Showing papers in "BMJ in 2009"
TL;DR: The meaning and rationale for each checklist item is explained, and an example of good reporting is included and, where possible, references to relevant empirical studies and methodological literature are included.
Abstract: Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
13,813 citations
TL;DR: The appropriate use and reporting of the multiple imputation approach to dealing with missing data is described by Jonathan Sterne and colleagues.
Abstract: Most studies have some missing data. Jonathan Sterne and colleagues describe the appropriate use and reporting of the multiple imputation approach to dealing with them
5,293 citations
TL;DR: All the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure, indicating that the benefit is explained by blood pressure reduction itself.
Abstract: Objectives To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. Data source Medline (1966-2007). Study selection Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) (“blood pressure difference trials”), and 46 trials compared drugs (“drug comparison trials”). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. Results In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). Conclusions With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.
2,490 citations
TL;DR: Goffman’s Asylums, a key text in the development of deinstitutionalisation, anticipated and indeed predicted some of these changes in psychiatry and has become a concept that is nearly impossible to criticise.
Abstract: “Deinstitutionalisation” has become one of the stated aims of modern, establishment psychiatry. Somewhat like motherhood and apple pie, it seems to have become a concept that is nearly impossible to criticise. Whether institutionalisation was ever exactly like its critics described it is a moot point; another is whether what we have seen since the move to community psychiatry is really “transinstitutionalisation”—with those patients who formerly would have been in asylums now in prison or homeless—rather than deinstitutionalisation. Goffman’s Asylums , a key text in the development of deinstitutionalisation, anticipated and indeed predicted some of these …
1,847 citations
TL;DR: This book introduces and explores subjects that are still at the forefront of child and adolescent psychiatry today, and highlights the work of the acknowledged “father of attachment theory,” John Bowlby.
Abstract: Consisting of seven lectures that John Bowlby gave between 1956 and 1977, this book introduces and explores subjects that are still at the forefront of child and adolescent psychiatry today It is impossible to overestimate Bowlby’s influence on subsequent psychiatric research and practice The acknowledged “father of attachment theory,” he focused on child development, though his interests were far wider
A clear thinker with a dislike of jargon, he could quote Oscar Wilde (“Each man kills the thing he loves”), Shakespeare (“Give sorrow words”), or (rather alarmingly) George Bernard Shaw (“Never hit a child except in hot blood”) Bowlby had …
1,277 citations
TL;DR: Douglas Altman and colleagues describe how to validate models and discuss some of the problems that need to be solved to validate prognostic models.
Abstract: Prognostic models are of little clinical value unless they are shown to work in other samples. Douglas Altman and colleagues describe how to validate models and discuss some of the problems
1,243 citations
TL;DR: Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D.
Abstract: Objective To test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals. Data sources We searched Medline, the Cochrane central register of controlled trials, BIOSIS, and Embase up to August 2008 for relevant articles. Further studies were identified by consulting clinical experts, bibliographies, and abstracts. We contacted authors for additional data when necessary. Review methods Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D 3 (cholecalciferol) or vitamin D 2 (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D 3 (1α-hydroxycalciferol) or 1,25-dihydroxyvitamin D 3 (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion. Results Eight randomised controlled trials (n=2426) of supplemental vitamin D met our inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D 3 concentration (25(OH)D concentration: v ≥60 nmol/l; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71 to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/l or more resulted in a 23% fall reduction (pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to 1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to 1.84). Two randomised controlled trials (n=624) of active forms of vitamin D met our inclusion criteria. Active forms of vitamin D reduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94). Conclusions Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.
1,213 citations
TL;DR: In this paper, the relation between the level of habitual salt intake and stroke or total cardiovascular disease outcome was assessed by a systematic review and meta-analysis of prospective studies published 1966-2008.
Abstract: Objective To assess the relation between the level of habitual salt intake and stroke or total cardiovascular disease outcome. Design Systematic review and meta-analysis of prospective studies published 1966-2008. Data sources Medline (1966-2008), Embase (from 1988), AMED (from 1985), CINAHL (from 1982), Psychinfo (from 1985), and the Cochrane Library. Review methods For each study, relative risks and 95% confidence intervals were extracted and pooled with a random effect model, weighting for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. Criteria for inclusion were prospective adult population study, assessment of salt intake as baseline exposure, assessment of either stroke or total cardiovascular disease as outcome, follow-up of at least three years, indication of number of participants exposed and number of events across different salt intake categories. Results There were 19 independent cohort samples from 13 studies, with 177 025 participants (follow-up 3.5-19 years) and over 11 000 vascular events. Higher salt intake was associated with greater risk of stroke (pooled relative risk 1.23, 95% confidence interval 1.06 to 1.43; P=0.007) and cardiovascular disease (1.14, 0.99 to 1.32; P=0.07), with no significant evidence of publication bias. For cardiovascular disease, sensitivity analysis showed that the exclusion of a single study led to a pooled estimate of 1.17 (1.02 to 1.34; P=0.02). The associations observed were greater the larger the difference in sodium intake and the longer the follow-up. Conclusions High salt intake is associated with significantly increased risk of stroke and total cardiovascular disease. Because of imprecision in measurement of salt intake, these effect sizes are likely to be underestimated. These results support the role of a substantial population reduction in salt intake for the prevention of cardiovascular disease.
1,207 citations
TL;DR: Why research into prognosis is important and how to design such research is explained are explained.
Abstract: Doctors have little specific research to draw on when predicting outcome. In this first article in a series Karel Moons and colleagues explain why research into prognosis is important and how to design such research
1,063 citations
TL;DR: In the second article in their series, Patrick Royston and colleagues describe different approaches to building clinical prognostic models.
Abstract: In the second article in their series, Patrick Royston and colleagues describe different approaches to building clinical prognostic models
1,026 citations
TL;DR: The results support efforts to inform the public about specific actions that can reduce the risks from swine flu and to communicate about the government’s plans and resources.
Abstract: Objective To assess whether perceptions of the swine flu outbreak predicted changes in behaviour among members of the public in England, Scotland, and Wales.
Design Cross sectional telephone survey using random digit dialling.
Setting Interviews by telephone between 8 and 12 May.
Participants 997 adults aged 18 or more who had heard of swine flu and spoke English.
Main outcome measures Recommended change in behaviour (increases in handwashing and surface cleaning or plans made with a “flu friend”) and avoidance behaviours (engaged in one or more of six behaviours such as avoiding large crowds or public transport).
Results 37.8% of participants (n=377) reported performing any recommended behaviour change “over the past four days . . . because of swine flu.” 4.9% (n=49) had carried out any avoidance behaviour. Controlling for personal details and anxiety, recommended changes were associated with perceptions that swine flu is severe, that the risk of catching it is high risk, that the outbreak will continue for a long time, that the authorities can be trusted, that good information has been provided, that people can control their risk of catching swine flu, and that specific behaviours are effective in reducing the risk. Being uncertain about the outbreak and believing that the outbreak had been exaggerated were associated with a lower likelihood of change. The strongest predictor of behaviour change was ethnicity, with participants from ethnic minority groups being more likely to make recommended changes (odds ratio 3.2, 95% confidence interval 2.0 to 5.3) and carry out avoidance behaviours (4.1, 2.0 to 8.4).
Conclusions The results support efforts to inform the public about specific actions that can reduce the risks from swine flu and to communicate about the government’s plans and resources. Tackling the perception that the outbreak has been “over-hyped” may be difficult but worthwhile. Additional research is required into differing reactions to the outbreak among ethnic groups.
TL;DR: Survivors of childhood and adolescent cancer are at substantial risk for cardiovascular disease, and healthcare professionals must be aware of these risks when caring for this growing population.
Abstract: 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 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.
TL;DR: An accurate prognostic model is of no benefit if it is not generalisable or doesn’t change behaviour.
Abstract: An accurate prognostic model is of no benefit if it is not generalisable or doesn’t change behaviour. In the last article in their series Karel Moons and colleagues discuss how to determine the practical value of models
TL;DR: In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.
Abstract: Objectives To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. Design Meta-analysis of randomised trials. Data sources Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with follow-up of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I 2 statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. Results 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed. There was no significant heterogeneity of the treatment effect in clinical subgroups. Conclusion In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.
TL;DR: Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura, and the results suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives.
Abstract: Objective To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. Design Systematic review and meta-analysis. Data sources Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. Data extraction Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. Results Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. Conclusion Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.
TL;DR: This review discusses the evidence that the major complications of “treated” HIV disease—including cardiovascular disease, malignancy, renal disease, …
Abstract: #### Summary points
More than 25 antiretroviral drugs from six therapeutic classes are now available for the management of HIV infection (box 1). Most patients who take medication achieve durable and perhaps lifelong viral suppression, so the classic AIDS related conditions are becoming less common. However, treated patients do not have completely restored health. Compared with people without HIV infection, patients with the infection who are treated with antiretrovirals have increased risk for several “non-AIDS” complications, many of which are commonly associated with ageing (box 2). This risk is particularly evident in patients whose CD4+ T cell counts are below normal during long term treatment, but it is also seen to some extent in those with higher CD4+ T cell counts. As a consequence of the changing spectrum of HIV associated disease, the medical management of HIV infection is evolving—a lower proportion of time is now spent managing drug resistance and short term toxicities and a higher proportion is spent managing these premature age associated complications. This review discusses the evidence that the major complications of “treated” HIV disease—including cardiovascular disease, malignancy, renal disease, …
TL;DR: Qualitative studies alongside randomised controlled trials remain uncommon, even where relatively complex interventions are being evaluated, with the findings seemed to be poorly integrated with those of the trials and often had major methodological shortcomings.
Abstract: Objective To examine the use of qualitative approaches alongside randomised trials of complex healthcare interventions. Design Review of randomised controlled trials of interventions to change professional practice or the organisation of care. Data sources Systematic sample of 100 trials published in English from the register of the Cochrane Effective Practice and Organisation of Care Review Group. Methods Published and unpublished qualitative studies linked to the randomised controlled trials were identified through database searches and contact with authors. Data were extracted from each study by two reviewers using a standard form. We extracted data describing the randomised controlled trials and qualitative studies, the quality of these studies, and how, if at all, the qualitative and quantitative findings were combined. A narrative synthesis of the findings was done. Results 30 of the 100 trials had associated qualitative work and 19 of these were published studies. 14 qualitative studies were done before the trial, nine during the trial, and four after the trial. 13 studies reported an explicit theoretical basis and 11 specified their methodological approach. Approaches to sampling and data analysis were poorly described. For most cases (n=20) we found no indication of integration of qualitative and quantitative findings at the level of either analysis or interpretation. The quality of the qualitative studies was highly variable. Conclusions Qualitative studies alongside randomised controlled trials remain uncommon, even where relatively complex interventions are being evaluated. Most of the qualitative studies were carried out before or during the trials with few studies used to explain trial results. The findings of the qualitative studies seemed to be poorly integrated with those of the trials and often had major methodological shortcomings.
TL;DR: In this paper, a systematic review and meta-analysis of observational studies was conducted to quantify the prevalence of incidental findings on magnetic resonance imaging (MRI) of the brain and found that the number of asymptomatic people needed to scan to detect any incidental brain finding was 37.
Abstract: Objective To quantify the prevalence of incidental findings on magnetic resonance imaging (MRI) of the brain. Design Systematic review and meta-analysis of observational studies. Data sources Ovid Medline (1950 to May 2008), Embase (1980 to May 2008), and bibliographies of relevant articles. Review methods Two reviewers sought and assessed studies of people without neurological symptoms who underwent MRI of the brain with or without intravenous contrast for research purposes or for occupational, clinical, or commercial screening. Main outcome measures Overall disease specific and age specific prevalence of incidental brain findings, calculated by meta-analysis of pooled proportions using DerSimonian-Laird weights in a random effects model. Results In 16 studies, 135 of 19 559 people had neoplastic incidental brain findings (prevalence 0.70%, 95% confidence interval 0.47% to 0.98%), and prevalence increased with age (χ2 for linear trend, P=0.003). In 15 studies, 375 of 15 559 people had non-neoplastic incidental brain findings (prevalence 2.0%, 1.1% to 3.1%, excluding white matter hyperintensities, silent infarcts, and microbleeds). The number of asymptomatic people needed to scan to detect any incidental brain finding was 37. The prevalence of incidental brain findings was higher in studies using high resolution MRI sequences than in those using standard resolution sequences (4.3% v 1.7%, P Conclusions Incidental findings on brain MRI are common, prevalence increases with age, and detection is more likely using high resolution MRI sequences than standard resolution sequences. These findings deserve to be mentioned when obtaining informed consent for brain MRI in research and clinical practice but are not sufficient to justify screening healthy asymptomatic people.
TL;DR: The results support the threshold effect hypothesis, which posits the existence of a threshold of income inequality beyond which adverse impacts on health begin to emerge, and need to be interpreted with caution given the heterogeneity between studies.
Abstract: Objective To provide quantitative evaluations on the association between income inequality and health.
Design Random effects meta-analyses, calculating the overall relative risk for subsequent mortality among prospective cohort studies and the overall odds ratio for poor self rated health among cross sectional studies.
Data sources PubMed, the ISI Web of Science, and the National Bureau for Economic Research database.
Review methods Peer reviewed papers with multilevel data.
Results The meta-analysis included 59 509 857 subjects in nine cohort studies and 1 280 211 subjects in 19 cross sectional studies. The overall cohort relative risk and cross sectional odds ratio (95% confidence intervals) per 0.05 unit increase in Gini coefficient, a measure of income inequality, was 1.08 (1.06 to 1.10) and 1.04 (1.02 to 1.06), respectively. Meta-regressions showed stronger associations between income inequality and the health outcomes among studies with higher Gini (≥0.3), conducted with data after 1990, with longer duration of follow-up (>7 years), and incorporating time lags between income inequality and outcomes. By contrast, analyses accounting for unmeasured regional characteristics showed a weaker association between income inequality and health.
Conclusions The results suggest a modest adverse effect of income inequality on health, although the population impact might be larger if the association is truly causal. The results also support the threshold effect hypothesis, which posits the existence of a threshold of income inequality beyond which adverse impacts on health begin to emerge. The findings need to be interpreted with caution given the heterogeneity between studies, as well as the attenuation of the risk estimates in analyses that attempted to control for the unmeasured characteristics of areas with high levels of income inequality.
TL;DR: The burden of treatment for many people with complex, chronic, comorbidities reduces their capacity to collaborate in their care, and care must be less disruptive to be effective.
Abstract: The burden of treatment for many people with complex, chronic, comorbidities reduces their capacity to collaborate in their care. Carl May, Victor Montori , and Frances Mair argue that to be effective, care must be less disruptive
TL;DR: The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose.
Abstract: Objective To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration. Design National cohort study. Setting Denmark, 1995-2005. Participants Danish women aged 15-49 with no history of cardiovascular or malignant disease. Main outcome measures Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period. Results 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use ( 4 years 2.76, 2.53 to 3.02; P Conclusion The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis.
TL;DR: A high risk of venous thrombosis during the first months of oral contraceptive use irrespective of the type of oral contraceptives is confirmed, and many women do not use the safest brands.
Abstract: Objective To assess the thrombotic risk associated with oral contraceptive use with a focus on dose of oestrogen and type of progestogen of oral contraceptives available in the Netherlands. Design Population based case-control study. Setting Six participating anticoagulation clinics in the Netherlands (Amersfoort, Amsterdam, The Hague, Leiden, Rotterdam, and Utrecht). Participants Premenopausal women Main outcome measures First objectively diagnosed episodes of deep venous thrombosis of the leg or pulmonary embolism. Odds ratios calculated by cross-tabulation with a 95% confidence interval according to Woolf’s method; adjusted odds ratios estimated by unconditional logistic regression, standard errors derived from the model. Results Currently available oral contraceptives increased the risk of venous thrombosis fivefold compared with non-use (odds ratio 5.0, 95% CI 4.2 to 5.8). The risk clearly differed by type of progestogen and dose of oestrogen. The use of oral contraceptives containing levonorgestrel was associated with an almost fourfold increased risk of venous thrombosis (odds ratio 3.6, 2.9 to 4.6) relative to non-users, whereas the risk of venous thrombosis compared with non-use was increased 5.6-fold for gestodene (5.6, 3.7 to 8.4), 7.3-fold for desogestrel (7.3, 5.3 to 10.0), 6.8-fold for cyproterone acetate (6.8, 4.7 to 10.0), and 6.3-fold for drospirenone (6.3, 2.9 to 13.7). The risk of venous thrombosis was positively associated with oestrogen dose. We confirmed a high risk of venous thrombosis during the first months of oral contraceptive use irrespective of the type of oral contraceptives. Conclusions Currently available oral contraceptives still have a major impact on thrombosis occurrence and many women do not use the safest brands with regard to risk of venous thrombosis.
TL;DR: The World Health Organization has launched a new global initiative to try to ensure that non-communicable diseases urgently get given much greater priority in the health and development policies of poor nations and on global aid agendas.
Abstract: The World Health Organization has launched a new global initiative to try to ensure that non-communicable diseases urgently get given much greater priority in the health and development policies of poor nations and on global aid agendas.
At present non-communicable diseases such as heart disease, stroke, cancer, diabetes, and chronic lung disease are responsible for about 35 million deaths each year, or 60% of all deaths worldwide, says WHO. Of these, 80% occur in low and middle income nations.
All four diseases share the same risk factors: tobacco use, unhealthy diets, physical inactivity, and harmful use of alcohol, say WHO experts.
The agency predicts that percentage increases in mortality from non-communicable diseases will reach double digits in the coming years, thus …
TL;DR: The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged ≥65.
Abstract: Objective To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults. Design Meta-analysis of 372 double blind randomised placebo controlled trials. Setting Drug development programmes for any indication in adults. Participants 99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were women. Indications for treatment were major depression (45.6%), other depression (4.6%), other psychiatric disorders (27.6%), and non-psychiatric disorders (22.2%). Main outcome measures Suicidal behaviour (completed suicide, attempted suicide, or preparatory acts) and ideation. Results For participants with non-psychiatric indications, suicidal behaviour and ideation were extremely rare. For those with psychiatric indications, risk was associated with age. For suicidal behaviour or ideation and for suicidal behaviour only, the respective odds ratios were 1.62 (95% confidence interval 0.97 to 2.71) and 2.30 (1.04 to 5.09) for participants aged Conclusions Risk of suicidality associated with use of antidepressants is strongly age dependent. Compared with placebo, the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents. The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged ≥65.
TL;DR: Skills in laparoscopic surgery can be increased in a clinically relevant manner using proficiency based virtual reality simulator training using a previously validated general and task specific rating scale.
Abstract: Objective To assess the effect of virtual reality training on an actual laparoscopic operation. Design Prospective randomised controlled and blinded trial. Setting Seven gynaecological departments in the Zeeland region of Denmark. Participants 24 first and second year registrars specialising in gynaecology and obstetrics. Interventions Proficiency based virtual reality simulator training in laparoscopic salpingectomy and standard clinical education (controls). Main outcome measure The main outcome measure was technical performance assessed by two independent observers blinded to trainee and training status using a previously validated general and task specific rating scale. The secondary outcome measure was operation time in minutes. Results The simulator trained group (n=11) reached a median total score of 33 points (interquartile range 32-36 points), equivalent to the experience gained after 20-50 laparoscopic procedures, whereas the control group (n=10) reached a median total score of 23 (22-27) points, equivalent to the experience gained from fewer than five procedures (P Conclusion Skills in laparoscopic surgery can be increased in a clinically relevant manner using proficiency based virtual reality simulator training. The performance level of novices was increased to that of intermediately experienced laparoscopists and operation time was halved. Simulator training should be considered before trainees carry out laparoscopic procedures. Trial registration ClinicalTrials.gov NCT00311792.
TL;DR: One in three breast cancers detected in a population offered organised screening is overdiagnosed, with data from three countries showing a drop in incidence as the women exceeded the age limit for screening, but the reduction was small.
Abstract: Objective To estimate the extent of overdiagnosis (the detection of cancers that will not cause death or symptoms) in publicly organised screening programmes. Design Systematic review of published trends in incidence of breast cancer before and after the introduction of mammography screening. Data sources PubMed (April 2007), reference lists, and authors. Review methods One author extracted data on incidence of breast cancer (including carcinoma in situ), population size, screening uptake, time periods, and age groups, which were checked independently by the other author. Linear regression was used to estimate trends in incidence before and after the introduction of screening and in older, previously screened women. Meta-analysis was used to estimate the extent of overdiagnosis. Results Incidence data covering at least seven years before screening and seven years after screening had been fully implemented, and including both screened and non-screened age groups, were available from the United Kingdom; Manitoba, Canada; New South Wales, Australia; Sweden; and parts of Norway. The implementation phase with its prevalence peak was excluded and adjustment made for changing background incidence and compensatory drops in incidence among older, previously screened women. Overdiagnosis was estimated at 52% (95% confidence interval 46% to 58%). Data from three countries showed a drop in incidence as the women exceeded the age limit for screening, but the reduction was small and the estimate of overdiagnosis was compensated for in this review. Conclusions The increase in incidence of breast cancer was closely related to the introduction of screening and little of this increase was compensated for by a drop in incidence of breast cancer in previously screened women. One in three breast cancers detected in a population offered organised screening is overdiagnosed.
TL;DR: Investigating whether pre-eclampsia is more common in first pregnancies solely because fewer affected women, who presumably have a higher risk of recurrence, go on to have subsequent pregnancies finds the existence of two distinct conditions: a severe recurrent early onset type affected by chronic factors, genetic or environmental, and a milder sporadic form affected by transient factors.
Abstract: Objective To investigate whether pre-eclampsia is more common in first pregnancies solely because fewer affected women, who presumably have a higher risk of recurrence, go on to have subsequent pregnancies. Design Prospective cohort study. Setting Swedish Medical Birth Register. Participants 763 795 primiparous mothers who had their first births in Sweden, 1987-2004. Main outcome measures Pre-eclampsia. Results The risk of pre-eclampsia was 4.1% in the first pregnancy and 1.7% in later pregnancies overall. However, the risk was 14.7% in the second pregnancy for women who had had pre-eclampsia in their first pregnancy and 31.9% for women who had had pre-eclampsia in the previous two pregnancies. The risk for multiparous women without a history of pre-eclampsia was around 1%. The incidence of pre-eclampsia associated with delivery before 34 weeks’ gestation was 0.42% in primiparous women, 0.11% in multiparous women without a history of pre-eclampsia, and 6.8% and 12.5% in women who had had one or two previous pregnancies affected, respectively. The proportion of women who went on to have a further pregnancy was 4-5% lower after having a pregnancy with any pre-eclampsia but over 10% lower if pre-eclampsia was associated with very preterm delivery. The estimated risk of pre-eclampsia in parous women did not change with standardisation for pregnancy rates. Conclusions Having pre-eclampsia in one pregnancy is a poor predictor of subsequent pregnancy but a strong predictor for recurrence of pre-eclampsia in future gestations. The lower overall risk of pre-eclampsia among parous women was not explained by fewer conceptions among women who had had pre-eclampsia in a previous gestation. Early onset pre-eclampsia might be associated with a reduced likelihood of a future pregnancy and with more recurrences than late onset pre-eclampsia when there are further pregnancies. Findings are consistent with the existence of two distinct conditions: a severe recurrent early onset type affected by chronic factors, genetic or environmental, and a milder sporadic form affected by transient factors.
TL;DR: It is suggested that simply increasing the amount of circulating high density lipoprotein cholesterol does not reduce the risk of coronaryHeart disease events, coronary heart disease deaths, or total deaths, and the results support reduction in lowdensity lipop protein cholesterol as the primary goal for lipid modifying interventions.
Abstract: Objective To investigate the association between treatment induced change in high density lipoprotein cholesterol and total death, coronary heart disease death, and coronary heart disease events (coronary heart disease death and non-fatal myocardial infarction) adjusted for changes in low density lipoprotein cholesterol and drug class in randomised trials of lipid modifying interventions. Design Systematic review and meta-regression analysis of randomised controlled trials. Data sources Medline, Embase, Central, CINAHL, and AMED to October 2006 supplemented by contact with experts in the field. Study selection In teams of two, reviewers independently determined eligibility of randomised trials that tested lipid modifying interventions to reduce cardiovascular risk, reported high density lipoprotein cholesterol and mortality or myocardial infarctions separately for treatment groups, and treated and followed participants for at least six months. Data extraction and synthesis Using standardised, pre-piloted forms, reviewers independently extracted relevant information from each article. The change in lipid concentrations for each trial and the weighted risk ratios for clinical outcomes were calculated. Results The meta-regression analysis included 108 randomised trials involving 299 310 participants at risk of cardiovascular events. All analyses that adjusted for changes in low density lipoprotein cholesterol showed no association between treatment induced change in high density lipoprotein cholesterol and risk ratios for coronary heart disease deaths, coronary heart disease events, or total deaths. With all trials included, change in high density lipoprotein cholesterol explained almost no variability ( Conclusions Available data suggest that simply increasing the amount of circulating high density lipoprotein cholesterol does not reduce the risk of coronary heart disease events, coronary heart disease deaths, or total deaths. The results support reduction in low density lipoprotein cholesterol as the primary goal for lipid modifying interventions.
TL;DR: Any delay inPrimary percutaneous coronary intervention after a patient arrives at hospital is associated with higher mortality in hospital in those admitted with ST elevation myocardial infarction, and time to treatment should be as short as possible, even in centres currently providing primary percutaneously coronary intervention within 90 minutes.
Abstract: Objective To evaluate the association between door-to-balloon time and mortality in hospital in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction to assess the incremental mortality benefit of reductions in door-to-balloon times of less than 90 minutes. Design Prospective cohort study of patients enrolled in the American College of Cardiology National Cardiovascular Data Registry, 2005-6. Setting Acute care hospitals. Participants 43 801 patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention. Main outcome measure Mortality in hospital. Results Median door-to-balloon time was 83 minutes (interquartile range 6-109, 57.9% treated within 90 minutes). Overall mortality in hospital was 4.6%. Multivariable logistic regression models with fractional polynomial models indicated that longer door-to-balloon times were associated with a higher adjusted risk of mortality in hospital in a continuous non-linear fashion (30 minutes=3.0%, 60 minutes=3.5%, 90 minutes=4.3%, 120 minutes=5.6%, 150 minutes=7.0%, 180 minutes=8.4%, P Conclusion Any delay in primary percutaneous coronary intervention after a patient arrives at hospital is associated with higher mortality in hospital in those admitted with ST elevation myocardial infarction. Time to treatment should be as short as possible, even in centres currently providing primary percutaneous coronary intervention within 90 minutes.
TL;DR: The intervention reduced fatigue and improved vitality, aerobic capacity, muscular strength, and physical and functional activity, and emotional wellbeing, but not quality of life.
Abstract: Objective To assess the effect of a multimodal group exercise intervention, as an adjunct to conventional care, on fatigue, physical capacity, general wellbeing, physical activity, and quality of life in patients with cancer who were undergoing adjuvant chemotherapy or treatment for advanced disease. Design Randomised controlled trial. Setting Two university hospitals in Copenhagen, Denmark. Participants 269 patients with cancer; 73 men, 196 women, mean age 47 years (range 20-65) representing 21 diagnoses. Main exclusion criteria were brain or bone metastases. 235 patients completed follow-up. Intervention Supervised exercise comprising high intensity cardiovascular and resistance training, relaxation and body awareness training, massage, nine hours weekly for six weeks in addition to conventional care, compared with conventional care. Main outcome measures European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Medical Outcomes Study Short Form (MOS SF-36), Leisure Time Physical Activity Questionnaire, muscular strength (one repetition maximum), maximum oxygen consumption (Vo 2 max). Statistical methods The general linear model was used for continuous outcome while analysis of associates between categorical outcomes was performed as analysis of marginal homogeneity in contingency tables. Results Adjusted for baseline score, disease, and demographic covariates, the intervention group showed an estimated improvement at six weeks for the primary outcome, fatigue, of −6.6 points (95% confidence interval −12.3 to −0.9, P=0.02; effect size=0.33, 0.04 to 0.61). Significant effects were seen on vitality (effect size 0.55, 95% CI 0.27 to 0.82), physical functioning (0.37, 0.09 to 0.65), role physical (0.37, 0.10 to 0.64), role emotional (0.32, 0.05 to 0.59), and mental health (0.28, 0.02 to 0.56) scores. Improvement was noted in physical capacity: estimated mean difference between groups for maximum oxygen consumption was 0.16 l/min (95% CI 0.1 to 0.2, P Conclusion A supervised multimodal exercise intervention including high and low intensity components was feasible and could safely be used in patients with various cancers who were receiving adjuvant chemotherapy or treatment for advanced disease. The intervention reduced fatigue and improved vitality, aerobic capacity, muscular strength, and physical and functional activity, and emotional wellbeing, but not quality of life. Trial registration Current Controlled trials ISRCTN05322922.