ORCID Profile
0000-0001-5804-2295
Current Organisation
University of Queensland
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Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.RADONC.2016.02.009
Abstract: This study aimed to examine the rate and type of p53 mutation in oropharyngeal cancer (OSCC). Relationships were sought between human papillomavirus (HPV) status and p53 mutation. The role of p53 mutation as a prognostic factor independent of HPV status and as a modifier of the effect of HPV on outcomes was also examined. The HPV status of 202 cases was determined by HPV DNA by RT-PCR and p16 immunohistochemistry. P53 mutation in exon 5-8 was determined by pyrosequencing. Findings were correlated with known clinicopathological factors and outcomes. 48% of the cases were HPV positive and they were significantly less likely to have a p53 mutation than HPV-negative OSCCs (25.8% vs 46.7%, p=0.0021). Mutation was most common in exon 5. Among patients with HPV-positive OSCC, there was no significant difference in p53 mutation by smoking status (22.2% for never smokers and 30.8% for current or ex-smokers). Patients with p53 mutant OSCC had significantly worse overall survival (p=0.01). There was no statistical evidence that p53 mutation modified the effect of HPV status on outcomes. In the multivariate analysis, positive HPV status remained the strongest predictor of outcomes. p53 mutation status was not a significant predictor of outcome after adjusting for age, gender, T stage, N stage and HPV status. In summary, HPV-positive OSCC are less likely to have mutant p53 than HPV-negative OSCC. Our study did not show any evidence that p53 mutation could modify the effect of HPV status on outcomes.
Publisher: Oxford University Press (OUP)
Date: 25-01-2017
DOI: 10.1111/BJD.15204
Publisher: Wiley
Date: 06-02-2020
DOI: 10.1111/IJPO.12618
Publisher: European Respiratory Society (ERS)
Date: 30-04-2016
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.JGO.2018.11.004
Abstract: The use of geriatric assessment (GA) and the Cancer and Aging Research Group (CARG) Toxicity Score by Australian oncologists is low. We sought oncologists' views about the value of GA and the CARG Score when making decisions about chemotherapy for their older patients. Patients aged ≥65 yrs. with a plan to start chemotherapy for a solid organ cancer underwent a GA and had their CARG Score calculated. Results of the GA and CARG Score were provided to treating oncologists who then completed a questionnaire on the value of these measures for each patient. We enrolled 30 patients from eight oncologists. Patients had a median age of 76 years and most (77%) were ECOG performance status 0 or 1. Risk category for severe chemotherapy toxicity by CARG Score was low in 7 patients (23%), intermediate in 18 (60%), and high in 5 (17%). The GA provided oncologists new information for 12 patients (40%), most frequently in the domains of function and nutrition. Knowledge of the GA prompted supportive interventions for 7 patients (23%). Oncologists considered modifications to recommended chemotherapy based on the CARG Score for 2 patients (7%) (one more intensive and one less intensive), and based on GA for no patients. Oncologists judged the GA and CARG Score as useful in 26 (87%) and 25 (83%) patients, respectively. Although oncologists valued the GA and CARG Score, they rarely used them to modify chemotherapy. The GA provided new information that prompted supportive interventions in one quarter of patients.
Publisher: Massachusetts Medical Society
Date: 25-02-2016
DOI: 10.1056/NEJMC1514791
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.JGO.2019.07.026
Abstract: Patients with cancer have varied preferences for involvement in decision-making. We sought older adults' preferred and perceived roles in decision-making about palliative chemotherapy priorities and information received and desired. Patients ≥65y who had made a decision about palliative chemotherapy with an oncologist completed a written questionnaire. Preferred and perceived decision-making roles were assessed by the Control Preferences Scale. Wilcoxon rank-sum tests evaluated associations with preferred role. Factors important in decision-making were rated and ranked, and receipt of, and desire for information was described. Characteristics of the 179 respondents: median age 74y, male (64%), having chemotherapy (83%), vulnerable (Vulnerable Elders Survey-13 score ≥ 3) (52%). Preferred decision-making roles (n = 173) were active in 39%, collaborative in 27%, and passive in 35%. Perceived decision-making roles (n = 172) were active in 42%, collaborative in 22%, and passive in 36% and matched the preferred role for 63% of patients. Associated with preference for an active role: being single/widowed (p = .004, OR = 1.49), having declined chemotherapy (p = .02, OR = 2.00). Ranked most important (n = 159) were "doing everything possible" (30%), "my doctor's recommendation" (26%), "my quality of life" (20%), and "living longer" (15%). A minority expected chemotherapy to cure their cancer (14%). Most had discussed expectations of cure (70%), side effects (88%) and benefits (82%) of chemotherapy. Fewer had received quantitative prognostic information (49%) than desired this information (67%). Older adults exhibited a range of preferences for involvement in decision-making about palliative chemotherapy. Oncologists should seek patients' decision-making preferences, priorities, and information needs when discussing palliative chemotherapy.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-02-2022
DOI: 10.1200/JCO.2022.40.6_SUPPL.010
Abstract: 10 Background: The TheraP trial showed that LuPSMA improved PSA≥50% response rate (PSA50-RR), PSA-PFS, and radiographic PFS (rPFS) compared with cabazitaxel in mCRPC progressing after docetaxel. Study inclusion required high PSMA uptake (SUVmax≥20) and no lesions that were FDG+ and PSMA-. Here we report on PSMA PET and FDG PET as potential predictive and prognostic biomarkers. Methods: We prospectively analysed semi-automated quantitative PET parameters in centrally- collected 68 Ga-PSMA-11 PET and 18 F-FDG PET in 200 eligible men. SUVmean ≥10 on PSMA PET was evaluated as a predictive biomarker for response to Lu-PSMA vs cabazitaxel. Metabolic tumor volume (MTV) ≥200mL on FDG PET was tested as a prognostic biomarker accounting for the randomly assigned treatment. Quantitative PET cut-offs were pre-specified from prior research (PMID:32140802). Responses were defined according to PSA50-RR (primary endpoint), PSA-PFS and rPFS. Binary and PFS endpoints were analyzed using logistic and Cox regression, respectively. Results: Very high PSMA uptake on PSMA PET (SUVmean≥10) was seen in 35/99 (35%) assigned LuPSMA and 30/101 (30%) assigned cabazitaxel. The odds of a response to LuPSMA vs. cabazitaxel were significantly higher for men with SUVmean≥10 (OR 12.2, 95%CI 3.4-59 vs. 2.2, 95%CI 1.1-4.5 p = 0.03). In men with SUVmean≥10, the PSA50-RR for LuPSMA vs. cabazitaxel were 32/35 (91%) vs. 14/30 (47%). In men with PSMA SUVmean 10, the PSA50-RR were 33/64 (52%) vs. 23/71 (32%). High-volume metabolic disease on FDG PET (MTV ≥200mL) was seen in 30/99 (30%) assigned LuPSMA and 30/101 (30%) assigned cabazitaxel. The PSA50-RR in these men was 17/30 (57%) for LuPSMA vs. 6/30 (20%) for cabazitaxel. In comparison, the PSA50-RR for men with MTV 200mL on FDG PET was 48/69 (70%) for LuPSMA vs. 31/71 (44%) for cabazitaxel. After accounting for treatment, the odds of a PSA50-response was lower among men with high MTV (OR 0.44 p = 0.01). The HR for PSA-PFS for LuPSMA vs cabazitaxel was 0.45 (95%CI 0.25-0.80) for SUVmean≥10 vs. 0.77 (95%CI 0.53-1.12) for SUVmean 10 (p = 0.2). Findings were similar for rPFS. The HRs for high MTV on FDG PET adjusted for treatment were 1.44 (95%CI 1.03-2.02) for PSA-PFS (p = 0.03) and 1.79 (95%CI 1.28-2.52) for rPFS (p 0.001). Conclusions: In men with mCRPC, PSMA SUVmean≥10 was predictive of a higher likelihood of favourable response to LuPSMA than cabazitaxel, whilst a high volume of disease on FDG PET was associated with a worse prognosis regardless of randomly assigned treatment. Clinical trial information: NCT03392428.
Publisher: Springer Science and Business Media LLC
Date: 21-11-2019
DOI: 10.1007/S10549-018-5054-X
Abstract: Adding cyclin-dependent kinase (CDK) 4/6 inhibitor to endocrine therapy improves progression-free survival (PFS) in advanced breast cancer but the impact of ethnicity on efficacy and toxicity is unclear. We aimed to estimate the relative treatment efficacy and toxicity of endocrine therapy with and without CDK4/6 inhibitors, and compare between Asian/non-Asian subgroups. This meta-analysis included published first-line randomized trials comparing CDK4/6 inhibitor-endocrine therapy versus endocrine monotherapy. Hazard ratios (HR) and 95% confidence intervals (CI) for the overall population and Asian/non-Asian subgroups were extracted. The inverse-variance-weighted method was used to pool treatment estimates of PFS. Four trials (N = 2499) were included. Patients received combination CDK4/6 inhibitor-endocrine therapy (N = 1441 ribociclib, [46.4%] palbociclib, [30.8%] or abemaciclib, [22.8%]) versus endocrine monotherapy (N = 1058). CDK4/6 inhibitor-endocrine therapy was associated with prolonged PFS compared with endocrine monotherapy (HR 0.56 95% CI 0.50-0.62). In Asians (N = 492), PFS HR was 0.39 (95% CI 0.29-0.51, P < 0.0001). In non-Asians (N = 2007), PFS HR was 0.62 (95% CI 0.54-0.71, P < 0.0001). There was a significant treatment-by-ethnicity interaction (P = 0.002). Toxicity data by ethnic subgroup were only available from two trials (n = 1334) with no convincing evidence that the risk of toxicity between CDK4/6 inhibitor-endocrine therapy and endocrine monotherapy varied by ethnicity. Adding CDK4/6 inhibitor to endocrine therapy prolongs PFS compared to endocrine therapy alone as first-line treatment in advanced breast cancer. The magnitude of PFS benefit is ethnicity-dependent but there is no interethnic differences in relative treatment-related toxicities. These findings may assist in the design and interpretation of trials, inform economic analyses, and stimulate pharmacogenomic research.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 02-07-2014
DOI: 10.1007/S11764-014-0378-Y
Abstract: This study aimed to explore differences in physical activity and fitness between women with metastatic breast cancer compared to healthy controls and factors associated with their physical activity levels. Seventy-one women with metastatic breast cancer, aged (mean (SD)) 57.7 (9.5) and 2.9 (3.1) years after the onset of metastatic disease, and 71 healthy controls aged 55.0 (9.4) years participated. Of those with metastatic disease, 27% had bone-only metastases, 35% visceral-only metastases and 38% bone and visceral metastases. Patient-reported outcomes and physical measures of muscle strength and aerobic fitness assessments were obtained. Participants wore a SenseWear® physical activity monitor over 7 days, and the average steps/day and the time spent in moderate-to-vigorous intensity physical activity were determined. Women with metastases were significantly (i) less aerobically fit than the control group (25.3 (5.4) vs. 31.9 (6.1) mL • kg(-1) • min(-1) P < 0.001) (ii) weaker (e.g. lower limb strength for the metastatic and control groups was 53.5 (23.7) vs. 76.0 (27.4) kg, respectively P < 0.001) (iii) less active, with the metastatic group attaining only 56% of the mean daily step counts of the healthy women and (iv) more symptomatic, reporting higher levels of fatigue and dyspnoea (P < 0.001). Women living in the community with metastatic breast cancer possessed lower aerobic fitness, reduced muscular strength and less daily physical activity compared to healthy counterparts. They also experienced poorer functioning and higher symptom burden. Women living with metastatic breast cancer may benefit from a physical activity programme to address their physical impairments.
Publisher: American Medical Association (AMA)
Date: 28-02-2020
Publisher: Informa UK Limited
Date: 05-2013
DOI: 10.3109/10641955.2013.784786
Abstract: To examine the effect of hypertensive disease of pregnancy (HDP) on the development of respiratory distress syndrome (RDS) in preterm neonates. A retrospective cohort study. All neonatal intensive care units in New South Wales and the Australian Capital Territory. A total of 18,845 preterm neonates aged between 24 and 36 weeks gestation admitted to the units from 1998 to 2006 were included for study purpose. Exclusion criteria were multiple pregnancies, chorioamnionitis, antepartum hemorrhage and neonates who developed respiratory diagnoses other than RDS. Effect of HDP on the development of RDS was measured. A total of 1093 neonates from hypertensive and 2274 from normotensive pregnancies with complete datasets were included. The association between HDP and the development of RDS was modified by gestational age (HDP-by-gestational age interaction p value <0.0001). Therefore the cohort was ided into extreme (24-28 weeks gestation, n = 752), severe (29-32 weeks gestation, n = 1448) and moderate (33-36 weeks gestation, n = 1167) preterm groups. HDP was associated with a decreased risk of RDS in the moderate preterm group (OR: 0.68 95% CI: 0.48-0.98, p = 0.04) and a non-significant change in risk for the severe preterm group. Almost all neonates in the extreme preterm group experienced RDS. HDP is associated with a lower risk of developing RDS in moderate preterm neonates. This could have clinical implications in terms of risk stratification for this group of neonates.
Publisher: BMJ
Date: 12-09-2013
DOI: 10.1136/ARCHDISCHILD-2012-303288
Abstract: The Parent Report of Children's Abilities-Revised (PARCA-R) assesses cognitive and language development at 24 months. It was validated against the Mental Development Index of the Bayley Scales of Infant Development II (BSID II), but this has now been superseded by BSID III. To compare the PARCA-R against the BSID III. PARCA-R and BSID III assessments scheduled at 24 months of age (corrected for prematurity) were completed in 204 infants with suspected or proven neonatal sepsis in the International Neonatal Immunotherapy Study. Associations between the scales were measured and the predictive accuracy of the PARCA-R for moderate cognitive delay and moderate language delay was assessed using Receiver Operating Characteristic (ROC) analysis. Median birthweight was 911 g, median gestational age at birth was 27 weeks and 100 (49.0%) were girls. 4.4% and 8.4% met standard BSID III criteria for cognitive delay and language delay, respectively. These rates increased to 19.6% and 12.6% when an independent s le of normal term infants were used as the reference group suggesting standard BSID III reference norms may tend to underestimate delay. The Spearman correlation between PARCA-R and BSID scales were 0.43 for cognition and 0.71 for language. The PARCA-R successfully predicted cases of cognitive delay and language delay with the area under the ROC curves ranging from 0.83 to 0.97 depending on reference norms used. The results support the PARCA-R as a practical tool for the identification of appreciable cognitive and language delay at 24 months among critically ill premature and extremely low birthweight neonates.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2022
DOI: 10.1007/S00432-022-04404-4
Abstract: Activity estimates should be accurately evaluated in phase 2 clinical trials to ensure appropriate decisions about proceeding to phase 3 trials. RECIST v1.1. progression-free survival (PFS) is a common endpoint in oncology however, it can be influenced by assessment criteria and trial design. We assessed the value of central adjudication of investigator-assessed PFS times of participants in a double-blind, randomised phase 2 trial evaluating regorafenib versus placebo in advanced gastro-oesophageal cancer (AGITG INTEGRATE) to inform plans for central review in future trials. We calculated the proportion of participants with a disagreement between the site investigator assessment and blinded independent central review and in whom central review resulted in a change, then evaluated the effect of central review on study conclusions by comparing hazard ratios (HRs) for PFS based on site review versus central review. Post-progression unblinding was assessed with similar methods. Simulation studies explored the effect of differential and non-differential measurement error on treatment effect estimation and study power. Disagreements between site assessments versus central review occurred in 8/147 (5.4%) participants, 5 resulting in amended date of progression (3.4%). PFS HRs (sites vs central review progression dates) were similar (0.39 vs 0.40). RECIST progression occurred in 82/86 (95%) of cases where post-progression unblinding was requested by the site investigator. Blinded independent central review was feasible and supported the reliability of site assessments, trial results, and conclusions. Modelling showed that when treatment effects were large and outcome assessments blinded, central review was unlikely to affect conclusions.
Publisher: Wiley
Date: 22-10-2019
DOI: 10.1111/BJU.14876
Abstract: To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs
Publisher: SAGE Publications
Date: 09-08-2019
Abstract: Research on the nocebo effect has shown that some words can hurt. Pain is defined as ‘unpleasant’ and ‘associated with actual or potential tissue damage’. So, a sensation described as ‘pain’ may function as a negative suggestion or nocebo communication. This can lead to pain being experienced or exacerbated where it would not have been otherwise. The nocebo effect has also been implicated as adversely affecting the pain experience during the assessment of pain postoperatively. Words that avoid this potential nocebo effect such as ‘comfort’ may represent a more satisfactory alternative. We therefore aimed to determine whether ‘comfort’ and ‘pain’ scores correlate when assessing patients postoperatively at the same timepoint. Patients were questioned before routine post-anaesthesia rounds to rate their pain and comfort levels, with the sequence of questions randomised. Patients were asked to rate pain and comfort on a 0–10 verbal numerical rating scale, where 0 represents ‘no pain’ or ‘no comfort’ and 10 ‘worst pain’ or ‘most comfort’ imaginable, respectively. To provide a clinically relevant correlation of approximately 0.7 between pain and inverted comfort scores, a s le size of 100 would provide adequate precision (95% confidence interval (CI) 0.58–0.79). A P-value of .05 was considered significant. We recruited 100 patients. A positive correlation of 0.62 was found between pain and inverted comfort scores (95% CI 0.47–0.72 P .0001). The question sequence of asking about pain or comfort did not affect either score. Comfort and pain scores are moderately correlated. This finding represents a first step in validating comfort scores and suggests that they could be considered a suitable alternative to pain scores when assessing patients postoperatively. As comfort is not an exact antonym to pain, caution is required when using these measures interchangeably.
Publisher: Wiley
Date: 12-2020
DOI: 10.1111/IMJ.14739
Abstract: People with incurable cancer require information about their prognosis to make informed decisions about their future. To determine the frequency, form and documentation of prognostic discussions between oncologists and their patients with incurable cancer. We surveyed medical oncologists in Australia and New Zealand about their practices communicating prognosis. A total of 206 medical oncologists completed the survey. Respondent characteristics were: median age 40 years (range 27-75), female 51%, trainee 22% and 71% had completed specific training on communicating prognosis. Respondents reported discussing prognosis with a patient a median of 10 times per month (interquartile range 4-15) 88% reported explaining that 'the cancer is incurable' to all their patients with incurable cancer and 84% reported always or usually providing a quantitative estimate of survival time. The preferred method for explaining expected survival time (EST) was providing 'multiple ranges of time with probabilities, for ex le best-case, typical and worst-case scenarios' (52% of respondents). The most frequently reported barriers to discussing EST were: 'family members requesting that prognostic information not be discussed' (57% of respondents), and 'not knowing the EST' (46% of respondents). Twenty percent reported always documenting prognostic discussions and the EST in the patient's medical record, and 11% reported always documenting this information in their letters to other doctors. Most oncologists reported providing quantitative estimates of EST to their patients with incurable cancer, but very few reported documenting this information. Methods to help oncologists estimate, explain and document survival time are needed to improve communication of prognosis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
DOI: 10.1016/J.PAIN.2010.12.023
Abstract: Pregabalin has demonstrated efficacy in several forms of neuropathic pain, but its long-term efficacy in central post-stroke pain (CPSP) is unproven. We evaluated the efficacy and safety of pregabalin versus placebo in patients with CPSP. A 13-week, randomized, double-blind, multicenter, placebo-controlled, parallel group study of 150 to 600 mg/day pregabalin was conducted in patients aged ≥18 years with CPSP. The primary efficacy endpoint was the mean pain score on the Daily Pain Rating Scale over the last 7 days on study drug up to week 12 or early termination visit. Secondary endpoints included other pain parameters and patient-reported sleep and health-related quality-of-life measures. A total of 219 patients were treated (pregabalin n=110 placebo n=109). A mean pain score at baseline of 6.5 in the pregabalin group and 6.3 in the placebo group reduced at endpoint to 4.9 in the pregabalin group and 5.0 in the placebo group (LS mean difference=-0.2 95% CI=-0.7, 0.4 P=0.578). Treatment with pregabalin resulted in significant improvements, compared with placebo, on secondary endpoints including MOS-sleep, HADS-A anxiety, and clinician global impression of change (CGIC) P<0.05. Adverse events were more frequent with pregabalin than with placebo and caused discontinuation in 9 (8.2%) of pregabalin patients versus 4 (3.7%) of placebo patients. Although pain reductions at endpoint did not differ significantly between pregabalin and placebo, improvements in sleep, anxiety, and CGIC suggest some utility of pregabalin in the management of CPSP.
Publisher: Oxford University Press (OUP)
Date: 20-09-2016
DOI: 10.1111/BJD.14648
Publisher: Springer Science and Business Media LLC
Date: 23-12-2015
DOI: 10.1007/S00192-015-2916-1
Abstract: Functional anatomy of the bladder neck and proximal urethra has been studied extensively because of the belief that it is important for urinary continence. The aim of this study was to explore the limits of normality for pelvic floor ultrasound parameters of bladder neck and urethral mobility associated with stress urinary incontinence (SUI) and urodynamic stress incontinence (USI). A retrospective study was conducted on 589 women seen for urodynamic testing in a tertiary urogynaecology clinic. All women were assessed following a protocol including interview, clinical examination, flowmetry, urodynamic testing and 4D pelvic floor ultrasound. Volume data sets were analysed offline to assess for bladder neck descent (BND), urethral rotation and the retrovesical angle (RVA) on maximal Valsalva. After excluding women with previous incontinence or prolapse surgery, 429 datasets were available. SI was significantly associated with the RVA (p = 0.033) and BND (p = 0.036) USI was associated with urethral rotation (p = 0.021) and BND (p < 0.001). On multivariate logistic regression analysis, controlling for confounders including age, BMI, parity, previous hysterectomy and maximal urethral pressure, the association between SUI and BND remained significant (OR [per 10 mm] = 1.23 95 % CI: 1.01 to 1.51 p = 0.043), as did the association between USI and BND (OR [per 10 mm] = 1.58 95 % CI: 1.3 to 1.91 p < 0.001). ROC statistics for BND suggested a cut-off of 25 mm in describing the limit of normality. Measures of functional bladder neck anatomy are weakly associated with SUI and USI (with association between BND and USI being the strongest). It is suggested that a BND of 25 mm or higher be defined as abnormal ("hypermobile") on the basis of its association with USI.
Publisher: Wiley
Date: 05-10-2015
Abstract: To analyse the associations between delivery mode and symptoms and signs of pelvic organ prolapse (POP) in a cohort of symptomatic women. Retrospective observational study. A total of 1258 consecutive women attending a tertiary urogynaecological unit for the investigation of lower urinary tract or pelvic floor disorders between January 2012 and December 2014. Obstetric history and clinical examination data were obtained from the unit database. Prolapse quantification on imaging was performed using stored four-dimensional translabial ultrasound volume data sets. Women were grouped into four groups according to the most traumatic delivery reported. The presence of symptoms and signs of POP were compared between delivery groups while controlling for potential confounders. Prolapse symptoms, visual analogue score for prolapse bother, International Continence Society Prolapse Quantification System findings and ultrasound findings of anterior, central and posterior compartment descent. Nulliparae showed the lowest prevalence of most measures of POP, followed by women exclusively delivered by caesarean section. Highest prevalences were consistently found in women delivered at least once by forceps, although the differences between this group and women delivered by normal vaginal delivery and/or vacuum extraction were significant in three out of eight measures only. Compared with women in the caesarean section group, the adjusted odds ratios for reporting symptoms of prolapse were 2.4 (95% CI 1.30-4.59) and 3.2 (95% CI 1.65-6.12) in the normal vaginal delivery/vacuum extraction group and forceps group, respectively. There is a clear link between vaginal delivery and symptoms and signs of pelvic organ prolapse in urogynaecological patients. Compared with caesarean section a history of vaginal delivery more than doubles the risk for POP.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2019
Publisher: European Respiratory Society (ERS)
Date: 08-2017
DOI: 10.1183/13993003.00157-2017
Abstract: There is uncertainty regarding whether patients with cancer should be screened for latent tuberculosis infection (LTBI). We performed a systematic review and meta-analysis to estimate the relative incidence of tuberculosis (TB) in cancer.We searched MEDLINE and Embase for studies published before December 21, 2016. We included studies that evaluated the incidence of TB in patients with solid cancers and haematological malignancies relative to a reference group (study control or general population). A pooled estimate of the incidence rate ratio (IRR) was obtained using standard meta-analysis methods.The search strategy identified 13 unique studies including 921 464 patients with cancer. The IRR of TB for adult patients with cancer was 2.61 (95% CI 2.12-3.22
Publisher: Wiley
Date: 04-2017
DOI: 10.1111/IMJ.13350
Abstract: Australians access anticancer drugs predominantly through the Pharmaceutical Benefits Scheme (PBS). To determine why the Pharmaceutical Benefits Advisory Committee (PBAC) rejects submissions to list anticancer drugs on the PBS. We reviewed publicly available information about submissions made to the PBAC for PBS listing of anticancer drugs from 2005 to 2014. Submission characteristics, including clinical and economic evidence, PBAC recommendations, and the reasons offered for rejection were recorded. Two reviewers independently categorised the reason for rejection offered by the PBAC. Logistic regression was used to determine submission characteristics associated with rejection. We identified 213 submissions for 110 unique indications of 60 anticancer drugs. The overall rejection rate was 56% (119/213). Of the 110 indications assessed, 69% (76/110) were rejected at least once. The annual rejection rate ranged from 50 to 73% with little evidence of a trend over time (P = 0.2). Submission characteristics strongly associated with rejection in multivariable analysis included: PBAC judged the clinical evidence to be problematic or uncertain (P < 0.001) PBAC judged the economic evidence to be problematic or uncertain (P < 0.001) and, inactive comparator used (P < 0.001). The most frequent reasons for rejection offered by the PBAC was 'inadequate cost-effectiveness or drug price too high' (75/109, 69%). Inadequate cost-effectiveness and PBAC uncertainty about the clinical and economic evidence were the most frequent reasons for rejection. Clarity of information about PBAC deliberations and their reasons for rejection are important for patients and doctors grappling with decisions about the use of expensive unfunded anticancer drugs.
Publisher: Wiley
Date: 04-2018
DOI: 10.1002/UOG.17567
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-02-2022
DOI: 10.1200/JCO.2022.40.6_SUPPL.TPS205
Abstract: TPS205 Background: 177 Lu‐PSMA‐617 (LuPSMA) is a novel radionuclide with promising activity and tolerability in metastatic castration-resistant prostate cancer (mCRPC). Pre-clinical studies have shown that androgen receptor blockade with enzalutamide upregulates PSMA-receptor expression, and that PSMA-receptor blockade increases treatment response to enzalutamide. We hypothesize that concurrent administration of LuPSMA and enzalutamide will be synergistic in mCRPC. The aims of ENZA-p are to determine the activity and safety of LuPSMA combined with enzalutamide in men with mCRPC at high-risk of early progression on enzalutamide alone and to identify prognostic and predictive biomarkers from imaging, blood, and tissue. Methods: This open-label, randomized, multicentre, phase 2 trial will recruit 160 men with mCRPC. Key eligibility criteria include progression on androgen deprivation therapy, 2 or more risk factors for early cancer progression on enzalutamide (LDH ≥ULN ALP ≥ULN albumin 35 g/L M1 disease at diagnosis 3 years since initial diagnosis 5 bone metastases visceral metastases PSA doubling time 3 months pain requiring opiates 14 days for castration-sensitive disease), no prior treatment with an androgen receptor pathway inhibitor (except abiraterone), no prior chemotherapy for mCRPC, and PSMA-avid disease on positron emission tomography (PET) with 68 Ga-PSMA. Participants are randomly assigned (1:1) to enzalutamide 160 mg daily or enzalutamide 160 mg daily plus LuPSMA 7.5 GBq on days 15 and 57. Two subsequent doses of Lu-PSMA will be administered if the 68 Ga-PSMA PET on day 92 shows persistent PSMA expression in the tumour. Imaging assessments include CT and technetium bone scan at baseline, day 99, then every 12 weeks 68 Ga-PSMA-11 PET at baseline, days 15, 92, and first progression and 18 F FDG PET at baseline and first progression. Translational s les including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and biopsies (optional) will be collected at baseline, day 92, and first progression. The primary endpoint is PSA progression-free survival (PSA-PFS). Secondary endpoints include radiological-PFS, PSA-response rate, pain response and PFS, clinical-PFS, overall survival, health related quality of life, adverse events, and cost-effectiveness. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga-PSMA, 18 F FDG PET/CT, CTCs, and ctDNA. A s le size of 160 provides 80% power with a 2-sided type 1- error rate of 5% to detect a HR of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. Accrual was 90 on 12 October 2021. Clinical trial information: NCT04419402.
Publisher: Springer Science and Business Media LLC
Date: 22-02-2023
DOI: 10.1186/S12885-023-10642-7
Abstract: Advanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases. Regorafenib 160 mg daily prolonged progression free survival compared to placebo (INTEGRATE, phase 2). Regorafenib 80 mg daily in combination with nivolumab 3 mg/kg showed promising objective response rates (REGONIVO). INTEGRATE II (INTEGRATE IIa and IIb) platform comprises two international phase III randomised controlled trials (RCT) with 2:1 randomisation in favor of experimental intervention. INTEGRATE IIa (double-blind) compares regorafenib 160 mg daily on days 1 to 21 of each 28-day cycle to placebo. INTEGRATE IIb (open label) compares REGONIVO, regorafenib 90 mg days 1 to 21 in combination with intravenous nivolumab 240 mg days 1 and 15 each 28-day cycle with investigator’s choice of chemotherapy (control). Treatment continues until disease progression or intolerable adverse events as per protocol. Eligible participants include adults with AGOC who have failed two or more lines of treatment. Stratification is by location of tumour (INTEGRATE IIa only), geographic region, prior VEGF inhibitor and prior immunotherapy use (INTEGRATE IIb only). Primary endpoint is overall survival. Secondary endpoints are progression free survival, objective response rate, quality of life, and safety. Tertiary/correlative objectives include biomarker and pharmacokinetic evaluation. INTEGRATE II provides a platform to evaluate the clinical utility of regorafenib alone, as well as regorafenib in combination with nivolumab in treatment of participants with refractory AGOC. INTEGRATE IIa prospectively registered 1 April 2016 Australia New Zealand Clinical Trial Registry: ACTRN12616000420448 (ClinicalTrials.gov NCT02773524). INTEGRATE IIb prospectively registered 10 May 2021 ClinicalTrials.gov: NCT04879368.
Publisher: American Association for Cancer Research (AACR)
Date: 09-02-2021
DOI: 10.1158/1535-7163.MCT-20-0836
Abstract: Amplification or overexpression of the FGFR family of receptor tyrosine kinases occurs in a significant proportion of gastric cancers. Regorafenib is a multikinase inhibitor of angiogenic and oncogenic kinases, including FGFR, which showed activity in the randomized phase II INTEGRATE clinical trial in advanced gastric cancer. There are currently no biomarkers that predict response to this agent, and whether regorafenib is preferentially active in FGFR-driven cancers is unknown. Through screening 25 gastric cancer cell lines, we identified five cell lines that were exquisitely sensitive to regorafenib, four of which harbored lification or overexpression of FGFR family members. These four cell lines were also sensitive to the FGFR-specific inhibitors, BGJ398, erdafitinib, and TAS-120. Regorafenib inhibited FGFR-driven MAPK signaling in these cell lines, and knockdown studies confirmed their dependence on specific FGFRs for proliferation. In the INTEGRATE trial cohort, lification or overexpression of FGFRs 1–4 was detected in 8%–19% of cases, however, this was not associated with improved progression-free survival and no objective responses were observed in these cases. Further preclinical analyses revealed FGFR-driven gastric cancer cell lines rapidly reactivate MAPK/ERK signaling in response to FGFR inhibition, which may underlie the limited clinical response to regorafenib. Importantly, combination treatment with an FGFR and MEK inhibitor delayed MAPK/ERK reactivation and synergistically inhibited proliferation of FGFR-driven gastric cancer cell lines. These findings suggest that upfront combinatorial inhibition of FGFR and MEK may represent a more effective treatment strategy for FGFR-driven gastric cancers.
Publisher: Wiley
Date: 10-03-2017
DOI: 10.1111/AOGS.13103
Abstract: Damage to the pelvic floor during vaginal childbirth is common, and may take the form of levator avulsion or irreversible overdistension of the levator hiatus (microtrauma). Such trauma is a major risk factor for pelvic organ prolapse later in life. In this study we aimed to identify intrapartum risk factors for levator trauma. This is a retrospective analysis of data obtained in two perinatal studies on primiparous women. Between 2005 and 2014, 1148 women carrying an uncomplicated singleton pregnancy in the late third trimester were seen for 4D pelvic floor ultrasound and an interview. They were invited for a repeat assessment at three months postpartum. Of 1148 women, 871 (76%) returned for assessment at a mean of five months postpartum. The datasets of 844 women were analyzed due to missing data or concurrent pregnancy in 27. In all, 452 (54%) had a normal vaginal delivery, 102 (12%) a vacuum, 55 (6%) a forceps, and 235 (28%) a cesarean section. On multivariate analysis forceps, length of second stage and obstetric anal sphincter tears were significantly associated with levator avulsion. There were no significant predictors identified for irreversible overdistension. The use of forceps, a prolonged second stage, and obstetric anal sphincter tears were associated with levator avulsion. There were no associated intrapartum predictors for hiatal overdistension.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.CLINPH.2016.10.088
Abstract: To explore the benefits of modified-release f ridine on walking distance in MS. This was a randomised double-blind, placebo-controlled crossover trial of f ridine in 25 MS patients. The primary outcome measure was the six minute walk test (6MWT). A p-value<10% led to rejection of the null hypothesis. The pre-specified criterion for statistical significance was met, with a 17m improvement in 6MWT in the treatment arm. In addition, baseline S2 accommodation, a nerve excitability parameter that reflects slow K The study provides evidence that f ridine may improve walking distance. Nerve excitability assessment may be useful in selecting those patients who are most likely to gain benefit from f ridine. F ridine may improve walking distance in MS. Nerve excitability assessment may assist in identifying those patients most likely to respond to f ridine.
Publisher: Massachusetts Medical Society
Date: 22-10-2015
Publisher: American Society of Clinical Oncology (ASCO)
Date: 02-2022
DOI: 10.1200/JCO.2022.40.4_SUPPL.TPS366
Abstract: TPS366 Background: Advanced Gastro-oesophageal Carcinoma (AGOC) has a poor prognosis, and there is no established standard treatment following failure of first- and second-line chemotherapy. Regorafenib (BAY 73-4506) is an investigational oral multi-targeted tyrosine kinase inhibitor (TKI) which targets angiogenic (VEGF, TIE-2), stromal (PDGF-β), and oncogenic (RAF, RET and KIT) receptor tyrosine kinases, and has shown activity in this setting. Single agent regorafenib prolonged progression free survival (PFS) versus placebo across all regions/subgroups in the INTEGRATE randomised phase 2 trial. Current options in refractory AOGC involves sequencing through chemotherapy with the latest active agent approved being trifluridine/tipiracil, TAS-102. Promising activity in refractory AOGC has been seen with the combination of regorafenib & nivolumab. INTEGRATE IIb–will compare the effectiveness of the combination of regorafenib & nivolumab in pre-treated patients with AGOC to current standard chemotherapy. Methods: Randomised phase III, open label study with 2:1 randomisation (RegoNivo : standard chemotherapy) and stratification by: Geographic region (Asia vs. Rest of World) Prior VEGF inhibitors (Yes vs No) Prior immunotherapy (Yes vs No). RegoNivo arm will receive 90mg (3x30mg) of regorafenib days 1-21 of each 28-day treatment cycle with intravenous nivolumab 240 mg day 1 of each 14 day cycle until disease progression or prohibitive adverse events as per protocol. The control arm will receive the investigator’s choice of the following chemotherapy a taxane (paclitaxel or docetaxel), irinotecan or oral trifluridine/tipiracil (TAS102). Primary endpoint: OS. Secondary endpoints: PFS, response rate, quality of life, toxicity, exploratory correlative biomarkers. Clinical trial information: NCT04879368.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-2013
Abstract: To determine the accuracy and usefulness of oncologists' estimates of survival time in in idual patients with advanced cancer. Twenty-one oncologists estimated the “median survival of a group of identical patients” for each of 114 patients with advanced cancer. Accuracy was defined by the proportions of patients with an observed survival time bounded by prespecified multiples of their estimated survival time. We expected 50% to live longer (or shorter) than their oncologist's estimate (calibration), 50% to live from half to double their estimate (typical scenario), 5% to 10% to live ≤ one quarter of their estimate (worst-case scenario), and 5% to 10% to live three or more times their estimate (best-case scenario). Estimates within 0.67 to 1.33 times observed survival were deemed precise. Discriminative value was assessed with Harrell's C-statistic and prognostic significance with proportional hazards regression. Median survival time was 11 months. Oncologists' estimates were relatively well-calibrated (61% shorter than observed), imprecise (29% from 0.67 to 1.33 times observed), and moderately discriminative (Harrell C-statistic 0.63 P = .001). The proportion of patients with an observed survival half to double their oncologist's estimate was 63%, ≤ one quarter of their oncologist's estimate was 6%, and three or more times their oncologist's estimate was 14%. Independent predictors of observed survival were oncologist's estimate (hazard ratio [HR] = 0.92 P = .004), dry mouth (HR = 5.1 P .0001), alkaline phosphatase more than 101U/L (HR = 2.8 P = .0002), Karnofsky performance status ≤ 70 (HR = 2.3 P = .007), prostate primary (HR = 0.23 P = .002), and steroid use (HR = 2.4 P = .02). Oncologists' estimates of survival time were relatively well-calibrated, moderately discriminative, independently associated with observed survival, and a reasonable basis for estimating worst-case, typical, and best-case scenarios for survival.
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1038/JID.2011.459
Publisher: Elsevier BV
Date: 02-2021
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-03-2022
DOI: 10.1200/JCO.21.00941
Abstract: We previously reported that enzalutamide improved overall survival when added to standard of care in metastatic, hormone-sensitive prostate cancer. Here, we report its effects on aspects of health-related quality of life (HRQL). HRQL was assessed with the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire and QLM-PR25 at weeks 0, 4, 12, and then every 12 weeks until progression. Scores from week 4 to 156 were analyzed with repeated measures modeling to calculate group means and differences. Deterioration-free survival was from random assignment until the earliest of death, clinical progression, discontinuation of study treatment, or a worsening of 10 points or more from baseline in fatigue, physical function, cognitive function, or overall health and quality of life (OHQL). HRQL scores range from 0 (lowest possible) to 100 (highest possible). HRQL was assessed in 1,042 of 1,125 participants (93%). Differences in means favored control over enzalutamide for fatigue (5.2, 95% CI, 3.6 to 6.9 P .001), cognitive function (4.0, 95% CI, 2.5 to 5.5 P .001), and physical function (2.6, 95% CI, 1.3 to 3.9 P .001), but not OHQL (1.2, 95% CI, −0.2 to 2.7 P = .1). Deterioration-free survival rates at 3 years, and log-rank P values comparing the whole distributions, favored enzalutamide over control for OHQL (31% v 17% P .0001), cognitive function (31% v 20% P = .001), and physical function (31% v 22% P .001), but not fatigue (24% v 18% P = .16). The effects of enzalutamide on HRQL were independent of baseline characteristics. Enzalutamide was associated with worsening of self-reported fatigue, cognitive function, and physical function, but not OHQL. Enzalutamide was associated with improved deterioration-free survival for OHQL, physical function, and cognitive function because delays in disease progression outweighed early deteriorations in these aspects of HRQL.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
Publisher: Springer Science and Business Media LLC
Date: 19-10-2013
DOI: 10.1007/S11126-013-9278-Y
Abstract: Several studies have linked obsessive-compulsive symptoms to specific obsessive-compulsive cognitions, however methodologies have varied, and no study has determined obsessive-compulsive symptoms using the most widely used clinician rating scale, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Considering that almost all studies that used factor analysis to ascertain OCD symptom dimensions were based on the Y-BOCS and that self-report instruments assessing obsessive-compulsive symptoms correlate poorly with the Y-BOCS, there is a need to use the Y-BOCS to examine the relationship between obsessive-compulsive cognitions and obsessive-compulsive symptom dimensions. This study examined the relationship between five Y-BOCS-derived obsessive-compulsive symptom dimensions and the three obsessive-compulsive cognitive domains identified by the obsessive-beliefs questionnaire (OBQ). The symmetry/ordering symptom dimension was associated with increased perfectionism/intolerance of uncertainty, the unacceptable/taboo thoughts symptom dimension was associated with increased importance/control of thoughts and the doubt/checking symptom dimension was associated with increased responsibility/threat estimation. There was no statistical evidence of an association between any OBQ belief sub-scale and the hoarding symptom dimension nor the contamination/cleaning symptom dimension. The findings encourage symptom-based approaches to cognitive-behavioural therapy for some OCD symptoms and call for further research on cognitions associated with contamination/cleaning symptoms and hoarding.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-02-2022
DOI: 10.1200/JCO.2022.40.6_SUPPL.TPS284
Abstract: TPS284 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analog (LHRHA), is standard of care for men with very high-risk localized prostate cancer (PC), or with very high-risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high-risk features. Darolutamide is a structurally distinct oral androgen receptor antagonist with low blood-brain-barrier penetration, a demonstrated favorable safety profile, and low potential for drug-drug interactions. Our aim is to determine the efficacy of adding darolutamide to ADT and RT in the setting of either primary definitive therapy, or salvage therapy for very high-risk PC. Methods: This study is a randomized (1:1), phase 3, placebo-controlled, double-blind international trial for men planned for RT who have very high-risk localized PC on conventional imaging or very high-risk features with PSA persistence or rise within one year following RP. The trial is stratified by: RP use of adjuvant docetaxel pelvic nodal involvement. 1100 participants will be randomized to darolutamide 600 mg or placebo twice daily for 96 weeks in combination with SOC: LHRHA for 96 weeks, plus RT starting week 8-24 from randomization. Participants are allowed nonsteroidal antiandrogen in addition to LHRHA for up to 90 days prior to randomization. Early treatment with up to 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival (ICECaP-validated), with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety, and resistance to study treatment. Clinical trial information: NCT04136353.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.MATURITAS.2013.06.012
Abstract: To explore the effect of menopause and hormone replacement therapy on pelvic organ prolapse and pelvic floor muscle function. The records of patients who attended a tertiary urogynaecological center were reviewed retrospectively. A standardised interview included menopausal age, i.e. years since last period or onset of menopausal symptoms, current or previous hormone use. The clinical examination included prolapse assessment (POP-Q) and palpation of the levator ani muscle. 4D transperineal ultrasound, supine and after voiding, was performed in all patients. Volume data sets were analysed for pelvic organ descent and measures of contractility and distensibility of the pelvic floor at a later date, blinded to all clinical data. Of 311 women seen during the inclusion period, 65% were postmenopausal. Current systemic or local hormone use was reported by 7% and 6%, respectively. 163 women (52%) reported prolapse symptoms with a mean bother of 5.7/10. Significant pelvic organ prolapse was found on clinical examination (POP-Q stage≥2) in 77%, and diagnosed on ultrasound in 61%. On multivariate analysis, controlling for calendaric age, parity and levator avulsion, there was no evidence for menopausal age as an independent predictor of any symptom and sign of pelvic organ prolapse and pelvic floor muscle function. Local oestrogen use and past or present hormone replacement therapy had no detectable effect on any pelvic floor parameter. Hormone deficiency following menopause is unlikely to play a major role in pelvic organ support and levator ani function. Hence, both do not appear to be substantially influenced by local or systemic hormone replacement therapy.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2013
DOI: 10.1007/S00192-012-2032-4
Abstract: Multichannel urodynamic testing is commonly used to diagnose urodynamic stress incontinence (USI). It has been claimed that USI may be diagnosed by imaging. In this study we determined the predictive value of ultrasound findings for USI. This is an observational study utilising data obtained during urodynamic testing. Data sets were analysed in 209 patients in order to determine the predictive value of sonographic findings for the diagnosis of USI. Bladder neck descent and maximal urethral pressure were the only independent predictors of USI identified by multivariate logistic regression. The finding of a cystourethrocele with funnelling increased the odds of a diagnosis of USI by 2.5 (95 % confidence interval 1.17-5.4, p = 0.018). Translabial ultrasound can identify an anatomical configuration that is associated with USI. However, sonographic findings are insufficient to predict USI and can not replace urodynamic testing.
Publisher: Elsevier BV
Date: 2018
DOI: 10.2139/SSRN.3234852
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.PSYCHRES.2016.03.047
Abstract: This study aimed to assess whether a family history of specific OCD symptoms was associated with the same OCD symptoms in study participants. Participants were s led from the Nepean OCD study (N=206) and were assessed with the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (YBOCS-SC) and the Vancouver Obsessional Compulsive Inventory (VOCI) in order to determine their OCD symptoms. A family history screen was used to determine whether participants had a first-degree relative with a history of any of the following specific symptoms: hoarding, contamination/cleaning, symmetry/ordering, doubt/checking and/or other OCD symptoms. The characteristics of participants with a family history of a specific OCD symptom were compared to those of participants with a family history of any other OCD symptom. This was repeated for each specific OCD symptom. The roles of co-occurring tics and age of onset of OCD were also assessed. Distinct familial associations were detected for the symptoms of hoarding and contamination/cleaning. Age of onset of OCD was significantly younger in participants who reported a family history of "other" symptoms. These findings suggest that certain OCD symptom dimensions are more familial than others, which has significant implications for aetiology of OCD.
Publisher: AMPCo
Date: 06-2013
DOI: 10.5694/MJA12.11597
Abstract: To apply the most recent evidence from randomised trials of prostate-specific antigen (PSA) screening and explore the potential value of risk assessments to guide the use of PSA screening in practice. A decision model that incorporated a Markov process was developed in 2012 to estimate the net benefit and cost of PSA screening versus no screening as a function of baseline risk. Quality-adjusted life-2013s (QALYs) and costs. The harms of screening outweighed the benefits under a number of plausible scenarios. Conclusions were sensitive to the estimated quality-of-life impacts of prostate cancer treatment as well as the incidence of cancers not detected by screening tests (poorer prognosis) and those that were detected by screening tests (better prognosis). The base-case incremental cost-effectiveness ratio of PSA screening was $168,611 per QALY for men with average risk, $73,452 per QALY for men with two times the average risk, and $22,938 [corrected] per QALY for men with five times the average risk. PSA screening was not found to be cost-effective for men at an average-to-high risk of prostate cancer, but may be cost-effective for men at very high risk. Inexpensive approaches for identifying men at very high risk are needed, as is further research on the size of clinical benefit of early detection in this population. The potential for the costs of risk assessment to be offset by reduced costs of PSA screening also warrants investigation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2018
Publisher: Elsevier BV
Date: 02-2019
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: Wiley
Date: 02-06-2019
DOI: 10.1111/APHA.13294
Abstract: Urinary oxygen tension (uPO In 28 sheep urine flow, uPO In conscious sheep breathing room air, uPO uPO
Publisher: Springer Science and Business Media LLC
Date: 03-2012
DOI: 10.1038/BJC.2012.62
Publisher: Springer Science and Business Media LLC
Date: 21-08-2012
Publisher: BMJ
Date: 03-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1995
DOI: 10.1097/00008483-199501000-00006
Abstract: Patients who have undergone coronary artery bypass graft surgery (CABG) are obvious candidates for rehabilitation programs because of the potential for progression of disease. Such programs have been shown to foster risk-factor modification, improve quality of life, and prolong survival among post-myocardial infarction (MI) patients. However, the efficacy of these programs has not been established among patients who have undergone CABG. A randomized controlled trial was employed to evaluate whether a behavioral and educational cardiac rehabilitation program was effective in modifying cardiovascular disease risk factors and improving quality of life in a cohort of 86 patients after CABG. Patients were recruited from the cardiac ward of a large teaching hospital and were block-randomized to either an intervention group or routine care. Subjects in the intervention group attended 6 weekly group sessions following hospital discharge, and booster sessions at 8 months and 1 year. They also received a personalized behavior modification program based on their baseline risk factors. Risk factor and quality of life measures were recorded at baseline (6 weeks after surgery), 4 months, 8 months, and 1 year. The results indicated few differences between the study groups. However, the intervention group's aerobic capacity (VO2max) improved over that of the routine care group. With regard to the quality of life variables, all patients tended to improve steadily over time. The relatively moderate success of this intervention program compared with various post-MI studies may be indicative of differences between the treatment needs of patients after acute myocardial infarction or CABG. Future post-CABG rehabilitation research should explore these patients' unique treatment needs, and investigate a variety of program strategies.
Publisher: BMJ
Date: 09-1999
Abstract: To investigate the psychometric properties of a cardiovascular extension of an existing utility-based quality of life questionnaire (Health Measurement Questionnaire). The new instrument has been named the Utility Based Quality of life--Heart questionnaire, or UBQ-H. Explored the test-retest reliability, construct validity, and responsiveness of the UBQ-H. A s le of 322 patients attending cardiac outpatient clinics were recruited from two large metropolitan teaching hospitals. A second s le of 1112 patients taking part in the LIPID trial was also used to investigate the validity and responsiveness of the UBQ-H. Ninety per cent of all UBQ-H questionnaires were returned, and item completion rates were high (median of less than 1% missing or N/A answers). Cronbach's alpha measure of internal consistency for the scales ranged between 0.79-0.91, and each item was also most strongly correlated with its hypothesised domain than alternative domains. The intra-class test-retest reliability of the UBQ-H scales ranged from 0.65 to 0.81 for patients with stable health. Results supported the construct validity of the UBQ-H. The UBQ-H was significantly correlated with other information on quality of life (for ex le, General Health Questionnaire) as anticipated. The instrument was able to distinguish between contrasted groups of patients (for ex le, with versus without symptoms of dyspnoea, prior myocardial infarction versus none, etc), and was responsive to changes in health associated with adverse events requiring hospitalisation. The modifications made to the Health Measurement Questionnaire has resulted in an assessment designed for cardiovascular patients that has proved to be both reliable and valid.
Publisher: Elsevier BV
Date: 11-2018
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-02-2022
DOI: 10.1200/JCO.2022.40.6_SUPPL.483
Abstract: 483 Background: The sub-urothelial administration of checkpoint inhibitors has not been reported. This approach could be safer and more efficacious than systemic delivery for patients with non-muscle-invasive bladder cancer (NMIBC). Methods: This phase 1b study employed a 3+3 dose-escalation design to explore tolerability, safety and immunological efficacy of sub-urothelial durvalumab, a programmed death-ligand 1 (PDL1) monoclonal antibody. Eligible participants had high risk NMIBC or MIBC without prior chemotherapy or immunotherapy (BCG allowed) and were planned for cystectomy. Participants received 25/75/150mg durvalumab diluted in 25mL normal saline injected into the sub-urothelium at 25 locations (25x1mL injections), at least 2 weeks prior to radical cystectomy. Systematic four quadrant cold cup bladder biopsies were taken immediately prior to durvalumab injection and immediately prior to cystectomy. Tumour, if present, was biopsied before and after injection and bladder maps recorded. International Prostate Symptom Index (IPSS) and O’Leary symptom score at various time points and adverse events (AE) as per CTCAE (Version 4) were recorded. Relative changes in immune cell counts (RCI) on bladder biopsy for CD3, CD8, CD68 and CD168 expressing cells are reported (value .0 designating increase). Results: Nine participants were recruited eight male (89%), 1 female mean age 72 years (range 56 – 82). No dose-limiting toxicities were observed. No evidence of treatment-related effect on IPSS or O’Leary Symptom scores was seen. Fourteen AEs were reported by six (67%) patients: 10 were Grade 1, 3 Grade 2, 1 Grade 3. None were considered immune- or treatment-related by investigators. Transient elevation of peri-operative thyroid stimulating hormone was seen in two subjects, which normalised without intervention. No hepatitis was seen. All patients underwent planned cystectomy. RCI of different immune populations was calculated (see Table). Visible tumour was present in only 4 patients limiting interpretation of RCI. RCI varied significantly between cell types (p=0.008*). RCI numerically increased by dose but did not reach statistical significance (p=0.076**). A numeric increase in monocytes was seen at 150mg dose. RCI of different immune populations by dose of sub-urothelial durvalumab. Conclusions: Sub-urothelial injection of durvalumab was safe at all 3 dose levels without any drug-related adverse events. Immunological studies showed differential effects on immune cells with macrophage population most affected. Further studies investigating the role of 150mg sub-urothelial durvalumab in the management of NMIBC are planned. Clinical trial information: ACTRN12620000063910.[Table: see text]
Publisher: Elsevier BV
Date: 05-2004
Publisher: Massachusetts Medical Society
Date: 11-07-2019
Publisher: Society of Nuclear Medicine
Date: 25-08-2023
Publisher: Wiley
Date: 06-07-2015
DOI: 10.1111/AJD.12359
Abstract: Australian doctors perform over one million skin excisions yearly. There are few randomised trials studying wound repair. The objective was to compare two suture techniques with controls for simple elliptical excisions in a prospective, randomised, single-blinded study. One half of each wound was randomised to either one-layer closure with percutaneous nylon or modified two-layer closure where superficial closure was effected with adhesive tape. The control was the standard two-layer closure. Primary outcome measure was wound width at 6 months, with cosmesis as the secondary outcome. A total of 161 participants with 214 excisions were recruited from general practice. There was no significant difference in the primary outcome of wound width at 6 months between the groups. One-layer closure showed slight inferiority for cosmesis at 6 months versus the control. There was significant superiority for the modified two-layer closure versus the control for cosmesis at 6 months, and early wound erythema. Multivariate regression models adjusted for suture technique showed that younger age, wound infection and truncal location were predictors of increased scar width. Older age, wound erythema, and male gender were predictors of poorer patient-rated outcome. One-layer closure is an acceptable choice for elliptical excision wound closure. Modified two-layer closure may be preferable to standard two-layer closure for elliptical wounds.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2018
Publisher: Springer Science and Business Media LLC
Date: 15-06-2022
DOI: 10.1007/S00520-022-07167-3
Abstract: To evaluate a web-based tool for estimating and explaining three scenarios for expected survival time to people with advanced cancer (patients), their family members (FMs), and other healthcare professionals (HCPs). Thirty-three oncologists estimated the “median survival of a group of similar patients” for patients seeking quantitative prognostic information. The web-based tool generated worst-case, most likely, and best-case scenarios for survival based on the oncologist’s estimate. Oncologists presented the scenarios to each patient and provided a printed summary to patients, FMs, and HCPs. Attitudes to the information were assessed by questionnaires. Observed survival for each patient was compared with the oncologist’s estimated survival and the three scenarios. Prognosis was discussed with 222 patients: median age 67 years 61% male most common primary sites pancreas 15%, non-small-cell lung 15%, and colorectal 12%. The median (range) for observed survival times was 9 months (0.5–43) and for oncologist’s estimated survival times was 12 months (2–96). Ninety-one percent of patients, 91% of FMs, and 84% of HCPs agreed that it was helpful having life expectancy explained as three scenarios. The majority (77%) of patients judged the information presented about their life expectancy to be the same or better than they had expected before the consultation. The survival estimates met a priori criteria for calibration, precision, and accuracy. Patients, FMs, and HCPs found it helpful to receive personalized prognostic information formatted as three scenarios for survival. It was feasible, acceptable, and safe to use a web-based resource to do this.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2017
Publisher: BMJ
Date: 18-05-2015
Publisher: Elsevier BV
Date: 04-2023
Publisher: Wiley
Date: 07-06-2016
DOI: 10.1002/HUP.2541
Abstract: To assess rates of psychotropic medication use in patients with obsessive-compulsive disorder (OCD) in seven different countries on five continents and to compare these with international treatment guidelines. Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their patients with OCD and on their incidence of psychotropic use. Consistency of summary statistics across countries was evaluated. The data came from Brazil (n = 955), Italy (n = 750), South Africa (n = 555), Japan (n = 382), Australia (n = 213), India (n = 202) and Spain (n = 82). The majority (77.9% n = 2445) of the total s le of 3139 participants received a psychotropic medication. Consistent with international guidelines, selective serotonin reuptake inhibitors (SSRIs) were most commonly used (73.5%, n = 1796), but their use ranged from 59% in Australia to 96% in Japan. Clomipramine use varied from 5% in Japan and South Africa to 26% in India and Italy. Atypical antipsychotic use ranged from 12% in South Africa to 50% in Japan. Pharmacotherapy for OCD varied significantly across sites. Prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that may play a role in the variation in prescribing practices internationally and whether these variations influence treatment outcomes. Copyright © 2016 John Wiley & Sons, Ltd.
Publisher: Oxford University Press (OUP)
Date: 14-03-2018
DOI: 10.1093/NDT/GFY047
Abstract: Acute kidney injury (AKI) is common after cardiac surgery and profoundly affects postoperative mortality and morbidity. There are no validated methods to assess risk of AKI intraoperatively. We determined the association between postoperative AKI and intraoperative urinary oxygen tension (PO2), measured via a fiber optic probe in the tip of the urinary catheter, in 65 patients undergoing high-risk cardiac surgery requiring cardiopulmonary bypass (CPB). AKI was diagnosed by modified Kidney Disease: Improving Global Outcomes criteria. Urinary PO2 fell during the operation, often reaching its nadir during rewarming or after weaning from CPB. Nadir urinary PO2 was lower in the 26 patients who developed AKI (mean ± SD, 8.9 ± 5.6 mmHg) than in the 39 patients who did not (14.9 ± 10.2 mmHg, P = 0.008). Patients who developed AKI had longer periods of urinary PO2 ≤15 and 10 mmHg than patients who did not. Odds of AKI increased when urinary PO2 fell to ≤10 mmHg {3.60 [95% confidence interval (CI) 1.27-10.21]} or ≤5 mmHg [3.60 (95% CI 1.04-12.42), P = 0.04] during the operation. When urinary PO2 fell to ≤15 mmHg, for more than or equal to the median duration for all patients (4.8 min/h surgery), the odds of AKI were 4.85 (95% CI 1.64-14.40), P = 0.004. The area under the receiver-operator curve for this parameter alone was 0.69, and was 0.89 when other variables with P ≤ 0.10 in univariable analysis were included in the model. Low urinary PO2 during adult cardiac surgery requiring CPB predicts AKI, so may identify patients in which intervention to improve renal oxygenation might reduce the risk of AKI.
Publisher: BMJ
Date: 10-2018
DOI: 10.1136/BMJOPEN-2018-023044
Abstract: Very-low birthweight (VLBW, g) infants comprise about 1%–1.4% of all births in high-income countries. Every year, about 3000 VLBW babies in Australia and New Zealand receive intensive care. Many die or else survive with severe brain injury, retinopathy, late-onset sepsis or necrotising enterocolitis (NEC), each of which carries substantial risk of disability. This trial tests whether adding bovine lactoferrin (bLF) to feeds in VLBW infants improves (1) survival to hospital discharge free from brain injury, late-onset sepsis, NEC and treated retinopathy of prematurity (primary composite end point) (2) each component of the primary composite end point and (3) time to reach full enteral feeds, number of blood transfusions, chronic lung disease and length of hospital stay. It includes a cost-effectiveness analysis of bLF in improving survival free from major morbidity, and evaluates the effect of bLF on survival and developmental outcomes at 24 to 36 months corrected gestational age. This is a multicentre, two-arm, randomised trial comparing the treatment group receiving bLF added to breast milk or formula milk daily (up to 250 mg/kg/day bLF) versus the control group receiving no bLF supplementation. The intervention is administered until 34 completed weeks corrected gestation or for 2 weeks, whichever is longer, or until discharge home, if earlier. The target s le size of 1500 participants yields 85% power, at the two-sided 5% level significance, to detect a difference in proportions meeting the primary outcome assuming the true probability is 74% in controls and 80.5% in the bLF group. This protocol was approved by Northern Sydney Local Human Research Ethics Committee in January 2017 (Version 2.0, Reference 1003-118M) and other relevant ethics committees. The findings of the trial will be disseminated through peer-reviewed journals and conference presentations. ACTRN12611000247976 Pre-results.
Publisher: Springer Science and Business Media LLC
Date: 11-03-2017
DOI: 10.1007/S00192-017-3297-4
Abstract: Female pelvic organ prolapse is highly prevalent and childbirth has been shown to be an important risk factor. The study was carried out to observe if pelvic organ support deteriorates over time following a first birth. This is a retrospective review using archived data sets of women seen in the context of two prospective perinatal imaging studies. All subjects had undergone a standardised interview, a clinical examination and 4D translabial ultrasound, 3 months and 2-5 years post-partum. Main outcome measures were pelvic organ descent and hiatal area at maximum Valsalva manoeuvre. Means at the two time points were compared using paired Student's t test. Predictors of change over time in continuous variables were explored using linear modelling methods. A total of 300 women had at least two postnatal follow-ups. They were first seen on average 0.39 (SD 0.2, range 0.2-2.1) years and again 3.1 (SD 1.5, range 1.4-8) years after the index delivery, with a mean interval of 2.71 (SD 1.5, range 0.7-7.7) years, providing a total of 813 (300 × 2.71) woman-years of observation. On univariate analysis, there was a significant decrease in mobility over time of the bladder neck, bladder, and rectal ulla (P = < 0.004) and hiatal area (P = 0.012). The degree of improvement was less marked in women with levator avulsion. A significant reduction in pelvic organ descent and hiatal area was noted over a mean of 2.7 years after a first birth.
Publisher: Wiley
Date: 29-12-2015
Abstract: To assess maternal abdominal subcutaneous fat thickness (SFT) measured by ultrasound as an independent predictor of adverse pregnancy outcomes. A prospective longitudinal cohort study performed on pregnancies delivered between 2012 and 2014. Sydney, Australia. About 1510 pregnant women attending routine obstetric ultrasounds. Maternal SFT was measured on routine ultrasounds at 11-14 weeks' gestation (SFT1) and 18-22 weeks' gestation (SFT2). SFT measurements were assessed for estimating risks for obesity-related pregnancy outcomes using logistic regression modelling adjusted for maternal age, parity, smoking status and body mass index (BMI). Hypertensive disease, gestational diabetes, caesarean section, low birthweight, preterm delivery, neonatal respiratory distress, Apgar scores, and admission to a neonatal intensive care unit. SFT1 and SFT2 were measured on 1461 and 1363 women, respectively. Mean thickness (range) were 21.2 mm (6.9-73.9) for SFT1 and 20.3 mm (7.5-68.0) for SFT2. Complete outcome data were available for 1385 pregnancies. In all, 54% of the women were overweight/obese. The SFT measures decreased from early to mid-pregnancy in overweight/obese women. There was moderate correlation between BMI and SFT1 (R(2) = 0.56) and BMI and SFT2 (R(2) = 0.55). In a multivariate model, SFT1 and SFT2 were better predictors for adverse pregnancy outcomes than BMI. Maternal SFT is a significant independent predictor of adverse pregnancy outcomes. Incorporation of SFT into future models for adverse pregnancy outcome may prove valuable.
Publisher: Wiley
Date: 12-02-2010
DOI: 10.1111/J.1753-6405.1994.TB00226.X
Abstract: The number of injecting drug users in the Central and Eastern Sydney Area Health Services (CSAHS and ESAHS) in 1989-1990 was estimated by applying the Petersen mark-recapture method to data obtained from the Australian National AIDS and Injecting Drug Use Surveys conducted in 1989 and in 1990. The population estimates for injecting drug users were 8368 (95 per cent confidence interval (CI) 6099 to 11,829) for ESAHS and 1466 (CI 742 to 2841) for CSHS. An estimate was also obtained for the number of injecting opioid users residing within the ESAHS our figure of 3597 (CI 2731 to 5737) was consistent with previously reported estimates obtained using mark-recapture but based on different data sets.
Publisher: BMJ
Date: 03-2017
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.HRTHM.2013.06.014
Abstract: Pulmonary vein isolation by cryoballoon ablation is an accepted method of treating atrial fibrillation. Little data exist regarding factors affecting late electrical reconnection of pulmonary veins following cryoballoon ablation. To investigate factors determining pulmonary vein reconnection in patients undergoing repeat catheter ablation for recurrent atrial fibrillation following cryoballoon ablation. Fifty-one consecutive patients undergoing repeat catheter ablation for recurrent atrial fibrillation following initial cryoballoon ablation underwent retrospective assessment of initial cryoablation characteristics, including balloon and vein sizes, venogram occlusion score, balloon freezing time from 0 to -30 °C, nadir temperature, and balloon warming time from -30 to +15 °C, recorded during the initial cryoballoon procedure. Of 199 veins assessed, 91 had reconnected (1.8 per patient). Balloon warming time (odds ratio [OR] 3.21 95% confidence interval [CI] 2.00-5.13 P < .0001), nadir temperature (OR 1.94 95% CI 1.42-2.66 P < .0001), vein occlusion score (OR 1.74 95% CI 1.29-2.34 P = .0003), and balloon freezing time (OR 1.58 95% CI 1.03-2.42 P = .037) predicted pulmonary vein reconnection. On multivariate analysis, balloon warming time (OR 3.71 95% CI 2.2-6.24 P ≤ .0001), pulmonary vein size (OR 1.63 95% CI 1.08-2.43 P = .020), and vein occlusion score (OR 1.48 95% CI 1.06-2.08 P = .021) remained statistically significant independent predictors of pulmonary vein reconnection. The receiver operating characteristic for the multivariate model yielded an area under the curve of 0.82. Balloon warming time, vein occlusion score, and pulmonary vein size predict pulmonary vein reconnection. Balloon warming time was the most important predictive factor, and the manipulation of balloon warming may be a novel therapeutic strategy for improving outcomes of cryoballoon ablation for atrial fibrillation.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.JOCN.2013.02.032
Abstract: Impulse control and related disorders (ICRD) are not uncommon in patients with idiopathic Parkinson's disease (PD). The present study aimed to investigate the effects of ICRD on quality of life (QoL) and disability in PD. From two movement disorder clinics in Sydney, Australia, 100 consecutive patients with PD were included in the trial. The Unified Parkinson's Disease Rating Scale (UPDRS), Mini Mental State Examination and the Parkinson's Disease Questionnaire-39 were used to measure disease severity, cognition and disease-specific QoL. The diagnosis of ICRD was based on face-to-face structured clinical interviews by three psychiatrists with experience in ICRD using the Expanded Structured Clinical Interview for the Diagnostic and Statistical Manual IV for Obsessive-Compulsive Disorder Related/Spectrum Disorders. ICRD were present in 15% of our patient population, and had a negative impact on QoL and Activity of Daily Living (ADL) scores. After adjusting for the presence of major depressive disorders and PD duration, the effect on emotional wellbeing remained statistically significant (p<0.004). Disease duration also correlated with worse QoL and ADL scores. Major depression disorders reduced QoL but not ADL. Patients with ICRD tended to suffer more from depression than those without ICRD. There were no statistically significant differences in age, sex, major depressive disorders, PD duration, total levodopa equivalent daily dose, use of dopamine agonists, or UPDRS motor score between patients with and without ICDR.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2012
DOI: 10.1007/S00192-012-1769-0
Abstract: Urogynaecological assessment routinely includes determination of postvoid residual urine volume (PVR). This study was designed to generate a formula for determining PVR by translabial ultrasound (US). This was an observational study using imaging data obtained during urodynamic testing between July 2009 and November 2010. Bladder dimensions were determined by translabial US (midsagittal plane) and blinded against PVR on catheterisation. The relationship between PVR and bladder dimensions was modelled using linear regression. Predictive performance was quantified using Pearson's correlation and R (2) statistic. In 207 in iduals, 243 PVRs were obtained by catheterisation (0-650 ml). An optimal regression model comprised the product of height and depth US measurements and a coefficient of 5.59 [95 % confidence interval (CI): 5.41-5.76, p < 0.0001)] This regression equation yielded an R(2) = 0.94 Pearson's correlation was 0.97. Translabial US is a convenient and accurate method for measuring PVR. We propose the formula height × depth × 5.6 = postvoid residual in millilitres.
Publisher: Elsevier BV
Date: 2013
Abstract: Despite the association with more advanced nodal stage, patients with human papillomavirus (HPV) positive oropharyngeal cancers have better outcomes. We examined whether the HPV can modify the effect of known prognostic factors in tonsillar cancer. A total of 489 patients from 10 centres were followed up for recurrence or death for a median of 3.2 years. Determinants of the rate of locoregional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression. The prognostic value of T and N stages were modified by HPV as indicated by statistically significant interaction terms. After adjusting for age, gender and treatment, T stage appeared relevant only for HPV-positive cancers (where a higher T stage was associated with worse outcomes). There was some evidence that N stage was a more relevant prognostic factor for HPV-negative than -positive cancers. There was no evidence that the HPV modifies the effect of age, gender or grade on outcomes. This study suggests that the prognostic significance of the conventional staging system in tonsillar cancer is modified by HPV.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2020
DOI: 10.1007/S00520-019-05158-5
Abstract: To compare estimates of expected survival time (EST) made by patients with advanced cancer and their oncologists. At enrolment patients recorded their "understanding of how long you may have to live" in best-case, most-likely, and worst-case scenarios. Oncologists estimated survival time for each of their patients as the "median survival of a group of identical patients". We hypothesized that oncologists' estimates of EST would be unbiased (~ 50% longer or shorter than the observed survival time [OST]), imprecise (< 33% within 0.67 to 1.33 times OST), associated with OST, and more accurate than patients' estimates of their own survival. Twenty-six oncologists estimated EST for 179 patients. The median estimate of EST was 6.0 months, and the median OST was 6.2 months. Oncologists' estimates were unbiased (56% longer than OST), imprecise (27% within 0.67 to 1.33 times OST), and significantly associated with OST (HR 0.88, 95% CI 0.82 to 0.93, p < 0.01). Only 41 patients (23%) provided a numerical estimate of their survival with 107 patients (60%) responding "I don't know". The median estimate by patients for their most-likely scenario was 12 months. Patient estimates of their most-likely scenario were less precise (17% within 0.67 to 1.33 times OST) and more likely to overestimate survival (85% longer than OST) than oncologist estimates. Oncologists' estimates were unbiased and significantly associated with survival. Most patients with advanced cancer did not know their EST or overestimated their survival time compared to their oncologist, highlighting the need for improved prognosis communication training. Trial registration ACTRN1261300128871.
Publisher: Wiley
Date: 15-10-2016
DOI: 10.1111/AOGS.13018
Abstract: The study aimed to analyze the relation between the degree of puborectalis muscle trauma and subjective symptoms and objective findings of pelvic organ prolapse (POP), comparing two continuous scoring systems with a discrete scoring system for translabial ultrasound imaging. In this retrospective observational study the records of patients attending a tertiary urogynecological unit between January 2012 and December 2014 were analyzed. POP assessment included a standardized interview, clinical examination using Pelvic Organ Prolapse Quantification and four-dimensional translabial ultrasound. Puborectalis muscle trauma was assessed with tomographic ultrasound imaging using two continuous scoring systems and a previously established discrete system. Receiver operating characteristics and adjusted odds ratios were used for comparison of scoring systems in predicting symptoms and signs of POP. Of 1258 women analyzed, 52.6% complained of prolapse symptoms. On ultrasound imaging, 65.7% of women had sonographically significant POP. Complete avulsion was diagnosed in 25.3% of women, being unilateral in 13.9% and bilateral in 11.4%. A maximum score in the 6-point and the 12-point tomographic ultrasound imaging scale increased the odds for a diagnosis of any significant POP on ultrasound by 4.4 and 4.8 times, respectively, compared with 4.6 times for the discrete diagnosis of bilateral avulsion. For all avulsion scoring systems the relation was strongest for cystocele and uterine prolapse. A continuous avulsion scoring system based on tomographic findings does not provide superior performance for the prediction of subjective symptoms and objective findings of prolapse compared with a discrete diagnostic system of unilateral or bilateral avulsion.
Publisher: Wiley
Date: 29-08-2017
DOI: 10.1111/BJU.13593
Abstract: To test the feasibility and efficacy of a multifaceted model of shared care for men after completion of treatment for prostate cancer. Men who had completed treatment for low- to moderate-risk prostate cancer within the previous 8 weeks were eligible. Participants were randomized to usual care or shared care. Shared care entailed substituting two hospital visits with three visits in primary care, a survivorship care plan, recall and reminders, and screening for distress and unmet needs. Outcome measures included psychological distress, prostate cancer-specific quality of life, satisfaction and preferences for care and healthcare resource use. A total of 88 men were randomized (shared care n = 45 usual care n = 43). There were no clinically important or statistically significant differences between groups with regard to distress, prostate cancer-specific quality of life or satisfaction with care. At the end of the trial, men in the intervention group were significantly more likely to prefer a shared care model to hospital follow-up than those in the control group (intervention 63% vs control 24% P<0.001). There was high compliance with prostate-specific antigen monitoring in both groups. The shared care model was cheaper than usual care (shared care AUS$1411 usual care AUS$1728 difference AUS$323 [plausible range AUS$91-554]). Well-structured shared care for men with low- to moderate-risk prostate cancer is feasible and appears to produce clinically similar outcomes to those of standard care, at a lower cost.
Publisher: Wiley
Date: 06-07-2021
DOI: 10.1111/BJU.15491
Abstract: To determine the activity and safety of lutetium‐177 ( 177 Lu)‐prostate‐specific membrane antigen (PSMA)‐617 in men with metastatic castration‐resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. ENZA‐p (ANZUP 1901) is an open‐label, randomized, two‐arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177 Lu‐PSMA‐617 7.5 GBq on Days 15 and 57. Two additional 177 Lu‐PSMA‐617 doses are allowed, informed by Day‐92 Gallium‐68 ( 68 Ga)‐PSMA positron emission tomography (PET up to four doses in total). The primary endpoint is prostate‐specific antigen (PSA) progression‐free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health‐related quality of life, adverse events and cost‐effectiveness. Key eligibility criteria include: biochemical and/or clinical progression 68 Ga‐PSMA PET‐avid disease no prior androgen signalling inhibitor, excepting abiraterone no prior chemotherapy for mCRPC and ≥2 high‐risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68 Ga‐PSMA PET at baseline, Days 15 and 92, and at progression, and 18 F‐fluorine deoxyglucose ( 18 F‐FDG) PET at baseline and progression. Translational s les include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga‐PSMA and 18 F‐FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two‐sided type‐1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA‐PFS of 5 months with enzalutamide alone. The combination of 177 Lu‐PSMA‐617 and enzalutamide may be synergistic. ENZA‐p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.
Publisher: Springer Science and Business Media LLC
Date: 12-1998
Abstract: The Utility-based Quality of Life--Heart Questionnaire (UBQ-H) is a cardiovascular extension of the Health Measurement Questionnaire. It is a multidimensional instrument that can be scored to yield a utility estimate using the Rosser Index and a classification algorithm developed for the Health Measurement Questionnaire. The aim of this study was to employ a statistical modelling approach to devise an improved scoring system. A s le of 201 cardiovascular patients completed the UBQ-H and assessed the utility of their own health state using standard gamble and time trade-off questions in an interview. Two new scoring methods were devised by regressing the UBQ-H data against patients' self-assessed utilities. The new methods gave utility estimates that correlated with angina/dyspnoea grades, life satisfaction scores and General Health Questionnaire (GHQ) scores. In a second s le of 1,112 cardiovascular patients, the UBQ-H utilities were able to distinguish between patients who had/had not experienced an adverse event (e.g. myocardial infarction) and were responsive to changes in health over time. The new scoring methods were not particularly more sensitive to quality of life effects than the original method based on the Rosser Index. However, they produced significantly lower estimates and more accurately reflected patients' self-assessed utilities.
Publisher: Cambridge University Press (CUP)
Date: 2000
DOI: 10.1017/S0266462300161124
Abstract: Objective: To adjust patients' time trade-off (TTO) scores using information on their utility functions for survival time to derive a measure of health state utility equivalent to the standard gamble (SG). Methods: A s le of 199 cardiovascular patients were asked three TTO and SG questions (to assess their own health state), and three certainty equivalent questions (to assess their utility function for survival time) in an interview. Results: Patients' utility functions for time were increasingly concave, but being unable to model this successfully, a constant function with an averaged level of concavity was used. The raw TTO scores were significantly higher than SG scores, while the adjusted TTO scores were equivalent to the SG. Conclusions: Raw time trade-off scores will give biased estimates of health state utility when patients' utility functions for time are not linear, but these can be adjusted to yield true utilities. The constant proportional risk-posture assumption of the conventional QALY model, on which previous attempts to adjust time trade-offs have been based, was not supported by the data.
Publisher: Public Library of Science (PLoS)
Date: 21-02-2017
Publisher: Elsevier BV
Date: 02-2003
DOI: 10.1111/J.1467-842X.2003.TB00377.X
Abstract: To estimate the effects of key uncertainties on the effectiveness and cost-effectiveness of breast cancer prevention with tamoxifen. The incremental cost-effectiveness ratio of tamoxifen therapy relative to placebo was estimated using decision analysis with Markov modelling of health states, outcomes and costs for a simulated cohort of women at high risk for breast cancer. Relative effects of tamoxifen's benefits and harms were estimated from meta-analyses of randomised controlled trials. Cost estimates were based on Australian treatment patterns and costs. The main outcome measure was cost per quality-adjusted life year (QALY) gained with costs and effects discounted at a 5% annual rate. Tamoxifen therapy over five years reduces the incidence of breast cancer by approximately 1.4%, which is offset by an increase in endometrial cancer of 0.7% and pulmonary embolism of 0.2%. If the reduction is permanent (preventing new breast cancers emerging over five years and no further treatment effect thereafter), the model estimates an increase in life expectancy of 0.057 QALYs and an extra cost of $2,193 or $38,271/QALY gained. A model assuming further treatment effects of tamoxifen preventing new breast cancers emerging for up to 10 years results in an incremental cost of $19,354/QALY. However, if five years of tamoxifen therapy merely delays when these breast cancers appear (such that by 10 years there is no longer a reduced incidence), the incremental cost per QALY saved is estimated to be $199,149. Tamoxifen is potentially cost-effective in preventing breast cancer in women at high risk. However, its cost-effectiveness as a preventive therapy is highly sensitive to whether these cancers are permanently prevented or their clinical presentation is only delayed. Long-term follow-up in randomised controlled trials is therefore crucial in forming health policy.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.CLINTHERA.2011.02.007
Abstract: Several classes of medications such as tricyclic antidepressants, anticonvulsants, narcotic analgesics, and α2-δ ligands, such as pregabalin, have been reported to be efficacious in the treatment of painful diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN) in whites. However, no large double-blind, placebo-controlled trials have been reported that evaluated the efficacy of pregabalin for the treatment of neuropathic pain in a Chinese population in China. The aim of this study was to evaluate the efficacy and tolerability of flexible-dose pregabalin in treatment of Chinese patients diagnosed with painful DPN or PHN. This was a double-blind, parallel-group study in which patients were randomized in a 2:1 ratio and treated with either flexible-dose pregabalin, 150 to 600 mg/d, or corresponding flexible-dose placebo for 8 weeks. The primary efficacy end point was change in the mean pain score based on a daily pain rating scale (DPRS ranging from 0 [no pain] to 10 [worst possible pain]). Secondary end points included Daily Sleep Interference scale, short form-McGill Pain Questionnaire (SF-MPQ) scale, and the Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) scales. Adverse events and physical and laboratory examination results were also collected. Pregabalin and placebo treatment groups were well-matched in terms of demographic and patient characteristics. On the primary outcome, end point change in mean DPRS score, treatment with pregabalin (N = 206) resulted in significant improvement compared with results with placebo (N = 102), with a least squares mean difference score of -0.6 (P = 0.005). With regard to responder rates, 64% and 52% of patients treated with pregabalin and placebo, respectively, reported ≥30% improvement in DPRS scores (P = 0.04). Treatment with pregabalin also resulted in significant efficacy compared with that of placebo on secondary measures, including SF-MPQ VAS score (P = 0.012), SF-MPQ present pain intensity index score (P = 0.003), sleep interference score (P = 0.023), and PGIC and CGIC scores (P = 0.004 and P = 0.001, respectively). Adverse events were observed in 50.0% of pregabalin patients and 40.2% of placebo patients (P = 0.105), with the most common adverse event being dizziness (11.2%). Study results suggest that relative to placebo, pregabalin in daily doses of 150 to 600 mg/d was effective and well tolerated in Chinese patients diagnosed with moderate-to-severe DPN or PHN, indicated through improved pain scores and PGIC scores.
Publisher: MDPI AG
Date: 25-03-2019
DOI: 10.3390/GERIATRICS4010031
Abstract: Nicotinamide (vitamin B3) has photoprotective effects and reduces skin cancer incidence in high risk patients. Nicotinamide also improves cognition in animal models. As part of the ONTRAC (Oral Nicotinamide To Reduce Actinic Cancer) phase III placebo-controlled, randomized trial to assess nicotinamide’s efficacy in skin cancer prevention, we included clinical neurocognitive function and patient-reported quality of life assessments at baseline and after 12 months of intervention in in iduals with previous skin cancer in order to assess any effect of oral nicotinamide (500 mg po twice daily) on cognitive function and quality of life. In our s le of 310 participants who completed neurocognitive function testing at baseline and at 12 months, we were not able to detect any significant effect of oral nicotinamide on cognitive function nor on quality of life. Further studies of nicotinamide’s effects on cognition in humans might include in iduals with pre-existing mild cognitive impairment, and it may be that higher doses of nicotinamide are required to significantly influence cognitive function compared to doses required to reduce skin cancer.
Publisher: Springer Science and Business Media LLC
Date: 29-01-2020
DOI: 10.1186/S12887-020-1938-0
Abstract: In Canada alone, almost 3000 VLBW infants are born and treated annually with almost 1200 going onto death or survival with severe brain injury, chronic lung disorders, aggressive retinopathy of prematurity, late-onset sepsis, or significant necrotizing enterocolitis. Lactoferrin is an antimicrobial, antioxidant, anti-inflammatory iron-carrying, bifidogenic glycoprotein found in all vertebrates and in mammalian milk, leukocytes and exocrine secretions. Lactoferrin aids in creating an environment for growth of beneficial bacteria in the gut, thus reducing colonization with pathogenic bacteria. It is hypothesized that oral bovine lactoferrin (bLF), through its antimicrobial, antioxidant and anti-inflammatory properties, will reduce the rate of mortality or major morbidity in very low birth weight preterm infants. Lactoferrin Infant Feeding Trial_Canada (LIFT_Canada) is a multi-centre, double-masked, randomized controlled trial with the aim to enroll 500 infants whose data will be combined with the data of the 1542 infants enrolled from Lactoferrin Infant Feeding Trial_Australia/New Zealand (LIFT_ANZ) in a pooled intention-to-treat analysis. Eligible infants will be randomized and allocated to one of two treatment groups: 1) a daily dose of 200 mg/kg bLF in breast/donor human milk or formula milk until 34 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer, or until discharge home or transfer, if earlier 2) no bLF with daily feeds. The primary outcome will be determined at 36 weeks corrected gestation for the presence of neonatal morbidity and at discharge for survival and treated retinopathy of prematurity. The duration of the trial is expected to be 36 months. Currently, there continues to be no clear answer related to the benefit of bLF in reducing mortality or any or all of the significant neonatal morbidities in very low birth weight infants. LIFT_Canada is designed with the hope that the pooled results from Australia, New Zealand, and Canada may help to clarify the situation. Clinical Trials.Gov, Identifier: NCT03367013 , Registered December 8, 2017.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.CCT.2021.106544
Abstract: Clinical trialists may regard an observed imbalance on a prognostic covariate as sufficiently troubling to warrant action. To elucidate the issues associated with selecting, and switching between, an unadjusted versus an adjusted analysis in response to an observed covariate imbalance. Simulation study performed under the null hypothesis of no treatment effect using data from a large secondary prevention trial of statin therapy. The operating characteristics of three reaction strategies to baseline imbalances observed post-hoc were assessed. Unadjusted analyses produced valid p-values irrespective of chance imbalance on a prognostic covariate. Switching to an adjusted analysis introduced no bias when the decision was made without knowledge of the direction of the imbalance. When the decision was based on the direction of the imbalance, the risk of incorrectly declaring the experimental treatment superior was inflated (by up to 48% in the scenarios investigated). Overreaction to baseline imbalances observed post-hoc is unwarranted and we support adherence to the ICH guideline recommendations on the use of covariates. A legitimate case for switching to an adjusted analysis prior to finalisation of the statistical analysis plan (SAP) could nevertheless be potentially made provided that the direction of an observed covariate imbalance is unknown. Investigators should avoid reviewing the distribution of baseline characteristics across randomised groups in an unblinded fashion, for open-label and blinded studies alike, prior to finalisation of the SAP. ICH guidelines on adjustment for covariates in RCT analyses appropriately advise against overreaction to baseline imbalances observed post-hoc. CONSORT reporting guidelines nevertheless place an emphasis on comparability of baseline characteristics across randomised groups. We demonstrate through a series of simulation studies why the ICH guidance is sound, but that a switch to an adjusted analysis in reaction to an observed prognostic covariate imbalance could legitimately be made provided that, when reaching the decision, treatment allocation is masked, and the direction of the imbalance is unknown. Trialists should therefore consider preserving the masking of actual treatment assignment when assessing the distribution of baseline characteristics across randomised groups.
Publisher: Oxford University Press (OUP)
Date: 04-2019
DOI: 10.1634/THEONCOLOGIST.2018-0613
Abstract: Worst-case, typical, and best-case scenarios for survival, based on simple multiples of an in idual's expected survival time (EST), estimated by their oncologist, are a useful way of formulating and explaining prognosis. We aimed to determine the accuracy and prognostic significance of oncologists’ estimates of EST, and the accuracy of the resulting scenarios for survival time, in advanced gastric cancer. Sixty-six oncologists estimated the EST at baseline for each of the 152 participants they enrolled in the INTEGRATE trial. We hypothesized that oncologists’ estimates of EST would be unbiased (∼50% would be longer or shorter than the observed survival time [OST]) imprecise (& % within 0.67–1.33 times the OST) independently predictive of overall survival (OS) and accurate at deriving scenarios for survival time with approximately 10% of patients dying within a quarter of their EST (worst-case scenario), 50% living within half to double their EST (typical scenario), and 10% living three or more times their EST (best-case scenario). Oncologists’ estimates of EST were unbiased (45% were shorter than the OST, 55% were longer) imprecise (29% were within 0.67–1.33 times observed) moderately discriminative (Harrell's C-statistic 0.62, p = .001) and an independently significant predictor of OS (hazard ratio, 0.89 95% confidence interval, 0.83–0.95 p = .001) in a Cox model including performance status, number of metastatic sites, neutrophil-to-lymphocyte ratio ≥3, treatment group, age, and health-related quality of life (EORTC-QLQC30 physical function score). Scenarios for survival time derived from oncologists’ estimates were remarkably accurate: 9% of patients died within a quarter of their EST, 57% lived within half to double their EST, and 12% lived three times their EST or longer. Oncologists’ estimates of EST were unbiased, imprecise, moderately discriminative, and independently significant predictors of OS. Simple multiples of the EST accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer. Results of this study demonstrate that oncologists’ estimates of expected survival time for their patients with advanced gastric cancer were unbiased, imprecise, moderately discriminative, and independently significant predictors of overall survival. Simple multiples of the expected survival time accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer.
Publisher: Physicians Postgraduate Press, Inc
Date: 15-10-2005
DOI: 10.4088/JCP.V66N1015
Abstract: The comparative efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) was recently debated. Meta-analyses, based mainly on fluoxetine comparator data, suggest that the SNRI venlafaxine has superior efficacy to SSRIs in treatment of major depression. To compare quality of life (QOL), efficacy, safety, and tolerability associated with sertraline and venlafaxine extended release (XR) for treatment of DSM-IV major depression. This was an 8-week, double-blind, randomized study of sertraline (50-150 mg/day) versus venlafaxine XR (75-225 mg/day), followed by a 2-week taper period. Subjects were recruited from 7 sites in Turkey and 6 sites in Australia between October 2002 and July 2003. The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Questionnaire. Secondary outcome measures included measures of depression (including response and remission), anxiety, pain, safety (e.g., blood pressure), and tolerability (e.g., discontinuation symptoms). A total of 163 subjects received study treatment (women, 69% mean age, 37.0 [SD = 12.9] years). No significant differences in QOL or efficacy were noted between treatments on the primary or secondary endpoints for the total study population or the anxious depression and severe depression subgroups. A priori analyses of symptoms associated with treatment discontinuation demonstrated no difference between treatment groups. However, in post hoc analyses, sertraline was associated with less burden of moderate to severe discontinuation symptoms. Venlafaxine XR was associated with a relative increase in mean blood pressure (supine diastolic blood pressure, -4.4 mm Hg difference at week 8/last observation carried forward). Sertraline and venlafaxine XR demonstrated comparable effects on QOL and efficacy in treatment of major depression, although sertraline may be associated with a lower symptom burden during treatment discontinuation and a reduced risk of blood pressure increase.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.RADONC.2014.03.020
Abstract: Intensity modulated radiation therapy (IMRT) is a radiation therapy technology that facilitates the delivery of an improved dose distribution with less dose to surrounding critical structures. This study estimates the longer term effectiveness and cost-effectiveness of IMRT in patients post radical prostatectomy. A Markov decision model was developed to calculate the incremental quality adjusted life years (QALYs) and costs of IMRT compared with three dimensional conformal radiation therapy (3DCRT). Costs were estimated from the perspective of the Australian health care system. IMRT was both more effective and less costly than 3DCRT over 20 years, with an additional 20 QALYs gained and over $1.1 million saved per 1000 patients treated. This result was robust to plausible levels of uncertainty. IMRT was estimated to have a modest long term advantage over 3DCRT in terms of both improved effectiveness and reduced cost. This result was reliant on clinical judgement and interpretation of the existing literature, but provides quantitative guidance on the cost effectiveness of IMRT whilst long term trial evidence is awaited.
Publisher: Elsevier BV
Date: 2018
DOI: 10.2139/SSRN.3225497
Publisher: Springer Science and Business Media LLC
Date: 23-05-2014
DOI: 10.1007/S00192-014-2331-Z
Abstract: The levator ani is thought to play an important role in sexual function however, to date little literature has been published on the impact of delivery-related levator trauma on female sexual function. We hypothesised that delivery-related levator trauma has a negative impact on women's reports of pelvic floor and sexual function postpartum. In 294 primigravid women with a singleton pregnancy, four-dimensional (4D) translabial ultrasound imaging was used to assess delivery-related levator avulsion and levator hiatal over-distension, and postpartum pelvic floor and sexual function was assessed by an in-house validated questionnaire. Associations between questionnaire responses and levator avulsion and hiatal over-distension were investigated using standard linear modelling methods. Levator avulsion was diagnosed in 14% of women (42 out of 292 25 unilateral, 17 bilateral) and was found to be significantly associated with lower scores for the pelvic floor integrity and function domain of the questionnaire (P < 0.0005). Avulsion was associated with lower scores for this domain (no avulsion = 2.78, unilateral avulsion = 2.61, bilateral avulsion = 2.29). This association remained significant after controlling for potential confounders (p = 0.013). Avulsion was not associated with any of the other domains of sexual function and levator hiatal over-distension was not associated with scores for any of the questionnaire domains. The effect of levator avulsion on pelvic floor and sexual function an average of 5.2 months after childbirth seems to be limited to a perception of increased vaginal and pelvic floor muscle laxity, and reduced pelvic floor muscle efficiency. The impact of levator hiatal over-distension on postpartum pelvic floor and sexual function appears to be negligible.
Publisher: Wiley
Date: 05-2017
DOI: 10.1111/BJU.13873
Publisher: Wiley
Date: 05-10-2016
Abstract: We tested the ability of the Assessment of New Radiation Oncology Technology and Treatments framework to determine the clinical efficacy and safety of intensity-modulated radiation therapy (IMRT) compared with 3-dimensional radiation therapy (3DCRT) for post-prostatectomy radiation therapy (PPRT) to support its timely health economic evaluation. Treatment plans produced using FROGG guidelines provided dosimetry parameters for both techniques at 64 Gy and 70 Gy and were also used to model early and late outcome probabilities. Clinical parameters were derived from early toxicity and quality of life patient data, systematic literature review and expert opinion. Dosimetry parameters were correlated with the measures of clinical efficacy and safety. Data from two patient cohorts (29 and 27 respectively) were collected within the project timeframe, providing evidence for acute toxicity and quality of life, and dosimetric comparisons. Relative rates of tumour control probability (TCP) and normal tissue control probability (NTCP) modelling were readily derived from the planning exercise and demonstrated advantages in uncomplicated TCP for IMRT over 3DCRT, predominantly due to normal tissue sparing. The safety of IMRT delivery was demonstrated with TCP uncompromised by IMRT protocol violations, which achieved rectal sparing only by reducing minimum target dose and coverage. Sources of desk-top and patient-based evidence were successfully used to demonstrate potential improved clinical efficacy and safety of applying dose escalation using IMRT instead of 3DCRT in PPRT.
Publisher: Elsevier BV
Date: 12-2016
Publisher: Hindawi Limited
Date: 26-07-2021
DOI: 10.1111/ECC.13492
Publisher: Wiley
Date: 27-10-2015
Abstract: The study aim was to develop a generic framework to derive the parameters to populate health-economic models for the rapid evaluation of new techniques and technologies in radiation oncology. A draft framework was developed through horizon scanning for relevant technologies, literature review to identify framework models, and a workshop program with radiation oncology professionals, biostatisticians, health economists and consumers to establish the Framework's structure. It was tested using four clinical protocols, comparing intensity modulated with 3D conformal therapy (post-prostatectomy, anal canal and nasopharynx) and image-guided radiation therapy techniques with off-line review of portal imaging (in the intact prostate). The draft generic research framework consisted of five sequential stages, each with a number of components, and was assessed as to its suitability for deriving the evidence needed to populate the decision-analytic models required for the health-economic evaluations. A final Framework was established from this experience for use by future researchers to provide evidence of clinical efficacy and cost-utility for other novel techniques. The four clinical treatment sites tested during the project were considered suitable to use in future evaluations. Development of a generic research framework to predict early and long-term clinical outcomes, combined with health-economic data, produced a generally applicable method for the rapid evaluation of new techniques and technologies in radiation oncology. Its application to further health technology assessments in the radiation oncology sector will allow further refinement and support its generalisability.
Publisher: Massachusetts Medical Society
Date: 05-11-1998
Publisher: Elsevier BV
Date: 2017
Publisher: Elsevier BV
Date: 11-2022
Publisher: Springer Science and Business Media LLC
Date: 30-06-2020
Publisher: Wiley
Date: 2019
DOI: 10.1002/HUP.2686
Abstract: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive-compulsive disorder (OCD). Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their s les. Consistency of summary statistics across countries was evaluated. The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total s le of 7,340 participants. Fluoxetine (n = 972 13.2%) and fluvoxamine (n = 913 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428 7.3%) and aripiprazole (n = 415 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the s le. There was significant variation in the use and accessibility of exposure and response prevention for OCD. The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2017
DOI: 10.1007/S10120-017-0754-1
Abstract: The INTEGRATE phase II multinational randomized controlled trial demonstrated the activity of regorafenib on progression-free survival (PFS) in patients with refractory advanced gastric adenocarcinoma. We sought to evaluate whether these PFS gains had the potential to be offset by quality of life (QoL) impacts from treatment side effects and to thereby determine the appropriateness of continuing development to phase III. QoL was assessed in INTEGRATE at baseline and at each 4 weeks thereafter, until discontinuation of study treatment, using the QLQ-C30, STO22, and EQ-5D questionnaires. The patient disease and treatment assessment (PTDATA) form was also provided to English-speaking participants. Randomized groups were compared on the QLQ-C30, STO22, and EQ-5D scales using a repeated-measures model the frequency of troublesome symptoms and side effects measured by the PTDATA form and deterioration-free survival (DFS). The prognostic value of baseline QoL information was also evaluated. Of the 147 eligible randomized patients, 142 consented to participate in the QoL substudy, 136 completed a baseline QoL assessment, and 95 completed at least one post-baseline QoL assessment. The DFS rate was significantly improved with regorafenib, and there was no compelling statistical evidence that regorafenib had a broad negative effect across the spectrum of QoL indices evaluated. Fatigue, anxiety, appetite loss, and pain were among the issues most commonly reported for both randomized groups. Baseline levels of pain, appetite, constipation, and physical functioning were prognostic factors for survival. Regorafenib improved DFS without an excessively negative effect on QoL. Progressing development to the phase III setting is warranted.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.JGO.2018.08.010
Abstract: The Cancer and Aging Research Group's (CARG) Toxicity Score was designed to predict grade ≥3 chemotherapy-related toxicity in adults aged ≥65 yrs. commencing chemotherapy for a solid organ cancer. We aimed to evaluate the CARG Score and compare it to oncologists' estimates for predicting severe chemotherapy toxicity in older adults. Patients aged ≥65 yrs. starting chemotherapy for a solid organ cancer had their CARG Score (range 0-23) calculated. Their treating oncologist, blinded to these results, independently estimated each patient's risk of severe chemotherapy toxicity (0-100%). Toxicities were captured prospectively. The predictive value of the CARG Score and oncologists' estimates was estimated using logistic regression and in terms of Area Under the Receiver Operating Characteristic curve (AU-ROC). 126 patients from ten oncologists at two sites participated. The median age was 72 yrs. (range 65-84). The median CARG Score was 7 (range 0-17) the median oncologist estimate of risk was 30% (range 3-80%), and these measures were not correlated (r = -0.01). 64 patients (52%) experienced grade ≥ 3 toxicity. Rates of severe toxicity in low-, intermediate-, and high-risk groups by CARG Score were 58%, 47%, and 58% respectively, and 63%, 44%, and 67% by oncologist estimate. Severe chemotherapy toxicity was not predicted by the CARG Score (OR 1.04, 95%CI 0.92-1.18, p = .54, AU-ROC 0.52), or oncologists' estimates (OR 1.00, 95%CI 0.98-1.02, p = .82, AU-ROC 0.52). Neither the CARG Score, nor oncologists' estimates based on clinical judgement, predicted severe chemotherapy-related toxicity in our population of older adults with cancer. Methods to improve risk prediction are needed.
Publisher: Oxford University Press (OUP)
Date: 28-11-2020
Abstract: SCOT was an international, randomized phase 3 trial of 3 months vs 6 months of adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine in patients with colorectal cancer. We sought patients’ preferences for 3 months vs 6 months of adjuvant chemotherapy in the SCOT trial. SCOT participants from Australia and New Zealand completed a validated questionnaire (at 3 and 18 months) to elicit the minimum survival benefits judged necessary to make an extra 3 months of adjuvant chemotherapy worthwhile, based on their experience. Standardized hypothetical scenarios used the following baseline survivals (with 3 months of chemotherapy): life expectancies (LE) of 5 years and 15 years and 5-year survival rates (5YS) of 65% and 85%. Of the 160 participants, 82 were assigned 3 months adjuvant chemotherapy, and 78 were assigned 6 months. Adjuvant chemotherapy was FOLFOX in 121 (75.6%) and XELOX in 39 (24.4%). Preferences varied substantially and did not differ according to treatment group. The median survival benefits judged necessary to make the extra 3 months of chemotherapy worthwhile were an extra 3 years beyond a LE of 5 years 3 years beyond a LE of 15 years 15% beyond a 5YS of 65% and 5% beyond a 5YS of 85%. Preferences were similar at 3 months and 18 months. Preferences were not predicted by participants’ baseline characteristics. Preferences varied substantially, and the benefits many required to warrant an extra 3 months of adjuvant chemotherapy were larger than the benefits of an extra 3 months of chemotherapy calculated in the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) meta-analysis.
Publisher: Massachusetts Medical Society
Date: 02-03-2023
Publisher: Springer Science and Business Media LLC
Date: 21-07-2018
Publisher: Springer Science and Business Media LLC
Date: 03-06-2020
DOI: 10.1186/S13063-020-04374-3
Abstract: Despite careful planning, changes to some aspects of an ongoing randomised clinical trial (RCT), with a fixed design, may be warranted. We sought to elucidate the distinction between legitimate versus illegitimate changes to serve as a guide for less experienced clinical trialists and other stakeholders. Using data from a large trial of statin therapy for secondary prevention, we generated a set of simulated trial datasets under the null hypothesis (H0) and a set under an alternative hypothesis (H1). Through analysis of these simulated trials, we assessed the performance of the strategy of changing aspects of the design/analysis with knowledge of treatment allocation (illegitimate) versus the strategy of making changes without knowledge of treatment allocation (legitimate). Performance was assessed using the type 1 error, as well as measures of absolute and relative bias in the treatment effect. Illegitimate changes led to a relative bias of 61% under H1, and a type 1 error rate under H0 of 23%—well in excess of the 5% significance level targeted. Legitimate changes produced unbiased estimates under H1 and did not inflate the type 1 error rate under H0. Changes to pre-specified aspects of the design and analysis of an ongoing RCT may be a necessary response to unforeseen circumstances. Such changes risk introducing a bias if undertaken with knowledge of treatment allocation. Legitimate changes need to be adequately documented to provide assurance to all stakeholders of their validity.
Publisher: Society of Nuclear Medicine
Date: 23-06-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-07-2018
DOI: 10.1097/SPV.0000000000000608
Abstract: Genital hiatus (Gh) and perineal body (Pb) are part of the Pelvic Organ Prolapse Quantification assessment system, but it is unclear whether measurements should be taken at rest or on Valsalva. This study was designed to assess the predictive value of Gh and Pb measurements obtained at rest and on Valsalva for signs and symptoms of pelvic organ prolapse (POP). This is a retrospective study involving 416 women who presented to a tertiary urogynecology unit with symptoms of pelvic floor dysfunction. Genital hiatus and Pb were measured at rest and on maximal Valsalva. The strength of association between binary markers of POP and measurements of Gh/Pb was estimated using logistic regression analysis. Receiver operator characteristic statistics were used to compare predictive values of Gh and Pb measurements obtained at rest and on Valsalva. A total of 451 women were seen during the study period. Thirty-five were excluded owing to missing data, leaving 416. Fifty-four percent (n = 223) complained of POP symptoms. On examination, 80% (n = 332) had significant POP (stage 2+ in anterior or posterior compartments or stage 1+ in the central compartment). On imaging, significant POP was diagnosed in 66% (n = 275). Mean hiatal area was 22 cm 2 (SD, 7 range, 5–49 cm 2 ) at rest and 30 cm 2 (SD, 10 range, 11–69 cm 2 ) on Valsalva. Genital hiatus and Pb measured on Valsalva were consistently stronger predictors of prolapse symptoms and objective prolapse (by clinician examination and by ultrasound) than at Gh and Pb measured at rest. The corresponding area under the curve values were significantly larger for Gh/Pb measures on Valsalva after adjusting for multiple confounders. Genital hiatus/Pb measured on maximal Valsalva is a superior predictor of symptoms and signs of POP compared with Gh/Pb at rest.
Publisher: Oxford University Press (OUP)
Date: 10-08-2016
DOI: 10.1111/BJD.14662
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JPAINSYMMAN.2019.07.022
Abstract: Physical activity for women with early-stage breast cancer is well recognized for managing cancer-related symptoms and improving quality of life. While typically excluded from interventions, women with metastatic breast cancer may also benefit from physical activity. To 1) determine the safety and feasibility of a physical activity program for women with metastatic breast cancer and 2) explore the efficacy of the program. Fourteen women with metastatic breast cancer were randomized to either a control group or an 8-week home-based physical activity intervention comprising twice weekly supervised resistance training and an unsupervized walking program. The recruitment rate was 93%. Adherence to the resistance and walking components of the program was 100% and 25%, respectively. No adverse events were reported. When mean change scores from baseline to postintervention were compared, trends in favor of the exercise group over the control group were observed for the Functional Assessment of Chronic Illness Therapy-Fatigue score (+5.6 ± 3.2 vs. -1.8 ± 3.9, respectively), VO A partially supervised home-based physical activity program for women with metastatic breast cancer is feasible and safe. The dose of the resistance training component was well tolerated and achievable in this population. In contrast, adherence and compliance to the walking program were poor. Preliminary data suggest a physical activity program, comprising predominantly resistance training, may lead to improvements in physical capacity and may help women to live well with their disease.
Publisher: Wiley
Date: 30-07-2021
DOI: 10.1111/BJU.15552
Abstract: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography‐guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. We conducted a multicentre, placebo‐controlled, double‐blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient‐controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0–10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists’ ratings, biopsy completion, and adverse events. The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] −0.75 to 0.14 P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference −0.48, 95% CI −0.92 to −0.03 P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference −0.50, 95% CI −0.92 to −0.08 P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12–2.49 P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21–2.07 P 0.001, adj. P 0.001) and dizziness (difference +1.78, 95% CI 1.31–2.24 P 0.001, adj. P 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events. We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient‐reported discomfort, overall experience, and willingness to undergo repeat biopsies.
Publisher: Wiley
Date: 18-02-2014
DOI: 10.1111/AJO.12171
Abstract: Female pelvic organ prolapse is a common condition. Prolapse recurrence following surgical treatment is a significant clinical issue. The aim of this study was to determine risk factors for recurrence, attempting to improve clinical practice by allowing better patient selection prior to surgery. This was a retrospective study utilising patient records and ultrasound volume imaging data sets obtained in four clinical audits following anterior colporrhaphy ± mesh. Prolapse recurrence was diagnosed clinically and by ultrasound findings were analysed against potential predictors. Symptomatic prolapse recurrence was demonstrated in 86 (26%), on clinical examination in 141 (42%) and on ultrasound in 113/334 women (34%). None of the tested predictors were predictive of recurrent symptoms, likely due to a lack of power. However, both levator avulsion and hiatal area on Valsalva were shown to be highly significant predictors of objective prolapse recurrence on clinical examination and ultrasound. Prolapse recurrence following surgery is a common complaint. The state of the patient's pelvic floor muscle seems to be the strongest determinant.
Publisher: SAGE Publications
Date: 20-02-2013
Abstract: To describe the use of psychotropic agents in a s le of subjects with obsessive–compulsive disorder (OCD), and in particular the differences associated with different OCD symptoms. A total of 154 subjects participated in a study assessing OCD symptom subtypes, called the Nepean OCD Study. In addition to a comprehensive evaluation of the subjects’ OCD symptoms using the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS), Vancouver Obsessive–Compulsive Inventory (VOCI), and the Sheehan Disability Scale (SDS), the subjects’ medication history was recorded. The association between symptom severity, disability, OCD symptom subtypes and the use of psychotropic agents was examined. Psychotropic medication was taken by 93 (60.4%) participants. In the majority of cases ( n=55, 59.1%), selective serotonin reuptake inhibitors (SSRIs) were taken, and of the SSRIs, the most commonly used agent was escitalopram ( n=21, 22.6%). Psychotropic agents were more likely to be taken by subjects with higher Y-BOCS and SDS scores. Hoarding was associated with a lower likelihood of psychotropic use, whereas unacceptable/taboo thoughts were associated with an increased likelihood of psychotropic and antipsychotic use. Patients with OCD are more likely to be taking psychotropic agents if they have a more severe illness, greater disability and more prominent unacceptable/taboo thoughts.
Publisher: Springer Science and Business Media LLC
Date: 02-2020
DOI: 10.1039/C9PP00388F
Abstract: Nicotinamide (NAM), an amide form of vitamin B3, replenishes cellular energy after ultraviolet radiation (UVR) exposure, thereby enhancing DNA repair and reducing UVR's immunosuppressive effects. NAM reduces actinic keratoses and new keratinocyte cancers in high risk in iduals, but its effects on melanoma are unknown. Melanomas arising on NAM or placebo within the ONTRAC skin cancer chemoprevention trial (Oral Nicotinamide To Reduce Actinic Cancer) were examined by immunohistochemistry. The effects of NAM (50 μM, 5 mM and 20 mM) on the viability, proliferation and invasiveness of four human melanoma cell lines and on the viability and proliferation of two human melanocyte lines, with and without UV irradiation were also investigated. 50 μM NAM did not affect viability, proliferation or invasion of melanoma or melanocyte cell lines, whereas concentrations too high to be achievable in vivo reduced viability and proliferation. Nicotinamide did not enhance melanoma viability, proliferation or invasiveness in vitro, providing additional confidence in its safety for use in clinical trials in high risk patients. Peritumoral and tumour infiltrating CD4+ and CD8+ lymphocytes were significantly increased in melanomas arising on NAM compared to those arising on placebo. Given the chemopreventive activity of nicotinamide against keratinocyte cancers, its DNA repair enhancing effects in melanocytes and now its potential enhancement of tumour-infiltrating lymphocytes and lack of adverse effects on melanoma cell growth and proliferation, clinical trials of nicotinamide for melanoma chemoprevention are now indicated.
Publisher: Springer Science and Business Media LLC
Date: 23-10-2020
DOI: 10.1007/S00520-019-05095-3
Abstract: The causal link between chemotherapy and cognitive impairment is unclear. We studied testicular cancer patients' objective and subjective cognitive function longitudinally, comparing a surgery group with a surgery + chemotherapy group, addressing prior methodological issues using a computerized test to limit assessment issues, and controlling for confounding variables. Prospectively, of 145 patients from 16 centres with sufficient data, n = 61 receiving surgery + chemotherapy (etoposide and cisplatin ± bleomycin, BEP/EP or single agent carboplatin) were compared to n = 41 receiving surgery alone. CogHealth assessed six objective cognitive tasks. The Cognitive Failures Questionnaire assessed self-perceived cognitive dysfunction. The Functional Assessment of Chronic Illness Therapy-Fatigue and the Hospital Anxiety and Depression Scale assessed psychological influences. Linear mixed models compared changes from baseline (< 6 months post-surgery re-chemotherapy) to follow-up (12-18 months post-baseline), controlling covariates. There were no significant interaction effects for five objective cognitive function tasks suggesting that changes over time were not due to group membership. However, psychomotor function (controlling for age) and physical well-being were significantly worse for the chemotherapy versus the surgery group at baseline, with groups converging by follow-up. Groups showed no differences in subjective cognitive dysfunction. The chemotherapy group showed higher anxiety, poorer functional well-being and worse fatigue compared to the surgery-only group at baseline, but not by follow-up. For both groups, emotional well-being, functional well-being and anxiety significantly improved over time. No substantive differences in objective or subjective cognitive dysfunction in either group persisted 12-18 months post-baseline. Patients undergoing chemotherapy for testicular cancer differ from findings in breast cancer populations. ClinicalTrials.gov Identifier: ACTRN12609000545268.
Publisher: Springer Science and Business Media LLC
Date: 22-01-2021
DOI: 10.1186/S13063-020-04984-X
Abstract: For prospective meta-analyses (PMAs), eligible studies are identified, and the PMA hypotheses, selection criteria, and analysis methods are pre-specified before the results of any of the studies are known. This reduces publication bias and selective outcome reporting and provides a unique opportunity for outcome standardisation/harmonisation. We conducted a world-first PMA of four trials investigating interventions to prevent early childhood obesity. The aims of this study were to quantitatively analyse the effects of prospective planning on variations across trials, outcome harmonisation, and the power to detect intervention effects, and to derive recommendations for future PMA. We examined intervention design, participant characteristics, and outcomes collected across the four trials included in the EPOCH PMA using their registration records, protocol publications, and variable lists. The outcomes that trials planned to collect prior to inclusion in the PMA were compared to the outcomes that trials collected after PMA inclusion. We analysed the proportion of matching outcome definitions across trials, the number of outcomes per trial, and how collaboration increased the statistical power to detect intervention effects. The included trials varied in intervention design and participants, this improved external validity and the ability to perform subgroup analyses for the meta-analysis. While in idual trials had limited power to detect the main intervention effect (BMI z -score), synthesising data substantially increased statistical power. Prospective planning led to an increase in the number of collected outcome categories (e.g. weight, child’s diet, sleep), and greater outcome harmonisation. Prior to PMA inclusion, only 18% of outcome categories were included in all trials. After PMA inclusion, this increased to 91% of outcome categories. However, while trials mostly collected the same outcome categories after PMA inclusion, some inconsistencies in how the outcomes were measured remained (such as measuring physical activity by hours of outside play versus using an activity monitor). Prospective planning led to greater outcome harmonisation and greater power to detect intervention effects, while maintaining acceptable variation in trial designs and populations, which improved external validity. Recommendations for future PMA include more detailed harmonisation of outcome measures and careful pre-specification of analyses to avoid research waste by unnecessary over-collection of data.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.EURURO.2021.05.016
Abstract: Men who initially present with localized prostate cancer and later develop metachronous metastases have a better prognosis than men with de novo metastatic disease and often have a low burden of disease on conventional imaging. Some have disease amenable to metastasis-directed therapy for lymph node or bone metastases, a strategy used by some because no documented overall survival (OS) benefit of combination systemic therapy in this setting. We report data for patients prospectively classified as "M0" at initial diagnosis from the interim analysis of the ENZAMET trial, with 34 mo of median follow-up for survivors. A total of 312 (28%) of the 1125 enrolled patients were classified as M0 at diagnosis, and 205 (66%) of the 312 patients had low-volume disease at study entry as per the CHAARTED criteria. The hazard ratio for OS, that is, HR(OS), was 0.56 (95% confidence interval [CI]: 0.29-1.06) with the addition of enzalutamide for all patients with metachronous metastatic hormone-sensitive prostate cancer, and for the low-volume subset the HR(OS) was 0.40 (95% CI: 0.16-0.97). The 3-yr OS was 83% without and 89% with enzalutamide for all patients with metachronous metastases, and 83% and 92%, respectively, for the low-volume subset. Intensification of hormonal therapy should strongly be considered for these men. PATIENT SUMMARY: Many men present with prostate cancer that has spread to distant sites beyond the prostate gland years after their initial diagnosis and treatment, while others have distant spread at the time the cancer is diagnosed. On average, men whose cancer comes back years after the initial diagnosis often survive much longer than men whose cancer has been found to spread to distant sites when it is first diagnosed. In this report, we demonstrate strong evidence for the first time that the survival of men whose cancer comes back years later is improved when drugs such as enzalutamide or apalutamide are added to testosterone suppression in this setting.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2017
DOI: 10.1007/S00520-017-3843-0
Abstract: Oncologists are making treatment decisions on increasing numbers of older patients with cancer. Due to comorbidities and frailty that increase with age, such decisions are often complex. We determined factors influencing oncologists' decisions to prescribe chemotherapy for older adults. Members of the Medical Oncology Group of Australia (MOGA) were invited to complete an online survey in February to April 2016. Ninety-three oncologists completed the survey of which 69 (74%) were consultants and 24 (26%) were trainees, with most (72, 77%) working predominantly in a public hospital-associated practice. The three highest ranked factors influencing decisions about (a) adjuvant chemotherapy were performance status, survival benefit of treatment, and life expectancy in the absence of cancer and about (b) palliative chemotherapy were performance status, patient preference, and quality of life. Most geriatric health domains are reportedly assessed routinely by the majority of respondents, though few routinely use geriatric screening tools (14%) or geriatric assessments (5%). In hypothetical patient scenarios, oncologists were less likely to prescribe palliative and adjuvant chemotherapy as age and rates of severe toxicity increased. Performance status was the most influential factor for oncologists when making a decision about chemotherapy for their older patients, and the importance of other factors differed according to treatment intent. Oncologists were less likely to recommend chemotherapy as patient age and treatment toxicity increased. The low uptake of geriatric assessments or screening tools provides scope for improved clinical assessment of older adults in treatment decision-making.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-02-2022
DOI: 10.1200/JCO.2022.40.6_SUPPL.166
Abstract: 166 Background: 177 Lutetium PSMA-617 (LuPSMA) is an effective therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance may occur. We developed a quantitative workflow for serial PSMA PET/CT to optimise predictive and prognostic imaging biomarker capability for progression free (PFS) and overall survival (OS). Methods: 56 men with mCRPC previously treated with taxane chemotherapy and androgen signaling inhibitor were enrolled, receiving up to 6 doses of LuPSMA and a radiation sensitizer idronoxil (NOX66). 68 Ga-PSMA-11 PET/CT was performed at study entry and exit. Traffic Light (TL) quantification workflow was developed to track changes in both tumour volume and intensity at a total body and lesional level. Lesions were classified as responding in green ( % decline in volume), stable in yellow ( % change in volume/intensity), progressive in red ( % increase in volume/intensity, or new). Overall response pattern was categorised as responding ( green/yellow), low volume red ( % progressive disease) or high volume red ( % progressive disease). TL workflow results were correlated with PFS and OS. Results: 37/56 men underwent both entry and exit imaging. The median PSA decline was 77% (IQR 34-92%), and 70% (26/37) achieved PSA response %. PSA progression occurred in 54% (20/37) at exit imaging. Median PFS was 8.6 months (95%CI 5.6-11.6) and median OS 22 months (95% CI 18.6-25.6). 95% (35/37) had reduction in PSMA SUVmax (-26.1 (IQR +11.7 to -89.4)) and SUVmean (-3.3 (+2.9 to -14.2)). PSMA total tumor volume reduced in 68% (25/37) (median -0.64 liters (range +1.44 to -1.1)). On TL workflow, 24% (9/37) had responding/stable disease ( green/ yellow), 76% (28/37) had progressive disease ( red) of whom 41% (15/37) had low volume progression and 35% (13/37) high volume progression. Men with high volume progression had worse OS compared to responders (HR 0.18 (0.05-0.59), p 0.005), and low volume progression (HR 0.30 (0.11-0.80), p 0.02). 68% (19/28) had progression on both TL workflow and PSA, while 32% (9/28) had progression on TL workflow without PSA progression. In multivariable analysis, TL workflow and PSA progression at time of exit scans were independent predictors of OS (Table). Conclusions: This study demonstrates the feasibility of characterizing lesional response on molecular imaging with a quantification TL workflow. TL workflow response independently correlated with survival outcomes, indicating serial PSMA PET has prognostic biomarker potential. Clinical trial information: ACTRN12618001073291.[Table: see text]
Publisher: Wiley
Date: 10-2012
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.COMPPSYCH.2013.02.005
Abstract: In the quest to unravel the heterogeneity of obsessive-compulsive disorder (OCD), an increasing number of factor analytic studies are recognising unacceptable/taboo thoughts as one of the symptom dimensions of OCD. This study aims to examine the characteristics associated with unacceptable/taboo thoughts. Using the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (YBOCS-SC) with 154 in iduals with OCD, obsessive-compulsive symptoms were subjected to principal components analysis. The characteristics associated with the resulting symptom dimensions were then assessed using logistic and linear regression techniques. Unacceptable/taboo thoughts comprised of sexual, religious and impulsive aggressive obsessions, and mental rituals. Higher scores on an unacceptable/taboo thoughts symptom dimension were predicted by higher Y-BOCS obsession subscores, Y-BOCS time preoccupied by obsessions scores, Y-BOCS distress due to obsessions scores, importance of control of thought ratings, male gender, and having had treatment prior to entering into the study. Unacceptable/taboo thoughts were also predicted by greater levels of hostility, and a past history of non-alcohol substance dependence. An unacceptable/taboo thought symptom dimension of OCD is supported by a unique set of associated characteristics that should be considered in the assessment and treatment of in iduals with these symptoms.
Publisher: Wiley
Date: 13-12-2013
DOI: 10.1002/IJC.27956
Abstract: It is now clear that the two separate entitles of tonsillar cancer, HPV induced and non-HPV induced (smoking induced), have significantly different presenting stage and outcomes. A significant proportion of patients with human papillomavirus positive tonsillar cancer have had exposure to smoking. We examined the combined effect of human papillomavirus and smoking on the outcomes and determined whether smoking can modify the beneficial effect of human papillomavirus. A total of 403 patients from nine centers were followed up for recurrence or death for a median of 38 months. Determinants of the rate of loco-regional recurrence, death from tonsillar cancer and overall survival were modeled using Cox regression. Smoking status was a significant predictor of overall survival (p = 0.04). There were nonstatistically significant trends favoring never smokers for loco-regional recurrence and disease specific survival. In addition, there was no statistically significant interactions between smoking and human papillomavirus (p-values for the interaction were 0.26 for loco-regional recurrence, 0.97 for disease specific survival and 0.73 for overall survival). The effect of smoking on loco-regional recurrence and disease specific survival outcomes was not statistically significant, nor was there significant evidence that the effect of smoking status on these outcomes was modified by HPV status. Irrespective of HPV status, however, smokers did have poorer overall survival than never-smokers, presumably due to effects of smoking that are unrelated to the primary cancer.
Publisher: Springer Science and Business Media LLC
Date: 27-05-2015
Publisher: European Respiratory Society (ERS)
Date: 24-09-2015
DOI: 10.1183/13993003.00577-2015
Abstract: We aimed to develop a decision aid that estimates whether treatment of latent tuberculosis infection (LTBI) is likely to have a net gain in quality-adjusted life-years for an in idual. A Markov model was developed which incorporated personalised estimates for risk of tuberculosis (TB) reactivation, TB death, quality-of-life impairments and treatment side-effects. The net effect of LTBI treatment was quantified in terms of quality-adjusted life-years gained or lost. Analyses were conducted for a representative set of hypothetical patients. LTBI treatment was estimated to be beneficial when the annual risk of TB reactivation exceeded 13/100 000 to 93/100 000 for females aged 10–75 years and 15/100 000 to 119/100 000 for males aged 10–75 years the numbers needed to treat to avoid one case of TB were 93, 77, 85 and 72, respectively, at these threshold levels. LTBI treatment was estimated to confer a positive net benefit across a broad range of patients with characteristics typically seen in a low incidence setting for TB. Use of the decision aid has the potential to facilitate and increase confidence with LTBI treatment decisions by providing clinicians and patients with personalised estimates of likely net benefit.
Publisher: AMPCo
Date: 04-2010
DOI: 10.5694/J.1326-5377.2002.TB04883.X
Abstract: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels. Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo. 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992. Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life. The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subs le of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health) the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107 730 (95% CI, $68 626-$209 881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%). Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.
Publisher: Elsevier BV
Date: 09-2019
Publisher: SAGE Publications
Date: 06-1998
DOI: 10.1177/016327879802100202
Abstract: This article reviews the different ways in which quality-of-life assessment has been applied to and has affected health care research and practice. A schema that describes the steps involved in the ongoing challenge of improving health outcomes is used to structure the review. The role of quality-of-life assessment is addressed with regard to: the identification of health problems, the evaluation of new treatments, the formulation of treatment guidelines and health policies, the delivery of optimal care in practice, and the assessment of outcomes in the wider community. The benefit of quality-of-life assessment has been demonstrated in a number of these areas (e.g., in identifying problems and evaluating treatments). Its role in other applications (e.g., in clinical practice to assess patients' needs) shows great promise and requires additional evaluation.
Publisher: Society of Nuclear Medicine
Date: 29-11-8022
No related grants have been discovered for Andrew Martin.