A brief introduction of meta-analyses in clinical practice and research

With the explosive growth of medical information, it is almost impossible for healthcare providers to review and evaluate all relevant evidence to make the best clinical decisions. Meta-analyses, which summarize all existing evidence and quantitatively synthesize individual studies, have become the best available evidence for informing clinical practice. This article introduces the common methods, steps, principles, strengths and limitations of meta-analyses and aims to help healthcare providers and researchers obtain a basic understanding of meta-analyses in clinical practice and research.     

Retrospective analysis of evidence base for tests used in diagnosis and monitoring of disease in respiratory medicine

Objectives To determine how many common clinical tests used in a respiratory medicine outpatient clinic are based on high quality evidence.Design Retrospective review of case notes. Record of first three tests for each patient. Diagnostic tests, tests used to assess existing condition, explicit trials of therapy were included. Literature search for supporting evidence and grading of best evidence for each test.Setting Inner city university teaching hospital in the United Kingdom.Participants All new outpatients referred to a single respiratory medicine team over a period of three months.Main outcome measures Proportion of tests supported by level 1a-1c evidence (scale developed by Centre for Evidence Based Medicine).Results Only half the tests that were used to make or exclude a diagnosis and a fifth of the tests used to assess a known condition were supported by level 1a-1c evidence. There was no evidence to support trials of therapy.Conclusions A large proportion of clinical tests in respiratory medicine are not supported by level 1a-1c evidence. None of the therapeutic trials that were used were supported by evidence.     

In the era of systematic reviews, does the size of an individual trial still matter

BACKGROUND TO THE DEBATE: Systematic reviews that combine high-quality evidence from several trials are now widely considered to be at the top of the hierarchy of clinical evidence. Given the primacy of systematic reviews-and the fact that individual clinical trials rarely provide definitive answers to a clinical research question-some commentators question whether the sample size calculation for an individual trial still matters. Others point out that small trials can still be potentially misleading.     

Evidence-Based Laboratory Medicine: Is It Working in Practice?

The principles of Evidence-Based Medicine have been established for about two decades, with the need for evidence-based clinical practice now being accepted in most health systems around the world. These principles can be employed in laboratory medicine. The key steps in evidence-based practice, namely (i) formulating the question; (ii) searching for evidence; (iii) appraising evidence; (iv) applying evidence; and (v) assessing the experience are all accepted but, as yet, translation into daily clinical and laboratory practice has been slow. Furthermore, the demand for evidence-based laboratory medicine (EBLM) has been slow to develop.There are many contrasting observations about laboratory medicine, for example (i) there is too much testing vs insufficient testing; (ii) testing is expensive vs laboratories are expected to generate income; and (iii) test results have little impact on outcomes vs test results are crucial to clinical decision making. However, there is little evidence to support any of these observations. Integrating the principles of EBLM into routine practice will help to resolve some of these issues by identifying (a) where laboratory medicine fits into the care pathway; (b) where testing is appropriate; (c) the nature and quality of evidence required to demonstrate the clinical utility of a test; (d) how the test result impacts on clinical actions; (e) where changes in the care pathway will occur; and (f) where benefit/value can be achieved. These answers will help to establish the culture of EBLM in clinical and laboratory practice.     

Randomized controlled trials

Proponents of evidence-based medicine would acknowledge that several sources of evidence inform clinical decision making. Hierarchies of evidence have, however, been developed to help describe the quality of evidence that may be found to answer our clinical questions. According to this classification, the randomized clinical trial is the most effective way to determine whether a cause-and-effect relationship exists between an intervention and a predefined outcome. The basic principles of clinical trial design are reviewed, and the unique challenges of trial design in surgery are discussed.     

Prognostic factors for progression of clinical osteoarthritis of the knee: a systematic review of observational studies

IntroductionWe performed a systematic review of prognostic factors for the progression of symptomatic knee osteoarthritis (OA), defined as increase in pain, decline in physical function or total joint replacement.MethodWe searched for available observational studies up to January 2015 in Medline and Embase according to a specified search strategy. Studies that fulfilled our initial inclusion criteria were assessed for methodological quality. Data were extracted and the results were pooled, or if necessary summarized according to a best evidence synthesis.ResultsOf 1,392 articles identified, 30 met the inclusion criteria and 38 determinants were investigated. Pooling was not possible due to large heterogeneity between studies. The best evidence synthesis showed strong evidence that age, ethnicity, body mass index, co-morbidity count, magnetic resonance imaging (MRI)-detected infrapatellar synovitis, joint effusion and baseline OA severity (both radiographic and clinical) are associated with clinical knee OA progression. There was moderate evidence showing that education level, vitality, pain-coping subscale resting, MRI-detected medial femorotibial cartilage loss and general bone marrow lesions are associated with clinical knee OA progression. However, evidence for the majority of determinants was limited (including knee range of motion or markers) or conflicting (including age, gender and joint line tenderness).ConclusionStrong evidence was found for multiple prognostic factors for progression of clinical knee OA. A large variety in definitions of clinical knee OA (progression) remains, which makes it impossible to summarize the evidence through meta-analyses. More research on prognostic factors for knee OA is needed using symptom progression as an outcome measure. Remarkably, only few studies have been performed using pain progression as an outcome measure. The pathophysiology of radiographic factors and their relation with symptoms should be further explored.     

Biofeedback of Heart Rate Variability and Related Physiology: A Critical Review

Low heart rate variability (HRV) characterizes several medical and psychological diseases. HRV biofeedback is a newly developed approach that may have some use for treating the array of disorders in which HRV is relatively low. This review critically appraises evidence for the effectiveness of HRV and related biofeedback across 14 studies in improving (1) HRV and baroreflex outcomes and (2) clinical outcomes. Results revealed that HRV biofeedback consistently effectuates acute improvements during biofeedback practice, whereas the presence of short-term and long-term carry-over effects is less clear. Some evidence suggests HRV biofeedback may result in long-term carry-over effects on baroreflex gain, which is an area most promising for future investigations. On the other hand, concerning clinical outcomes, there is ample evidence attesting to efficacy of HRV biofeedback. However, because clinical and physiological outcomes do not improve concurrently in all cases, the mechanism by which HRV biofeedback results in salutary effects in unclear. Considerations for the field in addressing shortcomings of the reviewed studies and advancing understanding of the way in which HRV biofeedback may improve physiological and clinical outcomes are offered in light of the reviewed evidence.     

Transforming scientific evidence into better consumer choices

Translational research using evidence-based and comparative effectiveness research continues to evolve, becoming a useful tool in improving informed consent and decision-making in the clinical setting. While in development, emerging technologies, including cellular and molecular biology, are leading to establishing evidence-based dental practices. One emerging technology, which conjoins bench proteomic findings to clinical decision-making for treatment intervention, is the Translational Evidence Mechanism. This mechanism was developed to be a foundation for a compact between researcher, translational researcher, clinician, and patient. The output of such a mechanism is the clinical practice guideline (CPG), an interactive tool for dentists and patients to game evidence in reaching optimum clinical decisions that correspond to individual patient preferences and values. As such, the clinical practice guideline requires the vesting of decision, utility, and cost best evidence. Evidence-based research provides decision data, a first attempt at supporting decision-making by providing best outcome data. Since then comparative effectiveness research has emerged, using systematic review analysis to compare similar treatments or procedures in maximizing the choice of the most effective cost/benefit option within the context of best evidence. With innovation in the clinical practice guideline for optimizing efficacy and comparative effectiveness research, evidence-based practices will shape a new approach to health-based systems that adhere to shared decision-making between bench scientists, healthcare providers and patients.     

Evidence based medicine: an approach to clinical problem-solving.

Doctors within the NHS are confronting major changes at work. While we endeavour to improve the quality of health care, junior doctors'' hours have been reduced and the emphasis on continuing medical education has increased. We are confronted by a growing body of information, much of it invalid or irrelevant to clinical practice. This article discusses evidence based medicine, a process of turning clinical problems into questions and then systematically locating, appraising, and using contemporaneous research findings as the basis for clinical decisions. The computerisation of bibliographies and the development of software that permits the rapid location of relevant evidence have made it easier for busy clinicians to make best use of the published literature. Critical appraisal can be used to determine the validity and applicability of the evidence, which is then used to inform clinical decisions. Evidence based medicine can be taught to, and practised by, clinicians at all levels of seniority and can be used to close the gulf between good clinical research and clinical practice. In addition it can help to promote self directed learning and teamwork and produce faster and better doctors.     

Transforming scientific evidence into better consumer choices

Translational research using evidence-based and comparative effectiveness research continues to evolve, becoming a useful tool in improving informed consent and decision-making in the clinical setting. While in development, emerging technologies, including cellular and molecular biology, are leading to establishing evidence-based dental practices. One emerging technology, which conjoins bench proteomic findings to clinical decision-making for treatment intervention, is the Translational Evidence Mechanism. This mechanism was developed to be a foundation for a compact between researcher, translational researcher, clinician, and patient. The output of such a mechanism is the clinical practice guideline (CPG), an interactive tool for dentists and patients to game evidence in reaching optimum clinical decisions that correspond to individual patient preferences and values. As such, the clinical practice guideline requires the vesting of decision, utility, and cost best evidence. Evidence-based research provides decision data, a first attempt at supporting decision-making by providing best outcome data. Since then comparative effectiveness research has emerged, using systematic review analysis to compare similar treatments or procedures in maximizing the choice of the most effective cost/benefit option within the context of best evidence. With innovation in the clinical practice guideline for optimizing efficacy and comparative effectiveness research, evidence-based practices will shape a new approach to health-based systems that adhere to shared decision-making between bench scientists, healthcare providers and patients.     

Psoriatic arthritis in severe psoriasis.

Summary: Of 100 patients admitted to hospital for treatment of psoriasis, 32 had clinical or radiologic evidence of psoriatic arthritis and 17 had both types of evidence. Eight had radiologic evidence of spinal or sarroiliac involvement without symptoms and seven had clinical evidence of peripheral arthritis without radiologic evidence. Patients with psoriatic sacroilitis and spondylitis were most likely to have typical radiograpic changes. It was concluded that psoriatic arthritis is common in patients with severe psoriasis and that is associated with more extensive skin disease than is found in patients without arthritis.     

Evidence-Based Medicine,Clinical Practice Guidelines,and Common Sense in the Management of Osteoporosis

ObjectiveTo evaluate the benefits and limitations of randomized controlled trials (RCTs), clinical practice guidelines (CPGs), and clinical judgment in the management of osteoporosis.MethodsA review was conducted of the English-language literature on the origins and applications of RCTs, CPGs, evidence-based medicine, and clinical judgment in the management of osteoporosis.ResultsEvidence-based medicine is use of the currently available best evidence in making clinical decisions for individual patients. CPGs are recommendations for making clinical decisions based on research evidence, sometimes with consideration of expert opinion, health care policy, and costs of care. The highest levels of medical evidence are usually thought to be RCTs and meta-analyses of high-quality RCTs. Although it is desirable and appropriate for clinicians to consider research evidence from RCTs and recommendations presented in CPGs in making clinical decisions, other factors—such as patient preference, comorbidities, affordability, and availability of care—are important for the actual implementation of evidence-based medicine.ConclusionDecisions about who to treat, which drug to use, how best to monitor, and how long to treat require clinical skills in addition to knowledge of medical research. The necessity of integrating common sense and clinical judgment is highlighted by the fact that many patients treated for osteoporosis in clinical practice would not qualify for participation in the pivotal clinical trials that demonstrated efficacy and safety of the drugs used to treat them. (Endocr Pract. 2009;15:573-579)     

From type 2 diabetes to antioxidant activity: a systematic review of the safety and efficacy of common and cassia cinnamon bark

Common (Cinnamomum verum, C. zeylanicum) and cassia (C. aromaticum) cinnamon have a long history of use as spices and flavouring agents. A number of pharmacological and clinical effects have been observed with their use. The objective of this study was to systematically review the scientific literature for preclinical and clinical evidence of safety, efficacy, and pharmacological activity of common and cassia cinnamon. Using the principles of evidence-based practice, we searched 9 electronic databases and compiled data according to the grade of evidence found. One pharmacological study on antioxidant activity and 7 clinical studies on various medical conditions were reported in the scientific literature including type 2 diabetes (3), Helicobacter pylori infection (1), activation of olfactory cortex of the brain (1), oral candidiasis in HIV (1), and chronic salmonellosis (1). Two of 3 randomized clinical trials on type 2 diabetes provided strong scientific evidence that cassia cinnamon demonstrates a therapeutic effect in reducing fasting blood glucose by 10.3%-29%; the third clinical trial did not observe this effect. Cassia cinnamon, however, did not have an effect at lowering glycosylated hemoglobin (HbA1c). One randomized clinical trial reported that cassia cinnamon lowered total cholesterol, low-density lipoprotein cholesterol, and triglycerides; the other 2 trials, however, did not observe this effect. There was good scientific evidence that a species of cinnamon was not effective at eradicating H. pylori infection. Common cinnamon showed weak to very weak evidence of efficacy in treating oral candidiasis in HIV patients and chronic salmonellosis.     

Clinical effectiveness and cost effectiveness of zanamivir (Relenza): translating the evidence into clinical practice, a National Institute for Clinical Excellence view.

The UK National Institute for Clinical Excellence (NICE) is charged with the duty of providing informed guidance on clinical practice (clinical effectiveness and cost effectiveness) to patients and health professionals. The Appraisal Committee through its process of review of evidence advises NICE on the clinical effectiveness and cost effectiveness of new and existing technologies and their appropriate use within the National Health Service in England and Wales. The appraisal process takes into account both published and unpublished evidence as well as input from professional and patient and carer groups when coming to its decisions. The appraisal of a new technology often has to bridge the gap between the evidence required for licensing purposes and that needed to provide pragmatic advice to practising clinicians. The appraisal of zanamivir (Relenza) is an excellent working example of this difficult and important process.     

Autonomic control during sleep and risk for sudden death in infancy

A variety of clinical pathology and experimental animal evidence suggests that cerebellar and vestibular structures mediate marked challenges to blood pressure and breathing, and are particularly involved in compensatory somatomotor and breathing efforts to overcome substantial losses in blood pressure. At least a subset of victims of the Sudden Infant Death Syndrome (SIDS), a sleep-related disorder, succumbs to a profound bradycardia and hypotension prior to respiratory cessation, suggesting a failure of autonomic control, or incompetent compensation of somatomotor and respiratory efforts, to overcome the cardiovascular collapse. The clinical and neurotransmitter evidence from SIDS victims implicates afferent and efferent components within vestibular/cerebellar blood pressure control systems in SIDS victims. Experimental evidence from animals suggests vestibular and cerebellar structures exercise critical roles in mediating autonomic responses to body position and extreme changes in blood pressure. The position-dependent risk for SIDS, together with the neuropathological evidence, suggests a significant role for vestibular/cerebellar structures in mediating the fatal outcome for the syndrome.     

抑郁症治疗的循证医学研究进展

循证医学是近年来国际上临床医学领域迅速发展起来的新学科,已成为当前国际医学研究中的热点之一,是指对病人的诊 断、治疗、预防、康复和其他决策应建立在当前最佳临床研究证据,是遵循证据的临床医学,强调收集最佳证据。其理念的科学性 和有效性迅速渗透到医学领域的众多学科,循证精神卫生也相继提出并发展。抑郁症是由各种原因引起的以抑郁为主要症状的 一组心境障碍或情感性障碍,近几年能够有效运用循证医学方法为治疗抑郁症寻找最佳临床证据,制定循证诊疗指南成为了临 床医生的迫切要求。本文就抑郁症治疗方面的循证医学研究进展做一综述。     

Disseminating the best available evidence: New challenges in public reporting of health care

As a direct benefit of the Health Care Reform Act (2010), concerted effort has been deployed to define and characterize the process by which the best available evidence for diagnosis or treatment intervention prognosis can be obtained. The science of research synthesis in health care has established the systematic research protocol by which randomized clinical trials and other clinical studies must be reviewed and compared for the level and quality of the evidence presented, as well as the consensus of the best available evidence synthesized and shared. This process of systematic review yields a reliable and valid approach in comparing different interventions and strategies to prevent, diagnose, treat and monitor health conditions in terms of efficacy, and or of effectiveness. The resulting bioinformation outcome of comparative effectiveness and efficacy research review of the available clinical data is expressed as a consensus of the best available evidence, which finds its way in evidence-based clinical practice guidelines, standards of care and eventually, in policies: hence, the acronym CEERAP (comparative effectiveness and efficacy review and policy). The methodological and the procedural criteria that determine and regulate the public reporting dissemination of this sort of bioinformation, and the extent of benefit to the patient's health literacy, which have remained a bit more elusive to this date, are investigated and discussed in this paper.     

The Evidence Based Medicine approach to diagnostic testing: practicalities and limitations

Evidence-Based Medicine (EBM) has become a popular approach to medical decision making and is increasingly part of undergraduate and postgraduate medical education. EBM follows four steps: 1. formulate a clear clinical question from a patient's problem; 2. search the literature for relevant clinical articles; 3. evaluate (critically appraise) the evidence for its validity and usefulness; 4. implement useful findings into clinical practice. This review describes the concepts, terminology and skills taught to attendees at EBM courses, focusing specifically on the approach taken to diagnostic questions. It covers how to ask an answerable clinical question, search for evidence, construct diagnostic critically appraised topics (CATs), and use sensitivity, specificity, likelihood ratios, kappa and phi statistics. It familiarises readers with the lexicon and techniques of EBM and allows better understanding of the needs of EBM practitioners.     

Physiological origins and functional correlates of EEG rhythmic activities: Implications for self-regulation

Recent neurophysiological findings in relation to thalamocortical mechanisms for sensory processing, together with established anatomical and expanding functional evidence, have provided a rational theoretical framework for the interpretation of normal and abnormal EEG rhythmic activities. This perspective is integrated here with earlier animal studies which were the foundation for many current applications of EEG self-regulation as a clinical tool. Basic evidence concerning the origins, frequency modulation, and functional significance of normal EEG rhythmic activities is reviewed here in an effort to provide guiding principles for the interpretation of clinical abnormalities and their remediation with EEG feedback training.