (IRIS) were determined. Seven of 10 patients with lung infection received hotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC] for a median of 2 weeks) median duration of therapy including azole eradication therapy was 41 weeks, with a complete artial clinical response in 78%. For neurologic disease, 88% of patients received AMB, 78% with 5-FC, for a median of 6 weeks. The median total course was 18 months. Nine patients receiving fluconazole induction therapy were reinduced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurologic sequelae and/or death at 12 months (both P = .02) cerebrospinal fluid drains/shunts were placed in 58% of patients and in 64% of 22 patients with hydrocephalus. IRIS developed 2-12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation, and higher median CD4 counts (all P < .05) corticosteroids reduced cryptococcoma-associated edema. Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.
Publisher: Wiley
Date: 16-03-2016
Abstract: Perceived incivility during ED medical phone consultations is poorly researched. We aimed to determine frequency and factors influencing perceived incivility during ED phone consultations. We conducted a prospective self-reported survey of 40 consecutive phone consultations for 21 ED volunteer doctors. Consultations were classified based on the aim of consultation and deemed as 'positive', 'neutral' or 'negative' based on the perceptions of the consulting doctor. Training levels, time bands and specialty data were collected for both consulting and consulted parties. Fifty-seven of 714 included consultations (7.98%, 95% CI 6.2-10.2%) were reported as negative by ED medical staff. Factors associated with significant incidence of negative grading of consultation involved requests for investigations (19.3% vs 5.3%, P 4 (9.1% vs 3.8%, P < 0.01) and those involving radiology specialty (18% vs 5.32%, P < 0.01). The risk was lower when the consulted professional was a specialist medical practitioner as compared to specialist trainee (4.1% vs 9.4%, P = 0.02). Multiple logistical modelling suggests that female (adjusted OR 2.4, 95% CI 1.1-5.2) medical staff are more likely to report perceived incivility during ED phone consultations. Perceived incivility occurs infrequently during ED phone consultations. ED female medical staff are at an increased risk of perceived incivility during phone consultations with non-ED medical professionals. Health organisations should actively pursue programmes to investigate the occurrence of incivility during healthcare consultations and implement programmes to mitigate the risk of developing a negative workplace culture.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.CGH.2021.01.007
Abstract: Although perforation is the most feared adverse event associated with endoscopic mucosal resection (EMR), limited data exists concerning its management. Therefore, we sought to evaluate the short- and long-term outcomes of intra-procedural deep mural injury (DMI) in an international multi-center observational cohort of large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs). Consecutive patients who underwent EMR for a LNPCP ≥20 mm were evaluated. Significant DMI (S-DMI) was defined as Sydney DMI Classification type III (muscularis propria injury, target sign) or type IV/V (perforation without or with contamination, respectively). The primary outcome was successful S-DMI defect closure. Secondary outcomes included technical success (removal of all visible polypoid tissue during index EMR), surgical referral and recurrence at first surveillance colonscopy (SC1). Between July 2008 to May 2020, 3717 LNPCPs underwent EMR. Median lesion size was 35mm (interquartile range (IQR) 25 to 45mm). Significant DMI was identified in 101 cases (2.7%), with successful defect closure in 98 (97.0%) using a median of 4 through-the-scope clips (TTSCs IQR 3 to 6 TTSCs). Three (3.0%) patients underwent S-DMI-related urgent surgery. Technical success was achieved in 94 (93.1%) patients, with 46 (45.5%) admitted to hospital (median duration 1 day IQR 1 to 2 days). Comparing LNPCPs with and without S-DMI, no differences in technical success (94 (93.1%) vs 3316 (91.7%) P = .62) or SC1 recurrence (12 (20.0%) vs 363 (13.6%) P = .15) were identified. Significant DMI is readily managed endoscopically and does not appear to affect technical success or recurrence.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1994
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-1994
DOI: 10.1097/00002826-199406000-00007
Abstract: Previous studies have reported the resting tremor (RT) of Parkinson's disease to occur at frequencies between 3-7 Hz and to be characterised by an alternating pattern of electromyographic (EMG) bursting activity between opposing muscles. A postural tremor (PT), of higher frequency (> 6 Hz) and with a synchronous pattern of EMG activity, has also been previously described in Parkinson's disease. We investigated the electrophysiological and pharmacological properties of both the RT and PT of 11 patients with Parkinson's disease and 10 patients with essential tremor in a double-blind, placebo-controlled study of L-Dopa/benserazide and propranolol. Tremor litude and frequency were assessed via bidirectional accelerometry, and the pattern of activation of the antagonist muscles of the forearm was determined with use of surface EMG. In the Parkinson's disease group studied, the frequency, EMG pattern of bursts, and response to L-Dopa were similar for the two tremors (median improvement of RT by 70% and PT by 61%). Despite some overlap between the Parkinson's disease and essential tremor groups in the electrophysiology of the tremor, there was no such dramatic pharmacological response in the latter group. These results suggest that the RT and PT of Parkinson's disease share a common pathophysiology and are distinct from essential tremor.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2015
Publisher: Informa UK Limited
Date: 12-09-2020
DOI: 10.1080/10428194.2019.1660968
Abstract: Patients with relapsed-refractory diffuse large B-cell lymphoma (RR-DLBCL) ineligible for autologous stem cell transplantation (autoSCT) have poor survival. Thirty transplant-ineligible patients older than 60 years were administered rituximab 375 mg/m2 day 1, ifosfamide 1333 mg/m
Publisher: Oxford University Press (OUP)
Date: 08-2000
DOI: 10.1086/313992
Abstract: A prospective population-based study was conducted in Australia and New Zealand during 1994-1997 to elucidate the epidemiology of cryptococcosis due to Cryptococcus neoformans var. neoformans (CNVN) and C. neoformans var. gattii (CNVG) and to relate clinical manifestations to host immune status and cryptococcal variety. The mean annual incidence per 10(6) population was 6.6 in Australia and 2.2 in New Zealand. Of 312 episodes, CNVN caused 265 (85% 98% of the episodes in immunocompromised hosts) and CNVG caused 47 (15% 44% of the episodes in immunocompetent hosts). The incidence of AIDS-associated cases in Australia declined annually (P<.001). Aborigines in rural or semirural locations (P<.001) and immunocompetent males (P<.001) were at increased risk of CNVG infection. Cryptococcomas in lung or brain were more common in immunocompetent hosts (P< or =.03) in whom there was an association only between lung cryptococcomas and CNVG. An AIDS-associated genetic profile of CNVN serotype A was confirmed by random lification of polymorphic DNA analysis. Resistance to antifungal drugs was uncommon. The epidemiology of CNVN infection has changed substantially. Clinical manifestations of disease are influenced more strongly by host immune status than by cryptococcal variety.
Publisher: Elsevier BV
Date: 2021
DOI: 10.2139/SSRN.3790444
Publisher: Wiley
Date: 02-1986
DOI: 10.1111/J.1445-5994.1986.TB01110.X
Abstract: Fourteen of 100 geriatric nursing home patients were shown to have evidence of carotid sinus hypersensitivity. The incidence of syncope and falls was noted in prospective follow-up over 33 months. Falls were classified as either simple or complicated by laceration or fracture. Patients experienced simple falls at similar rates whether carotid sinus hypersensitivity was present or absent. For patients with carotid sinus hypersensitivity, the risk of a laceration was increased more than twofold, that of fracture more than threefold, and that of syncope tenfold. Carotid sinus hypersensitivity warrants greater attention as a contributory factor to serious falls and syncope in the elderly and its importance may have been underestimated in the past.
Publisher: Wiley
Date: 17-03-2021
DOI: 10.1002/PST.2113
Abstract: Most clinical studies, which investigate the impact of therapy simultaneously, record the frequency of adverse events in order to monitor safety of the intervention. Study reports typically summarise adverse event data by tabulating the frequencies of the worst grade experienced but provide no details of the temporal profiles of specific types of adverse events. Such 'toxicity profiles' are potentially important tools in disease management and in the assessment of newer therapies including targeted treatments and immunotherapy where different types of toxicity may be more common at various times during long‐term drug exposure. Toxicity profiles of commonly experienced adverse events occurring due to exposure to long‐term treatment could assist in evaluating the costs of the health care benefits of therapy. We show how to generate toxicity profiles using an adaptation of the ordinal time‐to‐event model comprising of a two‐step process, involving estimation of the multinomial response probabilities using multinomial logistic regression and combining these with recurrent time to event hazard estimates to produce cumulative event probabilities for each of the multinomial adverse event response categories. Such a model permits the simultaneous assessment of the risk of events over time and provides cumulative risk probabilities for each type of adverse event response. The method can be applied more generally by using different models to estimate outcome/response probabilities. The method is illustrated by developing toxicity profiles for three distinct types of adverse events associated with two treatment regimens for patients with advanced breast cancer.
Publisher: S. Karger AG
Date: 1995
DOI: 10.1159/000117175
Abstract: The tremor present in a small number of patients who present with features of both Parkinson's disease (PD) and essential tremor (ET) is ill-defined. We therefore studied 8 such patients with 'atypical' tremor and compared them clinically to 11 PD and 10 ET patients in a double-blind, cross-over, placebo-controlled trial. Tremor was assessed via accelerometry and surface EMG. Tremor frequency and the acute tremorlytic response to propranolol were not useful in discriminating between groups. Over 80% of atypical and PD patients showed alternating EMG, whereas 90% of ET patients had synchronous EMG activity. Tremor litude improved by > 90% in 38% of atypical, 27% of PD and none of the ET patients after single-dose L-dopa/benserazide (300/75 mg), a response which was significantly different between the ET and PD groups. Failure to differentiate electrophysiologically and pharmacologically between the atypical and other groups probably relates to clinical heterogeneity in the atypical group.
Publisher: Wiley
Date: 18-06-2012
DOI: 10.1111/J.1528-1167.2012.03547.X
Abstract: Fluorine-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolism has been used to localize the epileptogenic zone. However, glucose hypometabolism remote to the ictal focus is common and its relationship to surgical outcome has not been considered in many studies. We investigated the relationship between surgical outcome and FDG-PET hypometabolism topography in a large cohort of patients with neocortical epilepsy. We identified all patients (n = 68) who had interictal FDG-PET between 1994 and 2004 and who underwent resective epilepsy surgery with follow up for more than 2 years. The volumes of significant FDG-PET hypometabolism involving the resected epileptic focus and its surrounding regions (perifocal hypometabolism) and those distant to and not contiguous with the perifocal hypometabolism (remote hypometabolism) were determined statistically using Statistical Parametric Mapping (voxel threshold p = 0.01, extent threshold ≥ 250 voxels, uncorrected cluster-level significance p < 0.05) and were compared with magnetic resonance imaging (MRI) and clinical and demographic variables using a multiple logistic regression model to identify independent predictors of seizure outcome. Remote hypometabolism was present in 39 patients. Seizure freedom was 49% (19 of 39 patients) in patients with glucose hypometabolism remote from the epileptogenic zone compared to 90% (26 of 29 patients) in patients without remote hypometabolism. In 43 patients with an MRI-identified lesion, seizure freedom was 79% (34 of 43 patients). In patients with normal MRI, cortical dysplasia was the predominant pathologic substrate. Multiple logistic regression analysis identified a larger volume of significant remote hypometabolism (p < 0.005) and absence of a MRI-localized lesion (p = 0.006) as independent predictors of continued seizures after surgery. In patients with widespread glucose hypometabolism that is statistically significant when compared to controls, epilepsy surgery may not result in complete seizure freedom despite complete removal of the MRI-identified lesion. The volume of significant glucose hypometabolism remote to the ictal-onset zone may be an independent predictor of the success of epilepsy surgery.
Publisher: Wiley
Date: 24-11-2021
DOI: 10.1111/AJO.13419
Abstract: Iodine supplements are recommended for women planning pregnancy, but their impact on thyroid function during controlled ovarian hyperstimulation (COH) and into pregnancy is unknown. The aim of this study was to assess the impact of iodine supplementation on thyroid function during COH. One‐hundred and six euthyroid women (thyroid stimulating hormone (TSH) 0.4–2.5 mIU/L) planning their first COH cycle were sub ided according to iodine supplementation (nil, months, ≥6 months) and compared to levothyroxine (LT4)‐treated controls. Serial TSH, free thyroxine, free triiodothyronine and thyroglobulin (Tg) levels were recorded at four time points: (i) baseline, (ii) day 7 ovarian stimulation, (iii) ovulation trigger and (iv) two weeks post oocyte retrieval. Oocyte numbers, fertilisation rates and pregnancy outcome were recorded. TSH increased during COH for those women taking iodine supplements for ≥6 months ( P = 0.025). One quarter recorded a TSH level .5 mIU/L before embryo transfer. A similar increase in TSH was demonstrated by LT4‐dependent controls ( P = 0.024) but not the remaining subgroups. Tg levels did not change during COH in any group but decreased significantly post oocyte retrieval if nil iodine ( P 0.0001) or supplemented for ≥6 months ( P 0.005). Iodine supplementation did not influence oocyte count, fertilisation or implantation rates. Women taking iodine for months were four times more likely to achieve a live birth than women taking iodine for longer. Women taking iodine supplements for ≥6 months are less able to adapt to the thyroidal demands of COH, with responses comparable to LT4‐dependent patients.
Publisher: No publisher found
Date: 2016
Publisher: BMJ
Date: 02-03-2015
DOI: 10.1136/GUTJNL-2014-308603
Abstract: The serrated neoplasia pathway accounts for up to 30% of all sporadic colorectal cancers (CRCs). Sessile serrated adenomas olyps (SSA/Ps) with cytological dysplasia (SSA/P-D) are a high-risk serrated CRC precursor with little existing data. We aimed to describe the clinical and endoscopic predictors of SSA/P-D and high grade dysplasia (HGD) or cancer. Prospective multicentre data of SSA/Ps ≥20 mm referred for treatment by endoscopic mucosal resection (September 2008-July 2013) were analysed. Imaging and lesion assessment was standardised. Histological findings were correlated with clinical and endoscopic findings. 268 SSA/Ps were found in 207/1546 patients (13.4%). SSA/P-D comprised 32.4% of SSA/Ps ≥20 mm. Cancer occurred in 3.9%. On multivariable analysis, SSA/P-D was associated with increasing age (OR=1.69 per decade 95% CI (1.19 to 2.40), p0.004) and increasing lesion size (OR=1.90 per 10 mm 95% CI (1.30 to 2.78), p0.001), an 'adenomatous' pit pattern (Kudo III, IV or V) (OR=3.98 95% CI (1.94 to 8.15), p<0.001) and any 0-Is component within a SSA/P (OR=3.10 95% CI (1.19 to 8.12) p0.021). Conventional type dysplasia was more likely to exhibit an adenomatous pit pattern than serrated dysplasia. HGD or cancer was present in 7.2% and on multivariable analysis, was associated with increasing age (OR=2.0 per decade 95% CI 1.13 to 3.56) p0.017) and any Paris 0-Is component (OR=10.2 95% CI 3.18 to 32.4, p<0.001). Simple assessment tools allow endoscopists to predict SSA/P-D or HGD/cancer in SSA/Ps ≥20 mm. Correct prediction is limited by failure to recognise SSA/P-D which may mimic conventional adenoma. Understanding the concept of SSA/P-D and the pitfalls of SSA/P assessment may improve detection, recognition and resection and potentially reduce interval cancer. NCT01368289.
Publisher: Wiley
Date: 12-2010
DOI: 10.1111/J.1742-6723.2010.01349.X
Abstract: To determine whether CO₂ GAP [(a-ET) PCO₂] value differs consistently in patients presenting with shortness of breath to the ED requiring ventilatory support. To determine a cut-off value of CO₂ GAP, which is consistently associated with measured outcome and to compare its performance against other derived variables. This prospective observational study was conducted in ED on a convenience s le of 412 from 759 patients who underwent concurrent arterial blood gas and ETCO₂ (end-tidal CO₂) measurement. They were randomized to test s le of 312 patients and validation set of 100 patients. The primary outcome of interest was the need for ventilatory support and secondary outcomes were admission to high dependency unit or death during stay in ED. The randomly selected training set was used to select cut-points for the possible predictors that is, CO₂ GAP, CO₂ gradient, physiologic dead space and A-a gradient. The sensitivity, specificity and predictive values of these predictors were validated in the test set of 100 patients. Analysis of the receiver operating characteristic curves revealed the CO₂ GAP performed significantly better than the arterial-alveolar gradient in patients requiring ventilator support (area under the curve 0.950 vs 0.726). A CO₂ GAP ≥10 was associated with assisted ventilation outcomes when applied to the validation test set (100% sensitivity 70% specificity). The CO₂ GAP [(a-ET) PCO₂] differs significantly in patients requiring assisted ventilation when presenting with shortness of breath to EDs and further research addressing the prognostic value of CO₂ GAP in this specific aspect is required.
Publisher: Public Library of Science (PLoS)
Date: 16-11-2015
Publisher: Elsevier BV
Date: 10-1995
DOI: 10.1016/0270-9139(95)90610-X
Abstract: To determine whether hepatic metabolic function affects the response to interferon treatment, we measured antipyrine clearance (APC) in 85 patients with chronic active hepatitis C and compared the results with treatment outcome. Among 55 patients who responded to interferon by normalization of alanine transaminase (ALT), median APC before treatment was 0.47 (range, 0.12 to 0.98 normal range, 0.34 to 1.02 mL/min/kg body wt), a value that was significantly greater than in 30 nonresponders (0.23 0.08 to 0.67 mL/min/kg body wt, P 0.25 mL/min/kg body weight was 79%, the same as in cases without cirrhosis. Cases without cirrhosis and with APC of > 0.25 mL/min/kg body weight had an 85% chance of responding to interferon this was unlikely a simple reflection of histological activity, because the correlation with Scheuer score was poor in this subgroup (r = -.31, P < .05). A second, independent group of 43 patients was used to test the predictive value of APC (using 0.25 mL/min/kg body wt as a cut-off) for response to interferon treatment. In this group, APC correctly predicted positive response to interferon in 75% of cases. APC was also used to measure the effects of treatment on hepatic metabolic function. Regardless of outcome, there was no change in APC at the end of a 6-month course of interferon treatment. Six months later, however, improvement in APC (14% P < .05) was evident among responders but not in those who had failed to respond to interferon.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 03-1996
DOI: 10.1111/J.1440-1746.1996.TB00064.X
Abstract: In order to determine the value of serum bile acids in predicting the course of chronic cholestatic liver diseases, we measured in idual serum bile acids serially, using high-performance liquid chromatography, over a 4 year observation period in 12 patients with primary biliary cirrhosis and six patients with primary sclerosing cholangitis. The changes in in idual serum bile acids and the ratios thereof, conventional liver tests and Child-Turcotte and Mayo scores were compared between survivors (n = 10) and patients who underwent liver transplantation for (n = 3) or died of the liver disease (n = 5). Patients with a serum total chenodeoxycholic acid concentration at study entry that exceded 15 mumol/L were 10 times more likely to die or need a liver transplant in the following 4 years than those with chenodeoxycholic acid levels < 15 mumol/L (P < 0.05). None of the other biochemical parameters or clinicopathological scores could similarly discriminate between the two groups at entry. Time-dependent analyses for the cholic acid/chenodeoxycholic acid ratio, serum total bilirubin and albumin concentrations and Child-Turcotte and Mayo scores were able to differentiate between primary sclerosing cholangitis patients who died or were transplanted and those who were not, whereas age of the patients and other parameters did not. The taurocholic acid/taurochenodeoxycholic acid ratio fell during progression of primary biliary cirrhosis but rose in temporal relationship with primary sclerosing cholangitis. This differential pattern of change was unique compared with other clinical and laboratory indices. In conclusion, serum chenodeoxycholic acid levels and the cholic acid/chenodeoxycholic acid ratio in both diseases were independent indices that allowed for the prediction of survival or the need for liver transplantation. These indices are worthy of further examination in a larger group of patients as prognostic criteria for chronic cholestatic liver disease and in the assessment of the efficacy of therapeutic interventions, including liver transplantations.
Publisher: AMPCo
Date: 03-1992
DOI: 10.5694/J.1326-5377.1992.TB139846.X
Abstract: To determine risk levels for the development of cirrhosis in Australian men who consume alcohol and to compare this risk with that of Australian women. A case-control study using an interview technique, based in two major tertiary referral hospitals in Sydney. Forty-three men with newly diagnosed cirrhosis of the liver and a total of 115 male control subjects, age matched with the case subjects. The data for women (36 cases and 99 controls) have been reported previously. The risk of men developing cirrhosis increases significantly above the baseline when the alcohol intake exceeds 40 g per day. The risk to women is significant at a similar intake level. Dietary intake and past major illnesses appear to have no role in determining risk. The recommended safe drinking level for men and women should be 40 g per day, as suggested by the National Health and Medical Research Council.
Publisher: Springer Science and Business Media LLC
Date: 05-11-2015
Abstract: Although postmenopausal combined hormone replacement therapy reduces the risk of hip fracture, long-term use may be associated with an increased risk of breast cancer, and in women more than 10 years after menopause it is associated with an increased risk of cardiovascular disease. Isoflavones, because of preferential binding to estrogen receptor beta, may retain the beneficial effects on bone but lessen the adverse effects on the breast. The objective of this study was to study the effects of an isoflavone obtained from red clover (Rimostil) on bone mineral density, and on low-density lipoprotein (LDL) cholesterol. In a double-blind, randomized, placebo-controlled trial, 50 mg of Rimostil was given to women who were menopausal for at least 1 year. Bone mineral density of the spine, femoral neck and forearm and serum LDL cholesterol were measured at baseline and at 6-month intervals. The duration of follow-up was 2 years. There was no beneficial effect of Rimostil on bone density at any site. There was a 12% fall in serum LDL cholesterol in the Rimostil-treated arm, which was significantly greater than the 2% drop seen in the control arm (P=0.005).
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JAD.2012.12.005
Abstract: Shortening the pulse width to 0.3 ms holds neurophysiological and clinical promise of making ECT safer by limiting cognitive side effects. However, the antidepressant effects of right ultra-brief unilateral ECT are under contention. In an acute ECT course, antidepressant equivalence of ultra-brief right unilateral ECT to the high-dose brief pulse right unilateral ECT was investigated. Severely depressed patients were randomised to 1 ms-brief pulse (n=18) or 0.3 ms ultra-brief pulse (n=17) right unilateral ECT, both at high-dose (6 times threshold stimulus dose) given thrice weekly. Depression severity was measured using the Montgomery Asberg Depression Rating Scale at baseline, after 8 treatments and after the acute course of ECT. Depression severity declined equally in both groups: F (1.27,41.97)=0.31, p=0.63. Median time in days to remission (95%CI) was in brief pulse ECT: 26 (18.6-33.4) and ultra-brief pulse ECT:28 (17.9-38.0). The small s le study in the study increases the likelihood of type 2 error. In severe depression, high-dose ultra-brief right unilateral ECT appears to show matching acute antidepressant response to an equally high-dose brief pulse right unilateral ECT.
Publisher: Elsevier BV
Date: 03-1995
DOI: 10.1016/0006-2952(94)00515-N
Abstract: We have recently reported that disease-specific differential alterations in the hepatic expression of xenobiotic-metabolizing cytochrome P450 (CYP P450) enzymes occur in patients with advanced liver disease. In order to determine whether the observed changes in CYP proteins are modulated at pre- or post-translational levels, we have now examined the hepatic levels of mRNA for CYPs 1A2, 2C9, 2E1 and 3A4 by solution hybridization in the same livers of 20 controls (surgical waste from histologically normal livers), 32 cases of hepatocellular and 18 of cholestatic severe chronic liver disease. CYP1A2 mRNA and CYP1A immunoreactive protein were both reduced in livers with hepatocellular and cholestatic types of cirrhosis. In contrast, CYP3A4 mRNA and protein were reduced only in livers from patients with hepatocellular diseases. For 1A2 and 3A4 there were significant correlations between mRNA species and the respective protein contents (rS1A2 = 0.74, rS3A4 = 0.64, P < 0.0001). CYP2C9 mRNA was reduced in patients with both cholestatic and hepatocellular types of liver disease, but 2C protein was reduced only in patients with cholestatic dysfunction. The correlation between CYP2C9 mRNA and protein, was also significant (rs = 0.36, P < 0.005) but mRNA levels accounted for only 13% of the variability in protein rankings. This is probably a consequence of other CYP2C proteins apart from 2C9 being detected by the anti-2C antibody. CYP2E1 mRNA and protein were reduced in patients with cholestatic liver disease, but in hepatocellular disease the expression of only CYP2E1 mRNA was decreased. CYP2E1 mRNA was significantly correlated with CYP2E1 protein but accounted for only 18% of the variability in protein rankings (rs = 0.43, P < 0.0005). Taken collectively these data indicate that the disease-specific alterations of xenobiotic-metabolizing CYP enzymes among patients with cirrhosis is due, at least in part, to pre-translational mechanisms. The lack of a strong correlation between CYP2E1 mRNA and protein suggests that this gene, like its rat orthologue, may be subject to pre-translational as well as translational and/or post-translational regulation.
Publisher: Springer Science and Business Media LLC
Date: 28-04-2015
DOI: 10.1007/S10549-015-3397-0
Abstract: Progesterone receptor (PR) function, while essential in normal human breast, is also implicated in breast cancer risk. The two progesterone receptors, PRA and PRB, are co-expressed at equivalent levels in normal breast, but early in carcinogenesis normal levels of PRA:PRB are frequently disrupted, and predominance of one isoform, usually PRA, results. In model systems, PRA and PRB have different activities, and altering the PRA:PRB ratio in cell lines alters PR signaling. The purpose of this study was to determine whether hormonal or reproductive factors contribute to imbalanced PRA:PRB expression in breast tumors and the impact of PRA:PRB imbalance on disease outcome. The relative expression of PRA and PRB proteins was determined by dual immunofluorescence histochemistry in archival breast tumors and associations with clinical and reproductive history assessed. PRA:PRB expression was not influenced by reproductive factors, whereas exogenous hormone use (menopausal hormone treatment, MHT) favored PRB expression (p < 0.035). The PRA:PRB ratio may be a discriminator of response to endocrine therapy in the TransATAC s le collection, with high PRA:PRB ratio predicting earlier relapse for women on tamoxifen, but not anastrozole (mean lnPRA:PRB ratio HR (95 % CI) tamoxifen 2.45 (1.20-4.99) p value 0.02 anastrozole 0.80 (0.36-1.78) p value 0.60). The results of this study show that PRA:PRB imbalance in breast cancers is not associated with lifetime endogenous endocrine and reproductive factors, but is associated with MHT use, and that PRA predominance can discriminate those women who will relapse earlier on tamoxifen treatment. These data support a role for imbalanced PRA:PRB expression in breast cancer progression and relative benefit from endocrine treatment.
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1016/J.GIE.2011.12.025
Abstract: Whether early Barrett's neoplasia has a predilection for particular spatial locations in shorter segment disease is currently unknown. Anatomic factors may play a role in lesion location because of differing levels of mucosal acid exposure. To identify high-risk lesion locations, which has important implications for surveillance strategies. We interrogated a prospectively maintained database of patients who underwent endoscopic resection (ER) for Barrett's neoplasia at 2 Australian tertiary centers. Lesions targeted for ER were characterized and their location in the distal esophagus was noted as on a clock face. A Z test of proportions was used to test for deviation from uniformity in the distribution of lesions. Two Australian tertiary centers. Patients who underwent ER for Barrett's neoplasia. Lesion location in the distal oesophagus, resected specimen histology. A total of 146 consecutive patients had ER for biopsy-proven high-grade dysplasia or esophageal adenocarcinoma. A total of 75 patients had Barrett's segment length of 5 cm or less and a visible lesion. Five patients had 2 visible lesions giving a total of 80 lesions. ER of 66 lesions (82.5%) led to the identification of advanced pathology: 37 high-grade dysplasia (46%), 24 mucosal adenocarcinoma (30%), 5 submucosal adenocarcinoma (6%). Of a total of 80 lesions, 43 (53.8%) (95% CI, 42.9%-64.7%) were centered within the 2- to 5-o'clock arc, comprising 25% of the circumference. This area also accounted for 36 (54.5%) of the 66 lesions with advanced histology (95% CI, 42.5%-66.5%). All confidence intervals lie wholly above the 25% expected in a uniform circular distribution (P < .05). Observational study in a tertiary center. In Barrett's maximal segments of 5 cm or less, the 2- to 5-o'clock arc, accounts for approximately 50% of macroscopically visible lesions and associated early neoplasia. This finding has important implications for surveillance strategies.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1998
DOI: 10.1097/00007890-199810150-00011
Abstract: Systemic viral disease after renal transplantation, especially after treatment with OKT3 or antithymocyte globulin, has usually been attributed to cytomegalovirus (CMV) infection. Identification of human herpesvirus 6 (HHV6) has raised the possibility that infection or reactivation of this virus may also occur in the same setting. We thus examined the incidence of CMV and HHV6 infection in a prospective blinded consecutive series of 30 renal and renal ancreas transplant patients, 22 of whom received OKT3, antithymocyte globulin, or both. Clinical diagnosis of a viral syndrome was made in 15 patients. Three patients with only HHV6 DNA in urine or serum had fever and abnormal liver function but not neutropenia. All five CMV-seronegative patients who received positive kidneys developed moderate to severe disease with fever and neutropenia but also had HHV6 DNA in urine or serum. Seven CMV-seropositive patients developed disease, mostly after OKT3/antithymocyte globulin, but six shed both CMV and HHV6 in urine or serum. The simultaneous detection of both HHV6 and CMV DNA in either urine or serum was the strongest predictor of disease (and also the severity of disease), with an odds ratio of 99.0 (95% confidence intervals 5.4-1814, P<0.002). Most systemic viral disease after renal transplantation may be due to either coinfection or reactivation of CMV and HHV6 together. A wider understanding of risk factors for severe viral disease in this setting may come from testing for both viruses in all donors and patients in both clinical practice and clinical trials.
Publisher: Wiley
Date: 20-05-2005
DOI: 10.1111/J.1478-3231.2005.01049.X
Abstract: This study addressed the suggested association between levels of the antioxidants glutathione (GSH), vitamin C and vitamin E in peripheral blood and the histological activity and fibrosis stage in chronic hepatitis C (CHC). We then determined whether regular antioxidant supplementation influenced these antioxidant levels or disease severity. Clinical, biochemical, histological and demographic data were collected from 247 CHC patients at the time of liver biopsy. Whole blood total GSH, plasma vitamin C and E were assessed by high-performance liquid chromatography. Statistical analyses were performed to test for associations between the variables and to identify independent predictors for hepatic necroinflammatory and fibrosis scores. GSH and vitamin C, but not vitamin E correlated with both portal eriportal activity (r = -0.19, P = 0.004 r = -0.19, P = 0.009 respectively) and fibrosis stage (r = -0.18, P = 0.007 r = -0.18, P = 0.009 respectively). GSH was an independent negative predictor of portal eriportal inflammation (P = 0.02) and fibrosis (P = 0.01). Vitamin C was an independent negative predictor of fibrosis stage (P = 0.02). Antioxidant intake was associated with higher vitamin C (P < 0.0001) and vitamin E (P = 0.005) levels, but not GSH. Whole blood GSH and plasma vitamin C are negatively associated with hepatic portal eriportal inflammation and fibrosis stage in CHC. Controlled intervention studies with vitamin C and agents that boost endogenous GSH levels are warranted.
Publisher: SAGE Publications
Date: 12-2019
DOI: 10.1177/0310057X0303100603
Abstract: A number of European studies have documented the ability of procalcitonin (PCT), a novel inflammatory marker, to discriminate patients with sepsis from those with other causes of systemic inflammatory response syndrome (SIRS). The aim of this study was to assess procalcitonin's performance in an Australian intensive care unit (ICU) setting to examine whether it could discriminate between these two conditions. One hundred and twenty-three consecutive adult ICU patients fulfilling criteria for SIRS were enlisted in the study. Over a period of five days, daily serum PCT and C-reactive protein (CRP) levels were measured. At least two sets of cultures were taken of blood, sputum/broncho-alveolar lavage (BAL) and urine. Other cultures were taken as clinically indicated. Questionnaires to ascertain clinical suspicion of sepsis were prospectively answered by the ICU senior registrars. PCT values were ten times higher in patients with positive blood cultures CRP values were also significantly higher in the bacteraemic patients. Both PCT and CRP had a good ability to discriminate bacteraemia from non-infectious SIRS, with the area under receiver operating characteristics (ROC) curves for PCT being 0.8 and for CRP being 0.82. However neither PCT or CRP was able to discriminate patients with localized sepsis from those without. Utilizing both tests resulted in a more sensitive screen than either one alone, while PCT was a more accurate diagnostic test for bacteraemia than CRP. The PCT value also differed between those who died in hospital and those who survived. Measurement of PCT alone or in combination with CRP can aid discrimination of septicaemia/bacteraemia with associated SIRS from non-infectious SIRS in an Australian ICU setting.
Publisher: Elsevier BV
Date: 07-2004
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.EJCA.2013.06.046
Abstract: Anthracycline agents are undermined by their cardiotoxicity. As life expectancy following treatment is greatly improved, techniques that ensure early detection and timely management of cardiotoxicity are essential. The aim of the present study was to evaluate left ventricular (LV) systolic function with LV ejection fraction (LVEF) and two-dimensional myocardial strain up to 12 months after anthracycline chemotherapy, specifically in HER2/neu negative breast cancer patients. Seventy-eight consecutive anthracycline naïve breast cancer patients were studied before and immediately after anthracycline chemotherapy. Fifty HER2/neu negative patients were studied over 12 months with serial echocardiograms at four time points. All patients were treated with standard regimens containing anthracyclines. Global systolic strain was significantly reduced immediately after, and 6 months after anthracyclines (-19.0 ± 2.3% to -17.5 ± 2.3% (P<0.001) and -18.2 ± 2.2% (P=0.01) respectively). A non-uniform reduction in strain was observed each time with relative sparing of the LV apex. LVEF remained largely unchanged at both time points. Global strain normalised by 12 months in the majority of patients. Persistently reduced strain was observed in 16% (n=8) these patients had a greater reduction in strain at 6 months (≤ -17.2%), and had received higher cumulative anthracycline doses. Myocardial strain imaging is more sensitive than LVEF for the early detection and intermediate term monitoring of LV systolic function following anthracycline chemotherapy in HER2/neu negative breast cancer patients, and may aid in the development of improved monitoring protocols.
Publisher: BMJ
Date: 07-07-2015
Abstract: To assess the utility of rate of disease progression (ΔFS) as a prognostic biomarker in amyotrophic laterals sclerosis (ALS). A total of 203 patients with ALS were prospectively recruited over a 10-year period. At initial visit, the following variables were collected: demographic details, symptom duration, site of onset, phenotype, riluzole use and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. The ΔFS score at initial visit was calculated by iding the ALSFRS-R total score by symptom duration (months). The primary end point was survival. Kaplan-Meier survival curves were used to illustrate the distribution of survival from a specified point, while multiple Cox proportional hazards modelling with backward stepwise variable selection was used to identify the independent predictors of survival at initial visit. The ΔFS score at initial visit was a significant predictor of survival in ALS (p<0.001), and remained significant when adjusted for age and site of onset (p<0.001). 3 prognostic subgroups emerged, with a ΔFS score of <0.47 associated with a median survival of 2.4 years, which was significantly greater when compared with an initial ΔFS score of between 0.47 and 1.11 (1.6 years, p 1.11 (0.7 years, p<0.001). Importantly, multiple Cox proportional hazards modelling identified ΔFS as a highly significant independent predictor of survival in ALS (p<0.001) along with site of disease onset (p<0.01). Rate of disease progression appears to be a simple and sensitive clinical prognostic biomarker in ALS that could be potentially utilised in clinical practice and future therapeutic trials.
Publisher: American Medical Association (AMA)
Date: 06-2013
DOI: 10.1001/JAMADERMATOL.2013.2466
Abstract: Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. To determine the dermoscopy features of NM. Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. Predominantly hospital-based clinics from 5 continents. Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red ink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.
Publisher: Impact Journals, LLC
Date: 09-12-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2008
Publisher: SAGE Publications
Date: 09-07-2020
Abstract: To determine the impact of a peer-led, school-based programme (Students As LifeStyle Activists SALSA) on energy balance–related behaviours (EBRBs) in Grade 8 students, and the cost of implementing the programme. Pre–post test High schools in New South Wales, Australia. Grade 10 students (15- to 16-year-olds) were trained by university students to deliver four lessons on healthy eating and physical activity to Grade 8 students (13- to 14-year-olds). Students completed an online questionnaire pre–post lessons on EBRBs and intentions to change EBRBs over the next month. Items included fruit, vegetable and sugar-sweetened beverage (SSB) intake, frequency of eating breakfast, participation in moderate-to-vigorous physical activity (MVPA) and school-day recreational screen-time. Pre–post changes were analysed using generalised estimating equations, adjusted for clustering. Standard methods were used to estimate implementation costs. In total, 2,056 Grade 8 students from 23 high schools participated. Significant changes included 5.2% increase in eating fruit serves/day ( p .001), 2.5% increase in eating vegetable serves/day ( p .05), a 4.3% increase in drinking cup/day of SSB ( p .001) but limiting screen-time hours/day decreased by 4.4% ( p .001). There were significant improvements in students’ intentions to change EBRBs over the next month, with the exception of MVPA. The average actual cost of implementing the SALSA programme in 2014–2015 was AU$1,388 (US$958) per school and AU$9.97 (US$6.88) per student. The SALSA peer education programme had a positive impact on most of the dietary EBRBs examined. The cost evaluation showed that it is a relatively low-cost programme to implement.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2014
DOI: 10.1161/CIRCEP.113.001112
Abstract: Cardiac and respiratory movements cause catheter instability. Lateral catheter sliding over target endocardial surface can lead to poor tissue contact and unpredictable lesion formation. We describe a novel method of overcoming the effects of lateral catheter sliding movements using an electrogram-gated pulsed power ablation. All ablations were performed on a thermochromic gel myocardial phantom. Ablation settings were randomized to conventional (nongated) 30 W versus electrogram-gated at 20% duty cycle (30 W average power) at 0-, 3-, 6-, and 9-mm lateral sliding distances. Forty-eight radiofrequency ablations were performed. Deeper lesions were created in electrogram-gated versus conventional ablations at 3 mm (4.36±0.08 versus 4.05±0.17 mm P =0.009), 6 mm (4.39±0.10 versus 3.44±0.15 mm P .001), and 9 mm (4.41±0.06 versus 2.94±0.16 mm P .001) sliding distances. Electrogram-gated ablations created consistent lesions at a quicker rate of growth in depth when compared with conventional ablations ( P .001). (1) Lesion depth decreases and length increases in conventional ablations with greater degrees of lateral catheter movements (2) electrogram-gated pulsed radiofrequency delivery negated the effects from lateral catheter movement by creating consistently deeper lesions irrespective of the degree of catheter movement and (3) target lesion depths were reached significantly faster in electrogram-gated than in conventional ablations.
Publisher: Georg Thieme Verlag KG
Date: 08-11-2011
Abstract: Complete Barrett's excision (CBE) of short-segment Barrett's high grade dysplasia (HGD) and early esophageal adenocarcinoma by stepwise endoscopic resection is a precise staging tool, detects covert synchronous disease, and may produce a sustained treatment response. Esophageal stricture is the most commonly reported complication of CBE although risk factors have not yet been clearly defined. Data were recorded prospectively on patients with limited co-morbidity and age ≤ 80 years undergoing CBE for histologically proven HGD or esophageal adenocarcinoma within ≤ C3M5 segments. Endoscopic resection was performed by standardized protocol every 6 - 8 weeks until CBE was achieved. Esophageal dilation was performed when patients reported dysphagia. Dysphagia scores were recorded at scheduled endoscopic surveillance or by telephone interview. By intention-to-treat analysis, complete eradication of neoplasia and intestinal metaplasia was achieved in 95 % and 82 %, respectively, in 77 patients undergoing a median of 2 resection sessions (interquartile range [IQR] 1 - 3). Esophageal dilation was required in 33 % (median 3 dilations, IQR 1 - 3.5) at median follow-up of 20 months (IQR 6 - 40). Independent risk factors for dilation requirement were the number of mucosal resections at the index procedure (odds ratio [OR] 1.3 per resection, 95 % confidence interval [CI] 1.0 - 1.9 P = 0.043) and maximal extent of the Barrett's segment (OR 2.2 per cm, 95 %CI 1.2 - 3.9 P = 0.009). Although CBE is highly effective in the treatment of Barrett's HGD and esophageal adenocarcinoma, the risk of post-CBE dysphagia increases with the maximal extent of the Barrett's segment and the number of mucosal resections at the index procedure. These data could be used to inform treatment decisions and identify those patients who may benefit from prophylactic therapies such as dilation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2018
Publisher: Annals of Laboratory Medicine
Date: 2014
Publisher: Wiley
Date: 30-05-2014
DOI: 10.1111/JOOR.12186
Abstract: Few prospective studies have investigated risk factors associated with severe tooth surface loss. This case-control study assessed the possible association between medical history, diet, psychological profile and salivary pH and flow [Delongis 1982, Johansson 1993] with the incidence of severe tooth surface loss. A total of 80 subjects (40 cases and 40 age- and gender-matched controls) aged 25-85 years were recruited. Cases were subjects with severe tooth surface loss, and controls with mild tooth surface loss. Conditional logistic regression analysis estimated the odds of severe tooth surface loss to be 15·4 times higher for those with cardiovascular disease and 16 times for gastrointestinal disturbances. Most domains of the psychological profile were associated with elevated risk of severe tooth surface loss, particularly the effects of finance and health. Recreational drug use and prescription medications were also associated with severe tooth surface loss. There was no association between salivary flow and severe tooth surface loss. Although not statistically significant, the pH was slightly lower in the severe tooth surface loss group.
Publisher: The Endocrine Society
Date: 11-2005
DOI: 10.1210/ME.2005-0126
Abstract: The ovarian hormone progesterone is essential for normal breast development and function. However, it is also implicated in breast cancer development. Progesterone signals through two nuclear receptors [progesterone receptor A (PRA) and progesterone receptor B (PRB)], which display striking differences in transcriptional activity when analyzed separately. The two species are coexpressed equally in normal breast, but expression becomes markedly disrupted in breast cancer, where a predominance of PRA is common. To determine the impact on PR transcriptional activity of the shift from coexpression of PRA and PRB, observed in normal cells, to predominance of PRA, common in cancers, we modeled these changes in PR expression patterns using an inducible model of PRA predominance. At short treatment times progestin regulation was directed toward transcriptional modulators, whereas longer exposure more frequently targeted genes associated with regulation of cell shape, adhesion, and metabolism, and a number of these targets acquired responsiveness only when PRA predominance was achieved. Consistent with this, overexpression of PRA altered progestin effects on cell-substrate attachment and focal adhesion signaling. Our data suggest that disrupted balance of PRA and PRB remodels progestin responsiveness and that altered regulation of morphology and adhesion are important components of altered progestin response in breast cancer.
Publisher: Elsevier BV
Date: 2019
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.GIE.2016.11.027
Abstract: EMR is the primary treatment of large laterally spreading lesions (LSLs) in the colon. Residual or recurrent adenoma (RRA) is a major limitation. We aimed to identify a robust method to stratify the risk of RRA. Prospective multicenter data on consecutive LSLs ≥20 mm removed by piecemeal EMR from 8 Australian tertiary-care centers were included (September 2008 until May 2016). A logistic regression model for endoscopically determined recurrence (EDR) was created on a randomly selected half of the cohort to yield the Sydney EMR recurrence tool (SERT), a 4-point score to stratify the incidence of RRA based on characteristics of the index EMR. SERT was validated on the remainder of the cohort. Analysis was performed on 1178 lesions that underwent first surveillance colonoscopy (SC1) (median 4.9 months, interquartile range [IQR] 4.9-6.2). EDR was detected in 228 of 1178 (19.4%) patients. LSL size ≥40 mm (odds ratio [OR] 2.47 P < .001), bleeding during the procedure (OR 1.78 P = .024), and high-grade dysplasia (OR 1.72 P = .029) were identified as independent predictors of EDR and allocated scores of 2, 1, and 1, respectively to create SERT. Lesions with SERT scores of 0 (SERT = 0) had a negative predictive value of 91.3% for RRA at SC1, and SERT was shown to stratify RRA to specific follow-up intervals by using Kaplan Meier curves (log-rank P < .001). Guidelines recommend SC1 within 6 months of EMR. SERT accurately stratifies the incidence of RRA after EMR. SERT = 0 lesions could safely undergo first surveillance at 18 months, whereas lesions with SERT scores between 1 and 4 (SERT 1-4) require surveillance at 6 and 18 months. (Clinical trial registration number: NCT01368289.).
Publisher: American Society of Hematology
Date: 02-07-2009
DOI: 10.1182/BLOOD-2008-12-194845
Abstract: Dendritic cells (DCs) play a key role in the pathogenesis of HIV infection. HIV interacts with these cells through 2 pathways in 2 temporal phases, initially via endocytosis and then via de novo replication. Here the transcriptional response of human DCs to HIV-1 was studied in these phases and at different stages of the virus replication cycle using purified HIV-1 envelope proteins, and inactivated and viable HIV-1. No differential gene expression was detected in response to envelope. However, more than 100 genes were differentially expressed in response to entry of viable and inactivated HIV-1 in the first phase. A completely different set of genes was differentially expressed in the second phase, predominantly in response to viable HIV-1, including up-regulation of immune regulation genes, whereas genes encoding lysosomal enzymes were down-regulated. Cathepsins B, C, S, and Z RNA and protein decreased, whereas cathepsin L was increased, probably reflecting a concomitant decrease in cystatin C. The net effect was markedly diminished cathepsin activity likely to result in enhanced HIV-1 survival and transfer to contacting T lymphocytes but decreased HIV-1 antigen processing and presentation to these T cells.
Publisher: Elsevier BV
Date: 08-1992
DOI: 10.1016/0002-9149(92)90616-7
Abstract: The coronary sinus (CS) orifice is an important reference point for determining electrode and, thereby, accessory pathway location at electrophysiologic study. The reliability of fluoroscopic landmarks used to identify the CS orifice is not known. This study compared the accuracy of several fluoroscopic landmarks for identifying the CS orifice with the location defined by radiopaque contrast injection of the CS. Forty patients were studied. Radiographic markers of the CS orifice that were examined included: (1) the point at which the CS catheter prolapsed during advancement, (2) the point of maximum convexity of the CS catheter when a superior vena caval approach was used, (3) the right side of the ventricular septum, and (4) the relation to the underlying vertebrae. The least-significant difference method of multiple comparisons was used for statistical analysis. The point at which the CS catheter prolapsed was the most accurate noncontrast method for determining the location of the CS orifice (p less than 0.05), but was possible without the use of excessive force in only 48% of patients. The point of catheter prolapse was a median of 1 mm (range 0 to 11) from the true location of the os. Errors with other examined landmarks ranged up to 3 cm. Identification of the CS orifice is best performed by radiopaque contrast injection. The point of prolapse during catheter advancement in the CS is an accurate alternative when contrast injection is not feasible. Other noncontrast fluoroscopic landmarks are less reliable and are best avoided.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Springer Science and Business Media LLC
Date: 13-06-2008
DOI: 10.1007/S00221-008-1439-0
Abstract: To study the effects of masseter muscle pain on jaw muscle electromyographic (EMG) activity during goal-directed tasks. Mandibular movement was tracked and EMG activity was recorded from bilateral masseter, and right posterior temporalis, anterior digastric, and inferior head of lateral pterygoid muscles in 22 asymptomatic subjects at postural jaw position, and during three tasks: (a) protrusion, (b) contralateral (left), (c) open jaw movement. Tasks were performed during three conditions: control (no infusion), test 1 [continuous infusion into right masseter of 4.5% hypertonic saline to achieve 30-60 mm pain intensity on 100-mm visual analog scale (VAS)], and test 2 (isotonic saline infusion in 16 subjects only) the sequence of hypertonic and isotonic saline was randomized. The average EMG root-mean-square values at 0.5 mm increments of mid-incisor-point displacement were analysed using linear mixed effects model statistics (significance: P < 0.05). Right masseter hypertonic saline infusion resulted in significantly (P < 0.0005) more pain (mean +/- SD VAS 47.3 +/- 14.3 mm) than isotonic infusion (12.2 +/- 17.3 mm). Although there was evidence of inter-subject variation, the principal EMG findings were that the significant effects of hypertonic saline-induced pain on EMG activity varied with the task in which the muscle participated irrespective of whether the muscle was an agonist or an antagonist in the tasks. The direction of the hypertonic saline-induced pain effect on EMG activity (i.e., whether the hypertonic saline-induced EMG activity was less than or greater than control EMG activity) could change with the magnitude of jaw displacement. Hypertonic saline infusion had no significant effect on postural EMG activity in any of the recorded jaw muscles. The data suggest that under constrained goal-directed tasks, the pattern of pain-induced changes in jaw muscle EMG activity is not clear cut, but can vary with the task performed, jaw displacement magnitude, and the subject being studied.
Publisher: Georg Thieme Verlag KG
Date: 04-04-2017
Abstract: Background and study aims Adenomas of the duodenum and ulla are uncommon. For lesions ≤ 20 mm in size and confined to the papillary mound, endoscopic resection is well supported by systematic study. However, for large laterally spreading lesions of the duodenum or papilla (LSL-D/P), surgery is often performed despite substantial associated morbidity and mortality. We aimed to compare actual endoscopic outcomes of such lesions and costs with those predicted for surgery using validated prediction tools. Patients and methods Patients who underwent endoscopic resection of LSL-D/P were analyzed. Two surgeons assigned the hypothetical surgical management. The National Surgical Quality Improvement Program (NSQIP), and the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) were used to predict morbidity, mortality, and length of hospital stay. Actual endoscopic and hypothetical surgical outcomes and costs were compared. Results A total of 102 lesions were evaluated (mean age of patients 69 years, 52 % male, mean lesion size 40 mm). Complete endoscopic resection was achieved in 93.1 % at the index procedure. Endoscopic adverse events occurred in 18.6 %. Recurrence at first surveillance endoscopy was seen in 17.7 %. For patients with ≥ 2 surveillance endoscopies (n = 55), 90 % were clear of disease and considered cured (median follow-up 27 months). Compared with hypothetical surgical resection, endoscopic resection had less morbidity (18 % vs. 31 % P = 0.001) and shorter hospital stay (median 1 vs. 4.75 days P 0.001), and was less costly than surgery (mean $ 11 093 vs. $ 19 358 P 0.001). Conclusion In experienced centers, even extensive LSL-D/P can be managed endoscopically with favorable morbidity and mortality profiles, and reduced costs, compared with surgery.
Publisher: Wiley
Date: 25-06-2019
DOI: 10.1111/JOP.12913
Abstract: Pemphigus vulgaris (PV) is an autoimmune blistering disease driven by pathogenic antibodies to desmoglein-1 and -3, levels of which correlate with disease activity. Anti-desmoglein-3 IgG4 isotype antibodies are said to predominate in active disease and anti-desmoglein-3 IgG1 in remission however, these observations arose from vertical studies, with limited assessments of clinical activity. The objective of this study was to examine the relationship between desmoglein autoantibodies, sub ided by isotype and disease activity using the validated PV activity tool "Pemphigus Disease Area Index (PDAI)." Forty PV patients with predominantly mucosal disease were studied prospectively, 24 serially, and PDAI and anti-desmoglein antibodies recorded at each visit over a period of up to 15 months. At enrolment, only anti-desmoglein-3 IgG4 levels were significantly associated with disease activity but the correlation was weak. During follow-up, within-patient changes in disease activity correlated with changes in anti-desmoglein-3 IgG levels, but correlations were similar for both anti-desmoglein-3 IgG1 and IgG4. These trends were not observed in anti-desmoglein-1 IgG levels, although the majority of patients were negative at baseline. Anti-desmoglein-3 IgG4 levels correlated only weakly with PDAI scores at a single time point. Reciprocity of IgG1 vs IgG4 anti-desmoglein-3 with changes in disease activity over time could not be confirmed, but rather, changes in levels of anti-desmoglein-3 IgG, irrespective of isotype, were useful in following in idual patient responses.
Publisher: Oxford University Press (OUP)
Date: 04-2010
Abstract: Identification of arrhythmogenic scar using non-contact (NC) sinus rhythm (SR) mapping is limited. Dynamic substrate mapping (DSM) overcomes these limitations but is less accurate than plunge needle electrode mapping. We developed a revised method for calculating DSM which was validated using detailed histological analysis and compared with conventional mapping modalities. Mapping was performed in eight sheep, >9 weeks post-myocardial infarction. Twenty multielectrode needles were deployed at thoracotomy in the left ventricle within and surrounding scar, and located using Ensite. Simultaneous catheter, needle, and NC electrograms were recorded during SR and multisite pacing. Dynamic substrate mapping maps were calculated as the maximum local peak negative voltage (PNV). Absolute mean DSM (AMDSM) maps, based on peak-peak voltage (P-PV), were calculated to minimize local pacing effects and take into account anisotropic influence. Dynamic substrate mapping and AMDSM maps were normalized based on global maximum voltages attained. Histologically quantified scar and mapping criteria were compared using Spearman's correlation and receiver operator curves (area under the curve, AUC) using 50% scar cut-off. For unipolar mapping, needles had greatest sensitivity at identifying scar which was better for P-PV (AUC needle = 0.90, catheter = 0.70, NC = 0.66) than for PNV (AUC needle = 0.79, NC = 0.38). AMDSM (AUC = 0.75) had superior scar discrimination than either catheter (AUC unipolar = 0.70, bipolar = 0.71) or DSM (AUC = 0.67). Absolute mean DSM accuracy was improved when valvular geometries were excluded (AUC = 0.77). Absolute mean DSM was comparably accurate in identifying scarred myocardium as PNV needle mapping but was superior to conventional catheter and NC mapping.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1053/J.GASTRO.2017.05.047
Abstract: Among patients with large colorectal sessile polyps or laterally spreading lesions, it is important to identify those at risk for submucosal invasive cancer (SMIC). Lesions with overt endoscopic evidence of SMIC are referred for surgery, although those without these features might still contain SMIC that is not visible on endoscopic inspection (covert SMIC). Lesions with a high covert SMIC risk might be better suited for endoscopic submucosal dissection than for endoscopic mucosal resection (EMR). We analyzed a group of patients with large colon lesions to identify factors associated with SMIC, and examined lesions without overt endoscopic high-risk signs to determine factors associated with covert SMIC. We performed a prospective cohort study of consecutive patients referred for EMR of large sessile or flat colorectal polyps or laterally spreading lesions (≥20 mm) at academic hospitals in Australia from September 2008 through September 2016. We collected data on patient and lesion characteristics, outcomes of procedures, and histology findings. We excluded serrated lesions from the analysis of covert SMIC due to their distinct phenotype and biologic features. We analyzed 2277 lesions (mean size, 36.9 mm) from 2106 patients (mean age, 67.7 years 53.2% male). SMIC was evident in 171 lesions (7.6%). Factors associated with SMIC included Kudo pit pattern V, a depressed component (0-IIc), rectosigmoid location, 0-Is or 0-IIa+Is Paris classification, non-granular surface morphology, and increasing size. After exclusion of lesions that were obviously SMIC or serrated, factors associated with covert SMIC were rectosigmoid location (odds ratio, 1.87 P = .01), combined Paris classification, surface morphology (odds ratios, 3.96-22.5), and increasing size (odds ratio, 1.16/10 mm P = .012). In a prospective study of 2106 patients who underwent EMR for large sessile or flat colorectal polyps or laterally spreading lesions, we associated rectosigmoid location, combined Paris classification and surface morphology, and increasing size with increased risk for covert malignancy. Rectosigmoid 0-Is and 0-IIa+Is non-granular lesions have a high risk for malignancy, whereas proximally located 0-Is or 0-IIa granular lesions have a low risk. These findings can be used to inform decisions on which patients should undergo endoscopic submucosal dissection, EMR, or surgery. ClinicalTrials.gov, Number: NCT02000141.
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.JOCN.2005.03.026
Abstract: Planum temporale volumes were determined for 42 control children (ages 4.2-15.7 years) using magnetic resonance imaging. The mean left planum temporale volume was 2729 mm3 (SD = 567) and the mean right planum temporale volume was 2758 mm3 (SD = 546). No significant hemispheric asymmetry was demonstrated. Analysis of co-variance (ANCOVA) showed that the absolute and proportional planum temporale volumes were not significantly associated with age or gender. We also demonstrated a reproducible method for planum temporale volume measurement by acquiring images in the coronal plane and then visualising the sagittal plane to improve accuracy for the posterior border.
Publisher: SAGE Publications
Date: 07-2018
Abstract: Application of medicated honey (MH) to peritoneal dialysis (PD) catheter exit sites has been found to be as effective as intra-nasal mupirocin for preventing PD catheter-related infections (CRIs), but was associated with increased risk for CRIs in diabetics. The efficacy of topical MH as a prophylactic agent has not been compared with the exit-site application of povidone iodine (PI). This retrospective multicentre cohort study compared cumulative incidence rates of PD CRIs (peritonitis or exit-site infections) and the number of PD CRIs observed per patient over the study period with PD exit-site application of MH or PI, in both diabetic and non-diabetic patients. Outcomes were compared in incident patients in 2 eras: January 2011 – December 2012, when 147 received exit-site care with PI (PI group), and July 2013 – June 2015, when 171 patients applied MH (MH group). Patients were followed until technique failure, death, transplant, or end of study treatment era. Cumulative incidence of PD CRIs was higher in the PI group (hazard ratio [HR] = 1.7, 95% confidence interval [CI] 1.1 – 2.6, p = 0.019) and the benefit of MH was not modified by diabetic status (present/absent, interaction p = 0.723). A similar trend was observed in the cumulative incidence of peritonitis (HR = 1.6, 95% CI 0.99 – 2.6, p = 0.059). After adjusting for months of exposure, the rate ratio for PD CRIs was 1.58 for PI compared to MH (95% CI, 1.03 – 2.42, p = 0.035). We conclude that exit-site application of MH is more effective than PI in preventing PD CRIs, and this effect is not modified by the presence or absence of diabetes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-10-2003
DOI: 10.1212/01.WNL.0000086373.32347.16
Abstract: To define the phenotypic variation in a large population of patients with Huntington disease (HD) and to identity clinical features that predict disability and the rate of disease progression. The authors analyzed data on 1,026 patients, followed for a median of 2.7 years, using a mixed effects model. The factors studied included the age at onset, the major clinical feature at onset, the severity of motor and cognitive impairment, and the level of disability. The mean age at onset was 41.5 (range 8 to 83) years, and patients were enrolled at all stages of disease. Younger onset was associated with more dystonia, less chorea, and a faster rate of motor, cognitive, and functional progression. The rate of progression was not related to the major clinical feature at onset or the sex of the affected parent. Disability correlated with the motor score (excluding chorea and dystonia) and the symbol-digit modalities test. Weight loss correlated with severe chorea. The rate of progression of HD was significantly more rapid with a younger age at onset. Therefore, CAG repeat length may be an important determinant of not only the age at onset, but also the rate of disease progression. Chorea was associated with weight loss, but chorea and dystonia were not major determinants of disability.
Publisher: Wiley
Date: 12-2006
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.YGYNO.2004.12.030
Abstract: BRCA1 mutations predispose to cancer in hormone responsive tissues. A predominance of estrogen receptor (ER)-negative breast cancers in BRCA1 mutation carriers and potential interactions between ERalpha and BRCA1 suggest a link between hormones and BRCA1. However, the expression pattern of ERalpha and other hormone receptors in BRCA1-associated ovarian cancer was unknown. Twenty-two BRCA1-associated ovarian cancer cases were matched with sporadic cases (no family history of ovarian or breast cancer) for FIGO stage, grade, histologic subtype, and patient age and hormone receptor expression was measured immunohistochemically. ERalpha expression was similar in BRCA1-associated ovarian cancer compared with matched sporadic counterparts, in contrast with previous findings in BRCA1-linked breast cancer. There was also no significant difference in expression of progesterone receptors and androgen receptor between the matched cases in the two groups. However, differences were noted in the relative expression of receptor isotypes, in particular, levels of ERalpha and ERbeta were positively correlated in sporadic tumors but inversely related in BRCA1-associated tumors. Similar hormone receptor expression in BRCA1-associated ovarian cancer and matched sporadic counterparts may be further evidence that at least a proportion of sporadic ovarian tumors and BRCA1-associated tumors develop through similar pathways.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2016
DOI: 10.1038/AJG.2016.235
Abstract: Clinically significant bleeding (CSPEB) is the most frequent adverse event following wide-field endoscopic mucosal resection (WF-EMR) of large sessile and laterally spreading colorectal lesions (LSL). There is limited knowledge regarding accurate prediction of CSPEB. We aimed to derive a score to predict the risk of CSPEB. Data on patient and lesion characteristics and outcomes from WF-EMRs of LSL ≥20 mm at 8 referral hospitals were analyzed. The cohort was ided at random into equal sized training and test groups. Independent predictors of CSPEB in the training cohort were identified by multiple logistic regression analysis and used to develop a risk score. The performance of this score was assessed in the independent test cohort. Over 80 months to June 2015, 2,128 patients with 2,424 LSL were referred for WF-EMR. Two thousand and twelve patients were eligible for analysis. There were 135 cases of CSPEB (6.7%). In the training cohort of 1,006 patients, the independent predictors of CSPEB were lesion size >30 mm (odds ratio (OR) 2.5), proximal colonic location (OR 2.3), presence of a major comorbidity (OR 1.5), and epinephrine in injection solution (OR 0.57). The derived risk score comprised lesion size >30 mm (2 points), proximal colon (2 points), presence of major comorbidity (1 point), and absence of epinephrine use (1 point). The probabilities of CSPEB for scores of 0, 1, 2, 3, 4, and ≥5 in the training cohort were 1.5, 2.0, 5.6, 7.8, 9.1, and 17.5% and were 0.9, 6.7, 4.9, 6.2, 9.0, and 15.7% in the test cohort. The probabilities of CSPEB in those with low (score 0-1), medium (score 2-4), and elevated (score 5-6) risk levels were 1.7, 7.1, and 17.5% in the training cohort and 3.4, 6.2, and 15.7% in the test cohort. Patients at elevated risk of CSPEB can be identified using four readily available variables. This knowledge may improve the management of those undergoing WF-EMR and assist in designing studies evaluating CSPEB.
Publisher: Elsevier BV
Date: 11-1998
DOI: 10.1016/S0046-8177(98)90257-X
Abstract: Patients with hepatitis C have an increased risk of developing hepatocellular carcinoma (HCC). This is related to the stage of chronic liver disease, as characterized histologically by hepatic fibrosis and architectural distortion, but it is unclear whether histological markers can define the risk of developing HCC. We conducted a case-control immunohistochemical study of Ki-67, a marker for hepatocellular proliferation, in livers of 18 patients who had developed HCC more than 2 years after the biopsy specimen had been taken. Using conditional logistic regression analysis, the results were compared with 18 selected controls, who were age-matched patients with hepatitis C of similar histological stage who had not developed HCC. We also examined livers for cellular dysplasia, p53 mutations, and bcl-2 overexpression, and assessed whether the results could be correlated with demographic and disease-related variables, such as gender, region of birth, alcohol consumption, severity of liver disease, HCV genotype, and markers of hepatitis B virus (HBV) infection. Livers from patients who developed HCC were more often positive for Ki-67 (13 of 18 [72%] v 9 of 18 [50%] P = .06) and tended to have higher mean Ki-67 scores (6 +/- 7.5 v 3 +/- 4.4 P = .10) compared with control cases. In the HCC-predisposed group, three livers showed large cell dysplasia, two were positive for p53 mutations, and two for bcl-2 overexpression. In contrast, in the non-HCC group, only one case had dysplasia, and none were positive for immunostaining for p53 or bcl-2 mutations. With the exception of one case, all livers with large cell dysplasia or p53 mutations and bcl-2 overexpression were also positive for Ki-67. Twelve (55%) of the 22 Ki-67-positive cases were anti-HBc-positive in the serum, in contrast to 2 of 14 (14%) patients in the Ki-67-negative group (P = .01). Patients with evidence of past infection with HBV were more often Ki-67 positive than those who had no evidence of past infection (85% [11 of 13] v 45% [10 of 22] P = .02). There were no other associations between demographic or disease-related variables and Ki-67 expression. Increased hepatocellular proliferative activity, as assessed by Ki-67 expression, may be one factor indicative of an increased risk of developing HCC among patients with chronic hepatitis C. Furthermore, past infection with HBV appears to be an important correlate of increased hepatocellular proliferation in hepatitis C.
Publisher: Wiley
Date: 28-06-2005
DOI: 10.1002/IJC.21250
Abstract: Recurrent chromosome 8q gain in ovarian carcinoma is likely to reflect the existence of multiple target loci, as the separate gain of chromosome bands 8q21 and 8q24 has been reported in independent studies. Since tumor protein D52 (TPD52) has been identified as a chromosome 8q21 lification target in breast and prostate carcinoma, we compared TPD52 expression in normal ovarian epithelium (n = 9), benign serous adenomas (n = 11), serous borderline tumors (n = 6) and invasive carcinomas of the major histologic subtypes (n = 57) using immunohistochemistry. These analyses revealed that all normal ovarian epithelium s les and benign serous tumors were predominantly TPD52-negative, whereas TPD52 was overexpressed in most (44/57 77%) ovarian carcinomas regardless of histologic subtype. TPD52 subcellular localization was predominantly cytoplasmic, although nuclear localization was also frequently observed in mucinous and clear cell carcinomas. In an independent cohort of stage III serous carcinomas (n = 18), we also directly compared in situ TPD52 expression using immunohistochemistry and TPD52 copy number using interphase FISH analyses. This revealed that TPD52 dosage and TPD52 expression were significantly positively correlated. TPD52 therefore represents a novel molecular marker in ovarian cancer, which is broadly expressed across the different histologic subtypes and whose upregulation frequently reflects increased TPD52 copy number.
Publisher: Wiley
Date: 2006
DOI: 10.1111/J.1540-8167.2005.00324.X
Abstract: Reentrant circuits causing ventricular tachycardia are closely associated with previously scarred myocardium. The presence of scar has been blamed for the poor success rate of radiofrequency ablation (RFA) in that context. This article investigates the in vivo effects of radiofrequency ablation in myocardium scarred from acute myocardial infarction. Anterior myocardial infarction was induced in five dogs by ligating the left anterior descending artery. The mean left ventricular ejection fraction after infarction was 38%. At a mean of 15 weeks following myocardial infarction, 50 RFA lesions were created in random order, 25 in scarred and 25 in normal myocardium using a needle electrode (21 gauge, 5 mm in length) introduced from the epicardium of the left ventricle at thoracotomy. During unipolar temperature-controlled RFA (90 degrees C for 60 seconds), intramural temperatures were measured by thermistors at distances of 1, 2, 3, 4, and 5 mm from the ablating electrode. The margins of the lesions were clearly discernible in scar at histological examination in 64% of ablations where the scarring was patchy. There were no significant differences between lesion sizes, intramural temperatures at different distances, total energy required for ablation, or mean impedance during ablation of normal versus scarred myocardium. Scar does not affect lesion size or intramural temperature profile during RFA if electrode size, tissue contact, and tip temperature are controlled. More radiofrequency energy is not required to maintain tip temperature at 90 degrees C in scar compared to normal myocardium.
Publisher: Elsevier BV
Date: 12-2004
DOI: 10.1016/J.YGYNO.2004.08.035
Abstract: Mutation of the BRCA1 gene, which has incomplete penetrance, is involved in ovarian cancer development. Cell cycle check point inactivation via acquired somatic mutations in the check point regulatory genes, particularly p53, may be required for BRCA1-linked ovarian tumorigenesis. In the few studies directly comparing p53 mutations in BRCA1-linked and sporadic ovarian cancers, data have been contradictory. This study aimed to clarify the role of p53 mutation in BRCA1-associated and sporadic ovarian cancer by comparing two, large, matched cohorts from two different populations who developed BRCA1-linked or sporadic ovarian cancers. Forty-eight BRCA1-associated ovarian tumor s les (22 from Australia and 26 from Norway) were collected and matched with 48 sporadic ovarian cancers for tumor stage, grade, histological subtype, and patient age. Expression of p53 protein was measured by immunohistochemistry (IHC). Consistent with the presence of a mutated p53 protein, the majority of BRCA1-associated (79%) and sporadic (73%) ovarian carcinomas from Australia and Norway overexpressed p53 protein. There was no significant difference between BRCA1-linked ovarian cancers and their sporadic counterparts with regard to p53 protein expression (P = 0.5). Our results suggest that p53 inactivation is associated with both BRCA1-associated and sporadic ovarian tumorigenesis, and that BRCA1-linked and sporadic ovarian cancers may develop through a similar carcinogenic pathway.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1053/J.GASTRO.2011.02.062
Abstract: Large sessile colonic polyps usually are managed surgically, with significant morbidity and potential mortality. There have been few prospective, intention-to-treat, multicenter studies of endoscopic mucosal resection (EMR). We investigated whether endoscopic criteria can predict invasive disease and direct the optimal treatment strategy. The Australian Colonic Endoscopic (ACE) resection study group conducted a prospective, multicenter, observational study of all patients referred for EMR of sessile colorectal polyps that were 20 mm or greater in size (n=479, mean age, 68.5 y mean lesion size, 35.6 mm). We analyzed data on lesion characteristics and procedural, clinical, and histologic outcomes. Multiple logistic regression analysis identified independent predictors of EMR efficacy and recurrence of adenoma, based on findings from follow-up colonoscopy examinations. Risk factors for submucosal invasion were as follows: Paris classification 0-IIa+c morphology, nongranular surface, and Kudo pit pattern type V. The most commonly observed lesion (0-IIa granular) had a low rate of submucosal invasion (1.4%). EMR was effective at completely removing the polyp in a single session in 89.2% of patients risk factors for lack of efficacy included a prior attempt at EMR (odds ratio [OR], 3.8 95% confidence interval, 1.77-7.94 P=.001) and ileocecal valve involvement (OR, 3.4 95% confidence interval, 1.20-9.52 P=.021). Independent predictors of recurrence after effective EMR were lesion size greater than 40 mm (OR, 4.37 95% confidence interval, 2.43-7.88 P<.001) and use of argon plasma coagulation (OR, 3.51 95% confidence interval, 1.69-7.27 P=.0017). There were no deaths from EMR 83.7% of patients avoided surgery. Large sessile colonic polyps can be managed safely and effectively by endoscopy. Endoscopic assessment identifies lesions at increased risk of containing submucosal cancer. The first EMR is an important determinant of patient outcome-a previous attempt is a significant risk factor for lack of efficacy.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 1996
DOI: 10.1111/J.1440-1746.1996.TB00015.X
Abstract: This study examined the associations of in idual coexisting illnesses, septicaemia, intra-abdominal abscess, marital status, smoking and alcohol use, with mortality following perforation of peptic ulcer without pre-operative evidence of haemorrhage. Patients who died in hospital following ulcer perforation (cases n = 300) were compared with patients who survived following ulcer perforation (controls n = 276). The controls were frequency-matched to the cases on age, sex and perforation site. Data were analysed by logistic regression. Cardiac, respiratory, cerebrovascular, renal, liver and malignant diseases, and septicaemia and intra-abdominal abscess were associated with mortality and the coexisting illnesses were significantly increased in cases compared to controls both on admission and at the end of hospital stay. During hospitalization, the odds of pneumonia decreased in cases, otherwise there was little change in strengths of associations over this period. Being widowed or never married was positively associated with mortality, and moderate alcohol use was negatively associated. In conclusion, this study identifies several coexisting illnesses, septicaemia and intra-abdominal abscess as risk factors for mortality following ulcer perforation. The results suggest that, with little exception, the same level of mortality risk is associated with coexisting illnesses whether the beginning or end of hospital stay is used as the index time point.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2003
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-01-2021
Abstract: Left atrial (LA) function plays a pivotal role in modulating left ventricular performance. The aim of our study was to evaluate the relationship between resting LA function by strain analysis and exercise capacity in patients with chronic kidney disease (CKD) and evaluate its utility compared with exercise E/e'. Consecutive patients with stage 3 and 4 CKD without prior cardiac history were prospectively recruited from outpatient nephrology clinics and underwent clinical evaluation and resting and exercise stress echocardiography. Resting echocardiographic parameters including E/e' and phasic LA strain (LA reservoir [LASr], conduit, and contractile strain) were measured and compared with exercise E/e'. A total of 218 (63.9±11.7 years, 64% men) patients with CKD were recruited. Independent clinical parameters associated with exercise capacity were age, estimated glomerular filtration rate, body mass index, and sex ( P .01 for all), while independent resting echocardiographic parameters included E/e', LASr, and LA contractile strain ( P .01 for all). Among resting echocardiographic parameters, LASr demonstrated the strongest positive correlation to metabolic equivalents achieved (r=0.70 P .01). Receiver operating characteristic curves demonstrated that LASr (area under the curve, 0.83) had similar diagnostic performance as exercise E/e' (area under the curve, 0.79 P =0.20 on DeLong test). A model combining LASr and clinical metrics showed robust association with metabolic equivalents achieved in patients with CKD. LASr, a marker of decreased LA compliance is an independent correlate of exercise capacity in patients with stage 3 and 4 CKD, with similar diagnostic value to exercise E/e'. Thus, LASr may serve as a resting biomarker of functional capacity in this population.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.PATHOL.2016.04.004
Abstract: Extractable nuclear antigen (ENA) antibody testing is often requested in patients with suspected connective tissue diseases. Most laboratories in Australia use a two step process involving a high sensitivity screening assay followed by a high specificity confirmation test. Multiplexing technology with Addressable Laser Bead Immunoassay (e.g., FIDIS) offers simultaneous detection of multiple antibody specificities, allowing a single step screening and confirmation. We compared our current diagnostic laboratory testing algorithm [Organtec ELISA screen / Euroimmun line immunoassay (LIA) confirmation] and the FIDIS Connective Profile. A total of 529 s les (443 consecutive+86 known autoantibody positivity) were run through both algorithms, and 479 s les (90.5%) were concordant. The same autoantibody profile was detected in 100 s les (18.9%) and 379 were concordant negative s les (71.6%). The 50 discordant s les (9.5%) were sub ided into 'likely FIDIS or current method correct' or 'unresolved' based on ancillary data. 'Unresolved' s les (n = 25) were subclassified into 'potentially' versus 'potentially not' clinically significant based on the change to clinical interpretation. Only nine s les (1.7%) were deemed to be 'potentially clinically significant'. Overall, we found that the FIDIS Connective Profile ENA kit is non-inferior to the current ELISA screen/LIA characterisation. Reagent and capital costs may be limiting factors in using the FIDIS, but potential benefits include a single step analysis and simultaneous detection of dsDNA antibodies.
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.BREAST.2012.09.001
Abstract: The aim of this study was to determine the impact of universal HER2 testing on the clinico-pathologic profile of HER2+ breast cancer. Data were extracted from breast cancer pathology reports spanning two periods: before (2003/4, n = 379), and after (2008/9, n = 560) the introduction of universal testing. In 2003/4, 43.3% of breast cancers were tested for HER2 with 16% of tested cases HER2+. In 2008/9, 98.4% of cases were tested with 14.7% HER2+. In 2008/9, HER2+ status was associated with younger age, higher grade, increased tumour size, lymph node involvement, negative oestrogen and/or progesterone receptor status. HER2+ cases diagnosed in 2003/4 were not significantly different in respect of these features. The rate of HER2+ breast cancer amongst screen detected cases in 2008/9 was 8.3%. The phenotype of HER2+ breast cancer was stable following the introduction of universal testing. The overall rate of HER2+ breast cancer was influenced by screen detection.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2003
DOI: 10.1111/J.1572-0241.2003.07468.X
Abstract: We tested whether fibrotic progression in chronic hepatitis C could be predicted by liver tests, antipyrine clearance, or platelet count. In 58 patients (6 untreated, 52 interferon-treated), a second liver biopsy was taken median 4.5 yr after first histologic diagnosis. We used receiver operating characteristic curves to determine whether changes in conventional liver tests, antipyrine clearance, or platelet count were predictive of altered hepatic fibrosis score. Apart from a weak association with change in ALT, conventional liver tests (albumin, bilirubin, prothrombin time) failed to correlate with changes (Delta) in hepatic fibrosis, but there were significant correlations between deltaantipyrine clearance or deltaplatelet count and deltafibrosis score (p < 0.01). As indicated by areas under the receiver operating characteristic curves, the diagnostic accuracy of deltaantipyrine clearance for fibrotic progression was 68% for Deltaplatelet count it was 80%. With defined cut-off values (-0.05 ml/min/kg for deltaantipyrine clearance -41 x 10(9)/L for deltaplatelet count), the negative predictive values for fibrotic progression were 85% with antipyrine clearance and 89% with platelet count. Corresponding positive predictive values were 48% and 91%, respectively. Changes in antipyrine clearance and platelet count are more sensitive than conventional tests for indicating fibrotic change in chronic hepatitis C. Both could be used to reliably identify those who do not have fibrotic progression, and platelet count also has a high positive predictive value for disease progression.
Publisher: AMPCo
Date: 10-1986
Publisher: Springer Science and Business Media LLC
Date: 19-07-2013
DOI: 10.1038/EYE.2013.143
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.GIE.2016.02.049
Abstract: Large sporadic duodenal adenomas are uncommon but they harbor malignant potential, which requires consideration of definitive treatment. EMR is gaining acceptance as an effective and safe alternative to high-risk surgical procedures, but data on long-term outcomes are limited. Herein we describe the short- and long-term outcomes of these lesions in a tertiary referral center. Prospectively collected data were analyzed to identify risk factors for adverse events and outcomes. Patient demographics, lesion characteristics, and procedural technical data were collected. From 2007 to 2015, 106 adenomas ≥10 mm were resected (mean patient age, 69 years 54% male median size, 25 mm interquartile range [IQR], 19-40). Complete endoscopic resection was achieved in 96%. Intraprocedural bleeding occurred in 43% of cases and was associated with lesion size (P < .001), number of resected specimens (P = .003), and longer procedures (P = .001). Delayed bleeding occurred in 15% (56% did not require active intervention) and was associated with lesion size (P = .03). Perforation occurred in 3 patients. The 30-day mortality was 0%. Median follow-up was 22 months (IQR, 7-45). Histologically proven adenoma recurrence was identified and treated in 12 of 83 patients (14.4%) on first surveillance endoscopy. For the 53 patients for whom follow-up ≥12 months was available (median follow-up, 36 months IQR, 24-51), 48 patients (90.6%) were free of adenoma and considered cured. In a tertiary referral center, endoscopic resection of duodenal adenomas is a safe and effective alternative to surgery. Lesion size is strongly associated with adverse events, particularly intraprocedural bleeding and delayed bleeding. Good long-term outcomes are demonstrated.
Publisher: Wiley
Date: 14-02-2015
DOI: 10.1111/JCE.12598
Abstract: Steam pop is an explosive rupture of cardiac tissue caused by tissue overheating above 100 °C, resulting in steam formation, predisposing to serious complications associated with radiofrequency (RF) ablations. However, there are currently no reliable techniques to predict the occurrence of steam pops. We propose the utility of acoustic signals emitted during RF ablation as a novel method to predict steam pop formation and potentially prevent serious complications. Radiofrequency generator parameters (power, impedance, and temperature) were temporally recorded during ablations performed in an in vitro bovine myocardial model. The acoustic system consisted of HTI-96-min hydrophone, microphone pre lifier, and sound card connected to a laptop computer. The hydrophone has the frequency range of 2 Hz to 30 kHz and nominal sensitivity in the range -240 to -165 dB. The sound was s led at 96 kHz with 24-bit resolution. Output signal from the hydrophone was fed into the camera audio input to synchronize the video stream. An automated system was developed for the detection and analysis of acoustic events. Nine steam pops were observed. Three distinct sounds were identified as warning signals, each indicating rapid steam formation and its release from tissue. These sounds had a broad frequency range up to 6 kHz with several spectral peaks around 2-3 kHz. Subjectively, these warning signals were perceived as separate loud clicks, a quick succession of clicks, or continuous squeaking noise. Characteristic acoustic signals were identified preceding 80% of pops occurrence. Six cardiologists were able to identify 65% of acoustic signals accurately preceding the pop. An automated system identified the characteristic warning signals in 85% of cases. The mean time from the first acoustic signal to pop occurrence was 46 ± 20 seconds. The automated system had 72.7% sensitivity and 88.9% specificity for predicting pops. Easily identifiable characteristic acoustic emissions predictably occur before imminent steam popping during RF ablations. Such acoustic emissions can be carefully monitored during an ablation and may be useful to prevent serious complications during RF delivery.
Publisher: SAGE Publications
Date: 09-2004
DOI: 10.1177/021849230401200310
Abstract: This study aimed to evaluate the risk factors for sternal wound complications in patients undergoing myocardial revascularization using bilateral semi-skeletonized internal mammary arteries. Prospectively collected data on 751 patients undergoing coronary artery surgery from September 1994 to August 2002 were analyzed. The mean age of the patients was 56 years, 633 (84%) were male, 44 (6%) were over 66 years of age, and 170 (23%) were diabetic. Forty-four (5.9%) patients developed sternal wound complications. Among these cases, sternal infection occurred in 22 (2.9%) patients, of which 15 (2.0%) had sternal infection with mediastinitis and 7 (0.9%) had sternal infection alone. Independent risk factors for any sternal wound complications were peripheral vascular disease, diet-controlled diabetes, and delayed sternal closure. The risk factors for sternal infection were diabetes, postoperative pulmonary complications, and postoperative stroke. The perioperative mortality rate was 1.5% (11 patients), including 2 patients who had sternal wound complications. The use of bilateral semi-skeletonized internal mammary artery conduits carries a comparable sternal wound complication rate as conduits harvested by other techniques.
Publisher: Wiley
Date: 04-1998
DOI: 10.1111/J.1440-1746.1998.TB00657.X
Abstract: In order to determine the contribution of alcohol intake to the severity of hepatic fibrosis in patients with chronic hepatitis C, we studied associations between various levels of alcohol intake, other demographic variables and semiquantitative liver histology in 434 cases of chronic hepatitis C. Clinical, demographic and disease-related data were entered into a relational database. Liver histology was scored according to Scheuer. The average daily alcohol intake for the year preceding liver biopsy (recent exposure) and for earlier periods (past exposure) was categorized into five levels of intake. One-third of patients gave a history of alcohol intake that had exceeded 40 g/day for at least 5 years. By univariate analysis, age, but not recent or past alcohol intake or other baseline variables, was associated with portal score (r = 0.14, P = 0.004), fibrosis score (r = 0.46, P < 0.001), total Scheuer score (r = 0.35, P < 0.001). However, by multivariate analysis, age (P < 0.001), past (but not present) alcohol intake (P < 0.001) and birth in Egypt (P = 0.006) were independently associated with fibrosis score. Age, past alcohol and birth place in Egypt contributed 27% to total variance of the hepatic fibrosis score, while age alone accounted for 23%. Age also independently predicted portal activity (P = 0.02) and total Scheuer score (P < 0.001), whereas past alcohol intake correlated with total Scheuer score (P = 0.002) but not with other histological indices. A separate multivariate analysis was performed on a more homogeneous subgroup of 196 patients who acquired hepatitis C by injection drug use. In this subgroup, age (P < 0.05) and past alcohol (P 80 g/day) beyond which the risk of fibrosis increased significantly. It is concluded that toxic levels of alcohol exposure for at least 5 years accentuate hepatic fibrosis in hepatitis C but the influence of alcohol appears to be minor compared with age and other variables and is exerted only at toxic levels of intake.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1987
Publisher: Public Library of Science (PLoS)
Date: 04-06-2021
DOI: 10.1371/JOURNAL.PONE.0252569
Abstract: The impact of sleep disordered breathing (SDB) on arterial intima-media thickness (IMT), a surrogate measure for cardiovascular disease, remains uncertain, in part because of the potential for non-SDB vascular risk factor interactions. In the present study, we determined predictors for common carotid (CCA) and femoral (CFA) artery IMT in an adult, sleep clinic cohort where non-SDB vascular risk factors (particularly diabetes) were eliminated or controlled. We recruited 296 participants for polysomnography (standard SDB severity metrics) and CCA/CFA ultrasound examinations, followed by a 12 month vascular risk factor minimisation (RFM) and continuous positive pressure (CPAP) intervention for participants with a range of SDB severity (RFM Sub-Group, n = 157 apnea hyponea index [AHI]: 14.7 (7.2–33.2), median [IQR]). Univariable and multivariable linear regression models determined independent predictors for IMT. Linear mixed effects modelling determined independent predictors for IMT change across the intervention study. P .05 was considered significant. Age, systolic blood pressure and waist:hip ratio were identified as non-SDB predictive factors for CCA IMT and age, weight and total cholesterol:HDL ratio for CFA IMT. No SDB severity metric emerged as an independent predictor for either CCA or CFA IMT, except in the RFM Sub-Group, where a 2-fold increase in AHI predicted a 2.4% increase in CFA IMT. Across the intervention study, CCA IMT decreased in those who lost weight, but there was no CPAP use interaction. CFA IMT, however, decreased by 12.9% (95%CI 6.8, 18.7%, p = 0.001) in those participants who both lost weight and used CPAP = 4hours/night. We conclude that SDB severity has little impact on CCA IMT values when non-SDB vascular risk factors are minimised or not present. This is the first study, however, to suggest a potential linkage between SDB severity and CFA IMT values. Australian New Zealand Clinical Trials Registry, ACTRN12611000250932 and ACTRN12620000694910 .
Publisher: Wiley
Date: 17-02-2022
DOI: 10.1002/JBM4.10607
Abstract: The earliest reports of atypical femur fractures (AFF) emerged from Asia. In the West, epidemiologic studies report a greater incidence of AFFs among subjects of Asian background. Asian ethnicity is an established risk factor for AFF, but clear mechanisms to explain this risk and implications for the general development of AFF are open questions. Ethno‐specific differences in bisphosphonate action and femoral geometry have been proposed as hypotheses. In a retrospective cohort of 163 female patients presenting with AFFs or typical femur fractures (TFF), relative contributions of Asian ethnicity, proximal femoral geometry, and bisphosphonate use in AFF status were examined. There was a fourfold higher proportion of Asian subjects in the AFF compared with TFF groups (31.6%, 30/95 versus 7.4%, 5/68). Asian subjects had smaller femurs in femoral head, neck, and axial dimensions. A multiple logistic regression model for AFF status was fitted adding Asian ethnicity to three previously reported independent predictors of AFF including femoral geometry, which together comprise the Sydney AFF Score (age ≤80 years, femoral neck width mm than non‐Asian, lateral cortical width at lesser trochanter ≥5 mm). Asian ethnicity was a robust independent predictor of AFF, imparting sevenfold increase in the odds of AFF after adjusting for all three variables (95% confidence interval [CI] 2.2–23.2, p = 0.001) or for overall AFF score (95% CI 2.2–22.3 p = 0.001). Overall Asian subjects had higher rates of bisphosphonate use than non‐Asian subjects (67.6% versus 47.2%, p = 0.034). Among AFF bisphosphonate users, Asian subjects had lower AFF scores than non‐Asians (Sydney AFF Score ≤1, 45.5% Asian subjects versus 22.2% non‐Asian subjects, p = 0.05). Asian ethnicity is a strong independent risk factor for AFF, unaccounted for by ethno‐specific differences in proximal femoral geometry. Bisphosphonate use may be associated with a greater predisposition for AFF in Asian subjects compared with non‐Asian subjects. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Publisher: Wiley
Date: 06-1999
DOI: 10.1111/J.1445-5994.1999.TB00716.X
Abstract: The relative efficacy of antitachycardia pacing implantable cardioverter defibrillators (ATPICD) and sotalol in the treatment of ventricular tachyarrhythmias is controversial. To compare the mortality in patients treated with ATPICD and sotalol for documented spontaneous sustained ventricular tachyarrhythmias occurring late after previous myocardial infarction. In this non-randomised retrospective study of 139 consecutive patients all patients had inducible ventricular tachycardia at baseline electrophysiological studies. Before the availability of ATPICD, 22 patients were treated with sotalol as part of a randomised study comparing the efficacy of sotalol to amiodarone. After ATPICD became available sotalol was used in 49 patients in whom intravenous testing predicted sotalol to be effective and ATPICD were implanted in 68 patients in whom sotalol was predicted to be ineffective at electrophysiological testing. Thus, 68 patients were treated with an ATPICD and 71 with sotalol. The two groups were well-matched for age, type of presenting arrhythmia, severity of coronary artery disease and ventricular function. At 36 months Kaplan-Meier estimates of mortality from ventricular tachyarrhythmia were 0% with ATPICD and 15% with sotalol (p=0.03). Kaplan-Meier estimates of total mortality at 36 months were 12% with ATPICD and 25% with sotalol (p=0.09). Multivariate analysis showed hazard ratio of 7.9 (p=0.06) for death from ventricular tachyarrhythmia in patients treated with sotalol compared to ATPICD. While no difference in total mortality was demonstrated, treatment with ATPICD is probably superior to sotalol for preventing deaths due to ventricular tachyarrhythmia.
Publisher: Elsevier BV
Date: 07-1990
DOI: 10.1016/0016-5085(90)91230-4
Abstract: Ability to taste phenylthiocarbamide is genetically determined and has been investigated as a possible genetic marker for disease. This study examined phenylthiocarbamide taste sensitivity in gastric and duodenal ulcer disease. The study s le included 164 patients with gastric ulcer, 134 with duodenal ulcer, and 299 community controls. Eight concentrations of phenylthiocarbamide in distilled water were obtained by binary serial dilution. The lowest concentration distinguished by taste from distilled water defined taste threshold. Bimodality of threshold distributions distinguished nontasters from tasters. Comparisons of patients with controls gave odds ratios of nontaste in gastric ulcer and duodenal ulcer of, respectively, 0.7 (P greater than 0.1) and 1.3 (P greater than 0.03). The power of detecting at least a twofold difference between patients and controls in the odds of nontaste was 80%. Nontaste was more common in duodenal than in gastric ulcer patients (odds ratio = 2.0, P = 0.02). Taste sensitivity was unassociated with other genetic factors related to ulcer--ABO blood group, secretor status, and serum pepsinogen 1 level. The difference between gastric and duodenal ulcer patients in the ability to taste phenylthiocarbamide may be genetic however, this study's inability, despite substantial power, to detect at least a twofold difference between patients and controls suggests that if phenylthiocarbamide taste sensitivity is a genetic factor in peptic ulcer, the relationship is weak.
Publisher: Springer Science and Business Media LLC
Date: 09-12-2016
DOI: 10.1007/S00701-015-2647-6
Abstract: A study of the risk factors associated with complications during intracranial EEG monitoring led to a change in protocol for monitoring and implantation at our centres. We conducted a study to identify any reduction in complications following the changed protocols involving the use of smaller subdural electrode arrays, continuous ICP monitoring, use of a central line, and intake of prophylactic antibiotics and dexamethasone. We prospectively collected data on patient outcomes between 2005 and 2012 (group B) compared with patients between 1988 and 2004 (group A) before the protocol changes. Seventy-one patients in group A and 58 patients in group B underwent intracranial electrode implantation. Complications directly related to grids occurred in 25 % of group A vs. 8.6 % in group B (p < 0.05) and those indirectly related to grids were 11.2 % in group A vs. none in group B. The rate of transient complications requiring no treatment was 12.5 % in group A versus 1.7 % in group B. The rate of transient complications requiring treatment was 10 % in group A and 6.9 % in group B. There were two deaths in group A. The infection rate was higher in group B than group A (5.2 % vs. 2.8 % p = 0.90). Since 2008 there have been no infective complications. Complications directly related to intracranial EEG monitoring were significantly reduced using the revised protocol (p < 0.05). Regression analysis identifying only the size of the grids (≤4 × 8 grid arrays) implanted was an independent predictor of more complications in group A (P < 0.05). Complication rates following intracranial implantation decreased following the use of a small grid size and adherence to a stringent protocol.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Wiley
Date: 10-1993
DOI: 10.1111/J.1445-5994.1993.TB01832.X
Abstract: Trephine biopsy of the bone marrow is integral to both diagnosis and prognosis in B-cell lymphocytic leukaemia (B-CLL), but its usefulness would be enhanced by more information on the type, degree and rate of change that occur over time in histologic pattern and lymphocytic infiltration. To investigate these changes by serial trephine biopsy in totally untreated patients, in treatment-free intervals in treated patients and during intervals of treatment. In 82 patients with predominantly early B-CLL observed for a median of 65 months (13-331), 309 trephine biopsies were carried out, a median of three (two to eight) per patient. The biopsies were classified into nodular, interstitial, mixed and diffuse patterns. Lymphocytic infiltration was subjectively graded into minimal ( 50%) categories and all changes were compared. Intensity of infiltration increased through this histologic range, as did the relative risk of death. Survival of patients with > 50% involvement was significantly poorer than those with < 50%. Changes in both lymphocyte numbers and pattern occurred slowly in early disease but quickened as the leukaemia advanced. Under treatment, lymphocytes decreased but the histology did not alter significantly. Examining the marrow for disease progression should be part of regular follow-up. It may help identify the minority of patients with early disease which will run a more active course and in whom early therapy may yet be indicated. We recommend biopsy at two-yearly intervals in early disease, more frequently as the leukaemia advances. The minimal, intermediate and majority classification in addition to the histologic pattern is a useful grading.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.CGH.2014.01.026
Abstract: Bleeding is the main complication of wide-field endoscopic mucosal resection (WF-EMR) for large colonic lesions. Few studies have examined bleeding outcomes after WF-EMR, and there are no evidence-based guidelines for management of bleeding in this group. We analyzed outcomes of patients with clinically significant post-EMR bleeding (CSPEB) and present a management algorithm based on our findings. In a prospective study, we collected data from WF-EMR of sessile colorectal polyps 20 mm or larger from 1039 patients who participated in the Australian Colonic Endoscopic resection multicenter study from July 2008 through May 2012. Data included patient and lesion characteristics and procedural, clinical, and histologic outcomes. Patients participated in a structured telephone interview 14 days after the procedure independent predictors of a moderate or severe outcome by American Society of Gastrointestinal Endoscopists criteria, or any intervention for hemostasis, were identified. Sixty-two patients had CSPEB (6.0%) 34 were managed conservatively (55%) and 27 underwent colonoscopy (44%). One patient had primary embolization. Endoscopic therapy was applied in 21 cases 14 had active bleeding. Two of the conservatively managed cases underwent colonoscopy for rebleeding after discharge. On multivariable analysis, moderate or severe bleeding events were associated with hemodynamic instability (odds ratio, 12.3 P = .046) and low level of hemoglobin at presentation (odds ratio, 0.50 per 1.0 g/dL P = .005). Intervention for hemostasis was associated with hourly or more frequent hematochezia (odds ratio, 36.7 P = .001), American Society of Anesthesiologists grade 2 or higher (odds ratio, 20.1 P < .001), and transfusion (odds ratio, 18.7 P = .003). Based on a multicenter prospective study, CSPEB resolves spontaneously in 55% of patients. We developed a risk factor-based algorithm that might assist physicians in the management of bleeding. Patients responding to initial resuscitation can be observed, with a lower threshold for intervention in those with the identified risk factors.
Publisher: BMJ
Date: 20-01-2022
Abstract: Local anesthetic wound infusion catheters are increasingly used postmidline laparotomy to reduce pain and opioid use, however there is little evidence to support any particular infusion regime. A retrospective cohort study was undertaken of patients after midline laparotomy who had bilateral local anesthetic wound infusion catheters surgically placed. Patients were recruited into 3 cohorts: ropivacaine 0.2% 5–8 mL/hour continuous wound infusion, 10 mL programmed intermittent bolus 2 hourly, 20 mL programmed intermittent bolus 4 hourly. The primary outcome was the maximum daily Numerical Rating Pain Score with movement (dynamic pain score) recorded during first 96 hours postprocedure. Secondary outcomes included the maximum daily resting pain score and opioid utilization. In three cohorts of 70 patients (n=210), the maximum daily dynamic pain score in the intermittent bolus 2-hourly and 4-hourly cohorts was lower when compared with the continuous infusion group over the first 4 postoperative days. The mean difference in maximum daily pain score with respect to the continuous infusion regime was 0.8 (95% CI 0.2 to 1.4) for the intermittent bolus 2-hourly group and 0.6 (95% CI 0.0 to 1.2) for the 4-hourly group. Generalized estimating equation modeling indicates the reduction in dynamic pain score is greatest with the intermittent bolus 2-hourly regime over the first 72 hours postprocedure. The 2-hourly intermittent bolus regime was also associated with lower opioid utilization and local anesthetic exposure. Intermittent wound infusion catheter infusion regimes were associated with lower maximum daily dynamic pain scores, although the magnitude of this change may be of limited clinical significance.
Publisher: American Association for Cancer Research (AACR)
Date: 15-12-2008
DOI: 10.1158/1078-0432.CCR-08-0939
Abstract: Purpose: Increased incidence of ductal carcinoma in situ (DCIS) associated with mammographic screening for breast cancer has emphasized the challenges of managing this condition. The aim of this study was to identify informative clinical indicators of DCIS biology by molecular profiling. Experimental Design: Areas of in situ carcinoma, atypical ductal hyperplasia, and benign epithelium were microdissected from 46 invasive breast cancers. Oligonucleotide probes showing differential expression between DCIS associated with grade 1 and 3 invasive cancer were identified by microarray-based gene expression profiling. Expression at these probes was used to define a “molecular grade” subcategorization of all s les. The genomic basis of molecular grade was examined by array-based comparative genomic hybridization. Clinical course was examined in a cohort of 134 patients with DCIS treated by surgery alone. Results: DCIS s les were designated as low or high molecular grade based on expression at 173 probes. The low molecular grade subgroup included low (n = 10) and intermediate (n = 11) nuclear grade DCIS as well as all s les of atypical ductal hyperplasia (n = 4) and benign epithelium (n = 7). The high molecular grade subgroup included DCIS of intermediate (n = 7) and high (n = 19) nuclear grade. The character and degree of genomic aberration were distinct between molecular grade subgroups. A classification tree model including nuclear grade and Ki67 score accurately predicted molecular grade for 95.7% of s les. In an independent cohort, this showed a pattern of rapid disease recurrence for high molecular grade DCIS. Conclusions: Molecular profiling indicates a binary grading scheme for DCIS. This practical approach has potential to improve clinical evaluation of DCIS.
Publisher: BMJ
Date: 07-2014
DOI: 10.1136/GUTJNL-2013-305516
Abstract: Wide-field endoscopic mucosal resection (WF-EMR) is an alternative to surgery for treatment of advanced colonic mucosal neoplasia up to 120 mm in size, but has been criticised for its potentially high recurrence rates. We aimed to quantify recurrence at 4 months (early) and 16 months (late) following successful WF-EMR and identify its risk factors and clinical significance. Ongoing multicentre, prospective, intention-to-treat analysis of sessile or laterally spreading colonic lesions ≥20 mm in size referred for WF-EMR to seven academic endoscopy units. Surveillance colonoscopy (SC) was performed 4 months (SC1) and 16 months (SC2) after WF-EMR, with photographic documentation and biopsy of the scar. 1134 consecutive patients were enrolled when 1000 successful EMRs were achieved, of whom 799 have undergone SC1. 670 were normal. Early recurrent/residual adenoma was present in 128 (16.0%, 95% CI 13.6% to 18.7%). One case was unknown. The recurrent/residual adenoma was diminutive in 71.7% of cases. On multivariable analysis, risk factors were lesion size >40 mm, use of argon plasma coagulation and intraprocedural bleeding. Of 670 with normal SC1, 426 have undergone SC2, with late recurrence present in 17 cases (4.0%, 95% CI 2.4% to 6.2%). Overall, recurrent/residual adenoma was successfully treated endoscopically in 135 of 145 cases (93.1%, 95% CI 88.1% to 96.4%). If the initial EMR was deemed successful and did not contain submucosal invasion requiring surgery, 98.1% (95% CI 96.6% to 99.0%) were adenoma-free and had avoided surgery at 16 months following EMR. Following colonic WF-EMR, early recurrent/residual adenoma occurs in 16%, and is usually unifocal and diminutive. Risk factors were identified. Late recurrence occurs in 4%. Overall, recurrence was managed endoscopically in 93% of cases. Recurrence is not a significant clinical problem following WF-EMR, as with strict colonoscopic surveillance, it can be managed endoscopically with high success rates. NCT01368289.
Publisher: Wiley
Date: 2022
Abstract: Metabolic dysfunction‐associated fatty liver disease (MAFLD) can develop in any patient, including those with chronic hepatitis C (CHC). The recently proposed diagnostic criteria for MAFLD provide a unique opportunity to investigate the impact of concomitant fatty liver in patients with another established cause for their liver disease. The objective of our study was to assess the characteristics and outcomes of patients with a dual etiology liver disease. We evaluated 1181 patients including 744 with CHC and 437 with MAFLD. All patients in both cohorts underwent liver biopsy indicating disease activity and fibrosis stage. Nearly half (43.1%) the patients with CHC had concomitant MAFLD. Comparing patients with CHC alone with those with a dual etiology disease, we found that the latter had more severe liver injury, hepatic inflammation and fibrosis (all P 0.001). Interestingly, lean or normal‐weight patients with CHC and MAFLD had a similar fibrosis stage compared to the two other subgroups of MAFLD (obesity and/or diabetes mellitus). There was no statistical significance in hepatic steatosis and fibrosis between genotype 3 CHC and MAFLD group compared to other genotypes. Patients with CHC and concomitant MAFLD had more severe liver disease than those with viral hepatitis alone. Recognizing coexisting MAFLD in patients with CHC is important for the delivery of holistic care.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.APMR.2021.07.802
Abstract: To investigate the pattern of change in muscle overactivity during repetitive grasp/release using dynamic computerized dynamometry (DCD objective 1) and the effect of botulinum toxin A (BTX-A objective 2). Secondary analysis of an observational cohort study. Hospital outpatient spasticity management service. A convenience s le (N=65), comprising adults with upper motor neuron syndrome affecting the arm after acquired brain injury (ABI n=38) and participants without ABI (n=27). After clinical assessment, a subgroup of participants with ABI (n=28) underwent BTX-A injections as part of their spasticity management. Post hoc DCD data processing extracted the values of minimum force generation between 10 sequential contractions. The pattern of change was analyzed. The ABI injected group exerted greater force at baseline than both other groups (ABI injected=1.04 kg, ABI noninjected=0.74 kg, participants without ABI=0.53 kg P=.011). After the first contraction, minimum force values increased for all groups and were greatest in the ABI injected group. With subsequent cycles, the group without ABI showed a linear pattern of decreasing force generation, whereas both ABI groups showed a quadratic increasing pattern, which was of greater magnitude in the ABI injected group. After injection, values for the ABI injected group showed a 51% reduction in inducible muscle overactivity (P=.003) to magnitudes similar to those of the ABI noninjected group. This study showed that hand relaxation deteriorated during repetitive movements in people with spasticity, a feature hypothesized to adversely influence everyday hand function. After BTX-A injection, the magnitude but not the pattern of this inducible muscle overactivity improved.
Publisher: Wiley
Date: 08-1998
DOI: 10.1111/J.1440-1746.1998.TB00732.X
Abstract: The aims of the present study were to identify characteristics that are more often associated with hepatitis G virus (HGV) coinfection in Australian patients infected with the hepatitis C virus (HCV) and to investigate the effects of HGV on the histological and functional severity of chronic hepatitis C. Serum s les from 209 patients with chronic hepatitis C were tested for HGV-RNA using single-round reverse transcriptase-polymerase chain reaction to primers directed at the NS5 region of the HGV genome. Hepatitis G virus RNA was detected in 40 cases (19%). Hepatitis G virus-coinfected patients tended to be younger and parenteral risks could be identified in all but six. Although country of birth did not differ significantly between the coinfected and HCV-alone groups, HGV-positive patients appeared to be less likely to have originated from Asia. On logistic regression analysis, HCV genotype 3a was found in a significantly higher proportion of patients with HGV coinfection than other genotypes (P < 0.01). Liver histology and response to interferon were similar in the HGV-coinfected and HCV-alone groups and liver-related complications appeared to occur less frequently in patients with both HGV and HCV. On univariate analysis, antipyrine clearance was found to be higher in the coinfected group (P < 0.05), implying better preservation of hepatic metabolic function, but this difference was lost when adjusted for HCV genotype. In conclusion, coinfection with HGV was more commonly associated with HCV genotype 3a, a genotype associated with injection drug use in younger patients. However, the presence of HGV coinfection did not adversely affect liver disease or the response to interferon treatment in patients with chronic hepatitis C.
Publisher: AMPCo
Date: 09-1990
DOI: 10.5694/J.1326-5377.1990.TB136900.X
Abstract: Sera from 172 intravenous drug users were tested for the presence of antibodies to hepatitis C virus (anti-HCV). The results were analysed in relation to aspects of the history of drug use and evidence of liver disease. The presence of anti-HCV was strongly associated with duration of intravenous drug use. Two-thirds of patients were anti-HCV seropositive within two years of commencing regular intravenous drug use, and there was 100% seropositivity among people injecting drugs for more than eight years. Seropositivity for hepatitis C virus closely paralleled exposure to hepatitis B virus, which was also endemic in this population. In contrast, only one patient tested positive for antibodies to the human immunodeficiency virus. The presence of anti-HCV correlated poorly with biochemical markers of hepatitis. About half the patients with anti-HCV had normal serum levels of alanine aminotransferase, whereas an abnormal liver biochemistry was frequently observed in anti-HCV seronegative subjects. Previous studies of non-A, non-B hepatitis that have used abnormal liver biochemistry as a marker have underestimated the prevalence of chronic hepatitis among intravenous drug users the use of a specific screening test reveals that infection with hepatitis C virus is very common in this population.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.AMJCARD.2019.04.039
Abstract: Pulmonary embolism (PE) is associated with a high mortality whether echocardiographic evaluation at presentation predicts long-term adverse outcomes is of importance. We sought to determine if a composite of routinely obtained echocardiographic parameters could determine long-term adverse events in PE patients. Right ventricular (RV) size and function and right atrial (RA) size were retrospectively evaluated in 233 consecutive PE patients with an inpatient echocardiogram, and compared with 70 healthy controls mortality at 3 years was confirmed. PE patients had increased RV size (RV parasternal long-axis diameter [RVPLAX] and RV end-diastolic volume [p < 0.001 for both]) and RA area (p < 0.001). RV function was reduced in PE patients (RV fractional area change and RV ejection fraction [p 37 mm (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.3 to 4.2 p = 0.005), RA area >20 cm
Publisher: BMJ
Date: 08-1985
DOI: 10.1136/GUT.26.8.789
Abstract: The aim of the present study was to determine whether there is indication that either smoking, alcohol ingestion, or ingestion of analgesic or non-salicylate non-steroidal anti-inflammatory drugs plays any role in the development of chronic gastric ulcer disease. A group of 104 patients with gastric ulcer was compared with an age, sex and social grade matched community control population as regards exposure to the above factors during three time periods--the lifetime, five year and one year periods before the initial onset of the patients' ulcer symptoms. In all three study periods a statistically significant risk of gastric ulcer was found to be associated with smoking, and the daily use of aspirin, indomethacin and of other non-salicylate non-steroidal anti-inflammatory drugs as a group, but not with alcohol or daily use of paracetamol. As exposure to the environmental factors preceded the initial onset of ulcer symptoms, causal relationships are suggested. Assuming the association are causal, it can be calculated that possibly up to 80% of gastric ulcer disease is attributable to smoking and the daily ingestion of analgesic and anti-inflammatory drugs.
Publisher: Informa UK Limited
Date: 04-0011
DOI: 10.2147/IJWH.S399085
Publisher: BMJ
Date: 05-1987
DOI: 10.1136/GUT.28.5.533
Abstract: The aim of this prospective study of 370 community based duodenal ulcer patients was to define the effect on duodenal ulcer course (from the aspect of symptom occurrence) of demographic and environmental factors, and of proven healing of index ulcer within four months. Follow up was three monthly, for up to three years. By survival analysis, it was found that marriage breakup adversely affected duodenal ulcer course, that age 50 years and under, female sex, and aspirin use tended to do so, and that smoking, alcohol ingestion, and paracetamol use did not. Proven healing of index ulcer within four months was associated with a small and non-significant reduction in symptom occurrence over time.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1038/MODPATHOL.2010.81
Abstract: The management of asymptomatic intraductal papillary lesions of the breast diagnosed on core biopsy poses a challenge for patients and clinicians, as the distinction between common benign lesions and atypical or malignant varieties may be difficult without formal excision. The aim of this study was to determine whether a combination of histopathologic and biomarker features could be used to accurately identify benign papillary lesions on core biopsy. An inclusive group of 127 excised papillary lesions was characterized by detailed histopathologic review and immunohistochemical staining for the basal markers cytokeratin 5/6 (CK5/6) and P63 and the proliferation marker Ki67. Comparison of benign, atypical, and malignant lesions revealed that the combination of broad, sclerotic fibrovascular cores, and epithelial CK5/6 staining was most commonly seen in benign papillomas. Ki67 staining revealed striking intralesional heterogeneity, but there was no difference between the high scores of benign, atypical, or malignant lesions (P=0.173). In a non-overlapping set of 42 cases, a binary classifier specifying benign lesions on the basis of thick fibrovascular cores and epithelial CK5/6 staining on core biopsy gave an overall misclassification rate of 4/42 (10%) when compared with the final excision diagnosis. Misclassified cases included 2/27 lesions ultimately diagnosed as benign and 2/2 atypical papillomas. All malignant lesions (n=13) were correctly assigned. The combined assessment of fibrovascular core thickness and CK5/6 staining on core biopsy distinguished benign from malignant papillary lesions, but did not separate benign from atypical cases. This approach may form a useful addition to the clinicopathologic evaluation of papillary lesions of the breast.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Oxford University Press (OUP)
Date: 14-04-2005
DOI: 10.1093/BIOSTATISTICS/KXI017
Abstract: Suppose measurements of a particular feature are collected at baseline and at a number of subsequent time points and that for each in idual there is a roughly linear trend in time. This paper takes three approaches to testing whether there is a relation between the initial value and the slope. It also considers whether the initial value for an in idual is a useful predictor of the slope for that in idual. The problems are formulated in terms of regression models with random coefficients. The solutions are illustrated using data from an observational study of clinical correlates of disability and progression in Huntington's disease.
Publisher: American Society of Hematology
Date: 12-1993
DOI: 10.1182/BLOOD.V82.11.3437.BLOODJOURNAL82113437
Abstract: Normal B lymphopoiesis is dependent on a close relationship between B- cell precursors and the bone marrow (BM) microenvironment. To further understand the mechanisms regulating the proliferation of the malignant counterpart of B-cell precursors, namely precursor-B acute lymphoblastic leukemia (ALL), we examined the adhesion to BM fibroblasts (BMF) of 19 cases of precursor-B ALL using a chromium labeling assay. Eleven of 19 cases showed greater than 10% binding to BMF (range 2.3% to 54.8%, mean 19.1%). Binding was increased approximately twofold by preincubation of BMF with tumor necrosis factor and interleukin-4, which also resulted in upregulation of expression of vascular cell adhesion molecule-1 (VCAM-1) on BMF. The mechanism of attachment was investigated using murine monoclonal antibodies to leukocyte integrins, principally the beta, integrins VLA- 4 and VLA-5, which were demonstrated to be present on most cases by flow cytometry. Statistically significant inhibition of adhesion was observed with antibodies to the beta 1 common subunit, VLA-4, and VLA- 5, whereas little effect was seen with antibodies to VLA-6 or the beta 2 integrin subunit. Preincubation of fibroblasts with an antibody to VCAM-1 (a ligand of VLA-4) inhibited leukemic cell binding in the majority of cases, which was an effect also observed on cytokine- stimulated BMF. However, a minority of cases, as well as the pre-B lines NALM-6 and KM-3, showed no evidence of inhibition of adhesion with anti-VCAM-1 antibodies. Treatment of BMF with antifibronectin antibody alone had little effect on ALL adhesion and did not enhance the inhibitory effect of anti-VCAM-1. These data indicate that precursor-B ALL cells bind to BM stroma through the beta 1 integrins VLA-4 and VLA-5 and that this effect is partly mediated by VCAM-1 on stromal cells, although other undefined VLA ligands are also likely to be involved. Attachment of ALL cells to stroma is likely to play a key role in regulating the survival and growth of these cells through exposure to stromal cytokines.
Publisher: Cambridge University Press (CUP)
Date: 09-2009
DOI: 10.1017/S1368980008004497
Abstract: To evaluate the iodine nutritional status of children living on the island of Tanna, Republic of Vanuatu. Cross-sectional study. Urine and household salt s les were collected for iodine measurement. Thyroid volumes were measured by ultrasound. A food consumption frequency survey was carried out, particularly in relation to salt, iodine-rich foods and foods that containing thiocyanate, a potentially goitrogenic substance. Urinary thiocyanate levels were also measured. Island rural communities in Tanna, Vanuatu. One hundred and fifty-three schoolchildren between 8 and 10 years of age from four locations on the island participated. The median urinary iodine excretion (UIE) among the children was 49mg/l, indicating moderate iodine deficiency. This was corroborated by 27% of boys and 33% of girls having thyroid glands greater than the international standard for their age, and 36% of boys and 45% of girls having thyroid glands greater than the international standard for their body surface area based on ultrasonography. There was a highly statistically significant inverse correlation between thyroid volume and UIE for boys and girls ( r = −0·444, P = 0·001 and r = −0·319, P = 0·005, respectively). There was no correlation between thiocyanate and UIE or thyroid volume. Only 34% of children reported to consume fish (tinned or fresh) on a weekly basis. Against the common perception, the study has demonstrated that the children on the island of Tanna were in a state of moderate iodine deficiency. More data need to be collected from other Pacific Island countries in order to provide evidence for formulating public policy in prevention and control of iodine deficiency disorders in these nations.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2018
DOI: 10.1200/PO.17.00221
Abstract: Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma–mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic BRAF. However, response to BRAF inhibitors is tumor-type specific. Significant improvement in survival is seen in patients with BRAF-mutant melanoma, but other cancer types, such as colorectal cancers, are generally less sensitive. We examined the frequency and characteristics of BRAF-mutated LGSC and described the response to treatment with BRAF inhibitors. Mutations were assessed in LGSC (N = 65) by using targeted, exome, and whole-genome sequencing. Patient characteristics, treatment, and clinical outcome were assessed, and the median follow-up time was more than 5 years. BRAF inhibitors were trialed in two patients with a somatic BRAF V600E mutation: one patient received dabrafenib monotherapy and was monitored clinically, biochemically (cancer antigen [CA]-125 levels), and with positron emission tomography (PET) imaging. Expression of the BRAF V600E protein in this patient was assessed by immunohistochemistry. Among patients with LGSC, nine (13.8%) of 65 had a somatic BRAF mutation. Of the nine patients with BRAF mutation–positive LGSC, four experienced progressive disease that did not respond to conventional chemotherapy. Two of the patients experienced progression quickly and died as a result of disease progression, and two received targeted treatment. Two patients with BRAF V600E mutation received BRAF inhibitors at relapse and both achieved durable responses. BRAF mutations are not uncommon in patients with LGSC and should be routinely tested, because BRAF inhibitors can be an effective treatment for these patients. The results highlight the need for targeted treatment in this rare tumor type, and a prospective study is needed to formally assess the response rate and clinical benefit.
Publisher: SAGE Publications
Date: 06-2004
DOI: 10.1191/1740774504CN026OA
Abstract: The presence of possible treatment interaction when designing a factorial study can be either greeted with dismay (for an antagonistic or negative interaction) or can be welcome (in the case of a synergistic effect). The type of potential interaction may greatly influence the choice of study design. Depending on the magnitude of an expected additive or multiplicative interaction, a three-arm study, instead of a 2 × 2 factorial, may yield greater statistical power. A graphical aid for examining the loss of power due to the presence of such interaction is developed. The technique can also be applied to designing studies where prespecified subgroup analyses are of particular interest. Tests for interaction effects between subgroups are usually underpowered, even if the subgroups have been prespecified in the protocol. The technique can be used to determine the appropriate s le sizes in the subgroups to ensure adequate power to detect potential interaction effects. The method is illustrated with respect to a published 2 × 2 factorial study. In this study, interaction reduced the power of the final analysis to detect significant main effects.
Publisher: Wiley
Date: 08-2002
DOI: 10.1046/J.1440-1746.2002.02813.X
Abstract: Hepatic steatosis is common in hepatitis C, but the relative importance of host and viral factors is controversial. In the present prospective study, we examined metabolic factors associated with non-alcoholic fatty liver and viral genotype as predictors of steatosis and fibrosis in chronic hepatitis C infection. In 124 chronic hepatitis C patients, the association between liver histology and the following was investigated: demographic and anthropometric data, alcohol intake, alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglyceride, transferrin saturation, ferritin, insulin, c-peptide, glucose and insulin resistance (homeostasis model). By multivariate analysis, genotype 3 was associated with increased steatosis grade (P = 0.02). There were significant pairwise interactions between genotype 3 status and total cholesterol (P = 0.01), current alcohol intake (P = 0.04) and serum ALT (P = 0.01). This showed that the etiology of steatosis was different in patients with genotype 3 and those with non-genotype 3 chronic hepatitis C infection. In genotype 3 patients, the degree of steatosis was inversely associated with serum cholesterol (P = 0.005) and positively associated with serum triglyceride (P = 0.02). There was no association between body mass index (BMI) and the extent of steatosis. Among patients with other genotypes, the steatosis grade was strongly influenced by BMI (P < 0.0001) and serum ALT (P < 0.01). Independent predictors of fibrosis were age (P = 0.001), past alcohol intake (P = 0.04), ALT (P = 0.002), serum insulin (P = 0.001) and portal inflammation (P < 0.001). Hepatitis C genotype 3 may interfere with pathways of hepatic lipid metabolism, whereas increased BMI appears to be a more important pathogenic factor in other genotypes. Although steatosis and BMI were not associated with hepatic fibrosis, their relationship with serum insulin suggests that metabolic factors related to insulin action could influence fibrogenesis in hepatitis C.
Publisher: Public Library of Science (PLoS)
Date: 05-05-2016
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.DIABRES.2022.110038
Abstract: To determine the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its association on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). 380 women with GDM had a FibroScan® performed between 24 and 32 weeks. A Controlled Attenuation Parameter (CAP) ≥ 233.5 dB/m signified MAFLD. Gestational hypertension, pre-ecl sia and ecl sia contributed to a composite of adverse maternal outcomes. A composite of adverse neonatal outcomes included pre-term birth, hypoglycaemia, small/large-for-gestational age and admission to neonatal high dependency. Multiple logistic regression was used to determine independent associations with MAFLD. 147 (38.7 %) women had MAFLD. Higher pre-pregnancy BMI (median 28.4, IQR 24.7-33.0 kg/m Within this GDM cohort, almost 40% had FibroScan®-detected MAFLD in mid-to-late gestation. MAFLD was not associated with worse pregnancy outcomes.
Publisher: Elsevier BV
Date: 10-2004
Publisher: Wiley
Date: 02-10-2020
DOI: 10.1002/PST.2057
Publisher: American Association for Cancer Research (AACR)
Date: 15-10-2008
DOI: 10.1158/1078-0432.CCR-08-0701
Abstract: Purpose: Identification of biologically and clinically distinct breast cancer subtypes could improve prognostic assessment of primary tumors. The characteristics of “molecular” breast cancer subtypes suggest that routinely assessed histopathologic features in combination with limited biomarkers may provide an informative classification for routine use. Experimental Design: Hierarchical cluster analysis based on components of histopathologic grade (tubule formation, nuclear pleomorphism, and mitotic score), expression of ER, cytokeratin 5/6, and HER2 lification identified four breast cancer subgroups in a cohort of 270 cases. Cluster subgroup membership was compared with observed and Adjuvant! Online predicted 10-year survival. Survival characteristics were confirmed in an independent cohort of 300 cases assigned to cluster subgroups using a decision tree model. Results: Four distinct breast cancer cluster subgroups (A-D) were identified that were analogous to molecular tumor types and showed a significant association with survival in both the original and validation cohorts (P & 0.001). There was a striking difference between survival for patients in cluster subgroups A and B with ER+ breast cancer (P & 0.001). Outcome for all tumor types was well estimated by Adjuvant! Online, with the exception of cluster B ER+ cancers where Adjuvant! Online was too optimistic. Conclusions: Breast cancer subclassification based on readily accessible pathologic features could improve prognostic assessment of ER+ breast cancer.
Publisher: Wiley
Date: 2011
Publisher: National Shellfisheries Association
Date: 08-2005
Publisher: Wiley
Date: 23-07-2007
Publisher: Wiley
Date: 2011
Publisher: Cambridge University Press (CUP)
Date: 12-1981
DOI: 10.2307/3213061
Abstract: The concept of θ-stationarity for a simple second-order point process in R 2 is introduced. This concept is closely related to that of isotropy. Some θ-stationary processes are defined. Techniques are given for simulating realisations of these processes. The second-order analysis of these processes which have an obvious point of reference or origin is considered. Methods are suggested for modelling spatial patterns which are realisations of such processes. These methods are illustrated using simulated data. The ideas are extended to multitype point processes.
Publisher: Elsevier BV
Date: 10-1986
DOI: 10.1016/0016-5085(86)90682-7
Abstract: We have prospectively studied changes in serum postprandial cholylglycine (CG) concentration during 297 pregnancies. We found an increase in CG concentration from 0.3 mumol/L at 15 weeks' pregnancy to 0.6 mumol/L at 40 weeks' pregnancy. Although this increase was statistically significant (p less than 0.005), median concentrations of CG remained well within the normal range (0-1.5 mumol/L). However, 10% of the group showed markedly elevated serum CG concentrations at 30 weeks' pregnancy, and the CG level in this group continued to rise during the third trimester. Pruritus was significantly more common in the group with elevated CG concentrations (48%) than in the group with normal CG levels (20%) (p less than 0.005). Serum CG was a much more sensitive predictor of pruritus during pregnancy than other biochemical liver tests. Elevated CG levels were found more commonly in Mediterranean and Asian patients than patients of other ethnic origins (p less than 0.025). No statistically significant associations were found between elevated CG concentrations and maternal age, number of previous pregnancies, pruritus during previous pregnancies, contraceptive-induced cholestasis, and fetal maturity. We conclude that obstetric cholestasis is probably much more common than previously suspected and that consideration should be given to the measurement of serum bile acids in all pregnant in iduals with unexplained pruritus.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.GIE.2018.11.023
Abstract: Clinically significant post-EMR bleeding (CSPEB) is the most-frequent serious adverse event after EMR of large laterally spreading colonic lesions (LSLs). There is no proven prophylactic therapy, and it remains a significant drawback of EMR. We aimed to systematically describe and evaluate the features of the post-EMR mucosal defect (PED) and their relationship to CSPEB. A prospective study of LSLs referred for EMR at a tertiary center was performed. PEDs without visible features were recorded as bland blue. Nonbland blue (NBB) PED features included size, number, and herniation of submucosal vessels and presence of submucosal hemorrhage, fibrosis, fat, and exposed muscle. NBB PEDs were analyzed for association with CSPEB, defined as bleeding occurring after completion of the procedure necessitating readmission or reintervention. From April 2012 to May 2017, 501 lesions in 501 patients were eligible for analysis. The frequency of CSPEB was 30 of 501 (6.0%). More than or equal to 3 visible vessels was a significant predictor of CSPEB (P = .016). None of the following showed a significant correlation with CSPEB: presence of visible vessels, their diameter, herniation, or other nonvascular PED features. Submucosal vessels were more common in the left-sided colon segment (88.6% vs 78.3%, P = .004) and were significantly larger (20.8% vs 12.1% ≥1 mm, P = .037), more numerous (median 4 vessels [interquartile range, 2-7] vs 2 vessels [interquartile range, 1-4], P < .001), and more often herniated (32% vs 22.2%, P = .022). More than or equal to 3 visible vessels within the PED may be predictive for CSPEB and may define a target group for real-time prophylactic intervention. No other endoscopically visible features of the PEDs were predictive of CSPEB. (Clinical trial registration number: NCT03117400.).
Publisher: Wiley
Date: 07-1995
DOI: 10.1111/J.1365-2141.1995.TB05590.X
Abstract: Two hundred and twenty-six patients were diagnosed with myelodysplastic syndrome (MDS), according to the French-American-British (FAB) criteria, over a 13-year period, and studied retrospectively in a single institution in order to study indicators which were prognostically significant. Analysis of clinical and laboratory data indicated that the FAB classification, the Bournemouth, Dusseldorf, Goasguen, Sanz and FAB Scoring Systems were all good predictors of survival. We found advancing age, haemoglobin (Hb) < or = 9 g/dl, platelet count < or = 50 x 10(9)/l, increased peripheral total white cell count (WCC) and monocytosis, increased bone marrow blasts, dysgranulopoiesis, and bone marrow fibrosis were significant adverse prognostic variables. The commonest complication and cause of death was infection however, infective episodes were not significantly associated with low neutrophil counts (either < or = 1.5 x 10(9)/l or < or = 0.8 x 10(9)/l) and there was also no significant association between neutropenia and survival. These findings indicate that neutrophil dysfunction plays an important role in the clinical progression of patients with MDS. The effect of new therapeutic modalities, such as the haemopoietic growth factors, on reducing infective episodes may be as significant as their effect on increasing neutrophil counts.
Publisher: Wiley
Date: 28-06-2007
Publisher: BMJ
Date: 23-04-2019
DOI: 10.1136/EMERMED-2017-207431
Abstract: Mechanical cardiopulmonary resuscitation (M-CPR) is increasingly used in the management of cardiac arrest. There are no previously reported randomised studies investigating M-CPR training. This study of newly trained M-CPR providers hypothesised that a brief simulation-based intervention after 4 months would improve M-CPR performance at 6 months. This study used a simulated ‘in situ’ cardiac arrest model. The M-CPR device used was a proprietary Lund University Cardiac Assist System 3 machine (Physio Control, Redmond, Washington, USA). Standardised baseline training was provided to all participants. Following training, baseline performance was assessed. The primary outcome measure was the time taken to initiate M-CPR and the secondary outcome was performance against a checklist of errors. Participants were then randomised to intervention group (simulation training) or control group (routine clinical use of M-CPR). After 6 months the outcome measures were reassessed. Comparative statistical tests used an intention-to-treat analysis. 112 participants were enrolled. The intervention group (n=60) and control group (n=52) had similar demographic characteristics. At the 6-month assessment, median time to M-CPR initiation was 27.0 s (IQR 22.0–31.0) in the intervention group and 31.0 s (IQR 25.6–46.0) in the control group (p=0.003). The intervention group demonstrated fewer errors compared with controls at 6 months (p .001) In this randomised study of approaches to M-CPR training, providers receiving additional simulation-based training had higher retention levels of M-CPR skills. Therefore, when resuscitation skills are newly learnt, provision follow-up training should be an important consideration.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.JAAD.2015.01.018
Abstract: BRAF inhibitors (BRAFi) cause paradoxical activation of the MAPK pathway in keratinocytes resulting in cutaneous squamous cell carcinoma (cuSCC). We sought to examine the clinical factors involved in BRAFi-induced cuSCC development. We studied 134 patients with BRAF-mutant metastatic melanoma treated with a BRAFi at Westmead Hospital, Sydney, Australia. Details of cuSCC development and associations with melanoma clinicopathologic features and treatment outcome were examined. In all, 32 (24%) patients developed 110 cuSCC after commencing treatment. In all, 61 (55%) cuSCC developed within the first 3 months. Age was the only independent risk factor for cuSCC development. After 3 months of therapy 4% of patients younger than 40 years developed cuSCC compared with 33% who were older than 60 years, and the hazard ratio of developing a cuSCC increased by 1.7 (95% confidence interval 1.3-2.3) per decade (P < .001). BRAFi cuSCC occurred more often in sun-protected areas (42%) compared with sporadic cuSCC (21%) (P < .001). cuSCC was not associated with progression-free survival. The study was from a single center and patients were also at risk of sporadic cuSCC. Most BRAFi-induced cuSCC develop within 3 months of BRAFi therapy. The only independent risk factor is increasing age. cuSCC may present in anatomical locations with low ultraviolet exposure such that thorough dermatologic assessment is required.
Publisher: Oxford University Press (OUP)
Date: 05-06-2012
DOI: 10.1093/CID/CIS529
Abstract: Longer-term morbidity and outcomes of Cryptococcus gattii infection are not described. We analyzed clinical, microbiological, and outcome data in Australian patients followed for 12 months, to identify prognostic determinants. Culture-confirmed C. gattii cases from 2000 to 2007 were retrospectively evaluated. Clinical, microbiological, radiological, and outcome data were recorded at diagnosis and at 6 weeks, 6 months, and 12 months. Clinical and laboratory variables associated with mortality and with death and/or neurological sequelae were determined. Annual C. gattii infection incidence was 0.61 per 10(6) population. Sixty-two of 86 (72%) patients had no immunocompromise 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia, and 1 had human immunodeficiency virus/AIDS. Clinical and microbiological characteristics of infection were similar in immunocompromised and healthy hosts. Isolated lung, combined lung and central nervous system (CNS), and CNS only disease was reported in 12%, 51% and 34% of the cases, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27% 6% developed during therapy) and immune reconstitutionlike syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titers in CNS disease were 563.9 (vs 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. An initial cerebrospinal fluid CRAG titer of ≥256 predicted death and/or neurological sequelae (P = .05). Neurological C. gattii disease predominates in the Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titers are ≥512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important because host immunocompromise is associated with reduced survival.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2008
DOI: 10.1158/1078-0432.CCR-07-5189
Abstract: Purpose: The standard of care for ovarian cancer includes platinum-based chemotherapy. It is not possible, however, to predict clinical platinum sensitivity or to design rational strategies to overcome resistance. We used a novel approach to identify altered gene expression associated with high sensitivity to cisplatin, to define novel targets to sensitize tumor cells to platins and ultimately improve the effectiveness of this widely used class of chemotherapeutics. Experimental Design: Using differential display PCR, we identified genes differentially expressed in a mutagenized cell line with unusual sensitivity to cisplatin. The most highly differentially expressed gene was selected, and its role in determining cisplatin sensitivity was validated by gene transfection and small interfering RNA (siRNA) approaches, by association of expression levels with cisplatin sensitivity in cell lines, and by association of tumor expression levels with survival in a retrospective cohort of 71 patients with serous ovarian adenocarcinoma. Results: The most highly differently expressed gene identified was ANKRD1, ankyrin repeat domain 1 (cardiac muscle). ANKRD1 mRNA levels were correlated with platinum sensitivity in cell lines, and most significantly, decreasing ANKRD1 using siRNA increased cisplatin sensitivity & -fold. ANKRD1 was expressed in the majority of ovarian adenocarcinomas tested (62/71, 87%), and higher tumor levels of ANKRD1 were found in patients with worse outcome (overall survival, P = 0.013). Conclusions: These findings suggest that ANKRD1, a gene not previously associated with ovarian cancer or with response to chemotherapy, is associated with treatment outcome, and decreasing ANKRD1 expression, or function, is a potential strategy to sensitize tumors to platinum-based drugs.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-04-2021
Abstract: Subclinical left ventricular dysfunction detected by 2‐dimensional global longitudinal strain post breast radiotherapy has been described in patients with breast cancer. We hypothesized that left ventricular dysfunction postradiotherapy may be site specific, based on differential segmental radiotherapy dose received. Transthoracic echocardiograms were performed at baseline, 6 weeks, and 12 months postradiotherapy on 61 chemotherapy‐naïve women with left‐sided breast cancer undergoing tangential breast radiotherapy. Radiation received within basal, mid, and apical regions for the 6 left ventricular walls was quantified from the radiotherapy treatment planning system. Anterior, anteroseptal, and anterolateral walls received the highest radiation doses, while inferolateral and inferior walls received the lowest. There was a progressive increase in the radiation dose received from basal to apical regions. At 6 weeks, the most significant percentage deterioration in strain was seen in the apical region, with greatest reductions in the anterior wall followed by the anteroseptal and anterolateral walls, with a similar pattern persisting at 12 months. There was a within‐patient dose–response association between the segment‐specific percentage deterioration in strain at 6 weeks and 12 months and the radiation dose received. Radiotherapy for left‐sided breast cancer causes differential segmental dysfunction, with myocardial segments that receive the highest radiation dose demonstrating greatest strain impairment. Percentage deterioration in strain observed 6 weeks postradiotherapy persisted at 12 months and demonstrated a dose–response relationship with radiotherapy dose received. Radiotherapy‐induced subclinical cardiac dysfunction is of importance because it could be additive to chemotherapy‐related cardiotoxicity in patients with breast cancer. Long‐term outcomes in patients with asymptomatic strain reduction require further investigation.
Publisher: AMPCo
Date: 21-02-2021
DOI: 10.5694/MJA2.50941
Publisher: SAGE Publications
Date: 09-2013
Publisher: Springer Science and Business Media LLC
Date: 08-09-2016
DOI: 10.1038/NCOMMS12731
Abstract: The ‘shock and kill’ approach to cure human immunodeficiency virus (HIV) includes transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with targeted immunotherapy to purge infected cells. The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected in iduals on antiretroviral therapy induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4 + T cells. However, it is important to discern whether the increases in CA-US HIV-1 RNA are due to limited or broad activation of HIV-1 proviruses. Here we use single-genome sequencing to find that the RNA transcripts observed following LRA administration are genetically erse, indicating activation of transcription from an extensive range of proviruses. Defective sequences are more frequently found in CA HIV-1 RNA than in HIV-1 DNA, which has implications for developing an accurate measure of HIV-1 reservoir size. Our findings provide insights into the effects of panobinostat and vorinostat as LRAs for latent HIV-1.
Publisher: SAGE Publications
Date: 10-08-2020
Abstract: Grindr is a geolocation smartphone application popular among men who have sex with men (MSM) to find sexual partners. We conducted a study to assess if attendance and HIV testing amongst MSM increased due to advertisements on Grindr that promoted our service. We measured clinic website hits by users clicking through from Grindr we counted self-reported registrations that nominated referral from Grindr and we compared new patient attendances and HIV tests in MSM with heterosexual men, for the 18 months preceding the intervention and the 18 months of the intervention. During the intervention the clinic’s website received 11,799 unique hits from Grindr users. The average monthly rate of attendances by new MSM increased 70.3% from 19.0 to 32.3, compared with a 5.5% increase among new heterosexual men from 45.6 to 48.1. The average monthly rate of HIV tests among MSM increased 43.6% from 47.0 to 67.6, compared with a 3.9% increase amongst heterosexual men from 40.0 to 41.6. The MSM:heterosexual men rate ratio for new patient attendances changed from 0.42 to 0.67 ( p 0.001, adjusted for possible underlying time trends in each period), and for HIV tests this rate ratio changed from 1.18 to 1.63 ( p 0.001, adjusted for possible underlying time trends in each period). The effects of the intervention did not significantly change over the course of the 18-month intervention. This study suggests that advertising on Grindr was effective and durable as a means of increasing attendance and HIV testing rates among MSM in northern Sydney.
Publisher: The Endocrine Society
Date: 06-2002
Abstract: Even mild iodine deficiency during early childhood and pregnancy has the potential to impair neurological development. Often considered a problem of developing nations, a number of industrialized countries are at risk of deficiency. Despite past success with intentional and unintentional iodine fortification, recurrence of deficiency is an ever-present risk. Tasmania, an island state of the Commonwealth of Australia, has a history of endemic iodine deficiency, which was successfully eliminated by iodine prophylaxis initiated in 1950. In this report we describe a formal assessment of iodine nutrition in the Tasmanian population, 50 yr after initiation of the prophylaxis program. The requirements and obstacles to achieving sustainable iodine prophylaxis in an otherwise affluent community are considered. A cross-sectional study was undertaken during the yr 2000. Urinary iodine excretion (UIE) and thyroid ultrasonography were assessed in a representative statewide s le of school-age children. Children (n = 225) aged 4 to 17 yr from throughout Tasmania were studied. The s le comprised 99 girls and 126 boys. The median UIE was 84 microg/liter (87 microg/liter for males and 81 microg/liter for females), with UIE 50 microg/liter or less in 20%. Based on age-specific World Health Organization/International Council for the Control of Iodine Deficiency Disorders normative data for thyroid volume, the prevalence of elevated thyroid volume was 5.3% for boys and 3.5% for girls. However, after correcting the World Health Organization/International Council for the Control of Iodine Deficiency Disorders reference data, the prevalence increased to 24.6% for boys and 20.7% for girls. No significant difference in the thyroid volumes was found between males and females in this study. These data confirm the recurrence of mild iodine deficiency in Tasmania. The failure of sustained iodine prophylaxis highlights the universal importance of persistent surveillance, use of sustainable measures, public awareness, and a specific legislative framework for managing ongoing iodine prophylaxis. Our findings also emphasize the importance of accurate reference data for assessment thyroid volume.
Publisher: Wiley
Date: 16-02-2021
DOI: 10.1002/JBMR.4255
Abstract: Atypical femur fractures (AFF) are a rare but serious complication of long‐term bisphosphonate use. Although clearly defined by ASBMR criteria, a proportion of patients with AFFs may go unrecognized and the use of qualitative fracture criteria may lead to uncertainty in AFF diagnosis, with significant therapeutic implications. A score that rapidly and accurately identifies AFFs among subtrochanteric femur fractures using quantitative, measurable parameters is needed. In a retrospective cohort of 110 female patients presenting with AFFs or typical femur fractures (TFFs), multiple logistic regression and decision tree analysis were used to develop the Sydney AFF score. This score, based on demographic and femoral geometry variables, uses three dichotomized independent predictors and adds one point for each: (age ≤80 years) + (femoral neck width mm) + (lateral cortical width at lesser trochanter ≥5 mm), (score, 0 to 3). In an independent validation set of 53 female patients at a different centre in Sydney, a score ≥2 demonstrated 73.3% sensitivity and 69.6% specificity for AFF (area under the receiver‐operating characteristic curve [AUC] 0.775, SE 0.063) and remained independently associated with AFF after adjustment for bisphosphonate use. The Sydney AFF score provides a quantitative means of flagging female patients with atraumatic femur fractures who have sustained an AFF as opposed to a TFF. This distinction has clear management implications and may augment current ASBMR diagnostic criteria. © 2021 American Society for Bone and Mineral Research (ASBMR).
Publisher: BMJ
Date: 25-06-2021
DOI: 10.1136/GUTJNL-2021-324140
Abstract: Endoscopic mucosal resection (EMR) in the colon has been widely adopted, but there is limited data on the histopathological effects of the differing electrosurgical currents (ESCs) used. We used an in vivo porcine model to compare the tissue effects of ESCs for snare resection and adjuvant margin ablation techniques. Standardised EMR was performed by a single endoscopist in 12 pigs. Two intersecting 15 mm snare resections were performed. Resections were randomised 1:1 using either a microprocessor-controlled current (MCC) or low-power coagulating current (LPCC). The lateral margins of each defect were treated with either argon plasma coagulation (APC) or snare tip soft coagulation (STSC). Colons were surgically removed at 72 hours. Two specialist pathologists blinded to the intervention assessed the specimens. 88 defects were analysed (median 7 per pig, median defect size 29×17 mm). For snare ESC effects, 156 tissue sections were assessed. LPCC was comparable to MCC for deep involvement of the colon wall. For margin ablation, 172 tissue sections were assessed. APC was comparable to STSC for deep involvement of the colon wall. Islands of preserved mucosa at the coagulated margin were more likely with APC compared with STSC (16% vs 5%, p=0.010). For snare resection, MCC and LPCC did not produce significantly different tissue effects. The submucosal injectate may protect the underlying tissue, and technique may more strongly dictate the depth and extent of final injury. For margin ablation, APC was less uniform and complete compared with STSC.
Publisher: American Medical Association (AMA)
Date: 09-2008
DOI: 10.1001/ARCHDERM.144.9.1120
Abstract: To determine the predictive dermoscopic features of amelanotic and hypomelanotic melanoma. A total of 105 melanomas (median Breslow thickness, 0.76 mm), 170 benign melanocytic lesions, and 222 nonmelanocytic lesions lacking significant pigment (amelanotic, partially pigmented, and light colored) were imaged using glass-plate dermoscopy devices and scored for 99 dermoscopic features. Diagnostic models were derived from and tested on independent randomly selected lesions. Predominantly hospital-based clinics from 5 continents. Sensitivity, specificity, and odds ratios for in idual features and models for the diagnosis of melanoma and malignancy. The most significant negative predictors of melanoma were having multiple (>3) milialike cysts (odds ratio, 0.09 95% confidence interval, 0.01-0.64), comma vessels with a regular distribution (0.10 0.01-0.70), comma vessels as the predominant vessel type (0.16 0.05-0.52), symmetrical pigmentation pattern (0.18 0.09-0.39), irregular blue-gray globules (0.20 0.05-0.87), and multiple blue-gray globules (0.28 0.10-0.81). The most significant positive predictors were having a blue-white veil (odds ratio,13 95% confidence interval, 3.9-40.0), scarlike depigmentation (4.4 2.4-8.0), multiple blue-gray dots (3.5 1.9-6.4), irregularly shaped depigmentation (3.3 2.0-5.3), irregular brown dots/globules (3.2 1.8-5.6), 5 to 6 colors (3.2 1.6-6.3), and predominant central vessels (3.1 1.6-6.0). A simple model distinguishing melanomas from all nonmelanomas had a sensitivity of 70% and a specificity of 56% in the test set. A model distinguishing all malignant lesions from benign lesions had a sensitivity of 96% and a specificity of 37%. Conclusion Although the diagnostic accuracy of dermoscopy for melanoma lacking significant pigment is inferior to that of more pigmented lesions, features distinguishing the former from benign lesions can be visualized on dermoscopic evaluation.
Publisher: The Endocrine Society
Date: 07-2004
DOI: 10.1210/EN.2004-0212
Abstract: Progesterone plays a central role in the regulation of ovarian function. The progesterone receptor (PR) has been shown to be essential for ovulation because mice lacking PR fail to ovulate and are infertile. PR is expressed as two isoforms, PRA and PRB, which have been shown to have different functional activities. In this study, we investigated the cellular distribution of PRA and PRB in the ovaries and oviducts of cycling mice using immunohistochemistry with isoform-specific monoclonal antibodies. In the ovary, on the evening of proestrus before ovulation, both the granulosa and theca cells of the preovulatory follicles expressed both PR isoforms. PRA and PRB staining was also observed in the theca cells of preantral and antral follicles, whereas only PRB was observed in the granulosa cells of primary, preantral, and antral follicles and in the corpus luteum. In the oviduct, PRA was the predominant isoform observed, expressed in both the epithelial and stromal cells, whereas PRB was only detected in the epithelial cells. The differences in PRA and PRB localization in the ovary and oviduct may reflect erse functions for PRA and PRB in reproductive tissues and may have important implications in understanding the mechanisms of progesterone action.
No related grants have been discovered for Karen Byth Wilson.