Objective To quantify the link between lower, subclinically symptomatic, levels of psychological distress and cause-specific mortality in a large scale, population based study.

Design Individual participant meta-analysis of 10 large prospective cohort studies from the Health Survey for England. Baseline psychological distress measured by the 12 item General Health Questionnaire score, and mortality from death certification.

Participants 68 222 people from general population samples of adults aged 35 years and over, free of cardiovascular disease and cancer, and living in private households in England at study baseline.

Main outcome measures Death from all causes (n=8365), cardiovascular disease including cerebrovascular disease (n=3382), all cancers (n=2552), and deaths from external causes (n=386). Mean follow-up was 8.2 years (standard deviation 3.5).

Results We found a dose-response association between psychological distress across the full range of severity and an increased risk of mortality (age and sex adjusted hazard ratio for General Health Questionnaire scores of 1-3 v score 0: 1.20, 95% confidence interval 1.13 to 1.27; scores 4-6: 1.43, 1.31 to 1.56; and scores 7-12: 1.94, 1.66 to 2.26; P<0.001 for trend). This association remained after adjustment for somatic comorbidity plus behavioural and socioeconomic factors. A similar association was found for cardiovascular disease deaths and deaths from external causes. Cancer death was only associated with psychological distress at higher levels.

Conclusions Psychological distress is associated with increased risk of mortality from several major causes in a dose-response pattern. Risk of mortality was raised even at lower levels of distress.

Objective To determine the relative effectiveness of second generation ablation techniques in the treatment of heavy menstrual bleeding.

Design Network meta-analysis on the primary outcome measures of amenorrhoea, heavy bleeding, and patients’ dissatisfaction with treatment.

Data sources Nineteen randomised controlled trials (involving 3287 women) were identified through electronic searches of the Cochrane Library, Medline, Embase and PsycINFO databases from inception to April 2011. The reference lists of known relevant articles were searched for further articles. Two reviewers independently selected articles without language restrictions.

Eligibility criteria for selecting studies Randomised controlled trials involving second generation endometrial destruction techniques for women with heavy menstrual bleeding unresponsive to medical treatment.

Results Of the three most commonly used techniques, network meta-analysis showed that bipolar radiofrequency and microwave ablation resulted in higher rates of amenorrhoea than thermal balloon ablation at around 12 months (odds ratio 2.51, 95% confidence interval 1.53 to 4.12, P<0.001; and 1.66, 1.01 to 2.71, P=0.05, respectively), but there was no evidence of a convincing difference between the three techniques in the number of women dissatisfied with treatment or still experiencing heavy bleeding. Compared with bipolar radio frequency and microwave devices, an increased number of women still experienced heavy bleeding after free fluid ablation (2.19, 1.07 to 4.50, P=0.03; and 2.91, 1.23 to 6.88, P=0.02, respectively). Compared with radio frequency ablation, free fluid ablation was associated with reduced rates of amenorrhoea (0.36, 0.19 to 0.67, P=0.004) and increased rates of dissatisfaction (4.79, 1.07 to 21.5, P=0.04). Of the less commonly used devices, endometrial laser intrauterine thermotherapy was associated with increased rates of amenorrhoea compared with all the other devices, while cryoablation led to a reduced rate compared with bipolar radio frequency and microwave.

Conclusions Bipolar radio frequency and microwave ablative devices are more effective than thermal balloon and free fluid ablation in the treatment of heavy menstrual bleeding with second generation endometrial ablation devices.

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.

Objectives To determine the incidence of any and referable diabetic retinopathy in people with type 2 diabetes mellitus attending an annual screening service for retinopathy and whose first screening episode indicated no evidence of retinopathy.

Design Retrospective four year analysis.

Setting Screenings at the community based Diabetic Retinopathy Screening Service for Wales, United Kingdom.

Participants 57 199 people with type 2 diabetes mellitus, who were diagnosed at age 30 years or older and who had no evidence of diabetic retinopathy at their first screening event between 2005 and 2009. 49 763 (87%) had at least one further screening event within the study period and were included in the analysis.

Main outcome measures Annual incidence and cumulative incidence after four years of any and referable diabetic retinopathy. Relations between available putative risk factors and the onset and progression of retinopathy.

Results Cumulative incidence of any and referable retinopathy at four years was 360.27 and 11.64 per 1000 people, respectively. From the first to fourth year, the annual incidence of any retinopathy fell from 124.94 to 66.59 per 1000 people, compared with referable retinopathy, which increased slightly from 2.02 to 3.54 per 1000 people. Incidence of referable retinopathy was independently associated with known duration of diabetes, age at diagnosis, and use of insulin treatment. For participants needing insulin treatment with a duration of diabetes of 10 years or more, cumulative incidence of referable retinopathy at one and four years was 9.61 and 30.99 per 1000 people, respectively.

Conclusions Our analysis supports the extension of the screening interval for people with type 2 diabetes mellitus beyond the currently recommended 12 months, with the possible exception of those with diabetes duration of 10 years or more and on insulin treatment.

Objective An economic evaluation of therapeutic massage, exercise, and lessons in the Alexander technique for treating persistent back pain.

Design Cost consequences study and cost effectiveness analysis at 12 month follow-up of a factorial randomised controlled trial.

Participants 579 patients with chronic or recurrent low back pain recruited from primary care.

Interventions Normal care (control), massage, and six or 24 lessons in the Alexander technique. Half of each group were randomised to a prescription for exercise from a doctor plus behavioural counselling from a nurse.

Main outcome measures Costs to the NHS and to participants. Comparison of costs with Roland-Morris disability score (number of activities impaired by pain), days in pain, and quality adjusted life years (QALYs). Comparison of NHS costs with QALY gain, using incremental cost effectiveness ratios and cost effectiveness acceptability curves.

Results Intervention costs ranged from £30 for exercise prescription to £596 for 24 lessons in Alexander technique plus exercise. Cost of health services ranged from £50 for 24 lessons in Alexander technique to £124 for exercise. Incremental cost effectiveness analysis of single therapies showed that exercise offered best value (£61 per point on disability score, £9 per additional pain-free day, £2847 per QALY gain). For two-stage therapy, six lessons in Alexander technique combined with exercise was the best value (additional £64 per point on disability score, £43 per additional pain-free day, £5332 per QALY gain).

Conclusions An exercise prescription and six lessons in Alexander technique alone were both more than 85% likely to be cost effective at values above £20 000 per QALY, but the Alexander technique performed better than exercise on the full range of outcomes. A combination of six lessons in Alexander technique lessons followed by exercise was the most effective and cost effective option.

Objective To review the effectiveness and safety of clinical officers (healthcare providers trained to perform tasks usually undertaken by doctors) carrying out caesarean section in developing countries compared with doctors.

Design Systematic review with meta-analysis.

Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, BioMed Central, the Reproductive Health Library, and the Science Citation Index (inception-2010) without language restriction.

Study selection Controlled studies.

Data extraction Information was extracted from each selected article on study characteristics, quality, and outcome data. Two independent reviewers extracted data.

Results Six non-randomised controlled studies (16 018 women) evaluated the effectiveness of clinical officers carrying out caesarean section. Meta-analysis found no significant differences between the clinical officers and doctors for maternal death (odds ratio 1.46, 95% confidence interval 0.78 to 2.75; P=0.24) or for perinatal death (1.31, 0.87 to 1.95; P=0.19). The results were heterogeneous, with some studies reporting a higher incidence of both outcomes with clinical officers. Clinical officers were associated with a higher incidence of wound infection (1.58, 1.01 to 2.47; P=0.05) and wound dehiscence (1.89, 1.21 to 2.95; P=0.005). Two studies accounted for confounding factors.

Conclusion Clinical officers and doctors did not differ significantly in key outcomes for caesarean section, but the conclusions are tentative owing to the non-randomised nature of the studies. The increase in wound infection and dehiscence may highlight a particular training need for clinical officers.

Objective To systematically evaluate the effects of physical activity in adult patients after completion of main treatment related to cancer.

Design Meta-analysis of randomised controlled trials with data extraction and quality assessment performed independently by two researchers.

Data sources Pubmed, CINAHL, and Google Scholar from the earliest possible year to September 2011. References from meta-analyses and reviews.

Study selection Randomised controlled trials that assessed the effects of physical activity in adults who had completed their main cancer treatment, except hormonal treatment.

Results There were 34 randomised controlled trials, of which 22 (65%) focused on patients with breast cancer, and 48 outcomes in our meta-analysis. Twenty two studies assessed aerobic exercise, and four also included resistance or strength training. The median duration of physical activity was 13 weeks (range 3-60 weeks). Most control groups were considered sedentary or were assigned no exercise. Based on studies on patients with breast cancer, physical activity was associated with improvements in insulin-like growth factor-I, bench press, leg press, fatigue, depression, and quality of life. When we combined studies on different types of cancer, we found significant improvements in body mass index (BMI), body weight, peak oxygen consumption, peak power output, distance walked in six minutes, right handgrip strength, and quality of life. Sources of study heterogeneity included age, study quality, study size, and type and duration of physical activity. Publication bias did not alter our conclusions.

Conclusions Physical activity has positive effects on physiology, body composition, physical functions, psychological outcomes, and quality of life in patients after treatment for breast cancer. When patients with cancer other than breast cancer were also included, physical activity was associated with reduced BMI and body weight, increased peak oxygen consumption and peak power output, and improved quality of life.

Objective To investigate the association between tea drinking habits in Golestan province, northern Iran, and risk of oesophageal squamous cell carcinoma.

Design Population based case-control study. In addition, patterns of tea drinking and temperature at which tea was drunk were measured among healthy participants in a cohort study.

Setting Golestan province, northern Iran, an area with a high incidence of oesophageal squamous cell carcinoma.

Participants 300 histologically proved cases of oesophageal squamous cell carcinoma and 571 matched neighbourhood controls in the case-control study and 48 582 participants in the cohort study.

Main outcome measure Odds ratio of oesophageal squamous cell carcinoma associated with drinking hot tea.

Results Nearly all (98%) of the cohort participants drank black tea regularly, with a mean volume consumed of over one litre a day. 39.0% of participants drank their tea at temperatures less than 60°C, 38.9% at 60-64°C, and 22.0% at 65°C or higher. A moderate agreement was found between reported tea drinking temperature and actual temperature measurements (weighted κ 0.49). The results of the case-control study showed that compared with drinking lukewarm or warm tea, drinking hot tea (odds ratio 2.07, 95% confidence interval 1.28 to 3.35) or very hot tea (8.16, 3.93 to 16.9) was associated with an increased risk of oesophageal cancer. Likewise, compared with drinking tea four or more minutes after being poured, drinking tea 2-3 minutes after pouring (2.49, 1.62 to 3.83) or less than two minutes after pouring (5.41, 2.63 to 11.1) was associated with a significantly increased risk. A strong agreement was found between responses to the questions on temperature at which tea was drunk and interval from tea being poured to being drunk (weighted κ 0.68).

Conclusion Drinking hot tea, a habit common in Golestan province, was strongly associated with a higher risk of oesophageal cancer.

Objectives To assess the incidence of and risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities among adult survivors of childhood and adolescent cancers.

Design Retrospective cohort study.

Setting 26 institutions that participated in the Childhood Cancer Survivor Study.

Participants 14 358 five year survivors of cancer diagnosed under the age of 21 with leukaemia, brain cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, kidney cancer, neuroblastoma, soft tissue sarcoma, or bone cancer between 1970 and 1986. Comparison group included 3899 siblings of cancer survivors.

Main outcome measures Participants or their parents (in participants aged less than 18 years) completed a questionnaire collecting information on demographic characteristics, height, weight, health habits, medical conditions, and surgical procedures occurring since diagnosis. The main outcome measures were the incidence of and risk factors for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities in survivors of cancer compared with siblings.

Results Survivors of cancer were significantly more likely than siblings to report congestive heart failure (hazard ratio (HR) 5.9, 95% confidence interval 3.4 to 9.6; P<0.001), myocardial infarction (HR 5.0, 95% CI 2.3 to 10.4; P<0.001), pericardial disease (HR 6.3, 95% CI 3.3 to 11.9; P<0.001), or valvular abnormalities (HR 4.8, 95% CI 3.0 to 7.6; P<0.001). Exposure to 250 mg/m2 or more of anthracyclines increased the relative hazard of congestive heart failure, pericardial disease, and valvular abnormalities by two to five times compared with survivors who had not been exposed to anthracyclines. Cardiac radiation exposure of 1500 centigray or more increased the relative hazard of congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities by twofold to sixfold compared to non-irradiated survivors. The cumulative incidence of adverse cardiac outcomes in cancer survivors continued to increase up to 30 years after diagnosis.

Conclusion Survivors of childhood and adolescent cancer are at substantial risk for cardiovascular disease. Healthcare professionals must be aware of these risks when caring for this growing population.

Yes, but we do not know why

Objective To explore how transitions to a palliative care approach are perceived to be managed in acute hospital settings in England.

Design Qualitative study.

Setting Secondary or primary care settings in two contrasting areas of England.

Participants 58 health professionals involved in the provision of palliative care in secondary or primary care.

Results Participants identified that a structured transition to a palliative care approach of the type advocated in UK policy guidance is seldom evident in acute hospital settings. In particular they reported that prognosis is not routinely discussed with inpatients. Achieving consensus among the clinical team about transition to palliative care was seen as fundamental to the transition being effected; however, this was thought to be insufficiently achieved in practice. Secondary care professionals reported that discussions about adopting a palliative care approach to patient management were not often held with patients; primary care professionals confirmed that patients were often discharged from hospital with “false hope” of cure because this information had not been conveyed. Key barriers to ensuring a smooth transition to palliative care included the difficulty of “standing back” in an acute hospital situation, professional hierarchies that limited the ability of junior medical and nursing staff to input into decisions on care, and poor communication.

Conclusion Significant barriers to implementing a policy of structured transitions to palliative care in acute hospitals were identified by health professionals in both primary and secondary care. These need to be addressed if current UK policy on management of palliative care in acute hospitals is to be established.

Objective To determine the comparative effects of the thiazolidinediones (rosiglitazone and pioglitazone) on myocardial infarction, congestive heart failure, and mortality in patients with type 2 diabetes.

Design Systematic review and meta-analysis of observational studies.

Data sources Searches of Medline and Embase in September 2010.

Study selection Observational studies that directly compared the risk of cardiovascular outcomes for rosiglitazone and pioglitazone among patients with type 2 diabetes mellitus were included.

Data extraction Random effects meta-analysis (inverse variance method) was used to calculate the odds ratios for cardiovascular outcomes with thiazolidinedione use. The I2 statistic was used to assess statistical heterogeneity.

Results Cardiovascular outcomes from 16 observational studies (4 case-control studies and 12 retrospective cohort studies), including 810 000 thiazolidinedione users, were evaluated after a detailed review of 189 citations. Compared with pioglitazone, use of rosiglitazone was associated with a statistically significant increase in the odds of myocardial infarction (n=15 studies; odds ratio 1.16, 95% confidence interval 1.07 to 1.24; P<0.001; I2=46%), congestive heart failure (n=8; 1.22, 1.14 to 1.31; P<0.001; I2=37%), and death (n=8; 1.14, 1.09 to 1.20; P<0.001; I2=0%). Numbers needed to treat to harm (NNH), depending on the population at risk, suggest 170 excess myocardial infarctions, 649 excess cases of heart failure, and 431 excess deaths for every 100 000 patients who receive rosiglitazone rather than pioglitazone.

Conclusion Among patients with type 2 diabetes, use of rosiglitazone is associated with significantly higher odds of congestive heart failure, myocardial infarction, and death relative to pioglitazone in real world settings.

Objective To examine the hypothesis that mid-life adiposity is associated with a reduced probability of maintaining an optimal health status among those who survive to older ages.

Design Prospective cohort study.

Setting The Nurses’ Health Study, United States.

Participants 17 065 women who survived until at least the age of 70, provided information on occurrence of chronic disease, cognitive function, physical function, and mental health at older ages, and were free from major chronic diseases at mid-life (mean age was 50 at baseline in 1976).

Main outcome measures Healthy survival to age 70 and over was defined as having no history of 11 major chronic diseases and having no substantial cognitive, physical, or mental limitations.

Results Of the women who survived until at least age 70, 1686 (9.9%) met our criteria for healthy survival. Increased body mass index (BMI) at baseline was significantly associated with linearly reduced odds of healthy survival compared with usual survival, after adjustment for various lifestyle and dietary variables (P<0.001 for trend). Compared with lean women (BMI 18.5-22.9), obese women (BMI ≥30) had 79% lower odds of healthy survival (odds ratio 0.21, 95% confidence interval 0.15 to 0.29). In addition, the more weight gained from age 18 until mid-life, the less likely was healthy survival after the age of 70. The lowest odds of healthy survival were among women who were overweight (BMI ≥25) at age 18 and gained ≥10 kg weight (0.18, 0.09 to 0.36), relative to women who were lean (BMI 18.5-22.9) and maintained a stable weight.

Conclusions These data provide evidence that adiposity in mid-life is strongly related to a reduced probability of healthy survival among women who live to older ages, and emphasise the importance of maintaining a healthy weight from early adulthood.

Objectives To assess the prevalence of honorary and ghost authors in six leading general medical journals in 2008 and compare this with the prevalence reported by authors of articles published in 1996.

Design Cross sectional survey using a web based questionnaire.

Setting International survey of journal authors.

Participants Sample of corresponding authors of 896 research articles, review articles, and editorial/opinion articles published in six general medical journals with high impact factors in 2008: Annals of Internal Medicine, JAMA, Lancet, Nature Medicine, New England Journal of Medicine, and PLoS Medicine.

Main outcome measures Self reported compliance with International Committee of Medical Journal Editors (ICMJE) criteria for authorship for all authors on the selected articles.

Results A total of 630/896 (70.3%) corresponding authors responded to the survey. The prevalence of articles with honorary authorship or ghost authorship, or both, was 21.0% (95% CI 18.0% to 24.3%), a decrease from 29.2% reported in 1996 (P=0.004). Based on 545 responses on honorary authorship, 96 articles (17.6% (95% CI 14.6% to 21.0%)) had honorary authors (range by journal 12.2% to 29.3%), a non-significant change from 1996 (19.3%; P=0.439). Based on 622 responses on ghost authorship, 49 articles (7.9% (6.0% to 10.3%)) had ghost authors (range by journal 2.1% to 11.0%), a significant decline from 1996 (11.5%; P=0.023). The prevalence of honorary authorship was 25.0% in original research reports, 15.0% in reviews, and 11.2% in editorials, whereas the prevalence of ghost authorship was 11.9% in research articles, 6.0% in reviews, and 5.3% in editorials.

Conclusions Evidence of honorary and ghost authorship in 21% of articles published in major medical journals in 2008 suggests that increased efforts by scientific journals, individual authors, and academic institutions are essential to promote responsibility, accountability, and transparency in authorship, and to maintain integrity in scientific publication.

Objective To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.

Design National historical registry based cohort study.

Setting Four registries in Denmark.

Participants Non-pregnant Danish women aged 15-49 with no history of thrombotic disease and followed from January 2001 to December 2009.

Main outcome measures Relative and absolute risks of first time venous thromboembolism.

Results Within 8 010 290 women years of observation, 4307 first ever venous thromboembolic events were recorded and 4246 included, among which 2847 (67%) events were confirmed as certain. Compared with non-users of hormonal contraception, the relative risk of confirmed venous thromboembolism in users of oral contraceptives containing 30-40 µg ethinylestradiol with levonorgestrel was 2.9 (95% confidence interval 2.2 to 3.8), with desogestrel was 6.6 (5.6 to 7.8), with gestodene was 6.2 (5.6 to 7.0), and with drospirenone was 6.4 (5.4 to 7.5). With users of oral contraceptives with levonorgestrel as reference and after adjusting for length of use, the rate ratio of confirmed venous thromboembolism for users of oral contraceptives with desogestrel was 2.2 (1.7 to 3.0), with gestodene was 2.1 (1.6 to 2.8), and with drospirenone was 2.1 (1.6 to 2.8). The risk of confirmed venous thromboembolism was not increased with use of progestogen only pills or hormone releasing intrauterine devices. If oral contraceptives with desogestrel, gestodene, or drospirenone are anticipated to increase the risk of venous thromboembolism sixfold and those with levonorgestrel threefold, and the absolute risk of venous thromboembolism in current users of the former group is on average 10 per 10 000 women years, then 2000 women would need to shift from using oral contraceptives with desogestrel, gestodene, or drospirenone to those with levonorgestrel to prevent one event of venous thromboembolism in one year.

Conclusion After adjustment for length of use, users of oral contraceptives with desogestrel, gestodene, or drospirenone were at least at twice the risk of venous thromboembolism compared with users of oral contraceptives with levonorgestrel.

Objectives To determine the efficacy of intraoperative treatment with low dose tranexamic acid in reducing the rate of perioperative transfusions in patients undergoing radical retropubic prostatectomy.

Design Double blind, parallel group, randomised, placebo controlled trial.

Setting One university hospital in Milan, Italy.

Participants 200 patients older than 18 years and undergoing radical retropubic prostatectomy agreed to participate in the trial. Exclusion criteria were atrial fibrillation, coronary artery disease treated with drug eluting stent, severe chronic renal failure, congenital or acquired thrombophilia, and known or suspected allergy to tranexamic acid.

Interventions Intravenous infusion of tranexamic acid or equivalent volume of placebo (saline) according to the following protocol: loading dose of 500 mg tranexamic acid 20 minutes before surgery followed by continuous infusion of tranexamic acid at 250 mg/h during surgery.

Main outcome measures Primary outcome: number of patients receiving blood transfusions perioperatively. Secondary outcome: intraoperative blood loss. Six month follow-up to assess long term safety in terms of mortality and thromboembolic events.

Results All patients completed treatment and none was lost to follow-up. Patients transfused were 34 (34%) in the tranexamic acid group and 55 (55%) in the control group (absolute reduction in transfusion rate 21% (95% CI 7% to 34%); relative risk of receiving transfusions for patients treated with tranexamic acid 0.62 (0.45 to 0.85); number needed to treat 5 (3 to 14); P=0.004). At follow-up, no patients died and the occurrence of thromboembolic events did not differ between the two groups.

Conclusions Intraoperative treatment with low dose tranexamic acid is safe and effective in reducing the rate of perioperative blood transfusions in patients undergoing radical retropubic prostatectomy.

Trial registration ClinicalTrials.gov identifier NCT00670345.

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.

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<0.001). By contrast, female breast cancer mortality decelerated significantly after age 45 years (decreasing from 19.3% to 2.6% per age-year, P<0.001). We found similar results in US data.

Conclusions Proportional age related changes in ischaemic heart disease mortality, suggesting a loss of reparative reserve, fit longitudinal mortality data from England, Wales, and the United States better than absolute age related changes in mortality. Acceleration in male heart disease mortality at younger ages could explain sex differences rather than any menopausal changes in women.

Objective To determine the preventive effect of manual lymph drainage on the development of lymphoedema related to breast cancer.

Design Randomised single blinded controlled trial.

Setting University Hospitals Leuven, Leuven, Belgium.

Participants 160 consecutive patients with breast cancer and unilateral axillary lymph node dissection. The randomisation was stratified for body mass index (BMI) and axillary irradiation and treatment allocation was concealed. Randomisation was done independently from recruitment and treatment. Baseline characteristics were comparable between the groups.

Intervention For six months the intervention group (n=79) performed a treatment programme consisting of guidelines about the prevention of lymphoedema, exercise therapy, and manual lymph drainage. The control group (n=81) performed the same programme without manual lymph drainage.

Main outcome measures Cumulative incidence of arm lymphoedema and time to develop arm lymphoedema, defined as an increase in arm volume of 200 mL or more in the value before surgery.

Results Four patients in the intervention group and two in the control group were lost to follow-up. At 12 months after surgery, the cumulative incidence rate for arm lymphoedema was comparable between the intervention group (24%) and control group (19%) (odds ratio 1.3, 95% confidence interval 0.6 to 2.9; P=0.45). The time to develop arm lymphoedema was comparable between the two group during the first year after surgery (hazard ratio 1.3, 0.6 to 2.5; P=0.49). The sample size calculation was based on a presumed odds ratio of 0.3, which is not included in the 95% confidence interval. This odds ratio was calculated as (presumed cumulative incidence of lymphoedema in intervention group/presumed cumulative incidence of no lymphoedema in intervention group)×(presumed cumulative incidence of no lymphoedema in control group/presumed cumulative incidence of lymphoedema in control group) or (10/90)×(70/30).

Conclusion Manual lymph drainage in addition to guidelines and exercise therapy after axillary lymph node dissection for breast cancer is unlikely to have a medium to large effect in reducing the incidence of arm lymphoedema in the short term.

Trial registration Netherlands Trial Register No NTR 1055.

Objectives To investigate socioeconomic inequalities in outcome of pregnancy and neonatal mortality associated with congenital anomalies.

Design Retrospective population based registry study.

Setting East Midlands and South Yorkshire regions of England (representing about 10% of births in England and Wales).

Participants All registered cases of nine selected congenital anomalies with poor prognostic outcome audited as part of the United Kingdom’s fetal anomaly screening programme with an end of pregnancy date between 1 January 1998 and 31 December 2007.

Main outcome measures Socioeconomic variation in the risk of selected congenital anomalies; outcome of pregnancy; incidence of live birth and neonatal mortality over time. Deprivation measured with the index of multiple deprivation 2004 at super output area level.

Results There were 1579 fetuses registered with one of the nine selected congenital anomalies. There was no evidence of variation in the overall risk of these anomalies with deprivation (rate ratio for the most deprived 10th with the least deprived 10th: 1.05, 95% confidence interval 0.89 to 1.23). The rate ratio varied with type of anomaly and maternal age (deprivation rate ratio adjusted for maternal age: 1.43 (1.17 to 1.74) for non-chromosomal anomalies; 0.85 (0.63 to 1.15) for chromosomal anomalies). Of the nine anomalies, 86% were detected in the antenatal period, and there was no evidence that this varied with deprivation (rate ratio 0.99, 0.84 to 1.17). The rate of termination after antenatal diagnosis of a congenital anomaly was lower in the most deprived areas compared with the least deprived areas (63% v 79%; rate ratio 0.80, 0.65 to 0.97). Consequently there were significant socioeconomic inequalities in the rate of live birth and neonatal mortality associated with the presence of any of these nine anomalies. Compared with the least deprived areas, the most deprived areas had a 61% higher rate of live births (1.61, 1.21 to 2.15) and a 98% higher neonatal mortality rate (1.98, 1.20 to 3.27) associated with a congenital anomaly.

Conclusions Antenatal screening for congenital anomalies has reduced neonatal mortality through termination of pregnancy. Socioeconomic variation in decisions regarding termination of pregnancy after antenatal detection, however, has resulted in wide socioeconomic inequalities in liveborn infants with a congenital anomaly and subsequent neonatal mortality.

Objective To measure the sensitivity of modern third generation computed tomography in emergency patients being evaluated for possible subarachnoid haemorrhage, especially when carried out within six hours of headache onset.

Design Prospective cohort study.

Setting 11 tertiary care emergency departments across Canada, 2000-9.

Participants Neurologically intact adults with a new acute headache peaking in intensity within one hour of onset in whom a computed tomography was ordered by the treating physician to rule out subarachnoid haemorrhage.

Main outcome measures Subarachnoid haemorrhage was defined by any of subarachnoid blood on computed tomography, xanthochromia in cerebrospinal fluid, or any red blood cells in final tube of cerebrospinal fluid collected with positive results on cerebral angiography.

Results Of the 3132 patients enrolled (mean age 45.1, 2571 (82.1%) with worst headache ever), 240 had subarachnoid haemorrhage (7.7%). The sensitivity of computed tomography overall for subarachnoid haemorrhage was 92.9% (95% confidence interval 89.0% to 95.5%), the specificity was 100% (99.9% to 100%), the negative predictive value was 99.4% (99.1% to 99.6%), and the positive predictive value was 100% (98.3% to 100%). For the 953 patients scanned within six hours of headache onset, all 121 patients with subarachnoid haemorrhage were identified by computed tomography, yielding a sensitivity of 100% (97.0% to 100.0%), specificity of 100% (99.5% to 100%), negative predictive value of 100% (99.5% to 100%), and positive predictive value of 100% (96.9% to 100%).

Conclusion Modern third generation computed tomography is extremely sensitive in identifying subarachnoid haemorrhage when it is carried out within six hours of headache onset and interpreted by a qualified radiologist.

Objective To determine whether a systematic approach to the treatment of pain can reduce agitation in people with moderate to severe dementia living in nursing homes.

Design Cluster randomised controlled trial.

Setting 60 clusters (single independent nursing home units) in 18 nursing homes within five municipalities of western Norway.

Participants 352 residents with moderate to severe dementia and clinically significant behavioural disturbances randomised to a stepwise protocol for the treatment of pain for eight weeks with additional follow-up four weeks after the end of treatment (33 clusters; n=175) or to usual treatment (control, 27 clusters; n=177).

Intervention Participants in the intervention group received individual daily treatment of pain for eight weeks according to the stepwise protocol, with paracetamol (acetaminophen), morphine, buprenorphine transdermal patch, or pregabaline. The control group received usual treatment and care.

Main outcome measures Primary outcome measure was agitation (scores on Cohen-Mansfield agitation inventory). Secondary outcome measures were aggression (scores on neuropsychiatric inventory-nursing home version), pain (scores on mobilisation-observation-behaviour-intensity-dementia-2), activities of daily living, and cognition (mini-mental state examination).

Results Agitation was significantly reduced in the intervention group compared with control group after eight weeks (repeated measures analysis of covariance adjusting for baseline score, P<0.001): the average reduction in scores for agitation was 17% (treatment effect estimate −7.0, 95% confidence interval −3.7 to −10.3). Treatment of pain was also significantly beneficial for the overall severity of neuropsychiatric symptoms (−9.0, −5.5 to −12.6) and pain (−1.3, −0.8 to −1.7), but the groups did not differ significantly for activities of daily living or cognition.

Conclusion A systematic approach to the management of pain significantly reduced agitation in residents of nursing homes with moderate to severe dementia. Effective management of pain can play an important part in the treatment of agitation and could reduce the number of unnecessary prescriptions for psychotropic drugs in this population.

Trial registration ClinicalTrials.gov NCT01021696 and Norwegian Medicines Agency EudraCTnr 2008-007490-20.