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Objective To estimate the one year prognosis and identify prognostic factors in cases of recent onset low back pain managed in primary care. Design Cohort study with one year follow-up. Setting Primary care clinics in Sydney, Australia. Participants An inception cohort of 973 consecutive primary care patients (mean age 43.3, 54.8% men) with non-specific low back pain of less than two weeks’ duration recruited from the clinics of 170 general practitioners, physiotherapists, and chiropractors. Main outcome measures Participants completed a baseline questionnaire and were contacted six weeks, three months, and 12 months after the initial consultation. Recovery was assessed in terms of return to work, return to function, and resolution of pain. The association between potential prognostic factors and time to recovery was modelled with Cox regression. Results The follow-up rate over the 12 months was more than 97%. Half of those who reduced their work status at baseline had returned to previous work status within 14 days (95% confidence interval 11 to 17 days) and 83% had returned to previous work status by three months. Disability (median recovery time 31 days, 25 to 37 days) and pain (median 58 days, 52 to 63 days) took much longer to resolve. Only 72% of participants had completely recovered 12 months after the baseline consultation. Older age, compensation cases, higher pain intensity, longer duration of low back pain before consultation, more days of reduced activity because of lower back pain before consultation, feelings of depression, and a perceived risk of persistence were each associated with a longer time to recovery. Conclusions In this cohort of patients with acute low back pain in primary care, prognosis was not as favourable as claimed in clinical practice guidelines. Recovery was slow for most patients. Nearly a third of patients did not recover from the presenting episode within a year.

OBJECTIVE: To determine the incidence of and mortality from bullous pemphigoid and pemphigus vulgaris in the United Kingdom. DESIGN: Retrospective historical cohort study. SETTING: Computerised medical records from the health improvement network, a large population based UK general practice database. PARTICIPANTS: Patients with pemphigus vulgaris and bullous pemphigoid diagnostic codes and age, sex, and practice matched controls. MAIN OUTCOME MEASURES: Incidence and mortality compared with the control population by calendar period, age group, sex, geographical region, and degree of social deprivation. RESULTS: 869 people with bullous pemphigoid and 138 people with pemphigus vulgaris were identified. The median age at presentation for bullous pemphigoid was 80 (range 23-102) years, and 534 (61%) patients were female. The median age at presentation for pemphigus vulgaris was 71 (21-102) years, and 91 (66%) patients were female. Incidences of bullous pemphigoid and pemphigus vulgaris were 4.3 (95% confidence interval 4.0 to 4.6) and 0.7 (0.6 to 0.8) per 100 000 person years. The incidence of bullous pemphigoid increased over time; the average yearly increase was 17% (incidence rate ratio=1.2, 95% confidence interval 1.1 to 1.2). An average yearly increase in incidence of pemphigus vulgaris of 11% (incidence rate ratio=1.1, 1.0 to 1.2) occurred. The risk of death for patients with bullous pemphigoid was twice as great as for controls (adjusted hazard ratio=2.3, 95% confidence interval 2.0 to 2.7). For pemphigus vulgaris, the risk of death was three times greater than for controls (adjusted hazard ratio=3.3, 2.2 to 5.2). CONCLUSIONS: Incidences of bullous pemphigoid and pemphigus vulgaris are increasing. The reasons for the changes in incidence are not clearly understood but have implications for identifying causative factors. Both disorders are associated with a high risk of death. Previous estimates may have underestimated the risk of death associated with these diseases.

Objective To study secular trends in self reported sexual behaviour among 70 year olds. Design Cross sectional survey. Settings Four samples representative of the general population in Gothenburg, Sweden. Participants 1506 adults (946 women, 560 men) examined in 1971-2, 1976-7, 1992-3, and 2000-1. Main outcome measures Sexual intercourse, attitudes to sexuality in later life, sexual dysfunctions, and marital satisfaction. Results From 1971 to 2000 the proportion of 70 year olds reporting sexual intercourse increased among all groups: married men from 52% to 68% (P=0.002), married women from 38% to 56% (P=0.001), unmarried men from 30% to 54% (P=0.016), and unmarried women from 0.8% to 12% (P

Objective: To investigate the association between low functional health literacy (ability to read and understand basic health related information) and mortality in older adults.Design: Population based longitudinal cohort study based on a stratified random sample of households.Setting: England.Participants: 7857 adults aged 52 or more who participated in the second wave (2004-5) of the English Longitudinal Study of Ageing and survived more than 12 months after interview. Participants completed a brief four item test of functional health literacy, which assessed understanding of written instructions for taking an aspirin tablet.Main outcome measure: Time to death, based on all cause mortality through October 2009.Results: Health literacy was categorised as high (maximum score, 67.2%), medium (one error, 20.3%), or low (more than one error, 12.5%). During follow-up (mean 5.3 years) 621 deaths occurred: 321 (6.1%) in the high health literacy category, 143 (9.0%) in the medium category, and 157 (16.0%) in the low category. After adjusting for personal characteristics, socioeconomic position, baseline health, and health behaviours, the hazard ratio for all cause mortality for participants with low health literacy was 1.40 (95% confidence interval 1.15 to 1.72) and with medium health literacy was 1.15 (0.94 to 1.41) compared with participants with high health literacy. Further adjustment for cognitive ability reduced the hazard ratio for low health literacy to 1.26 (1.02 to 1.55).Conclusions: A third of older adults in England have difficulties reading and understanding basic health related written information. Poorer understanding is associated with higher mortality. The limited health literacy capabilities within this population have implications for the design and delivery of health related services for older adults in England.

Objective To determine the relative costs and health effects of interventions to combat cardiovascular disease, diabetes, and tobacco related disease in order to guide the allocation of resources in developing countries. Design Cost effectiveness analysis of 123 single or combined prevention and treatment strategies for cardiovascular disease, diabetes, and smoking by means of a lifetime population model. Setting Two World Health Organization sub-regions of the world: countries in sub-Saharan Africa with very high adult and high child mortality (AfrE) and countries in South East Asia with high adult and high child mortality (SearD). Data sources Demographic and epidemiological data were taken from the WHO databases of mortality and global burden of disease. Estimates of intervention coverage, effectiveness, and resource needs were drawn from clinical trials, observational studies, and treatment guidelines. Unit costs were taken from the WHO-CHOICE (Choosing Interventions that are Cost-Effective) price database. Main outcome measures Cost per disability adjusted life year (DALY) averted, expressed in international dollars ($Int) for the year 2005. Results Most of the interventions studied were considered highly cost effective, meaning they generate one healthy year of life at a cost of 25% chance of experiencing a cardiovascular event over the next decade, either alone or together with specific multidrug regimens for the secondary prevention of post-acute ischaemic heart disease and stroke (

OBJECTIVE: To determine whether mobile phone based monitoring improves asthma control compared with standard paper based monitoring strategies. DESIGN: Multicentre randomised controlled trial with cost effectiveness analysis. SETTING: UK primary care. PARTICIPANTS: 288 adolescents and adults with poorly controlled asthma (asthma control questionnaire (ACQ) score ≥ 1.5) from 32 practices. INTERVENTION: Participants were centrally randomised to twice daily recording and mobile phone based transmission of symptoms, drug use, and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring. MAIN OUTCOME MEASURES: Changes in scores on asthma control questionnaire and self efficacy (knowledge, attitude, and self efficacy asthma questionnaire (KASE-AQ)) at six months after randomisation. Assessment of outcomes was blinded. Analysis was on an intention to treat basis. RESULTS: There was no significant difference in the change in asthma control or self efficacy between the two groups (ACQ: mean change 0.75 in mobile group v 0.73 in paper group, mean difference in change -0.02 (95% confidence interval -0.23 to 0.19); KASE-AQ score: mean change -4.4 v -2.4, mean difference 2.0 (-0.3 to 4.2)). The numbers of patients who had acute exacerbations, steroid courses, and unscheduled consultations were similar in both groups, with similar healthcare costs. Overall, the mobile phone service was more expensive because of the expenses of telemonitoring. CONCLUSIONS: Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines standards. The mobile technology was not cost effective. TRIAL REGISTRATION: Clinical Trials NCT00512837.

Objective To determine whether the acute consumption of cannabis (cannabinoids) by drivers increases the risk of a motor vehicle collision. Design Systematic review of observational studies, with meta-analysis. Data sources We did electronic searches in 19 databases, unrestricted by year or language of publication. We also did manual searches of reference lists, conducted a search for unpublished studies, and reviewed the personal libraries of the research team. Review methods We included observational epidemiology studies of motor vehicle collisions with an appropriate control group, and selected studies that measured recent cannabis use in drivers by toxicological analysis of whole blood or self report. We excluded experimental or simulator studies. Two independent reviewers assessed risk of bias in each selected study, with consensus, using the Newcastle-Ottawa scale. Risk estimates were combined using random effects models. Results We selected nine studies in the review and meta-analysis. Driving under the influence of cannabis was associated with a significantly increased risk of motor vehicle collisions compared with unimpaired driving (odds ratio 1.92 (95% confidence interval 1.35 to 2.73); P=0.0003); we noted heterogeneity among the individual study effects (I2=81). Collision risk estimates were higher in case-control studies (2.79 (1.23 to 6.33); P=0.01) and studies of fatal collisions (2.10 (1.31 to 3.36); P=0.002) than in culpability studies (1.65 (1.11 to 2.46); P=0.07) and studies of non-fatal collisions (1.74 (0.88 to 3.46); P=0.11). Conclusions Acute cannabis consumption is associated with an increased risk of a motor vehicle crash, especially for fatal collisions. This information could be used as the basis for campaigns against drug impaired driving, developing regional or national policies to control acute drug use while driving, and raising public awareness.

Objective To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes. Design Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality. Setting Nursing homes in the United States. Participants 75 445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥65, were eligible for Medicaid, and lived in a nursing home in 2001-5. Main outcome measures Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders. Results Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine. Conclusions Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.

Objective To determine whether vitamin A supplementation administered in the preschool years can lower the risk of hearing loss in adolescence and adulthood. Design Follow-up study of adolescents and young adults who, as preschool aged children in 1989, were enrolled into a cluster randomised, double blinded, placebo controlled trial of vitamin A supplementation. Setting South central, rural Nepal. Participants 2378 adolescents and young adults aged 14 to 23, representing 51% of those who finished the original trial and 71% of those living in the study area in 2006. Interventions Every four months for 16 months preschool children were visited at home, given an oral 200 000 IU dose of vitamin A (half dose at age 1-11 months, quarter dose at

Objectives To examine how much of the observed rapid decrease in mortality from coronary heart disease in Poland after the political, social, and economic transformation in the early 1990s could be explained by the use of medical and surgical treatments and how much by changes in cardiovascular risk factors. Design A modelling study. Setting Sources of data included controlled trials and meta-analyses, national surveys, and official statistics. Participants Population of adults aged 25-74 in Poland in 1991-2005. Main outcome measures Number of deaths prevented or postponed in 2005 attributable to specific treatments for coronary heart disease and changes in risk factors. A previously validated epidemiological model for coronary heart disease was used to combine and analyse data on the uptake and effectiveness of specific cardiac treatments and changes in risk factors. The observed fall in deaths from coronary heart disease from 1991 to 2005 was then partitioned among specific treatments and risk factor changes. Results From 1991 to 2005, the death rate from coronary heart disease in Poland halved, resulting in 26 200 fewer coronary deaths in 2005 in people aged 25-74. About 37% (minimum estimate 13%, maximum estimate 77%) of this decrease was attributable to treatments, including treatments for heart failure (12%), initial treatments for acute coronary syndrome (9%), secondary prevention treatments after myocardial infarction or revascularisation (7%), chronic angina treatments (3%), and other treatments (6%). About 54% of the fall was attributed to changes in risk factors (minimum estimate 41%, maximum estimate 65%), mainly reductions in total cholesterol concentration (39%) and an increase in leisuretime physical activity (10%); however, these were partially offset by increases in body mass index (−4%) and prevalence of diabetes (−2%). Blood pressure fell in women, explaining about 29% of their decrease in mortality, but rose in men generating a negative influence (−8%). About 15% of the observed decrease in mortality was attributable to reduced smoking in men but was negligible in women. Conclusions Over half of the recent fall in mortality from coronary heart disease in Poland can be attributed to reductions in major risk factors and about one third to evidence based medical treatments.

Evolutionary biology provides an essential perspective on the determinants of health and disease, believe Peter Gluckman and Carl Bergstrom. It needs to be further integrated into medical research and teaching

Objective To estimate the lost investment of domestically educated doctors migrating from sub-Saharan African countries to Australia, Canada, the United Kingdom, and the United States. Design Human capital cost analysis using publicly accessible data. Settings Sub-Saharan African countries. Participants Nine sub-Saharan African countries with an HIV prevalence of 5% or greater or with more than one million people with HIV/AIDS and with at least one medical school (Ethiopia, Kenya, Malawi, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe), and data available on the number of doctors practising in destination countries. Main outcome measures The financial cost of educating a doctor (through primary, secondary, and medical school), assuming that migration occurred after graduation, using current country specific interest rates for savings converted to US dollars; cost according to the number of source country doctors currently working in the destination countries; and savings to destination countries of receiving trained doctors. Results In the nine source countries the estimated government subsidised cost of a doctor’s education ranged from $21 000 (£13 000; €15 000) in Uganda to $58 700 in South Africa. The overall estimated loss of returns from investment for all doctors currently working in the destination countries was $2.17bn (95% confidence interval 2.13bn to 2.21bn), with costs for each country ranging from $2.16m (1.55m to 2.78m) for Malawi to $1.41bn (1.38bn to 1.44bn) for South Africa. The ratio of the estimated compounded lost investment over gross domestic product showed that Zimbabwe and South Africa had the largest losses. The benefit to destination countries of recruiting trained doctors was largest for the United Kingdom ($2.7bn) and United States ($846m). Conclusions Among sub-Saharan African countries most affected by HIV/AIDS, lost investment from the emigration of doctors is considerable. Destination countries should consider investing in measurable training for source countries and strengthening of their health systems.

The most important step is to improve society’s attitudes towards older people Longevity increased in most countries during the first half of the 20th century mainly as a result of reduced infant mortality from infections and other preventable causes. However, since the 1950s the average lifespan has again increased, mainly because older people with chronic illnesses such as cancer, heart disease, and stroke are living longer. Data showing that the proportion of older people with depression and other mental illnesses will grow disproportionately faster than the overall older population are less well known. One reason for this is a higher risk of these mental illnesses in people born in the post-second world war baby boom than in those born before the war.1 The changing demographics have been described as a “silver tsunami,” pointing to the high healthcare costs of the ageing population. A more constructive socioscientific approach would be to develop means of keeping older adults healthy. The linked randomised controlled trial by Von Korff and colleagues (doi:10.1136/bmj.d6612) assessed an important model for promoting healthy ageing in people with multiple chronic illnesses.2 The authors sought to improve hyperglycaemia, …

Objective To determine comparative safety and effectiveness of combinations of bearing surfaces of hip implants. Design Systematic review of clinical trials, observational studies, and registries. Data sources Medline, Embase, Cochrane Controlled Trials Register, reference lists of articles, annual reports of major registries, summaries of safety and effectiveness for pre-market application and mandated post-market studies at the United States Food and Drug Administration. Study selection Criteria for inclusion were comparative studies in adults reporting information for various combinations of bearings (such as metal on metal and ceramic on ceramic). Data search, abstraction, and analyses were independently performed and confirmed by at least two authors. Qualitative data syntheses were performed. Results There were 3139 patients and 3404 hips enrolled in 18 comparative studies and over 830 000 operations in national registries. The mean age range in the trials was 42-71, and 26-88% were women. Disease specific functional outcomes and general quality of life scores were no different or they favoured patients receiving metal on polyethylene rather than metal on metal in the trials. While one clinical study reported fewer dislocations associated with metal on metal implants, in the three largest national registries there was evidence of higher rates of implant revision associated with metal on metal implants compared with metal on polyethylene. One trial reported fewer revisions with ceramic on ceramic compared with metal on polyethylene implants, but data from national registries did not support this finding. Conclusions There is limited evidence regarding comparative effectiveness of various hip implant bearings. Results do not indicate any advantage for metal on metal or ceramic on ceramic implants compared with traditional metal on polyethylene or ceramic on polyethylene bearings.

Objective To determine the prevalence of financial conflicts of interest among members of panels producing clinical practice guidelines on screening, treatment, or both for hyperlipidaemia or diabetes. Design Cross sectional study. Setting Relevant guidelines published by national organisations in the United States and Canada between 2000 and 2010. Participants Members of guideline panels. Main outcome measures Prevalence of financial conflicts of interest among members of guideline panels and chairs of panels. Results Fourteen guidelines met our search criteria, of which five had no accompanying declaration of conflicts of interest by panel members. 288 panel members had participated in the guideline development process. Among the 288 panel members, 138 (48%) reported conflicts of interest at the time of the publication of the guideline and 150 (52%) either stated that they had no such conflicts or did not have an opportunity to declare any. Among 73 panellists who formally declared no conflicts, 8 (11%) were found to have one or more. Twelve of the 14 guideline panels evaluated identified chairs, among whom six had financial conflicts of interest. Overall, 150 (52%) panel members had conflicts, of which 138 were declared and 12 were undeclared. Panel members from government sponsored guidelines were less likely to have conflicts of interest compared with guidelines sponsored by non-government sources (15/92 (16%) v 135/196 (69%); P

Objective To quantify randomness and cost when choosing health and medical research projects for funding. Design Retrospective analysis. Setting Grant review panels of the National Health and Medical Research Council of Australia. Participants Panel members’ scores for grant proposals submitted in 2009. Main outcome measures The proportion of grant proposals that were always, sometimes, and never funded after accounting for random variability arising from differences in panel members’ scores, and the cost effectiveness of different size assessment panels. Results 59% of 620 funded grants were sometimes not funded when random variability was taken into account. Only 9% (n=255) of grant proposals were always funded, 61% (n=1662) never funded, and 29% (n=788) sometimes funded. The extra cost per grant effectively funded from the most effective system was $A18 541 (£11 848; €13 482; $19 343). Conclusions Allocating funding for scientific research in health and medicine is costly and somewhat random. There are many useful research questions to be addressed that could improve current processes.

Objectives To use changes in heart disease mortality rates with age to investigate the plausibility of attributing women’s lower heart disease mortality than men to the protective effects of premenopausal sex hormones. Design Modelling study of longitudinal mortality data with models assuming (i) a linear association between mortality rates and age (absolute mortality) or (ii) a logarithmic association (proportional mortality). We fitted models to age and sex specific mortality rates in the census years 1950 to 2000 for three birth cohorts (1916-25, 1926-35, and 1936-45). Data sources UK Office for National Statistics and the US National Center for Health Statistics. Main outcome measure(s) Fit of models to data for England and Wales and for the US. Results For England-Wales data, proportional increases in ischaemic heart disease mortality fitted the data better than absolute increases (improvement in deviance statistics: women, 58 logarithmic units; men, 37). We identified a deceleration in male mortality after age 45 years (decreasing from 30.3% to 5.2% per age-year, P=0.042), although the corresponding difference in women was non-significant (P=0.43, overall trend 7.9% per age-year, P

Objective To evaluate the ability of international point of care information summaries to update evidence relevant to medical practice. Design Prospective cohort bibliometric analysis. Setting Top five point of care information summaries (Clinical Evidence, EBMGuidelines, eMedicine, Dynamed, UpToDate) ranked for coverage of medical conditions, editorial quality, and evidence based methodology. Main outcome measures From June 2009 to May 2010 we measured the incidence of research findings relating to potentially eligible newsworthy evidence. As samples, we chose systematic reviews rated as relevant by international research networks (such as, Evidence-Based Medicine, ACP Journal Club, and the Cochrane Collaboration). Every month we assessed whether each sampled review was cited in at least one chapter of the five summaries. The cumulative updating rate was analysed with Kaplan-Meier curves. Results From April to December 2009, 128 reviews were retrieved; 53% (68) from the literature surveillance journals and 47% (60) from the Cochrane Library. At nine months, Dynamed had cited 87% of the sampled reviews, while the other summaries had cited less than 50%. The updating speed of Dynamed clearly led the others. For instance, the hazard ratios for citations in EBM Guidelines and Clinical Evidence versus the top performer were 0.22 (95% confidence interval 0.17 to 0.29) and 0.03 (0.01 to 0.05). Conclusions Point of care information summaries include evidence relevant to practice at different speeds. A qualitative analysis of updating mechanisms is needed to determine whether greater speed corresponds to more appropriate incorporation of new information.

Serious consideration is needed about which non-communicable diseases to discuss at this month’s United Nations meeting if people in low income countries are to benefit.1 The diseases selected are more problematic in high income than in low income countries. Stroke, heart disease, diabetes, and chronic obstructive lung disease primarily affect older adults while low income countries remain largely populated by youth. According to World Health Organization data,2 upper middle income countries stand …

Objective To assess the impact of the 2004 extension of the CONSORT guidelines on the reporting and methodological quality of cluster randomised trials. Design Methodological review of 300 randomly sampled cluster randomised trials. Two reviewers independently abstracted 14 criteria related to quality of reporting and four methodological criteria specific to cluster randomised trials. We compared manuscripts published before CONSORT (2000-4) with those published after CONSORT (2005-8). We also investigated differences by journal impact factor, type of journal, and trial setting. Data sources A validated Medline search strategy. Eligibility criteria for selecting studies Cluster randomised trials published in English language journals, 2000-8. Results There were significant improvements in five of 14 reporting criteria: identification as cluster randomised; justification for cluster randomisation; reporting whether outcome assessments were blind; reporting the number of clusters randomised; and reporting the number of clusters lost to follow-up. No significant improvements were found in adherence to methodological criteria. Trials conducted in clinical rather than non-clinical settings and studies published in medical journals with higher impact factor or general medical journals were more likely to adhere to recommended reporting and methodological criteria overall, but there was no evidence that improvements after publication of the CONSORT extension for cluster trials were more likely in trials conducted in clinical settings nor in trials published in either general medical journals or in higher impact factor journals. Conclusion The quality of reporting of cluster randomised trials improved in only a few aspects since the publication of the extension of CONSORT for cluster randomised trials, and no improvements at all were observed in essential methodological features. Overall, the adherence to reporting and methodological guidelines for cluster randomised trials remains suboptimal, and further efforts are needed to improve both reporting and methodology.

Objective To determine the effect of mammography screening on surgical treatment for breast cancer. Design Comparative analysis of data from Norwegian cancer registry. Setting Mammography screening, Norway (screening of women aged 50-69 was introduced sequentially from 1996 to 2004). Participants 35 408 women aged 40-79 with invasive breast cancer or ductal carcinoma in situ treated surgically from 1993 to 2008. Main outcome measures Rates of breast surgery (mastectomy plus breast conserving treatment) and rates of mastectomy for three age groups of women: 40-49, 50-69, and 70-79. Changes in rates from pre-screening period (1993-5) to introduction of screening phase (1996-2004) and then to screening period (2005-8) are presented as hazard ratios in invited and non-invited women. Results The annual rate for breast surgery from the pre-screening period (1993-5) to screening period (2005-8) in Norway increased by 70% (hazard ratio 1.70, 95% confidence interval 1.62 to 1.78), from 180 to 305 per 100 000 women in the invited age group (50-69 years). In the younger, non-invited age group (40-49 years), however, the increase was only 8% (1.08, 1.00 to 1.16), from 133 to 144 per 100 000 women per year, whereas in the older, non-invited age group (70-79 years) the rate decreased by 8% (0.92, 0.86 to 1.00), from 227 to 214 per 100 000 women per year. The rates for mastectomy decreased similarly from the pre-screening period to screening period in invited and non-invited women. From the pre-screening period to the introduction phase of screening (1996-2004), however, the annual mastectomy rate in women aged 50-69 invited to screening increased by 9% (1.09, 1.03 to 1.14), from 156 to 167 per 100 000 women, and in the younger non-invited women declined by 17% (0.83, 0.78 to 0.90), from 109 to 91 per 100 000 women. In consequence, the mastectomy rate was 31% (1.31, 1.20 to 1.43) higher in the invited than in the non-invited younger age group. Conclusions Mammography screening in Norway was associated with a noticeable increase in rates for breast cancer surgery in women aged 50-69 (the age group invited to screening) and also an increase in mastectomy rates. Although over-diagnosis is likely to have caused the initial increase in mastectomy rates and the overall increase in surgery rates in the age group screened, the more recent decline in mastectomy rates has affected all age groups and is likely to have resulted from changes in surgical policy.

Objective To examine short and long term time trends in mortality among patients with early onset (age 0-14 years) and late onset (15-29 years) type 1 diabetes and causes of deaths over time. Design Population based nationwide cohort study. Setting Finland. Participants All Finnish patients diagnosed as having type 1 diabetes below age 30 years between 1970 and 1999 (n=17 306). Main outcome measures Crude mortality, standardised mortality ratios, time trends, and cumulative mortality. Results A total of 1338 deaths occurred during 370 733 person years of follow-up, giving an all cause mortality rate of 361/100 000 person years. The standardised mortality ratio was 3.6 in the early onset cohort and 2.8 in the late onset cohort. Women had higher standardised mortality ratios than did men in both cohorts (5.5 v 3.0 in the early onset cohort; 3.6 v 2.6 in the late onset cohort). The standardised mortality ratio at 20 years’ duration of diabetes in the early onset cohort decreased from 3.5 in the patients diagnosed in 1970-4 to 1.9 in those diagnosed in 1985-9. In contrast, the standardised mortality ratio in the late onset cohort increased from 1.4 in those diagnosed in 1970-4 to 2.9 in those diagnosed in 1985-9. Mortality due to chronic complications of diabetes decreased with time in the early onset cohort but not in the late onset cohort. Mortality due to alcohol related and drug related causes increased in the late onset cohort and accounted for 39% of the deaths during the first 20 years of diabetes. Accordingly, mortality due to acute diabetic complications increased significantly in the late onset cohort. Conclusion Survival of people with early onset type 1 diabetes has improved over time, whereas survival of people with late onset type 1 diabetes has deteriorated since the 1980s. Alcohol has become an important cause of death in patients with type 1 diabetes, and the proportion of deaths caused by acute complications of diabetes has increased in patients with late onset type 1 diabetes.

Objective To evaluate the association of chocolate consumption with the risk of developing cardiometabolic disorders. Design Systematic review and meta-analysis of randomised controlled trials and observational studies. Data sources Medline, Embase, Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, reference lists of relevant studies to October 2010, and email contact with authors. Study selection Randomised trials and cohort, case-control, and cross sectional studies carried out in human adults, in which the association between chocolate consumption and the risk of outcomes related to cardiometabolic disorders were reported. Data extraction Data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The primary outcome was cardiometabolic disorders, including cardiovascular disease (coronary heart disease and stroke), diabetes, and metabolic syndrome. A meta-analysis assessed the risk of developing cardiometabolic disorders by comparing the highest and lowest level of chocolate consumption. Results From 4576 references seven studies met the inclusion criteria (including 114 009 participants). None of the studies was a randomised trial, six were cohort studies, and one a cross sectional study. Large variation was observed between these seven studies for measurement of chocolate consumption, methods, and outcomes evaluated. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels.Conclusions Based on observational evidence, levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders. Further experimental studies are required to confirm a potentially beneficial effect of chocolate consumption

Objectives To examine the extent of multiplicity of data in trial reports and to assess the impact of multiplicity on meta-analysis results. Design Empirical study on a cohort of Cochrane systematic reviews. Data sources All Cochrane systematic reviews published from issue 3 in 2006 to issue 2 in 2007 that presented a result as a standardised mean difference (SMD). We retrieved trial reports contributing to the first SMD result in each review, and downloaded review protocols. We used these SMDs to identify a specific outcome for each meta-analysis from its protocol. Review methods Reviews were eligible if SMD results were based on two to ten randomised trials and if protocols described the outcome. We excluded reviews if they only presented results of subgroup analyses. Based on review protocols and index outcomes, two observers independently extracted the data necessary to calculate SMDs from the original trial reports for any intervention group, time point, or outcome measure compatible with the protocol. From the extracted data, we used Monte Carlo simulations to calculate all possible SMDs for every meta-analysis. Results We identified 19 eligible meta-analyses (including 83 trials). Published review protocols often lacked information about which data to choose. Twenty-four (29%) trials reported data for multiple intervention groups, 30 (36%) reported data for multiple time points, and 29 (35%) reported the index outcome measured on multiple scales. In 18 meta-analyses, we found multiplicity of data in at least one trial report; the median difference between the smallest and largest SMD results within a meta-analysis was 0.40 standard deviation units (range 0.04 to 0.91). Conclusions Multiplicity of data can affect the findings of systematic reviews and meta-analyses. To reduce the risk of bias, reviews and meta-analyses should comply with prespecified protocols that clearly identify time points, intervention groups, and scales of interest.

Objective To investigate the agreement between direct and indirect comparisons of competing healthcare interventions. Design Meta-epidemiological study based on sample of meta-analyses of randomised controlled trials. Data sources Cochrane Database of Systematic Reviews and PubMed. Inclusion criteria Systematic reviews that provided sufficient data for both direct comparison and independent indirect comparisons of two interventions on the basis of a common comparator and in which the odds ratio could be used as the outcome statistic. Main outcome measure Inconsistency measured by the difference in the log odds ratio between the direct and indirect methods. Results The study included 112 independent trial networks (including 1552 trials with 478 775 patients in total) that allowed both direct and indirect comparison of two interventions. Indirect comparison had already been explicitly done in only 13 of the 85 Cochrane reviews included. The inconsistency between the direct and indirect comparison was statistically significant in 16 cases (14%, 95% confidence interval 9% to 22%). The statistically significant inconsistency was associated with fewer trials, subjectively assessed outcomes, and statistically significant effects of treatment in either direct or indirect comparisons. Owing to considerable inconsistency, many (14/39) of the statistically significant effects by direct comparison became non-significant when the direct and indirect estimates were combined. Conclusions Significant inconsistency between direct and indirect comparisons may be more prevalent than previously observed. Direct and indirect estimates should be combined in mixed treatment comparisons only after adequate assessment of the consistency of the evidence.

Objective To determine the prevalence, impact, and stability of different subtypes of headache in a 30 year prospective follow-up study of a general population sample. Design Prospective cohort study. Setting Canton of Zurich, Switzerland. Participants 591 people aged 19-20 from a cohort of 4547 residents of Zurich, Switzerland, interviewed seven times across 30 years of follow-up. Main outcome measures Prevalence of headache; stability of the predominant subtype of headache over time; and age of onset, severity, impact, family history, use of healthcare services, and drugs for headache subtypes. Results The average one year prevalences of subtypes of headache were 0.9% (female:male ratio of 2.8) for migraine with aura, 10.9% (female:male ratio of 2.2) for migraine without aura, and 11.5% (female:male ratio of 1.2) for tension-type headache. Cumulative 30 year prevalences of headache subtypes were 3.0% for migraine with aura, 36.0% for migraine without aura, and 29.3% for tension-type headache. Despite the high prevalence of migraine without aura, most cases were transient and only about 20% continued to have migraine for more than half of the follow-up period. 69% of participants with migraine and 58% of those with tension-type headache manifested the same predominant subtype over time. However, the prospective stability of the predominant headache subtypes was quite low, with substantial crossover among the subtypes and no specific ordinal pattern of progression. A gradient of severity of clinical correlates and service use was present across headache subtypes; the greatest effect was for migraine with aura followed by migraine without aura, and then tension-type headache and unclassified headaches. Conclusions These findings highlight the importance of prospective follow-up of people with headache. The substantial longitudinal overlap among subtypes of headache shows the developmental heterogeneity of headache syndromes. Studies of the causes of headache that apply diagnostic nomenclature based on distinctions between discrete headache subtypes may not capture the true nature of headache in the general population.

Objective To examine the rise in the rate of involuntary admissions for mental illness in England that has occurred as community alternatives to hospital admission have been introduced.\ud Design Ecological analysis.\ud Setting England, 1988-2008.\ud Data source Publicly available data on provision of beds for people with mental illness in the National Health Service from Hospital Activity Statistics and involuntary admission rates from the NHS Information Centre.\ud Main outcome measures Association between annual changes in\ud provision of mental illness beds in the NHS and involuntary admission rates, using cross correlation. Partial correlation coefficients were calculated and regression analysis carried out for the time lag (interval) over which the largest association between these variables was identified.\ud Results The rate of involuntary admissions per annum in the NHS increased by more than 60%, whereas the provision of mental illness beds decreased by more than 60% over the same period; these changes seemed to be synchronous. The strongest association between these variables was observed when a time lag of one year was introduced, with bed reductions preceding increases in involuntary admissions (cross correlation −0.60, 95% confidence interval −1.06 to −0.15). This association increased in magnitude when analyses were restricted to civil (non-forensic) involuntary admissions and non-secure mental illness beds.\ud Conclusion The annual reduction in provision of mental illness beds was associated with the rate of involuntary admissions over the short to medium term, with the closure of two mental illness beds leading to one additional involuntary admission in the subsequent year. This study\ud provides a method for predicting rates of involuntary admissions and what may happen in the future if bed closures continue.

Objective To determine the association of resting echocardiography before elective intermediate to high risk non-cardiac surgery with survival and length of hospital stay. Design Population based retrospective cohort study. Setting Acute care hospitals in Ontario, Canada, between 1 April 1999 and 31 March 2008. Participants Patients aged over 40 years who had elective intermediate to high risk non-cardiac surgery. Intervention Resting echocardiography within 6 months before surgery. Main outcome measures Postoperative survival (30 days and 1 year) and length of hospital stay; postoperative surgical site infection as an outcome for which no association with echocardiography would be expected. Results Of the 264 823 patients in the entire cohort, 15.1% (n=40 084) had echocardiography. After use of propensity score methods to assemble a matched cohort (n=70 996) that reduced differences between patients who had or had not had echocardiography, echocardiography was associated with increases in 30 day mortality (relative risk 1.14, 95% confidence interval 1.02 to 1.27), 1 year mortality (1.07, 1.01 to 1.12), and length of hospital stay but no difference in surgical site infections (1.03, 0.98 to 1.06). The association with mortality was influenced (P=0.02) by whether patients had had stress testing or had risk factors for cardiac complications. No association existed between echocardiography and mortality among patients who had stress testing (relative risk 1.01, 0.92 to 1.11) or among patients at high risk who had not had stress testing (1.00, 0.87 to 1.13). However, echocardiography was associated with mortality in patients at low risk (relative risk 1.44, 1.14 to 1.82) and intermediate risk (1.10, 1.02 to 1.18) who had not had stress testing. Conclusions Preoperative echocardiography was not associated with improved survival or shorter hospital stay after major non-cardiac surgery. These findings highlight the need for further research to guide better use of this common preoperative test.

Possibly, and it could have other effects on long term ill health In the linked longitudinal study (doi:10.1136/bmj.d2712), Carter and colleagues assess the association between reduced sleep and differences in body composition and the risk of becoming overweight in young children.1 We spend about a third of our life asleep. We spend more time asleep as babies and children and then generally settle into a pattern of seven to eight hours a night. Sufficient sleep is necessary for optimal daytime performance and wellbeing, yet the amount of sleep that people get varies greatly.2 The quantity and quality of sleep have shown secular trends alongside changes in modern society that require longer hours of work, more shift work, and “24/7” availability of commodities. These changes have reduced the average duration of sleep across westernised populations, with increased reporting of fatigue, tiredness, and excessive daytime sleepiness.2 This sleep curtailment has been attributed mainly to lifestyle changes.2 Too little sleep is associated with adverse health outcomes, including total mortality,3 stroke and coronary heart disease,4 type 2 diabetes,5 hypertension,6 respiratory disorders, poor self rated health,2 and obesity in adults and children.7 Obesity in childhood has now reached epidemic proportions and is a cause of psychosocial problems including low self esteem. It often continues into adulthood, where it causes major morbidity, disability, and premature death. Several studies have reported associations between short duration of sleep …

Objectives To evaluate the association between thyroid autoantibodies and miscarriage and preterm birth in women with normal thyroid function. To assess the effect of treatment with levothyroxine on pregnancy outcomes in this group of women. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Library, and SCISEARCH (inception-2011) without any language restrictions. We used a combination of key words to generate two subsets of citations, one indexing thyroid autoantibodies and the other indexing the outcomes of miscarriage and preterm birth. Study selection Studies that evaluated the association between thyroid autoantibodies and pregnancy outcomes were selected in a two stage process. Two reviewers selected studies that met the predefined and explicit criteria regarding population, tests, and outcomes. Data synthesis Odds ratios from individual studies were pooled separately for cohort and case-control studies with the random effects model. Results 30 articles with 31 studies (19 cohort and 12 case-control) involving 12 126 women assessed the association between thyroid autoantibodies and miscarriage. Five studies with 12 566 women evaluated the association with preterm birth. Of the 31 studies evaluating miscarriage, 28 showed a positive association between thyroid autoantibodies and miscarriage. Meta-analysis of the cohort studies showed more than tripling in the odds of miscarriage with the presence of thyroid autoantibodies (odds ratio 3.90, 95% confidence interval 2.48 to 6.12; P

Objectives To determine the effectiveness of corticosteroids in reducing respiratory disorders in infants born at 34-36 weeks’ gestation. Design Randomised triple blind clinical trial. Setting A large tertiary teaching hospital in northeast of Brazil. Participants Women at 34-36 weeks of pregnancy at risk of imminent premature delivery. Interventions Betamethasone 12 mg or placebo intramuscularly for two consecutive days. Main outcomes measures Primary outcome was the incidence of respiratory disorders (respiratory distress syndrome and transient tachypnoea of the newborn). Secondary outcomes included the need for ventilatory support, neonatal morbidity, and duration of stay in hospital. Results 320 women were randomised, 163 of whom were assigned to the treatment group and 157 to the controls. Final analysis included 143 and 130 infants, respectively. The rate of respiratory distress syndrome was low (two (1.4%) in the corticosteroid group; one (0.8%) in the placebo group; P=0.54), while the rate of transient tachypnoea was high in both groups (34 (24%) v 29 (22%); P=0.77). There was no reduction in the risk of respiratory morbidity with corticosteroid use even after adjustment for subgroups of gestational age (34-34 +6 weeks, 35-35 +6 weeks, and ≥36 weeks). The adjusted risk of respiratory morbidity was 1.12 (95% confidence interval 0.74 to 1.70). The need for ventilatory support was around 20% in both groups. There was no difference in neonatal morbidity (88 (62%) v 93 (72%); P=0.08) or in the duration of stay in hospital between the two groups (5.12 v 5.22 days; P=0.87). Phototherapy for jaundice was required less often in babies whose mothers received corticosteroids (risk ratio 0.63, 0.44 to 0.91). Conclusions Antenatal treatment with corticosteroids at 34-36 weeks of pregnancy does not reduce the incidence of respiratory disorders in newborn infants. Trial registration Clinical Trials NCT00675246.

Objectives To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated. Design Prospective multicentre cohort. Setting Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland. Participants 3572 “healthy” nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%). Main outcome measure Pre-eclampsia defined as ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks’ gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37 +0 weeks’ gestation. In the stepwise logistic regression the comparison group was women without pre-eclampsia. Results Of the 3529 women, 186 (5.3%) developed pre-eclampsia, including 47 (1.3%) with preterm pre-eclampsia. Clinical risk factors at 14-16 weeks’ gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors. Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop pre-eclampsia. The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively. Conclusions The ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added. Trial registration ACTRN12607000551493.

Objective To compare the safety and efficacy of overnight closed loop delivery of insulin (artificial pancreas) with conventional insulin pump therapy in adults with type 1 diabetes. Design Two sequential, open label, randomised controlled crossover, single centre studies. Setting Clinical research facility. Participants 24 adults (10 men, 14 women) with type 1 diabetes, aged 18-65, who had used insulin pump therapy for at least three months: 12 were tested after consuming a medium sized meal and the other 12 after consuming a larger meal accompanied by alcohol. Intervention During overnight closed loop delivery, sensor measurements of glucose were fed into a computer algorithm, which advised on insulin pump infusion rates at 15 minute intervals. During control nights, conventional insulin pump settings were applied. One study compared closed loop delivery of insulin with conventional pump therapy after a medium sized evening meal (60 g of carbohydrates) at 1900, depicting the scenario of “eating in.” The other study was carried out after a later large evening meal (100 g of carbohydrates) at 2030, accompanied by white wine (0.75 g/kg ethanol) and depicted the scenario of “eating out.” Main outcome measures The primary outcome was the time plasma glucose levels were in target (3.91-8.0 mmol/L) during closed loop delivery and a comparable control period. Secondary outcomes included pooled data analysis and time plasma glucose levels were below target (≤3.9 mmol/L). Results For the eating in scenario, overnight closed loop delivery of insulin increased the time plasma glucose levels were in target by a median 15% (interquartile range 3-35%), P=0.002. For the eating out scenario, closed loop delivery increased the time plasma glucose levels were in target by a median 28% (2-39%), P=0.01. Analysis of pooled data showed that the overall time plasma glucose was in target increased by a median 22% (3-37%) with closed loop delivery (P

Objectives To evaluate whether country of medical qualification is associated with “higher impact” decisions at different stages of the UK General Medical Council’s (GMC’s) “fitness to practise” process after allowing for other characteristics of doctors and inquiries. Design Retrospective cohort study. Setting Medical practice in the United Kingdom. Participants 7526 inquiries to the GMC concerning 6954 doctors. Main outcome measures Proportion of inquiries referred for further investigation at initial triage by the GMC, proportion of inquiries investigated that were subsequently referred for adjudication, and proportion of inquiries resulting in doctors being erased or suspended from the medical register; relative odds of higher impact decisions, by country of qualification, adjusted for doctors’ sex, years since primary medical qualification, medical specialty, source and type of inquiry, and nature of allegations. Results Of 7526 inquiries, 4702 concerned doctors who qualified in the UK, 624 concerned doctors who qualified elsewhere in the European Union (EU), and 2190 concerned doctors who qualified outside the EU. At the initial triage, 30% (n=1398) of inquiries concerning doctors who qualified in the UK had a high impact decision, compared with 43% (267) for doctors who qualified elsewhere in the EU and 46% (998) for those who qualified outside the EU. The adjusted relative odds of an inquiry being referred for further investigation were 1.67 (95% confidence interval 1.28 to 2.17) for doctors who qualified elsewhere in the EU and 1.61 (1.38 to 1.88) for those who qualified outside the EU, compared with doctors who qualified in the UK. At the investigation stage, 5% (228) of inquiries received concerning UK qualified doctors were referred for adjudication, compared with 10% for EU (63) or non-EU (221) qualified doctors. The adjusted relative odds of referral for adjudication were 2.14 (1.46 to 3.16) for doctors who qualified elsewhere in the EU and 1.68 (1.31 to 2.16) for those who qualified outside the EU. At the adjudication stage, 1% (69) of inquiries received concerning UK qualified doctors led to erasure or suspension, compared with 4% (24) for doctors who qualified elsewhere in the EU and 3% (71) for non-EU qualified doctors. The adjusted relative odds of erasure or suspension were 2.16 (1.22 to 3.80) for doctors who qualified elsewhere in the EU and 1.48 (1.00 to 2.19) for those who qualified outside the EU. Conclusions Inquiries to the GMC concerning doctors qualified outside the UK are more likely to be associated with higher impact decisions at each stage of the fitness to practice process. These associations were not explained by measured inquiry related and doctor related characteristics, but residual confounding cannot be excluded.

OBJECTIVE: To determine whether statins protect against all cause mortality after a diagnosis of pneumonia. DESIGN: Cohort study using propensity score based method to control for differences between people prescribed and not prescribed statins. SETTING: United Kingdom Health Improvement Network database, which contains electronic primary care medical records of more than six million patients. PARTICIPANTS: Every patient starting a statin between 1995 and 2006 (129,288) matched with up to five non-statin users (n = 600,241); 9073 patients had a recorded diagnosis of pneumonia, of whom 1398 were using a statin. MAIN OUTCOME MEASURE: All cause mortality within six months of diagnosis of pneumonia. RESULTS: Among users and non-users of statins with comparable propensity scores, 95/942 users and 686/3615 non-users died on the day that pneumonia was diagnosed. In the following six month period, 109/847 statin users died compared with 578/2927 non-users, giving an adjusted hazard ratio of 0.67 (0.49 to 0.91). If these observed benefits translated into clinical practice, 15 patients would need to be treated with a statin for six months after pneumonia to prevent one death. CONCLUSIONS: Compared with people who were not taking statins, the risk of dying in the six month period after pneumonia was substantially lower among people who were already established on long term statin treatment when the pneumonia occurred. Whether some or all of this protective effect would be obtained if statin treatment begins when a patient first develops pneumonia is not known. However, given that statins are cheap, safe, and well tolerated, a clinical trial in which people with pneumonia are randomised to a short period of statin treatment is warranted.

Objective To determine whether the ethnicity of UK trained doctors and medical students is related to their academic performance. Design Systematic review and meta-analysis. Data sources Online databases PubMed, Scopus, and ERIC; Google and Google Scholar; personal knowledge; backwards and forwards citations; specific searches of medical education journals and medical education conference abstracts. Study selection The included quantitative reports measured the performance of medical students or UK trained doctors from different ethnic groups in undergraduate or postgraduate assessments. Exclusions were non-UK assessments, only non-UK trained candidates, only self reported assessment data, only dropouts or another non-academic variable, obvious sampling bias, or insufficient details of ethnicity or outcomes. Results 23 reports comparing the academic performance of medical students and doctors from different ethnic groups were included. Meta-analyses of effects from 22 reports (n=23 742) indicated candidates of “non-white” ethnicity underperformed compared with white candidates (Cohen’s d=−0.42, 95% confidence interval −0.50 to −0.34; P

Objectives To investigate time trends in receipt of effective acute stroke care and to determine the factors associated with provision of care. Design Population based stroke register. Setting South London. Participants 3800 patients with first ever ischaemic stroke or primary intracerebral haemorrhage registered between January 1995 and December 2009. Main outcome measures Acute care interventions, admission to hospital, care on a stroke unit, acute drugs, and inequalities in access to care. Results Between 2007 and 2009, 5% (33/620) of patients were still not admitted to a hospital after an acute stroke, particularly those with milder strokes, and 21% (124/584) of patients admitted to hospital were not admitted to a stroke unit. Rates of admission to stroke units and brain imaging, between 1995 and 2009, and for thrombolysis, between 2005 and 2009, increased significantly (P

Objective To independently evaluate the impact of the second phase of the Health Foundation’s Safer Patients Initiative (SPI2) on a range of patient safety measures.\ud \ud Design A controlled before and after design. Five substudies: survey of staff attitudes; review of case notes from high risk (respiratory) patients in medical wards; review of case notes from surgical patients; indirect evaluation of hand hygiene by measuring hospital use of handwashing materials; measurement of outcomes (adverse events, mortality among high risk patients admitted to medical wards, patients’ satisfaction, mortality in intensive care, rates of hospital acquired infection).\ud \ud Setting NHS hospitals in England.\ud \ud Participants Nine hospitals participating in SPI2 and nine matched control hospitals.\ud \ud Intervention The SPI2 intervention was similar to the SPI1, with somewhat modified goals, a slightly longer intervention period, and a smaller budget per hospital.\ud \ud Results One of the scores (organisational climate) showed a significant (P=0.009) difference in rate of change over time, which favoured the control hospitals, though the difference was only 0.07 points on a five point scale. Results of the explicit case note reviews of high risk medical patients showed that certain practices improved over time in both control and SPI2 hospitals (and none deteriorated), but there were no significant differences between control and SPI2 hospitals. Monitoring of vital signs improved across control and SPI2 sites. This temporal effect was significant for monitoring the respiratory rate at both the six hour (adjusted odds ratio 2.1, 99% confidence interval 1.0 to 4.3; P=0.010) and 12 hour (2.4, 1.1 to 5.0; P=0.002) periods after admission. There was no significant effect of SPI for any of the measures of vital signs. Use of a recommended system for scoring the severity of pneumonia improved from 1.9% (1/52) to 21.4% (12/56) of control and from 2.0% (1/50) to 41.7% (25/60) of SPI2 patients. This temporal change was significant (7.3, 1.4 to 37.7; P=0.002), but the difference in difference was not significant (2.1, 0.4 to 11.1; P=0.236). There were no notable or significant changes in the pattern of prescribing errors, either over time or between control and SPI2 hospitals. Two items of medical history taking (exercise tolerance and occupation) showed significant improvement over time, across both control and SPI2 hospitals, but no additional SPI2 effect. The holistic review showed no significant changes in error rates either over time or between control and SPI2 hospitals. The explicit case note review of perioperative care showed that adherence rates for two of the four perioperative standards targeted by SPI2 were already good at baseline, exceeding 94% for antibiotic prophylaxis and 98% for deep vein thrombosis prophylaxis. Intraoperative monitoring of temperature improved over time in both groups, but this was not significant (1.8, 0.4 to 7.6; P=0.279), and there were no additional effects of SPI2. A dramatic rise in consumption of soap and alcohol hand rub was similar in control and SPI2 hospitals (P=0.760 and P=0.889, respectively), as was the corresponding decrease in rates of Clostridium difficile and meticillin resistant Staphylococcus aureus infection (P=0.652 and P=0.693, respectively). Mortality rates of medical patients included in the case note reviews in control hospitals increased from 17.3% (42/243) to 21.4% (24/112), while in SPI2 hospitals they fell from 10.3% (24/233) to 6.1% (7/114) (P=0.043). Fewer than 8% of deaths were classed as avoidable; changes in proportions could not explain the divergence of overall death rates between control and SPI2 hospitals. There was no significant difference in the rate of change in mortality in intensive care. Patients’ satisfaction improved in both control and SPI2 hospitals on all dimensions, but again there were no significant changes between the two groups of hospitals.\ud \ud Conclusions Many aspects of care are already good or improving across the NHS in England, suggesting considerable improvements in quality across the board. These improvements are probably due to contemporaneous policy activities relating to patient safety, including those with features similar to the SPI, and the emergence of professional consensus on some clinical processes. This phenomenon might have attenuated the incremental effect of the SPI, making it difficult to detect. Alternatively, the full impact of the SPI might be observable only in the longer term. The conclusion of this study could have been different if concurrent controls had not been used.

Objectives To estimate the rates and timing of mother to infant transmission of HIV associated with breast feeding in mothers who seroconvert postnatally, and their breast milk and plasma HIV loads during and following seroconversion, compared with women who tested HIV positive at delivery. Design Prospective cohort study. Setting Urban Zimbabwe. Participants 14 110 women and infants enrolled in the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial (1997-2001). Main outcome measures Mother to child transmission of HIV, and breast milk and maternal plasma HIV load during the postpartum period. Results Among mothers who tested HIV positive at baseline and whose infant tested HIV negative with polymerase chain reaction (PCR) at six weeks (n=2870), breastfeeding associated transmission was responsible for an average of 8.96 infant infections per 100 child years of breast feeding (95% CI 7.92 to 10.14) and varied little over the breastfeeding period. Breastfeeding associated transmission for mothers who seroconverted postnatally (n=334) averaged 34.56 infant infections per 100 child years (95% CI 26.60 to 44.91) during the first nine months after maternal infection, declined to 9.50 (95% CI 3.07 to 29.47) during the next three months, and was zero thereafter. Among women who seroconverted postnatally and in whom the precise timing of infection was known (≤90 days between last negative and first positive test; n=51), 62% (8/13) of transmissions occurred in the first three months after maternal infection and breastfeeding associated transmission was 4.6 times higher than in mothers who tested HIV positive at baseline and whose infant tested HIV negative with PCR at six weeks. Median plasma HIV concentration in all mothers who seroconverted postnatally declined from 5.0 log10 copies/mL at the last negative enzyme linked immunosorbent assay (ELISA) to 4.1 log10 copies/mL at 9-12 months after infection. Breast milk HIV load in this group was 4.3 log10 copies/mL 0-30 days after infection, but rapidly declined to 2.0 log10 copies/mL and

Objective To determine for how long after a first unprovoked seizure a driver must be seizure-free before the risk of recurrence in the next 12 months falls below 20%, enabling them to regain their driving licence. Design Randomised controlled trial: Multicentre study of early Epilepsy and Single Seizures (MESS). Setting UK hospital outpatient clinics from 1 January 1993 to 31 December 2000. Participants People entered MESS if they had had one or more unprovoked seizures and both the participant and the clinician were uncertain about the need to start antiepileptic drug treatment. The subset of people used for this analysis comprised participants aged at least 16 years with a single unprovoked seizure. Main outcome measure Risk of seizure recurrence in the 12 months after a seizure-free period of 6, 12, 18, or 24 months from the date of the first (index) seizure. Regression modelling was used to investigate how antiepileptic treatment and several clinical factors influence the risk of seizure recurrence. Results At six months after the index seizure the risk of recurrence in the next 12 months for those who start antiepileptic drugs was significantly below 20% (unadjusted risk 14%, 95% confidence interval 10% to 18%). For patients who did not start treatment the risk estimate was less than 20% but the upper limit of the confidence interval was greater than 20% (18%, 13% to 23%). Multivariable analyses identified subgroups with a significantly greater than 20% risk of seizure recurrence in the 12 months after a six month seizure-free period, such as those with a remote symptomatic seizure with abnormal electroencephalogram results. Conclusion After a single unprovoked seizure this reanalysis of MESS provides estimates of seizure recurrence risks that will inform policy and guidance about regaining an ordinary driving licence. Further guidance is needed as to how such data should be utilised; in particular, whether a population approach should be taken with a focus on the unadjusted results or whether attempts should be made to individualise risk. Guidance is also required as to whether the focus should be on risk estimates only or on the confidence interval as well. If the focus is on the estimate only our unadjusted estimates suggest that treated and untreated patients are eligible to drive after being seizure-free for six months. If the focus is also on confidence intervals, direction is needed as to whether a conservative or liberal approach should be taken. Trial registration Current Controlled Trials [ISRCTN98767960][1]. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN98767960

Objective To determine whether the author’s 20.9 lb (9.5 kg) carbon frame bicycle reduced commuting time compared with his 29.75 lb (13.5 kg) steel frame bicycle. Design Randomised trial. Setting Sheffield and Chesterfield, United Kingdom, between mid-January 2010 and mid-July 2010. Participants One consultant in anaesthesia and intensive care. Main outcome measure Total time to complete the 27 mile (43.5 kilometre) journey from Sheffield to Chesterfield Royal Hospital and back. Results The total distance travelled on the steel frame bicycle during the study period was 809 miles (1302 km) and on the carbon frame bicycle was 711 miles (1144 km). The difference in the mean journey time between the steel and carbon bicycles was 00:00:32 (hr:min:sec; 95% CI –00:03:34 to 00:02:30; P=0.72). Conclusions A lighter bicycle did not lead to a detectable difference in commuting time. Cyclists may find it more cost effective to reduce their own weight rather than to purchase a lighter bicycle.

OBJECTIVE: To examine whether treatment of periodontal disease with scaling and root planing during pregnancy is associated with a reduction in the preterm birth rate. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Cochrane Central Trials Registry, ISI Web of Science, Medline, and reference lists of relevant studies to July 2010; hand searches in key journals. STUDY SELECTION: Randomised controlled trials including pregnant women with documented periodontal disease randomised to either treatment with scaling and root planing or no treatment. DATA EXTRACTION: Data were extracted by two independent investigators, and a consensus was reached with the involvement a third. Methodological quality of the studies was assessed with the Cochrane's risk of bias tool, and trials were considered either high or low quality. The primary outcome was preterm birth (

Objective To investigate the effect of alcohol intake patterns on ischaemic heart disease in two countries with contrasting lifestyles, Northern Ireland and France. Design Cohort data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) were analysed. Weekly alcohol consumption, incidence of binge drinking (alcohol >50 g on at least one day a week), incidence of regular drinking (at least one day a week, and alcohol

Objective To determine the cost effectiveness of one-off population based screening for chronic kidney disease based on estimated glomerular filtration rate. Design Cost utility analysis of screening with estimated glomerular filtration rate alone compared with no screening (with allowance for incidental finding of cases of chronic kidney disease). Analyses were stratified by age, diabetes, and the presence or absence of proteinuria. Scenario and sensitivity analyses, including probabilistic sensitivity analysis, were performed. Costs were estimated in all adults and in subgroups defined by age, diabetes, and hypertension. Setting Publicly funded Canadian healthcare system. Participants Large population based laboratory cohort used to estimate mortality rates and incidence of end stage renal disease for patients with chronic kidney disease over a five year follow-up period. Patients had not previously undergone assessment of glomerular filtration rate. Main outcome measures Lifetime costs, end stage renal disease, quality adjusted life years (QALYs) gained, and incremental cost per QALY gained. Results Compared with no screening, population based screening for chronic kidney disease was associated with an incremental cost of $C463 (Canadian dollars in 2009; equivalent to about £275, €308, US $382) and a gain of 0.0044 QALYs per patient overall, representing a cost per QALY gained of $C104 900. In a cohort of 100 000 people, screening for chronic kidney disease would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 675 to 657. In subgroups of people with and without diabetes, the cost per QALY gained was $C22 600 and $C572 000, respectively. In a cohort of 100 000 people with diabetes, screening would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 1796 to 1741. In people without diabetes with and without hypertension, the cost per QALY gained was $C334 000 and $C1 411 100, respectively. Conclusions Population based screening for chronic kidney disease with assessment of estimated glomerular filtration rate is not cost effective overall or in subgroups of people with hypertension or older people. Targeted screening of people with diabetes is associated with a cost per QALY that is similar to that accepted in other interventions funded by public healthcare systems.

OBJECTIVES: To systematically assess the type of outcomes selected and the prevalence of patient reported outcomes in contemporary cardiovascular trials and to quantify any misuse or underuse of patient reported outcomes using a specially developed tool that would allow estimation of the relevance of such outcomes to clinical decision making.DESIGN: Systematic review.DATA SOURCES: Medline and Embase.STUDY SELECTION: Randomised controlled trials of the treatment for or prevention of cardiovascular disease published in 10 leading general medical and cardiology journals from January 2005 to December 2008.RESULTS: Primary outcomes were patient important (death, morbidity, or patient reported outcomes) in only 93 of 413 trials (23%, SE 2%), whereas another 92 (22%, SE 2%) combined these outcomes with other less important ones into a composite. Sixty five trials (16%; SE 2%) used at least one instrument to measure patient reported outcomes, mostly in trials where such information would have been important or crucial for clinical decision making (52 trials). Patient reported outcomes were judged to be of little incremental value to a large number of, mostly explanatory, cardiovascular trials (152 trials). However, many trials in which patient reported outcomes would have been important or crucial for clinical decision making did not report such outcomes (122 of 174 trials, 70%). These included several trials that primarily aimed to improve symptoms or functional status, trials that tested interventions with a considerable potential for causing harm (mainly bleeding) that were not meaningfully measured, and trials with composite outcomes that were dominated by outcomes of questionable importance to patients.CONCLUSIONS: Despite a continued rise in the reporting of patient reported outcomes with no evidence for their misuse in more recent cardiovascular trials, they seem to be still underused once their relevance to clinical decision making has been taken into account. This was largely explained by inappropriate use of composite outcomes and inadequate measurement of harms.

OBJECTIVES: To evaluate the association between a simple lifestyle index based on the recommendations for five lifestyle factors and the incidence of colorectal cancer, and to estimate the proportion of colorectal cancer cases attributable to lack of adherence to the recommendations.DESIGN: Prospective cohort study.SETTING: General population of Copenhagen and Aarhus, Denmark.PARTICIPANTS: 55 487 men and women aged 50-64 years at baseline (1993-7), not previously diagnosed with cancer.MAIN OUTCOME MEASURE: Risk of colorectal cancer in relation to points achieved in the lifestyle index (based on physical activity, waist circumference, smoking, alcohol intake, and diet (dietary fibre, energy percentage from fat, red and processed meat, and fruits and vegetables)) modelled through Cox regression.RESULTS: During a median follow-up of 9.9 years, 678 men and women had colorectal cancer diagnosed. After adjustment for potential confounders, each additional point achieved on the lifestyle index, corresponding to one additional recommendation that was met, was associated with a lower risk of colorectal cancer (incidence rate ratio 0.89 (95% confidence interval 0.82 to 0.96). In this population an estimated total of 13% (95% CI 4% to 22%) of the colorectal cancer cases were attributable to lack of adherence to merely one additional recommendation among all participants except the healthiest. If all participants had followed the five recommendations 23% (9% to 37%) of the colorectal cancer cases might have been prevented. Results were similar for colon and rectal cancer, but only statistically significant for colon cancer.CONCLUSIONS: Adherence to the recommendations for physical activity, waist circumference, smoking, alcohol intake, and diet may reduce colorectal cancer risk considerably, and in this population 23% of the cases might be attributable to lack of adherence to the five lifestyle recommendations. The simple structure of the lifestyle index facilitates its use in public health practice.

Objective: To evaluate the effectiveness of offering antenatal screening for sickle cell disease and thalassaemia in primary care as a way of facilitating earlier uptake of screening.\ud Design: Partial factorial cluster randomised controlled trial.\ud Setting: 25 UK general practices from deprived inner city areas.\ud Participants: Anonymised data on all pregnant women attending participating practices during a six month period before randomisation and a seven month period after randomisation. This included 1708 eligible women.\ud Intervention: Practices were randomised to three groups for seven months: parallel testing in general practice (tests for sickle cell disease and thalassaemia offered to both parents when pregnancy was first reported); sequential testing in general practice (tests offered to mothers when pregnancy was first reported, and subsequently to the partners of women who were found to be carriers); and midwife care (tests offered to mothers at first consultation with a midwife).\ud Main outcome measures: The primary outcome (available for all women) was the proportion of eligible women screened before 10 weeks’ (70 days’) gestation. Secondary outcomes were an offer of screening to women before 10 weeks’ gestation, gestational age at testing, mean interval from first visit to the general practice visit to screening, and women’s knowledge of the carrier status of their baby’s father before 77 days’ (11 weeks’) gestation. The study was designed to detect a 20% absolute increase in screening uptake. Cluster level analyses were adjusted for age group, parity, ethnic group, primary care organisation, and number of general practitioners per practice.\ud Results: Data were analysed for 1708 eligible women. In the midwife care arm, 2% (9/441) of women were screened before 10 weeks’ gestation compared with 24% (161/677) in the GP parallel testing arm and 28% (167/590) in the GP sequential testing arm. The estimated adjusted difference between the midwife care and GP parallel testing arms was 16.5% (95% confidence interval 7.1% to 25.8%; P=0.002) and between the midwife care and GP sequential testing arms was 27.8% (14.8% to 40.7%; P

Objective To do a quantitative systematic review, including published and unpublished data, examining the associations between individual objective measures of physical capability (grip strength, walking speed, chair rising, and standing balance times) and mortality in community dwelling populations.\ud \ud Design Systematic review and meta-analysis.\ud \ud Data sources Relevant studies published by May 2009 identified through literature searches using Embase (from 1980) and Medline (from 1950) and manual searching of reference lists; unpublished results were obtained from study investigators.\ud \ud Study selection Eligible observational studies were those done in community dwelling people of any age that examined the association of at least one of the specified measures of physical capability (grip strength, walking speed, chair rises, or standing balance) with mortality.\ud \ud Data synthesis Effect estimates obtained were pooled by using random effects meta-analysis models with heterogeneity between studies investigated.\ud \ud Results Although heterogeneity was detected, consistent evidence was found of associations between all four measures of physical capability and mortality; those people who performed less well in these tests were found to be at higher risk of all cause mortality. For example, the summary hazard ratio for mortality comparing the weakest with the strongest quarter of grip strength (14 studies, 53 476 participants) was 1.67 (95% confidence interval 1.45 to 1.93) after adjustment for age, sex, and body size (I2=84.0%, 95% confidence interval 74% to 90%; P from Q statistic \ud \ud Conclusions Objective measures of physical capability are predictors of all cause mortality in older community dwelling populations. Such measures may therefore provide useful tools for identifying older people at higher risk of death.

Objective To determine whether initial isoniazid resistance is associated with death during the treatment of tuberculous meningitis. Design Retrospective cohort study. Setting National Tuberculosis Surveillance System at the Centers for Disease Control in the United States. Participants Patients with a clinical diagnosis of tuberculous meningitis, reported to the National Tuberculosis Surveillance System between 1 January 1993 and 31 December 2005. Main outcome measure All cause mortality during antituberculous treatment. Results Between 1993 and 2005, 1896 patients had a clinical diagnosis of tuberculous meningitis and positive cultures from any site. In 123 (6%) of these patients, isoniazid resistance was present on initial susceptibility testing. The unadjusted association between initial isoniazid resistance and subsequent death among these 1896 patients did not reach statistical significance (odds ratio 1.38, 95% confidence interval 0.94 to 2.02). However, among 1614 patients with positive cerebrospinal fluid cultures, a significant unadjusted association was found between initial isoniazid resistance and subsequent death (odds ratio 1.61, 1.08 to 2.40). This association increased after adjustment for age, race, sex, and HIV status (odds ratio 2.07, 1.30 to 3.29). Conclusions Isoniazid resistance on initial susceptibility testing was associated with subsequent death among cases of tuberculous meningitis with positive cerebrospinal fluid cultures. Randomised controlled trials are needed to evaluate the optimal empirical regimen for treating patients with tuberculous meningitis who are at high risk for both initial isoniazid resistance and poor clinical outcomes.

Objective To determine whether a general societal preference for prioritising treatment of rare diseases over common ones exists and could provide a justification for accepting higher cost effectiveness thresholds for orphan drugs. Design Cross sectional survey using a web based questionnaire. Setting Norway. Participants Random sample of 1547 Norwegians aged 40-67. Main outcome measure Choice between funding treatment for a rare disease versus a common disease and how funds should be allocated if it were not possible to treat all patients, for each of two scenarios: identical treatment costs per patient and higher costs for the rare disease. Respondents rated five statements concerning attitudes to equity on a five point Likert scale (5=completely agree). Results For the equal cost scenario, 11.2% (9.6% to 12.8%) of respondents favoured treating the rare disease, 24.9% (21.7% to 26.0%) the common disease, and 64.9% (62.6% to 67.3%) were indifferent. When the rare disease was four times more costly to treat, the results were, respectively, 7.4% (6.1% to 8.7%), 45.3% (42.8% to 47.8%), and 47.3% (44.8% to 49.8%). Rankings for attitude on a Likert scale indicated strong support for the statements “rare disease patients should have the right to treatment even if more expensive” (mean score 4.5, SD 0.86) and “resources should be used to provide the greatest possible health benefits” (3.9, 1.23). Conclusions Despite strong general support for statements expressing a desire for equal treatment rights for patients with rare diseases, there was little evidence that a societal preference for rarity exists if treatment of patients with rare diseases is at the expense of treatment of those with common diseases.