Sydne Newberry

Probiotics for the Prevention and Treatment of Antibiotic-Associated Diarrhea: A Systematic Review and Meta-analysis

CONTEXT Probiotics are live microorganisms intended to confer a health benefit when consumed. One condition for which probiotics have been advocated is the diarrhea that is a common adverse effect of antibiotic use. OBJECTIVE To evaluate the evidence for probiotic use in the prevention and treatment of antibiotic-associated diarrhea (AAD). DATA SOURCES Twelve electronic databases were searched (DARE, Cochrane Library of Systematic Reviews, CENTRAL, PubMed, EMBASE, CINAHL, AMED, MANTIS, TOXLINE, ToxFILE, NTIS, and AGRICOLA) and references of included studies and reviews were screened from database inception to February 2012, without language restriction. STUDY SELECTION Two independent reviewers identified parallel randomized controlled trials (RCTs) of probiotics (Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus) for the prevention or treatment of AAD. DATA EXTRACTION Two independent reviewers extracted the data and assessed trial quality. RESULTS A total of 82 RCTs met inclusion criteria. The majority used Lactobacillus-based interventions alone or in combination with other genera; strains were poorly documented. The pooled relative risk in a DerSimonian-Laird random-effects meta-analysis of 63 RCTs, which included 11 811 participants, indicated a statistically significant association of probiotic administration with reduction in AAD (relative risk, 0.58; 95% CI, 0.50 to 0.68; P < .001; I(2), 54%; [risk difference, -0.07; 95% CI, -0.10 to -0.05], [number needed to treat, 13; 95% CI, 10.3 to 19.1]) in trials reporting on the number of patients with AAD. This result was relatively insensitive to numerous subgroup analyses. However, there exists significant heterogeneity in pooled results and the evidence is insufficient to determine whether this association varies systematically by population, antibiotic characteristic, or probiotic preparation. CONCLUSIONS The pooled evidence suggests that probiotics are associated with a reduction in AAD. More research is needed to determine which probiotics are associated with the greatest efficacy and for which patients receiving which specific antibiotics.

Pregnancy and fertility following bariatric surgery: a systematic review.

CONTEXT Use of bariatric surgery has increased dramatically during the past 10 years, particularly among women of reproductive age. OBJECTIVES To estimate bariatric surgery rates among women aged 18 to 45 years and to assess the published literature on pregnancy outcomes and fertility after surgery. EVIDENCE ACQUISITION Search of the Nationwide Inpatient Sample (1998-2005) and multiple electronic databases (Medline, EMBASE, Controlled Clinical Trials Register Database, and the Cochrane Database of Reviews of Effectiveness) to identify articles published between 1985 and February 2008 on bariatric surgery among women of reproductive age. Search terms included bariatric procedures, fertility, contraception, pregnancy, and nutritional deficiencies. Information was abstracted about study design, fertility, and nutritional, neonatal, and pregnancy outcomes after surgery. EVIDENCE SYNTHESIS Of 260 screened articles, 75 were included. Women aged 18 to 45 years accounted for 49% of all patients undergoing bariatric surgery (>50,000 cases annually for the 3 most recent years). Three matched cohort studies showed lower maternal complication rates after bariatric surgery than in obese women without bariatric surgery, or rates approaching those of nonobese controls. In 1 matched cohort study that compared maternal complication rates in women after laparoscopic adjustable gastric band surgery with obese women without surgery, rates of gestational diabetes (0% vs 22.1%, P < .05) and preeclampsia (0% vs 3.1%, P < .05) were lower in the bariatric surgery group. Findings were supported by 13 other bariatric cohort studies. Neonatal outcomes were similar or better after surgery compared with obese women without laparoscopic adjustable gastric band surgery (7.7% vs 7.1% for premature delivery; 7.7% vs 10.6% for low birth weight, P < .05; 7.7% vs 14.6% for macrosomia, P < .05). No differences in neonatal outcomes were found after gastric bypass compared with nonobese controls (26.3%-26.9% vs 22.4%-20.2% for premature delivery, P = not reported [1 study] and P = .43 [1 study]; 7.7% vs 9.0% for low birth weight, P = not reported [1 study]; and 0% vs 2.6%-4.3% for macrosomia, P = not reported [1 study] and P = .28 [1 study]). Findings were supported by 10 other studies. Studies regarding nutrition, fertility, cesarean delivery, and contraception were limited. CONCLUSION Rates of many adverse maternal and neonatal outcomes may be lower in women who become pregnant after having had bariatric surgery compared with rates in pregnant women who are obese; however, further data are needed from rigorously designed studies.

Diagnosing and Managing Common Food Allergies: A Systematic Review

CONTEXT There is heightened interest in food allergies but no clear consensus exists regarding the prevalence or most effective diagnostic and management approaches to food allergies. OBJECTIVE To perform a systematic review of the available evidence on the prevalence, diagnosis, management, and prevention of food allergies. DATA SOURCES Electronic searches of PubMed, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials. Searches were limited to English-language articles indexed between January 1988 and September 2009. STUDY SELECTION Diagnostic tests were included if they had a prospective, defined study population, used food challenge as a criterion standard, and reported sufficient data to calculate sensitivity and specificity. Systematic reviews and randomized controlled trials (RCTs) for management and prevention outcomes were also used. For foods where anaphylaxis is common, cohort studies with a sample size of more than 100 participants were included. DATA EXTRACTION Two investigators independently reviewed all titles and abstracts to identify potentially relevant articles and resolved discrepancies by repeated review and discussion. Quality of systematic reviews and meta-analyses was assessed using the AMSTAR criteria, the quality of diagnostic studies using the QUADAS criteria most relevant to food allergy, and the quality of RCTs using the Jadad criteria. DATA SYNTHESIS A total of 12,378 citations were identified and 72 citations were included. Food allergy affects more than 1% to 2% but less than 10% of the population. It is unclear if the prevalence of food allergies is increasing. Summary receiver operating characteristic curves comparing skin prick tests (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.81-0.93) and serum food-specific IgE (AUC, 0.84; 95% CI, 0.78-0.91) to food challenge showed no statistical superiority for either test. Elimination diets are the mainstay of therapy but have been rarely studied. Immunotherapy is promising but data are insufficient to recommend use. In high-risk infants, hydrolyzed formulas may prevent cows milk allergy but standardized definitions of high risk and hydrolyzed formula do not exist. CONCLUSION The evidence for the prevalence and management of food allergy is greatly limited by a lack of uniformity for criteria for making a diagnosis.

Diagnosis, Microbial Epidemiology, and Antibiotic Treatment of Acute Otitis Media in Children: A Systematic Review

CONTEXT Acute otitis media (AOM) is the most common condition for which antibiotics are prescribed for US children; however, wide variation exists in diagnosis and treatment. OBJECTIVES To perform a systematic review on AOM diagnosis, treatment, and the association of heptavalent pneumococcal conjugate vaccine (PCV7) use with AOM microbiology. DATA SOURCES PubMed, Cochrane Databases, and Web of Science, searched to identify articles published from January 1999 through July 2010. STUDY SELECTION Diagnostic studies with a criterion standard, observational studies and randomized controlled trials comparing AOM microbiology with and without PCV7, and randomized controlled trials assessing antibiotic treatment. DATA EXTRACTION Independent article review and study quality assessment by 2 investigators with consensus resolution of discrepancies. RESULTS Of 8945 citations screened, 135 were included. Meta-analysis was performed for comparisons with 3 or more trials. Few studies examined diagnosis; otoscopic findings of tympanic membrane bulging (positive likelihood ratio, 51 [95% confidence interval {CI}, 36-73]) and redness (positive likelihood ratio, 8.4 [95% CI, 7-11]) were associated with accurate diagnosis. In the few available studies, prevalence of Streptococcus pneumoniae decreased (eg, 33%-48% vs 23%-31% of AOM isolates), while that of Haemophilus influenzae increased (41%-43% vs 56%-57%) pre- vs post-PCV7. Short-term clinical success was higher for immediate use of ampicillin or amoxicillin vs placebo (73% vs 60%; pooled rate difference, 12% [95% CI, 5%-18%]; number needed to treat, 9 [95% CI, 6-20]), while increasing the rate of rash or diarrhea by 3% to 5%. Two of 4 studies showed greater clinical success for immediate vs delayed antibiotics (95% vs 80%; rate difference, 15% [95% CI, 6%-24%] and 86% vs 70%; rate difference, 16% [95% CI, 6%-26%]). Data are absent on long-term effects on antimicrobial resistance. Meta-analyses in general showed no significant differences in antibiotic comparative effectiveness. CONCLUSIONS Otoscopic findings are critical to accurate AOM diagnosis. AOM microbiology has changed with use of PCV7. Antibiotics are modestly more effective than no treatment but cause adverse effects in 4% to 10% of children. Most antibiotics have comparable clinical success.

Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease

AbstractOBJECTIVE: To evaluate and synthesize the evidence on the effect of supplements of vitamin E on the prevention and treatment of cardiovascular disease. DESIGN: Systematic review of placebo-controlled randomized controlled trials; meta-analysis where justified. MEASUREMENTS AND MAIN RESULTS: Eighty-four eligible trials were identified. For the outcomes of all-cause mortality, cardiovascular mortality, fatal or nonfatal myocardial infarction, and blood lipids, neither supplements of vitamin E alone nor vitamin E given with other agents yielded a statistically significant beneficial or adverse pooled relative risk (for example, pooled relative risk of vitamin E alone=0.96 [95% confidence interval (CI), 0.84 to 1.10]; 0.97 [95% CI, 0.80 to 1.90]; and 0.72 [95% CI, 0.51 to 1.02] for all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction, respectively. CONCLUSIONS: There is good evidence that vitamin E supplementation does not beneficially or adversely affect cardiovascular outcomes.

Systematic review of the effects of n−3 fatty acids in inflammatory bowel disease

BACKGROUND n-3 Fatty acids are purported to have health effects in patients with inflammatory bowel disease (IBD), but studies have reported mixed results. OBJECTIVE We aimed to synthesize published and unpublished evidence to determine estimates of the effect of n-3 fatty acids on clinical outcomes in IBD and whether n-3 fatty acids modify the effects of or need for treatment with other agents. DESIGN Computerized databases were searched for studies of n-3 fatty acids in immune-mediated diseases from 1966 to 2003. We also contacted experts in the nutraceutical industry to identify unpublished studies; however, none were identified. RESULTS Reviewers identified 13 controlled trials that assessed the effects of n-3 fatty acids on clinical, sigmoidoscopic, or histologic scores; rates of induced remission or relapse; or requirements for steroids and other immunosuppressive agents in Crohn disease or ulcerative colitis. Most clinical trials were of good quality. Fewer than 6 were identified that assessed the effects of n-3 fatty acids on any single outcome of clinical, endoscopic, or histologic scores or remission or relapse rates. Consistent across 3 studies was the finding that n-3 fatty acids reduce corticosteroid requirements, although statistical significance was shown in only 1 of these studies. CONCLUSION The available data are insufficient to draw conclusions about the effects of n-3 fatty acids on clinical, endoscopic, or histologic scores or remission or relapse rates.

Safety of Vaccines Used for Routine Immunization of US Children: A Systematic Review

BACKGROUND: Concerns about vaccine safety have led some parents to decline recommended vaccination of their children, leading to the resurgence of diseases. Reassurance of vaccine safety remains critical for population health. This study systematically reviewed the literature on the safety of routine vaccines recommended for children in the United States. METHODS: Data sources included PubMed, Advisory Committee on Immunization Practices statements, package inserts, existing reviews, manufacturer information packets, and the 2011 Institute of Medicine consensus report on vaccine safety. We augmented the Institute of Medicine report with more recent studies and increased the scope to include more vaccines. Only studies that used active surveillance and had a control mechanism were included. Formulations not used in the United States were excluded. Adverse events and patient and vaccine characteristics were abstracted. Adverse event collection and reporting was evaluated by using the McHarm scale. We were unable to pool results. Strength of evidence was rated as high, moderate, low, or insufficient. RESULTS: Of 20 478 titles identified, 67 were included. Strength of evidence was high for measles/mumps/rubella (MMR) vaccine and febrile seizures; the varicella vaccine was associated with complications in immunodeficient individuals. There is strong evidence that MMR vaccine is not associated with autism. There is moderate evidence that rotavirus vaccines are associated with intussusception. Limitations of the study include that the majority of studies did not investigate or identify risk factors for AEs; and the severity of AEs was inconsistently reported. CONCLUSIONS: We found evidence that some vaccines are associated with serious AEs; however, these events are extremely rare and must be weighed against the protective benefits that vaccines provide.

Comparative Effectiveness of Pharmacologic Treatments to Prevent Fractures: An Updated Systematic Review

Osteoporosis is a skeletal disorder characterized by compromised bone strength, increasing the risk for fracture (1). Risk factors include, but are not limited to, increasing age, female sex, postmenopause for women, low body weight, parental history of a hip fracture, cigarette smoking, race, hypogonadism, certain medical conditions (particularly rheumatoid arthritis), and certain medications for chronic diseases (such as glucocorticoids). During ones expected remaining life, 1 in 2 postmenopausal women and 1 in 5 older men are at risk for an osteoporosis-related fracture (2). The increasing prevalence and cost of osteoporosis have heightened interest in the effectiveness and safety of the many interventions currently available to prevent osteoporotic fracture. In 2007, we conducted a systematic review of the comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis (3, 4). Since that time, new drugs have been approved for treatment, and new studies have been published about existing drugs. Additional issues about pharmacologic treatments for osteoporosis that have become particularly salient include the optimal duration of therapy; the safety of long-term therapy; and the role of bone mineral density (BMD) measurement, both for screening and for monitoring treatment. Therefore, we updated our original systematic review. Methods This article is a condensed and further updated version of an evidence review conducted for the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Centers program (5). This article focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density. In addition, we address issues regarding monitoring and duration of therapy. For this updated review, we followed the same methods as our 2007 review, with a few exceptions. A protocol for this review was developed and posted on the Effective Health Care Program Web site (6). Data Sources and Searches We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the ACP Journal Club database, the National Institute for Clinical Excellence, the Food and Drug Administrations (FDA) MedWatch database, and relevant pharmacologic databases from 2 January 2005 to 3 June 2011. The search strategy followed that of the original report, with the addition of terms for new FDA-approved drugs (such as denosumab) and newly reported adverse events. The full search strategies are in our evidence report (5). We later updated this search to 21 January 2013 and used a machine learning method that a previous study showed had high sensitivity for detecting relevant evidence for updating a search of the literature on osteoporosis treatments (7) and then updated the searches to 4 March 2014 using the full search strategy. Study Selection Eligible studies were systematic reviews and randomized, controlled trials (RCTs) that studied FDA-approved pharmacotherapy (excluding calcitonin and etidronate) for women or men with osteoporosis that was not due to a secondary cause (such as glucocorticoid therapy and androgen-deprivation therapy) and also measured fractures as an outcome at a minimum follow-up of 6 months. In addition, we included observational studies with more than 1000 participants for adverse events and case reports for rare events. As in our original review, only English-language studies were included. Data Extraction and Quality Assessment Reviews were done in duplicate by pairs of reviewers. Study characteristics were extracted in duplicate, and outcomes data (both benefits and harms) were extracted by the study statistician. Study quality was assessed as it was in the 2007 report using the Jadad scale for clinical trials (with several questions added to assess allocation concealment and other factors) and the NewcastleOttawa Scale for observational studies (8, 9). Systematic reviews were assessed using a modified version of the 11 AMSTAR (A Measurement Tool to Assess Systematic Reviews) criteria (the modifications included eliminating the requirements to list all of the excluded studies and assess the conflicts of interest for all of the included studies) (10). The assessments of efficacy and effectiveness used reduction in fracture (all, vertebral, nonvertebral, spine, hip, wrist, or other) as the outcome (studies reporting changes in BMD but not fracture were excluded). Data Synthesis and Analysis Evidence on efficacy and effectiveness was synthesized narratively. For adverse events, we pooled data as in the 2007 report: We compared agent versus placebo and agent versus agent for agents within the same class and across classes. For groups of events that occurred in 3 or more trials, we estimated the pooled odds ratio (OR) and its associated 95% CI. Because many events were rare, we used exact conditional inference to perform the pooling rather than applying the usual asymptotic methods that assume normality. StatXact PROCs software was used for the analysis (11, 12). Large cohort and casecontrol studies were included to assess adverse events. Strength of evidence was assessed using the criteria of the Agency for Healthcare Research and Quality Evidence-based Practice Centers program, which are similar to those proposed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group (13). Role of the Funding Source The update that included studies identified in the 3 June 2011 search was funded by AHRQ. Subsequent updating received no external funding. Although AHRQ formulated the initial study questions for the original report, it did not participate in the literature search, determination of study eligibility criteria, data analysis, or interpretation of the data. Staff from AHRQ reviewed and provided comments on the report. Results The first search yielded 26366 titles, 2440 of which were considered potentially relevant (Figure). Of these, 661 full-text articles were reviewed, resulting in 255 articles that were included in the update report. Of these, 174 articles were relevant to this article. The second update search plus hand searching initially yielded 16589 titles, and machine learning and full-text review identified 107 as relevant. The third update yielded 12131 titles. After title, abstract, and full-text screening, 34 were relevant. Thus, 55086 titles were screened and 315 articles met eligibility criteria for inclusion. Not every eligible study is cited in this article. A complete list of studies that met eligibility criteria is available at www.rand.org/health/centers/epc. Figure. Summary of evidence search and selection. FRAX = Fracture Risk Assessment Tool; HRT = hormone replacement therapy; LBD = low bone density. *Original LBD report (4). Fracture Prevention Our previous review (3) identified 76 randomized trials and 24 meta-analyses and concluded that there was good-quality evidence that alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen, parathyroid hormone, and raloxifene prevented osteoporotic fractures, although not all of these agents prevented hip fractures. The principal new efficacy findings since that time are additional data about zoledronic acid and data about a new agent, denosumab (Tables 1 and 2). The data for zoledronic acid came from 6 placebo-controlled studies of various doses in postmenopausal women (1419), the 2 largest of which enrolled 7230 women (15) and 2127 women (14). Both studies showed statistically significant reductions in nearly all types of fractures assessed, with relative risk reductions ranging from 0.23 to 0.73 at time points from 24 to 36 months after initiation of treatment. The data for denosumab came from 2 placebo-controlled trials in postmenopausal women, one small (332 enrolled women) (20) and one much larger that followed 7521 women for 36 months (21). This latter study found statistically significant reductions in each anatomical fracture type measured (hip, nonvertebral, vertebral, and new clinical vertebral), with hazard ratios of 0.31 to 0.80. Many secondary analyses and open-label extension results of this trial report the effectiveness of denosumab in various subpopulations and other circumstances (2228). Table 1. Principal Conclusions About Drug Efficacy/Effectiveness and Adverse Events Table 2. Principal Conclusions About Monitoring and Treatment Duration Despite some difficulties in comparing results across trials because of differences in the outcomes reported, high-strength evidence shows that bisphosphonates (alendronate, ibandronate, risedronate, and zoledronic acid), denosumab, and teriparatide (the 1,34 amino acid fragment of the parathyroid hormone) reduce fractures compared with placebo in postmenopausal women with osteoporosis, with relative risks for fractures generally in the range of 0.40 to 0.60 for vertebral fractures and 0.60 to 0.80 for nonvertebral fractures. This range translates into a number needed to treat of 60 to 89 to prevent 1 vertebral fracture and 50 to 67 to prevent 1 hip fracture over 1 to 3 years of treatment, using a pooled average of the incidence of these fractures in the placebo groups from included studies. The effect of ibandronate on hip fracture risk reduction is unclear because hip fracture was not a separately reported outcome in placebo-controlled trials of this agent. The selective estrogen receptor modulator raloxifene has been shown in placebo-controlled trials to reduce only vertebral fractures; reduction in the risk for hip or nonvertebral fractures was not statistically significant. There is only one randomized, controlled trial of men with osteoporosis that was designed with a primary fracture reduction outcome. Nearly 1200 men with osteoporosis were randomly assigned to placebo or zoledronic acid intravenously once per year for 2 years. At follow-up, 1.6% of treated men had new radio

The Efficacy of Omega–3 Fatty Acids on Cognitive Function in Aging and Dementia: A Systematic Review

We systematically reviewed the published literature on the effects of omega–3 fatty acids on measures of cognitive function in normal aging, incidence and treatment of dementia. Computerized databases were searched for published literature to identify potentially relevant studies with the intent to conduct a meta-analysis. We screened 5,865 titles, reviewed 497 studies of which 49 underwent a detailed review, and found 5 studies that pertained to our objectives. We included controlled clinical trials and observational studies, including prospective cohort, case-control, and case series designs; we excluded case reports. We had no language restrictions. We abstracted data on the effects of omega–3 fatty acids and on study design, relevant outcomes, study population, source, type, amount, and duration of omega–3 fatty acid consumption, and parameters of methodological quality. A single cohort study has assessed the effects of omega–3 fatty acids on cognitive function with normal aging and found no association for fish or total omega–3 consumption. In four studies that assessed the effects of omega–3 fatty acids on incidence and treatment of dementia, a trend in favor of omega–3 fatty acids (fish and total omega–3 consumption) toward reducing risk of dementia and improving cognitive function was reported. The available data are insufficient to draw strong conclusions about the effects of omega–3 fatty acids on cognitive function in normal aging or on the incidence or treatment of dementia. However, limited evidence suggests a possible association between omega–3 fatty acids and reduced risk of dementia.

Hospital fall prevention: a systematic review of implementation, components, adherence, and effectiveness

To systematically document the implementation, components, comparators, adherence, and effectiveness of published fall prevention approaches in U.S. acute care hospitals.