scispace - formally typeset
Search or ask a question

Showing papers by "Gordon H. Guyatt published in 2005"


Journal ArticleDOI
01 Jan 2005-Chest
TL;DR: None of the pooled metaanalyses showed a significant difference between devices in any efficacy outcome in any patient group for each of the clinical settings that was investigated.

755 citations


Journal ArticleDOI
02 Nov 2005-JAMA
TL;DR: RCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small, which suggests clinicians should view the results of such trials with skepticism.
Abstract: ContextRandomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown.ObjectiveTo evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit.Data SourcesSystematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit.Study SelectionRandomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria.Data ExtractionTwelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping.Data SynthesisOf 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P<.001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range [IQR], 3-25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23-195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28-0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11-73).ConclusionsRCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.

681 citations


Journal ArticleDOI
TL;DR: The magnitude of the problem, the pathophysiology of these events, approaches to risk assessment and communication of risk, and methods to facilitate the estimation of perioperative cardiac risk are reviewed.
Abstract: This is the first of 2 articles evaluating cardiac events in patients undergoing noncardiac surgery. In this article, we review the magnitude of the problem, the pathophysiology of these events, approaches to risk assessment and communication of risk. The number of patients undergoing noncardiac surgery worldwide is growing, and annually 500,000 to 900,000 of these patients experience perioperative cardiac death, nonfatal myocardial infarction (MI) or nonfatal cardiac arrest. Although the evidence is limited, a substantial proportion of fatal perioperative MIs may not share the same pathophysiology as nonoperative MIs. A clearer understanding of the pathophysiology is needed to direct future research evaluating prophylactic, acute and long-term interventions. Researchers have developed tools to facilitate the estimation of perioperative cardiac risk. Studies suggest that the Lee index is the most accurate generic perioperative cardiac risk index. The limitations of the studies evaluating the ability of noninvasive cardiac tests to predict perioperative cardiac risk reveals considerable uncertainty as to the role of these popular tests. Similarly, there is uncertainty as to the predictive accuracy of the American College of Cardiology/American Heart Association algorithm for cardiac risk assessment. Patients are likely to benefit from improved estimation and communication of cardiac risk because the majority of noncardiac surgeries are elective and accurate risk estimation is important to allow informed patient and physician decision-making.

568 citations


Journal ArticleDOI
04 Aug 2005-BMJ
TL;DR: The evidence that perioperative β blocker treatment in patients having non-cardiac surgery reduces major cardiovascular events is encouraging but too unreliable to allow definitive conclusions to be drawn.
Abstract: Objective To determine the effect of perioperative β blocker treatment in patients having non-cardiac surgery Design Systematic review and meta-analysis Data sources Seven search strategies, including searching two bibliographic databases and hand searching seven medical journals Study selection and outcomes We included randomised controlled trials that evaluated β blocker treatment in patients having non-cardiac surgery Perioperative outcomes within 30 days of surgery included total mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal cardiac arrest, non-fatal stroke, congestive heart failure, hypotension needing treatment, bradycardia needing treatment, and bronchospasm Results Twenty two trials that randomised a total of 2437 patients met the eligibility criteria Perioperative β blockers did not show any statistically significant beneficial effects on any of the individual outcomes and the only nominally statistically significant beneficial relative risk was 044 (95% confidence interval 020 to 097, 99% confidence interval 016 to 124) for the composite outcome of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal cardiac arrest Methods adapted from formal interim monitoring boundaries applied to cumulative meta-analysis showed that the evidence failed, by a considerable degree, to meet standards for forgoing additional studies The individual safety outcomes in patients treated with perioperative β blockers showed a relative risk for bradycardia needing treatment of 227 (95% CI 153 to 336, 99% CI 136 to 380) and a nominally statistically significant relative risk for hypotension needing treatment of 127 (95% CI 104 to 156, 99% CI 097 to 166) Conclusion The evidence that perioperative β blockers reduce major cardiovascular events is encouraging but too unreliable to allow definitive conclusions to be drawn

441 citations


Journal ArticleDOI
06 Jan 2005-BMJ
TL;DR: Evidence is presented to support the argument that increased use of the expertise based design will enhance the validity, applicability, feasibility, and ethical integrity of randomised controlled trials in surgery, as well as in other areas.
Abstract: Surgical procedures are less likely to be rigorously evidence based than drug treatments because of difficulties with randomisation. Expertise based trials could be the way forward Although conventional randomised controlled trials are widely recognised as the most reliable method to evaluate pharmacological interventions,1 2 scepticism about their role in nonpharmacological interventions (such as surgery) remains.3–6 Conventional randomised controlled trials typically randomise participants to one of two intervenions (A or B) and individual clinicians give intervention A to some participants and B to others. An alternative trial design, the expertise based randomised controlled trial, randomises participants to clinicians with expertise in intervention A or clinicians with expertise in intervention B, and the clinicians perform only the procedure they are expert in. We present evidence to support our argument that increased use of the expertise based design will enhance the validity, applicability, feasibility, and ethical integrity of randomised controlled trials in surgery, as well as in other areas. We focus on established surgical interventions rather than new surgical procedures in which clinicians have not established expertise. Investigators have used the expertise based design when conventional randomised controlled trials were impossible because different specialty groups provided the interventions under evaluation—for example, percutaneous transluminal coronary angioplasty versus coronary artery bypass graft surgery.7–9 In 1980, Van der Linden suggested randomising participants to clinicians committed to performing different interventions in an area in which a conventional randomised controlled trial was possible.10 Since that time, however, the expertise based design has been little used, even in areas where it has high potential (such as, surgery, physiotherapy, and chiropractic). ### Differential expertise between procedures Because it takes training and experience to develop expertise in surgical interventions, individual surgeons tend to solely or primarily use a single surgical approach to treat a specific problem.10 11 …

410 citations


Journal ArticleDOI
TL;DR: Despite universal thromboprophylaxis, medical-surgical critically ill patients remain at risk for lower extremity deep venousThrombosis, and further research is needed to evaluate the risks and benefits of more intense venous thromboembolism prophylaxis.
Abstract: Objective: Critically ill patients may be at high risk of venous thromboembolism. The objective was to determine the prevalence, incidence, and risk factors for proximal lower extremity deep venous thrombosis among critically ill medical-surgical patients. Design: Prospective cohort. Setting: Closed university-affiliated intensive care unit. Patients: We enrolled consecutive patients >18 yrs of age expected to be in intensive care unit for >72 hrs. Exclusion criteria were an admitting diagnosis of trauma, orthopedic surgery, pregnancy, and life support withdrawal. Interventions: Interventions included bilateral lower extremity compression ultrasound within 48 hrs of intensive care unit admission, twice weekly, and if venous thromboembolism was clinically suspected. Thromboprophylaxis was protocol directed and universal. We recorded deep venous thrombosis risk factors at baseline and daily, using multivariate regression analysis to determine independent predictors. Patients were followed to hospital discharge. Results: Among 261 patients with a mean Acute Physiology and Chronic Health Evaluation II score of 25.5 (8.4), the prevalence of deep venous thrombosis was 2.7% (95% confidence interval 1.1‐5.5) on intensive care unit admission, and the incidence was 9.6% (95% confidence interval 6.3‐13.8) over the intensive care unit stay. We identified four independent risk factors for intensive care unit-acquired deep venous thrombosis: personal or family history of venous thromboembolism (hazard ratio 4.0, 95% confidence interval 1.5‐ 10.3), end-stage renal failure (hazard ratio 3.7, 95% confidence interval 1.2‐11.1), platelet transfusion (hazard ratio 3.2, 95% confidence interval 1.2‐8.4), and vasopressor use (hazard ratio 2.8, 95% confidence interval 1.1‐7.2). Patients with deep venous thrombosis had a longer duration of mechanical ventilation (p .03), intensive care unit stay (p .005), and hospitalization (p < .001) than patients without deep venous thrombosis. Conclusions: Despite universal thromboprophylaxis, medicalsurgical critically ill patients remain at risk for lower extremity deep venous thrombosis. Further research is needed to evaluate the risks and benefits of more intense venous thromboembolism prophylaxis. (Crit Care Med 2005; 33:1565‐1571)

370 citations


Journal ArticleDOI
10 Mar 2005-BMJ
TL;DR: In this article, a strategy to interpret the results of clinical trials when investigators measure the effect of treatment on an aggregate of end points of varying importance is provided.
Abstract: Use of composite end points as the main outcome in randomised trials can hide wide differences in the individual measures How should you apply the results to clinical practice?

370 citations


Book
21 Sep 2005
TL;DR: Becoming a Clinical Researcher * Becoming a Successful Clinician-Investigator * Preparing a Research Protocol to improve its Chances for Success.
Abstract: PART ONE: Performing Clinical Research * Forming Research Questions... 3 * Conducting Systematic Reviews... 15 * Finding Information About the Burden of Disease... 49 * An Introduction to Performing Therapeutic Trials... 59 * The Tactics of Performing Therapeutic Trials... 66 * The Principles Behind the Tactics of Performing Therapeutic Trials... 173 * Testing Quality Improvement Interventions... 244 * Evaluating Diagnostic Tests... 273 * Determining Prognosis and Creating Clinical Decision Rules... 323 * Assessing Claims of Causation... 356 * Generating Outcome Measurements, Especially for Quality of Life... 388 PART TWO: Becoming a Clinical Researcher * Becoming a Successful Clinician-Investigator... 415 * Preparing a Research Protocol to Improve its Chances for Success... 429 * Online Data Collection... 440 * Analyzing Data... 446 * Preparing Reports for Publication and Responding to Reviewers' Comments... 461 * Dealing with the Media... 474 Index... 487

326 citations


Journal ArticleDOI
TL;DR: A pilot test of the GRADE approach to grading evidence and recommendations found the approach to be clear, understandable and sensible and some modifications were made in the approach and it was agreed that more information was needed in the evidence profiles.
Abstract: Background Systems that are used by different organisations to grade the quality of evidence and the strength of recommendations vary. They have different strengths and weaknesses. The GRADE Working Group has developed an approach that addresses key shortcomings in these systems. The aim of this study was to pilot test and further develop the GRADE approach to grading evidence and recommendations.

317 citations


Journal ArticleDOI
TL;DR: A systematic review of the literature on the chronic respiratory questionnaire and a methodological framework for using anchor based approaches to establish the minimal important difference pioneered by Jaeschke and colleagues are included.
Abstract: The chronic respiratory questionnaire, available as an interviewer and a self-administered instrument, includes 20 items across four domains: dyspnea (5 items), fatigue (4 items), emotional function (7 items), and mastery (4 items). When completing this instrument, patients rate their experience on a 7-point scale ranging from 1 (maximum impairment) to 7 (no impairment). The Chronic Respiratory Questionnaire has demonstrated excellent measurement properties for both discriminative and evaluative purposes and served as a model in numerous methodological studies in chronic airflow limitation and patients with chronic obstructive pulmonary disease. We performed a systematic review of the literature on the chronic respiratory questionnaire to summarize the key qualities of the chronic respiratory questionnaire and to appraise the work regarding the minimal important difference of the chronic respiratory questionnaire. This paper includes a revision of our initial definition of the minimal important difference and a methodological framework for using anchor based approaches to establish the minimal important difference pioneered by Jaeschke and colleagues. Other approaches to evaluate the minimal important difference include distribution-based methods and panel-based methods. Investigators have used all of these approaches to establish the minimal important difference for the chronic respiratory questionnaire and the results are in general agreement with the minimal important difference of 0.5 for the mean domain scores of the chronic respiratory questionnaire. As a result of this literature review and discussion at the workshop, we established several research objectives. These objectives include the exploration of presentation of quality of life information and prospective anchor-based approaches.

246 citations


Journal ArticleDOI
TL;DR: The substantial reduction in risk of death, low adverse events reported and low costs related to this intervention suggest great potential for melatonin in treating cancer.
Abstract: Most observational studies show an association between melatonin and cancer in humans. We conducted a systematic review of randomized controlled trials (RCTs) of melatoni ni n solid tumor cancer patients and its effect on survival at 1 yr. With the aid of an information specialist, we searched 10 electronic databases from inception to October 2004. We included trials using melatonin as either sole treatment or as adjunct treatment. Prespecified criteria guided our assessment of trial quality. We conducted a meta-analysis using a random effects model. We included 10 RCTs published between 1992 and 2003 and included 643 patients. All trials included solid tumor cancers. All trials were conducted at the same hospital network, and were unblinded. Melatonin reduced the risk of death at 1 yr (relative risk: 0.66, 95% confidence interval: 0.59-0.73, I 2 ¼ 0%, heterogeneity P £ 0.56). Effects were consistent across melatonin dose, and type of cancer. No severe adverse events were reported. The substantial reduction in risk of death, low adverse events reported and low costs related to this intervention suggest great potential for melatonin in treating cancer. Confirming the efficacy and safety of melatonin in cancer treatment will require completion of blinded, independently conducted RCTs.

Journal ArticleDOI
TL;DR: The best evidence does not support a management strategy of preoperative coronary revascularization before noncardiac surgery, and a proposed diagnostic criteria that reflect the unique features of perioperative MIs is proposed.
Abstract: THIS IS THE SECOND OF 2 ARTICLES EVALUATING cardiac events in patients undergoing noncardiac surgery. Unrecognized myocardial infarctions (MIs) are common, and up to 50% of perioperative MIs may go unrecognized if physicians rely only on clinical signs or symptoms. In this article, we summarize the evidence regarding monitoring strategies for perioperative MI in patients undergoing noncardiac surgery. Perioperative troponin measurements and 12-lead electrocardiograms can detect clinically silent MIs and provide independent prognostic information. Currently, there are no standard diagnostic criteria for perioperative MIs in patients undergoing noncardiac surgery. We propose diagnostic criteria that reflect the unique features of perioperative MIs. Finally, we review the evidence for perioperative prophylactic cardiac interventions. There is encouraging evidence that some perioperative interventions (e.g., β-blockers, α2-adrenergic agonists, statins) may prevent major cardiac ischemic events, but firm conclusions await the results of large definitive trials. The best evidence does not support a management strategy of preoperative coronary revascularization before noncardiac surgery.

Journal ArticleDOI
TL;DR: Patients who developed thrombocytopenia in the intensive care unit (ICU) were more likely to die, required longer duration of mechanical ventilation, and were morelikely to require blood product transfusion.

Journal ArticleDOI
TL;DR: This commentary argues that research on the interpretability of HRQL instruments should focus primarily on the patient's view, and defines the minimal important difference (MID) as the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important.
Abstract: Health-related quality of life (HRQL) has overcome many barriers that limited its acceptance as an important outcome in health care. One of the remaining barriers relates to how one should interpret HRQL scores when they change over time within patients, or differ between patients. Indeed, because there is no gold standard methodology, interpreting HRQL scores is a challenging task. While daunting, addressing the challenge of interpretability is crucial to moving the field forward. The choice of what constitutes an important difference in a HRQL score will influence judgments about the success of a health care intervention, the required sample size of clinical studies, and the design of these studies. The issue is relevant to clinicians, payers, funding agencies, and regulatory agencies, and most relevant to patients for whose health care these groups claim responsibility. Several approaches to assessing interpretability exist. Anchor-based approaches rely on examining the relation between scores on a HRQL instrument that is under investigation and an anchor, an independent measure of HRQL that clinicians can easily interpret (Guyatt et al. 2002). Other approaches for evaluation of interpretability of HRQL scores include distribution-based or statistical methods and reliance on experts (panel-based methods) (Lassere et al. 2001). Wyrwich and colleagues utilized the last of these alternatives to determine interpretability of the SF-36 by elegantly combining outcomes research with qualitative research methods (Wyrwich et al. 2003; 2005). This approach focuses on how clinician researchers view patients in relation to their HRQL scores and changes in HRQL scores. The article by Wyrwich's et al. is ingenious for several reasons. First, despite the wealth of literature evaluating the SF-36 as an outcome measure, evidence for the interpretability of the instrument is surprisingly limited. Second, Wyrwich and colleagues focus on three different clinician groups and estimates whether interpretability differs across these groups. Third, the judgments the clinician researchers made were based on detailed patient scenarios. In this commentary we will provide two arguments that readers should consider in the context of the work by Wyrwich and colleagues. First, we argue that research on the interpretability of HRQL instruments should focus primarily on the patient's view. Early work by our group pioneered the methodology of assessing interpretability of HRQL instruments (Jaeschke, Singer, and Guyatt 1989). In that work, we described what became widely known as the minimal clinical important difference (MCID). Because this terminology focuses attention on the clinical arena rather than patients' experience in their day-to-day lives, we subsequently removed the focus on “clinical” interpretations, and the “C” from MCID to focus on the minimal important difference (MID) (Juniper et al. 1994; Schunemann et al. 2005). HRQL is a patient important outcome because it is the patients who experience their HRQL, and only they are in a position to ultimately judge whether a difference is important (Guyatt et al. 2004). We now define the MID as the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important, either beneficial or harmful, and which would lead the patient or clinician to consider a change in the management (Schunemann et al. 2005). The revised description of the MID precludes making MID estimates for outcomes that are remote from those important, in themselves, to patients, such as spirometry or laboratory exercise capacity. Further, the definition suggests that only if one had reason to question the reliability or accuracy of data from patients would one rely on proxies to provide estimates of the MID. Investigators or clinicians may differ in the perspective or the methodology they adopt to determine the MID. Thus, readers, when they interpret the results of research on the MID, must attend to who rated the importance of an HRQL change and the specific instructions provided for making the assessment. If one accepts that HRQL measurement must be fundamentally patient-centered, the first choice for establishing the MID should be a patient-based approach. Relative to patients, clinicians may overemphasize treatment effects (Puhan et al. 2004) and agreement between patients and proxies in rating of HRQL is not perfect (Sneeuw, Sprangers, and Aaronson 2002; Ubel, Loewenstein, and Jepson 2003; von Essen 2004). Again, if one accepts that patients are at the center in HRQL measurement, then investigators, when they do use proxies, should instruct those proxies to focus on what they believe patients consider important. Wrywich and colleagues took a different approach. “Panelists were not provided with any specific definition of a CID (clinically important difference), but left to determine their own meaning for this term” (p. 580). Thus, the investigators did not specify to the participants that they were to estimate the difference that patients consider important. Further, they used the term “CID,” further permitting ambiguity about the group to whom the difference is important. Our second argument concerns the results of the study. If readers dismiss our appeal to focus on the patient, they should examine the result of the study. While the results, including the difference in the MID between heart failure clinician researchers and those working in asthma or chronic obstructive pulmonary disease (COPD) provide intriguing insights into clinicians' perspectives, the extent to which they enlighten us concerning differences in SF-36 scores that patients consider important remains questionable. At least two issues are worth considering. First, readers should ask whether the differences in the MID for the three evaluated diseases are true. Methodological issues, such as sampling bias in terms of the physician researchers selected for this exercise, or randomness around the consensus estimates could explain these MID differences. There were no statistical approaches—and perhaps there are none for this study design—to compare the magnitude of the MID differences across diseases obtained from the physician researchers. Although Wyrwich and colleagues performed a laborious study, readers should ask how large would the variation around the obtained MID estimates be if they had conducted multiple focus groups for each disease category. Could chance explain the observed differences in the MIDs from the three focus groups? Readers should not ignore this possible explanation. Second, if the MID on the SF-36 was truly greater for heart failure patients compared with patients suffering from asthma or COPD, it might also have implications for the comparability of SF-36 scores. The SF-36 is a generic HRQL instrument. To be applicable to different patient populations, similar scores across different patient population should signify similar levels or impairment of HRQL. For instance, a mean score of 50 on the 0–100 scale of the physical functioning domain should indicate a similar level of physical function for different patient populations such as patients with asthma, COPD, and heart failure. If interventions caused an improvement of HRQL to 60, the result of the study by Wyrwich and colleagues would suggest that the change is important for the former two groups but not the latter. Would the post-intervention scores of 60 still be comparable across these populations? It is conceivable that differences between patient groups in what constitutes an important change could impair the comparability of generic instruments. Thus, the implications of an MID for the SF-36 that varies by population could be far reaching. Such results could question the SF-36 as a generic instrument that allows a straightforward comparison across diseases. In summary, the MID provides an important strategy to make interpretable the results of HRQL studies. To be maximally informative, representative samples of informed patients or their proxies should provide estimates of the MID.


Journal ArticleDOI
TL;DR: The development of explicit, hypothesis-driven, and iterative approaches to outcome measure development, patterned on approaches used in the fields of rheumatology and oncology, may improve the conduct of clinical studies in the critically ill.
Abstract: Background and Objectives: Sepsis is the leading cause of morbidity and mortality for patients admitted to an intensive care unit. The evaluation of new therapies has been hampered by the underdevelopment of outcome measures used to detect biological activity and patient-centered benefit in a complex and highly heterogeneous patient population. We sought to evaluate existing approaches and to draw on insights from other disciplines to propose a comprehensive approach to outcome evaluation in sepsis clinical trials. Methods: An expert colloquium organized by the International Sepsis Forum brought together sepsis researchers, clinical epidemiologists, and experts in the development and implementation of outcome measures in rheumatology, neurology, and oncology. Results: The translation of an evolving understanding of the biology of sepsis into effective new therapies for critically ill patients requires a reevaluation of the end points used to determine response to intervention. These represent a continuum that measures biological activity against the target at one end and sustained improvement in survival or quality of life at the other. Early phase research should determine whether an intervention works in vivo, using measures that are responsive and informative to provide proof of principle, to aid in selecting optimal patient populations for study, and to gain insights into optimal dose and duration of therapy. After in vivo biology has been demonstrated and the possibility of efficacy inferred by plausible improvements in surrogate physiologic measures, definitive studies should seek robust evidence of benefit using end points that measure important, patient-centered benefit, including intermediate and longer term survival and health-related quality of life. Nonmortal measures of benefit assume particular importance for populations, such as children, whose mortality risk is low, or who have significant rates of comorbidities that independently limit survival. Composite measures that integrate morbidity and mortality effects may provide the most meaningful information about therapeutic efficacy. Conclusions: The development of explicit, hypothesis-driven, and iterative approaches to outcome measure development, patterned on approaches used in the fields of rheumatology and oncology, may improve the conduct of clinical studies in the critically ill. LEARNING OBJECTIVES On completion of this article, the reader should be able to: LEARNING OBJECTIVES Dr. Marshall has disclosed that he was formerly a consultant for Edwards and Wyeth-Ayerst and is currently a consultant for BRAHMS Diagnostics, and GlaxoSmithKline. Dr. Bernard has disclosed that he has been the recipient of grant/research funds from Eli Lilly, Novo Nordisk, and Takeda Pharmaceuticals. Dr. Bonbardier has disclosed that she has been the recipient of grant/research funds from Abbott and Amgen, is a consultant/advisor for and is on the speakers bureau of Merck, Pfizer, Schering-Plough Corp., and Wyeth. Dr. Calandra has disclosed that he is the recipient of direct grant/research funding from Baxter, Wako, and Merck and was the recipient of direct grant/research funding from Pfizer, Natimmune, Bristol-Myers Squibb in the past; a consultant/advisor for Baxter, Pfizer, Merck, GlaxoSmithKline, CAT, Roche; and on the speakers bureau of Pfizer and Merck and was formerly on the speakers bureau of GlaxoSmithKline. The remaining authors have disclosed that they have no financial relationships or interest in any commercial companies pertaining to this educational activity. LEARNING OBJECTIVES Wolters Kluwer Health has identified and resolved all faculty conflicts of interests regarding this educational activity. LEARNING OBJECTIVES Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

Journal ArticleDOI
TL;DR: Clinicians wishing to quickly answer a clinical question may seek a systematic review, rather than searching for primary articles, when the investigators have used statistical techniques to combine results across studies.
Abstract: Clinicians wishing to quickly answer a clinical question may seek a systematic review, rather than searching for primary articles. Such a review is also called a meta-analysis when the investigators have used statistical techniques to combine results across studies. Databases useful for this purpose

Journal ArticleDOI
TL;DR: Consuming 5 or more cups of green tea a day shows a non-statistically significant trend towards the prevention of breast cancer development, and evidence indicates that green tea consumption may possibly help prevent breast cancer recurrence in early stage (I and II) cancers.
Abstract: Background: Green tea is widely used by women for the prevention and treatment of breast cancer. The authors aimed to determine the efficacy of green tea ingestion on the risk of breast cancer development and the risk of breast cancer recurrence. Methods: The authors conducted a systematic review and meta-analyses of observational studies from systematic searches of 8 electronic data sources and contact with authors. They included studies assessing breast cancer incidence and recurrence. Results from cohort studies and case-control studies were pooled separately using a random effects model with testing of a priori hypotheses to explain heterogeneity. Results: The pooled relative risk (RR) of developing breast cancer for the highest levels of green tea consumption in cohort studies was 0.89 (95% confidence interval [CI], 0.71-1.1; P = .28; I 2 = 0%), and in case control studies, the odds ratio was 0.44 (95% CI, 0.14-1.31; P = .14; I 2 = 47%). The pooled RR of cohort studies for breast cancer recurrence in all stages was 0.75 (95% CI, 0.47-1.19; P = .22; I 2 = 37%). A subgroup analysis of recurrence in stage I and II disease showed a pooled RR in cohort studies of 0.56 (95% CI, 0.38-0.83; P = .004; I 2 = 0%). Dose-response relationships were evident in only 3 of the 7 studies. Conclusion: To date, the epidemiological data indicates that consumption of 5 or more cups of green tea a day shows a non-statistically significant trend towards the prevention of breast cancer development. Evidence indicates that green tea consumption may possibly help prevent breast cancer recurrence in early stage (I and II) cancers. However, conclusions as to the potential therapeutic application of green tea are currently impossible to make due to the small number of studies conducted, the lack of any clinical trial evidence, the lack of a consistent dose-response relationship, and the potential for interaction with standard care.

Journal ArticleDOI
TL;DR: A meta-analysis of six randomized controlled trials suggested that bisphosphonates have a beneficial effect with regard to maintaining more periprosthetic bone mineral density than that in controls.
Abstract: Background: Periprosthetic bone loss following total joint arthroplasty may threaten the survival of the implant. Bisphosphonates are effective in reducing bone loss in conditions associated with accelerated bone turnover. To determine the current understanding of the effect of bisphosphonates on pe

Journal ArticleDOI
TL;DR: An inhospital educational intervention improved knowledge and, possibly, quality of life and may be useful as part of a comprehensive compliance enhancing strategy in patients with HF.

Journal ArticleDOI
TL;DR: Self-administration and standardisation of the Chronic respiratory questionnaire maintains validity and responsiveness relative to the interviewer-administered chronic respiratory questionnaire, and challenges the assumption that interviewer- administered questionnaires are superior to self- Administered questionnaires in older patients with chronic respiratory disease.
Abstract: The original chronic respiratory questionnaire (CRQ), one of the most widely used measures of health-related quality of life (HRQL) in chronic respiratory disease (CRD), is traditionally interviewer administered (IA) and includes an individualised dyspnoea domain. The present authors studied the impact of self-administered (SA) and standardised dyspnoea questions on CRQ measurement properties. In a factorial design multicentre trial, 177 patients with CRD (mean age 67.7 yrs; mean forced expiratory volume in one second per cent predicted 44.6%) were randomised to CRQ-IA (n = 86) or CRQ-SA (n = 91), and to initially complete the standardised or individualised items before and after respiratory rehabilitation. While maintaining validity, the CRQ-SA proved more responsive to changes in HRQL than the CRQ-IA in all domains. Compared with the standardised dyspnoea domain, the individualised dyspnoea domain indicated greater responsiveness. The correlations of baseline scores and change scores with other HRQL instruments indicated good validity of the CRQ-SA. In conclusion, self-administration and standardisation of the chronic respiratory questionnaire maintains validity and responsiveness relative to the interviewer-administered chronic respiratory questionnaire. These results challenge the assumption that interviewer-administered questionnaires are superior to self-administered questionnaires in older patients with chronic respiratory disease.

Journal ArticleDOI
TL;DR: The use of fiber shows a consistent beneficial effect for relieving overall symptoms and bleeding in the treatment of symptomatic hemorrhoids, compatible with large treatment effects regarding prolapse, pain, itching, although the pooled analyses showed a tendency toward no-effect for these parametres.
Abstract: Background Symptomatic hemorrhoids are a common medical condition, which increase in prevalence in women during pregnancy and postpartum. Although the evidence appears to be inconclusive, narrative reviews and clinical practice guidelines recommend the use of laxatives (and fiber) for the treatment of hemorrhoids and relief of symptoms. This is due to their safety and low cost. Objectives To evaluate the impact of laxatives on a wide range of symptoms in people with symptomatic hemorrhoids. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to 2005), EMBASE (1980 to 2005), CINAHL (1982 to 2005), BIOSIS, and AMED (Allied and Alternative Medicine Database), for eligible trials (including conference proceedings). We sought missing and additional information from authors, industry, and experts in the field. Selection criteria We selected all published and unpublished randomised controlled trials that compared any type of laxative to placebo or no therapy in any patient population. Data collection and analysis Two authors independently screened studies for inclusion and retrieved all potentially relevant studies. Data were extracted from studies that met our selection criteria on study population, intervention used, pre-specified outcomes, and methodology. We extracted methodological information for the assessment of internal validity: existence and method of generation of the randomization schedule, and method of allocation concealment; blinding of caregivers and outcomes assessors; numbers of and reasons for participants lost to follow up; and use of validated outcome measures. Main results Seven randomised trials enrolling a total of 378 participants to fiber or a non-fiber control were identified. Meta-analyses using random-effects models showed that laxatives in the form of fiber had a beneficial effect in the treatment of symptomatic hemorrhoids. The risk of not improving hemorrhoids and having persisting symptoms decreased by 53% in the fiber group (risk reduction (RR) 0.47, 95% CI 0.32 to 0.68). These results are compatible with large treatment effects regarding prolapse, pain, itching, although the pooled analyses showed a tendency toward no-effect for these parametres. The effect on bleeding showed a significant difference in favour of the fiber (RR 0.50, 95% CI 0.28 to 0.89). Studies including data on multiple follow ups (usually after six weeks and three months) showed consistent results over time. However, we have to stress two possible limitations of this review: the risk of publication bias, and only moderate study quality. Authors' conclusions The use of fiber shows a consistent beneficial effect for relieving overall symptoms and bleeding in the treatment of symptomatic hemorrhoids.

Journal ArticleDOI
TL;DR: Venous thromboembolism appears to be an apparently infrequent, but likely underdiagnosed problem, occurring among patients receiving prophylaxis, suggesting the need for increased suspicion among clinicians, renewed efforts at thromboprophylactic, and evaluation of superior prevention strategies.

Journal ArticleDOI
TL;DR: Data suggest that in patients presenting with chest pain who have not yet experienced a serious cardiac event, IMA is a poor predictor of serious cardiac outcomes in the short term.
Abstract: Background: Ischemia-modified albumin (IMA) has been suggested as a marker of cardiac ischemia. Little, however, is known about its capacity to predict short-term serious cardiac outcomes (death, myocardial infarction, congestive heart failure, serious arrhythmia, or refractory ischemic cardiac pain) in patients arriving at the emergency department with symptoms that may indicate cardiac ischemia. Methods: We screened 546 patients over a 4-week period, of whom 189 fulfilled our entry criteria by presenting to an emergency department with potential cardiac-ischemia symptoms within 6 hours after chest pain, seeing an emergency physician who chose to order a troponin I test, and having no serious cardiac outcome before the troponin result became available. We followed the study patients for 72 hours to determine if any experienced a serious cardiac outcome. We calculated the likelihood ratios (LRs) of IMA findings predicting serious cardiac outcomes that could not be diagnosed at presentation with current techniques. Results: Of the 189 patients, 24 had a serious cardiac outcome within 72 hours after their arrival at the emergency department. The likelihood ratios for IMA measurement within 6 hours after chest pain predicting a serious cardiac outcome within the next 72 hours were 1.35 (95% confidence interval [CI] 0.315–5.79) for IMA ≤ 80 U/mL and 0.98 (95% CI 0.86– 1.11) for IMA > 80 U/mL. Conclusions: These data suggest that in patients presenting with chest pain who have not yet experienced a serious cardiac event, IMA is a poor predictor of serious cardiac outcomes in the short term.

Journal ArticleDOI
TL;DR: These findings suggest that children view OH and its impact on well-being as multidimensional concepts, and further research is needed to better understand the referents children use when responding to global ratings and the factors that determine their responses.
Abstract: – Objectives: To explore the constructs children incorporate in the responses to global ratings of their oral health (OH) and OH-related overall well-being (OWB) Methods: Data were collected as part of a project to validate the Child Perceptions Questionnaire for ages 11–14 (CPQ11−14), a self-report measure of OH-related quality of life Its 37 questions are organized in the symptoms, functional limitations, emotional and social well-being domains Children were recruited from paediatric dentistry, orthodontic and orofacial dental clinics To identify the CPQ11−14 domain scores and questions predicting the global ratings, correlation and multiple regression analyses were used Results: Of the 123 children, 228% rated their OH as ‘Fair/Poor’ and 301% reported that their OWB was affected by their oral/orofacial condition Positive significant correlations were observed between the OH ratings and the CPQ11−14 oral symptoms and emotional well-being domains, and between the OWB ratings and all four CPQ11−14 domains The number of the CPQ11−14 questions significantly correlated with the OH and OWB ratings were 8 and 19, respectively Only the symptoms domain entered the model for the OH (R2=005), while age, functional limitations and emotional well-being domains predicted the OWB (R2=018) The OH model included three questions (R2=013) and the OWB model included age and six questions (R2=025) In both models all but one of the questions came from the emotional and social well-being domains Conclusions: These findings suggest that children view OH and its impact on well-being as multidimensional concepts Further research, including qualitative studies, is needed to better understand the referents children use when responding to global ratings and the factors that determine their responses

Journal ArticleDOI
TL;DR: This pilot study suggests that a multicenter randomized clinical trial comparing LMWH with UFH in critically ill medical-surgical patients is feasible and can improve the design of larger trials and may enhance successful timely completion.

Journal ArticleDOI
TL;DR: To determine the prevalence and outcomes of clinical investigations of NHP-drug pharmacokinetic interactions, electronic databases were searched from inception through March 2004, as well as reference lists from published reports and experts in the field for unpublished studies.
Abstract: :Interactions between natural health products (NHP) and prescription medications are of increasing concern. This paper aims to identify all clinical trials of NHP-drug interactions. To determine the prevalence and outcomes of clinical investigations of NHP-drug pharmacokinetic interactions,

Journal ArticleDOI
TL;DR: The history and physical examination for DVT are not useful in detecting lower limb DVT in the ICU, and patients are allocated to low, moderate, and high risk strata for DVt.

Journal ArticleDOI
TL;DR: In the year after application, oxygen use was lower in the alternative arm with no between-group differences in mortality, quality of life, or resource use in the community.
Abstract: Rationale: Restricting oxygen administration to those who benefit is desirable. Objective: To determine the impact of alternative strategies for assessing eligibility for domiciliary oxygen on funded oxygen use, quality of life, and costs. Methods: We randomized applicants for domiciliary oxygen therapy to an assessment system that relied on data collected by oxygen providers at the time of application and judgments by Home Oxygen Program personnel (conventional assessment) or to a system of data collection by a respiratory therapist that included, in patients unstable at the time of initial assessment, a repeat assessment after 2 months of stability (alternative assessment). Measurements and Main Results: A total of 276 applicants were allocated to the conventional arm and 270 to the alternative assessment. In the year after application, oxygen use was lower in the alternative arm with no between-group differences in mortality, quality of life, or resource use in the community. Although alternative asses...

Journal ArticleDOI
TL;DR: For clinicians to use a diagnostic test in clinical practice, they need to know how well the test distinguishes between those who have the suspected disease or condition and those who do not.
Abstract: For clinicians to use a diagnostic test in clinical practice, they need to know how well the test distinguishes between those who have the suspected disease or condition and those who do not. If investigators choose clinically inappropriate populations for their study of a diagnostic test and