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Completed Systematic Reviews




Management and Outcomes of Binge-Eating Disorder (BED)


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Statistics: 84 Studies, 15 Key Questions, 3 Extraction Forms,
Date Published: Feb 17, 2016 06:19PM
Description: Objectives. To evaluate the effectiveness and comparative effectiveness of treatments for patients with binge-eating disorder (BED) and bariatric surgery patients and children with loss-of-control (LOC) eating. Studies of BED therapies include pharmacological interventions, psychological and behavioral interventions, or combinations of approaches. We examined whether treatment effectiveness differed in patient subgroups and described courses of illness for BED and LOC eating. Data Sources. We searched MEDLINE,® EMBASE,® the Cochrane Library, Academic OneFile, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) through 1/19/2015. Eligible studies included randomized controlled trials (RCTs), nonrandomized trials, meta-analyses, and, for course of illness, cohort and case-control studies. Review Methods. Pairs of reviewers independently selected, extracted data from, and rated the risk of bias of relevant studies; they graded the strength of evidence using established criteria. We conducted meta-analysis for some treatment outcomes. Results. Of 52 included RCTs of treatment; 48 concerned BED therapy. Course of illness evidence came from 15 observational studies. We examined four major outcomes: binge eating and abstinence, eating-related psychopathology, weight, and general psychological and other outcomes. Second-generation antidepressants (as a class), topiramate (an anticonvulsant), and lisdexamfetamine (a stimulant) were superior to placebo in achieving abstinence and reducing binge episodes and/or binge days and eating-related obsessions and compulsions. Second-generation antidepressants decreased depression. Topiramate and lisdexamfetamine produced weight reduction in study populations that were virtually all overweight or obese. A few formats of cognitive behavioral therapy (CBT)—therapist-led, partially therapist-led, and guided self-help—were superior to placebo in achieving abstinence and reducing binge frequency. CBT for BED was generally ineffective for reducing weight or depression in this population. Therapist-led CBT was not superior to either partially therapist-led CBT or structured self-help CBT for binge-eating and weight outcomes. Behavioral weight loss treatment produced greater weight loss than CBT at the end of treatment but not over the longer run. Topiramate, fluvoxamine, and lisdexamfetamine were associated with sleep disturbance including insomnia; topiramate and lisdexamfetamine were associated with sympathetic nervous system arousal, headache, and GI upset. We found no evidence on bariatric surgery patients. Treatments for LOC eating in children did not achieve superior weight reduction outcomes. Evidence on course of either illness was limited. Early adolescent BED and LOC eating predicts such behaviors in the future. Conclusions. BED patients may benefit from treatment with second-generation antidepressants, lisdexamfetamine, topiramate, and CBT. Additional studies should address other treatments, combinations of treatment, and comparisons between treatments, treatment for postbariatric surgery patients and children, as well as the course of these illnesses.
Contributor(s): Nancy D. Berkman, PhD Kimberly A. Brownley, PhD Christine M. Peat, PhD Kathleen N. Lohr, PhD Katherine E. Cullen, BA Laura C. Morgan, MA Carla M. Bann, PhD Cynthia M. Bulik, PhD Ina F. Wallace, PhD
Funding Source: Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: We conducted focused searches of MEDLINE® (via PubMed), EMBASE®, CINAHL (nursing and allied health database), Academic OneFile, and the Cochrane Library. An experienced research librarian used a predefined list of search terms and medical subject headings (MeSH). The librarian completed the searches for the draft report on 6/23/2014; she conducted a second (update) search on 1/19/2015 during peer review. We searched for relevant unpublished and grey literature, including trial registries, specifically ClinicalTrials.gov and Health Services Research Projects in Progress. AHRQ requested Scientific Information Packets (SIPs) from the developers and distributors of interventions identified in the literature review. We included unpublished studies that met all inclusion criteria and contained enough information to permit us to make a standard risk-of-bias assessment. We searched reference lists of pertinent review articles for studies that we should consider for inclusion in this review, including our earlier review on this topic. Trained members of the research team reviewed article abstracts and full-text articles. Two members independently reviewed each title and abstract using the predefined inclusion and exclusion criteria. Studies marked for possible inclusion by either reviewer underwent a full-text review. Two members of the team independently reviewed each full-text article. If both reviewers agreed that a study did not meet the eligibility criteria, it was excluded; each reviewer recorded the primary reason for exclusion. If reviewers disagreed, they resolved conflicts by discussion and consensus or by consulting a third member of the review team. We screened unpublished studies and reviewed SIPs using the same title/abstract and full-text review processes. The project coordinator tracked abstract and full-text reviews in an EndNote database (EndNote® X4). We developed a template for evidence tables using the PICOTS framework and abstracted relevant information into them using Microsoft Excel. We recorded characteristics of study populations, interventions, comparators, settings, study designs, methods, and results. Six trained members of the team participated in the data abstraction. One reviewer initially abstracted the relevant data from each included article; a second more senior member of the team reviewed each data abstraction against the original article for completeness and accuracy.

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Emerging Approaches to Diagnosis and Treatment of Non-Muscle-Invasive Bladder Cancer [Entered Retrospectively]


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Statistics: 199 Studies, 8 Key Questions, 1 Extraction Form,
Date Published: Feb 17, 2016 06:18PM
Description: Objectives. Non-muscle-invasive bladder cancer (NMIBC) frequently recurs and can progress to muscle-invasive disease. This report reviews the current evidence on emerging approaches to diagnosing and treating bladder cancer. Data Sources. Electronic databases (Ovid MEDLINE, January 1990 – October 2014; Cochrane Central Register of Controlled Trials, through September 2014; Cochrane Database of Systematic Reviews, through September 2014; Health Technology Assessment, through 3rd Quarter, 2014; National Health Sciences Economic Evaluation Database, through 3rd Quarter, 2014; and Database of Abstracts of Reviews of Effects, through 3rd Quarter, 2014), references lists, and clinical trials registries. Review Methods. Using predefined criteria, we selected studies on diagnostic accuracy of urinary biomarkers versus cystoscopy, and trials of fluorescent cystoscopy, intravesical therapy, and radiation therapy for NMIBC that evaluated bladder cancer recurrence, progression, mortality, or harms. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis. Results. Urinary biomarkers were associated with sensitivity for bladder cancer that ranged from 0.57 to 0.82 and specificity from 0.74 to 0.88, for positive likelihood ratios from 2.52 to 5.53 and negative likelihood ratios from 0.21 to 0.48 (strength of evidence [SOE]: moderate for quantitative nuclear matrix protein 22 [NMP22], qualitative bladder tumor antigen [BTA], fluorescent in situ hybridization [FISH], and ImmunoCyt; low for other biomarkers). Sensitivity increased for higher stage and grade tumors. Studies that directly compared the accuracy of quantitative NMP22 and qualitative BTA found no differences in diagnostic accuracy (SOE: moderate). Most trials found fluorescent cystoscopy associated with decreased risk of subsequent bladder recurrence versus white light cystoscopy, but results were inconsistent, and there was no difference in risk of progression or mortality (SOE: low). Intravesical therapy was more effective than no intravesical therapy for reducing risk of bladder cancer recurrence (for bacillus Calmette-Guérin [BCG], RR 0.56, 95% CI 0.43 to 0.71, SOE: moderate; for mitomycin C [MMC], doxorubicin, and epirubicin, RR 0.66 to 0.72, SOE: moderate). BCG was also associated with decreased risk of bladder cancer progression, but no intravesical agent was associated with decreased risk of all-cause or bladder-cancer specific mortality. Intravesical therapy appeared to be effective across subgroups defined by tumor stage, grade, multiplicity, recurrence status, and size (SOE: low). Evidence was too limited to draw strong conclusions regarding effects of dose or duration of therapy on effectiveness. Compared with no intravesical therapy, BCG was associated with a higher rate of local and systemic adverse events (granulomatous cystitis or irritative symptoms in 27% to 84% of patients, macroscopic hematuria in 21% to 72%, and fever in 27% to 44%) (SOE: low). Compared with MMC, BCG was also associated with an increased risk of local adverse events and fever (SOE: low). One randomized trial found no difference between radiation therapy and no radiation therapy in clinical outcomes in patients with T1G3 cancers. Conclusions. Urinary biomarkers miss a substantial proportion of patients with bladder cancer, and additional research is needed to clarify advantages of fluorescent cystoscopy over white light cystoscopy. Intravesical therapy reduces risk of bladder cancer recurrence versus no intravesical therapy. BCG is the only intravesical therapy shown to be associated with decreased risk of bladder cancer progression, but is associated with a high rate of adverse events. More research is needed to define optimal doses and regimens of intravesical therapy.
Contributor(s): Roger Chou, M.D., FACP David Buckley, M.D., MPH Rochelle Fu, PhD John L. Gore, M.D. Katie Gustafson, M.D. Jessica Griffin, M.S. Sara Grusing, B.A. Shelley Selph, MD
Funding Source: Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2012-00014-I. Rockville, MD: Agency for Healthcare Research and Quality. www.effectivehealthcare.ahrq.gov/reports/final.cfm
Methodology Description: Review Methods. Using predefined criteria, we selected studies on diagnostic accuracy of urinary biomarkers versus cystoscopy, and trials of fluorescent cystoscopy, intravesical therapy, and radiation therapy for NMIBC that evaluated bladder cancer recurrence, progression, mortality, or harms. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis.

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Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer [Entered Retrospectively]


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Statistics: 40 Studies, 4 Key Questions, 1 Extraction Form,
Date Published: Feb 17, 2016 06:17PM
Description: Structured Abstract Objectives. Although the standard treatment for non-metastatic muscle-invasive bladder cancer is cystectomy and neoadjuvant chemotherapy, there is interest in bladder-preserving therapy as an alternative, and uncertainty about the need for and optimal extent of lymph node dissection and optimal chemotherapy regimens and timing of administration. Data Sources. Electronic databases (Ovid MEDLINE, January 1990 to October 2014, Cochrane Central Register of Controlled Trials, through September 2014, Cochrane Database of Systematic Reviews, through September 2014, Health Technology Assessment, through 3rd Quarter, 2014, National Health Sciences Economic Evaluation Database, through 3rd Quarter, 2014, and Database of Abstracts of Reviews of Effects, through 3rd Quarter, 2014), references lists, and clinical trials registries. Review Methods. We selected randomized controlled trials, nonrandomized controlled clinical trials and nonrandomized cohort studies with concurrent comparators that evaluated bladder-preserving therapies against one another or versus radical cystectomy, that evaluated the effectiveness of lymph node dissection or effects of extent of dissection, and that compared neoadjuvant or adjuvant chemotherapy versus another chemotherapy regimen or versus no chemotherapy. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis. Results. One randomized controlled trial with methodological limitations found no difference between bladder preserving external beam radiation therapy (60 Gray) versus radical cystectomy plus radiation therapy (40 Gray) in median survival duration, though bladder-preserving treatment was associated with increased risk of local or regional recurrence (35.8% vs. 6.8%) (strength of evidence: insufficient). Cohort studies of bladder-preserving treatments versus radical cystectomy had methodological shortcomings and reported inconsistent results, precluding reliable conclusions (strength of evidence: insufficient). Cohort studies suggested that lymph node dissection was associated with lower risk of mortality than no lymph node dissection and that more extensive lymph node dissection with cystectomy might be more effective than less extensive lymph node dissection at improving survival, but studies had methodological limitations, there was some inconsistency in results, and there was variability in the lymph node dissection techniques evaluated (strength of evidence: low). Six randomized controlled trials consistently found neoadjuvant chemotherapy with cisplatin-based combination regimens associated with decreased risk, or a trend towards decreased risk, of mortality versus no neoadjuvant chemotherapy, including three trials that evaluated current regimens (cisplatin, methotrexate, and vinblastine and methotrexate, vinblastine, doxorubicin, and cisplatin (strength of evidence: moderate). Four trials found adjuvant chemotherapy associated with decreased risk of mortality versus no adjuvant chemotherapy, but no trial reported a statistically significant effect and there was some inconsistency in findings (strength of evidence: low). One trial and two cohort studies found no clear differences between neoadjuvant and adjuvant methotrexate, vinblastine, doxorubicin, and cisplatin in survival (strength of evidence: low). Evidence on harms, effectiveness of treatments for muscle-invasive bladder cancer in patient subgroups (including older patients, patients with comorbidities, and patients with renal dysfunction), and comparative effectiveness of different chemotherapy regimens was too limited to reach reliable conclusions. Conclusions. Neoadjuvant chemotherapy with cisplatinum-based regimens improved survival in patients with muscle-invasive bladder cancer, and extended lymph node dissection during cystectomy might be more effective than standard lymph node dissection for improving survival. More research is needed to clarify the effectiveness of bladder-preserving therapies versus radical cystectomy and define patient subgroups in which such therapies may be a potential option.
Contributor(s): Roger Chou, M.D., FACP Shelley Selph, M.D. David Buckley, M.D., MPH Katie Gustafson, M.D. Jessica Griffin, M.S. Sara Grusing, B.A. John L. Gore, M.D.
Funding Source: Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No. 290-2012-00014-I.) Rockville, MD: Agency for Healthcare Research and Quality; Month YEAR. www.effectivehealthcare.ahrq.gov/reports/final.cfm
Methodology Description: Review Methods. We selected randomized controlled trials, nonrandomized controlled clinical trials and nonrandomized cohort studies with concurrent comparators that evaluated bladder-preserving therapies against one another or versus radical cystectomy, that evaluated the effectiveness of lymph node dissection or effects of extent of dissection, and that compared neoadjuvant or adjuvant chemotherapy versus another chemotherapy regimen or versus no chemotherapy. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis.

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Catheter Ablation for Treatment of Atrial Fibrillation [Prospectively Entered]


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Statistics: 50 Studies, 7 Key Questions, 2 Extraction Forms,
Date Published: Feb 17, 2016 06:14PM
Description: Because catheter ablation is increasingly being used to treat AF patients in the Medicare population, and there is uncertainty regarding the efficacy and harms of this procedure in this population in particular, a systematic review to re-evaluate the current state of evidence, identify and evaluate inconsistencies in the evidence, and identify important research gaps is warranted to help inform clinical practice and policy.
Contributor(s): Andrea Skelly (PhD, MPH/Spectrum Research) Marian McDonagh (PharmD/OHSU) Robin Hashimoto (PhD/Spectrum Research) Gillian Sanders-Schmidler (PhD/Duke) Sana Al-Khatib (MD, MHS/Duke) Rochelle Fu (PhD/OHSU) Elaine Graham (MLS/OHSU) Tracy Dana (MLS/OHSU) Erika Brodt (BS/Spectrum Research) Katie Moran (BS/Spectrum Research) Kathryn Mihalovich (BS/Spectrum Research)
Funding Source: Agency for Healthcare Research and Quality (AHRQ). Prepared by the Pacific Nortwest Evidence-based Practice Center under Contract No. HHSA 290-2012-00014-I. The Technology Assessment is available at: http://www.cms.gov/Medicare/Coverage/DeterminationProce
Methodology Description: Using predefined criteria, randomized trials and observational studies comparing the efficacy, effectiveness, or safety of catheter ablation (radiofrequency or cryoballoon ablation) to medical therapy in patients with atrial fibrillation were included. Analyses were stratified by type of atrial fibrillation and length of followup (>12 months vs. ≤12 months). The quality of included studies was assessed, data were extracted, results were summarized qualitatively and using meta-analysis, and the strength of the evidence was graded for each primary outcome.

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Off-Label Use of Atypical Antipsychotics: An Update [Entered Retrospectively]


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Statistics: 129 Studies, 4 Key Questions, 1 Extraction Form,
Date Published: Dec 08, 2015 12:00PM
Description: Objectives: Antipsychotic medications are approved by the U.S. Food and Drug Administration (FDA) for treatment of schizophrenia, bipolar disorder, and for some drugs, depression. We performed a systematic review on the efficacy and safety of atypical antipsychotic drugs for use in conditions lacking FDA approval. Data Sources: We searched PubMed, Embase, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane DARE (Database of Abstracts of Reviews of Effects), and Cochrane CENTRAL (Cochrane Central Register of Controlled Trials) from inception to May 2011. We included only English-language studies. Review Methods: Controlled trials comparing an atypical antipsychotic (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, paliperidone) to either placebo, another atypical antipsychotic drug, or other pharmacotherapy, for the off-label conditions of anxiety disorder, attention deficit hyperactivity disorder, dementia and severe geriatric agitation, major depressive disorder, eating disorders, insomnia, obsessive compulsive disorder (OCD), post traumatic stress disorder (PTSD), personality disorders, substance abuse, and Tourette’s syndrome were included. Observational studies with sample sizes greater than 1,000 were included to assess rare adverse events. Two investigators conducted independent article review, data abstraction, and study quality assessment. Results: One hundred seventy trials contributed data to the efficacy review. Among the placebocontrolled trials of elderly patients with dementia reporting a total/global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effect sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, pooled analysis of three large trials showed that quetiapine was associated with a 26 percent greater likelihood of "responding," defined as at least 50 percent improvement on the Hamilton Anxiety Scale, compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of "responding," defined as a 25 to 35 percent improvement on the Yale Brown Obsessive Compulsive Scale (YBOCS) compared with placebo. We identified 6 trials on eating disorders, 12 on personality disorder, an existing metaanalysis and 10 trials of risperidone or olanzapine for PTSD, 36 trials for depression of which 7 assessed drugs without an FDA-approved indication, and 33 trials of aripiprazole, olanzapine, quetiapine, or risperidone for treating substance abuse disorders. We identified one small trial (N=13) of atypical antipsychotics for insomnia which was inconclusive. For eating disorder patients specifically, evidence shows that atypicals are do not cause significant weight gain. The level of evidence is mixed regarding personality disorders and moderate for an association of risperidone with improving post-traumatic stress disorder. Evidence does not support efficacy of atypical antipsychotics for substance abuse. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH]=87), stroke (for risperidone, NNH=53), extrapyramidal symptoms (for olanzapine (NNH=10) and risperidone (NNH=20), and urinary symptoms (NNH= from 16 to 36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akithisia (for aripiprazole) and extrapyramidal symptoms. Direct comparisons of different atypical antipsychotics for off-label conditions are rare. Conclusions: Benefits and harms vary among atypical antipsychotics for off-label usage. For symptoms associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of OCD; however, adverse events were common.
Contributor(s): Margaret Maglione, MPP; Alicia Ruelaz Maher, MD; Jianhui Hu, MPP; Zhen Wang, MS; Roberta Shanman, MLS; Paul G. Shekelle, MD, PhD; Beth Roth, MA; Lara Hilton, MPH; Marika J Suttorp, MS; Brett A Ewing, MS; Aneesa Motala, BA; Tanja Perry, BHM
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: We conducted an initial update search on June 1, 2008, as part of a project to determine if Comparative Effectiveness Reviews (CERs) funded by AHRQ needed updating; this search included only the drugs aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. Regular update searches continued through May 2011. The search for off-label use of the newly approved atypicals (iloperidone, paliperidone and asenapine) included all years available in the electronic databases through May 2011. Searches for utilization data were conducted, as were searches for use for new conditions (anxiety, ADHD, eating disorders, insomnia, and substance abuse). Databases searched include: DARE (Database of Abstracts of Reviews of Effects), Cochrane Database of Systematic Reviews, CENTRAL (Cochrane Central Register of Controlled Trials), PubMed (National Library of Medicine, includes MEDLINE), Embase (biomedical and pharmacological bibliographic database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PsycINFO. A summary of detailed search strategies is available in Appendix A. Other sources of literature include clinicaltrials.gov, references of included studies, references of relevant reviews, and personal files from related topic projects. In addition, the AHRQ Effective Health Care Program Scientific Resource Center (SRC) at Oregon Health Sciences University requested unpublished studies from pharmaceutical manufacturers and searched the FDA and Health Canada databases. Two trained researchers reviewed the list of titles resulting from our electronic searches and selected articles to obtain. Each article retrieved was reviewed with a brief screening form (see Appendix B: screener) that collected data on medication, psychiatric condition, study design, population, sample size, and study duration. Only studies on humans were included. Studies that did not report any outcomes of efficacy, effectiveness, safety/adverse events, or utilization patterns were excluded. As single dose or short term trials (less than 6 weeks in length) are common for several of the new uses, we decided, at the TEP’s suggestion, not to limit inclusion by study duration. Clinical trials were used to review efficacy outcomes. In the case that no clinical trials were found for a given condition or drug of interest, we turned to observational studies. All reported side effects and adverse events were abstracted from clinical trials, even if the trial did not report efficacy or effectiveness results. We also included large observational studies of adverse events. Reports of utilization and prescribing patterns were accepted if they discussed use in the United States since 1995. Data were independently abstracted by a health services researcher and a psychiatrist trained in the critical assessment of evidence. The following data were abstracted from included trials: trial name, setting, population characteristics (including sex, age, ethnicity, and diagnosis), eligibility and exclusion criteria, interventions (dose, frequency, and duration), any co-interventions, other allowed medication, comparisons, and results for each outcome.

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