ORCID Profile
0000-0003-0213-7652
Current Organisation
NHMRC Clinical Trials Centre
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Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 05-2014
DOI: 10.1111/IMJ.12399
Abstract: Anticancer drugs are often expensive and are contributing to the growing cost of cancer care. Concerns have been raised about the effect rising costs may have on availability of new anticancer drugs. This study aims to determine the recent changes in the costs of anticancer drugs in Australia. Publicly available expenditure and prices paid by the Australian Pharmaceutical Benefits Scheme (PBS) for anticancer drugs from 2000 to 2012 were reviewed. The measures used to determine changes in cost were total PBS expenditure and average price paid by the PBS per prescription for anticancer drugs and for all PBS listed drugs. An estimated monthly price paid for newly listed anticancer drugs was also calculated. Annual PBS expenditure on anticancer drugs rose from A$65 million in 1999-2000 to A$466 million in 2011-2012 an average increase of 19% per annum. The average price paid by the PBS per anticancer drug prescription, adjusted for inflation, increased 133% from A$337 to A$786. The real average annual increase in the price per anticancer drug prescription was more than double that for all other PBS drugs combined (7.6% vs 2.8%, difference 4.8%, 95% confidence interval -0.4% to 10.1%, P = 0.07). The median price for a month's treatment of the new anticancer drugs listed was A$4919 (range A$1003 to A$12 578, 2012 prices). PBS expenditure and the price of anticancer drugs in Australia rose substantially from 2000 to 2012. Dealing with these burgeoning costs will be a major challenge for our health system and for those affected by cancer.
Publisher: Wiley
Date: 26-01-2017
DOI: 10.1002/UOG.15828
Abstract: To examine the relationship of visual analog scale (VAS) ‘bother’ scores for obstructed defecation (OD) with demographic data, physical examination and sonographic findings of the posterior compartment. All patients seen at a urogynecology clinic between January and October 2013 were included. Patients were diagnosed with OD if they had any of the following: incomplete bowel emptying, straining with bowel movement or need for digitation. Patients used a VAS to rate OD bother on a scale of 0–10 (0, no bother 10, worst imaginable bother). For each patient, a comprehensive history was obtained, the International Continence Society Pelvic Organ Prolapse Quantification was performed and four‐dimensional translabial ultrasound volumes were recorded on maximal Valsalva maneuver. Linear and multiple regression models were used to correlate bother VAS scores with demographic, clinical and sonographic findings. Among 265 patients included in the analysis, 61% had OD symptoms with a mean VAS bother score of 5.6. OD bother scores were associated with a history of previous prolapse surgery ( P = 0.0001), previous hysterectomy ( P = 0.0006), descent of the posterior compartment (Bp P = 0.004) and hiatal dimensions (Pb and Gh + Pb P = 0.006 and P = 0.004). OD bother was associated with the following sonographic findings: true rectocele ( P = 0.01), depth of rectocele ( P = 0.04), descent of rectal ulla ( P = 0.02), enterocele ( P = 0.03) and rectal intussusception ( P 0.0001). VAS bother scores are associated with both clinical and sonographic measures of posterior compartment descent. Rectal intussusception was most likely to result in highly bothersome symptoms of OD. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Cold Spring Harbor Laboratory
Date: 19-12-2020
DOI: 10.1101/2020.12.17.20248441
Abstract: Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the in idual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of intervention-covariate interactions. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups. Systematic searches of Medline, Embase, CENTRAL, CINAHL, PsycInfo, and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2020 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis (PMA) will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index (BMI) z-score at age 24 +/- 6 months using World Health Organisation Growth Standards, and effect differences will be explored among pre-specified in idual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events. Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations, and media releases. Prospectively registered on PROSPERO: CRD42020177408 This will be the largest in idual participant data (IPD) meta-analysis evaluating behavioural interventions for the prevention of early childhood obesity to date, and will provide the most reliable and precise estimates of early intervention effects to inform future decision-making. IPD meta-analysis methodology will enable unprecedented exploration of important in idual and trial-level characteristics that may be associated with childhood obesity or that may be effect modifiers. The proposed innovative methodologies are feasible and have been successfully piloted by members of our group. It may not be possible to obtain IPD from all eligible trials in this instance, aggregate data will be used where available, and sensitivity analyses will be conducted to assess inclusion bias. Outcome measures may be collected and reported differently across included trials, potentially increasing imprecision however, we will harmonise available data where possible, and encourage those planning or conducting ongoing trials to collect common core outcomes following prospective meta-analysis methodology.
Publisher: The Endocrine Society
Date: 08-03-2021
Abstract: Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown. We aimed to determine the effect of testosterone treatment on bone microarchitecture using high resolution–peripheral quantitative computed tomography (HR-pQCT). Men ≥ 50 years of age were recruited from 6 Australian centers and were randomized to receive injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program. The primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (1 center). Secondary endpoints included other HR-pQCT parameters and bone remodeling markers. Areal BMD (aBMD) was measured by dual-energy x-ray absorptiometry (DXA) in 601 men (5 centers). Using a linear mixed model for repeated measures, the mean adjusted differences (95% CI) at 12 and 24 months between groups are reported as treatment effect. Over 24 months, testosterone treatment, versus placebo, increased tibial cortical vBMD, 9.33 mg hydroxyapatite (HA)/cm3) (3.96, 14.71), P & 0.001 or 3.1% (1.2, 5.0) radial cortical vBMD, 8.96 mg HA/cm3 (3.30, 14.62), P = 0.005 or 2.9% (1.0, 4.9) total tibial vBMD, 4.16 mg HA/cm3 (2.14, 6.19), P & 0.001 or 1.3% (0.6, 1.9) and total radial vBMD, 4.42 mg HA/cm3 (1.67, 7.16), P = 0.002 or 1.8% (0.4, 2.0). Testosterone also significantly increased cortical area and thickness at both sites. Effects on trabecular architecture were minor. Testosterone reduced bone remodeling markers CTX, −48.1 ng/L [−81.1, −15.1], P & 0.001 and P1NP, −6.8 μg/L[−10.9, −2.7], P & 0.001. Testosterone significantly increased aBMD at the lumbar spine, 0.04 g/cm2 (0.03, 0.05), P & 0.001 and the total hip, 0.01 g/cm2 (0.01, 0.02), P & 0.001. In men ≥ 50 years of age, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.
Publisher: Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology and Colposcopy
Date: 2022
Publisher: Massachusetts Medical Society
Date: 15-11-2018
Publisher: Springer Science and Business Media LLC
Date: 18-07-2015
Publisher: BMJ
Date: 20-03-2015
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.CLBC.2022.02.005
Abstract: Although digital breast tomosynthesis (DBT) improves breast cancer screen-detection compared to digital mammography (DM), there is less evidence on comparative screening outcomes by age and breast density, and inconsistent evidence on its effect on recall rate. We performed an in idual participant data (IPD) meta-analysis from DBT screening studies (identified to November, 30 2019) that contributed to the study protocol. We estimated and compared cancer detection rate (CDR), recall rate, and positive predictive value (PPV) for recall for DBT and DM screening. Two-stage random-effects meta-analyses of detection outcomes adjusted for study and age, and were estimated in age and density subgroups. Screen-detected cancer characteristics were summarized descriptively within studies and screening-groups. Four prospective studies, from European population-based programs, contributed IPD for 66,451 DBT-screened participants and 170,764 DM-screened participants. Age-adjusted pooled CDR difference between DBT and DM was 25.49 of 10,000 (95% CI:6.73-44.25). There was suggestive evidence of a higher CDR for DBT compared to DM in the high-density (35.19 of 10,000 95% CI:17.82-56.56) compared to low-density (17.4 of 10,000 95% CI:7.62-27.18) group (P = .08). Pooled CDR difference between DBT and DM did not differ across age-groups (P = .71). Age-adjusted recall rate difference was 0.18% (95% CI:-0.80-1.17), indicating no difference between DBT and DM- this finding did not differ across age-groups (P = .96). Recall PPV was higher for DBT than DM with an estimated rate ratio of 1.31 (95% CI:1.07-1.61). DBT improved CDR compared to DM in all age and density groups. DBT also had higher recall PPV than DM, although further research is needed to explore the heterogeneity in recall rates across studies.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 06-06-2010
DOI: 10.1007/S00125-010-1806-9
Abstract: The apolipoprotein B (ApoB):apolipoprotein A (ApoA)-I ratio may be a better indicator of cardiovascular disease (CVD) risk in people with type 2 diabetes than traditional lipid risk markers (LDL-cholesterol, HDL-cholesterol and triacylglycerol), but whether the ApoB:ApoA-I ratio should be used to indicate lipid-lowering therapy is still debated. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study randomised 9,795 patients with type 2 diabetes to fenofibrate (200 mg daily) or placebo and followed them up for a median of 5 years. We compared ApoB, ApoA-I, ApoAII and the ApoB:ApoA-I ratio with traditional lipid variables as predictors of CVD risk. We estimated the HR of the effect of 1 SD difference in baseline concentrations of lipids, apolipoproteins and respective ratios on the risk of CVD events and also used receiver operating characteristic curve analysis. In the placebo group, the variables best predicting CVD events were non-HDL-cholesterol:HDL-cholesterol, total cholesterol:HDL-cholesterol (HR 1.21, p < 0.001 for both), ApoB:ApoA-I (HR 1.20, p < 0.001), LDL-cholesterol:HDL-cholesterol (HR 1.17, p < 0.001), HDL-cholesterol (HR 0.84, p < 0.001) and ApoA-I (HR 0.85, p < 0.001). In the fenofibrate group, the first four predictors were very similar (but ApoB:ApoA-I was fourth), followed by non-HDL-cholesterol and ApoB. Lipid ratios and ApoB:ApoA-I performed better than any single lipid or apolipoprotein in predicting CVD risk. In patients with type 2 diabetes in the FIELD study, traditional lipid ratios were as strong as the ApoB:ApoA-I ratio in predicting CVD risk. The data provide little evidence for replacement of traditional lipids and their ratios with measures of ApoB, ApoA-I and their ratio.
Publisher: Elsevier BV
Date: 06-2020
Publisher: BMJ
Date: 2022
DOI: 10.1136/BMJOPEN-2020-048166
Abstract: Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the in idual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of in idual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups. Systematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified in idual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events. Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases. CRD42020177408.
Publisher: Massachusetts Medical Society
Date: 29-09-2011
Publisher: BMJ
Date: 2022
DOI: 10.1136/BMJOPEN-2020-048165
Abstract: Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity. Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components. The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study’s findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders. CRD42020177408.
Publisher: Elsevier BV
Date: 04-2021
Publisher: BMJ
Date: 07-2021
DOI: 10.1136/OPENHRT-2021-001678
Abstract: Significant gender disparities exist in some medical specialties, particularly cardiology. We assessed work, personal life and work-life balance in women in cardiology in Australia and New Zealand (NZ), compared with other specialties, to determine factors that may contribute to the lack of women in the specialty. This study is a prospective survey-based cohort study comparing cardiology and non-cardiology specialties. An online survey was completed by female doctors in Australia and NZ, recruited via email lists and relevant social media groups. The survey included demographics, specialty, stage of training, work hours/setting, children and relationships, career satisfaction, income and perceptions of specialty. 452 participants completed the survey (median age 36 years), of which 57 (13%) worked in cardiology. Of all respondents, 84% were partnered and 75% had children, with no difference between cardiology and non-cardiology specialties. Compared with non-cardiology specialties, women in cardiology worked more hours per week (median 50 hours vs 40 hours, p .001), were more likely to be on call more than once per week (33% vs 12%, p .001) and were more likely to earn an annual income $3 00 000 (35% vs 10%, p .001). Women in cardiology were less likely to agree that they led a balanced life (33% vs 51%, p=0.03) or that their specialty was female friendly (19% vs 75%, p .001) or family friendly (20% vs 63%, p .001). Compared with other specialties, women in cardiology reported poorer work-life balance, greater hours worked and on-call commitments and were less likely to perceive their specialty as female friendly or family friendly. Addressing work-life balance may attract and retain more women in cardiology.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 08-02-2019
DOI: 10.1007/S00192-019-03882-4
Abstract: Birthweight seems to be a risk factor for levator ani muscle (LAM) avulsion and a predictive factor for pelvic organ prolapse (POP). Most trauma seems due to first vaginal birth. One thousand one hundred twenty-five women with at least two vaginal deliveries underwent a physician-directed interview, followed by clinical examination (digital palpation and Pelvic Organ Prolapse Quantification-POPQ) and 4D translabial ultrasound. Ultrasound volume data were obtained at rest, on pelvic floor contraction and Valsalva. The investigator, blinded to all other data, performed offline analysis of the LAM integrity and hiatal area on Valsalva. We tested for associations between birthweight of the first and of the largest vaginally born baby on the one hand and avulsion and symptoms/signs of prolapse on the other hand. Between July 2014 and July 2017, 1575 patients were seen. After exclusion of nulliparae and women with just one vaginal birth, 1202 remained. Another 77 were excluded due to missing data, leaving 1125. A significant association was found between birthweight and LAM avulsion as well as significant prolapse on POPQ. The birthweight of the first vaginally born baby was at least as predictive for avulsion as the birthweight of any subsequent births, even when adjusted for maternal age at first delivery and use of forceps. The birthweight of the first vaginally born baby is associated with levator avulsion and subsequent POP. Maximum weight of vaginal births does not seem to be a stronger predictor.
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.IJCARD.2013.08.054
Abstract: The Warfarin Self-Management Anticoagulation Research Trial (Warfarin SMART) was designed to determine whether patients self-managing warfarin (PSM) using the CoaguChek device and a dosing algorithm developed for the trial could keep the INR (International Normalised Ratio) test in target range at least as often as patients managed by usual care by the family doctor or hospital clinic. 310 patients were randomly assigned to PSM or usual care. The PSM group was trained to perform home INR testing and warfarin dosing using a validated ColourChart algorithm. The primary endpoint was the proportion of times over 12 months that a monthly, blinded "outcome INR test", measured in a central laboratory, was outside the patient's target therapeutic range. The rate of out-of-range outcome INRs was lower in PSM, and non-inferior to the usual care group (PSM: 36% vs. usual care: 41%, P<0.001 for non-inferiority P=0.08 for superiority in closed-loop testing). The deviations from the patient's midpoint of target INR range (P=0.02) and number of extreme INRs (P=0.03) were significantly less in the PSM group than the usual-care group. There was no significant difference between groups in rates of bleeding or thrombotic adverse events. Patient self-management performed at least as well as usual care in maintaining the INR within the target range, without any safety concerns. This treatment modality for the long-term use of warfarin has the potential to change current local and international practice.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-04-2021
DOI: 10.1097/CCM.0000000000005034
Abstract: To examine the effect of premorbid β-blocker exposure on mortality and organ dysfunction in sepsis. Retrospective observational study. ICUs in Australia, the Czech Republic, and the United States. Total of 4,086 critical care patients above 18 years old with sepsis between January 2014 and December 2018. Premorbid beta-blocker exposure. One thousand five hundred fifty-six patients (38%) with premorbid β-blocker exposure were identified. Overall ICU mortality rate was 15.1%. In adjusted models, premorbid β-blocker exposure was associated with decreased ICU (adjusted odds ratio, 0.80 95% CI, 0.66–0.97 p = 0.025) and hospital (adjusted odds ratio, 0.83 95% CI, 0.71–0.99 p = 0.033) mortality. The risk reduction in ICU mortality of 16% was significant (hazard ratio, 0.84, 95% CI, 0.71–0.99 p = 0.037). In particular, exposure to noncardioselective β-blocker before septic episode was associated with decreased mortality. Sequential Organ Failure Assessment score analysis showed that premorbid β-blocker exposure had potential benefits in reducing respiratory and neurologic dysfunction. This study suggests that β-blocker exposure prior to sepsis, especially to noncardioselective β blockers, may be associated with better outcome. The findings suggest prospective evaluation of β-blocker use in the management of sepsis.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.IJCARD.2014.01.064
Abstract: Biomarkers may contribute to risk stratification in coronary heart disease (CHD). We examined whether plasma midregional proadrenomedullin (MR-proADM) concentration at baseline and its change over one year predicts long-term outcomes in stable CHD patients. The LIPID study randomised patients 3-36 months after an acute coronary syndrome with total cholesterol 4.0-7.0 mmol/L (155-271 mg/dL), to placebo or pravastatin 40 mg. Follow-up was 6.0 years. MR-proADM plasma concentrations at baseline and one year later were determined in 7863 and 6658 patients, respectively. These were categorised into quartiles to perform Cox regression analysis, adjusting for baseline parameters. Baseline MR-proADM concentrations predicted major CHD events (non-fatal myocardial infarction or CHD death hazard ratio (HR) 1.52, 1.26-1.84 for Q4-Q1), CHD death (HR 2.21, 1.67-2.92), heart failure (HR 2.30, 1.78-2.97) and all-cause mortality (HR 1.82, 1.49-2.23). Associations were still significant after adjustment for baseline B-type natriuretic peptide (BNP) concentration. Increase in MR-proADM after one year was associated with increased risk of subsequent CHD events (HR 1.34, 1.08-1.66), non-fatal myocardial infarction (HR 1.50, 1.12-2.03), heart failure (HR 1.78, 1.37-2.30) and all-cause mortality (HR 1.31, 1.04-1.64). Associations with heart failure and all-cause mortality remained significant after adjusting for baseline and change in BNP concentration. Change in MR-proADM moderately improved risk reclassification for major CHD events (net reclassification improvement (NRI) 3.48%) but strongly improved risk reclassification for heart failure (NRI 5.60%). Baseline and change in MR-proADM concentrations over one year are associated with risk of major clinical events, even after adjustment for BNP concentrations.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2014
DOI: 10.1007/S00192-014-2337-6
Abstract: Patient reported measures are important for the evaluation of symptom-specific bother and the distinction between different types of urinary incontinence. The aim of the study was to assess the validity of physician administered visual analogue scales (VAS) for the bother from stress urinary incontinence (SUI) and urge urinary incontinence (UUI). In this prospective cohort study based at a tertiary urogynecological unit, women attending for investigation of lower urinary tract symptoms (n = 504) were asked to indicate their subjective bother from SUI and UUI on a 10-cm VAS. Clinical assessment, including multichannel urodynamic testing and 4D translabial ultrasound was performed for clinical diagnosis. Linear regression was used to model the average increase in VAS bother score of SUI and UUI for each explanatory variable. 74 % (n = 375) reported symptoms of SUI, with mean bother of 5.7 out of 10 (SD 2.8), and 73 % (n = 370) symptoms of UUI, with a mean bother of 6.5 out of 10 (SD 2.6). Bother from UUI was positively associated with the symptoms of nocturia (p < 0.0001) and frequency (p = 0.002), and the urodynamic findings of detrusor overactivity (p < 0.0001). Bother from SUI was positively related to the urodynamic diagnosis of USI (p < 0.0001) and a low abdominal leak point pressure (ALPP) (p = 0.002), as well as to the ultrasound findings of cystourethrocele (p < 0.0001) and funnelling (p = 0.04). All univariate associations remained highly significant on multivariate analysis, controlling for age, BMI, parity, previous incontinence rolapse surgery and previous hysterectomy. Physician-administered VAS are a valid, reliable and practicable tool to measure bother related to SUI and UUI.
Publisher: Springer Science and Business Media LLC
Date: 03-2015
DOI: 10.1038/BJC.2015.37
Publisher: Wiley
Date: 09-2020
DOI: 10.1002/UOG.21996
Publisher: BMJ
Date: 06-2021
Abstract: In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)—mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR). A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1.1 modified for immune-based therapeutics. Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1–2. Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR. ANZGOG1601, ACTRN12617000106336, and NCT03015129 .
Publisher: Springer Science and Business Media LLC
Date: 23-08-2014
DOI: 10.1007/S00125-014-3344-3
Abstract: In the double-blind placebo-controlled Fenofibrate Intervention and Event Lowering in Diabetes trial (n = 9,795), fenofibrate reduced major cardiovascular events in type 2 diabetes. Sex-related differences in fenofibrate response could be clinically relevant and were pre-specified analyses. Women (n = 3,657) and men (n = 6,138) with type 2 diabetes not using statins were assigned fenofibrate (200 mg/day) or placebo for 5 years. Effects on lipoproteins and total cardiovascular events were evaluated by sex. Baseline total, LDL-, HDL- and non-HDL cholesterol and apolipoproteins A-I and B differed between sexes, and these and triacylglycerol levels improved with fenofibrate in both sexes (all p < 0.001). Fenofibrate reduced total, LDL- and non-HDL cholesterol and apolipoprotein B more in women (all p 0.1). In patients with high triacylglycerol levels and low HDL-cholesterol, fenofibrate reduced total cardiovascular outcomes by 30% (95% CI -7%, 54%) in women and 24% (95% CI 2%, 42%) in men, with no treatment-by-sex interaction (p > 0.1). Fenofibrate improved the lipoprotein profile more in women than men. Cardiovascular event reductions with fenofibrate were consistently similar in women and men, both overall and among those with low HDL-cholesterol and high triacylglycerol levels. These data provide reassurance about fenofibrate efficacy in women and men. Both sexes with type 2 diabetes should be considered for fenofibrate therapy for cardioprotection.
Publisher: Authorea, Inc.
Date: 04-2021
DOI: 10.22541/AU.161732012.21980938/V1
Abstract: Objective: To assess the general population’s knowledge regarding the utility and availability of tools to diagnosis endometriosis, with focus on ultrasound. Design: An international cross-sectional online survey study was performed between August and October 2019. Setting and Population: 5301 respondents, representing 73 countries. Methods: 23 questions survey focused on knowledge of endometriosis diagnosis distributed globally via patient- and community-endometriosis groups using social media. Main outcomes and measures: Descriptive data of the knowledge of diagnostic tools for diagnosing endometriosis, including details about diagnosis using ultrasound. Results: 84.0% of respondents had been previously diagnosed with endometriosis, 71.5% of which were diagnosed at the time of surgery. Ultrasound and MRI were the methods of diagnosis in 6.5% and 1.8%, respectively. 91.8%, 28.8%, and 16.6% of respondents believed surgery, ultrasound and MRI could diagnose endometriosis, respectively (more than one answer allowed). In those diagnosed by surgery, 21.7% knew about ultrasound as a diagnosis method compared to 51.5% knowing in those diagnosed non-surgically (p .001). 14.7%, 31.1%, and 18.2% stated superficial, ovarian, and deep endometriosis could be diagnosed with ultrasound (32.9% stated they did not know which phenotypes of endometriosis could be diagnosed). 58.4% of respondents do not believe they could access an advanced ultrasound in their region. Conclusions: There are significant gaps in the understanding of diagnosing endometriosis using non-surgical tools in this study population.
Publisher: MDPI AG
Date: 30-12-2022
Abstract: Women with advanced endometrial carcinoma (EC) with mismatch repair (MMR) deficiency have improved outcomes when treated with immune checkpoint inhibitors however, additional biomarkers are needed to identify women most likely to respond. Scores for programmed death ligand 1 (PD-L1), immunohistochemical staining of tumor (TC+), immune cells (IC+) and presence of tumor-associated immune cells (ICP) on MMR deficient (n = 34) and proficient (n = 33) EC from women treated with durvalumab in the PHAEDRA trial (ANZGOG1601/CTC0144) (trial registration number ACTRN12617000106336, prospectively registered 19 January 2017) are reported and correlated with outcome. Receiver operating characteristic (ROC) analyses and area under the ROC curve were used to determine optimal cutpoints. Performance was compared with median cutpoints and two algorithms a novel algorithm derived from optimal cutpoints (TC+ ≥ 1 or ICP ≥ 10 or IC+ ≥ 35) and the Ventana urothelial carcinoma (UC) algorithm (either TC+ ≥ 25, ICP 1 and IC+ ≥ 25 or ICP = 1 and IC+ = 100). The cutpoint ICP ≥ 10 had highest sensitivity (53%) and specificity (82%), being prognostic for progression-free survival (PFS) (p = 0.01), while the optimal cutpoints algorithm was associated with overall survival (p = 0.02) these results were not significant after adjusting for MMR status. The optimal cutpoints algorithm identified non-responders (p = 0.02) with high sensitivity (88%) and negative predictive value (92%), remaining significant after adjustment for MMR. Although MMR status had the strongest association with response, further work to determine the significance of ICP ≥ 10 and the novel optimal cutpoint algorithm is needed.
Publisher: Cureus, Inc.
Date: 04-08-2022
DOI: 10.7759/CUREUS.27693
Publisher: Springer Science and Business Media LLC
Date: 07-12-2019
DOI: 10.1007/S00192-019-04130-5
Abstract: Exo-anal ultrasound imaging of the anal sphincter is usually undertaken on pelvic floor muscle contraction (PFMC) as this seems to enhance tissue discrimination. Some women are unable to achieve a satisfactory PFMC, and in this situation, the sphincter is assessed at rest. We aimed to determine whether sphincter imaging at rest is inferior to imaging on PFMC. We analysed 441 women in this retrospective study. All underwent a standardised interview, including St Mark's incontinence score, clinical examination and 4D trans-labial ultrasound (TLUS). On analysing volume data, tomographic imaging was used to obtain a standardised set of slices at rest and on PFMC to evaluate external anal sphincter (EAS) and internal anal sphincter (IAS) trauma as described previously. When assessments obtained from volumes acquired at rest and on PFMC were tested against measures of anal incontinence (AI), all associations between the diagnosis of significant anal sphincter defects and AI were no stronger when imaging was performed on PFMC. On cross-tabulation, the percentage agreement for significant defects of the EAS and IAS at rest and on PFMC was 96.5% and 98.9% respectively, if discrepancy by one slice was allowed. Exo-anal tomographic imaging of sphincter defects at rest seems sufficiently valid for clinical use and may not be inferior to sphincter assessment on pelvic floor muscle contraction.
Publisher: American College of Physicians
Date: 19-03-2013
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.JACC.2013.08.1643
Abstract: This study sought to assess whether baseline and change in contemporary sensitive troponin I (TnI) levels predicts coronary heart disease (CHD) death and myocardial infarction (MI), and to determine the effects of pravastatin on TnI levels. The role of troponins in predicting long-term outcomes in patients with stable CHD is not clearly defined. The LIPID (Long-Term Intervention With Pravastatin in Ischaemic Disease) study randomized patients with cholesterol levels of 155 to 271 mg/dl 3 to 36 months after MI or unstable angina to placebo or pravastatin 40 mg per day. TnI levels were measured at baseline and after 1 year in 7,863 patients. Median follow-up was 6 years. Change in TnI was defined as moving up or down 1 tertile or ≥50% change. Baseline TnI tertiles were <0.006 ng/ml, 0.006 to <0.018 ng/ml, and ≥0.018 ng/ml. TnI levels were related to CHD death and MI after adjustment for 23 risk factors and treatment (≥0.018 ng/ml vs. <0.006 ng/ml hazard ratio [HR]: 1.64 95% CI: 1.41 to 1.90 p < 0.001). TnI levels increased in 23.0%, were unchanged in 51.3%, and decreased in 25.7% of patients. Pravastatin decreased TnI levels by 0.003 ng/ml versus placebo (p = 0.002). In landmark analyses, increases in TnI levels were associated with increased numbers of CHD death and MI (HR: 1.31 95% CI: 1.06 to 1.62) and decreases with decreased risk (HR: 0.90 95% CI: 0.74 to 1.09 overall p = 0.01). Data were similar with 50% change criteria. Net reclassification improvement by adding TnI to the baseline model for CHD death and MI was 4.8% (p = 0.01). Baseline TnI levels and change at 1 year are independent predictors of CHD death and MI. TnI levels are strong predictors of risk, and change modifies risk.
Publisher: Springer Science and Business Media LLC
Date: 07-10-2021
Publisher: Elsevier BV
Date: 08-2021
Publisher: Oxford University Press (OUP)
Date: 07-2023
Abstract: To determine if testosterone treatment effect on glycaemia is mediated through changes in total fat mass, abdominal fat mass, skeletal muscle mass, non-dominant hand-grip, oestradiol (E2), and sex hormone-binding globulin (SHBG). Mediation analysis of a randomised placebo-controlled trial of testosterone. Six Australian tertiary care centres recruited 1007 males, aged 50-74 years, with waist circumference ≥95 cm, serum total testosterone ≤14 nmol/L (immunoassay), and either impaired glucose tolerance or newly diagnosed type 2 diabetes on an oral glucose tolerance test (OGTT). Participants were enrolled in a lifestyle programme and randomised 1:1 to 3 monthly injections of 1000 mg testosterone undecanoate or placebo for 2 years. Complete data were available for 709 participants (70%). Mediation analyses for the primary outcomes of type 2 diabetes at 2 years (OGTT ≥ 11.1 mmol/L and change in 2-h glucose from baseline), incorporating potential mediators: changes in fat mass, % abdominal fat, skeletal muscle mass, non-dominant hand-grip strength, E2, and SHBG, were performed. For type 2 diabetes at 2 years, the unadjusted OR for treatment was 0.53 (95% CI:.35-.79), which became 0.48 (95% CI:.30-.76) after adjustment for covariates. Including potential mediators attenuated the treatment effect (OR 0.77 95% CI:.44-1.35 direct effect) with 65% mediated. Only fat mass remained prognostic in the full model (OR: 1.23 95% CI: 1.09-1.39 P & .001). At least part of the testosterone treatment effect was found to be mediated by changes in fat mass, abdominal fat, skeletal muscle mass, grip strength, SHBG, and E2, but predominantly by changes in fat mass.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.AJOG.2021.10.042
Abstract: There are no current standardized and accepted methods to characterize the surgical complexity of a laparoscopic hysterectomy. This leads to challenges when trying to understand the relationship between the patient and the surgical features and outcomes. The development of core feature sets for laparoscopic hysterectomy studies would enable future trials to measure the similar meaningful variables that can contribute to surgical complexity and outcomes. The purpose of this study was to develop a core feature set for the surgical complexity of a laparoscopic hysterectomy. This was an international Delphi consensus study. A comprehensive literature review was conducted to identify the features that were reported in studies on laparoscopic hysterectomy complexity. All the features were presented for evaluation and prioritization to key experts in 3 rounds of online surveys. A priori consensus criteria were used to reach agreement on the final outcomes for inclusion in the core feature set. Experts represented North America, South America, Europe, Africa, Asia, and Oceania. Most of them had fellowship training in minimally invasive gynecologic surgery. Sixty-four potential features were entered into round 1. Experts reached a consensus on 7 features to be included in the core feature set. These features were grouped under the following domains: 1) patient features, 2) uterine features, and 3) nonuterine pelvic features. The patient features include obesity and other nonobesity comorbidities that alter or limit the ability of a surgeon to perform the basic or routine steps in a laparoscopic hysterectomy. The uterine features include the size and presence of fibroids. The nonuterine pelvic features include endometriosis, ovarian cysts, and adhesions (bladder-to-uterus, rectouterine pouch, and other adhesions). Using robust consensus science methods, an international consortium of experts has developed a core feature set that should be assessed and reported in all future studies that aim to assess the relationship between the patient features and surgical outcomes of laparoscopic hysterectomy.
Publisher: Wiley
Date: 25-06-2018
DOI: 10.1002/AJUM.12100
Publisher: Springer Science and Business Media LLC
Date: 06-02-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2014
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JPEDS.2016.08.004
Abstract: To determine whether delayed cord cl ing improves systemic blood flow compared with immediate cord cl ing in very preterm infants in the first 24 hours. Women delivering at <30 weeks' gestation at 5 tertiary centers were randomized to receive immediate cord cl ing (<10 seconds) or delayed cord cl ing (≥60 seconds). Echocardiography and cardiorespiratory data were collected at 3, 9, and 24 hours after birth. The primary outcome was mean lowest superior vena cava (SVC) flow. Of 266 infants enrolled, 133 were randomized to immediate cord cl ing and 133 to delayed cord cl ing. The 2 groups were similar at baseline, including mean gestation (immediate cord cl ing 28 weeks vs delayed cord cl ing 28 weeks) and birth weight (immediate cord cl ing 1003 g vs delayed cord cl ing 1044 g). There was no significant difference between groups in the primary outcome of mean lowest SVC flow (immediate cord cl ing 71.4 mL/kg/min [SD 28.1] vs delayed cord cl ing 70.2 mL/kg/min [SD 26.9] P = .7). For secondary outcomes, hemoglobin increased by 0.9 g/dL at 6 hours in the group with delayed cord cl ing (95% CI 3.9, 14.4 P = .0005, adjusted for baseline). The group with delayed cord cl ing had lower right ventricular output (-21.9 mL/kg/min, 95% CI -39.0, -4.7 P = .01). Rates of treated hypotension, ductus arteriosus size and shunt direction, and treatment of the ductus arteriosus were similar. Delayed cord cl ing had no effect on systemic blood flow measured as mean lowest SVC flow in the first 24 hours in infants <30 weeks' gestation. Australia New Zealand Clinical Trials Registry: ACTRN12610000633088.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Cold Spring Harbor Laboratory
Date: 19-12-2020
DOI: 10.1101/2020.12.17.20248435
Abstract: Little is known about how early (e.g., commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to 1) characterise early obesity prevention interventions in terms of target behaviours, delivery features, and behaviour change techniques (BCTs), 2) explore similarities and differences in BCTs used to target behaviours, and 3) explore effectiveness of intervention components in preventing childhood obesity. Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the TOPCHILD Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components. The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study’s findings will be disseminated through peer-reviewed publications, conference presentations, and targeted communication with key stakeholders. Our study will provide an in depth understanding of behavioural components and delivery features used in obesity prevention interventions starting antenatally or in the first 12 months after birth. Understanding common intervention approaches in a systematic way will provide much needed insight to advance the design of early obesity prevention interventions and provide the opportunity to undertake future quantitative predictive modelling. PROSPERO registration no. CRD42020177408 This study provides an understanding of behaviours targeted, behaviour change techniques and delivery features used in early childhood obesity prevention trials identified in a systematic review as being eligible for inclusion in the Transforming Obesity Prevention in CHILDren (TOPCHILD) Collaboration. Extends previous methods by coding behaviour change techniques in published and unpublished intervention materials and performing cross validation with trialists through the TOPCHILD Collaboration. Using standardised coding taxonomies will allow for comparisons across studies, and we will pilot test new ontologies from the Human Behaviour Change Project. Explores the complex area of targeting parent and caregivers’ behaviours to impact child outcomes across four key obesity prevention behavioural domains (relating to infant feeding practices, food provision and parent feeding practices, movement practices, sleep health practices). This study will provide preliminary results regarding the examination of intervention components’ effectiveness based on exploratory analysis. Yet, the internationally unique database this project creates will further our understanding of effective intervention components in future research. To date we already have 38 out of 65 eligible trials agreeing to share data, since not all trials may provide unpublished material we may perform sensitivity analyses comparing trials that have shared data to trials that have not shared materials.
Publisher: Springer Science and Business Media LLC
Date: 07-02-2014
DOI: 10.1007/S00192-013-2307-4
Abstract: This study was undertaken to investigate the relationship between symptoms of prolapse and International Continence Society Pelvic Organ Prolapse Quantification (ICS POP-Q) measurements in order to establish optimal cutoffs for predicting prolapse symptoms using receiver operator characteristic (ROC) statistics. This was a retrospective study using 764 archived data sets of patients seen for symptoms of lower urinary tract and pelvic floor dysfunction between March 2011 and November 2012. Main outcome measure was symptoms of prolapse. Explanatory parameters were Ba, C, and Bp as defined by the ICS POP-Q. Patient age, body mass index (BMI), previous hysterectomy or incontinence rolapse surgery, and vaginal parity were tested for a confounding effect on the relationship between ICS POP-Q measurements and symptoms of prolapse. Optimal cutoffs for predicting prolapse symptoms were defined as follows: Ba = -0.5 (sensitivity 69 %, specificity 71 %), C =-5 (sensitivity 67 %, specificity 64 %), Bp = -0.5 (sensitivity 63 %, specificity 62 %). ROC statistics resulted in an area under the curve of 0.768 for Ba [confidence interval (CI) 0.729-0.807), for C of 0.724 (CI 0.672-0.776), and for Bp of 0.686 (CI 0.639-0.733). Our findings suggest that the ICS POP-Q staging system requires revision. Prolapse of the anterior and posterior vaginal wall of < -1 should probably be regarded as normal. On the other hand, stage 1 uterine prolapse as currently defined seems highly relevant.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2018
Publisher: Springer Science and Business Media LLC
Date: 27-02-2022
DOI: 10.1186/S12874-022-01534-8
Abstract: The classical linear model is widely used in the analysis of clinical trials with continuous outcomes. However, required model assumptions are frequently not met, resulting in estimates of treatment effect that can be inefficient and biased. In addition, traditional models assess treatment effect only on the mean response, and not on other aspects of the response, such as the variance. Distributional regression modelling overcomes these limitations. The purpose of this paper is to demonstrate its usefulness for the analysis of clinical trials, and superior performance to that of traditional models. Distributional regression models are demonstrated, and contrasted with normal linear models, on data from the LIPID randomized controlled trial, which compared the effects of pravastatin with placebo in patients with coronary heart disease. Systolic blood pressure (SBP) and the biomarker midregional pro-adrenomedullin (MR-proADM) were analysed. Treatment effect was estimated in models that used response distributions more appropriate than the normal (Box-Cox-t and Johnson’s S u for MR-proADM and SBP, respectively), applied censoring below the detection limit of MR-proADM, estimated treatment effect on distributional parameters other than the mean, and included random effects for longitudinal observations. A simulation study was conducted to compare the performance of distributional regression models with normal linear regression, under conditions mimicking the LIPID study. The R package gamlss (Generalized Additive Models for Location, Scale and Shape), which implements maximum likelihood estimation for distributional regression modelling, was used throughout. In all cases the distributional regression models fit the data well, in contrast to poor fits obtained for traditional models for MR-proADM a small but significant treatment effect on the mean was detected by the distributional regression model and not the normal model and for SBP a beneficial treatment effect on the variance was demonstrated. In the simulation study distributional models strongly outperformed normal models when the response variable was non-normal and heterogeneous and there was no disadvantage introduced by the use of distributional regression modelling when the response satisfied the normal linear model assumptions. Distributional regression models are a rich framework, largely untapped in the clinical trials world. We have demonstrated a s le of the capabilities of these models for the analysis of trials. If interest lies in accurate estimation of treatment effect on the mean, or other distributional features such as variance, the use of distributional regression modelling will yield superior estimates to traditional normal models, and is strongly recommended. The LIPID trial was retrospectively registered on ANZCTR on 27/04/2016, registration number ACTRN12616000535471 .
Publisher: Frontiers Media SA
Date: 21-07-2014
Publisher: Wiley
Date: 19-01-2020
DOI: 10.1002/AJUM.12196
Publisher: Elsevier BV
Date: 08-2023
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.CLON.2015.12.003
Abstract: To evaluate the learner's perspectives on a novel workshop programme designed to improve skills in biostatistics, research methodology and critical appraisal in oncology. Trainees were surveyed anonymously at the completion of each annual workshop from 2012 to 2015. In total, 103 trainees in years 2-4 of training in radiation oncology responded, giving a 94% survey response rate. A 1 day workshop, designed by biostatisticians and radiation oncologist facilitators, is the central component of a programme teaching skills in biostatistics, research methods and critical appraisal. This links short didactic lectures about statistical concepts to interactive trainee discussions around discipline-related publications. The workshop was run in conjunction with the major radiation oncology clinical trials group meeting with alternating programmes (A and B). Most of the participants (44-47/47 for A and 48-55/56 for B), reported that their understanding of one or more in idual topics improved as a result of teaching. Refinement of the workshop over time led to a more favourable perception of the 'optimal' balance between didactic/interactive teaching: nine of 27 (33%) 'optimal' responses seen in 2013 compared with 23 of 29 (79%) in 2015 (P < 0.001). Commonly reported themes were: clinician facilitators and access to biostatisticians helped contextualise learning and small group, structured discussions provided an environment conducive to learning. Overall, radiation oncology trainees reported positive perceptions of the educational value of this programme, with feedback identifying areas where this resource might be improved. This model could readily be adapted to suit other medical disciplines and/or other training environments, using specialty-specific research to illuminate key statistical concepts.
Publisher: Cold Spring Harbor Laboratory
Date: 31-07-2023
DOI: 10.1101/2023.07.30.23293383
Abstract: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor ( EGFR ) gene are a heterogenous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer generation targeted therapies in the central nervous system. We present a protocol for an in idual patient data prospective meta-analysis (IPD-PMA) to evaluate whether the addition of stereotactic radiosurgery (SRS) before Osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice. Randomised controlled trials (RCTs) will be eligible if they included: participants with BM arising from EGFR mutant NSCLC and suitable to receive Osimertinib both in the first- and second-line settings (P) comparisons of SRS followed by Osimertinib versus Osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the World Health Organisation’s International Clinical Trials Registry Platform’s Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intra-cranial progression free survival, as determined by RANO-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life and adverse events of special interest. Effect differences will be explored among pre-specified subgroups. Approved by each trials ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases. CRD42022330532 The use of an in idual patient data (IPD) meta-analysis will give increased statistical power for the relative comparison of SRS followed by Osimertinib versus Osimertinib alone on intracranial progression-free survival. Such a meta-analysis will also enable the exploration of subgroups. Frequency of outcome assessment and outcome measures may be collected and reported differently across included trials, which may lead to some imprecision. Harmonisation of clinical trial protocols through prospective meta-analysis will address some of these limitations. A limitation of this study is that the searches will only be conducted until late 2023 and any studies that are registered after this time will not be included.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Frontiers Media SA
Date: 17-10-2014
Publisher: Elsevier BV
Date: 2023
DOI: 10.2139/SSRN.4540289
Publisher: Elsevier BV
Date: 08-2012
Abstract: In the CALYPSO trial, carboplatin-pegylated liposomal doxorubicin (CD) demonstrated superior therapeutic index versus carboplatin-paclitaxel (CP) in patients with recurrent ovarian cancer. This paper reports the health-related quality of life (HRQoL) findings. HRQoL was measured with the EORTC QoL-QC30 questionnaire and OV28 ovarian cancer module. Mean change scores from baseline in HRQoL subscales (five functional scales and global health status) in each arm and the proportion of patients improved or worsened were calculated every 3 months until 12 months. Compliance was 90% at baseline and 76%, 64%, 57% at 3, 6, and 9 months, respectively. Baseline HRQoL showed already impaired global scores (mean 62/100) and considerable symptom burden (90% of patients reporting nonzero scores). Global QoL and abdominal symptom scores improved over time in both arms at 6 months, 36% of patients met criteria for improved symptoms. Treatment with CD resulted in less peripheral neuropathy (9.8 versus 24.2), fewer other chemotherapy side-effects (9.5 versus 16.2), and less impact on body image (3.8 versus 10.4) versus CP (all P<0.02) at 6 months. These patient-reported outcomes confirm the overall lower toxicity of CD versus CP. The improved disease-related outcomes achieved with CD were not at the expense of QoL.
Publisher: Springer Science and Business Media LLC
Date: 03-02-2021
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.PHYSIO.2017.02.002
Abstract: To evaluate the effects of continuous infusion of ropivacaine compared to sham infusion or usual care on pain scores before and after physiotherapy treatment, distance walked and time to discharge from physiotherapy, after coronary artery bypass graft (CABG) surgery. Prospective, randomised, double blind controlled trial. Seventy-five participants who underwent CABG surgery with left internal mammary artery grafts were allocated, to the ropivacaine group (n=26), the sham group (n=25), or usual care group (n=24). Participants in the ropivacaine group received 0.5% ropivacaine and participants in the sham group received normal saline, both as continuous infusions via two parasternally tunnelled catheters for 96hours continuously. The usual care group did not receive a device. All groups had patient-controlled analgesia and/or oral analgesia. Seventy-two participants completed the study. There was no significant between-group differences in pain scores, distance walked on any post operative day (POD) or number of participants discharged from physiotherapy by POD 4. For the group as a whole there was a significant linear decrease in pain score from mean (SD) 42 (24) mm on POD1 to 15 (16) mm on POD4 (p<0.001), (MD 27mm, 95% CI 22 to 32) and walking distance increased from 1 (5) m on POD1 to 183 (239) m on POD4 (p<0.001) MD 181m, 95% CI 126 to 236). Infusion of ropivacaine post CABG surgery was unable to reduce pain, increase distance walked or reduce time to physiotherapy discharge compared to sham or usual care. Trial registration number ACTRN12612001243808.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Wiley
Date: 06-2014
DOI: 10.1002/UOG.13222
Abstract: A specified anatomical degree of prolapse may cause no bother in one in idual and a severe form of bother in another. The aim of this study was to determine the factors contributing to the degree of bother due to a given degree of prolapse, to help with the clinical evaluation of patients and planning of preventive intervention trials and surgical treatment. Consecutive patient records of 654 women who had attended a urogynecology unit between August 2011 and December 2012 were reviewed. All patients underwent a standardized interview, clinical examination and four-dimensional translabial ultrasound scan. The degree of bother was evaluated using a visual analog scale. Six hundred and thirty-six women were included in the analysis, with ultrasound data available for cystocele, rectocele and enterocele descent and rectocele depth measurements and 442 for uterine descent. 313 women (49.2%) had subjective symptoms of female pelvic organ prolapse at a mean bother score of 6.0 ± 2.6. Average bother score for the complete dataset was 3.0 ± 3.5. Parity, vaginal delivery, levator avulsion, any significant clinical prolapse or prolapse seen on ultrasound were associated with prolapse bother and all clinical and ultrasound measures of pelvic organ descent remained significant or near significant on multivariate analysis. Quantification of prolapse bother using a visual analog scale is valid and repeatable and may represent a simple tool for use in clinical practice.
Publisher: Massachusetts Medical Society
Date: 21-12-2017
Publisher: The Endocrine Society
Date: 04-05-2021
Publisher: Elsevier BV
Date: 08-2001
DOI: 10.1016/J.JCLINEPI.2019.04.009
Abstract: The aim of the study was to compare the response rates and costs of phone call vs. short message service (SMS) screening reminders to prospective randomized controlled trial (RCT) participants. This study was a randomized evaluation within a large Australian diabetes prevention RCT. Participants were men aged 50-74 years, overweight or obese, without a previous type 2 diabetes diagnosis. Those eligible on a prescreening questionnaire who did not attend a further screening assessment within 4 weeks were randomized to receive an SMS or phone call reminder (N = 709). The primary outcome was attendance for further screening assessment within 8 weeks of prescreening. Attendance was 18% (62/354) in the SMS reminder group, and 23% (80/355) in the phone reminder group, with no statistically significant difference in response according to reminder type (relative risk = 1.29, 95% confidence interval [CI]: 0.96-1.73, P = 0.09). The lower confidence limits for response to SMS (95% CI: 14-22%) and phone reminders (95% CI: 18-27%) did not include the 8-week attendance rate before this evaluation, 12%. Phone reminders cost substantially more than SMS reminders (AU$6.21 vs. AU$0.53 per reminder). SMS reminders were as adequate a method as phone reminders to boost RCT screening uptake and were considerably more affordable.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2020
Publisher: Springer Science and Business Media LLC
Date: 20-03-2015
Publisher: Wiley
Date: 10-2021
DOI: 10.1002/UOG.23719
Abstract: Obstetric anal sphincter injury (OASI) is a common preventable cause of anal incontinence. Both diagnosis and primary repair of OASI are often suboptimal, partly owing to the absence of effective clinical audit. The aim of this study was to evaluate the location of scars or defects of the external anal sphincter (EAS), diagnosed by translabial ultrasound (TLUS), following primary OASI repair. This was a retrospective analysis of 309 women who were seen at a tertiary obstetric unit after primary repair of OASI between June 2012 and May 2019. All women underwent a standardized interview, including St Mark's incontinence score, followed by clinical examination and TLUS assessment within 2–9 months after OASI repair. Postprocessing of TLUS volume datasets was performed by an investigator who was blinded to all other information. Tomographic ultrasound imaging was used to evaluate the presence of a scar or defect in the proximal and distal parts of the EAS. Women were classified into four groups according to the imaging findings: (1) no visible defect or distortion (likely false positive) (2) only proximal OASI (3) only distal OASI and (4) both proximal and distal OASI. Of the 309 women seen during the study period, 34 were excluded because they were referred for reasons other than recent ( 1 year) OASI, 16 owing to missing data and four owing to poor image quality, leaving 255 patients for analysis. Women were seen on average 0.25 ± 0.1 years after the index birth, and their mean age at delivery was 29.1 ± 4.6 years. Anal incontinence was reported by 97 (38.0%) women. A scar or defect was seen only in the proximal part of the EAS in 64 (25.1%) women and only in the distal part in 19 (7.5%) ( P 0.001). In 165 (64.7%) women, the damage affected both the proximal and distal EAS. EAS scars after primary OASI repair commonly affect the entire length of the EAS however, partial tears seem to be more likely to occur proximally. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Publisher: Frontiers Media SA
Date: 07-10-2015
Publisher: Springer Science and Business Media LLC
Date: 15-04-2019
DOI: 10.1038/S41390-019-0382-Z
Abstract: A correction to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: Public Library of Science (PLoS)
Date: 15-03-2019
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.CLCC.2018.06.002
Abstract: The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. Patients were enrolled in an open-label, multicenter, phase II trial and randomly assigned to cetuximab 400 mg/m From 2012 to 2016, 48 patients were recruited. Two were ineligible, and 2 were not evaluable for response. Characteristics were balanced, except gender (male, 62% vs. 72%) and primary sidedness (left, 95% vs. 68%). For cetuximab compared with cetuximab-irinotecan, progression-free survival was 14% versus 41% (hazard ratio, 0.39 95% confidence interval, 0.20-0.78 P = .008) response rate was 10% (2 partial responses) versus 38% (1 complete, 8 partial) P = .04. Grade 3 to 4 toxicities were less with cetuximab monotherapy (23% vs. 50%) global and specific quality of life scores did not differ. In comparison with cetuximab alone, cetuximab plus irinotecan increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. This echoes data from molecularly unselected patients.
Publisher: Wiley
Date: 21-12-2012
DOI: 10.1111/J.1469-8749.2011.04161.X
Abstract: The collection of data on longer-term neurodevelopmental outcomes within large neonatal randomized controlled trials by trained assessors can greatly increase costs and present many operational difficulties. The aim of this study was to develop a more practical alternative for identifying major cognitive delay in infants at the age of 24 months, based on parental reports. A s le of 476 infants (206 female, 270 male) previously diagnosed with neonatal sepsis (mean birthweight 1329g [SD 865g], mean gestational age at birth 28.7wks [SD 4.5wks]) from the International Neonatal Immunotherapy Study were assessed using the Parent Report of Children's Abilities - Revised and the Bayley Scales of Infant Development, 2nd edition. Logistic regression was used to model the association between the risk of major cognitive delay (i.e. Bayley Scales of Infant Development Mental Development Index <55) and the Parent Report of Children's Abilities - Revised data. The receiver operating characteristic curves for a number of predictive models were constructed - each achieved an area under the curve of at least 90%. The sensitivity, specificity, positive predictive value, and negative predictive value of a number of points on the receiver operating characteristic curves are presented. The Parent Report of Children's Abilities - Revised is a practical tool for identifying major cognitive delay in infants at 24 months.
Publisher: Springer Science and Business Media LLC
Date: 19-06-2019
Publisher: BMJ
Date: 17-08-2018
DOI: 10.1136/ARCHDISCHILD-2016-312006
Abstract: Functional cardiac ultrasound measures are used clinically and in trials for assessing the haemodynamic status of newborn infants. Superior vena cava (SVC) flow and right ventricular output (RVO) are established measures of systemic blood flow on the first postnatal day. The objective was to assess image quality and interobserver agreement of these measures in preterm infants enrolled in a randomised trial of immediate versus delayed cord cl ing. Image quality and interobserver agreement for SVC flow, RVO and ductus arteriosus (DA) size were assessed on measurements taken at 3–6, 6–12 and 20–28 hours for the first 10 infants enrolled at each of four sites (total 40). Bland-Altman plots were constructed mean difference (bias) and limits of agreement (LOA) were calculated. Potential sources of variation were explored. Quality was judged satisfactory for % of images. The mean difference and LOA between the observers were 5.4 mL/kg/min and −49.0 to 59.8 mL/kg/min for SVC flow, −26.6 mL/kg/min and −131.4 to 78.2 mL/kg/min for RVO, and 0 mm and −0.8 to 0.8 mm for DA diameter, respectively. The principal source of measurement error for SVC flow was diameter, and for RVO, diameter and velocity time integral. The difference between observers for both SVC and RVO was significantly associated with site. Interobserver variability for SVC flow is consistent with that previously reported, but higher for RVO. The findings should be incorporated into clinical practice, training, accreditation and trial design.
Publisher: BMJ
Date: 03-2020
DOI: 10.1136/BMJOPEN-2019-034595
Abstract: Timing of cord cl ing and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord cl ing, and cord milking. In idual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons. (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA. Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks’ gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials aggregate summary data will be included where IPD are unavailable. First, deferred cl ing and cord milking will be compared with immediate cl ing in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored. Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases. Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12619001305112) and International Prospective Register of Systematic Reviews (PROSPERO, CRD42019136640).
Publisher: Wiley
Date: 04-01-2019
DOI: 10.1111/DOM.13601
Abstract: Low circulating testosterone is associated with an increased risk of developing type 2 diabetes (T2DM) in overweight men with impaired glucose tolerance (IGT). To determine in a multi-centre, double-blinded placebo-controlled randomized trial whether testosterone treatment combined with lifestyle intervention (Weight Watchers) relative to lifestyle intervention alone reduces T2DM incidence and improves glucose tolerance at 2 years. Overweight or obese men aged 50-74 years with a serum testosterone of ≤14 nmol/L and IGT or newly diagnosed T2DM established by an oral glucose tolerance test (OGTT). Six Australian capital city-based tertiary care centres. Participants were randomized 1:1 and injected with testosterone undecanoate (1000 mg/4 mL) or vehicle (4 mL castor oil), at baseline, 6 weeks and 3-monthly thereafter. PRIMARY ENDPOINTS: (a) Proportion of participants with 2-hour OGTT ≥11.1 mmol/L at 2 years, and (b) a difference at 2 years ≥0.6 mmol/L in the mean 2-hour OGTT glucose between treatments. Fasting insulin, HbA1c, body composition, maximal handgrip strength sexual function and lower urinary tract symptoms serum sex steroids and sex hormone binding globulin mood and psychosocial function adherence to lifestyle intervention and healthcare utilization and costs. Overseen by an Independent Data Safety Monitoring Committee. Haematocrit, lipids and prostate-specific antigen (PSA) are assessed 6-monthly and information relating to haematological, urological and cardiovascular adverse events from each clinic visit. SUB-STUDIES: (a) Changes in bone density and micro-architecture, (b) motivation and behaviour, (c) telomere length, (d) extended treatment up to 4 years, and (e) hypothalamo-pituitary testicular axis recovery at treatment end.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 07-2016
Abstract: RAS mutations predict lack of response to epidermal growth factor receptor monoclonal antibody therapy in patients with metastatic colorectal cancer (mCRC), but preclinical studies and retrospective clinical data suggest that patients with tumors harboring the exon 2 KRAS G13D mutation may benefit from cetuximab. We aimed to assess cetuximab monotherapy and cetuximab plus irinotecan in patients with molecularly selected (G13D mutation) chemotherapy-refractory mCRC in a randomized phase II trial of this rare molecular subtype. Patients with chemotherapy-refractory KRAS G13D mutation–positive mCRC who had progressed within 6 months of irinotecan therapy were randomly assigned to cetuximab 400 mg/m 2 loading dose and then 250 mg/m 2 once per week with or without irinotecan 180 mg/m 2 once every 2 weeks. The primary end point was 6-month progression-free survival secondary end points were response rate, overall survival, quality of life, and toxicity. Fifty-one of 53 patients recruited over 2 years were eligible. The 6-month progression-free survival rate was 10% (95% CI, 2% to 26%) for cetuximab versus 23% (95% CI, 9% to 40%) for cetuximab plus irinotecan with a hazard ratio of 0.74 (95% CI, 0.42 to 1.32). Response and stable disease rates were 0% and 58% for monotherapy versus 9% and 70% for combination treatment, respectively. Overall survival and quality of life were similar toxicities were higher with combination therapy. In patients with G13D-mutated chemotherapy-refractory mCRC, there was no statistically significant improvement in disease control at 6 months with either cetuximab monotherapy or cetuximab plus irinotecan. No responses were seen with single-agent cetuximab. The responses observed with the combination of cetuximab and irinotecan may reflect true drug synergy or persistent irinotecan sensitivity. The ICECREAM (Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation Among Patients with a G13D Mutation) study demonstrates the need to prospectively evaluate hypotheses that were previously supported by retrospective analyses and exemplifies the value of international collaboration in trials of rare molecular subtypes.
Publisher: Elsevier BV
Date: 12-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2022
Abstract: Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long‐term or is independent of renal function and other important biomarkers. Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long‐Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow‐up, 6 years) and long‐term (median follow‐up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR‐creatinine, then GFR‐creatinine‐cystatin C). Over 6 years, in fully adjusted multivariable time‐to‐event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07–1.74 P =0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19–1.82 P .001). Over 16 years, the association of baseline cystatin C with coronary heart disease, cardiovascular, and all‐cause mortality persisted (each P .001) and remained significant after adjustment for estimated GFR‐creatinine‐cystatin C. Cystatin C also predicted the development of chronic kidney disease for 6 years (odds ratio, 6.61 95% CI, 4.28–10.20) independently of estimated GFR‐creatinine and other risk factors. However, this association was no longer significant after adjustment for estimated GFR‐creatinine‐cystatin C. Cystatin C independently predicted major cardiovascular events, development of chronic kidney disease, and cardiovascular and all‐cause mortality. Prediction of long‐term mortality was independent of improved estimation of GFR. URL: anzctr.org.au Unique identifier: ACTRN12616000535471.
Publisher: Public Library of Science (PLoS)
Date: 31-05-2022
DOI: 10.1371/JOURNAL.PONE.0268972
Abstract: To analyse the effects of maternal diabetes mellitus (DM) and body mass Index (BMI) on central and peripheral fat accretion of large for gestational age (LGA) offspring. This retrospective study included LGA fetuses (n = 595) with ultrasound scans at early (19.23 ± 0.68 weeks), mid (28.98 ± 1.62 weeks) and late (36.20 ± 1.59 weeks) stages of adipogenesis and measured abdominal (AFT) and mid-thigh (TFT) fat as surrogates for central and peripheral adiposity. Women were categorised according to BMI and DM status [pre-gestational (P-DM n = 59), insulin managed (I-GDM n = 132) and diet managed gestational diabetes (D-GDM n = 29)]. Analysis of variance and linear regressions were applied. AFT and TFT did not differ significantly between BMI categories (normal, overweight and obese). In contrast, AFT was significantly higher in pregnancies affected by D-GDM compared to non-DM pregnancies from mid stage (0.44 mm difference, p = 0.002) and for all DM categories in late stage of adipogenesis (≥ 0.49 mm difference, p 0.008). Late stage TFT accretion was higher than controls for P-DM and I-GDM but not for D-GDM (0.67 mm difference, p 0.001 0.49 mm difference, p = 0.001, 0.56 mm difference, p = 0.22 respectively). In comparison to the early non-DM group with an AFT to TFT ratio of 1.07, the I-GDM group ratio was 1.25 (p 0.001), which normalised by 28 weeks becoming similar to control ratios. DM, independent of BMI, was associated with higher abdominal and mid-thigh fat accretion in fetuses. Use of insulin improved central to peripheral fat ratios in fetuses of GDM mothers.
Publisher: Informa UK Limited
Date: 18-02-2020
Publisher: Wiley
Date: 09-2021
Abstract: To assess the general population’s knowledge regarding the utility and availability of tools to diagnosis endometriosis, with a focus on ultrasound. An international cross‐sectional online survey study was performed between August and October 2019. 5301 respondents, representing 73 countries. In all, 23 questions survey focused on knowledge of endometriosis diagnosis distributed globally via patient‐ and community‐endometriosis groups using social media. Descriptive data of the knowledge of diagnostic tools for diagnosing endometriosis, including details about diagnosis using ultrasound. In all, 84.0% of respondents had been previously diagnosed with endometriosis, 71.5% of whom had been diagnosed at the time of surgery. Ultrasound and MRI were the methods of diagnosis in 6.5% and 1.8%, respectively. A total of 91.8%, 28.8% and 16.6% of respondents believed surgery, ultrasound and MRI could diagnose endometriosis, respectively (more than one answer allowed). In those diagnosed by surgery, 21.7% knew about ultrasound as a diagnosis method, whereas in those diagnosed non‐surgically, 51.5% knew ( P 0.001). In all, 14.7%, 31.1% and 18.2% stated superficial, ovarian and deep endometriosis could be diagnosed with ultrasound (32.9% stated they did not know which phenotypes of endometriosis could be diagnosed). Lastly, 58.4% of respondents do not believe they could access an advanced ultrasound in their region. There is a limited appreciation for the role of non‐surgical diagnostic tests for endometriosis among lay respondents to this survey. International survey shows limited awareness of lay respondents about non‐surgical endometriosis diagnostic tools.
Publisher: Radcliffe Media Media Ltd
Date: 04-04-2023
DOI: 10.15420/ECR.2022.39
Abstract: Objective: To investigate the extent to which multivessel disease, incomplete revascularisation and prescribing differences contribute to sex-based outcome disparities in patients with ST-elevation MI (STEMI) and establish whether differences in cardiac death and MI (CDMI) rates persist at long-term follow-up. Methods and results: This observational study evaluates sex-based outcome differences (median follow-up 3.6 years IQR [2.4–5.4]) in a consecutive cohort of patients (n=2,083) presenting with STEMI undergoing percutaneous coronary intervention). Of the studied patients 20.3% (423/2,083) were women and 38.3% (810/2,083) had multivessel disease (MVD). Incomplete revascularisation was common. The median residual SYNTAX score (rSS) was 5.0 (IQR [0–9]) in women and 5.0 (IQR [1–11]) in men (p=0.369), and in patients with MVD it was 9 (IQR [6–17]) in women and 10 (IQR [6–15]) in men (p=0.838). The primary endpoint CDMI occurred in 20.3% of women (86/423) and in 13.2% of men (219/1,660) (p=0.028). Differences persisted following multivariable risk adjustment: female sex was independently associated with CDMI (aHR 1.33 IQR [1.02–1.74]). Women with MVD had CDMI more often than all other groups (p .001 for all). Significant sex-based prescribing differences were evident: women were less likely to receive guideline-recommended potent P2Y12 inhibitors than men (31% versus 43% p=0.012), and differences were particularly evident in patients with MVD (25% in women versus 45% in men, p=0.011). Conclusion: Sex-based differences in STEMI patient outcome persist at long-term follow-up. Poor outcomes were disproportionately found in women with MVD and those with rSS . Observed differences in P2Y12 prescribing practices may contribute to poor outcomes for women with MVD and incomplete revascularisation.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Massachusetts Medical Society
Date: 22-11-2012
Publisher: SAGE Publications
Date: 03-10-2019
Abstract: Participant recruitment to diabetes prevention randomised controlled trials is challenging and expensive. The T4DM study, a multicentre, Australia-based, Phase IIIb randomised controlled trial of testosterone to prevent Type 2 diabetes in men aged 50–74 years, faced the challenge of screening a large number of prospective participants at a small number of sites, with few staff, and a limited budget for screening activities. This article evaluates a high-volume, low-cost, semi-automated approach to screen and enrol T4DM study participants. We developed a sequential multi-step screening process: (1) web-based pre-screening, (2) laboratory screening through a network of third-party pathology centres, and (3) final on-site screening, using online data collection, computer-driven eligibility checking, and automated, email-based communication with prospective participants. Phone- and mail-based data collection and communication options were available to participants at their request. The screening process was administered by the central coordinating centre through a central data management system. Screening activities required staffing of approximately 1.6 full-time equivalents over 4 years. Of 19,022 participants pre-screened, 13,108 attended a third-party pathology collection centre for laboratory screening, 1217 received final, on-site screening, and 1007 were randomised. In total, 95% of the participants opted for online pre-screening over phone-based pre-screening. Screening costs, including both direct and staffing costs, totalled AUD1,420,909 (AUD75 per subject screened and AUD1411 per randomised participant). A multi-step, semi-automated screening process with web-based pre-screening facilitated low-cost, high-volume participant enrolment to this large, multicentre randomised controlled trial. Centralisation and automation of screening activities resulted in substantial savings compared to previous, similar studies. Our screening approach could be adapted to other randomised controlled trial settings to minimise the cost of screening large numbers of participants.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 2020
Publisher: SAGE Publications
Date: 16-04-2014
Abstract: This study aims to examine the characteristics of obsessive compulsive disorder (OCD) associated with high levels of schizotypy. Using the Schizotypal Personality Questionnaire (SPQ) with 177 in iduals with OCD, patients with OCD and high levels of schizotypy (OCD-HS) were compared to patients with OCD and low levels of schizotypy (OCD-LS) on a range of clinical characteristics. Self-report and clinician-administered instruments were used. Results were adjusted for the severity of OCD symptoms, age, marital status and comorbidity using logistic regression. Patients with OCD-HS were younger and less likely to have been married. OCD-HS was associated with higher rates of symmetry/order obsessions, ordering/arranging compulsions, checking compulsions, co-occurring major depression, post-traumatic stress disorder, substance use disorders and greater general psychopathology. Previously reported associations, such as higher total scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) were not significant when adjusted for differences in demographic variables and comorbidity. Patients with OCD-HS were associated with specific OCD symptoms and comorbid conditions and may warrant a specific treatment approach.
Publisher: Springer Science and Business Media LLC
Date: 21-02-2019
DOI: 10.1038/S41390-019-0348-1
Abstract: To determine associations of low superior vena cava (SVC) flow (≤55 ml/kg/min) and low right ventricular output (RVO) (≤150 ml/kg/min) in preterm infants. An observational study in infants <30 weeks gestation randomized to receive immediate (<10 s) or delayed cord cl ing (DCC) (≥60 s). The study enrolled 265 infants with a mean (SD) gestation 28 (2) weeks. Eighty-six (33%) infants had low SVC flow and 81 (31%) infants had low RVO. In multivariate analysis, low SVC flow was associated with gestation low RVO was associated with DCC, gender and 5-minute Apgar whereas mean RVO was negatively associated with both FiO SVC flow was associated with gestation, whilst RVO was associated with placental transfusion, gender, condition at birth, and early respiratory adaptation. Compared to infants with normal values, more infants with low SVC flow were treated for DA, but infants with low RVO had no significant difference in mortality or morbidity.
Publisher: BMJ
Date: 02-11-2021
Abstract: Sentinel node biopsy is a surgical technique to explore lymph nodes for surgical staging of endometrial cancer, which has replaced full retroperitoneal lymph node dissection. However, the effectiveness of sentinel node biopsy, its value to patients, and potential harms compared with no-node dissection have never been shown in a randomized trial. Stage 1 will test recovery from surgery. Stage 2 will compare disease-free survival at 4.5 years between patients randomized to sentinel node biopsy versus no retroperitoneal node dissection. The primary hypothesis for stage 1 is that treatment with sentinel node biopsy will not cause detriment to patient outcomes (lymphedema, morbidity, loss of quality of life) and will not increase treatment-related morbidity or health services costs compared with patients treated without a retroperitoneal node dissection at 12 months after surgery. The primary hypothesis for stage 2 is that disease-free survival at 4.5 years after surgery in patients without retroperitoneal node dissection is not inferior to those receiving sentinel node biopsy. This phase III, open-label, two-arm, multistage, randomized non-inferiority trial (ENDO-3) will determine the value of sentinel node biopsy for surgical management of endometrial cancer. Patients with endometrial cancer are randomized to receive: (1) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy with sentinel node biopsy or (2) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection. In stage 1, 444 patients will be enrolled to demonstrate feasibility and quality of life. If this is demonstrated, we will enroll another 316 patients in stage 2. Inclusion criteria include women aged 18 years or older with histologically confirmed endometrial cancer clinical stage 1, who meet the criteria for laparoscopic or robotic total hysterectomy and bilateral salpingo-oophorectomy. Patients with uterine mesenchymal tumors are excluded. The endpoint for stage 1 is surgical recovery, with the proportion of patients returning to usual daily activities at 3 months post-surgery as measured with the EQ-5D. Stage 2 is disease-free survival at 4.5 years. 760 participants (both stages). Stage 1 commenced in January 2021 and is planned to be completed in December 2024 when 444 participants have completed 12 months' follow-up. Stage 2 will enroll a further 316 participants for a total of 760 patients. NCT04073706 .
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-08-2018
DOI: 10.1161/CIRCULATIONAHA.117.029901
Abstract: D-dimer, a degradation product of cross-linked fibrin, is a marker for hypercoagulability and thrombotic events. Moderately elevated levels of D-dimer are associated with the risk of venous and arterial events in patients with vascular disease. We assessed the role of D-dimer levels in predicting long-term vascular outcomes, cause-specific mortality, and new cancers in the LIPID trial (Long-Term Intervention with Pravastatin in Ischaemic Disease) in the context of other risk factors. LIPID randomized patients to placebo or pravastatin 40 mg/d 5 to 38 months after myocardial infarction or unstable angina. D-dimer levels were measured at baseline and at 1 year. Median follow-up was 6.0 years during the trial and 16 years in total. Baseline D-dimer levels for 7863 patients were grouped by quartile (≤112, 112–173, 173–273, ng/mL). Higher levels were associated with older age, female sex, history of hypertension, poor renal function, and elevated levels of B-natriuretic peptide, high-sensitivity C-reactive protein, and sensitive troponin I (each P .001). During the first 6 years, after adjustment for up to 30 additional risk factors, higher D-dimer was associated with a significantly increased risk of a major coronary event (quartile 4 versus 1: hazard ratio [HR], 1.45 95% confidence interval, 1.21–1.74), major cardiovascular disease (CVD) event (HR, 1.45 95% confidence interval, 1.23–1.71) and venous thromboembolism (HR, 4.03 95% confidence interval, 2.31–7.03 each P .001). During the 16 years overall, higher D-dimer was an independent predictor of all-cause mortality (HR, 1.59), CVD mortality (HR, 1.61), cancer mortality (HR, 1.54), and non-CVD noncancer mortality (HR, 1.57 each P .001), remaining significant for deaths resulting from each cause occurring beyond 10 years of follow-up (each P ≤0.01). Higher D-dimer also independently predicted an increase in cancer incidence (HR, 1.16 P =0.02).The D-dimer level increased the net reclassification index for all-cause mortality by 4.0 and venous thromboembolism by 13.6. D-dimer levels predict long-term risk of arterial and venous events, CVD mortality, and non-CVD noncancer mortality independent of other risk factors. D-dimer is also a significant predictor of cancer incidence and mortality. These results support an association of D-dimer with fatal events across multiple diseases and demonstrate that this link extends beyond 10 years’ follow-up.
Publisher: Wiley
Date: 02-01-2018
DOI: 10.1111/AJD.12759
Abstract: Organ transplant recipients (OTR) have an increased risk of skin cancers compared with the general population. A prospective study of renal (RTR) and liver transplant recipients (LTR) was conducted in a single New South Wales tertiary referral centre over 60 months. Initial and subsequent visit data were recorded in our transplant database. Only patients with a minimum of 11 months follow up were included. Altogether 142 RTR and 88 LTR were included in the analysis. Compared with RTR, the median age of liver transplant recipients was higher (64 vs 57 years), more men were patients (73 vs 60%) and there were higher rates of high-risk skin types (54 vs 33%) and heavy sun exposure (43 vs 30%). RTR developed 304 non-melanoma skin cancers (NMSC) with a squamous cell carcinoma:basal cell carcinoma ratio of 1.7:1. LTR developed 205 NMSC with a squamous cell carcinoma:basal cell carcinoma ratio of 1.6:1. The odds ratio of developing NMSC in LTR:RTR was 1.8:1 (95% CI: 1.02-3.11, P = 0.044) on univariate analysis but there was no difference on multivariate analysis. A previous history of NMSC, age, time from transplant from first visit, skin phenotype and previous sun exposure were significant risk factors for developing NMSC. Liver transplant recipients are not at a lower risk of NMSC than RTR. Our study supports routine and regular post-transplant skin surveillance of all LTR, like other OTR.
No related grants have been discovered for Kristy Robledo.