Grey literature in systematic reviews: a cross-sectional study of the contribution of non-English reports, unpublished studies and dissertations to the results of meta-analyses in child-relevant reviews.

BACKGROUND: Systematic reviews (SRs) are an important source of information about healthcare interventions. A key component of a well-conducted SR is a comprehensive literature search. There is limited evidence on the contribution of non-English reports, unpublished studies, and dissertations and their impact on results of meta-analyses. METHODS: Our sample included SRs from three Cochrane Review Groups: Acute Respiratory Infections (ARI), Infectious Diseases (ID), Developmental Psychosocial and Learning Problems (DPLP) (n = 129). Outcomes included: 1) proportion of reviews that searched for and included each study type; 2) proportion of relevant studies represented by each study type; and 3) impact on results and conclusions of the primary meta-analysis for each study type. RESULTS: Most SRs searched for non-English studies; however, these were included in only 12% of reviews and represented less than 5% of included studies. There was a change in results in only four reviews (total sample = 129); in two cases the change did not have an impact on the statistical or clinical significance of results. Most SRs searched for unpublished studies but the majority did not include these (only 6%) and they represented 2% of included studies. In most cases the impact of including unpublished studies was small; a substantial impact was observed in one case that relied solely on unpublished data. Few reviews in ARI (9%) and ID (3%) searched for dissertations compared to 65% in DPLP. Overall, dissertations were included in only nine SRs and represented less than 2% of included studies. In the majority of cases the change in results was negligible or small; in the case where a large change was noted, the estimate was more conservative without dissertations. CONCLUSIONS: The majority of SRs searched for non-English and unpublished studies; however, these represented a small proportion of included studies and rarely impacted the results and conclusions of the review. Inclusion of these study types may have an impact in situations where there are few relevant studies, or where there are questionable vested interests in the published literature. We found substantial variation in whether SRs searched for dissertations; in most reviews that included dissertations, these had little impact on results.

The contribution of databases to the results of systematic reviews: a cross-sectional study.

BACKGROUND: One of the best sources for high quality information about healthcare interventions is a systematic review. A well-conducted systematic review includes a comprehensive literature search. There is limited empiric evidence to guide the extent of searching, in particular the number of electronic databases that should be searched. We conducted a cross-sectional quantitative analysis to examine the potential impact of selective database searching on results of meta-analyses. METHODS: Our sample included systematic reviews (SRs) with at least one meta-analysis from three Cochrane Review Groups: Acute Respiratory Infections (ARI), Infectious Diseases (ID), Developmental Psychosocial and Learning Problems (DPLP) (n = 129). Outcomes included: 1) proportion of relevant studies indexed in each of 10 databases; and 2) changes in results and statistical significance of primary meta-analysis for studies identified in Medline only and in Medline plus each of the other databases. RESULTS: Due to variation across topics, we present results by group (ARI n = 57, ID n = 38, DPLP n = 34). For ARI, identification of relevant studies was highest for Medline (85 %) and Embase (80 %). Restricting meta-analyses to trials that appeared in Medline + Embase yielded fewest changes in statistical significance: 53/55 meta-analyses showed no change. Point estimates changed in 12 cases; in 7 the change was less than 20 %. For ID, yield was highest for Medline (92 %), Embase (81 %), and BIOSIS (67 %). Restricting meta-analyses to trials that appeared in Medline + BIOSIS yielded fewest changes with 1 meta-analysis changing in statistical significance. Point estimates changed in 8 of 31 meta-analyses; change less than 20 % in all cases. For DPLP, identification of relevant studies was highest for Medline (75 %) and Embase (62 %). Restricting meta-analyses to trials that appeared in Medline + PsycINFO resulted in only one change in significance. Point estimates changed for 13 of 33 meta-analyses; less than 20 % in 9 cases. CONCLUSIONS: Majority of relevant studies can be found within a limited number of databases. Results of meta-analyses based on the majority of studies did not differ in most cases. There were very few cases of changes in statistical significance. Effect estimates changed in a minority of meta-analyses but in most the change was small. Results did not change in a systematic manner (i.e., regularly over- or underestimating treatment effects), suggesting that selective searching may not introduce bias in terms of effect estimates.

Behavioral Programs for Type 1 Diabetes Mellitus: A Systematic Review and Meta-analysis.

BACKGROUND: Whether behavioral approaches for self-management programs benefit individuals with type 1 diabetes mellitus is unclear. PURPOSE: To determine the effects of behavioral programs for patients with type 1 diabetes on behavioral, clinical, and health outcomes and to investigate factors that might moderate effect. DATA SOURCES: 6 electronic databases (1993 to June 2015), trial registries and conference proceedings (2011 to 2014), and reference lists. STUDY SELECTION: 36 prospective, controlled studies involving participants of any age group that compared behavioral programs with usual care, active controls, or other programs. DATA EXTRACTION: One reviewer extracted and another verified data. Two reviewers assessed quality and strength of evidence (SOE). DATA SYNTHESIS: Moderate SOE showed reduction in glycated hemoglobin (HbA1c) at 6 months after the intervention compared with usual care (mean difference, -0.29 [95% CI, -0.45 to -0.13] percentage points) and compared with active controls (-0.44 [CI, -0.69 to -0.19] percentage points). At the end of the intervention and 12-month follow-up or longer, there were no statistically significant differences in HbA1c (low SOE) for comparisons with usual care or active control. Compared with usual care, generic quality of life at program completion did not differ (moderate SOE). Other outcomes had low or insufficient SOE. Adults appeared to benefit more for glycemic control at program completion (-0.28 [CI, -0.57 to 0.01] percentage points) than did youth (-0.12 [CI, -0.43 to 0.19] percentage points). Program intensity appeared not to influence effectiveness; some individual delivery appears beneficial. LIMITATIONS: All studies had medium or high risk of bias. There was scarce evidence for many outcomes. CONCLUSION: Behavioral programs for type 1 diabetes offer some benefit for glycemic control, at least at short-term follow-up, but improvement for other outcomes has not been shown. (PROSPERO registration number: CRD42014010515). PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERD registration number: CRD42014010515).

Behavioral Programs for Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-analysis.

BACKGROUND: Behavioral programs may improve outcomes for individuals with type 2 diabetes mellitus, but there is a large diversity of behavioral interventions and uncertainty about how to optimize the effectiveness of these programs. PURPOSE: To identify factors moderating the effectiveness of behavioral programs for adults with type 2 diabetes. DATA SOURCES: 6 databases (1993 to January 2015), conference proceedings (2011 to 2014), and reference lists. STUDY SELECTION: Duplicate screening and selection of 132 randomized, controlled trials evaluating behavioral programs compared with usual care, active controls, or other behavioral programs. DATA EXTRACTION: One reviewer extracted and another verified data. Two reviewers independently assessed risk of bias. DATA SYNTHESIS: Behavioral programs were grouped on the basis of program content and delivery methods. A Bayesian network meta-analysis showed that most lifestyle and diabetes self-management education and support programs (usually offering ≥ 11 contact hours) led to clinically important improvements in glycemic control (≥ 0.4% reduction in hemoglobin A1c [HbA1c]), whereas most diabetes self-management education programs without added support-especially those offering 10 or fewer contact hours-provided little benefit. Programs with higher effect sizes were more often delivered in person than via technology. Lifestyle programs led to the greatest reductions in body mass index. Reductions in HbA1c seemed to be greater for participants with a baseline HbA1c level of 7.0% or greater, adults younger than 65 years, and minority persons (subgroups with ≥ 75% nonwhite participants). LIMITATIONS: All trials had medium or high risk of bias. Subgroup analyses were indirect, and therefore exploratory. Most outcomes were reported immediately after the interventions. CONCLUSION: Diabetes self-management education offering 10 or fewer hours of contact with delivery personnel provided little benefit. Behavioral programs seem to benefit persons with suboptimal or poor glycemic control more than those with good control. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO registration number: CRD42014010515).

Lifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: The effect of multifaceted lifestyle interventions on clinically oriented outcomes across a spectrum of metabolic risk factors and abnormal glucose is unclear. PURPOSE: To systematically review the effectiveness of lifestyle interventions on minimizing progression to diabetes in high-risk patients or progression to clinical outcomes (such as cardiovascular disease and death) in patients with type 2 diabetes. DATA SOURCES: 5 electronic databases (1980 to June 2013), reference lists, and gray literature. STUDY SELECTION: Two reviewers independently identified randomized, controlled trials of lifestyle interventions (≥3 months' duration) that included exercise, diet, and at least 1 other component; the comparator was standard care. DATA EXTRACTION: One reviewer extracted and a second verified data. Two reviewers independently assessed methodological quality. DATA SYNTHESIS: Nine randomized, controlled trials with patients who were at risk for diabetes and 11 with patients who had diabetes were included. Seven studies reported that lifestyle interventions decreased the risk for diabetes from the end of intervention up to 10 years after it. In patients with diabetes, 2 randomized, controlled trials (which included pharmacotherapy) reported no improvement in all-cause mortality (risk ratio, 0.75 [95% CI, 0.53 to 1.06]). Composite outcomes for cardiovascular disease were too heterogeneous to pool. One trial reported improvement in microvascular outcomes at 13-year follow-up. LIMITATION: Most trials focused on surrogate measures (such as weight change, blood pressure, and lipids) for which clinical relevance was unclear. CONCLUSION: Comprehensive lifestyle interventions effectively decrease the incidence of type 2 diabetes in high-risk patients. In patients who already have type 2 diabetes, there is no evidence of reduced all-cause mortality and insufficient evidence to suggest benefit on cardiovascular and microvascular outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Screening tests for gestational diabetes: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: A 50-g oral glucose challenge test (OGCT) is a widely accepted screening method for gestational diabetes mellitus (GDM), but other options are being considered. PURPOSE: To systematically review the test characteristics of various screening methods for GDM across a range of recommended diagnostic glucose thresholds. DATA SOURCES: 15 electronic databases from 1995 to May 2012, reference lists, Web sites of relevant organizations, and gray literature. STUDY SELECTION: Two reviewers independently identified English-language prospective studies that compared any screening test for GDM with any reference standard. DATA EXTRACTION: One reviewer extracted and a second reviewer verified data from 51 cohort studies. Two reviewers independently assessed methodological quality. DATA SYNTHESIS: The sensitivity, specificity, and positive and negative likelihood ratios for the OGCT at a threshold of 7.8 mmol/L (140 mg/dL) were 70% to 88%, 69% to 89%, 2.6 to 6.5, and 0.16 to 0.33, respectively. At a threshold of 7.2 mmol/L (130 mg/dL), the test characteristics were 88% to 99%, 66% to 77%, 2.7 to 4.2, and 0.02 to 0.14, respectively. For a fasting plasma glucose threshold of 4.7 mmol/L (85 mg/dL), they were 87%, 52%, 1.8, and 0.25, respectively. Glycated hemoglobin level had poorer test characteristics than fasting plasma glucose level or the OGCT. No studies compared the OGCT with International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. LIMITATIONS: The lack of a gold standard for confirming GDM limits comparisons. Few data exist for screening tests before 24 weeks' gestation. CONCLUSION: The OGCT and fasting plasma glucose level (at a threshold of 4.7 mmol/L [85 mg/dL]) by 24 weeks' gestation are good at identifying women who do not have GDM. The OGCT is better at identifying women who have GDM. The OGCT has not been validated for the IADPSG diagnostic criteria.

Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research.

BACKGROUND: Outcomes of treating gestational diabetes mellitus (GDM) are not well-established. PURPOSE: To summarize evidence about the maternal and neonatal benefits and harms of treating GDM. DATA SOURCES: 15 electronic databases from 1995 to May 2012, gray literature, Web sites of relevant organizations, trial registries, and reference lists. STUDY SELECTION: English-language randomized, controlled trials (n = 5) and cohort studies (n = 6) of women without known preexisting diabetes. DATA EXTRACTION: One reviewer extracted data, and a second reviewer verified them. Two reviewers independently assessed methodological quality and evaluated strength of evidence for primary outcomes by using a Grading of Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: All studies compared diet modification, glucose monitoring, and insulin as needed with no treatment. Women who were treated had more prenatal visits than those in control groups. Moderate evidence showed fewer cases of preeclampsia, shoulder dystocia, and macrosomia in the treated group. Evidence was insufficient for maternal weight gain and birth injury. Low evidence showed no difference between groups for neonatal hypoglycemia. Evidence was insufficient for long-term metabolic outcomes among offspring. No difference was found for cesarean delivery (low evidence), induction of labor (insufficient evidence), small-for-gestational-age neonates (moderate evidence), or admission to a neonatal intensive care unit (low evidence). LIMITATIONS: Evidence is low or insufficient for many outcomes of greatest clinical importance. The strongest evidence supports reductions in intermediate outcomes; however, other factors (for example, maternal weight and gestational weight gain) may impart greater risk than GDM, particularly when glucose levels are modestly elevated. CONCLUSION: Treating GDM results in less preeclampsia, shoulder dystocia, and macrosomia; however, current evidence does not show an effect on neonatal hypoglycemia or future poor metabolic outcomes. There is little evidence of short-term harm of treating GDM other than an increased demand for services.

Efficacy of supplemental peripheral nerve blockade for hip fracture surgery: multiple treatment comparison.

PURPOSE: This study was designed to determine the most effective peripheral nerve block supplement to standard anesthesia management for hip fracture patients. METHODS: We systematically reviewed randomized controlled trials (RCTs) published from 1990 to 2010 and conducted multiple treatment comparisons using direct and indirect evidence for two outcomes, i.e., acute pain intensity and delirium. We combined trials by type of injection (regardless of time of insertion during the perioperative phase, use of nerve block catheter, local anesthetic type, additives, or duration of treatment). RESULTS: Twenty-one RCTs comprising 1,422 participants were included. In most cases, the trials were conducted in Europe; they excluded patients with cognitive impairment, and they were unclear or at high risk of bias. The combination of obturator and lateral femoral cutaneous nerve blockade had the highest probability of being the most effective against acute postoperative pain. Fascia iliaca blockade had the highest probability of being the most effective against delirium. There was no difference in outcomes among other nerve blocks. CONCLUSION: Not all nerve blocks are equally effective in improving outcomes after hip fracture. Multiple treatment comparison, a tool to compare the effectiveness of multiple treatments simultaneously, provides useful guidance to anesthesia providers seeking effective treatment when faced with a body of RCTs wherein each investigates one treatment. More RCTs comparing multiple nerve blocks in hip fracture are needed.

Comparative effectiveness of pain management interventions for hip fracture: a systematic review.

BACKGROUND: Pain management is integral to the management of hip fracture. PURPOSE: To review the benefits and harms of pharmacologic and nonpharmacologic interventions for managing pain after hip fracture. DATA SOURCES: 25 electronic databases (January 1990 to December 2010), gray literature, trial registries, and reference lists, with no language restrictions. STUDY SELECTION: Multiple reviewers independently and in duplicate screened 9357 citations to identify randomized, controlled trials (RCTs); nonrandomized, controlled trials (non-RCTs); and cohort studies of pain management techniques in older adults after acute hip fracture. DATA EXTRACTION: Independent, duplicate data extraction and quality assessment were conducted, with discrepancies resolved by consensus or a third reviewer. Data extracted included study characteristics, inclusion and exclusion criteria, participant characteristics, interventions, and outcomes. DATA SYNTHESIS: 83 unique studies (64 RCTs, 5 non-RCTs, and 14 cohort studies) were included that addressed nerve blockade (n = 32), spinal anesthesia (n = 30), systemic analgesia (n = 3), traction (n = 11), multimodal pain management (n = 2), neurostimulation (n = 2), rehabilitation (n = 1), and complementary and alternative medicine (n = 2). Overall, moderate evidence suggests that nerve blockades are effective for relieving acute pain and reducing delirium. Low-level evidence suggests that preoperative traction does not reduce acute pain. Evidence was insufficient on the benefits and harms of most interventions, including spinal anesthesia, systemic analgesia, multimodal pain management, acupressure, relaxation therapy, transcutaneous electrical neurostimulation, and physical therapy regimens, in managing acute pain. LIMITATIONS: No studies evaluated outcomes of chronic pain or exclusively examined participants from nursing homes or with cognitive impairment. Systemic analgesics (narcotics, nonsteroidal anti-inflammatory drugs) were understudied during the search period. CONCLUSION: Nerve blockade seems to be effective in reducing acute pain after hip fracture. Sparse data preclude firm conclusions about the relative benefits or harms of many other pain management interventions for patients with hip fracture. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Positron emission tomography/computed tomographic scans compared to computed tomographic scans for detecting colorectal liver metastases: a systematic review.

OBJECTIVE: To review diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) for colorectal liver metastases. BACKGROUND: Colorectal liver metastases can be treated with surgical resection; however, recurrence is seen in 58% of patients. PET/CT may better detect extra-hepatic disease before surgery to more accurately identify eligible candidates for surgery and, through better selection, improve patient prognosis. METHODS: We conducted a comprehensive systematic review on adults with colorectal liver metastases who received PET/CT and CT scans to detect metastases. The gold standard to confirm the diagnosis was histology. Study selection, quality assessment, and data extraction were completed independently by 2 investigators. Pooling of results was not feasible because of heterogeneity. A qualitative summary of results is presented. RESULTS: From 1083 citations, we identified 6 studies (440 patients) for the review. For extra-hepatic lesions (3 studies; 178 patients), PET/CT was more sensitive than CT, but specificities were similar (PET/CT sensitivity [SN] = 75%-89% and specificity [SP] = 95%-96% vs. CT SN = 58%-64% and SP = 87%-97%). For hepatic lesions (5 studies; 316 patients), PET/CT had higher SN and SP than CT (PET/CT SN = 91%-100% and SP = 75%-100%; CT SN = 78%-94% and SP = 25%-98%). For local recurrence (3 studies; 206 patients), PET/CT also had better accuracy than CT with SN = 93% to 100% and SP = 97% to 98% versus SN = 0 %-100% and SP = 97%-98%. CONCLUSION: Based on this systematic review, we conclude that PET/CT has a higher accuracy for detection of extra-hepatic and hepatic colorectal metastatic disease than CT alone. However, the results are based on a small number of studies and should be interpreted cautiously.

Accuracy of eucapnic hyperpnea or mannitol to diagnose exercise-induced bronchoconstriction: a systematic review.

BACKGROUND: Exercise challenge testing is the typical method for diagnosing exercise induced bronchoconstriction; however, alternate tests have been developed. OBJECTIVE: The purpose of this paper was to summarize the current literature comparing eucapnic voluntary hyperpnea and mannitol with standard exercise challenge testing to determine whether either test is a suitable alternative to standard exercise testing for the diagnosis of exercise-induced bronchoconstriction. METHODS: Using valid systematic review methods, a comprehensive search strategy to avoid publication bias, we identified 10 studies that compared exercise challenge testing with either eucapnic voluntary hyperpnea or mannitol. RESULTS: For the 7 diagnostic cross-sectional studies that examined eucapnic voluntary hyperpnea, the sensitivity and specificity values were heterogeneous, ranging from 25 to 90% for sensitivity and 0 to 71% for specificity. In the 3 diagnostic cross-sectional studies that evaluated mannitol, the sensitivity and specificity ranged from 58 to 96% and 65 to 78%, respectively. For most studies, a representative spectrum of participants being tested was not used. CONCLUSION: Given the heterogeneity in sensitivity and specificity of eucapnic voluntary hyperpnea studies and the relatively small number of studies that have examined mannitol, insufficient evidence is available to conclude that either of these tests are suitable alternatives to exercise challenge testing to detect exercise-induced bronchoconstriction. Additional research is required.

Risk factors for methamphetamine use in youth: a systematic review.

BACKGROUND: Methamphetamine (MA) is a potent stimulant that is readily available. Its effects are similar to cocaine, but the drug has a profile associated with increased acute and chronic toxicities. The objective of this systematic review was to identify and synthesize literature on risk factors that are associated with MA use among youth.More than 40 electronic databases, websites, and key journals/meeting abstracts were searched. We included studies that compared children and adolescents (< or = 18 years) who used MA to those who did not. One reviewer extracted the data and a second checked for completeness and accuracy. For discrete risk factors, odds ratios (OR) were calculated and when appropriate, a pooled OR with 95% confidence intervals (95% CI) was calculated. For continuous risk factors, mean difference and 95% CI were calculated and when appropriate, a weighted mean difference (WMD) and 95% CI was calculated. Results were presented separately by comparison group: low-risk (no previous drug abuse) and high-risk children (reported previous drug abuse or were recruited from a juvenile detention center). RESULTS: Twelve studies were included. Among low-risk youth, factors associated with MA use were: history of heroin/opiate use (OR = 29.3; 95% CI: 9.8-87.8), family history of drug use (OR = 4.7; 95% CI: 2.8-7.9), risky sexual behavior (OR = 2.79; 95% CI: 2.25, 3.46) and some psychiatric disorders. History of alcohol use and smoking were also significantly associated with MA use. Among high-risk youth, factors associated with MA use were: family history of crime (OR = 2.0; 95% CI: 1.2-3.3), family history of drug use (OR = 4.7; 95% CI: 2.8-7.9), family history of alcohol abuse (OR = 3.2; 95% CI: 1.8-5.6), and psychiatric treatment (OR = 6.8; 95% CI: 3.6-12.9). Female sex was also significantly associated with MA use. CONCLUSION: Among low-risk youth, a history of engaging in a variety of risky behaviors was significantly associated with MA use. A history of a psychiatric disorder was a risk factor for MA for both low- and high-risk youth. Family environment was also associated with MA use. Many of the included studies were cross-sectional making it difficult to assess causation. Future research should utilize prospective study designs so that temporal relationships between risk factors and MA use can be established.

Systematic review: implantable cardioverter defibrillators for adults with left ventricular systolic dysfunction.

BACKGROUND: Patients with left ventricular (LV) systolic dysfunction have an increased risk for ventricular arrhythmias. PURPOSE: To summarize the evidence about benefits and harms of implantable cardioverter defibrillators (ICDs) in adult patients with LV systolic dysfunction. DATA SOURCES: A search of electronic databases (including MEDLINE, EMBASE, Cochrane Central, and U.S. Food and Drug Administration reports) from 1980 through April 2007, not limited by language of publication, was supplemented by hand searches and contact with study authors and device manufacturers. STUDY SELECTION: Two reviewers independently selected studies on the basis of prespecified criteria. They selected 12 randomized, controlled trials (RCTs) (8516 patients) that reported on mortality and 76 observational studies (96 951 patients) that examined safety or effectiveness. DATA EXTRACTION: Data were extracted in duplicate and independently by 2 reviewers. DATA SYNTHESIS: In adult patients with LV systolic dysfunction, 86% of whom had New York Heart Association class II or III symptoms, ICDs reduced all-cause mortality by 20% (95% CI, 10% to 29%) in the RCTs and by 46% (CI, 32% to 57%) in the observational studies. Death associated with implantation of ICDs occurred during 1.2% (CI, 0.9% to 1.5%) of procedures. The frequency of postimplantation complications per 100 patient-years included 1.4 (CI, 1.2 to 1.6) device malfunctions, 1.5 (CI, 1.3 to 1.8) lead problems, and 0.6 (CI, 0.5 to 0.8) site infection. Rates of inappropriate discharges per 100 patient-years ranged from 19.1 (CI, 16.5 to 22.0) in RCTs to 4.9 (CI, 4.5 to 5.3) in observational studies. LIMITATIONS: Studies were of short duration and infrequently reported nonfatal outcomes. Few studies evaluated dual-chamber ICDs. Lack of individual-patient data prevents identification of subgroup-specific effects. CONCLUSIONS: Implantable cardioverter defibrillators are efficacious in reducing mortality for adult patients with LV systolic dysfunction, and this benefit extends to nontrial populations. Improved risk stratification tools to identify patients who are most likely to benefit from ICD are needed.

Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review.

CONTEXT: Left ventricular (LV) systolic dysfunction causes substantial morbidity and mortality, even with optimal pharmacotherapy. Atrial-synchronized biventricular pacemakers (cardiac resynchronization therapy [CRT]) received US Food and Drug Administration (FDA) approval for use in selected patients with LV systolic dysfunction in 2001. OBJECTIVE: To summarize the current evidence base for the efficacy, effectiveness, and safety of CRT in patients with LV systolic dysfunction. EVIDENCE ACQUISITION: A search of multiple electronic databases until November 2006 was supplemented by hand searches of reference lists of included studies and review articles, proceedings booklets from meetings, FDA reports, and contact with primary study authors and device manufacturers. A total of 14 randomized trials (4420 patients) were included for the CRT efficacy review, 106 studies (9209 patients) for the CRT effectiveness review, and 89 studies (9677 patients) reported safety outcomes with implantation of a CRT device. EVIDENCE SYNTHESIS: All patients in the CRT studies had LV systolic dysfunction (mean LV ejection fraction [LVEF] range, 21%-30%), prolonged QRS duration (mean range, 155-209 milliseconds), and 91% had New York Heart Association (NYHA) class 3 or 4 heart failure symptoms despite optimal pharmacotherapy. CRT improved LVEF (weighted mean difference, 3.0%; 95% confidence interval [CI], 0.9%-5.1%), quality of life (weighted mean reduction in Minnesota Living With Heart Failure Questionnaire, 8.0 points; 95% CI, 5.6-10.4 points), and functional status (improvements of >/=1 NYHA class were observed in 59% of CRT recipients in the randomized trials). CRT decreased hospitalizations by 37% (95% CI, 7%-57%), and all-cause mortality decreased by 22% (95% CI, 9%-33%). Implant success rate was 93.0% (95% CI, 92.2%-93.7%) and 0.3% of patients died during implantation (95% CI, 0.1%-0.6%). During a median 11-month follow-up, 6.6% (95% CI, 5.6%-7.4%) of CRT devices exhibited lead problems and 5% (95% CI, 4%-7%) malfunctioned. CONCLUSIONS: CRT reduces morbidity and mortality in patients with LV systolic dysfunction, prolonged QRS duration, and NYHA class 3 or 4 symptoms when combined with optimal pharmacotherapy. The incremental benefits of combined CRT plus implantable cardioverter-defibrillator devices vs CRT-alone devices in patients with LV systolic dysfunction remain uncertain.

How Safe Are Common Analgesics for the Treatment of Acute Pain for Children? A Systematic Review.

Background. Fear of adverse events and occurrence of side effects are commonly cited by families and physicians as obstructive to appropriate use of pain medication in children. We examined evidence comparing the safety profiles of three groups of oral medications, acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids, to manage acute nonsurgical pain in children (<18 years) treated in ambulatory settings. Methods. A comprehensive search was performed to July 2015, including review of national data registries. Two reviewers screened articles for inclusion, assessed methodological quality, and extracted data. Risks (incidence rates) were pooled using a random effects model. Results. Forty-four studies were included; 23 reported on adverse events. Based on limited current evidence, acetaminophen, ibuprofen, and opioids have similar nausea and vomiting profiles. Opioids have the greatest risk of central nervous system adverse events. Dual therapy with a nonopioid/opioid combination resulted in a lower risk of adverse events than opioids alone. Conclusions. Ibuprofen and acetaminophen have similar reported adverse effects and notably less adverse events than opioids. Dual therapy with a nonopioid/opioid combination confers a protective effect for adverse events over opioids alone. This research highlights challenges in assessing medication safety, including lack of more detailed information in registry data, and inconsistent reporting in trials.

Advancing knowledge of rapid reviews: an analysis of results, conclusions and recommendations from published review articles examining rapid reviews.

BACKGROUND: Rapid review (RR) products are inherently appealing as they are intended to be less time-consuming and resource-intensive than traditional systematic reviews (SRs); however, there is concern about the rigor of methods and reliability of results. In 2013 to 2014, a workgroup comprising representatives from the Agency for Healthcare Research and Quality's Evidence-based Practice Center Program conducted a formal evaluation of RRs. This paper summarizes results, conclusions, and recommendations from published review articles examining RRs. METHODS: A systematic literature search was conducted and publications were screened independently by two reviewers. Twelve review articles about RRs were identified. One investigator extracted data about RR methods and how they compared with standard SRs. A narrative summary is presented. RESULTS: A cross-comparison of review articles revealed the following: 1) ambiguous definitions of RRs, 2) varying timeframes to complete RRs ranging from 1 to 12 months, 3) limited scope of RR questions, and 4) significant heterogeneity between RR methods. CONCLUSIONS: RR definitions, methods, and applications vary substantially. Published review articles suggest that RRs should not be viewed as a substitute for a standard SR, although they have unique value for decision-makers. Recommendations for RR producers include transparency of methods used and the development of reporting standards.

A taxonomy of rapid reviews links report types and methods to specific decision-making contexts.

OBJECTIVES: Describe characteristics of rapid reviews and examine the impact of methodological variations on their reliability and validity. STUDY DESIGN AND SETTING: We conducted a literature review and interviews with organizations that produce rapid reviews or related products to identify methods, guidance, empiric evidence, and current practices. RESULTS: We identified 36 rapid products from 20 organizations (production time, 5 minutes to 8 months). Methods differed from systematic reviews at all stages. As time frames increased, methods became more rigorous; however, restrictions on database searching, inclusion criteria, data extracted, and independent dual review remained. We categorized rapid products based on extent of synthesis. "Inventories" list what evidence is available. "Rapid responses" present best available evidence with no formal synthesis. "Rapid reviews" synthesize the quality of and findings from the evidence. "Automated approaches" generate meta-analyses in response to user-defined queries. Rapid products rely on a close relationship with end users and support specific decisions in an identified time frame. Limited empiric evidence exists comparing rapid and systematic reviews. CONCLUSIONS: Rapid products have tremendous methodological variation; categorization based on time frame or type of synthesis reveals patterns. The similarity across rapid products lies in the close relationship with the end user to meet time-sensitive decision-making needs.

Utilization of the emergency department after self-inflicted injury.

OBJECTIVES: To compare emergency department (ED) utilization by individuals who present with self-inflicted injuries with utilization by control populations. Individuals with self-inflicted injuries commonly present to the ED, yet little research has been conducted on this population in this setting. METHODS: Individuals who had an ED presentation in 1995-1996 for a self-inflicted injury were tracked prospectively for three to four years of follow-up. This group was matched by age and gender to two groups: individuals who presented with asthma and individuals who presented with other complaints. Data on return visits to the ED were collected from an administrative database. Groups were compared on rates of return visits. RESULTS: There were 478 individuals randomly selected for each group. Individuals in the self-inflicted injury group had higher rates of return visits to the ED over the follow-up period: 232.7 visits per 100 person-years for the self-inflicted injury group, compared with 117.6 for the asthma group, and 83.0 for the "other" group (p < 0.001). The self-inflicted injury group had higher rates for many types of diagnoses: self-inflicted injuries, mental disorders, substance abuse, unintentional injuries, assault, headache pain, and other complaints (all p < 0.001). Patients with more than three repeat visits per year were more common in the self-inflicted injury group (20.1%) than the asthma or "other" groups (9.2% and 5.6%, respectively). CONCLUSIONS: Individuals who harm themselves are chronic users of the ED. The ED represents an opportune setting from which individuals can be directed to appropriate treatment programs.

The epidemiology of traumatic spinal cord injury in Alberta, Canada.

OBJECTIVES: To describe the incidence and pattern of traumatic spinal cord injury and cauda equina injury (SCI) in a geographically defined region of Canada. METHODS: The study period was April 1, 1997 to March 31, 2000. Data were gathered from three provincial sources: administrative data from the Alberta Ministry of Health and Wellness, records from the Alberta Trauma Registry, and death certificates from the Office of the Medical Examiner. RESULTS: From all three data sources, 450 cases of SCI were identified. Of these, 71 (15.8%) died prior to hospitalization. The annual incidence rate was 52.5/million population (95% CI: 47.7, 57.4). For those who survived to hospital admission, the incidence rate was 44.3/million/year (95% CI: 39.8, 48.7). The incidence rates for males were consistently higher than for females for all age groups. Motor vehicle collisions accounted for 56.4% of injuries, followed by falls (19.1%). The highest incidence of motor vehicle-related SCI occurred to those between 15 and 29 years (60/million/year). Fall-related injuries primarily occurred to those older than 60 years (45/million/year). Rural residents were 2.5 times as likely to be injured as urban residents. CONCLUSION: Prevention strategies for SCI should target males of all ages, adolescents and young adults of both sexes, rural residents, motor vehicle collisions, and fall prevention for those older than 60 years.