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Completed Systematic Reviews




Interventions to Reduce Antibiotic Prescribing for Uncomplicated Acute Respiratory Tract Infections [Entered Retrospectively]


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Statistics: 133 Studies, 6 Key Questions, 1 Extraction Form,
Date Published: Jul 23, 2015 02:34PM
Description: Objectives. To assess the comparative effectiveness of interventions for reducing antibiotic use for acute respiratory tract infections (RTIs) in adults and children. Data Sources. Electronic databases (MEDLINE® from 1990 and the Cochrane Library databases from 2005 to February 2015), reference lists of included systematic reviews, and scientific information packets from of point-of-care test manufacturers and experts. Review Methods. Using predefined criteria, we selected studies of any intervention designed to reduce antibiotic prescribing for acute RTIs. Interventions were organized into educational, communication, clinical, system level, and multifaceted categories. The key outcome was change in prescribing; secondary outcomes were undesirable consequences such as medical complications and satisfaction. The quality of included studies was rated and the strength of the evidence was assessed. Clinical and methodological heterogeneity limited quantitative analysis. Our synthesis focused on interventions that had evidence of net benefit: at least moderate strength of evidence for decreasing overall prescribing of antibiotics for acute RTI and at least low strength evidence for other outcomes. Results. Based on 132 studies, including 88 randomized controlled trials, several interventions had net benefit. Compared with usual care, reductions in overall prescribing were 21 percent for clinic-based educational programs for parents, 7 percent for public education campaigns combined with clinician education, 9 to 26 percent for communication training, 5 to 9 percent for electronic decision support, 2 to 34 percent for C-reactive protein (CRP), 12 to 72 percent for procalcitonin in adults, and >25 percent for clinician communication training plus CRP testing. Delayed prescribing reduced use by 34 to 76 percent compared with immediate prescribing. Additionally, public education campaigns combined with clinician education and electronic decision support possibly improved appropriate prescribing. Interventions varied in their effects on other outcomes. Few studies assessed impact on the most serious undesirable outcomes, but in those that did, there were no increases in medical complications for public education campaigns combined with clinician education or electronic decision support and, for hospitalizations, no increases for CRP or procalcitonin and only a slight increase for communication+CRP. Negative impacts on less serious outcomes were few and small: more return visits with CRP testing, slightly longer symptom duration with communication training plus CRP testing, and decreased patient satisfaction and slightly longer symptom duration with delayed prescribing. Direct comparisons of interventions were few; only clinician communication training plus CRP testing showed net benefit over CRP testing alone. Interventions with no or negative impact on antibiotic prescribing were procalcitonin in children, clinic-based education for parents of children ≤24 months with acute otitis media, and point-of-care testing for influenza in children. Conclusions. Interventions from all categories had evidence of net benefit and no serious adverse consequences. Magnitude of benefit varied widely and current evidence is inadequate to determine key modifying factors. Future studies need to better evaluate potential effect modifiers, and directly compare the effective interventions individually and combined, on net benefit, sustainability, and resource use.
Contributor(s): Marian McDonagh, Pharm.D., Kim Peterson, M.S., Kevin Winthrop, M.D., M.P.H., Amy Cantor, M.D., Brittany Holzhammer, M.P.H., David Buckley, M.D., M.P.H.
Funding Source: This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA290201200014I).
Methodology Description: Using predefined criteria, we selected studies of any intervention designed to reduce antibiotic prescribing for acute RTIs. Interventions were organized into educational, communication, clinical, system level, and multifaceted categories. The key outcome was change in prescribing; secondary outcomes were undesirable consequences such as medical complications and satisfaction. The quality of included studies was rated and the strength of the evidence was assessed. Clinical and methodological heterogeneity limited quantitative analysis. Our synthesis focused on interventions that had evidence of net benefit: at least moderate strength of evidence for decreasing overall prescribing of antibiotics for acute RTI and at least low strength evidence for other outcomes.

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Imaging Tests for the Diagnosis and Staging of Pancreatic Adenocarcinoma


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Statistics: 121 Studies, 6 Key Questions, 5 Extraction Forms,
Date Published: Jul 23, 2015 02:33PM
Description: Systematic review of imaging tests for diagnosis, staging, and/or screening of pancreatic adenocarcinoma
Contributor(s): Jonathan Treadwell, Ph.D., Matthew Mitchell, Ph.D., Kelley Eatmon, M.P.H., Jane Jue, M.D., M.Sc., Hanna Zafar, M.D., M.H.S., Ursina Teitelbaum, M.D., Karen Schoelles, M.D., S.M., F.A.C.P.
Funding Source: AHRQ
Methodology Description: EPC report

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Fructose Consumption and Non-alcoholic Fatty Liver Disease (NAFLD)


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Statistics: 23 Studies, 5 Key Questions, 4 Extraction Forms,
Date Published: Jul 23, 2015 02:30PM
Description: Background: There are growing concerns about the effects of dietary fructose on health outcomes because the intakes appear to have parallel trends in non-alcoholic fatty liver disease (NAFLD) and obesity prevalence in the United States. Purpose: To examine the effect of different levels and sources of dietary fructose on the incidence or prevalence of NAFLD and on indices of liver health in humans. Data Sources: English-language studies identified from MEDLINE, Cochrane Central Register of Controlled Trials, CAB Abstracts, and Global Health databases up to September 2012. Study Selection: Human studies of any design in children and adults with low to no alcohol intake and reporting at least one predetermined measure of liver health. Data Extraction: Study data was extracted by one investigator and corroborated by a second investigator. Differences were resolved by consensus. Data Synthesis: Twenty-two studies met the inclusion criteria, 3 reported NAFLD outcomes and 19 reported indices of liver health. Of these, all but 1 study were rated at medium or high risk of bias. The overall strength of evidence for an association between fructose intake and incidence of NAFLD was rated insufficient because of the biases and confounding in the study results. The 19 studies reporting indices of liver health were synthesized separately by each outcome: liver fat outcomes (7 studies), liver enzymes (11 studies), hepatic de novo lipogenesis rates (2 studies), and plasma bilirubin concentrations (2 studies). The overall strength of evidence was rated insufficient for all outcomes, except for some plasma liver enzymes. Our random-effects meta-analysis of 3 short-term RCTs (6 to 7 days) showed a significant increase in alanine aminotransferase (ALT) concentrations (+4.32 IU/L, 95% CI 0.20, 8.43, P=0.04) when a free fructose enriched excess energy diet was compared to a habitual weight maintenance diet. Limitations: Most studies were rated at medium or high risk of bias, were small in sample size, included healthy adult men only, and were highly heterogeneous in study design and intervention, and thus limiting comparability. Conclusions: Due to scarce, poor-quality, and heterogeneous data, we concluded that evidence is insufficient to draw conclusions regarding the effect of fructose consumption on NAFLD, while there is low level of evidence for a relationship between high free fructose intake in excess of energy needs and elevated liver enzyme concentrations. Large prospective cohort studies using standard NAFLD diagnosis are needed to examine the complex relationships between dietary factors and the risk of NAFLD.
Contributor(s): Mei Chung, PhD, MPH Jiantao Ma, MD, MS Kamal Patel, MPH, MBA Samantha Berger, BS Joseph Lau, MD Alice H. Lichtenstein, ScD
Funding Source: The International Life Sciences Institute (ILSI) North American Branch
Methodology Description: See Chung M, Ma J, Patel K, Berger S, Lau J, Lichtenstein AH. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr. 2014 Sep;100(3):833-49. doi: 10.3945/ajcn.114.086314. Epub 2014 Aug 6. PubMed PMID: 25099546; PubMed Central PMCID: PMC4135494.

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First- and Second- Generation Antipsychotics for Children and Young Adults [Entered Retrospectively]


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Statistics: 81 Studies, 4 Key Questions, 1 Extraction Form,
Date Published: Jul 23, 2015 02:29PM
Description: Methods: Two reviewers conducted study selection and quality assessment independently and resolved discrepancies by consensus. One reviewer extracted data, and a second reviewer verified the data. We conducted a descriptive analysis for all studies and performed metaanalyses when appropriate. Results: Eighty-one studies (64 trials and 17 cohort studies) examined the following conditions: pervasive developmental disorders (12 studies); attention deficit hyperactivity disorder (ADHD) or disruptive behavior disorders (8 studies); bipolar disorder (11 studies); schizophrenia and related psychosis (31 studies); Tourette syndrome (7 studies); behavioral issues (4 studies); and multiple conditions (9 studies). One study reported data on both bipolar disorder and schizophrenia. The majority of the trials had a high risk of bias. The methodological quality of the cohort studies was moderate. Results are presented by outcome below: Symptoms: The strength of evidence for all head-to-head comparisons of FGAs and SGAs was low or insufficient to draw conclusions. SGAs were favored over placebo for behavior symptoms (ADHD and disruptive behavior disorders), the Clinical Global Impressions scale (ADHD and disruptive behavior disorders, bipolar disorder, and schizophrenia), positive and negative symptoms (schizophrenia), and tics (Tourette syndrome) (moderate strength of evidence). Other short- and long-term outcomes: All head-to-head comparisons had low or insufficient strength of evidence. There was no significant difference between SGAs and placebo for suicide related behaviors (moderate strength of evidence). The evidence was rated as insufficient to draw conclusions for health-related quality of life, involvement with the legal system, and other patient-, parent-, or care provider-reported outcomes for all conditions. Adverse events: All outcomes comparing FGAs with SGAs had low or insufficient strength of evidence. Outcomes comparing FGAs versus FGAs and FGAs versus placebo had insufficient evidence. Risperidone was favored over olanzapine for dyslipidemia; olanzapine was favored over risperidone for prolactin-related events; and both quetiapine and risperidone were favored over olanzapine for weight gain (moderate strength of evidence). For nearly all outcomes and comparisons, placebo resulted in significantly fewer adverse events than SGAs. Subpopulations: Thirty-six studies examined the association between various patient subpopulations and outcomes. Most concluded that the results did not differ by subpopulations, or findings were discordant across studies. Conclusion: Evidence comparing FGAs with SGAs, various FGAs, and FGAs with placebo was very limited. Some SGAs appear to have a better side-effect profile than other SGAs. Compared with placebo, SGAs have better symptom improvement but more adverse events. Future high quality research examining head-to-head antipsychotic comparisons is needed.
Contributor(s): Jennifer C Seida, MPH; Janine Schouten, BSc; Shima S Mousavi, MD; Michele Hamm, MSc; Amy Beaith, MISt; Ben Vandermeer, MSc; Donna M Dryden, PhD; Khrista Boylan, MD, FRCPC; Amanda S Newton, RN, PhD; Normand Carrey, MD, FRCPC, ABPN
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: We systematically searched the following bibliographic databases: MEDLINE, Embase, CENTRAL, PsycINFO, International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, ProQuest Dissertations International, MedEffect Canada, and TOXLINE. The searches are up to date to February 2011. We limited the searches to studies published from 1987 or later to coincide with the Diagnostic and Statistical Manual of Mental Disorders III–Revised. We restricted the search results to studies published in the English language. We applied filters to restrict the results to children and young adults ≤24 years of age and to trials and cohort studies. We hand searched proceedings of the following scientific meetings that were identified by our clinical experts: American Academy of Child and Adolescent Psychiatry (2007–2008), International College of Neuropsychopharmacology (2007–2009), and International Society for Bipolar Disorders (2007–2009). We searched clinical trial registers for ongoing studies and reference lists of relevant studies to identify additional studies. In addition, we contacted drug manufacturers to request published and unpublished study data. We reviewed FDA documents related to the eligible drugs to identify additional data. Two reviewers independently screened titles and abstracts using broad inclusion criteria. We retrieved the full text of all articles identified as "include" or "unclear." Two reviewers independently assessed each article using a priori inclusion criteria and a standardized form. We resolved disagreements by consensus or third-party adjudication. Randomized controlled trials (RCTs), nonrandomized controlled trials (NRCTs), and cohort studies that examined a condition of interest (pervasive developmental disorders, ADHD and disruptive behavior disorders, bipolar disorder, schizophrenia or schizophrenia-related psychosis, Tourette syndrome, obsessive-compulsive disorder, post-traumatic stress disorder, anorexia nervosa, or behavioral issues) in children or young adults ≤24 years of age were considered for inclusion. Eligible studies compared a FDA-approved FGA or SGA with any other antipsychotic or with placebo. Studies were required to report at least one outcome of interest including symptom improvement, other short- or long-term outcomes, or adverse events. No minimum follow-up duration was specified. One reviewer extracted data using a standardized form, and a second reviewer verified the data for accuracy and completeness. We extracted information on study characteristics, inclusion and exclusion criteria, participant characteristics, interventions, and outcomes. Reviewers resolved discrepancies by consensus or in consultation with a third party.

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Effectiveness of Early Diagnosis, Prevention, and Treatment of Clostridium difficile Infection [Entered Retrospectively]


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Statistics: 112 Studies, 10 Key Questions, 10 Extraction Forms,
Date Published: Jul 23, 2015 02:29PM
Description: Objectives: To conduct a systematic review and synthesize evidence for differences in the accuracy of diagnostic tests, and the effects of interventions to prevent and treat Clostridium difficile infection (CDI) in adult patients. Data Sources: Searching for relevant literature was conducted in MEDLINE, the Cochrane Library, and Allied and Complementary Medicine (AMED). ClinicalTrials.gov and expert consultants provided leads to additional studies. We also manually searched reference lists from relevant literature. Review Methods: Standard Evidence-based Practice Center methods were employed. Screening of abstracts and full text articles to identify studies meeting inclusion/exclusion criteria was performed by two independent reviewers. High-quality direct comparison studies were used to examine differences in diagnostic tests. Randomized controlled trials (RCTs) were used to examine comparative effectiveness of antibiotic treatment for CDI. Quality of data extraction was checked by separate reviewers. Quality ratings and strength of evidence grading was performed on included studies. Evidence on diagnostic tests was quantitatively synthesized focusing on differences between test sensitivities and specificities. Evidence on antibiotic treatment was quantitatively examined using pooled analysis. Qualitative narrative analysis was used to synthesize evidence from all available study types for environmental prevention and nonstandard prevention and treatment, with the exception of probiotics as primary prevention, for which a forest plot is provided. Results: Overall, literature was sparse and strength of evidence was generally low due to small sample sizes or lack of adequate controls. For diagnostic testing, direct comparisons of commercially available enzyme immunoassays for C. difficile toxins A and B did not find major differences in sensitivity or specificity. Limited evidence suggests that tests for genes related to the production of C. difficile toxins may be more sensitive than immunoassays for toxins A and B while the comparisons of these test specificities were inconsistent. Moderate evidence in favor of antibiotic restriction policies for prevention was found. Environmental preventive interventions such as glove use and disposable thermometers have limited evidence. However, this literature is largely based on controlling outbreaks. Use of multiple component interventions further limits the ability to synthesize evidence in a meaningful way. Numerous potential new forms of treatment are being examined in placebo controlled RCTs, case series, and case reports. For standard treatment, no antimicrobial is clearly superior for the initial cure of CDI. Recurrence is less frequent with fidaxomicin than with vancomycin. Monoclonal antibodies for prevention and fecal flora reconstitution for multiple recurrences appear promising. Conclusions: Given the frequency and severity of CDI and the fact that future reimbursement policy may withhold payment for hospital-acquired infections, this is an under-researched topic. More precise estimates of the magnitude of differences in test sensitivities and specificities are needed. More importantly, studies have not established that any of the possible differences in test accuracy would lead to substantially different patient outcomes in clinical practice. More research on effective treatment and unintended consequences of treatment, such as resistance, is needed. Gut flora may be important, but improved understanding of healthy gut ecology and the complex interactions is necessary before continuing to pursue probiotics.
Contributor(s): Mary Butler, PhD, MBA; Donna Bliss, RN, PhD; Dimitri Drekonja, MD; Gregory Filice, MD; Thomas Rector, PharmD, PhD; Roderick MacDonald, MS; Timothy Wilt, MD, MPH
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: None Provided

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