Catherine D'Este

Data Resource Profile: The World Health Organization Study on global AGEing and adult health (SAGE)

Population ageing is rapidly becoming a global issue and will have a major impact on health policies and programmes. The World Health Organizations Study on global AGEing and adult health (SAGE) aims to address the gap in reliable data and scientific knowledge on ageing and health in low- and middle-income countries. SAGE is a longitudinal study with nationally representative samples of persons aged 50+ years in China, Ghana, India, Mexico, Russia and South Africa, with a smaller sample of adults aged 18-49 years in each country for comparisons. Instruments are compatible with other large high-income country longitudinal ageing studies. Wave 1 was conducted during 2007-2010 and included a total of 34 124 respondents aged 50+ and 8340 aged 18-49. In four countries, a subsample consisting of 8160 respondents participated in Wave 1 and the 2002/04 World Health Survey (referred to as SAGE Wave 0). Wave 2 data collection will start in 2012/13, following up all Wave 1 respondents. Wave 3 is planned for 2014/15. SAGE is committed to the public release of study instruments, protocols and meta- and micro-data: access is provided upon completion of a Users Agreement available through WHOs SAGE website (www.who.int/healthinfo/systems/sage) and WHOs archive using the National Data Archive application (http://apps.who.int/healthinfo/systems/surveydata).

Meta-analyses of molecular association studies: Methodologic lessons for genetic epidemiology

Meta-analyses of population-based molecular association studies have become increasingly common over the last 10 years, but little attention has been paid to methodology. In addition to the traditional considerations pertinent to any meta-analysis, there are genetic issues particular to molecular association studies: checking Hardy-Weinberg equilibrium, handling data from more than two groups while avoiding multiple comparisons, and pooling data in a way that is sensitive to genetic models. We systematically reviewed all meta-analyses of molecular association studies identified via MEDLINE. Of a total of 37 studies, eight (22%) described the search terms. Nineteen (51%) did not state inclusion or exclusion criteria. Heterogeneity was assessed in 28 (76%), but only 7 of 37 (19%) studies checked for publication bias. Nine (24%) studies assessed the goodness-of-fit of Hardy-Weinberg equilibrium, and eight (22%) gave any biological rationale to justify the choice of genetic model used for pooling. There is a need for greater communication between epidemiologists and geneticists to develop methods appropriate to this area.

Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial

BACKGROUND The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant androgen deprivation therapy (NADT) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer. Here we report the 10-year results. METHODS Between June, 1996, and February, 2000, 818 men with T2b, T2c, T3, and T4 N0 M0 prostate cancers were randomly assigned to receive radiotherapy alone, 3 months of NADT plus radiotherapy, or 6 months of NADT plus radiotherapy. The radiotherapy dose for all groups was 66 Gy, delivered to the prostate and seminal vesicles (excluding pelvic nodes) in 33 fractions of 2 Gy per day (excluding weekends) over 6·5-7·0 weeks. NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day. NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group. Primary endpoints were prostate-cancer-specific mortality and all-cause mortality. Treatment allocation was open label and randomisation was done with a minimisation technique according to age, clinical stage, tumour grade, and initial prostate-specific antigen concentration (PSA). Analysis was by intention-to-treat. The trial has been closed to follow-up and all main endpoint analyses are completed. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482. FINDINGS 802 men were eligible for analysis (270 in the radiotherapy alone group, 265 in the 3-month NADT group, and 267 in the 6-month NADT group) after a median follow-up of 10·6 years (IQR 6·9-11·6). Compared with radiotherapy alone, 3 months of NADT decreased the cumulative incidence of PSA progression (adjusted hazard ratio 0·72, 95% CI 0·57-0·90; p=0·003) and local progression (0·49, 0·33-0·73; p=0·0005), and improved event-free survival (0·63, 0·52-0·77; p<0·0001). 6 months of NADT further reduced PSA progression (0·57, 0·46-0·72; p<0·0001) and local progression (0·45, 0·30-0·66; p=0·0001), and led to a greater improvement in event-free survival (0·51, 0·42-0·61, p<0·0001), compared with radiotherapy alone. 3-month NADT had no effect on distant progression (0·89, 0·60-1·31; p=0·550), prostate cancer-specific mortality (0·86, 0·60-1·23; p=0·398), or all-cause mortality (0·84, 0·65-1·08; p=0·180), compared with radiotherapy alone. By contrast, 6-month NADT decreased distant progression (0·49, 0·31-0·76; p=0·001), prostate cancer-specific mortality (0·49, 0·32-0·74; p=0·0008), and all-cause mortality (0·63, 0·48-0·83; p=0·0008), compared with radiotherapy alone. Treatment-related morbidity was not increased with NADT within the first 5 years after randomisation. INTERPRETATION 6 months of neoadjuvant androgen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation. FUNDING Australian Government National Health and Medical Research Council, Hunter Medical Research Institute, AstraZeneca, and Schering-Plough.

Meta-Analysis of Molecular Association Studies: Vitamin D Receptor Gene Polymorphisms and BMD as a Case Study†

With the rise of molecular and genetic epidemiology, molecular association studies are increasingly common; however, meta‐analysis of these studies has been a neglected area. This study performed a meta‐analysis of the association of the vitamin D receptor (VDR) gene polymorphisms and BMD. We also highlight methodological issues that need to be resolved.

Postcards from the EDge project: randomised controlled trial of an intervention using postcards to reduce repetition of hospital treated deliberate self poisoning

Abstract Objective To determine whether an intervention using postcards (postcards from the EDge project) reduces repetitions of hospital treated deliberate self poisoning. Design Randomised controlled trial. Setting Regional referral service for general hospital treated deliberate self poisoning in Newcastle, Australia. Participants 772 patients aged over 16 years with deliberate self poisoning. Intervention Non-obligatory intervention using eight postcards over 12 months along with standard treatment compared with standard treatment alone. Main outcome measures Proportion of patients with one or more repeat episodes of deliberate self poisoning and the number of repeat episodes for deliberate self poisoning per person in 12 months. Results The proportion of repeaters with deliberate self poisoning in the intervention group did not differ significantly from that in the control group (57/378, 15.1%, 95% confidence interval 11.5% to 18.7% v 68/394, 17.3%, 13.5% to 21.0%: difference between groups -2%, -7% to 3%). In unadjusted analysis the number of repetitions were significantly reduced (incidence risk ratio 0.55, 0.35 to 0.87). Conclusion A postcard intervention reduced repetitions of deliberate self poisoning, although it did not significantly reduce the proportion of individual repeaters.

Postcards from the EDge: 24-month outcomes of a randomised controlled trial for hospital-treated self-poisoning

BACKGROUND Repetition of hospital-treated self-poisoning and admission to psychiatric hospital are both common in individuals who self-poison. AIMS To evaluate efficacy of postcard intervention after 5 years. METHOD A randomised controlled trial of individuals who have self-poisoned: postcard intervention (eight in 12 months) plus treatment as usual v. treatment as usual. Our primary outcomes were self-poisoning admissions and psychiatric admissions (proportions and event rates). RESULTS There was no difference between groups for any repeat-episode self-poisoning admission (intervention group: 24.9%, 95% CI 20.6-29.5; control group: 27.2%, 95% CI 22.8-31.8) but there was a significant reduction in event rates (incidence risk ratio (IRR) = 0.54, 95% CI 0.37-0.81), saving 306 bed days. There was no difference for any psychiatric admission (intervention group: 38.1%, 95% CI 33.1-43.2; control group: 35.5%, 95% CI 30.8-40.5) but there was a significant reduction in event rates (IRR = 0.66, 95% CI 0.47-0.91), saving 2565 bed days. CONCLUSIONS A postcard intervention halved self-poisoning events and reduced psychiatric admissions by a third after 5 years. Substantial savings occurred in general hospital and psychiatric hospital bed days.

Cohort Profile: The Hunter Community Study

In almost every country, the proportion of people aged 460 years is growing faster than any other age group and is expected to reach 2 billion worldwide by 2050. Internationally and nationally, considerable efforts are being made to promote active ageing. However, Australia lacks the kind of comprehensive longitudinal research underway in Europe and North America. Although Australia does have a number of longitudinal studies designed to address various issues of health and ageing among older adults, only a few of these studies include a broad and comprehensive range of physical and biological measures. The Hunter Community Study (HCS) is a collaborative study between the University of Newcastle’s School of Medicine and Public Health and the Hunter New England Area Health Service. It is a multi disciplinary initiative that was established to fill some existing gaps in ageing research in Australia and is unique in that it has collected detailed information across all six key policy themes as identified in the Framework for an Australian Ageing Research Agenda. What does the study cover?

Time to biochemical failure and prostate-specific antigen doubling time as surrogates for prostate cancer-specific mortality : evidence from the TROG 96.01 randomised controlled trial

BACKGROUND Surrogate endpoints for prostate cancer-specific mortality after curative primary treatment are not well established. We sought to assess time to biochemical failure (TTBF) and prostate-specific antigen doubling time (PSADT) after failure of curative treatment as candidates for this endpoint. METHODS PSA and survival data from the Trans-Tasman Radiation Oncology Group (TROG) 96.01 trial were used to assess surrogate candidates. Between June 28, 1996, and Feb 16, 2000, 802 eligible men with locally advanced prostate cancer were randomly allocated to prostatic irradiation alone, or to 3 or 6 months of maximum short-term androgen deprivation (STAD) before and during radiation. Successful surrogates were required to satisfy the Prentice criteria and to predict the trial finding. The TROG 96.01 trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482. FINDINGS 6 months of STAD was shown to significantly decrease prostate cancer-specific mortality compared with radiation alone, but 3 months of STAD did not result in a decrease. Relative to radiation alone, the hazard ratio of prostate cancer-specific mortality from randomisation was 0.95 (95% CI 0.63-1.41; p=0.79) in the 3-month STAD treatment arm and 0.56 (0.36-0.88; p=0.01) in the 6-month arm. PSADT predicted the trial finding and satisfied all four Prentice criteria at the cutpoints of less than 12 months and less than 15 months, with proportion of treatment effect ratios between 0.36 and 0.56. Time to biochemical failure was better than PSADT at predicting the trial finding and satisfying all four Prentice criteria at cutpoints of less than 1.5, less than 2, and less than 2.5 years, with proportion of treatment effect ratios between 0.45 and 0.64. INTERPRETATION This study provides proof of principle that TTBF and PSADT can be useful as surrogate endpoints for prostate cancer-specific mortality and offer potential to substantially reduce follow up in clinical trials. These endpoints now require assessment in multi-trial meta-analyses before use in clinical trials.

Prevalence and predictors of the short-term trajectory of anxiety and depression in the first year after a cancer diagnosis: a population-based longitudinal study.

PURPOSE Few studies have examined psychological adjustment for cancer survivors in late treatment and early survivorship stages. Our study investigated the prevalence and short-term trajectories of anxiety, depression, and comorbid anxiety-depression among adult cancer survivors, and identified the individual, disease, health behavior, psychological, and social predictors of chronic and late psychological morbidity. METHODS A heterogeneous sample of adult cancer survivors was recruited from two state-based cancer registries. A total of 1,154 survivors completed self-report questionnaires at 6 (Time 1) and 12 months (Time 2) postdiagnosis. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale with cases identified by a subscale cutoff score ≥ 8. Logistic regression analyses identified Time 1 characteristics associated with anxiety and/or depression at Time 2. RESULTS The point prevalence of anxiety (Time 1, 22%; Time 2, 21%), depression (13% at both timepoints) and comorbid anxiety-depression (9% at both timepoints) was similar at 6 and 12 months postdiagnosis. The most prevalent Time 1 to Time 2 trajectory was noncase for anxiety (70%), depression (82%), and comorbid anxiety-depression (87%). While psychological morbidity at Time 1 was the strongest predictor of psychological morbidity at Time 2, being diagnosed with lung cancer and health risk behaviors (smoking, insufficient physical activity) were also strong predictors. CONCLUSION Targeted psychological screening of vulnerable survivors and early intervention may prevent the onset and/or reduce the severity of psychological morbidity in early survivorship. Trials of risk reduction interventions targeting psychological functioning and health risk behaviors seem warranted.

Are prisoners reliable survey respondents? A validation of self-reported traumatic brain injury (TBI) against hospital medical records

Aims: To compare prisoners’ self-reported history of TBI associated with hospital attendance with details extracted from relevant hospital medical records and to identify factors associated with the level of agreement between the two sources. Methods: From a sample of prison entrants, this study obtained a history of TBIs for which medical attention was sought at a hospital. Audit tools were developed for data extraction relevant to any possible TBI from records at a total of 23 hospitals located within New South Wales, Australia. The level of agreement between self-report and hospital records was compared in relation to demographic, psychological and criminographic characteristics. Results: Of the 200 participants in the study, 164 (82%) reported having sustained a past TBI giving a total of 420 separate TBI incidents. Of these, 156 (37%) were alleged to have resulted in attendance at a hospital emergency department including 112 (72%) at a hospital accessible for the validation exercise. For 93/112 (83%) of reported TBIs, a corresponding hospital medical record was located of which 78/112 (70%) supported the occurrence of a TBI. Lower education and a lifetime history of more than seven TBIs were associated with less agreement between self-report and medical record data with regard to specific details of the TBI. Conclusions: Overall, these findings suggest that prisoners’ self-report of TBI is generally accurate when compared with the ‘gold standard’ of hospital medical record. This finding is contrary to the perception of this group as ‘dishonest’ and ‘unreliable’.