Showing papers in "BMJ in 2003"
TL;DR: A new quantity is developed, I 2, which the authors believe gives a better measure of the consistency between trials in a meta-analysis, which is susceptible to the number of trials included in the meta- analysis.
Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice?
Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.
Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4
Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?
A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …
45,105 citations
TL;DR: If medical journals adopt the STARD checklist and flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public.
Abstract: Objective: To improve the accuracy and completeness of reporting of studies of diagnostic accuracy, to allow readers to assess the potential for bias in a study, and to evaluate a study9s generalisability. Methods: The Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a two day consensus meeting, with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy. Results: The search for published guidelines about diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. At the consensus meeting, participants shortened the list to a 25 item checklist, by using evidence, whenever available. A prototype of a flow diagram provides information about the method of patient recruitment, the order of test execution, and the numbers of patients undergoing the test under evaluation and the reference standard, or both. Conclusions: Evaluation of research depends on complete and accurate reporting. If medical journals adopt the STARD checklist and flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public. The Standards for Reporting of Diagnostic Accuracy (STARD) steering group aims to improve the accuracy and completeness of reporting of studies of diagnostic accuracy. The group describes and explains the development of a checklist and flow diagram for authors of reports
2,550 citations
TL;DR: Interference is considered in terms of heterogeneity of treatment effect in subgroups in a randomised trial, such as two age groups, and interaction more generally.
Abstract: We often want to compare two estimates of the same quantity derived from separate analyses. Thus we might want to compare the treatment effect in subgroups in a randomised trial, such as two age groups. The term for such a comparison is a test of interaction. In earlier Statistics Notes we discussed interaction in terms of heterogeneity of treatment effect.1–3 Here we revisit interaction and consider the concept more generally.
The comparison of two estimated quantities, such as means or proportions, each with its standard error, is a general method that can be applied widely. The two estimates should be independent, not obtained from the same individuals—examples are the results from subgroups in a randomised trial or from two independent studies. The samples should be large. If the estimates are E 1 and E 2 with standard errors SE( E 1) and SE( E 2), then the difference d = E 1- E 2 has standard error SE( d )=√[SE( E …
2,391 citations
TL;DR: Investigating whether funding of drug studies by the pharmaceutical industry is associated with outcomes that are favourable to the funder and whether the methods of trials funded by pharmaceutical companies differ from the methods in trials with other sources of support found systematic bias favours products which are made by the company funding the research.
Abstract: Objective To investigate whether funding of drug studies by the pharmaceutical industry is associated with outcomes that are favourable to the funder and whether the methods of trials funded by pharmaceutical companies differ from the methods in trials with other sources of support
Methods Medline (January 1966 to December 2002) and Embase (January 1980 to December 2002) searches were supplemented with material identified in the references and in the authors' personal files Data were independently abstracted by three of the authors and disagreements were resolved by consensus
Results 30 studies were included Research funded by drug companies was less likely to be published than research funded by other sources Studies sponsored by pharmaceutical companies were more likely to have outcomes favouring the sponsor than were studies with other sponsors (odds ratio 405; 95% confidence interval 298 to 551; 18 comparisons) None of the 13 studies that analysed methods reported that studies funded by industry was of poorer quality
Conclusion Systematic bias favours products which are made by the company funding the research Explanations include the selection of an inappropriate comparator to the product being investigated and publication bias
1,917 citations
TL;DR: Time to stop arguing about the process and examine the outcomes of the EU referendum.
Abstract: Problem based learning is used in many medical schools in the United Kingdom and worldwide. This article describes this method of learning and teaching in small groups and explains why it has had an important impact on medical education.
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The group learning process: acquiring desirable learning skills
In problem based learning (PBL) students use “triggers” from the problem case or scenario to define their own learning objectives. Subsequently they do independent, self directed study before returning to the group to discuss and refine their acquired knowledge. Thus, PBL is not about problem solving per se, but rather it uses appropriate problems to increase knowledge and understanding. The process is clearly defined, and the several variations that exist all follow a similar series of steps.
#### Generic skills and attitudes
Group learning facilitates not only the acquisition of knowledge but also several other desirable attributes, such as communication skills, teamwork, problem solving, independent responsibility for learning, sharing information, and respect for others. PBL can therefore be thought of as a small group teaching method that combines the acquisition of knowledge with the development of generic skills and attitudes. Presentation of clinical material as the stimulus for learning enables students to understand the relevance of underlying scientific knowledge and principles in clinical practice.
However, when PBL is introduced into a curriculum, several other issues for curriculum design and implementation need to be tackled. PBL is generally introduced in the context of a defined core curriculum and integration of basic and clinical sciences. It has implications for staffing and learning resources and demands a different approach to timetabling, workload, and assessment. PBL is often used to deliver core material in non-clinical parts of the …
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1,860 citations
TL;DR: The aim was to develop a common understanding of the concept of continuity as a basis for valid and reliable measurement of practice in different settings.
Abstract: The concept—and reality—of continuity of care crosses disciplinary and organisational boundaries. The common definitions provided here should help healthcare providers evaluate continuity more rigorously and improve communication
Patients are increasingly seen by an array of providers in a wide variety of organisations and places, raising concerns about fragmentation of care. Policy reports and charters worldwide urge a concerted effort to enhance continuity,1–3 but efforts to describe the problem or formulate solutions are complicated by the lack of consensus on the definition of continuity. To add to the confusion, other terms such as continuum of care, coordination of care, discharge planning, case management, integration of services, and seamless care are often used synonymously. This synthesis was commissioned by three Canadian health services policy and research bodies. The aim was to develop a common understanding of the concept of continuity as a basis for valid and reliable measurement of practice in different settings.
We searched academic and policy literature for documents in which the principal focus was continuity of patient care or continuity. We searched electronic databases (Medline, HealthSTAR, Embase, CINAHL, Current Contents, PsychINFO, AIDSLINE, CancerLit, Cochrane Library, Dissertation abstracts, Papers1st (conferences and paper abstracts), Web of Science, WorldCat) as well as web library catalogues, peer reviewed internet sites, internet search engines, and several in-house databases. The search included documents dated from 1966 to November 2001 written in English, French, or Spanish. The reviewers (RJR, JLH, RMcK) used a data abstraction form to summarise relevant documents from every health discipline, and all reviewers read key documents.
We presented the results of an initial review of 314 documents to participants of a workshop on continuity held in Vancouver in June 2001. We obtained structured feedback to a discussion paper, problem based scenarios, and expert presentations. Participants validated the common themes …
1,836 citations
TL;DR: Statins can lower LDL cholesterol concentration by an average of 1.8 mmol/l which reduces the risk of IHD events by about 60% and stroke by 17% and is corroborated by results from the nine cohort studies.
Abstract: Objectives To determine by how much statins reduce serum concentrations of low density lipoprotein (LDL) cholesterol and incidence of ischaemic heart disease (IHD) events and stroke, according to drug, dose, and duration of treatment. Design Three meta-analyses: 164 short term randomised placebo controlled trials of six statins and LDL cholesterol reduction; 58 randomised trials of cholesterol lowering by any means and IHD events; and nine cohort studies and the same 58 trials on stoke. Main outcome measures Reductions in LDL cholesterol according to statin and dose; reduction in IHD events and stroke for a specified reduction in LDL cholesterol. Results Reductions in LDL cholesterol (in the 164 trials) were 2.8 mmol/l (60%) with rosuvastatin 80 mg/day, 2.6 mmol/l (55%) with atorvastatin 80 mg/day, 1.8 mmol/l (40%) with atorvastatin 10 mg/day, lovastatin 40 mg/day, simvastatin 40 mg/day, or rosuvastatin 5 mg/day, all from pretreatment concentrations of 4.8 mmol/l. Pravastatin and fluvastatin achieved smaller reductions. In the 58 trials, for an LDL cholesterol reduction of 1.0 mmol/l the risk of IHD events was reduced by 11% in the first year of treatment, 24% in the second year, 33% in years three to five, and by 36% thereafter (P Conclusions Statins can lower LDL cholesterol concentration by an average of 1.8 mmol/l which reduces the risk of IHD events by about 60% and stroke by 17%.
1,709 citations
TL;DR: In this paper, the combination of drugs and vitamins, and their doses, for use in a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects was proposed.
Abstract: Objectives To determine the combination of drugs and vitamins, and their doses, for use in a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects. The strategy was to simultaneously reduce four cardiovascular risk factors (low density lipoprotein cholesterol, blood pressure, serum homocysteine, and platelet function) regardless of pretreatment levels. Design We quantified the efficacy and adverse effects of the proposed formulation from published meta-analyses of randomised trials and cohort studies and a meta-analysis of 15 trials of low dose (50-125 mg/day) aspirin. Outcome measures Proportional reduction in ischaemic heart disease (IHD) events and strokes; life years gained; and prevalence of adverse effects. Results The formulation which met our objectives was: a statin (for example, atorvastatin (daily dose 10 mg) or simvastatin (40 mg)); three blood pressure lowering drugs (for example, a thiazide, a β blocker, and an angiotensin converting enzyme inhibitor), each at half standard dose; folic acid (0.8 mg); and aspirin (75 mg). We estimate that the combination (which we call the Polypill) reduces IHD events by 88% (95% confidence interval 84% to 91%) and stroke by 80% (71% to 87%). One third of people taking this pill from age 55 would benefit, gaining on average about 11 years of life free from an IHD event or stroke. Summing the adverse effects of the components observed in randomised trials shows that the Polypill would cause symptoms in 8-15% of people (depending on the precise formulation). Conclusion The Polypill strategy could largely prevent heart attacks and stroke if taken by everyone aged 55 and older and everyone with existing cardiovascular disease. It would be acceptably safe and with widespread use would have a greater impact on the prevention of disease in the Western world than any other single intervention.
1,445 citations
TL;DR: By making use of scientific evidence on the effects of tobacco, the member states of WHO have negotiated their first global health treaty and could act as a possible model for tackling other health issues.
Abstract: Many health problems require international action, but getting governments to agree on strategies for prevention or treatment is difficult. By making use of scientific evidence on the effects of tobacco, the member states of WHO have negotiated their first global health treaty. If the treaty can be implemented effectively, it could act as a possible model for tackling other health issues
When Dr Gro Harlem Brundtland became director general of the World Health Organization in 1998, she clearly stated that the tobacco epidemic should be tackled by an international collective action and that WHO should take a leadership role.1 In 1999, WHO started work on the WHO Framework Convention on Tobacco Control, which was endorsed by member states on 21 May 2003. It is the first time WHO has used its constitutional authority in global public health to develop a legal instrument aimed at improving population health. The initiation and negotiation of the framework convention was based strongly on the accumulation of scientific evidence.2 We review the development and scientific basis of the convention and discuss its implications and the potential of international collective action against threats to global public health.
The structural basis for framework conventions is to use an incremental process in making law. It begins with a framework convention that establishes a general consensus on the relevant facts and the system of governance for an issue. This is followed by the development of more specific commitments and institutional arrangements in subsequent protocols.3 However, depending on the political will, framework conventions can also include quite specific provisions. In the case of the WHO Framework Convention on Tobacco Control, the powerful political momentum behind the treaty has ensured that several detailed provisions have been incorporated into the final text.4
The framework convention is the first …
1,262 citations
TL;DR: Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community.
Abstract: Objective To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community. Design Randomised double blind controlled trial of 100 000 IU oral vitamin D3 (cholecalciferol) supplementation or matching placebo every four months over five years. Setting and participants 2686 people (2037 men and 649 women) aged 65›85 years living in the general community, recruited from the British doctors register and a general practice register in Suffolk. Main outcome measures Fracture incidence and total mortality by cause. Results After five years 268 men and women had incident fractures, of whom 147 had fractures in common osteoporotic sites (hip, wrist or forearm, or vertebrae). Relative risks in the vitamin D group compared with the placebo group were 0.78 (95% confidence interval 0.61 to 0.99, P=0.04) for any first fracture and 0.67 (0.48 to 0.93, P=0.02) for first hip, wrist or forearm, or vertebral fracture. 471 participants died. The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 (0.74 to 1.06, P=0.18). Findings were consistent in men and women and in doctors and the general practice population. Conclusion Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community.
1,229 citations
TL;DR: Combination low dose drug treatment increases efficacy and reduces adverse effects and three drugs at half standard dose are estimated to lower blood pressure and thereby reduce the risk of stroke by 63% and ischaemic heart disease events by 46% at age 60-69.
Abstract: Objective To determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination.
Design Meta-analysis of 354 randomised double blind placebo controlled trials of thiazides, β blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, and calcium channel blockers in fixed dose.
Subjects 40 000 treated patients and 16 000 patients given placebo.
Main outcome measures Placebo adjusted reductions in systolic and diastolic blood pressure and prevalence of adverse effects, according to dose expressed as a multiple of the standard (recommended) doses of the drugs.
Results All five categories of drug produced similar reductions in blood pressure. The average reduction was 9.1 mm Hg systolic and 5.5 mm Hg diastolic at standard dose and 7.1 mm Hg systolic and 4.4 mm Hg diastolic (20% lower) at half standard dose. The drugs reduced blood pressure from all pretreatment levels, more so from higher levels; for a 10 mm Hg higher blood pressure the reduction was 1.0 mm Hg systolic and 1.1 mm Hg diastolic greater. The blood pressure lowering effects of different categories of drugs were additive. Symptoms attributable to thiazides, β blockers, and calcium channel blockers were strongly dose related; symptoms caused by ACE inhibitors (mainly cough) were not dose related. Angiotensin II receptor antagonists caused no excess of symptoms. The prevalence of symptoms with two drugs in combination was less than additive. Adverse metabolic effects (such as changes in cholesterol or potassium) were negligible at half standard dose.
Conclusions Combination low dose drug treatment increases efficacy and reduces adverse effects. From the average blood pressure in people who have strokes (150/90 mm Hg) three drugs at half standard dose are estimated to lower blood pressure by 20 mm Hg systolic and 11 mm Hg diastolic and thereby reduce the risk of stroke by 63% and ischaemic heart disease events by 46% at age 60-69.
TL;DR: Evidence supports the use of two dimensional ultrasonography for central venous cannulation in adults and in infants.
Abstract: Objectives To assess the evidence for the clinical effectiveness of ultrasound guided central venous cannulation. Data sources 15 electronic bibliographic databases, covering biomedical, science, social science, health economics, and grey literature. Design Systematic review and meta-analysis of randomised controlled trials. Populations Patients scheduled for central venous access. Intervention reviewed Guidance using real time two dimensional ultrasonography or Doppler needles and probes compared with the anatomical landmark method of cannulation. Data extraction Risk of failed catheter placement (primary outcome), risk of complications from placement, risk of failure on first attempt at placement, number of attempts to successful catheterisation, and time (seconds) to successful catheterisation. Data synthesis 18 trials (1646 participants) were identified. Compared with the landmark method, real time two dimensional ultrasound guidance for cannulating the internal jugular vein in adults was associated with a significantly lower failure rate both overall (relative risk 0.14, 95% confidence interval 0.06 to 0.33) and on the first attempt (0.59, 0.39 to 0.88). Limited evidence favoured two dimensional ultrasound guidance for subclavian vein and femoral vein procedures in adults (0.14, 0.04 to 0.57 and 0.29, 0.07 to 1.21, respectively). Three studies in infants confirmed a higher success rate with two dimensional ultrasonography for internal jugular procedures (0.15, 0.03 to 0.64). Doppler guided cannulation of the internal jugular vein in adults was more successful than the landmark method (0.39, 0.17 to 0.92), but the landmark method was more successful for subclavian vein procedures (1.48, 1.03 to 2.14). No significant difference was found between these techniques for cannulation of the internal jugular vein in infants. An indirect comparison of relative risks suggested that two dimensional ultrasonography would be more successful than Doppler guidance for subclavian vein procedures in adults (0.09, 0.02 to 0.38). Conclusions Evidence supports the use of two dimensional ultrasonography for central venous cannulation.
TL;DR: Results of adjusted indirect comparison usually, but not always, agree with those of head to head randomised trials The validity ofadjusted indirect comparisons depends on the internal validity and similarity of the trials involved.
Abstract: Objective: To determine the validity of adjusted indirect comparisons by using data from published meta-analyses of randomised trials. Design: Direct comparison of different interventions in randomised trials and adjusted indirect comparison in which two interventions were compared through their relative effect versus a common comparator. The discrepancy between the direct and adjusted indirect comparison was measured by the difference between the two estimates. Data sources: Database of abstracts of reviews of effectiveness (1994-8), the Cochrane database of systematic reviews, Medline, and references of retrieved articles. Results: 44 published meta-analyses (from 28 systematic reviews) provided sufficient data. In most cases, results of adjusted indirect comparisons were not significantly different from those of direct comparisons. A significant discrepancy (P Conclusions: Adjusted indirect comparisons usually but not always agree with the results of head to head randomised trials. When there is no or insufficient direct evidence from randomised trials, the adjusted indirect comparison may provide useful or supplementary information on the relative efficacy of competing interventions. The validity of the adjusted indirect comparisons depends on the internal validity and similarity of the included trials. What is already known on this topic Many competing interventions have not been compared in randomised trials Indirect comparison of competing interventions has been carried out in systematic reviews, often implicitly Indirect comparison adjusted by a common control can partially take account of prognostic characteristics of patients in different trials What this study adds Results of adjusted indirect comparison usually, but not always, agree with those of head to head randomised trials The validity of adjusted indirect comparisons depends on the internal validity and similarity of the trials involved
TL;DR: It is thought that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
Abstract: Objectives To determine whether parachutes are effective in preventing major trauma related to gravitational challenge. Design Systematic review of randomised controlled trials. Data sources: Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists. Study selection: Studies showing the effects of using a parachute during free fall. Main outcome measure Death or major trauma, defined as an injury severity score > 15. Results We were unable to identify any randomised controlled trials of parachute intervention. Conclusions As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
TL;DR: In this article, the accuracy of physicians' clinical predictions of survival in terminally ill cancer patients was systematically reviewed, and the authors concluded that physicians' predictions were accurate in most cases.
Abstract: Objective To systematically review the accuracy of physicians’ clinical predictions of survival in terminally ill cancer patients.
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TL;DR: Research is endlessly seductive; writing is hard work; one has to sit down on that chair and think and …
Abstract: Research is endlessly seductive; writing is hard work. One has to sit down on that chair and think and …
TL;DR: People with acute low back pain and associated disability usually improve rapidly within weeks, pain and disability are typically ongoing, and recurrences are common.
Abstract: Objectives To describe the course of acute low back pain and sciatica and to identify clinically important prognostic factors for these conditions.
Design Systematic review.
Data sources Searches of Medline, Embase, Cinahl, and Science Citation Index and iterative searches of bibliographies.
Main outcome measures Pain, disability, and return to work.
Results 15 studies of variable methodological quality were included. Rapid improvements in pain (mean reduction 58% of initial scores), disability (58%), and return to work (82% of those initially off work) occurred in one month. Further improvement was apparent until about three months. Thereafter levels for pain, disability, and return to work remained almost constant. 73% of patients had at least one recurrence within 12 months.
Conclusions People with acute low back pain and associated disability usually improve rapidly within weeks. None the less, pain and disability are typically ongoing, and recurrences are common.
TL;DR: This article describes how to make best use of available evidence and reach a consensus on quality indicators to improve the quality of health care.
Abstract: Before we can take steps to improve the quality of health care, we need to define what quality care means. This article describes how to make best use of available evidence and reach a consensus on quality indicators
TL;DR: This chapter describes several educational theories and guiding principles and then shows how these could be applied to three case studies realting to the “real world.”
Abstract: How many times have we as teachers been confronted with situations in which we really were not sure what to do? We “flew by the seat of our pants,” usually doing with our learners what had been done with us. It would be useful to be able to turn to a set of guiding principles based on evidence, or at least on long term successful experience.
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Fortunately, a body of theory exists that can inform practice. An unfortunate gap between academics and practitioners, however, has led to a perception of theory as belonging to an “ivory tower” and not relevant to practice. Yet the old adage that “there is nothing more practical than a good theory” still rings true today. This chapter describes several educational theories and guiding principles and then shows how these could be applied to three case studies realting to the “real world.”
Malcolm Knowles introduced the term “andragogy” to North America, defining it as “the art and science of helping adults learn.” Andragogy is based on five assumptions—about how adults learn and their attitude towards and motivation for learning.
#### Andragogy—five assumptions about adult learning
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Learners need to feel safe and comfortable expressing themselves
Knowles later derived seven principles of andragogy. Most theorists agree that andragogy is not really a theory of adult learning, but they regard Knowles' principles as guidelines on how to teach learners who tend to be at least somewhat independent and self directed. His principles can be summarised …
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TL;DR: Non-invasive positive pressure ventilation should be considered early in the course of respiratory failure and before severe acidosis ensues, to avoid the need for endotracheal intubation and reduce mortality in patients with COPD.
Abstract: Objectives: To determine the effectiveness of non-invasive positive pressure ventilation (NPPV) in the management of respiratory failure secondary to acute exacerbation of chronic obstructive pulmonary disease. Design: Systematic review of randomised controlled trials that compared NPPV and usual medical care with usual medical care alone in patients admitted to hospital with respiratory failure resulting from an exacerbation of chronic obstructive pulmonary disease and with PaCO2 >6 kPa. Results: The eight studies included in the review showed that, compared with usual care alone, NPPV as an adjunct to usual care was associated with a lower mortality (relative risk 0.41 (95% confidence interval 0.26 to 0.64)), a lower need for intubation (relative risk 0.42 (0.31 to 0.59)), lower likelihood of treatment failure (relative risk 0.51 (0.38 to 0.67)), and greater improvements at 1 hour in pH (weighted mean difference 0.03 (0.02 to 0.04)), PaCO2 (weighted mean difference −0.40 kPa (−0.78 to −0.03)), and respiratory rate (weighted mean difference −3.08 breaths per minute (−4.26 to −1.89)). NPPV resulted in fewer complications associated with treatment (relative risk 0.32 (0.18 to 0.56)) and shorter duration of stay in hospital (weighted mean difference −3.24 days (−4.42 to −2.06)). Conclusions: NPPV should be the first line intervention in addition to usual medical care to manage respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease in all suitable patients. NPPV should be tried early in the course of respiratory failure and before severe acidosis, to reduce mortality, avoid endotracheal intubation, and decrease treatment failure. What is already known on this topic Prospective studies, especially the larger studies, have shown that non-invasive positive pressure ventilation (NPPV) reduces the need for intubation, improves survival, and reduces complications in patients with respiratory failure resulting from exacerbation of chronic obstructive pulmonary disease (COPD) A previous meta-analysis showed NPPV to be an effective intervention, including for acute exacerbations of COPD, but some studies in this meta-analysis contained mixed groups of patients and were not of good quality What this study adds Evidence from good quality, randomised controlled trials shows that NPPV is an effective treatment for acute exacerbations of COPD NPPV should be considered early in the course of respiratory failure and before severe acidosis ensues, to avoid the need for endotracheal intubation and reduce mortality in patients with COPD
TL;DR: It means no more than respect for persons or their autonomy for an ethical analysis of medical activities.
Abstract: It means no more than respect for persons or their autonomy
Appeals to human dignity populate the landscape of medical ethics. Claims that some feature of medical research or practice violates or threatens human dignity abound, often in connection with developments in genetics or reproductive technology. But are such charges coherent? Is dignity a useful concept for an ethical analysis of medical activities? A close inspection of leading examples shows that appeals to dignity are either vague restatements of other, more precise, notions or mere slogans that add nothing to an understanding of the topic.
Possibly the most prominent references to dignity appear in the many international human rights instruments, such as the United Nations' universal declaration of human rights.1 With few exceptions, these conventions do not address medical treatment or research. A leading exception is the Council of Europe's convention for the protection of human rights and dignity of the human being with regard to the application of biology and medicine.2 In this and other documents “dignity” seems to have no meaning beyond what is implied by the principle of medical ethics, respect for persons: the need to obtain voluntary, informed consent; the requirement to protect confidentiality; …
TL;DR: Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome and its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome.
Abstract: Objective To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome.
Design Systematic review and meta-analysis.
Data sources Randomised controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent.
Selection of studies 13 trials were included for analysis, including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence.
Main outcome measure Pregnancy and ovulation rates. Secondary outcomes of clinical and biochemical features of polycystic ovary syndrome.
Results Meta-analysis showed that metformin is effective in achieving ovulation in women with polycystic ovary syndrome, with odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with clomifene alone. An analysis of pregnancy rates shows a significant treatment effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol. We found no evidence of any effect on body mass index or waist:hip ratio. Metformin was associated with a higher incidence of nausea, vomiting, and other gastrointestinal disturbance.
Conclusions Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome. Its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome. No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy. It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.
TL;DR: Three constructs are explored: continuing medical education (CME), continuing professional development (CPD), and (the newest of the three) knowledge translation, which has the potential to improve understanding of, and overcome the barriers to, implementing evidence based practice.
Abstract: A large gulf remains between what we know and what we practise. Eisenberg and Garzon point to widespread variation in the use of aspirin, calcium antagonists, βblockers, and anti-ischaemic drugs in the United States, Europe, and Canada despite good evidence on their best use.1 Such variation is common not only internationally but within countries.2 Large gaps also exist between best evidence and practice in the implementation of guidelines. Failure to follow best evidence highlights issues of underuse, overuse, and misuse of drugs3 and has led to widespread interest in the safety of patients.4
Not surprisingly, many attempts have been made to reduce the gap between evidence and practice. These have included educational strategies to alter practitioners' behaviour5 and organisational and administrative interventions. We explore three constructs: continuing medical education (CME), continuing professional development (CPD), and (the newest of the three) knowledge translation (box). Knowledge translation both subsumes and broadens the concepts of CME and CPD and has the potential to improve understanding of, and overcome the barriers to, implementing evidence based practice.
### Continuing medical education
CME refers to education after certification and licensure. It is arguably the most complex, and clearly the longest, phase of medical education. Most physicians think of continuing medical education in terms of the traditional medical conference, with rows of tables, pitchers of ice water, green table cloths, and a lecturer at the front of the room.7 Many accreditation systems in the United States, United Kingdom, and Canada value attendance at such activities. This reinforces the teacher driven nature of continuing medical education, which gives little attention to the concept of professional development.
“Knowledge translation is defined as the exchange, synthesis and ethically sound application of knowledge—within a complex system of interactions among researchers and users—to accelerate the capture of …
TL;DR: A glance at the literature shows a shocking lack of statistical understanding of the outcomes of modern technologies, from standard screening tests for HIV infection to DNA evidence.
Abstract: Bad presentation of medical statistics such as the risks associated with a particular intervention can lead to patients making poor decisions on treatment. Particularly confusing are single event probabilities, conditional probabilities (such as sensitivity and specificity), and relative risks. How can doctors improve the presentation of statistical information so that patients can make well informed decisions?
TL;DR: Prospective recording of blood pressure and proteinuria shows that women who experienced raised blood pressure in pregnancy have a long term risk of hypertension, and long term cardiovascular risks are greater for women who had pre-eclampsia than those who experienced gestational hypertension (hypertension without proteinuria).
Abstract: Objective: To examine the association between hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) and the development of circulatory diseases in later life. Design: Cohort study of women who had pre-eclampsia during their first singleton pregnancy. Two comparison groups were matched for age and year of delivery, one with gestational hypertension and one with no history of raised blood pressure. Setting: Maternity services in the Grampian region of Scotland. Participants: Women selected from the Aberdeen maternity and neonatal databank who were resident in Aberdeen and who delivered a first, live singleton from 1951 to 1970. Main outcome measures: Current vital and cardiovascular health status ascertained through postal questionnaire survey, clinical examination, linkage to hospital discharge, and mortality data. Results: There were significant positive associations between pre-eclampsia/eclampsia or gestational hypertension and later hypertension in all measures. The adjusted relative risks varied from 1.13-3.72 for gestational hypertension and 1.40-3.98 for pre-eclampsia or eclampsia. The adjusted incident rate ratio for death from stroke for the pre-eclampsia/eclampsia group was 3.59 (95% confidence interval 1.04 to 12.4). Conclusions: Hypertensive diseases of pregnancy seem to be associated in later life with diseases related to hypertension. If greater awareness of this association leads to earlier diagnosis and improved management, there may be scope for reducing a proportion of the morbidity and mortality from such diseases. What is already known on this topic Much is known about the effect of cardiovascular risks factors that are shared by men and women, but less on those specific to women Retrospective studies, based on patient recall, suggest that hypertension in pregnancy may be associated with increased risk of cardiovascular diseases in later life What this study adds Prospective recording of blood pressure and proteinuria shows that women who experienced raised blood pressure in pregnancy have a long term risk of hypertension Women who experience raise blood pressure in pregnancy have an increased risk of stroke and, to a lesser extent, an increased risk of ischaemic heart disease Long term cardiovascular risks are greater for women who had pre-eclampsia than those who experienced gestational hypertension (hypertension without proteinuria)
TL;DR: The research in this field in the past decade is reviewed to explore all the available methods, establish their validity and reliability, and examine the possibility of using these methods on the basis of the available evidence.
Abstract: In the past few years, considerable developments have been made in the objective assessment of technical proficiency of surgeons. Technical skills should be assessed during training, and various methods have been developed for this purpose
Surgical competence entails a combination of knowledge, technical skills, decision making, communication skills, and leadership skills. Of these, dexterity or technical proficiency is considered to be of paramount importance among surgical trainees. The assessment of technical skills during training has been considered to be a form of quality assurance for the future.1 Typically surgical learning is based on an apprenticeship model. In this model the assessment of technical proficiency is the responsibility of the trainers. However, their assessment is largely subjective.2 Objective assessment is essential because deficiencies in training and performance are difficult to correct without objective feedback.3
The introduction of the Calman system in the United Kingdom, the implementation of the European Working Time Directive, and the financial pressures to increase productivity4 have reduced the opportunity to learn surgical skills in the operating theatre. Studies have shown that these changes have resulted in nearly halving the surgical case load that trainees are exposed to.5 Surgical proficiency must therefore be acquired in less time, with the risk that some surgeons may not be sufficiently skilled at the completion of training.6 This and increasing attention of the public and media on the performance of doctors have given rise to an interest in the development of robust methods of assessment of technical skills.7 We review the research in this field in the past decade. Our objectives are to explore all the available methods, establish their validity and reliability, and examine the possibility of using these methods on the basis of the available evidence.
We collected information for this review from …
TL;DR: Any attempt to recommend a specific selective serotonin reuptake inhibitor from the publicly available data only is likely to be based on biased evidence.
Abstract: Objectives To investigate the relative impact on publication bias caused by multiple publication, selective publication, and selective reporting in studies sponsored by pharmaceutical companies. Design 42 placebo controlled studies of five selective serotonin reuptake inhibitors submitted to the Swedish drug regulatory authority as a basis for marketing approval for treating major depression were compared with the studies actually published (between 1983 and 1999). Results Multiple publication: 21 studies contributed to at least two publications each, and three studies contributed to five publications. Selective publication: studies showing significant effects of drug were published as stand alone publications more often than studies with non-significant results. Selective reporting: many publications ignored the results of intention to treat analyses and reported the more favourable per protocol analyses only. Conclusions The degree of multiple publication, selective publication, and selective reporting differed between products. Thus, any attempt to recommend a specific selective serotonin reuptake inhibitor from the publicly available data only is likely to be based on biased evidence.
TL;DR: Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months without evidence of adverse effects.
Abstract: Objective: To assess the long term effectiveness of the “green prescription” programme, a clinician based initiative in general practice that provides counselling on physical activity. Design: Cluster randomised controlled trial. Practices were randomised before systematic screening and recruitment of patients. Setting: 42 rural and urban general practices in one region of New Zealand. Subjects: All sedentary 40–79 year old patients visiting their general practitioner during the study9s recruitment period. Intervention: General practitioners were prompted by the patient to give oral and written advice on physical activity during usual consultations. Exercise specialists continued support by telephone and post. Control patients received usual care. Main outcome measures: Change in physical activity, quality of life (as measured by the “short form 36” (SF-36) questionnaire), cardiovascular risk (Framingham and D9Agostino equations), and blood pressure over a 12 month period. Results: 74% (117/159) of general practitioners and 66% (878/1322) of screened eligible patients participated in the study. The follow up rate was 85% (750/878). Mean total energy expenditure increased by 9.4 kcal/kg/week (P=0.001) and leisure exercise by 2.7 kcal/kg/week (P=0.02) or 34 minutes/week more in the intervention group than in the control group (P=0.04). The proportion of the intervention group undertaking 2.5 hours/week of leisure exercise increased by 9.72% (P=0.003) more than in the control group (number needed to treat=10.3). SF-36 measures of self rated “general health,” “role physical,” “vitality,” and “bodily pain” improved significantly more in the intervention group (P Conclusion: Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months. What is already known on this topic Counselling patients in general practice on exercise has resulted in gains in physical fitness and activity, but no health benefits have been found What this study adds Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months without evidence of adverse effects The intervention may reduce blood pressure by an average of 1–2 mm Hg over 12 months No changes in the risk of coronary heart disease were observed The intervention is sustainable in usual general practice Prompting practice staff to deliver the intervention may have increased its effectiveness
TL;DR: Higher sun exposure during childhood and early adolescence is associated with a reduced risk of multiple sclerosis, and insufficient ultraviolet radiation may influence the development ofmultiple sclerosis.
Abstract: Objective To examine whether past high sun exposure is associated with a reduced risk of multiple sclerosis. Design Population based case-control study. Setting Tasmania, latitudes 41-3°S. Participants 136 cases with multiple sclerosis and 272 controls
randomly drawn from the community and matched on sex and year of birth. Main outcome measure Multiple sclerosis defined by both clinical and magnetic resonance imaging criteria. Results Higher sun exposure when aged 6-15 years (average 2-3 hours or more a day in summer during weekends and holidays) was associated with a decreased risk of multiple sclerosis (adjusted odds ratio 0.31, 95% confidence interval 0.16 to 0.59). Higher exposure in winter seemed more important than higher exposure in summer. Greater actinic damage was also independently associated with a decreased risk of multiple sclerosis (0.32, 0.11 to 0.88 for grades 4-6 disease). A dose-response relation was observed between multiple sclerosis and decreasing sun exposure when aged 6-15 years and with actinic damage. Conclusion Higher sun exposure during childhood and early adolescence is associated with a reduced risk of multiple sclerosis. Insufficient ultraviolet radiation may therefore influence the development of multiple sclerosis.
TL;DR: Abnormal haematological variables were common among patients with SARS and the depletion of T lymphocyte subsets may be associated with disease activity.
Abstract: Objectives To evaluate the haematological findings of patients with severe acute respiratory syndrome (SARS). Design Analysis of the demographic, clinical, and laboratory characteristics of patients with SARS. Setting Prince of Wales Hospital, Hong Kong. Subjects All patients with a diagnosis of SARS between 11 March and 29 March 2003 who had no pre-existing haematological disorders. Main outcome measures Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed to examine factors associated with adverse outcome. Results 64 male and 93 female patients were included in this study. The most common findings included lymphopenia in 153 (98%) of the 157 patients, neutrophilia in 129 (82%), thrombocytopenia in 87 patients (55%), followed by thrombocytosis in 77 (49%), and isolated prolonged activated partial thromboplastin time in 96 patients (63%). The haemoglobin count dropped by more than 20 g/l from baseline in 95 (61%) patients. Four patients (2.5%) developed disseminated intravascular coagulation. Lymphopenia was shown in haemato-lymphoid organs at postmortem examination. Multivariate analysis showed that advanced age and a high concentration of lactate dehydrogenase at presentation were independent predictors of an adverse outcome. Subsets of peripheral blood lymphocytes were analysed in 31 patients. The counts of CD4 positive and CD8 positive T cells fell early in the course of illness. Low counts of CD4 and CD8 cells at presentation were associated with adverse outcomes. Conclusions Abnormal haematological variables were common among patients with SARS. Lymphopenia and the depletion of T lymphocyte subsets may be associated with disease activity.