The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.

How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.

Monitoring indirect impact of COVID-19 pandemic on services for cardiovascular diseases in the UK.

OBJECTIVE: To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects. METHODS: Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends. RESULTS: Across nine hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1%-58.6%) and 52.9% (52.2%-53.5%), respectively, compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown and fell by 31%-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances relative reduction (RR) 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020. CONCLUSIONS: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.

Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study.

OBJECTIVES: To study the impact of blinding on estimated treatment effects, and their variation between trials; differentiating between blinding of patients, healthcare providers, and observers; detection bias and performance bias; and types of outcome (the MetaBLIND study). DESIGN: Meta-epidemiological study. DATA SOURCE: Cochrane Database of Systematic Reviews (2013-14). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Meta-analyses with both blinded and non-blinded trials on any topic. REVIEW METHODS: Blinding status was retrieved from trial publications and authors, and results retrieved automatically from the Cochrane Database of Systematic Reviews. Bayesian hierarchical models estimated the average ratio of odds ratios (ROR), and estimated the increases in heterogeneity between trials, for non-blinded trials (or of unclear status) versus blinded trials. Secondary analyses adjusted for adequacy of concealment of allocation, attrition, and trial size, and explored the association between outcome subjectivity (high, moderate, low) and average bias. An ROR lower than 1 indicated exaggerated effect estimates in trials without blinding. RESULTS: The study included 142 meta-analyses (1153 trials). The ROR for lack of blinding of patients was 0.91 (95% credible interval 0.61 to 1.34) in 18 meta-analyses with patient reported outcomes, and 0.98 (0.69 to 1.39) in 14 meta-analyses with outcomes reported by blinded observers. The ROR for lack of blinding of healthcare providers was 1.01 (0.84 to 1.19) in 29 meta-analyses with healthcare provider decision outcomes (eg, readmissions), and 0.97 (0.64 to 1.45) in 13 meta-analyses with outcomes reported by blinded patients or observers. The ROR for lack of blinding of observers was 1.01 (0.86 to 1.18) in 46 meta-analyses with subjective observer reported outcomes, with no clear impact of degree of subjectivity. Information was insufficient to determine whether lack of blinding was associated with increased heterogeneity between trials. The ROR for trials not reported as double blind versus those that were double blind was 1.02 (0.90 to 1.13) in 74 meta-analyses. CONCLUSION: No evidence was found for an average difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors. These results could reflect that blinding is less important than often believed or meta-epidemiological study limitations, such as residual confounding or imprecision. At this stage, replication of this study is suggested and blinding should remain a methodological safeguard in trials.

Directly Acting Oral Anticoagulants for the Prevention of Stroke in Atrial Fibrillation in England and Wales: Cost-Effectiveness Model and Value of Information Analysis.

Objectives. Determine the optimal, licensed, first-line anticoagulant for prevention of ischemic stroke in patients with non-valvular atrial fibrillation (AF) in England and Wales from the UK National Health Service (NHS) perspective and estimate value to decision making of further research. Methods. We developed a cost-effectiveness model to compare warfarin (international normalized ratio target range 2-3) with directly acting (or non-vitamin K antagonist) oral anticoagulants (DOACs) apixaban 5 mg, dabigatran 150 mg, edoxaban 60 mg, and rivaroxaban 20 mg, over 30 years post treatment initiation. In addition to death, the 17-state Markov model included the events stroke, bleed, myocardial infarction, and intracranial hemorrhage. Input parameters were informed by systematic literature reviews and network meta-analysis. Expected value of perfect information (EVPI) and expected value of partial perfect information (EVPPI) were estimated to provide an upper bound on value of further research. Results. At willingness-to-pay threshold £20,000, all DOACs have positive expected incremental net benefit compared to warfarin, suggesting they are likely cost-effective. Apixaban has highest expected incremental net benefit (£7533), followed by dabigatran (£6365), rivaroxaban (£5279), and edoxaban (£5212). There was considerable uncertainty as to the optimal DOAC, with the probability apixaban has highest net benefit only 60%. Total estimated population EVPI was £17.94 million (17.85 million, 18.03 million), with relative effect between apixaban versus dabigatran making the largest contribution with EVPPI of £7.95 million (7.66 million, 8.24 million). Conclusions. At willingness-to-pay threshold £20,000, all DOACs have higher expected net benefit than warfarin but there is considerable uncertainty between the DOACs. Apixaban had the highest expected net benefit and greatest probability of having highest net benefit, but there is considerable uncertainty between DOACs. A head-to-head apixaban versus dabigatran trial may be of value.

Clinical and cost-effectiveness of the Lightning Process in addition to specialist medical care for paediatric chronic fatigue syndrome: randomised controlled trial.

OBJECTIVE: Investigate the effectiveness and cost-effectiveness of the Lightning Process (LP) in addition to specialist medical care (SMC) compared with SMC alone, for children with chronic fatigue syndrome (CFS)/myalgic encephalitis (ME). DESIGN: Pragmatic randomised controlled open trial. Participants were randomly assigned to SMC or SMC+LP. Randomisation was minimised by age and gender. SETTING: Specialist paediatric CFS/ME service. PATIENTS: 12-18 year olds with mild/moderate CFS/ME. MAIN OUTCOME MEASURES: The primary outcome was the the 36-Item Short-Form Health Survey Physical Function Subscale (SF-36-PFS) at 6 months. Secondary outcomes included pain, anxiety, depression, school attendance and cost-effectiveness from a health service perspective at 3, 6 and 12 months. RESULTS: We recruited 100 participants, of whom 51 were randomised to SMC+LP. Data from 81 participants were analysed at 6 months. Physical function (SF-36-PFS) was better in those allocated SMC+LP (adjusted difference in means 12.5(95% CI 4.5 to 20.5), p=0.003) and this improved further at 12 months (15.1 (5.8 to 24.4), p=0.002). At 6 months, fatigue and anxiety were reduced, and at 12 months, fatigue, anxiety, depression and school attendance had improved in the SMC+LP arm. Results were similar following multiple imputation. SMC+LP was probably more cost-effective in the multiple imputation dataset (difference in means in net monetary benefit at 12 months £1474(95% CI £111 to £2836), p=0.034) but not for complete cases. CONCLUSION: The LP is effective and is probably cost-effective when provided in addition to SMC for mild/moderately affected adolescents with CFS/ME. TRIAL REGISTRATION NUMBER: ISRCTN81456207.

The duration of protection of school-aged BCG vaccination in England: a population-based case-control study.

Background: Evidence of protection from childhood Bacillus Calmette-Guerin (BCG) against tuberculosis (TB) in adulthood, when most transmission occurs, is important for TB control and resource allocation. Methods: We conducted a population-based case-control study of protection by BCG given to children aged 12-13 years against tuberculosis occurring 10-29 years later. We recruited UK-born White subjects with tuberculosis and randomly sampled White community controls. Hazard ratios and 95% confidence intervals (CIs) were estimated using case-cohort Cox regression, adjusting for potential confounding factors, including socio-economic status, smoking, drug use, prison and homelessness. Vaccine effectiveness (VE = 1 - hazard ratio) was assessed at successive intervals more than 10 years following vaccination. Results: We obtained 677 cases and 1170 controls after a 65% response rate in both groups. Confounding by deprivation, education and lifestyle factors was slight 10-20 years after vaccination, and more evident after 20 years. VE 10-15 years after vaccination was 51% (95% CI 21, 69%) and 57% (CI 33, 72%) at 15-20 years. Subsequently, BCG protection appeared to wane; 20-25 years VE = 25% (CI -14%, 51%) and 25-29 years VE = 1% (CI -84%, 47%). Based on multiple imputation of missing data (in 17% subjects), VE estimated in the same intervals after vaccination were similar [56% (CI 33, 72%), 57% (CI 36, 71%), 25% (-10, 48%), 21% (-39, 55%)]. Conclusions: School-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years, which is longer than previously thought. This has implications for assessing the cost-effectiveness of BCG vaccination and when evaluating new TB vaccines.

Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis.

Objective To compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation.Design Systematic review, network meta-analysis, and cost effectiveness analysis. Data sources Medline, PreMedline, Embase, and The Cochrane Library.Eligibility criteria for selecting studies Published randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation.Results 23 randomised trials involving 94 656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81), edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared with warfarin. The risk of stroke or systemic embolism was higher with edoxaban 60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35, 1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93), edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin. The risk of major bleeding was higher with dabigatran 150 mg twice daily than apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin, whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin.Conclusions The network meta-analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation. Several DOACs are of net benefit compared with warfarin. A trial directly comparing DOACs would overcome the need for indirect comparisons to be made through network meta-analysis.Systematic review registration PROSPERO CRD 42013005324.

The Diagnosis of Urinary Tract Infection in Young Children (DUTY) Study Clinical Rule: Economic Evaluation.

OBJECTIVE: To estimate the cost-effectiveness of a two-step clinical rule using symptoms, signs and dipstick testing to guide the diagnosis and antibiotic treatment of urinary tract infection (UTI) in acutely unwell young children presenting to primary care. METHODS: Decision analytic model synthesising data from a multicentre, prospective cohort study (DUTY) and the wider literature to estimate the short-term and lifetime costs and healthcare outcomes (symptomatic days, recurrent UTI, quality adjusted life years) of eight diagnostic strategies. We compared GP clinical judgement with three strategies based on a 'coefficient score' combining seven symptoms and signs independently associated with UTI and four strategies based on weighted scores according to the presence/absence of five symptoms and signs. We compared dipstick testing versus laboratory culture in children at intermediate risk of UTI. RESULTS: Sampling, culture and antibiotic costs were lowest in high-specificity DUTY strategies (£1.22 and £1.08) compared to clinical judgement (£1.99). These strategies also approximately halved urine sampling (4.8% versus 9.1% in clinical judgement) without reducing sensitivity (58.2% versus 56.4%). Outcomes were very similar across all diagnostic strategies. High-specificity DUTY strategies were more cost-effective than clinical judgement in the short- (iNMB = £0.78 and £0.84) and long-term (iNMB =£2.31 and £2.50). Dipstick tests had poorer cost-effectiveness than laboratory culture in children at intermediate risk of UTI (iNMB = £-1.41). CONCLUSIONS: Compared to GPs' clinical judgement, high specificity clinical rules from the DUTY study could substantially reduce urine sampling, achieving lower costs and equivalent patient outcomes. Dipstick testing children for UTI is not cost-effective.

Temporal growth and geographic variation in the use of laboratory tests by NHS general practices: using routine data to identify research priorities.

BACKGROUND: Laboratory tests are extensively used for diagnosis and monitoring in UK primary care. Test usage by GPs, and associated costs, have grown substantially in recent years. AIM: This study aimed to quantify temporal growth and geographic variation in utilisation of laboratory tests. DESIGN AND SETTING: Retrospective cohort study using data from general practices in the UK. METHOD: Data from the General Practice Research Database, including patient demographics, clinical details, and laboratory test results, were used to estimate rates of change in utilisation between 2005 and 2009, and identify tests with greatest inter-regional variation, by fitting random-effects Poisson regression models. The study also investigated indications for test requests, using diagnoses and symptoms recorded in the 2 weeks before each test. RESULTS: Around 660 000 tests were recorded in 230 000 person-years of follow-up. Test use increased by 24.2%, from 23 872 to 29 644 tests per 10 000 person-years, between 2005 and 2009. Tests with the largest increases were faecal occult blood (121%) and C-reactive protein (86%). There was substantial geographic variation in test utilisation; GPs in some regions requested tests such as plasma viscosity and cardiac enzymes at a rate more than three times the national average. CONCLUSION: Increases in the use of laboratory tests have substantial resource implications. Rapid increases in particular tests may be supported by evidence-based guidelines, but these are often vague about who should be tested, how often, and for how long. Substantial regional variation in test use may reflect uncertainty about diagnostic accuracy and appropriate indications for the laboratory test. There is a need for further research on the diagnostic accuracy, therapeutic impact, and effect on patient health outcomes of the most rapidly increasing and geographically variable tests.

Insurability of HIV-positive people treated with antiretroviral therapy in Europe: collaborative analysis of HIV cohort studies.

OBJECTIVE: To increase equitable access to life insurance for HIV-positive individuals by identifying subgroups with lower relative mortality. DESIGN: Collaborative analysis of cohort studies. METHODS: We estimated relative mortality from 6 months after starting antiretroviral therapy (ART), compared with the insured population in each country, among adult patients from European cohorts participating in the ART Cohort Collaboration (ART-CC) who were not infected via injection drug use, had not tested positive for hepatitis C, and started triple ART between 1996-2008. We used Poisson models for mortality, with the expected number of deaths according to age, sex and country specified as offset. RESULTS: There were 1236 deaths recorded among 34,680 patients followed for 174,906 person-years. Relative mortality was lower in patients with higher CD4 cell count and lower HIV-1 RNA 6 months after starting ART, without prior AIDS, who were older, and who started ART after 2000. Compared with insured HIV-negative lives, estimated relative mortality of patients aged 20-39 from France, Italy, United Kingdom, Spain and Switzerland, who started ART after 2000 had 6-month CD4 cell count at least 350 cells/µl and HIV-1 RNA less than 104 copies/ml and without prior AIDS was 459%. The proportion of exposure time with relative mortality below 300, 400, 500 and 600% was 28, 43, 61 and 64%, respectively, suggesting that more than 50% of patients (those with lower relative mortality) could be insurable. CONCLUSION: The continuing long-term effectiveness of ART implies that life insurance with sufficiently long duration to cover a mortgage is feasible for many HIV-positive people successfully treated with ART for more than 6 months.

Equity of access to specialist chronic fatigue syndrome (CFS/ME) services in England (2008-2010): a national survey and cross-sectional study.

OBJECTIVES: Provision of National Health Service (NHS) specialist chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) services in England has been deemed patchy and inconsistent. Our objective was to explore variation in the provision of NHS specialist CFS/ME services and to investigate whether access is related to measures of deprivation and inequality. DESIGN: Survey of all CFS/ME clinical teams in England, plus cross-sectional data from a subset of teams. SETTING: Secondary care. OUTCOME MEASURES: We used clinic activity data from CFS/ME clinical teams in England to describe provision of specialist CFS/ME services (referral, assessment and diagnosis rates per 1000 adults per year) during 2008-2011 according to Primary Care Trust (PCT) population estimates, and to investigate whether use of services was related to PCT-level measures of deprivation and inequality. We used postcode data from seven services to investigate variation in provision by deprivation. RESULTS: Clinic activity data were obtained from 93.9% (46/49) of clinical teams in England which between them received referrals from 84.9% (129/152) of PCTs. 12 PCTs, covering a population of 2.08 million adults, provided no specialist CFS/ME service. There was a six-fold variation in referral and assessment rates between services which could not be explained by PCT-level measures of deprivation and inequality. The median assessment rate in 2010 was 0.25 (IQR 0.17, 0.35) per 1000 adults per year. 91.9% (IQR 76.5%, 100.0%) of adults assessed were diagnosed with CFS/ME. Postcode data from seven clinical teams showed that assessment rates were equal across deprivation quartiles for four teams but were 40-50% lower in the most deprived compared with the most affluent areas for three teams. CONCLUSIONS: Two million adults in England do not have access to a specialist CFS/ME service. In some areas which do have a specialist service, access is inequitable. This inequity may worsen with the impending fragmentation of NHS commissioning across England.

QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.

The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database.

BACKGROUND: Few studies have investigated factors associated with discontinuation of employment in patients with CFS/ME or quantified its impact on productivity. METHODS: We used patient-level data from five NHS CFS/ME services during the period 01/04/2006-31/03/2010 collated in the UK CFS/ME National Outcomes Database. We used logistic regression to identify factors associated with discontinuation of employment. We estimated UK-wide productivity costs using patient-level data on duration of illness before assessment by a CFS/ME service, duration of unemployment, age, sex and numbers of patients, in conjunction with Office for National Statistics income and population data. RESULTS: Data were available for 2,170 patients, of whom 1,669 (76.9%) were women. Current employment status was recorded for 1,991 patients (91.8%), of whom 811 patients (40.7%) were currently employed and 998 (50.1%) had discontinued their employment "because of fatigue-related symptoms". Older age, male sex, disability, fatigue, pain, and duration of illness were associated with cessation of employment. In a multivariable model, age, male sex, and disability remained as independent predictors. Total productivity costs among the 2,170 patients due to discontinuation of employment in the years preceding assessment by a specialist CFS/ME service (median duration of illness=36 months) were £49.2 million. Our sample was equivalent to 4,424 UK adults accessing specialist services each year, representing productivity costs to the UK economy of £102.2 million. Sensitivity analyses suggested a range between £75.5-£128.9 million. CONCLUSIONS: CFS/ME incurs huge productivity costs amongst the small fraction of adults with CFS/ME who access specialist services.

Geography of suicide in Taiwan: spatial patterning and socioeconomic correlates.

In industrialised Western nations suicide rates tend to be high in inner city areas and socially fragmented neighbourhoods. Few studies have investigated spatial variations in suicide in non-Western settings. We estimated smoothed standardised mortality ratios (1999-2007) for suicide for each of the 358 Taiwanese districts (median population aged 15+: 27,000) and investigated their associations with area characteristics using Bayesian hierarchical models. The geographic distribution of suicide was similar in men and women; young people showed the greatest spatial variation in rates. Rates were highest in East Taiwan, a mostly mountainous rural area. There was no evidence of above average rates in large cities. Spatial patterns of method-specific suicide rates varied markedly, with solids/liquids poisonings showing the greatest geographic variation and hangings the least. Factors most strongly associated with area suicide rates were median household income, population density and lone-parent households. Spatial patterning of suicide in Taiwan differed from that observed in Western nations. Suicide prevention strategies should take into account unique local patterns.

Differences in access and patient outcomes across antiretroviral treatment clinics in the Free State province: a prospective cohort study.

OBJECTIVE: To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public sector treatment facilities in the Free State province, South Africa. DESIGN: Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across 36 facilities between May 2004 and December 2007, and assessed percentage initiating ART and percentage dead at 1 year after enrolment. Multivariable logistic regression was used to estimate associations of facility-level and patient-level characteristics with both mortality and treatment status. RESULTS: Of 44 866 patients enrolled, 15 219 initiated treatment within 1 year; 8 778 died within 1 year, 7 286 before accessing ART. Outcomes at 1 year varied greatly across facilities and more variability was explained by facility-level factors than by patient-level factors. The odds of starting treatment within 1 year improved over calendar time. Patients enrolled in facilities with treatment initiation available on site had higher odds of starting treatment and lower odds of death at 1 year compared with those enrolled in facilities that did not offer treatment initiation. Patients were less likely to start treatment if they were male, severely immunosuppressed (CD4 count ≤50 cells/µl), or underweight (<50 kg). Men were also more likely to die in the first year after enrolment. CONCLUSIONS: Although increasing numbers of patients started ART between 2004 and 2007, many patients died before accessing ART. Patient outcomes could be improved by decentralisation of treatment services, fast-tracking the most immunodeficient patients and improving access, especially for men.

Outcomes in patients waiting for antiretroviral treatment in the Free State Province, South Africa: prospective linkage study.

OBJECTIVE: In South Africa, many HIV-infected patients experience delays in accessing antiretroviral therapy (ART). We examined pretreatment mortality and access to treatment in patients waiting for ART. DESIGN: Cohort of HIV-infected patients assessed for ART eligibility at 36 facilities participating in the Comprehensive HIV and AIDS Management (CHAM) program in the Free State Province. METHODS: Proportion of patients initiating ART, pre-ART mortality and risk factors associated with these outcomes were estimated using competing risks survival analysis. RESULTS: Forty-four thousand, eight hundred and forty-four patients enrolled in CHAM between May 2004 and December 2007, of whom 22 083 (49.2%) were eligible for ART; pre-ART mortality was 53.2 per 100 person-years [95% confidence interval (CI) 51.8-54.7]. Median CD4 cell count at eligibility increased from 87 cells/µl in 2004 to 101 cells/µl in 2007. Two years after eligibility an estimated 67.7% (67.1-68.4%) of patients had started ART, and 26.2% (25.6-26.9%) died before starting ART. Among patients with CD4 cell counts below 25 cells/µl at eligibility, 48% died before ART and 51% initiated ART. Men were less likely to start treatment and more likely to die than women. Patients in rural clinics or clinics with low staffing levels had lower rates of starting treatment and higher mortality compared with patients in urban/peri-urban clinics, or better staffed clinics. CONCLUSIONS: Mortality is high in eligible patients waiting for ART in the Free State Province. The most immunocompromised patients had the lowest probability of starting ART and the highest risk of pre-ART death. Prioritization of these patients should reduce waiting times and pre-ART mortality.

Was the economic crisis 1997-1998 responsible for rising suicide rates in East/Southeast Asia? A time-trend analysis for Japan, Hong Kong, South Korea, Taiwan, Singapore and Thailand.

In 1997-1998 a widespread economic crisis hit the economies of many East/Southeast Asian countries; its impact on suicide rates across the region has not been systematically documented. We investigated the impact of the Asian economic crisis (1997-1998) on suicide in Japan, Hong Kong, South Korea, Taiwan, Singapore and Thailand. Suicide and population data for the period 1985-2006 were extracted from the World Health Organisation's mortality database and Taiwanese mortality statistics. Sex-specific age-standardised suicide rates for people aged 15years or above were analysed using joinpoint regression. Trends in divorce, marriage, unemployment, gross domestic product (GDP) per capita and alcohol consumption were compared with trends in suicide rates graphically and using time-series analysis. Suicide mortality decreased in the late 1980s and early 1990s but subsequently increased markedly in all countries except Singapore, which had steadily declining suicide rates throughout the study period. Compared to 1997, male rates in 1998 rose by 39% in Japan, 44% in Hong Kong and 45% in Korea; rises in female rates were less marked. Male rates also rose in Thailand, but accurate data were incomplete. The economic crisis was associated with 10,400 more suicides in 1998 compared to 1997 in Japan, Hong Kong and Korea. Similar increases in suicide rates were not seen in Taiwan and Singapore, the two countries where the economic crisis had a smaller impact on GDP and unemployment. Time-series analyses indicated that some of the crisis's impact on male suicides was attributable to increases in unemployment. These findings suggest an association of the Asian economic crisis with a sharp increase in suicide mortality in some, but not all, East/Southeast Asian countries, and that these increases were most closely associated with rises in unemployment.

Industry, incidents and casualties in South West England: what is their relationship and are there social inequalities in their distribution?

This ecological study aimed, through the analysis of 1,146 wards in the South West of England (1998-2002), firstly, to examine whether chemical incidents and public casualties are more likely near complex industry (emissions to land, air or water: Integrated Pollution Control industry, IPC) or industry with emissions to air only (Local Air Pollution Control industry, LAPC). Secondly, the study examined whether industry, incidents and casualties are found close to deprivation. Social inequalities were examined across quintiles of wards. Fifty-two wards (4.5%) contained an IPC industry and 712 (62.1%) an LAPC. Incidents occurred in 132 wards (11.5%), with casualties in 59 (5.1%). Chemical incidents occurred more frequently in wards with LAPC (152, IPC 20); the same was true of casualties (211, 12). With each additional LAPC site in a ward, the risk of an incident rose by 22% (95% confidence interval [CI] 8-38%), suggesting a dose-response relationship. No clear social inequalities were found. In the South West of England, the public are more likely to be affected by an incident occurring at a simple LAPC site rather than a complex IPC site. This has implications for emergency planning which, at present, focusses most attention on the larger, more complex IPC sites.

Inference from genome-wide association studies using a novel Markov model.

In this paper we propose a Bayesian modeling approach to the analysis of genome-wide association studies based on single nucleotide polymorphism (SNP) data. Our latent seed model combines various aspects of k-means clustering, hidden Markov models (HMMs) and logistic regression into a fully Bayesian model. It is fitted using the Markov chain Monte Carlo stochastic simulation method, with Metropolis-Hastings update steps. The approach is flexible, both in allowing different types of genetic models, and because it can be easily extended while remaining computationally feasible due to the use of fast algorithms for HMMs. It allows for inference primarily on the location of the causal locus and also on other parameters of interest. The latent seed model is used here to analyze three data sets, using both synthetic and real disease phenotypes with real SNP data, and shows promising results. Our method is able to correctly identify the causal locus in examples where single SNP analysis is both successful and unsuccessful at identifying the causal SNP.