Social deprivation predicts adverse health outcomes after hospital admission with hip fracture in England.

We found social deprivation to be associated with higher mortality in the year following hip fracture among men and women aged 60 years and older in England. In those who did survive, deprivation was associated with longer hospital stays and greater risk of subsequent emergency readmission particularly for patients with dementia. INTRODUCTION: Social deprivation predicts a range of adverse health outcomes; however, its impact on outcomes following hip fracture is not established. We examined the effect of area-level social deprivation on outcomes following hospital admission for hip fracture in England. METHODS: We used English Hospital Episodes Statistics linked to the National Hip Fracture Database (April 2011-March 2015) and Office for National Statistics mortality database, to identify patients aged 60+ years admitted with hip fracture. Deprivation was measured using Index of Multiple Deprivation quintiles; Q1-least deprived; Q5-most deprived, and outcomes by mortality over 1-year, length-of-stay in NHS acute and rehabilitation hospitals ('superspell'), and emergency 30-day readmission. RESULTS: We identified 218,907 admissions with an index hip fracture (mean age 82.8 [standard deviation, SD 8.4] years; 72.6% female). Each quintile of deprivation was associated with greater mortality; age-adjusted 30-day mortality odds ratio, OR 1.30 [95% confidence interval, CI: 1.24, 1.37], p < 0.001, equating to on average 1038 fewer deaths/year among those who are least deprived (Q1 versus 2-5). Similarly, at 365 days, those most deprived had 24% higher mortality (age-sex-comorbidity-adjusted OR:1.24 [1.20, 1.28], p < 0.001; Q5 versus Q1). Among survivors, mean superspell was longer in the most versus least deprived (Q5:24.4 [SD 21.7] days, Q1:23.3 [SD 22.1], p < 0.001). Readmission was more common in those most versus least deprived (age-sex-comorbidity-adjusted OR 1.27 [1.22, 1.32], p < 0.001). CONCLUSION: Greater deprivation is associated with reduced survival at all timepoints in the year following hip fracture. Among survivors, hospital stay is increased as is readmission risk. The extent to which configuration of English hospital services, rather than patient case-mix, explains these apparent health inequalities remains to be determined.

Socio-economic inequalities in fragility fracture incidence: a systematic review and meta-analysis of 61 observational studies.

Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fractures than individuals with high SES. Body mass index and lifestyle appear to mediate the effect of SES on fracture risk. Strategies to prevent fractures should aim to reduce unhealthy behaviours through tackling structural inequalities. INTRODUCTION: This systematic review and meta-analysis aimed to evaluate the impact of socio-economic status (SES) on fragility fracture risk. METHODS: Medline, Embase, and CINAHL databases were searched from inception to 28 April 2021 for studies reporting an association between SES and fragility fracture risk among individuals aged ≥50 years. Risk ratios (RR) were combined in meta-analyses using random restricted maximum likelihood models, for individual-based (education, income, occupation, cohabitation) and area-based (Index of Multiple Deprivation, area income) SES measures. RESULTS: A total of 61 studies from 26 different countries including more than 19 million individuals were included. Individual-based low SES was associated with an increased risk of fragility fracture (RR 1.27 [95% CI 1.12, 1.44]), whilst no clear association was seen when area-based measures were used (RR 1.08 [0.91, 1.30]). The strength of associations was influenced by the type and number of covariates included in statistical models: RR 2.69 [1.60, 4.53] for individual-based studies adjusting for age, sex and BMI, compared with RR 1.06 [0.92, 1.22] when also adjusted for health behaviours (smoking, alcohol, and physical activity). Overall, the quality of the evidence was moderate. CONCLUSION: Our results show that low SES, measured at the individual level, is a risk factor for fragility fracture. Low BMI and unhealthy behaviours are important mediators of the effect of SES on fracture risk. Strategies to prevent fractures and reduce unhealthy behaviours should aim to tackle structural inequalities in society thereby reducing health inequalities in fragility fracture incidence.

Cholinesterase inhibitor to prevent falls in Parkinson's disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease.

BACKGROUND: Falls are a common complication of Parkinson's disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson's disease. METHODS: This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson's motor and non-motor symptoms, quality of life and cost-effectiveness. DISCUSSION: This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson's disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population. TRIAL REGISTRATION: REC reference: 19/SW/0043. EudraCT: 2018-003219-23. ISCRTN: 41639809 (registered 16/04/2019). ClinicalTrials.gov Identifier: NCT04226248 PROTOCOL AT TIME OF PUBLICATION: Version 7.0, 20th January 2021.

How does deprivation influence secondary care costs after hip fracture?

We studied the association between deprivation and healthcare costs after hip fracture. Hospital costs in the year following hip fracture were £1120 higher for those living in more deprived areas. Most of this difference was explained by pre-existing health inequalities which should be targeted to reduce this disparity. INTRODUCTION: To quantify differences in hospital costs following hip fracture between those living in higher and lower deprivation areas of England, we investigate pre- and post-fracture variables that explain the association. METHODS: We used English Hospital Episodes Statistics linked to the National Hip Fracture Database (April 2011-March 2015) and national mortality data to identify patients admitted with hip fracture aged 60+ years. Hospital care was costed using 2017/2018 national reference costs, by index of multiple deprivation quintile. Three generalised linear model regressions estimated associations between deprivation and costs and the pre- and post-fracture variables that mediate this relationship. RESULTS: Patients from the most deprived areas had higher hospital costs in the year post-fracture (£1,120; 95% CI £993 to £1,247) than those from the least deprived areas. If all patients could have incurred similar costs to those in the least deprived quintile, this would equate to an annual reduction in expenditure of £28.8 million. Pre-fracture characteristics, particularly comorbidities and anaesthetic risk grade, accounted for approximately 50% of the association between deprivation and costs. No evidence was found that post-fracture variables, such as transfer to a residential or nursing home, contributed to the association between deprivation and costs. CONCLUSIONS: Socioeconomic inequalities are associated with substantial costs for the NHS after hip fracture. We did not identify post-fracture targets for intervention to reduce the impact of inequalities on post-fracture costs. The case for interventions to reduce comorbid conditions, improve health-related behaviours and prevent falls in deprived areas is clear but challenging to implement.

Admission patterns and survival from status epilepticus in critical care in the UK: an analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database.

BACKGROUND AND PURPOSE: Factors influencing the outcome after the critical care unit (CCU) for patients with status epilepticus (SE) are poorly understood. Survival for these patients was examined to establish (i) whether the risk of mortality has changed over time and (ii) whether admission to different unit types affects mortality risk over and above other risk factors. METHODS: The Intensive Care National Audit and Research Centre database and the Case Mix Programme database (January 2001 to December 2016) were analysed. Units were defined as neuro-CCU (NCCU), general CCU with 24-h neurological support (GCCU-N) or general CCU with limited neurological support (GCCU-L). RESULTS: There were 35 595 CCU cases of SE with a 3-fold increase over time (4739 in 2001-2004 to 14 166 in 2013-2016). More recent admissions were older and were more often unsedated on admission. Mortality declined for all units although this was more marked for NCCUs (8.1% in 2001-2004 to 4.4% in 2013-2016 compared to 5.1% and 4.1% for GCCU-L). Acute hospital mortality was two to three times higher than CCU mortality although this has also declined with time. GCCU-L appeared to have lower mortality than NCCUs (odds ratio 0.84, 95% confidence interval 0.72, 0.98) but after post hoc adjustment for case mix there were no differences. Older age and markers of seriousness of morbidity were all associated with increased mortality risk. CONCLUSIONS: The number of patients admitted to a CCU for SE is rising but critical care and acute hospital mortality is decreasing. Patients treated in an NCCU have higher mortality but this is explicable by more severe underlying disease.

Mid-life social participation and physical performance at age 60-64: evidence from the 1946 British Birth Cohort Study.

BACKGROUND: Previous studies linking social activity and disability have been limited by focussing on self-reported physical performance in older adults (>65). We examined whether social participation in mid-life is associated with objective and subjective measures of physical performance in older age. METHODS: Participants of the Medical Research Council National Survey of Health and Development reported their involvement in social activities at ages 43 and 60-64 years; frequency of such involvement was classified into thirds. Physical performance was measured at age 60-64 using: grip strength; standing balance; chair rises; timed get-up-and-go; self-reported physical function from the Short Form-36. Multivariable regression was used to examine longitudinal associations between social participation and each physical performance measure. We also investigated whether change in social participation between 43 and 60-64 was associated with each outcome. RESULTS: In fully adjusted models, higher frequency of social participation at 43 was associated with faster chair rise (1.42 repetitions/min, 95% CI 0.45-2.39) and timed get-up-and-go speed (2.47 cm/s, 95% CI 0.27-4.67) and lower likelihood of self-report limitations (OR of low physical function 0.67, 95% CI 0.50-0.91) at 60-64 compared with low frequency. Better performance in objectively measured outcomes was observed only if higher social participation persisted over time whereas lower odds of self-reported limitations were found in all groups when compared to those with persistently low participation (ORs 0.43-0.56, all P≤0.02). CONCLUSION: Our findings suggest that associations between higher levels of social participation in mid-life and better physical performance exist only if this social participation persists through to older age.

Direct access CT for suspicion of brain tumour: an analysis of referral pathways in a population-based patient group.

BACKGROUND: Brain tumour patients see their primary care doctor on average three or more times before diagnosis, so there may be an opportunity to identify 'at risk' patients earlier. Suspecting a brain tumour diagnosis is difficult because brain tumour-related symptoms are typically non-specific. METHODS: We explored the predictive value of referral guidelines (Kernick and NICE 2005) for brain imaging where a tumour is suspected, in a population-based patient group referred for direct access CT of the head. A consensus panel reviewed whether non-tumour findings were clinically important or whether further investigation was necessary. RESULTS: Over a 5-year period, 3257 head scans were performed; 318 scans were excluded according to pre-specified criteria. 53 patients (1.8%) were reported to have intracranial tumours, of which 42 were significant (diagnostic yield of 1.43%). There were no false negative CT scans for tumour. With symptom-based referral guidelines primary care doctors can identify patients with a 3% positive predictive value (PPV). 559 patients had non-tumour findings, 31% of which were deemed clinically significant. In 34% of these 559 patients, referral for further imaging and/or specialist assessment from primary care was still thought warranted. CONCLUSION: Existing referral guidelines are insufficient to stratify patients adequately based on their symptoms, according to the likelihood that a tumour will be found on brain imaging. Identification of non-tumour findings may be significant for patients and earlier specialist input into interpretation of these images may be beneficial. Improving guidelines to better identify patients at risk of a brain tumour should be a priority, to improve speed of diagnosis, and reduce unnecessary imaging and costs. Future guidelines may incorporate groups of symptoms, clinical signs and tests to improve the predictive value.

The effect of social deprivation on hip fracture incidence in England has not changed over 14 years: an analysis of the English Hospital Episodes Statistics (2001-2015).

Deprivation predicts increased hip fracture risk. Over 14 years, hip fracture incidence increased among men with persisting inequalities. Among women, inequalities in incidence were less pronounced; whilst incidence decreased overall, this improvement was seen marginally less in women from the most deprived areas. Hip fracture prevention programmes have not reduced inequalities. PURPOSE: Deprivation is associated with increased hip fracture risk. We examined the effect of area-level deprivation on hip fracture incidence in England over 14 years to determine whether inequalities have changed over time. METHODS: We used English Hospital Episodes Statistics (2001/2002-2014/2015) to identify hip fractures in adults aged 50+ years and mid-year population estimates (2001-2014) from the Office for National Statistics. The Index of Multiple Deprivation measured local area deprivation. We calculated age-adjusted incidence rate ratios (IRR) for hip fracture, stratified by gender and deprivation quintiles. RESULTS: Over 14 years, we identified 747,369 hospital admissions with an index hip fracture; the number increased from 50,640 in 2001 to 55,092 in 2014; the proportion of men increased from 22.2% to 29.6%. Whereas incidence rates decreased in women (annual reduction 1.1%), they increased in men (annual increase 0.6%) (interaction p < 0.001). Incidence was higher in more deprived areas, particularly among men: IRR most vs. least deprived quintile 1.50 [95% CI 1.48, 1.52] in men, 1.17 [1.16, 1.18] in women. Age-standardised incidence increased for men across all deprivation quintiles from 2001 to 2014. Among women, incidence fell more among those least compared to most deprived (year by deprivation interaction p < 0.001). CONCLUSIONS: Deprivation is a stronger relative predictor of hip fracture incidence in men than in women. However, given their higher hip fracture incidence, the absolute burden of deprivation on hip fractures is greater in women. Despite public health efforts to prevent hip fractures, the health inequality gap for hip fracture incidence has not narrowed for men, and marginally widened among women.

Sociodemographic inequalities in the management of depression in adults aged 55 and over: an analysis of English primary care data.

BACKGROUND: We do not know how primary care treatment of depression varies by age across both psychotropic medication and psychological therapies. METHODS: Cohort study including 19 710 people aged 55+ with GP recorded depression diagnoses and 26 276 people with recorded depression symptoms during the period 2009-2013, from 373 General Practices in The Health Improvement Network (THIN) database in England. Main outcomes were initiation of treatment with anti-depressants, anxiolytics, hypnotics, anti-psychotic drugs, referrals to psychological therapies within 6 months of onset. RESULTS: Treatment rates with antidepressants are high for those recorded with new depression diagnoses (87.1%) or symptoms of depression (58.7%). Treatment in those with depression diagnoses varies little by age. In those with depressive symptoms there was a J-shaped pattern with reduced antidepressant treatment in those in their 60s and 70s followed by increased treatment in the oldest age groups (85+ years), compared with those aged 55-59 years. Other psychotropic drug prescribing (hypnotics/anxiolytics, antipsychotics) all increase with increasing age. Recorded referrals for psychological therapies were low, and decreased steadily with increasing age, such that women aged 75-79 years with depression diagnoses had around six times lower odds of referral (OR 0.17, 95% CI 0.1-0.29) than those aged 55-59 years, and men aged 80-84 years had around seven times lower (OR 0.14, 95% CI 0.05-0.36). CONCLUSIONS: The oldest age groups with new depression diagnoses and symptoms have fewer recorded referrals to psychological therapies, and higher psychotropic drug treatment rates in primary care. This suggests potential inequalities in access to psychological therapies.

Apathy in rapid eye movement sleep behaviour disorder is common and under-recognized.

BACKGROUND AND PURPOSE: Apathy is an important neuropsychiatric feature of Parkinson's disease (PD), which often emerges before the onset of motor symptoms. Patients with rapid eye movement sleep behaviour disorder (RBD) have a high probability of developing PD in future. Neuropsychiatric problems are common in RBD, but apathy has not previously been detailed in this key prodromal population. METHODS: Eighty-eight patients with polysomnographically proven RBD, 65 patients with PD and 33 controls were assessed for apathy using the Lille Apathy Rating Scale. Cognition and depression were also quantified. The sensitivity of the Unified Parkinson's Disease Rating Scale screening questions for apathy and depression was calculated. RESULTS: A total of 46% of patients with RBD were apathetic, compared with 31% of patients with PD in our sample. Most patients with RBD with depression were apathetic but more than half of apathetic patients were not depressed. The sensitivity of the single Unified Parkinson's Disease Rating Scale screening question was only 33% for mild apathy and 50% for severe apathy. CONCLUSIONS: Apathy is common in RBD and is underestimated by a single self-report question. Recognition of apathy as a distinct neuropsychiatric feature in RBD could aid targeted treatment interventions and might contribute to the understanding of prodromal PD.

Inequalities in hip fracture incidence are greatest in the North of England: regional analysis of the effects of social deprivation on hip fracture incidence across England.

OBJECTIVES: Hip fracture risk varies by geography and by levels of deprivation. We examined the effect of local area-level deprivation on hip fracture incidence across nine regions in England, using 14 years of hospital data, to determine whether inequalities in hip fracture incidence rates vary across geographic regions in England. STUDY DESIGN: Sequential annual cross-sectional studies over 14 years. METHODS: We used English Hospital Episodes Statistics (2001/02-2014/15) to identify hip fractures in adults aged 50+ years and mid-year population estimates (2001-2014) from the Office for National Statistics. The Index of Multiple Deprivation was used to measure local area deprivation. We calculated age-standardised hip fracture incidence rates per 100,000 population, stratified by gender, geographic region, deprivation quintiles and time-period, using the 2001 English population as the reference population. Using Poisson regression, we calculated age-adjusted incidence rate ratios (IRRs) for hip fracture, stratified as above. RESULTS: Over 14 years, we identified 747,369 hospital admissions with an index hip fracture. Age-standardised hip fracture incidence was highest in the North East for both men and women. In North England (North East, North West and Yorkshire and the Humber), hip fracture incidence was relatively higher in more deprived areas, particularly among men: IRR most vs least deprived quintile 2.06 (95% confidence interval [CI] = 2.00-2.12) in men, 1.62 (95% CI 1.60-1.65) in women. A relationship, albeit less marked, between deprivation and hip fracture incidence was observed among men in the Midlands and South, but with no clear pattern among women. CONCLUSIONS: Regional variation in hip fracture incidence exists across England, with the greatest absolute burden of incident hip fractures observed in the North East for both men and women. Across local areas in North England, absolute and relative inequalities in hip fracture incidence were greater than in other regions. Our findings highlight the need for improved fracture prevention programmes that aim to reduce regional and social inequalities in hip fracture incidence.

Rates of hip and knee joint replacement amongst different ethnic groups in England: an analysis of National Joint Registry data.

OBJECTIVE: Despite a health care system that is free at the point of delivery, ethnic minorities may not always get care equitable to that of White patients in England. We examined whether ethnic differences exist in joint replacement rates and surgical practice in England. DESIGN: 373,613 hip and 428,936 knee National Joint Registry (NJR) primary replacement patients had coded ethnicity in Hospital Episode Statistics (HES). Age and gender adjusted observed/expected ratios of hip and knee replacements amongst ethnic groups were compared using indirect standardisation. Associations between ethnic group and type of procedure were explored and effects of demographic, clinical and hospital-related factors examined using multivariable logistic regression. RESULTS: Adjusted standardised observed/expected ratios were substantially lower in Blacks and Asians than Whites for hip replacement (Blacks 0.33 [95% CI, 0.31-0.35], Asians 0.20 [CI, 0.19-0.21]) and knee replacement (Blacks 0.64 [CI, 0.61-0.67], Asians 0.86 % [CI, 0.84-0.88]). Blacks were more likely to receive uncemented hip replacements (Blacks 52%, Whites 37%, Asians 44%; P < 0.001). Black men and women aged <70 years were less likely to receive unicondylar or patellofemoral knee replacements than Whites (men 10% vs 15%, P = 0.001; women 6% vs 14%, P < 0.001). After adjustment for demographic, clinical and hospital-related factors, Blacks were more likely to receive uncemented hip replacement (OR 1.43 [CI, 1.11-1.84]). CONCLUSIONS: In England, hip and knee replacement rates and prosthesis type given differ amongst ethnic groups. Whether these reflect differences in clinical need or differential access to treatment requires urgent investigation.

Olfaction in Parkin single and compound heterozygotes in a cohort of young onset Parkinson's disease patients.

BACKGROUND: Parkin related Parkinson's disease (PD) is differentiated from idiopathic PD by absent or sparse Lewy bodies, and preserved olfaction. The significance of single Parkin mutations in the pathogenesis of PD is debated. OBJECTIVES: To assess olfaction results according to Parkin mutation status. To compare the prevalence of Parkin single heterozygous mutations in patients diagnosed with PD to the rate in healthy controls in order to establish whether these single mutations could be a risk factor for developing PD. METHODS: Parkin gene mutation testing was performed in young onset PD (diagnosed <50 years old) to identify three groups: Parkin homozygous or compound heterozygote mutation carriers, Parkin single heterozygote mutation carriers, and non-carriers of Parkin mutations. Olfaction was tested using the 40-item British version of the University of Pennsylvania smell identification test (UPSIT). RESULTS: Of 344 young onset PD cases tested, 8 (2.3%) were Parkin compound heterozygotes and 13 (3.8%) were Parkin single heterozygotes. Olfaction results were available in 282 cases (eight compound heterozygotes, nine single heterozygotes, and 265 non-carriers). In Parkin compound heterozygotes, the median UPSIT score was 33, interquartile range (IQR) 28.5-36.5, which was significantly better than in single Parkin heterozygotes (median 19, IQR 18-28) and non-carriers (median score 22, IQR 16-28) (ANOVA P < 0.001). These differences persisted after adjusting for age, disease duration, gender, and smoking (P < 0.001). There was no significant difference in UPSIT scores between single heterozygotes and non-carriers (P = 0.90). CONCLUSIONS: Patients with Parkin compound heterozygous mutations have relatively preserved olfaction compared to Parkin single heterozygotes and non-carriers. The prevalence of Parkin single heterozygosity is similar to the 3.7% rate reported in healthy controls.

Parental mood during pregnancy and post-natally is associated with offspring risk of Tourette syndrome or chronic tics: prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC).

Little is known about risk factors for Tourette syndrome (TS) and chronic tic disorders (CT) but maternal psychological morbidity in pregnancy may be associated with TS/CT. We examined whether pre- and post-natal parental anxiety and/or depression are associated with risk of TS/CT in the Avon Longitudinal Study of Parents and Children. We compared self-reported anxiety and depression measures collected prospectively at four time points (18 and 32 weeks prenatally, and 8 weeks and 8 months post-natally) among parents of children who subsequently met criteria for TS/CT at 13 years of age as compared to other children from the cohort. We adjusted for various socioeconomic measures and tested both for time period-specific exposure and chronic exposure using multivariable logistic regression models. 122 children had TS/CT (50 TS, 72 CT) and 5968 children had no tics. In crude analyses, both pre- and post-natal maternal anxiety and depression, but only post-natal paternal depression at 8 months, showed associations with TS/CT. In the final, adjusted multivariable models, chronic maternal anxiety (odds ratio 2.17, 95% CI 1.23, 3.84, p = 0.007) and pre-natal maternal depression (odds ratio 1.86, 95% CI 1.02, 3.39, p = 0.04) showed associations with TS/CT though the latter was consistent with chance (p = 0.07) after adjustment for past maternal depression. We find associations between maternal psychological morbidity pre- and post-natally and risk of future TS/CT in offspring. These associations may reflect either shared genetic susceptibility or a pre-natal exposure. Further work is required to see if these findings can be replicated in larger datasets.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

BACKGROUND: Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. METHODS: Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. RESULTS: Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). CONCLUSIONS: The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Socio-economic position and cardiovascular risk in rural Indian adolescents: evidence from the Andhra Pradesh children and parents study (APCAPS).

OBJECTIVES: This study examined association between socio-economic position and cardiovascular risk factors in adolescents to investigate whether childhood socio-economic position is a risk factor for future cardiovascular disease, independently of adult behaviours. STUDY DESIGN AND METHODS: Participants (n = 1128, 46% girls, aged 13-18 years) were members of a birth cohort (Andhra Pradesh Children and Parents Study or APCAPS) established to investigate long-term effects of a pregnancy and childhood nutritional supplementation trial conducted in 29 villages near Hyderabad in South India. Cross-sectional associations between socio-economic position and cardiovascular risk factors were examined using linear regression models. RESULTS: The mean BMI was 16.7 kg/m(2) for boys and 17.8 kg/m(2) for girls. Socio-economic position was positively associated with fat mass index (0.15 kg/m(2); 95% CI: 0.05-0.25) and inversely associated with central-peripheral skinfold ratio (-0.04; 95% CI: -0.06 to -0.01) and, in boys, fasting triglycerides (-0.05; 95% CI: -0.09 to -0.01). Association of socio-economic position with other risk factors (blood pressure, arterial stiffness, fasting glucose, insulin and cholesterol) was weak and inconsistent, and did not persist after adjustment for potential confounders, including age, sex, pubertal stage, height, adiposity and nutrition supplementation. CONCLUSIONS: The study thus showed that lower socio-economic position may be associated with greater central adiposity and higher triglyceride levels in these settings. Socio-economic gradient in cardiovascular risk may strengthen in future with later economic and lifestyle changes. Cardiovascular disease prevention strategies should therefore focus on the youth from the low income group.

Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs.

AIMS/HYPOTHESIS: Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-ß), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population. METHODS: We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits. RESULTS: The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with ß values of 0.007 (p = 0.05), 0.01 (p = 0.01), 0.007 (p = 0.05), 0.01 (p = 0.003) and 0.08 (p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with ß values of -0.06 (p = 0.04), 0.05 (p = 0.05), -0.08 (p = 0.01) and -0.08 (p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2, ADAM30 and CDKN2A/B, with ß values of 0.05 (p = 0.04), -0.07 (p = 0.03) and -0.08 (p = 0.02), respectively. We also found significant associations of ADAM30 (ß = -0.05; p = 0.01) and CDKN2A/B (ß = -0.05; p = 0.03) with HOMA-ß. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03). CONCLUSIONS/INTERPRETATION: We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification.

Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis.

BACKGROUND: Age at onset modifies prognosis in multiple sclerosis (MS) and may also exert an effect on the characteristics of disease ignition. Understanding how age influences presentation informs disease management and may allow differentiation of distinct clinical sub-groups. OBJECTIVES: To determine the nature of age-specific presentations of relapsing-remitting MS (RRMS) with respect to onset symptoms, gender ratios and index event outcomes. METHODS: In a prospective, population-based sample of 1424 patients in South-East Wales we examined associations between age at onset, clinical features and outcome of the onset event, making specific comparisons between paediatric, adolescent and late-onset MS. RESULTS: Age at onset varied significantly between sexes (Male 31.2, Female 29.3, p = 0.002), 0.7% had paediatric onset, 2.7% adolescent onset and 2.8% late-onset MS (>50 years). Optic neuritis was common in younger patients and declined after age 30. Lower limb motor, facial sensory, sexual and sphincteric symptoms rose with age independent of sex and disease course. F:M ratios were highest <16 years of age and declined with increasing age, with a male excess in those over 50. Probability of complete recovery from index event declined with age from 87.4% in the youngest group to 68% in the eldest (p = 0.009). CONCLUSIONS: Age at disease onset in RRMS exerts a significant effect on gender ratios and presenting phenotype, and allows identification of specific clinical sub-groups. In addition, ability to recover from initial relapse declines with age, suggesting accumulation of disability in MS is an age-dependent response to relapse.

Health promotion and the social gradient: the free swimming initiative for children and young people in Bristol.

OBJECTIVES: To examine whether the free swimming initiative in Bristol was associated with higher uptake in more affluent areas ('inverse use law'). STUDY DESIGN: Secondary analysis of statistical data on free swimming session attendances in Bristol, recorded from January to June 2010. Individual postcode data were linked to lower-layer super output area (LSOA) of residence and the specific pool attended. METHODS: The dataset comprised 58,582 swims by 13,881 unique individuals between January and June 2010. The influence of age group, gender, season, distance from pool and area deprivation score (English Index of Multiple Deprivation) on swimming uptake rates was examined. RESULTS: Higher uptake rates were found amongst girls and older children. Higher attendance was also related to proximity to pool and warmer season. No association was found between area deprivation and uptake rate (P = 0.31). Lower uptake rates in deprived areas were more marked if they were further away from a pool and in the winter season (P-value for interactions <0.001). CONCLUSIONS: The termination of the free swimming initiative in England may have removed an opportunity to promote physical activity across the social gradient. The evaluation of public health initiatives should examine effects across the social gradient, and clarify which aspects of interventions enhance the participation of poorer sections of society.

Factors associated with symptoms of anxiety and depression in five cohorts of community-based older people: the HALCyon (Healthy Ageing across the Life Course) Programme.

BACKGROUND: Symptoms of anxiety and depression are common in older people, but the relative importance of factors operating in early and later life in influencing risk is unclear, particularly in the case of anxiety. METHOD: We used data from five cohorts in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme: the Aberdeen Birth Cohort 1936, the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study and the Lothian Birth Cohort 1921. We used logistic regression to examine the relationship between factors from early and later life and risk of anxiety or depression, defined as scores of 8 or more on the subscales of the Hospital Anxiety and Depression Scale, and meta-analysis to obtain an overall estimate of the effect of each. RESULTS: Greater neuroticism, poorer cognitive or physical function, greater disability and taking more medications were associated in cross-sectional analyses with an increased overall likelihood of anxiety or depression. Associations between lower social class, either in childhood or currently, history of heart disease, stroke or diabetes and increased risk of anxiety or depression were attenuated and no longer statistically significant after adjustment for potential confounding or mediating variables. There was no association between birth weight and anxiety or depression in later life. CONCLUSIONS: Anxiety and depression in later life are both strongly linked to personality, cognitive and physical function, disability and state of health, measured concurrently. Possible mechanisms that might underlie these associations are discussed.