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1.  Towards evidence‐based medicine for paediatricians 
To give the best care to patients and families, paediatricians need to integrate the highest quality scientific evidence with clinical expertise and the opinions of the family.1Archimedes seeks to assist practising clinicians by providing “evidence‐based” answers to common questions that are not at the forefront of research but are at the core of practice. In doing this, we are adapting a format that has been successfully developed by Kevin Mackway‐Jones and the group at the Emergency Medicine Journal—“BestBets”.
A word of warning. The topic summaries are not systematic reviews, although they are as exhaustive as a practising clinician can produce. They make no attempt to statistically aggregate the data, nor to search the grey, unpublished literature. What Archimedes offers is practical, best evidence‐based answers to practical, clinical questions.
The format of Archimedes may be familiar. A description of the clinical setting is followed by a structured clinical question. (These aid in focusing the mind, assisting searching2 and obtaining answers.3) A brief report of the search used follows—this has been performed in a hierarchical way, to search for the best quality evidence to answer the question (http://www.cebm.net). A table provides a summary of the evidence and key points of the critical appraisal. For further information on critical appraisal, and the measures of effect (such as the number needed to treat), books by Sackett4 and Moyer5 may help. To pull the information together, a commentary is provided, but to make it all much more accessible, a box provides the clinical bottom lines.
Electronics‐only topics that have been published on the BestBets site (www.bestbets.org) and may be of interest to paediatricians include the following.
Can steroids be used to reduce post tonsillectomy pain?
Readers wishing to submit their own questions—with best evidence answers—are encouraged to review those already proposed at www.bestbets.org. If your question still hasn't been answered, feel free to submit your summary according to the instructions for authors at www.archdischild.com. Three topics are covered in this issue of the journal:
Is teething the cause of minor ailments?
Should steroid creams be used in cases of labial fusion?
Does erythromycin cause pyloric stenosis?
References
1 Moyer VA, Ellior EJ. Preface. In: Moyer VA, Elliott EJ, Davis RL, et al, eds. Evidence based pediatrics and child health. Issue 1. London: BMJ Books, 2000.
2 Richardson WS, Wilson MC, Nishikawa J, et al. The well‐built clinical question: a key to evidence‐based decisions. ACP J Club 1995;123:A12–13.
3 Bergus GR, Randall CS, Sinift SD, et al. Does the structure of clinical questions affect the outcome of curbside consultations with specialty colleagues? Arch Fam Med 2000;9:541–7.
4 Sackett DL, Starus S, Richardson WS, et al. Evidence‐based medicine. How to practice and teach EBM. San Diego: Harcourt‐Brace, 2000.
5 Moyer VA, Elliott EJ, Davis RL, et al, eds. Evidence based pediatrics and child health. Issue 1. London: BMJ Books, 2000.
Can: doing, using and replicating evidence‐based child health
The practice of evidence‐based child health is said to be the five‐step way of asking questions, acquiring information, appraising the evidence, applying the results and assessing our performance.
If the truth be known, for the vast majority of the time, most of us perform our clinical practice replicating what we have done previously. Most of the time this is based on the combination of excellent education, skilled interpretation of clinical findings, and good discussions with children and families. We hope that the education we rely on was (and remains) based on the best available scientific evidence. If it is, we are practising a form of “micro‐evidence‐based healthcare (EBHC)” (doing just step 4).
Sometimes, we question our knowledge (or more uncomfortably, someone does this for us), and will head off to top up our understanding of an area. This “using” mode, if we use well‐appraised resources to supply our thirst for information, will also promote the practice of evidence‐based care. This midi‐EBHC asks us to go through steps 1, 2 and 4.
Occasionally, we also actually need to go through the entire process of getting “down and dirty” with the primary research and appraising it to influence our practice. Maxi‐EBHC is considerably more demanding in time, but largely more satisfying intellectually.
If we reframe the practice of EBHC as using the family and child values, the best evidence, and our clinical expertise, then we can do it by micro‐methods, midi‐methods or maxi‐methods, and choose the most appropriate approach for the situation we confront.
Acknowledgement
I thank Dr Sharon Straus, Director of the Center for Evidence‐based Medicine, University of Toronto, Toronto, Ontario, Canada.
doi:10.1136/adc.2006.110080
PMCID: PMC2083440
2.  Towards evidence based medicine for paediatricians 
In order to give the best care to patients and families, paediatricians need to integrate the highest quality scientific evidence with clinical expertise and the opinions of the family.1Archimedes seeks to assist practising clinicians by providing “evidence based” answers to common questions which are not at the forefront of research but are at the core of practice. In doing this, we are adapting a format which has been successfully developed by Kevin Macaway‐Jones and the group at the Emergency Medicine Journal—“BestBets”.
A word of warning. The topic summaries are not systematic reviews, through they are as exhaustive as a practising clinician can produce. They make no attempt to statistically aggregate the data, nor search the grey, unpublished literature. What Archimedes offers are practical, best evidence based answers to practical, clinical questions.
The format of Archimedes may be familiar. A description of the clinical setting is followed by a structured clinical question. (These aid in focusing the mind, assisting searching,2 and gaining answers.3) A brief report of the search used follows—this has been performed in a hierarchical way, to search for the best quality evidence to answer the question.4 A table provides a summary of the evidence and key points of the critical appraisal. For further information on critical appraisal, and the measures of effect (such as number needed to treat, NNT) books by Sackett5 and Moyer6 may help. To pull the information together, a commentary is provided. But to make it all much more accessible, a box provides the clinical bottom lines.
Readers wishing to submit their own questions—with best evidence answers—are encouraged to review those already proposed at www.bestbets.org. If your question still hasn't been answered, feel free to submit your summary according to the Instructions for Authors at www.archdischild.com. Three topics are covered in this issue of the journal:
Does neonatal BCG vaccination protect against tuberculous meningitis?
Does dexamethasone reduce the risk of extubation failure in ventilated children?
Should metformin be prescribed to overweight adolescents in whom dietary/behavioural modifications have not helped?
REFERENCES
1. Moyer VA, Ellior EJ. Preface. In: Moyer VA, Elliott EJ, Davis RL, et al, eds. Evidence based pediatrics and child health, Issue 1. London: BMJ Books, 2000.
2. Richardson WS, Wilson MC, Nishikawa J, et al. The well‐built clinical question: a key to evidence‐based decisions. ACP J Club 1995;123:A12–13.
3. Bergus GR, Randall CS, Sinift SD, et al. Does the structure of clinical questions affect the outcome of curbside consultations with specialty colleagues? Arch Fam Med 2000;9:541–7.
4. http://cebm.jr2.ox.ac.uk/docs/levels.htm (accessed July 2002).
5. Sackett DL, Starus S, Richardson WS, et al. Evidence‐based medicine. How to practice and teach EBM. San Diego: Harcourt‐Brace, 2000.
6. Moyer VA, Elliott EJ, Davis RL, et al, eds. Evidence based pediatrics and child health, Issue 1. London: BMJ Books, 2000.
How to read your journals
Most people have their journals land, monthly, weekly, or quarterly, on their desk, courtesy of their professional associations. Then they sit, gathering dust and guilt, for a period of time. When the layer of either is too great for comfort (or the desk space is needed for some proper work), the wrapper is removed and the journal scanned. But does how people read reflect their information needs or their entertainment requirements?
It is not uncommon to find people straying from the editorial introduction to the value added sections (like obituaries, Lucina‐like summary pages, and end‐of‐article fillers) rather than face the impenetrable science that sits between them. I think that this is probably unhelpful, and would urge readers to do one more thing before placing the journal in the recycling. Scan the table of contents; if it mentions a systematic review or a randomised trial, then read at least the title and the abstract's conclusions. If you agree, pat yourself warmly on the back for being evidence based and up‐to‐date. If you disagree, ask if it will make any impact on your clinical (or personal) life. If it might, run through the methods and quickly appraise them. Does it supply higher quality evidence than that you already possess? If it does, it's worth reading. If it doesn't, don't bother too much.
There are new innovations which might aid the tedious task of consuming research effort. The on‐line Précis section of the Archives provides a highly readable version of the contents page to whet one's appetite. Finally, it's worth mentioning that evidence based summary materials (like Archimedes, or Journal Watch) are always worth reading—and if you didn't think that you wouldn't be here, would you?
PMCID: PMC2082933
Archimedes; evidence based medicine
3.  Towards evidence‐based medicine for paediatricians 
To give the best care to patients and families, paediatricians need to integrate the highest‐quality scientific evidence with clinical expertise and the opinions of the family.1Archimedes seeks to assist practising clinicians by providing “evidence‐based” answers to common questions which are not at the forefront of research but are at the core of practice. In doing this, we are adapting a format that has been successfully developed by Kevin Macaway‐Jones and the group at the Emergency Medicine Journal—“BestBets”.
A word of warning. The topic summaries are not systematic reviews, although they are as exhaustive as a practising clinician can produce. They make no attempt to statistically aggregate the data, nor search the grey, unpublished literature. What Archimedes offers are practical, best evidence‐based answers to practical, clinical questions.
The format of Archimedes may be familiar. A description of the clinical setting is followed by a structured clinical question. (These aid in focusing the mind, assisting searching2 and gaining answers.3) A brief report of the search used follows—this has been carried out in a hierarchical way, to search for the best‐quality evidence to answer the question (http://www.cebm.net/levels_of_evidence.asp). A table provides a summary of the evidence and key points of the critical appraisal. For further information on critical appraisal and the measures of effect (such as number needed to treat), books by Sackett et al4 and Moyer et al5 may help. To pull the information together, a commentary is provided. But to make it all much more accessible, a box provides the clinical bottom lines.
Electronic‐only topics that have been published on the BestBets site (www.bestbets.org) and may be of interest to paediatricians include:
Are meningeal irritation signs reliable in diagnosing meningitis in children?
Is immobilisation effective in Osgood‐Schlatter's disease?
Do all children presenting to the emergency department with a needlestick injury require PEP for HIV to reduce HIV transmission?
Readers wishing to submit their own questions—with best evidence answers—are encouraged to review those already proposed at www.bestbets.org. If your question still has not been answered, feel free to submit your summary according to the Instructions for Authors at www.archdischild.com. Three topics are covered in this issue of the journal.
Is lumbar puncture necessary for evaluation of early neonatal sepsis?
Does the use of calamine or antihistamine provide symptomatic relief from pruritus in children with varicella zoster infection?
Is supplementary iron useful when preterm infants are treated with erythropoietin?
Is more research needed?
“More research is needed” is a phrase you might have read before. But is more research really needed? Two situations are offered to us in Archimedes this month where clinical questions are, as yet, unanswered. Is iron supplementation really necessary for premature infants treated with erythropoietin, and do antihistamines and calamine lotion help in children with chicken pox? How can we decide if these questions really do “need” research? It may be worth thinking of how likely benefits and harms may be, what the importance of these outcomes are and finally, how much would you consider reasonable to pay for the answer? For example, what chance is there that antihistamines work in chickenpox? What is the chance that side effects will occur? What is the relative severity of side effects versus the delight of being itch free? If we pay for research and spend hours and hours of time pressing through the increasing regulatory frameworks for clinical trials to define the answer to this question, what will be the opportunity cost? What would we fail to do by looking at this? The same questions can be asked of iron supplementation in premature infants, the salvage treatment of relapsing systemic histocytosis or the promotion of car‐seat use in low‐income families. Such value judgements are important; they will have different answers from different perspectives; they will be subject to political influences from pressure groups; being aware of them might stop us from frequently expounding “more research is needed”.
References
1Moyer VA, Ellior EJ. Preface. In: Moyer VA, Elliott EJ, Davis RL, et al, eds. Evidence based pediatrics and child health, Issue 1. London: BMJ Books, 2000.
2Richardson WS, Wilson MC, Nishikawa J, et al. The well‐built clinical question: a key to evidence‐based decisions. ACP J Club 1995;123:A12–13.
3Bergus GR, Randall CS, Sinift SD, et al. Does the structure of clinical questions affect the outcome of curbside consultations with specialty colleagues? Arch Fam Med 2000;9:541–7.
4Sackett DL, Starus S, Richardson WS, et al. Evidence‐based medicine. How to practice and teach EBM. San Diego: Harcourt‐Brace, 2000.
5Moyer VA, Elliott EJ, Davis RL, et al, eds. Evidence based pediatrics and child health, Issue 1. London: BMJ Books, 2000.
doi:10.1136/adc.2006.105379
PMCID: PMC2083019
4.  Towards evidence based medicine for paediatricians 
In order to give the best care to patients and families, paediatricians need to integrate the highest quality scientific evidence with clinical expertise and the opinions of the family.1Archimedes seeks to assist practising clinicians by providing “evidence‐based” answers to common questions which are not at the forefront of research but are at the core of practice. In doing this, we are adapting a format which has been successfully developed by Kevin Macaway‐Jones and the group at the Emergency Medicine Journal—“BestBets”.
A word of warning. The topic summaries are not systematic reviews, though they are as exhaustive as a practising clinician can produce. They make no attempt to statistically aggregate the data, nor search the grey, unpublished literature. What Archimedes offers are practical, best evidence‐based answers to practical, clinical questions.
The format of Archimedes may be familiar. A description of the clinical setting is followed by a structured clinical question. (These aid in focusing the mind, assisting searching2 and gaining answers.3) A brief report of the search used follows—this has been performed in a hierarchical way, to search for the best‐quality evidence to answer the question. (http://www.cebm.net). A table provides a summary of the evidence and key points of the critical appraisal. For further information on critical appraisal, and the measures of effect (such as number needed to treat), books by Sackett et al4 and Moyer et al5 may help. To pull the information together, a commentary is provided. But to make it all much more accessible, a box provides the clinical bottom lines.
Electronic‐only topics that have been published on the BestBets site (www.bestbets.org) and may be of interest to paediatricians include:
When is a second course of indomethacin effective for PDA in neonates?
Does delayed cord clamping prevent sepsis?
Readers wishing to submit their own questions—with best evidence answers—are encouraged to review those already proposed at www.bestbets.org. If your question still hasn't been answered, feel free to submit your summary according to the Instructions for Authors at www.archdischild.com. Three topics are covered in this issue of the journal:
In children aged <3 years does procalcitonin help exclude serious bacterial infection in fever without focus?
Does avoidance of breast feeding reduce mother‐to‐infant transmission of hepatitis C virus infection?
Should children under treatment for juvenile idiopathic arthritis receive flu vaccination?
CAN gambling with other people's children
When we use tests to “rule out” a condition, we generally accept that we are left with a small risk of being wrong. (I think we have all discharged a child with an “upper respiratory tract infection” on a Friday to be greeted with them on antibiotics for pneumonia the following Monday.) How much faith we place in a test result is a product of two things: our initial assumption about the likelihood of the diagnosis (pretest probability) and our opinion as to how effective the test is (accuracy), but our actions do not just reflect these factors.
For instance, a well, afebrile child with a scattering of petechiae over its wrist 8 hours before, is unlikely to have meningococcal disease. If you perform a couple of tests, you can find that it has a low C‐reactive protein and a normal full blood count. What we do with this varies widely; some people would treat this with 48 h of antibiotics, others would discharge the patient home.
It is interesting to reflect on two things: first, what chance of meningococcal disease would you put on this clinical picture (before the test), and what about with the test results? What about your colleagues? You may be surprised by how widely this varies. Second, even those who have the same estimates of risk of disease may have different preferred actions (depending on their attitude to risk).
In looking at the diagnostic test for the ruling out of a disease, we can make our arguments more useful by having some data on the assumptions we make, and then transparently discussing our attitudes to risk. It is only after doing this that we can really decide if a test is good enough for us, regardless of how accurate it might be.
References
1Moyer VA, Ellior EJ. Preface. In: Moyer VA, Elliott EJ, Davis RL, et al, eds. Evidence based pediatrics and child health, Issue 1. London: BMJ Books, 2000.
2Richardson WS, Wilson MC, Nishikawa J, et al. The well‐built clinical question: a key to evidence‐based decisions. ACP J Club 1995;123:A12–13.
3Bergus GR, Randall CS, Sinift SD, et al. Does the structure of clinical questions affect the outcome of curbside consultations with specialty colleagues? Arch Fam Med 2000;9:541–7.
4Sackett DL, Starus S, Richardson WS, et al. Evidence‐based medicine. How to practice and teach EBM. San Diego: Harcourt‐Brace, 2000.
5Moyer VA, Elliott EJ, Davis RL, et al, eds. Evidence based pediatrics and child health. Issue 1. London: BMJ Books, 2000.
PMCID: PMC2083694  PMID: 17376947
5.  Summary of Findings Tables: Presenting the Main Findings of Cochrane Complementary and Alternative Medicine–related Reviews in a Transparent and Simple Tabular Format 
The systematic review is widely accepted as the most reliable and objective method for evaluating the effects of healthcare interventions, including complementary and alternative medicine (CAM) therapies. Systematic reviews use explicit, transparent, and well-documented methods to find, evaluate, and synthesize the best available research studies related to a specific research question. Systematic reviews of healthcare treatment typically have focused on randomized controlled trials (RCTs) because RCTs are widely regarded as the study design providing the most reliable estimates of a healthcare treatment's effects. Systematic reviewers aim to evaluate and appraise relevant RCTs using objective and reproducible methods to provide an unbiased assessment of the evidence for a given therapy. Systematic reviews sometimes include a meta-analysis, the quantitative combining (pooling) of results from similar but separate RCTs to obtain an overall effect estimate.
doi:10.7453/gahmj.2012.1.1.015
PMCID: PMC3833472  PMID: 24278805
Summary of Findings; Cochrane; Collaboration; CAM; complementary and alternative medicine; systematic review; RCT; GRADE; randomized controlled trial
6.  Meta-Analyses and Orthodontic Evidence-Based Clinical Practice in the 21st Century 
The Open Dentistry Journal  2010;4:92-123.
Introduction:
Aim of this systematic review was to assess the orthodontic related issues which currently provide the best evidence as documented by meta-analyses, by critically evaluating and discussing the methodology used in these studies.
Material and Methods:
Several electronic databases were searched and handsearching was also performed in order to identify the corresponding meta-analyses investigating orthodontic related subjects. In total, 197 studies were retrieved initially. After applying specific inclusion and exclusion criteria, 27 articles were identified as meta-analyses treating orthodontic-related subjects.
Results:
Many of these 27 papers presented sufficient quality and followed appropriate meta-analytic approaches to quantitatively synthesize data and presented adequately supported evidence. However, the methodology used in some of them presented weaknesses, limitations or deficiencies. Consequently, the topics in orthodontics which currently provide the best evidence, include some issues related to Class II or Class III treatment, treatment of transverse problems, external apical root resorption, dental anomalies, such as congenital missing teeth and tooth transposition, frequency of severe occlusal problems, nickel hypersensitivity, obstructive sleep apnea syndrome, and computer-assisted learning in orthodontic education.
Conclusions:
Only a few orthodontic related issues have been so far investigated by means of MAs. In addition, for some of these issues investigated in the corresponding MAs no definite conclusions could be drawn, due to significant methodological deficiencies of these studies. According to this investigation, it can be concluded that at the begin of the 21st century there is evidence for only a few orthodontic related issues as documented by meta-analyses, and more well-conducted high quality research studies are needed to produce strong evidence in order to support evidence-based clinical practice in orthodontics.
doi:10.2174/1874210601004010092
PMCID: PMC3111736  PMID: 21673839
Evidence based orthodontics; evidence-based clinical practice; systematic review; meta-analysis.
7.  A protocol for a systematic review on the impact of unpublished studies and studies published in the gray literature in meta-analyses 
Systematic Reviews  2013;2:24.
Background
Meta-analyses are particularly vulnerable to the effects of publication bias. Despite methodologists’ best efforts to locate all evidence for a given topic the most comprehensive searches are likely to miss unpublished studies and studies that are published in the gray literature only. If the results of the missing studies differ systematically from the published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention’s effects.
As part of the OPEN project (http://www.open-project.eu) we will conduct a systematic review with the following objectives:
▪ To assess the impact of studies that are not published or published in the gray literature on pooled effect estimates in meta-analyses (quantitative measure).
▪ To assess whether the inclusion of unpublished studies or studies published in the gray literature leads to different conclusions in meta-analyses (qualitative measure).
Methods/Design
Inclusion criteria: Methodological research projects of a cohort of meta-analyses which compare the effect of the inclusion or exclusion of unpublished studies or studies published in the gray literature.
Literature search: To identify relevant research projects we will conduct electronic searches in Medline, Embase and The Cochrane Library; check reference lists; and contact experts.
Outcomes: 1) The extent to which the effect estimate in a meta-analyses changes with the inclusion or exclusion of studies that were not published or published in the gray literature; and 2) the extent to which the inclusion of unpublished studies impacts the meta-analyses’ conclusions.
Data collection: Information will be collected on the area of health care; the number of meta-analyses included in the methodological research project; the number of studies included in the meta-analyses; the number of study participants; the number and type of unpublished studies; studies published in the gray literature and published studies; the sources used to retrieve studies that are unpublished, published in the gray literature, or commercially published; and the validity of the methodological research project.
Data synthesis: Data synthesis will involve descriptive and statistical summaries of the findings of the included methodological research projects.
Discussion
Results are expected to be publicly available in the middle of 2013.
doi:10.1186/2046-4053-2-24
PMCID: PMC3682918  PMID: 23634657
Publication bias; Gray literature; Unpublished studies; Meta-analyses; The OPEN project
8.  Pharmacologic interventions for painful diabetic neuropathy: an umbrella systematic review and comparative effectiveness network meta-analysis (Protocol) 
Systematic Reviews  2012;1:61.
Background
Neuropathic pain can reduce the quality of life and independence of 30% to 50% of patients with diabetes. The comparative effectiveness of analgesics for patients with diabetic neuropathy remains unclear. The aim of the current work, therefore, was to summarize the evidence about the analgesic effectiveness of the most common oral and topical agents used for the treatment of peripheral diabetic neuropathy.
Methods
We will use an umbrella approach (systematic review of systematic reviews) to identify eligible randomized controlled trials (RCTs) for the most common oral or topical analgesics for painful diabetic neuropathy. Two reviewers will independently determine RCT eligibility. Disagreement will be solved by consensus and arbitrated by a third reviewer. We will extract descriptive, methodological and efficacy data in duplicate. Results will be pooled and analyzed using classic random-effects meta-analyses and network meta-analyses to compute the absolute and relative efficacy of therapeutic options. We will use the I2 statistic and Cochran’s Q test to assess heterogeneity. Risk of bias and publication bias, if appropriate, will be evaluated, as well as overall strength of the evidence.
Discussion
This network meta-analysis aims to synthesize available direct and indirect evidence of effectiveness of analgesics in the treatment of painful diabetic neuropathy. The network approach will offer the opportunity to generate a ranking based on efficacy and along with known side effects, costs, and administration burdens will enable patients and clinicians to make choices that best reflect their preferences for treatment of painful diabetic neuropathy.
doi:10.1186/2046-4053-1-61
PMCID: PMC3534585  PMID: 23198755
Comparative effectiveness research; Diabetic neuropathy; Network meta-analysis; Systematic review
9.  Role of systematic reviews and meta-analysis in evidence-based clinical practice 
Introduction:
Systematic reviews and meta-analyses of well-designed and executed randomized controlled trials have the potential to provide the highest levels of evidence to support diagnostic and therapeutic interventions in urology.
Materials and Methods:
The role of systematic reviews in the urological literature is described. A three-step appraisal of the validity, magnitude and applicability of results will permit an evidence-based approach to incorporating findings of systematic reviews and meta-analyses into practice.
Results:
The validity of systematic reviews depends on a focused clinical question that generates specific inclusion and exclusion criteria for identifying studies through an exhaustive literature search. The primary studies must be of high methodological quality and assessments should be reproducible. Informed consumers of the urological literature should be aware of the consistency of results between trials in a review, as well as the magnitude and precision of the best estimate of the treatment effects. When making decisions about implementing the results, urologists should consider all patient-important outcomes, the overall quality of the evidence and the balance between benefits, potential harms and costs.
Conclusion:
This framework will lead to a more evidence-based application of systematic reviews within the urological literature. Ideally, utilization of an evidence-based approach to systematic reviews will improve the quality of urological patient care.
doi:10.4103/0970-1591.91445
PMCID: PMC3263224  PMID: 22279322
Evidence-based medicine; systematic review; meta-analysis; randomized controlled trials
10.  Strengths and Limitations of Evidence-Based Dermatology 
Indian Journal of Dermatology  2014;59(2):127-133.
The need for understanding and reflecting on evidence-based dermatology (EBD) has never been greater given the exponential growth of new external evidence to inform clinical practice. Like any other branch of medicine, dermatologists need to acquire new skills in constructing answerable questions, efficiently searching electronic bibliographic databases, and critically appraising different types of studies. Secondary summaries of evidence in the form of systematic reviews (SR), that is, reviews that are conducted in a systematic, unbiased and explicit manner, reside at the top of the evidence hierarchy, because they are less prone to bias than traditional expert reviews. In addition to providing summaries of the best external evidence, systematic reviews and randomized controlled trials (RCTs) are also powerful ways of identifying research gaps and ultimately setting the agenda of future clinical research in dermatology. But like any paradigm, EBD can have its limitations. Wrong application, misuse and overuse of EBD can have serious consequences. For example, mindless pooling together of data from dissimilar studies in a meta-analysis may render it a form of reductionism that does not make any sense. Similarly, even highly protocolised study designs such as SRs and RCTs are still susceptible to some degree of dishonesty and bias. Over-reliance on randomized controlled trials (RCT) may be inappropriate, as RCTs are not a good source for picking up rare but important adverse effects such as lupus syndrome with minocycline. A common criticism leveled against SRs is that these frequently conclude that there is lack of sufficient evidence to inform current clinical practice, but arguably, such a perception is grounded more on the interpretation of the SRs than anything else. The apparent absence of evidence should not paralyze the dermatologist to adopt a state of therapeutic nihilism. Poor primary data and an SR based on evidence that is not up-to-date are also limitations that can only improve with better primary studies and updated reviews such as those done by the Cochrane Collaboration. Most dermatologists are interested in integrating the best external evidence with the care of individual patients and have been practicing good EBD without realizing it.
doi:10.4103/0019-5154.127670
PMCID: PMC3969670
Bias; dermatology; evidence-based; systematic review; trials; uncertainty
11.  RAMESES publication standards: meta-narrative reviews 
BMC Medicine  2013;11:20.
Background
Meta-narrative review is one of an emerging menu of new approaches to qualitative and mixed-method systematic review. A meta-narrative review seeks to illuminate a heterogeneous topic area by highlighting the contrasting and complementary ways in which researchers have studied the same or a similar topic. No previous publication standards exist for the reporting of meta-narrative reviews. This publication standard was developed as part of the RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) project. The project's aim is to produce preliminary publication standards for meta-narrative reviews.
Methods
We (a) collated and summarized existing literature on the principles of good practice in meta-narrative reviews; (b) considered the extent to which these principles had been followed by published reviews, thereby identifying how rigor may be lost and how existing methods could be improved; (c) used a three-round online Delphi method with an interdisciplinary panel of national and international experts in evidence synthesis, meta-narrative reviews, policy and/or publishing to produce and iteratively refine a draft set of methodological steps and publication standards; (d) provided real-time support to ongoing meta-narrative reviews and the open-access RAMESES online discussion list so as to capture problems and questions as they arose; and (e) synthesized expert input, evidence review and real-time problem analysis into a definitive set of standards.
Results
We identified nine published meta-narrative reviews, provided real-time support to four ongoing reviews and captured questions raised in the RAMESES discussion list. Through analysis and discussion within the project team, we summarized the published literature, and common questions and challenges into briefing materials for the Delphi panel, comprising 33 members. Within three rounds this panel had reached consensus on 20 key publication standards, with an overall response rate of 90%.
Conclusion
This project used multiple sources to draw together evidence and expertise in meta-narrative reviews. For each item we have included an explanation for why it is important and guidance on how it might be reported. Meta-narrative review is a relatively new method for evidence synthesis and as experience and methodological developments occur, we anticipate that these standards will evolve to reflect further theoretical and methodological developments. We hope that these standards will act as a resource that will contribute to improving the reporting of meta-narrative reviews.
To encourage dissemination of the RAMESES publication standards, this article is co-published in the Journal of Advanced Nursing and is freely accessible on Wiley Online Library (http://www.wileyonlinelibrary.com/journal/jan).
Please see related articles http://www.biomedcentral.com/1741-7015/11/21 and http://www.biomedcentral.com/1741-7015/11/22
doi:10.1186/1741-7015-11-20
PMCID: PMC3558334  PMID: 23360661
meta-narrative review; meta-narrative synthesis; publication standards
12.  Systematic Reviews and Meta-analysis: Understanding the Best Evidence in Primary Healthcare 
Healthcare decisions for individual patients and for public health policies should be informed by the best available research evidence. The practice of evidence-based medicine is the integration of individual clinical expertise with the best available external clinical evidence from systematic research and patient's values and expectations. Primary care physicians need evidence for both clinical practice and for public health decision making. The evidence comes from good reviews which is a state-of-the-art synthesis of current evidence on a given research question. Given the explosion of medical literature, and the fact that time is always scarce, review articles play a vital role in decision making in evidence-based medical practice. Given that most clinicians and public health professionals do not have the time to track down all the original articles, critically read them, and obtain the evidence they need for their questions, systematic reviews and clinical practice guidelines may be their best source of evidence. Systematic reviews aim to identify, evaluate, and summarize the findings of all relevant individual studies over a health-related issue, thereby making the available evidence more accessible to decision makers. The objective of this article is to introduce the primary care physicians about the concept of systematic reviews and meta-analysis, outlining why they are important, describing their methods and terminologies used, and thereby helping them with the skills to recognize and understand a reliable review which will be helpful for their day-to-day clinical practice and research activities.
doi:10.4103/2249-4863.109934
PMCID: PMC3894019  PMID: 24479036
Evidence-based medicine; meta-analysis; primary care; systematic review
13.  Evidence-Based Medicine: What Is It and How Does It Apply to Athletic Training? 
Journal of Athletic Training  2004;39(1):83-87.
Objective:
To introduce the concept of evidence-based medicine (EBM) to athletic trainers. This overview provides information on how EBM can affect the clinical practice of athletic training and enhance the care given to patients.
Data Sources:
We searched the MEDLINE and CINHAL bibliographic databases using the terms evidence-based medicine and best practice and the online Index to Abstracts of Cochrane Reviews by group (injury, musculoskeletal injuries, and musculoskeletal) to identify reviews on topics pertinent to athletic training.
Data Synthesis:
Evidence-based medical practice has 5 components: defining a clinically relevant question, searching for the best evidence, appraising the quality of the evidence, applying the evidence to clinical practice, and evaluating the process. Evidence-based medicine integrates the research evidence, clinician's expertise, and patient's preferences to guide clinical decision making. Critical to this effort is the availability of quality research on the effectiveness of sports medicine techniques. Athletic training outcomes research is lagging behind that of other health care professions.
Recommendations:
Athletic trainers need to embrace the critical-thinking skills to assess the medical literature and incorporate it into their clinical practice. The profession should encourage more clinically related research and enhance the scientific foundation of athletic training. Evidence-based medicine provides an important next step in the growth of the athletic training profession.
PMCID: PMC385266  PMID: 15085215
best practice; clinical research
14.  Is fine-needle aspiration diagnosis of malignancy adequate prior to major lung resections including pneumonectomy? 
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether a fine-needle aspiration (FNA) diagnosis is of sufficient reliability for the diagnosis of lung cancer prior to a major lung resection. Altogether, 112 papers were found using the reported search, of which 13 papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The tabulated studies include two meta-analyses, one systematic review, one randomized controlled trial (RCT) and nine cohort studies. The specificity reported for FNA in the diagnosis and staging of lung cancer ranged from 96.2 to 100%. One meta-analysis reported a specificity of 97%. Another meta-analysis reported a specificity of 98.8%. A systematic review reported a specificity of 97%. An RCT reported a specificity of 96.2–100%. We conclude that the FNA for lung cancer is reported to be highly specific prior to major lung resection with a very low false positive rate. However, although a false positive may occasionally be acceptable in lobectomies, where the lobes are often removed without histology, all steps should be taken to avoid a false positive result in pneumonectomy considering the serious consequences of embarking upon such an operation in the small number of patients with a false positive result, and we recommend that a positive FNA result should be confirmed by means of alternative sampling methods. We also acknowledge that obtaining an additional biopsy specimen would add to the risk of morbidity and costs; therefore, any benefits should be weighed against risks and additional costs.
doi:10.1093/icvts/ivs191
PMCID: PMC3397755  PMID: 22611184
Fine-needle aspiration; Lung neoplasms; Pneumonectomy; Specificity
15.  Critical appraisal of meta-analyses: an introductory guide for the practicing surgeon 
Meta-analyses are an essential tool of clinical research. Meta-analyses of individual randomized controlled trials frequently constitute the highest possible level of scientific evidence for a given research question and allow surgeons to rapidly gain a comprehensive understanding of an important clinical issue. Moreover, meta-analyses often serve as cornerstones for evidence-based surgery, treatment guidelines, and knowledge transfer. Given the importance of meta-analyses to the medical (and surgical) knowledge base, it is of cardinal importance that surgeons have a basic grasp of the principles that guide a high-quality meta-analysis, and be able to weigh objectively the advantages and potential pitfalls of this clinical research tool. Unfortunately, surgeons are often ill-prepared to successfully conduct, critically appraise, and correctly interpret meta-analyses. The objective of this educational review is to provide surgeons with a brief introductory overview of the knowledge and skills required for understanding and critically appraising surgical meta-analyses as well as assessing their implications for their own surgical practice.
doi:10.1186/1754-9493-3-16
PMCID: PMC2731030  PMID: 19624816
16.  Systematic reviews need systematic searchers 
Purpose: This paper will provide a description of the methods, skills, and knowledge of expert searchers working on systematic review teams.
Brief Description: Systematic reviews and meta-analyses are very important to health care practitioners, who need to keep abreast of the medical literature and make informed decisions. Searching is a critical part of conducting these systematic reviews, as errors made in the search process potentially result in a biased or otherwise incomplete evidence base for the review. Searches for systematic reviews need to be constructed to maximize recall and deal effectively with a number of potentially biasing factors. Librarians who conduct the searches for systematic reviews must be experts.
Discussion/Conclusion: Expert searchers need to understand the specifics about data structure and functions of bibliographic and specialized databases, as well as the technical and methodological issues of searching. Search methodology must be based on research about retrieval practices, and it is vital that expert searchers keep informed about, advocate for, and, moreover, conduct research in information retrieval. Expert searchers are an important part of the systematic review team, crucial throughout the review process—from the development of the proposal and research question to publication.
PMCID: PMC545125  PMID: 15685278
17.  Evidence-based periodontal therapy: An overview 
Dentists need to make clinical decisions based on limited scientific evidence. In clinical practice, a clinician must weigh a myriad of evidences every day. The goal of evidence-based dentistry is to help practitioners provide their patients with optimal care. This is achieved by integrating sound research evidence with personal clinical expertise and patient values to determine the best course of treatment. Periodontology has a rich background of research and scholarship. Therefore, efficient use of this wealth of research data needs to be a part of periodontal practice. Evidence-based periodontology aims to facilitate such an approach and it offers a bridge from science to clinical practice. The clinician must integrate the evidence with patient preference, scientific knowledge, and personal experience. Most important, it allows us to care for our patients. Therefore, evidence-based periodontology is a tool to support decision-making and integrating the best evidence available with clinical practice.
doi:10.4103/0972-124X.44097
PMCID: PMC2813561  PMID: 20142947
Evidence; periodontal therapy; study designs
18.  From Systematic Reviews to Clinical Recommendations for Evidence-Based Health Care: Validation of Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) for Grading of Clinical Relevance 
Research synthesis seeks to gather, examine and evaluate systematically research reports that converge toward answering a carefully crafted research question, which states the problem patient population, the intervention under consideration, and the clinical outcome of interest. The product of the process of systematically reviewing the research literature pertinent to the research question thusly stated is the “systematic review”.
The objective and transparent approach of the systematic review aims to minimize bias. Most systematic reviews yield quantitative analyses of measurable data (e.g., acceptable sampling analysis, meta-analysis). Systematic reviews may also be qualitative, while adhering to accepted standards for gathering, evaluating, and reporting evidence. Systematic reviews provide highly rated recommendations for evidence-based health care; but, systematic reviews are not equally reliable and successful in minimizing bias.
Several instruments are available to evaluate the quality of systematic reviews. The 'assessment of multiple systematic reviews' (AMSTAR) was derived from factor analysis of the most relevant items among them. AMSTAR consists of eleven items with good face and content validity for measuring the methodological quality of systematic reviews, has been widely accepted and utilized, and has gained in reliability, reproducibility. AMSTAR does not produce quantifiable assessments of systematic review quality and clinical relevance.
In this study, we have revised the AMSTAR instrument, detracting nothing from its content and construct validity, and utilizing the very criteria employed in the development of the original tool, with the aim of yielding an instrument that can quantify the quality of systematic reviews. We present validation data of the revised AMSTAR (R-AMSTAR), and discuss its implications and application in evidence-based health care.
doi:10.2174/1874210601004020084
PMCID: PMC2948145  PMID: 21088686
19.  Quality assessment of systematic reviews or meta-analyses of nursing interventions conducted by Korean reviewers 
Background
A systematic review is used to investigate the best available evidence of clinical safety and effectiveness of healthcare intervention. This requires methodological rigor in order to minimize bias and random error. The purpose of this study is to assess the quality of systematic reviews or meta-analyses for nursing interventions conducted by Korean researchers.
Methods
We searched electronic databases from 1950 to July 2010, including ovidMEDLINE, ovidEMBASE, and Korean databases, including KoreaMed, Korean Medical Database, and Korean studies Information Service System etc. Two reviewers independently screened and selected all references, and assessed the quality of systematic reviews or meta-analyses using the “Assessment of Multiple Systematic Reviews" (AMSTAR) tool.
Results
Twenty two systematic reviews or meta-analyses were included in this study. The median overall score (out of 11) for included reviews was 5 (range 2–11) and the mean overall score for AMSTAR was 4.7 (95% confidence interval 3.8-5.7). Nine out of 22 reviews were rated as low quality (AMSTAR score 0–4), 11 were rated as moderate quality (AMSTAR score 5–8), and two reviews were categorized as high quality (AMSTAR score 9–11).
Conclusions
The methodological quality of published reviews on nursing interventions conducted by Korean reviewers was assessed as low to moderate. In order to use the best available evidence in clinical decision making, reviewers should conduct systematic reviews or meta- analyses using rigorous research methods.
doi:10.1186/1471-2288-12-129
PMCID: PMC3552770  PMID: 22928687
Systematic review; Meta analysis; Quality assessment; Nursing intervention
20.  Tools for Identifying Reliable Evidence and Implementing it in Everyday Clinical Care  
Just as translational medicine follows a long winding path from bench-to-bedside, so can Evidence-Based Medicine be envisioned as comprising a multi-step pipeline, from building evidence from raw data through synthesizing best practices and providing clinical decision support in a process described as the “evidence pyramid”. 1 At one end, a heterogeneous mix of clinical and experimental studies including clinical trials, case reports, animal models and retrospective analyses are published as new knowledge. Then, experts collect and assess high-quality relevant evidence on specific issues and publish their conclusions (e.g., regarding efficacy and safety of treatments) as systematic reviews and meta-analyses. Finally, when an expert consensus has been reached, this must reach the attention of policy makers within the profession, the government and insurance companies, resulting in new practice guidelines and altered clinical practice within hospitals and clinics. At each stage, this process requires a large investment of time and effort from many individuals with a wide range of expertise.
Our panel will discuss the variety of innovative approaches that are being taken by different informatics research groups to improve each step within the evidence based medicine pipeline. These approaches are, in part, devoted to making existing data collection and synthesis practices faster and more efficient, but they also involve re-imagining and re-engineering the processes by which evidence is accumulated, evaluated and applied.
PMCID: PMC3845785  PMID: 24303233
21.  A systematic evaluation of the quality of meta-analyses in the critical care literature 
Critical Care  2005;9(5):R575-R582.
Introduction
Meta-analyses have been suggested to be the highest form of evidence available to clinicians to guide clinical practice in critical care. The purpose of this study was to systematically evaluate the quality of meta-analyses that address topics pertinent to critical care.
Methods
To identify potentially eligible meta-analyses for inclusion, a systematic search of Medline, EMBASE and the Cochrane Database of Systematic Reviews was undertaken, using broad search terms relevant to intensive care, including: intensive care, critical care, shock, resuscitation, inotropes and mechanical ventilation. Predetermined inclusion criteria were applied to each identified meta-analysis independently by two authors. To assess report quality, the included meta-analyses were assessed using the component and overall scores from the Overview Quality Assessment Questionnaire (OQAQ). The quality of reports published before and after the publication of the QUOROM statement was compared.
Results
A total of 139 reports of meta-analyses were included (kappa = 0.93). The overall quality of reports of meta-analyses was found to be poor, with an estimated mean overall OQAQ score of 3.3 (95% CI; 3.0–3.6). Only 43 (30.9%) were scored as having minimal or minor flaws (>5). We noted problems with the reporting of key characteristics of meta-analyses, such as performing a thorough literature search, avoidance of bias in the inclusion of studies and appropriately referring to the validity of the included studies. After the release of the QUOROM statement, however, an improvement in the overall quality of published meta-analyses was noted.
Conclusion
The overall quality of the reports of meta-analyses available to critical care physicians is poor. Physicians should critically evaluate these studies prior to considering applying the results of these studies in their clinical practice.
doi:10.1186/cc3803
PMCID: PMC1297628  PMID: 16277721
22.  Comparison of Treatment Effect Estimates for Pharmacological Randomized Controlled Trials Enrolling Older Adults Only and Those including Adults: A Meta-Epidemiological Study 
PLoS ONE  2013;8(5):e63677.
Context
Older adults are underrepresented in clinical research. To assess therapeutic efficacy in older patients, some randomized controlled trials (RCTs) include older adults only.
Objective
To compare treatment effects between RCTs including older adults only (elderly RCTs) and RCTs including all adults (adult RCTs) by a meta-epidemiological approach.
Methods
All systematic reviews published in the Cochrane Library (Issue 4, 2011) were screened. Eligible studies were meta-analyses of binary outcomes of pharmacologic treatment including at least one elderly RCT and at least one adult RCT. For each meta-analysis, we compared summary odds ratios for elderly RCTs and adult RCTs by calculating a ratio of odds ratios (ROR). A summary ROR was estimated across all meta-analyses.
Results
We selected 55 meta-analyses including 524 RCTs (17% elderly RCTs). The treatment effects differed beyond that expected by chance for 7 (13%) meta-analyses, showing more favourable treatment effects in elderly RCTs in 5 cases and in adult RCTs in 2 cases. The summary ROR was 0.91 (95% CI, 0.77–1.08, p = 0.28), with substantial heterogeneity (I2 = 51% and τ2 = 0.14). Sensitivity and subgroup analyses by type-of-age RCT (elderly RCTs vs RCTs excluding older adults and vs RCTs of mixed-age adults), type of outcome (mortality or other) and type of comparator (placebo or active drug) yielded similar results.
Conclusions
The efficacy of pharmacologic treatments did not significantly differ, on average, between RCTs including older adults only and RCTs of all adults. However, clinically important discrepancies may occur and should be considered when generalizing evidence from all adults to older adults.
doi:10.1371/journal.pone.0063677
PMCID: PMC3665786  PMID: 23723992
23.  Systematic Reviews and Meta Analysis of Published Studies: An overview and Best Practices 
Systematic reviews and meta-analytic approaches are widely used in the clinical arena to integrate outcome data from published studies in a patient population that address a set of related research hypotheses. The credibility of this line of research is dependent on how the studies are chosen, how the data are assembled and how the results are reported. In this brief report, we provide an overview of the minimum set of reporting requirements for systematic reviews and meta-analyses based on the PRISMA (Preferred Reporting Items of Systematic reviews and Meta-Analyses) guidelines. As with any research, following a set of established guidelines is essential for quality and consistency of the findings across studies, and for assessment of clinical utility.
doi:10.1097/JTO.0b013e31822461b0
PMCID: PMC3158384  PMID: 21847059
Bias; Heterogeneity; Meta-analysis; PRISMA; Systematic Reviews
24.  Sinus surgery and delivery method influence the effectiveness of topical corticosteroids for chronic rhinosinusitis: Systematic review and meta-analysis 
Background:
Published randomized controlled trials (RCTs) on the efficacy of intranasal corticosteroid (INCS) in chronic rhinosinusitis (CRS) use either nasal delivery (nasal drop or nasal spray) or sinus delivery (sinus catheter or sinus irrigation) in patients with or without sinus surgery. This influences topical drug delivery and distribution. The effect of these factors on the published results of RCTs is assessed. This systematic review explores the strength of evidence supporting the influence of sinus surgery and delivery methods on the effectiveness of topical steroids in studies for CRS with meta-analyses.
Methods:
A systematic review was conducted of RCTs comparing INCS with either placebo or no intervention for treating CRS. Data were extracted for meta-analysis and subgroup analyses by sinus surgery status and topical delivery methods.
Results:
Forty-eight studies (3961 patients) met the inclusion criteria. INCS improved overall symptoms (standardized mean difference [SMD], −0.49; p < 0.00001) and the proportion of responders (risk ratio [RR], 0.59; p < 0.00001) compared with placebo. It decreased nasal polyp size with a greater proportion of responders (RR, 0.48; p < 0.00001) and prevented polyp recurrence (RR, 0.59; p = 0.0004) compared with placebo. Reduction of polyp size was greater in patients with sinus surgery (RR, 0.31; 95% confidence interval [CI], 0.20, 0.48) than those without (RR, 0.61; 95% CI, 0.46, 0.81; p = 0.009). Greater symptom improvement occurred when sinus delivery methods (SMD, −1.32; 95% CI, −2.26, −0.38) were compared with nasal delivery methods (SMD, −0.38; 95% CI, −0.55, −0.22; p < 0.00001).
Conclusion:
INCS is effective for CRS. Prior sinus surgery and direct sinus delivery enhance the effectiveness of INCS in CRS.
doi:10.2500/ajra.2013.27.3880
PMCID: PMC3901441  PMID: 23710959
Chronic rhinosinusitis; intranasal corticosteroid; nasal drop; nasal polyps; nasal spray; sinus irrigation; sinusitis; sinus surgery; steroids
25.  PHARMACEUTICAL-INDUSTRY SPONSORED RESEARCH: PROMOTING TRANSPARENCY 
Strong, evidence-based practice requires that objective, unbiased research is available to inform individual clinical decisions, systematic reviews, meta-analyses, and expert guideline recommendations. Seeding trials, publication planning, messaging, and ghostwriting, as well as selective publication and reporting of trial outcomes have been used by industry to distort the medical literature and undermine clinical trial research, explicitly by obscuring information that is relevant to patients and physicians. Policies that promote transparency into the clinical trial research process, through improved and expanded disclosure of investigator contributions and funding, comprehensive publicly-available trial registration, and independent analysis of clinical trial data, have the potential to address these subversive practices by improving accountability among industry and investigators. Minimizing the impact of marketing on clinical trial research, and strengthening the science, will protect both the integrity of the medical literature as well as the public’s health.
doi:10.2105/AJPH.2011.300187
PMCID: PMC3319748  PMID: 22095335

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