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Completed Systematic Reviews




Psychosocial and Pharmacologic Interventions for Disruptive Behavior in Children and Adolescents


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Statistics: 97 Studies, 2 Key Questions, 1 Extraction Form,
Date Published: Jul 27, 2015 03:22PM
Description: None Provided
Contributor(s): None Provided
Funding Source: None Provided
Methodology Description: None Provided

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Venous Thromboembolism Prophylaxis in Orthopedic Surgery [Entered Retrospectively]


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Statistics: 149 Studies, 8 Key Questions, 8 Extraction Forms,
Date Published: Jul 23, 2015 02:45PM
Description: Objectives: This is an evidence report prepared by the University of Connecticut/Hartford Hospital Evidence-based Practice Center (EPC) examining the comparative efficacy and safety of prophylaxis for venous thromboembolism in major orthopedic surgery (total hip replacement [THR], total knee replacement [TKR], and hip fracture surgery [HFS]) and other nonmajor orthopedic surgeries (knee arthroscopy, injuries distal to the hip requiring surgery, and elective spine surgery). Data Sources. Medline, the Cochrane Central Register of Controlled Trials, and Scopus from 1980 to May 2011 with no language restrictions; Review Methods: Controlled trials of any size and controlled observational studies with >750 subjects were included in our comparative effectiveness review if they were in patients undergoing one of six a priori defined orthopedic surgeries; provided data on prespecified intermediate, final health, or harms outcomes; defined deep vein thrombosis (DVT) and pulmonary embolism (PE) according to rigorous criteria (where applicable), and included prophylactic products (pharmacologic or mechanical) available in the United States. Using predefined criteria, data on study design, interventions, quality criteria, study population, baseline characteristics, and outcomes were extracted. All of the available data were qualitatively evaluated and where possible, statistically pooled. We used random effects derived relative risks (RR) for most analyses and Peto’s Odds Ratios (OR) in comparisons of rare events both with 95 percent confidence intervals (CIs). I2 was used to detect statistical heterogeneity and Egger’s weighted regression statistics were used to assess for publication bias. The strength of evidence (SOE) and applicability of evidence (AOE) for each outcome was rated as insufficient (I), low (L), moderate (M), or high (H); Results: In major orthopedic surgery (THR, TKR, and HFS, respectively), the incidence of DVT (39 percent, 53 percent, 47 percent), PE (6 percent, 1 percent, 3 percent), major bleeding (1 percent, 3 percent, 8 percent), and minor bleeding (5 percent, 5 percent, not reported) were reported in the placebo/control groups of clinical trials. The SOE and AOE were predominantly low for THR and TKR and was insufficient HFS. In major orthopedic surgery, pharmacologic prophylaxis reduced major venous thromboembolism (VTE) (OR 0.21 [0.05 to 0.95], SOE: L, AOE: L), DVT (RR 0.56 [0.47 to 0.68], SOE: M, AOE: L), and proximal DVT (pDVT) (RR 0.53 [0.39 to 0.74], SOE: H, AOE: L), but increased minor bleeding (RR 1.67 [1.18 to 2.38], SOE: H, AOE: M). Prolonged prophylaxis for >28 days was superior to prophylaxis for 7 to 10 at reducing symptomatic objectively confirmed VTE (RR 0.38 [0.19 to 0.77], SOE: M, AOE: L), PE (OR 0.13 [0.04 to 0.47], SOE: H, AOE: L), DVT (RR 0.37 [0.21 to 0.64], SOE: M, AOE: M), and pDVT (RR 0.29 [0.16 to 0.52], SOE: H, AOE: M) but increased minor bleeding (OR 2.44 [1.41 to 4.20], SOE: H, AOE: M). Using both pharmacologic and mechanical prophylaxis reduced DVT (RR 0.48 [0.32 to 0.72] SOE: M, AOE: M) versus pharmacologic prophylaxis alone. Low molecular weight heparins (LMWHs) reduced PE (OR 0.48 [0.24 to 0.95], SOE: M, AOE: L), DVT (RR 0.80 [0.65 to 0.99], SOE: M, AOE: L), pDVT (RR 0.60 [0.38 to 0.93], SOE: H, AOE: L), major bleeding (OR 0.57 [0.37 to 0.88], SOE: H, AOE: L), and heparin induced thrombocytopenia (OR 0.12 [0.03 to 0.43], SOE: M, AOE: L) versus unfractionated heparin. LMWHs reduced DVT (RR 0.66 [0.55 to 0.79], SOE: L, AOE: M) but increased major bleeding (RR 1.92 [1.27 to 2.91], SOE: H, AOE: M), minor bleeding (RR 1.23 [1.06 to 1.43], SOE: M, AOE: M), and surgical site bleeding (OR 2.63 [1.31 to 5.28], SOE: L, AOE: L) versus vitamin K antagonists. LMWHs increased DVT (RR 1.99 [1.57 to 2.51], SOE: M, AOE: L) and pDVT (OR 2.19 [1.52 to 3.16], SOE: L, AOE: L) but reduced major bleeding (OR 0.65 [0.48 to 0.89], SOE: M, AOE: L) versus factor Xa inhibitors. Antiplatelets increased DVT (1.63 [1.11 to 2.39], SOE: M, AOE: L) versus mechanical prophylaxis. Unfractionated heparin increased DVT (RR 2.31 [1.34 to 4.00], SOE: M, AOE: L) and pDVT (OR 4.74 [2.99 to 7.49], SOE: M, AOE: L) versus direct thrombin inhibitors. Intermittent compression stocking decreased DVT (RR 0.06 [0.01 to 0.41], SOE: L, AOE: L) versus graduated compression stockings. We did not have adequate information to evaluate the role of inferior vena cava filter (IVC) filters or to evaluate the impact of prophylaxis on nonmajor orthopedic surgeries; Conclusions: In major orthopedic surgery, while the risk of developing deep vein thrombosis is highest followed by pulmonary embolism and major bleeding, there are inadequate data to say whether or not deep vein thrombosis causes pulmonary embolism or is an independent predictor of pulmonary embolism. The balance of benefits to harms is favorable for providing prophylaxis to these patients and to extend the period of prophylaxis beyond the standard 7–10 days. The comparative balance of benefits to harms for LMWHs are superior to unfractionated heparin. Other interclass comparisons either could not be made due to lack of data, showed similarities between classes on outcomes, or had offsetting effects where benefits of one class on efficacy was tempered by an increased risk of bleeding. The balance of benefits to harms for combined pharmacologic plus mechanical prophylaxis versus either strategy alone could not be determined. We could not determine the impact of IVC filters on outcomes or the impact of prophylaxis on the nonmajor orthopedic surgeries evaluated.
Contributor(s): Diana M. Sobieraj, PharmD; Craig I. Coleman, PharmD; Vanita Tongbram, MBBS, MPH; Soyon Lee, PharmD; Jennifer Colby, PharmD; Wendy T. Chen, PharmD; Sagar S. Makanji, PharmD; Ajibade Ashaye, MD, MPH; Jeffrey Kluger, MD, FACC; C. Michael White, PharmD, FCP, FCCP
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: A systematic literature search of Medline, the Cochrane Central Register of Controlled Trials, and Scopus from 1980 to September 2010 was conducted with no language restrictions. The year 1980 was used as a restriction to reflect contemporary practice. Two separate literature searches were conducted. The first search was used to identify studies that evaluated pharmacologic, mechanical, or inferior vena cava filter methods of thromboprophylaxis in patients undergoing major orthopedic surgery, describe the association between patient, surgical, or postsurgical characteristics and VTE or bleeding, or describe the association between intermediate and final health outcomes to answer KQs 1 through 9. The second search was used to identify studies which evaluate pharmacologic or mechanical methods of thromboprophylaxis in patients undergoing knee arthroscopy, surgical repair of a lower extremity injury distal to the hip, or elective spine surgery to answer KQs 10 and 11. Backward citation tracking was also conducted. A grey literature search of regulatory documents, abstracts, and ongoing clinical trials was conducted by the Scientific Resource Center and reviewed by two independent investigators for inclusion into our literature base by applying the same a priori defined inclusion criteria defined below. The literature searches were updated in May 2011. Two independent investigators assessed studies for inclusion in a parallel manner based on a priori defined criteria. In evaluating all KQs, randomized controlled trials (RCTs) of any size or controlled observational studies (case controlled or cohort studies) enrolling at least 750 patients were included if they explicitly reported the use of imaging studies to confirm VTE events (Doppler ultrasound or venography for DVT and spiral computed tomography [CT] angiography or ventilation/perfusion [V/Q] scan with either Prospective Investigation of Pulmonary Embolism Diagnosis [PIOPED] criteria or high clinical suspicion based on symptoms for PE). Observational studies that enrolled fewer than 750 subjects were excluded because numerous RCTs in this literature base enroll over 500 participants, with the most contemporary trials enrolling over 1,000 participants. Therefore observational studies would need to be of larger size to provide additional valuable information on outcomes of interest and applicability. Additional inclusion criteria were used specific to each KQ and are stated below.

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Treatments for Fibromyalgia in Adult Subgroups


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Statistics: 75 Studies, 12 Key Questions, 8 Extraction Forms,
Date Published: Jul 23, 2015 02:44PM
Description: We conducted a systematic literature review of clinical trials to assess the comparative effectiveness of treatments for fibromyalgia in subgroups of highly affected or clinically complex adults. We focused on patient subgroups rather than overall treatment effects to complement a large systematic review being conducted on fibromyalgia treatments at McMaster University.
Contributor(s): Mary L. Forte, Ph.D., D.C.;Mary Butler, Ph.D., M.B.A.;Katherine E. Andrade, M.P.H.;Ann Vincent, M.D.;John T. Schousboe, M.D., Ph.D.; and Robert L. Kane, M.D.
Funding Source: Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: Two investigators screened abstracts of identified references for eligibility (enrolled adults with fibromyalgia, examined treatment effects, had a control group, and assessed outcomes at least 3 months after treatment initiation). Full-text articles were reviewed to identify outcomes reporting for at least one adult subgroup: women, older or obese adults, individuals with coexisting mental health conditions, high severity or longer fibromyalgia duration, multiple medical comorbidities, or other chronic pain conditions. Primary outcomes included pain, symptom improvement, function, fatigue, sleep quality, participation, and health-related quality of life. We extracted data, assessed risk of bias of individual studies, and evaluated strength of evidence for each comparison and outcome.

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Treatments for Ankyloglossia and Ankyloglossia with Concomitant Lip-tie


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Statistics: 43 Studies, 6 Key Questions, 2 Extraction Forms,
Date Published: Jul 23, 2015 02:43PM
Description: Objectives. We systematically the reviewed the literature on surgical and nonsurgical treatments for infants and children with ankyloglossia and ankyloglossia and concomitant lip-tie. Data Sources. We searched MEDLINE (PubMed), PsycINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL®) and EMBASE (Excerpta Medica Database) as well as the reference lists of included studies and recent systematic reviews. We conducted the searches between September 2013 and May 2014. Review Methods. We included studies of interventions for ankyloglossia published in English. Two investigators independently screened studies against predetermined inclusion criteria and independently rated the quality of included studies. We extracted data into evidence tables and summarized them qualitatively. Results. We included 52 unique studies comprising six RCTs (three good, one fair, two poor quality), three cohort studies (all poor quality), 28 case series, 14 case reports, and one unpublished thesis. Most studies assessed the effects of frenotomy on breastfeeding-related outcomes. Four RCTs reported improvements in breastfeeding efficacy using either maternally reported or observer ratings, while two RCTs found no improvement with observer ratings. Although mothers consistently reported improved breastfeeding effectiveness after frenotomy, outcome measures were heterogeneous and short term. Future studies could provide additional data to confirm or change the measure of effectiveness; thus we consider the strength of the evidence (SOE; confidence in the estimate of effect) to be low at this time. Pain outcomes improved for mothers of frenotomized infants compared with control in one study of 6-day old infants but not in studies of infants a few weeks older. Given these inconsistencies and the small number of comparative studies and participants, the SOE is low for an immediate reduction in nipple pain. Three studies with significant limitations reported improvements in other feeding outcomes with frenotomy, and three poor quality studies reported some improvements in articulation but mixed results related to fluent speech. Three poor quality comparative studies noted some improvements in social concerns and gains in tongue mobility in treated participants. SOE for all of these outcomes is insufficient. SOE is moderate for minor and short-term bleeding following surgery and insufficient for other harms (reoperation, pain). Conclusions. A small body of evidence suggests that frenotomy may be associated with improvements in breastfeeding as reported by mothers, and potentially in nipple pain, but with small, short-term studies, inconsistently conducted, SOE is generally low to insufficient. Research is lacking on nonsurgical interventions as well as on outcomes other than breastfeeding.
Contributor(s): None Provided
Funding Source: Agency for Healthcare Research and Quality Contract No. 290-2012-00009-I
Methodology Description: None Provided

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Treatment To Prevent Fractures in Men and Women With Low Bone Density or Osteoporosis: Update of a 2007 Report [Entered Retrospectively]


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Statistics: 182 Studies, 5 Key Questions, 5 Extraction Forms,
Date Published: Jul 23, 2015 02:43PM
Description: Objectives: To update a 2007 systematic review on the effectiveness and safety of treatments to prevent fractures in persons with low bone density or osteoporosis and factors affecting adherence to these treatments, and to assess whether monitoring helps identify those most likely to benefit from treatment and the benefits of long-term treatment. Data Sources: MEDLINE®, Embase, the Cochrane Database of Systematic Reviews, and Clinical Trials.gov were searched from January 2005 through March 2011. Review Methods: After review by two investigators against predetermined inclusion/exclusion criteria, we included existing systematic reviews, randomized controlled clinical trials, and large observational studies, where appropriate, for assessment of treatment efficacy, safety, and adherence. Results: Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide reduce the risk of vertebral and nonvertebral fractures among postmenopausal women with osteoporosis. Ibandronate and raloxifene reduce the risk of vertebral but not nonvertebral fractures. Alendronate, risedronate, zoledronic acid, and denosumab prevent hip fractures among postmenopausal women with osteoporosis. Risedronate decreases the risk of vertebral and nonvertebral fracture among men with osteoporosis. Among those treated with glucocorticoids, fracture risk reduction was demonstrated for risedronate and alendronate compared to placebo; and for teriparatide compared to alendronate. Few studies have compared osteoporosis therapies head-to-head. Adherence to pharmacotherapy is poor in patients with osteoporosis, as with other chronic conditions. Many factors affect adherence to medications, including dosing frequency, side effects of medications, knowledge about osteoporosis, and cost. Age, prior history of fracture, and concomitant medication use do not appear to have an independent association with adherence. Dosing frequency appears to affect adherence: Adherence is improved with weekly compared to daily regimens, but evidence is lacking to show that monthly regimens improve adherence over that of weekly regimens. Decreased adherence to bisphosphonates is associated with less than optimal reduction in the risk of fracture. Insufficient evidence is available to make conclusions about how adherence to and persistence with newer osteoporosis therapies compare to that with bisphosphonates. Assessment of adverse effects finds that raloxifene is associated with an increased risk for pulmonary embolism and vasomotor flushing; and limited data support a possible association between bisphosphonate use and atypical subtrochanteric fractures of the femur. Evidence is limited on the utility of monitoring and long-term treatment. Conclusions: There is a high level of evidence that shows that fracture risk reduction is greatest in women with a diagnosis of osteoporosis and/or prevalent fractures. The level of evidence is low to moderate for fracture risk reduction in postmenopausal women with osteopenia and without prevalent fractures. The evidence is low for benefits of treatment for other populations, including men; for the benefits and risks of long-term treatment; and for the need (if any) for monitoring bone density; and mixed with regard to factors that influence adherence.
Contributor(s): Carolyn J. Crandall, MD, MS; Sydne J. Newberry, PhD; Allison Diamant, MD, MSHS; Yee-Wei Lim, MD, PhD; Walid F. Gellad, MD, MPH; Marika J. Suttorp, MS; Aneesa Motala, BA; Brett Ewing, MS; Beth Roth, MA; Roberta Shanman, MLS; Martha Timmer, MS; Paul G. Shekelle, MD, PhD.
Funding Source: The Agency for Healthcare Research and Quality (AHRQ)
Methodology Description: Search Strategy: Our basic search strategy used the National Library of Medicine’s Medical Subject Headings (MeSH) keyword nomenclature. Using the same basic search rules used for the original report (with the addition of several new terms for additional drugs), we searched MEDLINE® for the period from January 2005 through March 2011. We also searched Embase, the American College of Physicians (ACP) Journal Club database, the Cochrane controlled trials register, and relevant pharmacological databases. In searching for efficacy and effectiveness studies, we used terms for osteoporosis, osteopenia, low bone density, and the drugs listed in Key Question 1. In our search for the key adverse events (AE), we used terms for the AE and each of the drugs of interest. In our search for studies of adherence and persistence, we used terms for adherence and persistence and the drugs of interest. In all cases, both generic and trade names were used. In our search for studies on the effects of monitoring, we searched on terms related to monitoring and DXA in combination with the drugs of interest. For new drugs, we reviewed the list of excluded studies from the original report to retrieve articles that had been rejected on the basis of drugs that were now included within the scope of the update, to find studies prior to 2005. The search was not limited to English-language publications and not limited by study design (e.g., reports of randomized controlled trials (RCT), observational studies, systematic reviews). The texts of the major search strategies are given in Appendix A. To identify additional systematic reviews not captured in our primary search strategy, we also searched MEDLINE®, the Cochrane Database of Systematic Reviews, the websites of the National Institute for Clinical Excellence, and the NHA Health Technology Assessment Programme. We also manually searched the reference lists of review articles obtained as part of our search ("reference mining"). To augment those searches, the EPC’s Scientific Resource Center (SRC) conducted several "grey literature" searches, including a search of relevant trials in the NIH Clinical Trials database, the Web of Science, FDA Medwatch files, and Health Canada files. Study Selection: Each title list was screened separately by two reviewers with clinical training and experience in systematic review to eliminate obviously irrelevant titles. Abstracts were obtained for all selected titles. Full text articles were then obtained for all selected abstracts. The reviewers then conducted a second round of screening to ascertain which articles met the inclusion criteria and would go on to data abstraction. Selections at this stage were reconciled, and disagreements were settled by consensus (with the project leaders resolving remaining disagreements). During the second round of screening, we imposed inclusion criteria based on the particular Key Question(s) addressed by the study. For effectiveness/efficacy questions (Key Questions 1, 2, and 5), we accepted any abstracts that indicated the manuscript might include information on the treatment/prevention of osteoporotic fracture (but not bone density alone). Controlled clinical trials and large observational studies (N>1,000) that reported fracture outcomes for one or more of the drugs of interest were accepted for the efficacy analysis and went on to data extraction. Data Extraction: Study level details, such as population characteristics, comorbidities, inclusion and exclusion criteria, interventions, and outcomes assessed, were extracted and recorded onto specially designed forms.

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