The purpose of the AGREE II is more explicitly stated. The new version of the instrument is designed to assess the quality of practice guidelines across the spectrum of health, provide direction on guideline development, and guide what specific information ought to be reported in guidelines. The four-point response scale was replaced by a seven-point response scale, in compliance with key methodologic principles of test construction. 5 A score of 1 indicates an absence of information or that the concept is very poorly reported. A score of 7 indicates that the quality of reporting is exceptional and all of the criteria and considerations articulated in the user's manual were met. A score between 2 and 6 indicates that the reporting of the AGREE II item does not fully meet criteria or considerations. As more criteria are met and more considerations addressed, item scores increase (see user's manual below). Finally, modifications, deletions and additions were made to approximately half of the original 23 items (Table 1). From McMaster University ([Melissa C. Brouwers PhD], [Michelle E. Kho], [Steven E. Hanna PhD], [Julie Makarski]); the Program in Evidence-based Care, Cancer Care Ontario (Brouwers), Hamilton, Ont.; British Columbia Cancer Agency (Browman), Victoria, BC; the Dutch Institute for Healthcare Improvement CBO and IQ Healthcare (Burgers), Radboud University Nijmegen Medical Centre, the Netherlands; St. George's University of London (Cluzeau), London, UK; the University of Bristol (Feder), Bristol, UK; Unité Cancer et Environement (Fervers), Université de Lyon - Centre Léon Bérard, Université Lyon 1, EA 4129, Lyon, France; the Canadian Institutes of Health Re search ([Ian D. Graham PhD]), Ottawa, Ont.; the Ottawa Hospital Research Institute ([Jeremy Grimshaw MBChB PhD]), Ottawa, Ont.; the National Institute for Health and Clinical Excellence (Littlejohns), London, UK; and the Can adian Partnership Against Cancer ([Louise Zitzelsberger PhD]), Ottawa, Ont. Members of the AGREE Next Steps Consortium: Dr. Melissa C. Brouwers, McMaster University and Cancer Care Ontario, Hamilton, Ont.; Dr. [George P. Browman MD MSc], British Columbia Cancer Agency, Vancouver Island, BC; Dr. [Jako S. Burgers MD PhD], Dutch Institute for Healthcare Improvement CBO, and Radboud University Nijmegen Medical Centre, IQ Healthcare, Netherlands; Dr. [Francoise Cluzeau], Chair of AGREE Research Trust, St. George's University of London, London, UK; Dr. Dave Davis, Association of American Medical Colleges, Washington, USA; Prof. Gene Feder, University of Bristol, Bristol, UK; Dr. Béatrice Fervers, Unité Cancer et Environement, Université de Lyon - Centre Léon Bérard, Université Lyon 1, EA 4129, Lyon, France; Dr. Ian D. Graham, Canadian Institutes of Health Research, Ottawa, Ont.; Dr. Jeremy Grimshaw, Ottawa Hospital Research Institute, Ottawa, Ont.; Dr. Steven E. Hanna, McMaster University, Hamilton, Ont.; Ms. Michelle E. Kho, McMaster University, Hamilton, Ont.; Prof. Peter Littlejohns, National Institute for Health and Clinical Excellence, London, UK; Ms. Julie Makarski, McMaster University, Hamilton, Ont.; Dr. Louise Zitzelsberger, Canadian Partnership Against Cancer, Ottawa, Ont.
Background: The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding. Methods: We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing. Results: We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia-Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity. Interpretation: These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.
Competing interests: All authors received consulting fees and travel support from Osteoporosis Canada during the preparation of this article. In addition, [Alexandra Papaioannou MD MSc] has been an advisory board member for Amgen, Eli Lilly, Merck Frosst, Novartis and Procter & Gamble; has served as a consult - ant to Amgen, Aventis Pharma, Eli Lilly, Lundbeck Canada Inc., Merck Frosst, Novartis, Procter & Gamble, Servier, Warner Chillcott and WyethosteoAyerst; has received unrestricted research grants from Amgen, Eli Lilly, Merck Frosst, Procter & Gamble and Sanofi-Aventis; has received clinical trial grants from Novartis and Pfizer; has received a research grant from the Ontario Ministry of Health and Long-Term Care; and has served as a member of the Continuing Medical Education Steering Committee of the Ontario College of Family Physicians. Suzanne Morin has been an advisory board member for Amgen, Eli Lilly, Novartis and Warner-Chilcott and has received speaker's honoraria from Amgen, Novartis and Merck. Angela M. Cheung has been an advisory board member for Amgen and Eli Lilly; has served as a consultant for Merck; and has received speaker's honoraria from Amgen, Eli Lilly, Merck, Novartis and Warner Chilcott. [Stephanie Atkinson PhD] has served as a consultant to Pfizer and Wyeth Nutritionals and has participated in a multisite clinical trial funded by Novartis. [Jacques P. Brown MD] has been an advisory board member for Amgen, Eli Lilly, Merck, Novartis and Warner Chilcott; has served as a consultant for Amgen, Eli Lilly, Merck, Novartis and Warner Chilcott; has received grants from Abbott, Amgen, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier and Warner Chilcott; and has received speaker's honoraria from Amgen, Eli Lilly, Merck, Novartis and Warner Chilcott. [David A. Hanley MD] has served as an advisory board member for Amgen Canada, Eli Lilly Canada, Novartis Canada, NPS Pharmaceuticals, Servier Canada and Warner Chilcott; has participated in clinical trials funded by Amgen, Eli Lilly, Novartis, NPS Pharmaceuticals, Pfizer, Servier and Wyeth Ayerst; and has received speaker's honor aria from Amgen Canada, Eli Lilly Canada, Novartis Canada, NPS Pharmaceuticals and Servier Canada. Anthony Hodsman has been an advis - ory board member for Amgen Canada, Novartis Canada, Procter & Gamble Canada, Shire Pharmaceuticals Canada and Warner-Chilcott Canada; has served as a consultant to Cytochroma Canada; and has received speaker's honoraria from McGill University and Novartis Canada. [Stephanie M. Kaiser MD] has served as an advisory board member for Amgen, AstaZeneca, Bristol Myers Squibb, Eli Lilly Canada, Merck Frosst/Schering, Novartis and Servier; has received speaker's honoraria from Amgen, AstraZeneca, Eli Lilly, Merck Frosst/Schering Plough, Novartis, Procter and Gamble (now Warner Chilcott/Aventis), and Servier Canada; has received payment for development of educational presentations from Eli Lilly Canada Inc.; and has received travel funds for activities unrelated to this paper from Amgen Canada. Brent Kvern has been an advisory board member for the Alliance for Better Bone Health (sponsored by SanofiAventis and Warner) and for Amgen Canada; has served as a consultant for Servier Canada; has received honoraria from the Alliance for Better Bone Health, Amgen Canada, Eli Lilly, Merck Frosst Canada and Servier Canada; and has received payment for development of educational presentations from the Alliance for Better Bone Health, Amgen Canada, Eli Lilly, Merck Frosst Canada and Servier Canada. [William D. Leslie MD MSc] has been an advisory board member for Amgen, Genzyme and Novartis; has received unrestricted research grants from Amgen, Genzyme, Merck Frosst, Procter & Gamble and Sanofi-Aventis; has received speaker's fees from Amgen and Merck Frosst; and has received travel funds for activities unrelated to this paper from Genzyme. No additional competing interests declared for Sidney Feldman, [Sophie A. Jamal MD PhD] and [Kerry Siminoski MD].
Background: The brief Patient Health Questionnaire (PHQ-9) is commonly used to screen for depression with 10 often recommended as the cut-off score. We summarized the psychometric properties of the PHQ-9 across a range of studies and cut-off scores to select the optimal cut-off for detecting depression. Methods: We searched Embase, MEDLINE and PsycINFO from 1999 to August 2010 for studies that reported the diagnostic accuracy of PHQ-9 to diagnose major depressive disorders. We calculated summary sensitivity, specificity, likelihood ratios and diagnostic odds ratios for detecting major depressive disorder at different cut-off scores and in different settings. We used random-effects bivariate meta-analysis at cutoff points between 7 and 15 to produce summary receiver operating characteristic curves. Results: We identified 18 validation studies (n = 7180) conducted in various clinical settings. Eleven studies provided details about the diagnostic properties of the questionnaire at more than one cut-off score (including 10), four studies reported a cut-off score of 10, and three studies reported cut-off scores other than 10. The pooled specificity results ranged from 0.73 (95% confidence interval [CI] 0.63-0.82) for a cut-off score of 7 to 0.96 (95% CI 0.94-0.97) for a cut-off score of 15. There was major variability in sensitivity for cut-off scores between 7 and 15. There were no substantial differences in the pooled sensitivity and specificity for a range of cut-off scores (8-11). Interpretation: The PHQ-9 was found to have acceptable diagnostic properties for detecting major depressive disorder for cut-off scores between 8 and 11. Authors of future validation studies should consistently report the outcomes for different cut-off scores.
The brief Patient Health Questionnaire (PHQ-9) is commonly used to screen for depression with 10 often recommended as the cut-off score. We summarized the psychometric properties of the PHQ-9 across a range of studies and cut-off scores to select the optimal cut-off for detecting depression. We searched Embase, MEDLINE and PsycINFO from 1999 to August 2010 for studies that reported the diagnostic accuracy of PHQ-9 to diagnose major depressive disorders. We calculated summary sensitivity, specificity, likelihood ratios and diagnostic odds ratios for detecting major depressive disorder at different cut-off scores and in different settings. We used random-effects bivariate meta-analysis at cutoff points between 7 and 15 to produce summary receiver operating characteristic curves. We identified 18 validation studies (n = 7180) conducted in various clinical settings. Eleven studies provided details about the diagnostic properties of the questionnaire at more than one cut-off score (including 10), four studies reported a cut-off score of 10, and three studies reported cut-off scores other than 10. The pooled specificity results ranged from 0.73 (95% confidence interval [CI] 0.63-0.82) for a cut-off score of 7 to 0.96 (95% CI 0.94-0.97) for a cut-off score of 15. There was major variability in sensitivity for cut-off scores between 7 and 15. There were no substantial differences in the pooled sensitivity and specificity for a range of cut-off scores (8-11). The PHQ-9 was found to have acceptable diagnostic properties for detecting major depressive disorder for cut-off scores between 8 and 11. Authors of future validation studies should consistently report the outcomes for different cut-off scores.
Background: Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). Methods: We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation - Survival Using Glucose Algorithm Regulation) study. Results: We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83-1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5-8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44-0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78-1.28; mixed ICU: RR 0.99, 95% CI 0.86-1.12). The different targets of intensive insulin therapy (glucose level <= 6.1 mmol/L v. = 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. Interpretation: Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.
Background: Clinical trials are commonly done without blinded outcome assessors despite the risk of bias. We wanted to evaluate the effect of nonblinded outcome assessment on estimated effects in randomized clinical trials with outcomes that involved subjective measurement scales. Methods: We conducted a systematic review of randomized clinical trials with both blinded and nonblinded assessment of the same measurement scale outcome. We searched PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press and Google Scholar for relevant studies. Two investigators agreed on the inclusion of trials and the outcome scale. For each trial, we calculated the difference in effect size (i.e., standardized mean difference between nonblinded and blinded assessments). A difference in effect size of less than 0 suggested that nonblinded assessors generated more optimistic estimates of effect. We pooled the differences in effect size using inverse variance random-effects meta-analysis and used metaregression to identify potential reasons for variation. Results: We included 24 trials in our review. The main meta-analysis included 16 trials (involving 2854 patients) with subjective outcomes. The estimated treatment effect was more beneficial when based on nonblinded assessors (pooled difference in effect size -0.23 [95% confidence interval (CI) -0.40 to -0.06]). In relative terms, nonblinded assessors exaggerated the pooled effect size by 68% (95% CI 14% to 230%). Heterogeneity was moderate (P = 46%, p = 0.02) and unexplained by metaregression. Interpretation: We provide empirical evidence for observer bias in randomized clinical trials with subjective measurement scale outcomes. A failure to blind assessors of outcomes in such trials results in a high risk of substantial bias.
Background: Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. Methods: We conducted a population-based nested case-control study among patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002, and Dec. 31, 2007, following hospital discharge after treatment of acute myocardial infarction. The cases in our study were those readmitted with acute myocardial infarction within 90 days after discharge. We performed a secondary analysis considering events within 1 year. Event-free controls (at a ratio of 3: 1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. We categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31-90 days) or remote (91 180 days). Results: Among 13 636 patients prescribed clopidogrel following acute myocardial infarction, we identified 734 cases readmitted with myocardial infarction and 2057 controls. After extensive multivariable adjustment, current use of proton pump inhibitors was associated with an increased risk of reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03-1.57). We found no association with more distant exposure to proton pump inhibitors or in multiple sensitivity analyses. In a stratified analysis, pantoprazole, which does not inhibit cytochrome P450 2C19, had no association with readmission for myocardial infarction (adjusted OR 1.02, 95% CI0.70-1.47). Interpretation: Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction.
Background: Readmissions to hospital are increasingly being used as an indicator of quality of care. However, this approach is valid only when we know what proportion of readmissions are avoidable. We conducted a systematic review of studies that measured the proportion of readmissions deemed avoidable. We examined how such readmissions were measured and estimated their prevalence. Methods: We searched the MEDLINE and EMBASE databases to identify all studies published from 1966 to July 2010 that reviewed hospital readmissions and that specified how many were classified as avoidable. Results: Our search strategy identified 34 studies. Three of the studies used combinations of administrative diagnostic codes to determine whether readmissions were avoidable. Criteria used in the remaining studies were subjective. Most of the studies were conducted at single teaching hospitals, did not consider information from the community or treating physicians, and used only one reviewer to decide whether readmissions were avoidable. The median proportion of readmissions deemed avoidable was 27.1% but varied from 5% to 79%. Three study-level factors (teaching status of hospital, whether all diagnoses or only some were considered, and length of follow-up) were significantly associated with the proportion of admissions deemed to be avoidable and explained some, but not all, of the heterogeneity between the studies. Interpretation: All but three of the studies used subjective criteria to determine whether readmissions were avoidable. Study methods had notable deficits and varied extensively, as did the proportion of readmissions deemed avoidable. The true proportion of hospital readmissions that are potentially avoidable remains unclear.
Background: Recognizing and appropriately treating mental health problems among new immigrants and refugees in primary care poses a challenge because of differences in language and culture and because of specific stressors associated with migration and resettlement. We aimed to identify risk factors and strategies in the approach to mental health assessment and to prevention and treatment of common mental health problems for immigrants in primary care. Methods: We searched and compiled literature on prevalence and risk factors for common mental health problems related to migration, the effect of cultural influences on health and illness, and clinical strategies to improve mental health care for immigrants and refugees. Publications were selected on the basis of relevance, use of recent data and quality in consultation with experts in immigrant and refugee mental health. Results: The migration trajectory can be divided into three components: premigration, migration and postmigration resettlement. Each phase is associated with specific risks and exposures. The prevalence of specific types of mental health problems is influenced by the nature of the migration experience, in terms of adversity experienced before, during and after resettlement. Specific challenges in migrant mental health include communication difficulties because of language and cultural differences; the effect of cultural shaping of symptoms and illness behaviour on diagnosis, coping and treatment; differences in family structure and process affecting adaptation, acculturation and intergenerational conflict; and aspects of acceptance by the receiving society that affect employment, social status and integration. These issues can be addressed through specific inquiry, the use of trained interpreters and culture brokers, meetings with families, and consultation with community organizations. Interpretation: Systematic inquiry into patients' migration trajectory and subsequent follow-up on culturally appropriate indicators of social, vocational and family functioning over time will allow clinicians to recognize problems in adaptation and undertake mental health promotion, disease prevention or treatment interventions in a timely way.
Chronic noncancer pain includes any painful condition that persists for at least three months and is not associated with malignant disease. According to seven national surveys conducted between 1994-2008, 15%-19% of Canadian adults live with chronic noncancer pain. Chronic noncancer pain interferes with activities of daily living, has a major negative impact on quality of life and physical function, and is the leading cause of health resource utilization and disability among working-age adults. Here, Busse et al inform the prescribing of opioids for adults with chronic noncancer pain.
Background: Guidelines exist for the surgical treatment of hip fracture, but the effect of early surgery on mortality and other outcomes that are important for patients remains unclear. We conducted a systematic review and meta-analysis to determine the effect of early surgery on the risk of death and common postoperative complications among elderly patients with hip fracture. Methods: We searched electronic databases (including MEDLINE and EMBASE), the archives of meetings of orthopedic associations and the bibliographies of relevant articles and questioned experts to identify prospective studies, published in any language, that evaluated the effects of early surgery in patients undergoing procedures for hip fracture. Two reviewers independently assessed methodologic quality and extracted relevant data. We pooled data by means of the DerSimonian and Laird random-effects model, which is based on the inverse variance method. Results: We identified 1939 citations, of which 16 observational studies met our inclusion criteria. These studies had a total of 13 478 patients for whom mortality data were complete (1764 total deaths). Based on the five studies that reported adjusted risk of death (4208 patients, 721 deaths), irrespective of the cut-off for delay (24, 48 or 72 hours), earlier surgery (i.e., within the cut-off time) was associated with a significant reduction in mortality (relative risk [RR] 0.81, 95% confidence interval [CI] 0.68-0.96, p = 0.01). Unadjusted data indicated that earlier surgery also reduced in-hospital pneumonia (RR 0.59, 95% CI 0.37-0.93, p = 0.02) and pressure sores (RR 0.48, 95% CI 0.34-0.69, p < 0.001). Interpretation: Earlier surgery was associated with a lower risk of death and lower rates of postoperative pneumonia and pressure sores among elderly patients with hip fracture. These results suggest that reducing delays may reduce mortality and complications.
Background: Frailty is a multidimensional syndrome characterized by loss of physiologic and cognitive reserves that confers vulnerability to adverse outcomes. We determined the prevalence, correlates and outcomes associated with frailty among adults admitted to intensive care. Methods: We prospectively enrolled 421 critically ill adults aged 50 or more at 6 hospitals across the province of Alberta. The primary exposure was frailty, defined by a score greater than 4 on the Clinical Frailty Scale. The primary outcome measure was in-hospital mortality. Secondary outcome measures included adverse events, 1-year mortality and quality of life. Results: The prevalence of frailty was 32.8% (95% confidence interval [CI] 28.3%-37.5%). Frail patients were older, were more likely to be female, and had more comorbidities and greater functional dependence than those who were not frail. In-hospital mortality was higher among frail patients than among non-frail patients (32% v. 16%; adjusted odds ratio [OR] 1.81, 95% CI 1.09-3.01) and remained higher at 1 year (48% v. 25%; adjusted hazard ratio 1.82, 95% CI 1.28-2.60). Major adverse events were more common among frail patients (39% v. 29%; OR 1.54, 95% CI 1.01-2.37). Compared with nonfrail survivors, frail survivors were more likely to become functionally dependent (71% v. 52%; OR 2.25, 95% CI 1.03-4.89), had significantly lower quality of life and were more often readmitted to hospital (56% v. 39%; OR 1.98, 95% CI 1.22-3.23) in the 12 months following enrolment. Interpretation: Frailty was common among critically ill adults aged 50 and older and identified a population at increased risk of adverse events, morbidity and mortality. Diagnosis of frailty could improve prognostication and identify a vulnerable population that might benefit from follow-up and intervention.
The primary purpose of this narrative review was to evaluate the current literature and to provide further insight into the role physical inactivity plays in the development of chronic disease and premature death. We confirm that there is irrefutable evidence of the effectiveness of regular physical activity in the primary and secondary prevention of several chronic diseases ( e. g., cardiovascular disease, diabetes, cancer, hypertension, obesity, depression and osteoporosis) and premature death. We also reveal that the current Health Canada physical activity guidelines are sufficient to elicit health benefits, especially in previously sedentary people. There appears to be a linear relation between physical activity and health status, such that a further increase in physical activity and fitness will lead to additional improvements in health status.
Background: Readmissions to hospital are common, costly and often preventable. An easy-to-use index to quantify the risk of readmission or death after discharge from hospital would help clinicians identify patients who might benefit from more intensive poste discharge care. We sought to derive and validate an index to predict the risk of death or unplanned readmission within 30 days after discharge from hospital to the community. Methods: In a prospective cohort study, 48 patient-level and admission-level variables were collected for 4812 medical and surgical patients who were discharged to the community from 11 hospitals in Ontario. We used a split-sample design to derive and validate an index to predict the risk of death or nonelective readmission within 30 days after discharge. This index was externally validated using administrative data in a random selection of 1 000 000 Ontarians discharged from hospital between 2004 and 2008 Results: Of the 4812 participating patients, 385 (8.0%) died or were readmitted on an unplanned basis within 30 days after discharge. Variables independently associated with this outcome (from which we derived the nmemonic "LACE") included length of stay ("L"); acuity of the admission ("A"); comorbidity of the patient (measured with the Charlson comorbidity index score) ("C"); and emergency department use (measured as the number of visits in the six months before admission) ("E"). Scores using the LACE index ranged from 0 (2.0% expected risk of death or urgent readmission within 30 days) to 19 (43.7% expected risk). The LACE index was discriminative (C statistic 0.681) and very accurate (Hosmer-Lemeshow goodness-of-fit statistic 14.1, p = 0.59) at predicting outcome risk. Interpretation: The LACE index can be used to quantify risk of death or unplanned readmission within 30 days after discharge from hospital. This index can be used with both primary and administrative data. Further research is required to determine whether such quantification changes patient care or outcomes.
Background: We aimed to prospectively validate a novel 1-hour algorithm using high-sensitivity cardiac troponin T measurement for early rule-out and rule-in of acute myocardial infarction (MI). Methods: In a multicentre study, we enrolled 1320 patients presenting to the emergency department with suspected acute MI. The high-sensitivity cardiac troponin T 1-hour algorithm, incorporating baseline values as well as absolute changes within the first hour, was validated against the final diagnosis. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data and serial measurements of high-sensitivity cardiac troponin T levels. Results: Acute MI was the final diagnosis in 17.3% of patients. With application of the high-sensitivity cardiac troponin T 1-hour algorithm, 786 (59.5%) patients were classified as "rule-out," 216 (16.4%) were classified as "rule-in" and 318 (24.1%) were classified to the "observational zone." The sensitivity and the negative predictive value for acute MI in the rule-out zone were 99.6% (95% confidence interval [CI] 97.6%-99.9%) and 99.9% (95% CI 99.3%-100%), respectively. The specificity and the positive predictive value for acute MI in the rule-in zone were 95.7% (95% CI 94.3%-96.8%) and 78.2% (95% CI 72.1%-83.6%), respectively. The 1-hour algorithm provided higher negative and positive predictive values than the standard interpretation of highsensitivity cardiac troponin T using a single cut-off level (both p < 0.05). Cumulative 30-day mortality was 0.0%, 1.6% and 1.9% in patients classified in the rule-out, observational and rule-in groups, respectively (p = 0.001). Interpretation: This rapid strategy incorporating high-sensitivity cardiac troponin T baseline values and absolute changes within the first hour substantially accelerated the management of suspected acute MI by allowing safe rule-out as well as accurate rule-in of acute MI in 3 out of 4 patients. Trial registration: [GRAPHICS] , NCT00470587
Background: Although several tools to evaluate the credibility of health care guidelines exist, guidance on practical steps for developing guidelines is lacking. We systematically compiled a comprehensive checklist of items linked to relevant resources and tools that guideline developers could consider, without the expectation that every guideline would address each item. Methods: We searched data sources, including manuals of international guideline developers, literature on guidelines for guidelines (with a focus on methodology reports from international and national agencies, and professional societies) and recent articles providing systematic guidance. We reviewed these sources in duplicate, extracted items for the checklist using a sensitive approach and developed overarching topics relevant to guidelines. In an iterative process, we reviewed items for duplication and omissions and involved experts in guideline development for revisions and suggestions for items to be added. Results: We developed a checklist with 18 topics and 146 items and a webpage to facilitate its use by guideline developers. The topics and included items cover all stages of the guideline enterprise, from the planning and formulation of guidelines, to their implementation and evaluation. The final checklist includes links to training materials as well as resources with suggested methodology for applying the items. Interpretation: The checklist will serve as a resource for guideline developers. Consideration of items on the checklist will support the development, implementation and evaluation of guidelines. We will use crowdsourcing to revise the checklist and keep it up to date.
Background: There have been postmarketing reports of adverse cardiovascular events associated with the use of varenicline, a widely used smoking cessation drug. We conducted a systematic review and meta-analysis of randomized controlled trials to ascertain the serious adverse cardiovascular effects of varenicline compared with placebo among tobacco users. Methods: We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, websites of regulatory authorities and registries of clinical trials, with no date or language restrictions, through September 2010 (updated March 2011) for published and unpublished studies. We selected double-blind randomized controlled trials of at least one week's duration involving smokers or people who used smokeless tobacco that reported on cardiovascular events (ischemia, arrhythmia, congestive heart failure, sudden death or cardiovascular-related death) as serious adverse events asociated with the use of varenicline. Results: We analyzed data from 14 double-blind randomized controlled trials involving 8216 participants. The trials ranged in duration from 7 to 52 weeks. Varenicline was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo (1.06% [52/4908] in varenicline group v. 0.82% [27/3308] in placebo group; Peto odds ratio [OR] 1.72, 95% confidence interval [CI] 1.09-2.71; I-2 = 0%). The results of various sensitivity analyses were consistent with those of the main analysis, and a funnel plot showed no publication bias. There were too few deaths to allow meaningful comparisons of mortality. Interpretation: Our meta-analysis raises safety concerns about the potential for an increased risk of serious adverse cardiovascular events associated with the use of varenicline among tobacco users.
Background: Although low-back pain is a highly prevalent condition, its clinical course remains uncertain. Our main objective was to systematically review the literature on the clinical course of pain and disability in patients with acute and persistent low-back pain. Our secondary objective was to investigate whether pain and disability have similar courses. Methods: We performed a meta-analysis of inception cohort studies. We identified eligible studies by searching MEDLINE, Embase and CINAHL. We included prospective studies that enrolled an episode-inception cohort of patients with acute or persistent low-back pain and that measured pain, disability or recovery. Two independent reviewers extracted data and assessed methodologic quality. We used mixed models to determine pooled estimates of pain and disability over time. Results: Data from 33 discrete cohorts (11 166 participants) were included in the review. The variance-weighted mean pain score (out of a maximum score of 100) was 52 (95% CI 48-57) at baseline, 23 (95% CI 21-25) at 6 weeks, 12 (95% CI 9-15) at 26 weeks and 6 (95% CI 3-10) at 52 weeks after the onset of pain for cohorts with acute pain. Among cohorts with persistent pain, the variance-weighted mean pain score (out of 100) was 51 (95% CI 44-59) at baseline, 33 (95% CI 29-38) at 6 weeks, 26 (95% CI 20-33) at 26 weeks and 23 (95% CI 16-30) at 52 weeks after the onset of pain. The course of disability outcomes was similar to the time course of pain outcomes in the acute pain cohorts, but the pain outcomes were slightly worse than disability outcomes in the persistent pain cohorts. Interpretation: Patients who presented with acute or persistent low-back pain improved markedly in the first six weeks. After that time improvement slowed. Low to moderate levels of pain and disability were still present at one year, especially in the cohorts with persistent pain.
Background: Observational studies and randomized controlled trials have yielded inconsistent findings about the association between the use of acid-suppressive drugs and the risk of pneumonia. We performed a systematic review and meta-analysis to summarize this association. Methods: We searched three electronic databases (MEDLIN E [PubMed], Embase and the Cochrane Library) from inception to Aug. 28, 2009. Two evaluators independently extracted data. Because of heterogeneity, we used random-effects meta-analysis to obtain pooled estimates of effect. Results: We identified 31 studies: five case-control studies, three cohort studies and 23 randomized controlled trials. A meta-analysis of the eight observational studies showed that the overall risk of pneumonia was higher among people using proton pump inhibitors (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.11-1.46, I-2 90.5%) and histamine 2 receptor antagonists (adjusted OR 1.22, 95% CI 1.09-1.36, I-2 0.0%). In the randomized controlled trials, use of histamine 2 receptor antagonists was associated with an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI 1.01-1.48, I-2 30.6%). Interpretation: Use of a proton pump inhibitor or histamine 2 receptor antagonist may be associated with an increased risk of both community- and hospital-acquired pneumonia. Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk.