Recently Published Projects

Objectives: Objective. To assess the comparative benefits and harms across three airway management approaches (bag valve mask [BVM], supraglottic airway [SGA], and endotracheal intubation [ETI]) by emergency medical services in the prehospital setting and how the benefits and harms differ based on patient characteristics, techniques, and devices. Data sources. We searched electronic citation databases (Ovid® MEDLINE®, CINAHL®, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus®) from 1990 to September 2020, reference lists, and posted a Federal Register notice request for data. Review methods. Review methods followed Agency for Healthcare Research and Quality Evidence-based Practice Center Program Methods guidance. Using pre-established criteria, studies were selected, dual reviewed, data abstracted, and evaluated for risk of bias. Meta-analyses using profile-likelihood random effects models were conducted when data were available from studies reporting on similar outcomes, with analyses stratified by study design, emergency type, and age. We qualitatively synthesized results when meta-analysis was not indicated. Strength of evidence (SOE) was assessed for primary outcomes (survival, neurological function, return of spontaneous circulation [ROSC], and successful advanced airway insertion [for SGA and ETI only]). Results. We included 99 studies (22 randomized controlled trials and 77 observational studies) involving 630,397 patients. Overall, we found few differences in primary outcomes when airway management approaches were compared. • For survival, there was moderate SOE for findings of no difference for BVM versus ETI in adult and mixed-age cardiac arrest patients. There was low SOE for no difference in these patients for BVM versus SGA and SGA versus ETI. There was low SOE for all three comparisons in pediatric cardiac arrest patients, and in adult trauma patients when BVM was compared with ETI. • For neurological function, there was moderate SOE for no difference for BVM compared with ETI in adults with cardiac arrest. There was low SOE for no difference in pediatric cardiac arrest for BVM versus ETI and SGA versus ETI. In adults with cardiac arrest, neurological function was better for BVM and ETI compared with SGA (both low SOE). • ROSC was only applicable in cardiac arrest. For adults, there was low SOE that ROSC was more frequent with SGA compared with ETI, and no difference for BVM versus SGA or BVM versus ETI. In pediatric patients there was also low SOE of no difference for BVM versus ETI and SGA versus ETI. • For successful advanced airway insertion, low SOE supported better first-pass success with SGA in adult and pediatric cardiac arrest patients and adult patients in studies that mixed emergency types. Low SOE also supported no difference for first-pass success in adult medical patients. For overall success, there was moderate SOE of no difference for adults with cardiac arrest, medical, and mixed emergency types. • While harms were not always measured or reported, moderate SOE supported all available findings. There were no differences in harms for BVM versus SGA or ETI. When SGA was compared with ETI, there were no differences for aspiration, oral/airway trauma, and regurgitation; multiple insertion attempts was better for SGA, and inadequate ventilation was better for ETI. Conclusions. The most common findings, across emergency types and age groups, was of no differences in primary outcomes when prehospital airway management approaches were compared. As most of the included studies were observational, these findings may reflect study design and methodological limitations. Due to the dynamic nature of the prehospital environment, the results are susceptible to indication and survival biases as well as confounding; however, the current evidence does not favor more invasive airway approaches. No conclusion was supported by high SOE for any comparison and patient group. This supports the need for high-quality randomized controlled trials designed to account for the variability and dynamic nature of prehospital airway management to advance and inform clinical practice, emergency medical services education and policy, and improve patient-centered outcomes.

Objectives: To evaluate the effectiveness and comparative effectiveness of opioid, nonopioid pharmacologic, and nonpharmacologic therapy in patients with specific types of acute pain, including effects on pain, function, quality of life, adverse events, and long-term use of opioids.

Objectives: Background: A 2014 review for the US Preventive Services Task Force (USPSTF) found antiviral therapy for hepatitis B virus (HBV) infection associated with improved intermediate outcomes, although evidence on clinical outcomes was limited. Purpose: To update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF. Data Sources: We utilized the 2014 review, searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020. Study Selection: Eligible studies included randomized controlled trials (RCTs) and cohort studies on the benefits and harms of screening versus no screening, and the yield of alternative screening strategies; RCTs on the effects of antiviral therapy versus placebo or no therapy and preferred versus nonpreferred therapies on intermediate outcomes, clinical outcomes, and harms; and cohort studies on clinical outcomes and on the association between intermediate outcomes following antiviral therapy and clinical outcomes. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): Fifty total studies (30 trials and 20 cohort studies) with a total of 94,168 participants were included; of these, 22 were added for this update. No study directly evaluated the effects of screening for HBV infection versus no screening on clinical outcomes, such as mortality, hepatocellular carcinoma, or cirrhosis. Screening strategies that focused on risk factors such as ever having immigrated from high prevalence countries plus demographic and behavioral risk factors would identify nearly all HBV infection cases. In one study (N=21,008), only screening immigrants from high HBV prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (N=2,972), antiviral therapy was associated with greater likelihood than placebo or no treatment for achieving intermediate outcomes, such as virologic suppression and hepatitis B e antigen or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virological suppression to 17 for hepatitis B e antigen seroconversion. Based on 12 trials (N=4,127), preferred (first-line) antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (N=4,809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (N=3,893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes, but were heterogeneous (hazards ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events versus placebo or no antiviral therapy. Limitations: Only English-language articles were included, clinical outcome data for antiviral therapies were limited, observational studies were included on effects of antiviral therapy on long-term clinical outcomes and the association between intermediate and clinical outcomes, and some studies were conducted in countries where the prevalence and natural history of HBV infection are different from the United States. Conclusions: There was no direct evidence for the clinical benefits and harms of HBV screening versus no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes. Research is needed to clarify effects of screening and subsequent interventions on clinical outcomes and to identify optimal screening strategies.

Objectives: Objectives. To evaluate the effectiveness and comparative effectiveness of pharmacologic and non-pharmacologic therapies for the acute treatment of episodic migraine in adults. Data source. MEDLINE, Embase, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, Scopus and various grey literature sources from database inception to April 24, 2020. Comparative effectiveness evidence about triptans and nonsteroidal anti-inflammatory drugs (NSAIDs) were extracted from existing systematic reviews. Review methods. We included randomized controlled trials (RCTs) and comparative observational studies that enrolled adults who received an intervention to acutely treat episodic migraine. Pairs of independent reviewers selected and appraised studies. Results. Data on triptans were derived from 186 RCTs summarized in 9 systematic reviews (101,276 patients, most studied was sumatriptan, followed by zolmitriptan, eletriptan, naratriptan, almotriptan, rizatriptan, and frovatriptan). Compared with placebo, triptans resolved pain at 2 hours and 1 day, and increased the risk of mild and transient adverse events (high strength of the body of evidence [SOE]). Data on NSAIDs were derived from 5 systematic reviews (13,214 patients, most studied was ibuprofen, followed by diclofenac and ketorolac). Compared with placebo, NSAIDs probably resolved pain at 2 hours and 1 day, and increased the risk of mild and transient adverse events (moderate SOE). For other interventions, we included 135 RCTs and 6 comparative observational studies (37,653patients). Compared with placebo, antiemetics (low SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE) and acetaminophen (moderate SOE) reduced acute pain. Opioids were evaluated in 15 studies (2,208 patients). Tramadol in combination with acetaminophen, butorphanol, meperidine, morphine and hydromorphone may reduce pain at 2 hours and 1 day, compared with placebo (low SOE). Some opioids may be less effective than some antiemetics or dexamethasone (low SOE). No studies evaluated instruments for predicting risk of opioid misuse, opioid use disorder or overdose, or evaluated risk mitigation strategies to be used when prescribing opioids for the acute treatment of episodic migraine. Calcitonin gene-related peptide (CGRP) receptor antagonists improved headache relief at 2 hours and increased the likelihood of being headache-free at 2 hours, at 1 day, and at 1 week (low to high SOE). Lasmiditan (the first approved 5-HT1F receptor agonist) restored function at 2 hours and resolved pain at 2 hours, 1 day, and 1 week (moderate to high SOE). Sparse and low SOE suggested possible effectiveness of dexamethasone, dipyrone, flunarazine, magnesium sulfate, octreotide, tezampanel, and tonabersat. Compared with placebo, several non-pharmacologic treatments may improve various measures of pain, including remote electrical neuromodulation (moderate SOE), magnetic stimulation (low SOE), acupuncture (low SOE), chamomile oil (low SOE), external trigeminal nerve stimulation (low SOE), and eye movement desensitization re-processing (low SOE). However, these interventions, including the noninvasive neuromodulation devices, have only been evaluated by single or very few trials. Conclusions. A number of acute treatments for episodic migraine exist with varying degrees of evidence for effectiveness and harms. Use of triptans, NSAIDs, antiemetics, dihydroergotamine, CGRP antagonists, and lasmiditan is associated with improved pain and function. The evidence base for many other interventions for acute treatment, including opioids, remains limited.

Objectives: Structured Abstract Objectives. To assess the comparative effectiveness and potential harms of cervical ripening in the outpatient setting (vs. inpatient, vs. other outpatient intervention) and of fetal surveillance when a prostaglandin is used for cervical ripening. Data sources. Electronic databases (Ovid® MEDLINE®, Embase®, CINAHL®, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) to July 2020; reference lists; and a Federal Register notice. Review methods. Using predefined criteria and dual review, we selected randomized controlled trials (RCTs) and cohort studies of cervical ripening comparing prostaglandins and mechanical methods in outpatient versus inpatient settings; one outpatient method versus another (including placebo or expectant management); and different methods/protocols for fetal surveillance in cervical ripening using prostaglandins. When data from similar study designs, populations, and outcomes were available, random effects using profile likelihood meta-analyses were conducted. Inconsistency (using I2) and small sample size bias (publication bias, if ≥10 studies) were assessed. Strength of evidence (SOE) was assessed. All review methods followed Agency for Healthcare Research and Quality Evidence-based Practice Center methods guidance. Results. We included 30 RCTs and 10 cohort studies (73% fair quality) involving 9,618 women. The evidence is most applicable to women aged 25 to 30 years with singleton, vertex presentation and low-risk pregnancies. No studies on fetal surveillance were found. The frequency of cesarean delivery (2 RCTs, 4 cohort studies) or suspected neonatal sepsis (2 RCTs) was not significantly different using outpatient versus inpatient dinoprostone for cervical ripening (SOE: low). In comparisons of outpatient versus inpatient single-balloon catheters (3 RCTs, 2 cohort studies), differences between groups on cesarean delivery, birth trauma (e.g., cephalohematoma), and uterine infection were small and not statistically significant (SOE: low), and while shoulder dystocia occurred less frequently in the outpatient group (1 RCT; 3% vs. 11%), the difference was not statistically significant (SOE: low). In comparing outpatient catheters and inpatient dinoprostone (1 double-balloon and 1 single-balloon RCT), the difference between groups for both cesarean delivery and postpartum hemorrhage was small and not statistically significant (SOE: low). Evidence on other outcomes in these comparisons and for misoprostol, double-balloon catheters, and hygroscopic dilators was insufficient to draw conclusions. In head to head comparisons in the outpatient setting, the frequency of cesarean delivery was not significantly different between 2.5 mg and 5 mg dinoprostone gel, or latex and silicone single-balloon catheters (1 RCT each, SOE: low). Differences between prostaglandins and placebo for cervical ripening were small and not significantly different for cesarean delivery (12 RCTs), shoulder dystocia (3 RCTs), or uterine infection (7 RCTs) (SOE: low). These findings did not change according to the specific prostaglandin, route of administration, study quality, or gestational age. Small, nonsignificant differences in the frequency of cesarean delivery (6 RCTs) and uterine infection (3 RCTs) were also found between dinoprostone and either membrane sweeping or expectant management (SOE: low). These findings did not change according to the specific prostaglandin or study quality. Evidence on other comparisons (e.g., single-balloon catheter vs. dinoprostone) or other outcomes was insufficient. For all comparisons, there was insufficient evidence on other important outcomes such as perinatal mortality and time from admission to vaginal birth. Limitations of the evidence include the quantity, quality, and sample sizes of trials for specific interventions, particularly rare harm outcomes. Conclusions. In women with low-risk pregnancies, the risk of cesarean delivery and fetal, neonatal, or maternal harms using either dinoprostone or single-balloon catheters was not significantly different for cervical ripening in the outpatient versus inpatient setting, and similar when compared with placebo, expectant management, or membrane sweeping in the outpatient setting. This evidence is low strength, and future studies are needed to confirm these findings.

Objectives: Objectives. To evaluate availability, effectiveness, and implementation of interventions for integrating palliative care into ambulatory care for U.S.-based adults with serious life-threatening chronic illness or conditions other than cancer and their caregivers We evaluated interventions addressing identification of patients, patient and caregiver education, shared decision-making tools, clinician education, and models of care. Data sources. We searched key U.S. national websites (March 2020) and PubMed®, CINAHL, and the Cochrane Central Register of Controlled Trials (through May 2020). We also engaged Key Informants. Review methods. We completed a mixed-methods review; we sought, synthesized, and integrated Web resources; quantitative, qualitative and mixed-methods studies; and input from patient/caregiver and clinician/stakeholder Key Informants. Two reviewers screened websites and search results, abstracted data, assessed risk of bias or study quality, and graded strength of evidence (SOE) for key outcomes: health-related quality of life, patient overall symptom burden, patient depressive symptom scores, patient and caregiver satisfaction, and advance directive documentation. We performed meta-analyses when appropriate. Results. We included 46 Web resources, 20 quantitative effectiveness studies, and 16 qualitative implementation studies across primary care and specialty populations. Various prediction models, tools, and triggers to identify patients are available, but none were evaluated for effectiveness or implementation. Numerous patient and caregiver education tools are available, but none were evaluated for effectiveness or implementation. All of the shared decision-making tools addressed advance care planning; these tools may increase patient satisfaction and advance directive documentation compared with usual care (SOE: Low). Patients and caregivers prefer advance care planning discussions grounded in patient and caregiver experiences with individualized timing. Although numerous education and training resources for non-palliative care clinicians are available, we were unable to draw conclusions about implementation, and none have been evaluated for effectiveness. Models for integrating palliative care were not more effective than usual care for improving health-related quality of life or patient depressive symptom scores (SOE: Moderate) and may have little to no effect on increasing patient satisfaction or decreasing overall symptom burden (SOE: Low), but models for integrating palliative care were effective for increasing advance directive documentation (SOE: Moderate). Multimodal interventions may have little to no effect on increasing advance directive documentation (SOE: Low) and other graded outcomes were not assessed. For utilization, models for integrating palliative care were not more effective than usual care for decreasing hospitalizations; we were unable to draw conclusions about most other aspects of utilization or cost and resource use. We were unable to draw conclusions about caregiver satisfaction or specific characteristics of models for integrating palliative care. Patient preferences for appropriate timing of palliative care varied; costs, additional visits, and travel were seen as barriers to implementation. Conclusions. For integrating palliative care into ambulatory care for serious illness and conditions other than cancer, advance care planning shared decision-making tools and palliative care models were the most widely evaluated interventions and may be effective for improving only a few outcomes. More research is needed particularly on identification of patients for these interventions; education for patients, caregivers, and clinicians; shared decision-making tools beyond advance care planning and advance directive completion; and specific components, characteristics, and implementation factors in models for integrating palliative care.

Objectives: Structured Abstract Objective. To understand the evidence base for care interventions for people living with dementia (PLWD) and their caregivers, and to assess the potential for broad dissemination and implementation of that evidence. Data sources. We searched Ovid Medline, Ovid Embase, Ovid PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials, nonrandomized controlled trials, and quasi-experimental designs published and indexed in bibliographic databases through March, 2020. Review methods. We searched for nondrug interventions targeting PLWD, their informal or formal caregivers, or health systems. Two investigators screened abstracts and full-text articles of identified references for eligibility. Eligible studies included randomized controlled trials and quasi-experimental observational studies enrolling people with Alzheimer’s disease or related dementias or their informal or formal caregivers. We extracted basic study information from all eligible studies. We assessed risk of bias, and summarized results for studies not judged to be NIH Stage Model 0 to 2 (pilot or small sample size studies) or to have high risk of bias. We grouped interventions into categories based on intervention target. Results. We identified 9217 unique references, of which 627 unique studies with an additional 267 companion articles were eligible. We classified interventions into 37 major categories. With few exceptions, we did not combine data quantitatively due to variability of interventions, comparison groups, outcomes measured, and study timing. Low-strength evidence shows that an intensive multicomponent intervention for informal caregiver support, with education, group discussion, in-home and phone support, and caregiver feedback (i.e. discrete adaptations of REACH II), may improve informal caregiver depression at 6 months. Low-strength evidence also shows that collaborative care models (i.e. Care Ecosystems or discrete adaptations of the ACCESS models) may improve quality of life for PLWD and health system-level markers, including improvements in guideline-based quality indicators and reducing emergency room visits. The literature does not allow for further determination of whether the very small to small average effects in quality of life applied to all enrolled PLWD or if larger effects were concentrated in an unidentified subgroup. For all other interventions and outcomes, we found the evidence insufficient to draw conclusions. Insufficient evidence does not mean that the intervention is determined to be of no value to PLWD or their caregivers. Rather, it means that due to the uncertainty of the evidence, we could not draw meaningful conclusions at this time. Conclusions. Despite hundreds of studies, very little evidence supports widespread dissemination of any general care approaches for PLWD or caregivers. This review demonstrates the need for larger, longer-term, and more rigorous studies of interventions.

Objectives: Structured Abstract Objective. To identify new information that updates findings from previous AHRQ and AUA funded reviews evaluating therapies for clinically localized prostate cancer (CLPC). Sources. Bibliographic databases (2013-January 2020); ClinicalTrials.gov; systematic reviews Methods. Controlled studies of CLPC (T1-T3a) treatments with duration ≥5 years for mortality and metastases and ≥1 year for quality of life and harms. Interventions included watchful waiting (WW), active surveillance or monitoring (AS, AM), androgen deprivation (AD), focal and whole gland therapies or combinations. We evaluated how patient and tumor characteristics modify treatment outcomes and how provider/hospital characteristics modify effectiveness of radical prostatectomy (RP) compared to other therapies. One investigator rated risk of bias (ROB), extracted data, and assessed certainty of evidence; a second checked accuracy. We analyzed English-language studies with low or medium ROB. We incorporated findings from RCTs identified in the 2014 AHRQ and 2016 AUA funded reviews if new RCTs provided information on the same intervention comparison. We derived thresholds defining “small”, “moderate” and “large” effect, summarize key findings from prior reviews and the impact of new research. Results. We identified 67 eligible references; 17 unique RCTs. Among clinically, rather than PSA detected CLPC, WW may increase overall and prostate-cancer mortality, and metastases versus RP at 20+ years. Urinary and erectile dysfunction were lower with WW versus RP. WW‘s effect on mortality may have varied by tumor risk and age but not by race, health status, comorbidities or PSA. AM probably results in little to no difference in overall or prostate-cancer mortality in PSA detected CLPC versus RP or EBR plus AD through 10 years regardless of tumor risk. Metastases were infrequent but slightly higher with AM. Harms were greater with RP than AM and mixed between EBR plus AD versus AM. 3D-Conformal EBR and AD plus low-dose-rate brachytherapy (BT) provided a small reduction in all-cause mortality versus 3D-CRT and AD but little to no difference on metastases. EBR plus AD versus EBR alone may have resulted in a small reduction in overall and prostate-cancer mortality and metastases in higher risk disease but may increase sexual harms. EBR plus initiating neoadjuvant AD versus EBR plus initiating concurrent AD may result in little to no difference in mortality at 12 years and genitourinary toxicity at 3 years. Conventionally fractionated EBR versus ultra-hypofractionated EBR may result in little to no difference in mortality and metastasis at 5 years and urinary and bowel toxicity at 2 years. Limited evidence suggested that AS results in fewer harms than photodynamic therapy and laparoscopic RP resulted in more harms than robotic-assisted RP. There was little to no information on long-term comparative effectiveness of other treatments. No studies evaluated WW or AS in screen detected CLPC or MRI for risk assessment or were conducted since effective pharmacologic therapies for advanced disease. No studies assessed provider or hospital factors of RP comparative effectiveness. Conclusions. RP reduces mortality versus WW in clinically detected CLPC but causes more harms. Effectiveness may be limited to younger men, those with intermediate risk disease and requires many years to occur. AM results in little to no mortality difference versus RP or EBR plus AD. EBR plus AD reduces mortality versus EBR alone in higher risk CLPC but may worsen sexual function. Adding low-dose-rate BT to 3D-Conformal EBR and AD may reduce mortality in higher risk CLPC. Little information exists on other treatments or the effects of patient, tumor and provider factors. Large, long-term RCTs in PSA-detected and MRI staged CLPC are needed.

Objectives: Objectives. To evaluate the effectiveness of autologous platelet-rich plasma (PRP) in individuals with lower extremity diabetic ulcers, lower extremity venous ulcers, and pressure ulcers. Data sources. MEDLINE, Embase, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, Scopus and various grey literature sources from database inception to June 11, 2020. Review methods. We included randomized controlled trials (RCTs) and comparative observational studies that compared PRP to any other wound care without PRP in adult patients. Pairs of independent reviewers selected and appraised studies. Meta-analysis was conducted when appropriate and the strength of evidence (SOE) was determined based on a priori plan. Results. We included 27 studies (22 randomized, 5 comparative observational studies, total of 1,796 patients). 15 studies enrolled patients with lower extremity diabetic ulcers, 11 enrolled patients with lower extremity venous ulcers, and 2 enrolled patients with pressure ulcers in any location. Followup after intervention ranged from no followup to 11 months. The available studies suffered from important limitations, such as inadequate description of offloading and wound care procedures, wound characteristics, platelet-rich plasma formulation techniques, concentration and volume; inadequate length of followup; and lack of stratification by comorbidities and other patient characteristics including older adults. Compared with management without PRP, PRP therapy increased complete wound closure or healing in lower extremity diabetic ulcers (RR: 1.20; 95% CI: 1.09 to 1.32, moderate SOE), shortened the time to complete wound closure, and reduced wound area and depth (low SOE), although Medicare-eligible older adults were underrepresented in the included studies. No significant changes were found in terms of wound infection, amputation, wound recurrence, or hospitalization. In patients with lower extremity venous ulcers, the SOE was insufficient to estimate an effect on critical outcomes, such as complete wound closure or time to complete wound closure. Similarly, evidence was insufficient to estimate an effect on any outcome in pressure ulcers. There was no statistically significant difference in death, total adverse events or serious adverse events between PRP and management without PRP. Conclusions. Autologous platelet-rich plasma based on moderate SOE increases complete wound closure or healing, and low SOE shortens healing time and reduces wound size in individuals with lower extremity diabetic ulcers. The evidence is insufficient to estimate an effect of autologous platelet-rich plasma on wound healing in individuals with lower extremity venous ulcers or pressure ulcers.

Objectives: It is required to determine KRAS mutation status in tumor before anti-EGFR therapy is given to patients with colorectal cancer. However, in some recurrent or metastatic colorectal cancer patients, tumor tissue is not available. As an alternative, KRAS mutation detection in cell-free DNA/liquid biopsy samples has been intensively studied using highly sensitive methods. The aim of this systemic review and meta-analysis was to investigate the accuracy of KRAS mutation detection in cell-free DNA sample from patients with colorectal cancer, compared to paired tissue sample.

Objectives: 12% of patients with AML harbor mutation at Isocitrate dehydrogenase enzyme (IDH).Mutations at these enzymes result in high level of R2 hydroxyglutarate which competes with 2-alpha-hydroxygluterate resulted in DNA and histone hypermethylation. DNA and histone hypermethylation inhibits cell differentiation and promotes leukemic transformation. Ivosidenib and Enasidenib are IDH inhibitors that promotes cell differentiation and showed promising activity in phase1 and 2 trials in relapse/refractory AML patients and in elderly patients who are not candidate for traditional induction regimens. In this systematic review and meta-analysis, we intend to integrate the results of phase1 and 2 trials that looked at the efficacy and the side effects of IDH inhibitor. Therefore,we will have a clearer picture regarding the efficacy and side effect of these medications.

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Objectives: A review of the evidence about screening for bacterial vaginosis during pregnancy to prevent preterm delivery.

Objectives: Background: A U.S. Preventive Services Task Force (USPSTF) report found no consistent evidence that counseling interventions are effective at reducing drug use or improving other health outcomes in populations whose drug use was identified through primary care-based screening with questions about drug use or drug-related risks (i.e., “screen-detected populations”). Evidence from studies of persons seeking or referred for treatment for substance use or with clinical signs or symptoms of substance use (i.e., “treatment-seeking populations”) might also be useful for informing assessments regarding screening in primary care settings. Purpose: This report updates a 2008 USPSTF report on screening for illicit drug use and supplements an updated USPSTF report on screening for any drug use, focusing on the benefits and harms of pharmacotherapy and psychosocial interventions for persons whose drug use was identified when seeking substance use treatment, when presenting with signs or symptoms of drug use, when screened for drug use in primary care or other settings with questions about drug use or drug-related risks, or other means. Data Sources: The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Ovid MEDLINE, Embase, and PsycINFO from inception to September 2018; surveillance for new literature was conducted through November 22, 2019. Study Selection: We included trials of Food and Drug Administration (FDA)-approved pharmacotherapies for opioid use disorder (methadone, buprenorphine, and naltrexone) and trials of psychosocial interventions for persons engaging in opioid, stimulant, cannabis, and mixed drug or polysubstance use. We also included trials of preemptive prescribing of naloxone in primary care settings as a rescue medication for opioid-related overdose. Trials compared included interventions against placebo, a minimal intervention, waitlist control, or usual care, and evaluated outcomes at >3 months for drug use or other risky behaviors; health, social, and legal consequences of drug use; or harms of treatment. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): We included a total of 71 trials, with 19 trials of pharmacotherapies and 52 trials of psychosocial interventions. All trials of pharmacotherapies and 25 trials of psychosocial interventions were conducted in treatment-seeking populations. Psychosocial interventions commonly incorporated cognitive-behavioral or motivational interventions and ranged from brief interventions consisting of one or two sessions of no more than one hour to multiple treatment sessions over weeks or months. In most pharmacotherapy trials, drug use counseling was provided to all patients. No study evaluated benefits or harms of preemptive naloxone prescribed in primary care settings versus placebo or no naloxone as a rescue medication for opioid-related overdose. In treatment-seeking populations with opioid use disorder, naltrexone (12 trials; relative risk [RR] 0.73, 95% confidence interval [CI] 0.62 to 0.85; number needed to treat [NNT] 5.3) and opioid agonist therapy with methadone or buprenorphine (4 trials; RR 0.75, 95% CI 0.59 to 0.82; NNT 2.9) were associated with decreased risk of drug use relapse compared with placebo or no pharmacotherapy. Naltrexone and methadone/buprenorphine therapy were also associated with increased likelihood of retention in substance use treatment (9 trials; RR 1.71, 95% CI 1.13 to 2.49; NNT 6.7 and 7 trials; RR 2.58, 95% CI 1.78 to 4.59; NNT 2.6; respectively). Evidence on harms of pharmacotherapies was limited, but indicated no increased risk of serious adverse events. Psychosocial interventions were associated with increased likelihood of abstinence from drug use versus control conditions at 3 to 4 months (15 trials, RR 1.60, 95% CI 1.24 to 2.13; NNT 11) and at 6 to 12 months (14 trials; RR 1.25, 95% CI 1.11 to 1.52; NNT 17), based on trials primarily conducted in treatment-seeking populations. Psychosocial interventions were also associated with a greater decrease versus control conditions in the number of drug use days (19 trials; mean difference -0.49 day in the last 7 days, 95% CI -0.85 to -0.13) and a small but statistically significant greater decrease in drug use severity (16 trials; standard mean difference -0.18, 95% CI -0.32 to -0.05) at 3- to 4-month followup. There was no difference between psychosocial interventions versus controls on drug use days or severity at longer (6 to 12 month) followup. Effects of psychosocial interventions were generally stronger in trials of treatment-seeking than screen-detected populations, trials that evaluated cannabis use than other types of drug use, and trials of more intensive than brief interventions. Few trials evaluated effects of psychosocial interventions for opioid or stimulant use, and estimates were imprecise. Limitations: Limitations included restriction to English-language articles, statistical heterogeneity in pooled analyses, and little evidence on drug-related health, social, or legal outcomes; most trials had methodological limitations. Evidence was lacking on effectiveness of treatments for opioid use disorder related to prescription drug use or stimulant use and evidence was limited for adolescents or pregnant persons. Conclusions: Pharmacotherapy and psychosocial interventions are effective at improving drug use outcomes, but evidence of effectiveness remains primarily derived from trials conducted in treatment-seeking populations. Although the applicability of data from such trials to persons whose drug use is identified through primary care-based screening is uncertain, intervention trials that enrolled patients based on screening identified a spectrum of drug use, ranging from mild drug use to more severe, untreated disease. The applicability of current evidence on drug use interventions to screening might be greater for the subset of patients screened in primary care settings with severe, untreated drug use who could utilize pharmacotherapies or more intensive psychosocial interventions.

Objectives: This Technical Brief identifies the components that comprise asthma self-management education (AS-ME) packages used in the United States, and examines, compares, and organizes their key characteristics and available research to enable a better understanding of current practice and future needs.

Objectives: Technical brief for AHRQ on the evidence for whether PGHD devices and apps improve health outcomes for chronic conditions

Objectives: To address the comparative effectiveness of various types of face masks in healthcare workers and in the community and to address the effectiveness and safety of mask reuse. Surveillance Report, July 20, 2020 Version 2, June 24, 2020 Version 1, June 18, 2020

Objectives: The purpose of this review is to determine if hydroxychloroquine or chloroquine is effective and safe when used alone or when combined with azithromycin for the prophylaxis and treatment of COVID-19.

Objectives: To evaluate the effectiveness and comparative effectiveness of nonopioid pharmacologic agents in patients with specific types of chronic pain, considering the effects of on pain, function, quality of life, and adverse events.

Objectives: Systematic review to describe skin substitute products commercially available in the United States used to treat chronic wounds, examine systems used to classify skin substitutes, identify and assess randomized controlled trials (RCTs), and suggest best practices for future studies.

Objectives: Structured Abstract Objectives. We updated the evidence from our 2018 report assessing persistent improvement in outcomes following completion of therapy for noninvasive nonpharmacological treatment for selected chronic pain conditions. Data sources. Electronic databases (Ovid MEDLINE®, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews), through November 2017 (for priorAHRQreport) and from September 2017 through September 2019 (for this update report), reference lists, ClinicalTrials.gov, and our previous report. Review methods. Using predefined criteria, we selected randomized controlled trials (RCTs) of noninvasive nonpharmacological treatments for five common chronic pain conditions (chronic low back pain; chronic neck pain; osteoarthritis of the knee, hip, or hand; fibromyalgia; and tension headache) that reported results for a at least 1 month postintervention. We analyzed effects and assessed strength of evidence (SOE) at short term (1 to <6 months following treatment completion), intermediate term (≥6 to <12 months), and long term (≥12 months).Results. We included 233 RCTs (31 new to this update). Many were small (N<70), and evidence beyond 12 months after treatment completion was sparse. The most common comparison was with usual care. Evidence on harms was limited, with no evidence suggesting increased risk for serious treatment-related harms for any intervention. Effect sizes were generally small for function and pain. Chronic low back pain: Psychological therapies were associated with small improvements compared with usual care or an attention control for both function and pain at short-term, intermediate-term, and long-term followup (SOE: moderate). Function improved over short and/or intermediate term for exercise, low-level laser therapy, spinal manipulation, massage, yoga, acupuncture, and multidisciplinary rehabilitation (SOE moderate at short term for exercise, massage, and yoga; low for all others). Improvements in pain at short term were seen for massage, mindfulness-based stress reduction, acupuncture,and multidisciplinary rehabilitation (SOE: moderate), and exercise, low-level laser therapy, and yoga (SOE: low). At intermediate term, spinal manipulation, yoga, multidisciplinary rehabilitation (SOE: moderate) and exercise and mindfulness-based stress reduction (SOE: low) were associated with improved pain. Compared with exercise, multidisciplinary rehabilitation improved both function and pain at short and intermediate terms (small effects, SOE: moderate.) Chronic neck pain: In the short-term, low-level laser therapy (SOE: moderate) and massage (SOE: low) improved function and pain. Exercise in general improved function long term, and combination exercise improved function and pain both short and long term compared with usual care (SOE: low). Acupuncture improved function short and intermediate term, but there was no pain improvement compared with sham acupuncture (SOE: low). Compared with acetaminophen, Pilates improved both function and pain (SOE: low). Osteoarthritis pain: Exercise resulted in small improvements in function and pain at short-term(SOE: moderate) and long-term, and moderate improvement at intermediate-term (SOE: low) followup for knee osteoarthritis versus nonactive comparators. Small improvements in function and pain with exercise were seen for hip osteoarthritis short term (SOE: low). Functional improvement persisted into intermediate term, but pain improvement did not (SOE: low). Fibromyalgia: Functional improvements were seen with exercise, mind-body practices, multidisciplinary rehabilitation (SOE: low) and acupuncture (SOE: moderate) short term compared with usual care, attention control, or sham treatment. At intermediate term, there was functional improvement with exercise and acupuncture (SOE: moderate), cognitive-behavioral therapy (CBT), mindfulness-basdedstress reduction, myofascial release,and multidisciplinary rehabilitation (SOE: low). LLong term, functional improvements persisted for multidisciplinary rehabilitation without improvement in pain (SOE: low). Compared with exercise, tai chiconferred improvement in function short and intermediate term (SOE: low). Pain was improved with exercise (short and intermediate term, SOE moderate), and for CBT (shortterm),mindfulness practices,and multidisciplinary rehabilitation (MDR) (intermediate term)(SOE lowfor these three). Chronic tension headache: Evidence was sparse and the majority of trials were of poor quality. Spinal manipulation resulted in moderate improvement in pain short term. Conclusions. Trials identified subsequent to the earlier report largely support previous findings, —namely that exercise, multidisciplinary rehabilitation, acupuncture, CBT, mindfulness practices, massage,and mind-body practices most consistently improve function and/or pain beyond the course of therapy for specific chronic pain conditions. Additional research, including comparisons with pharmacological and other active controls, on effects beyond the immediate post-treatment period is needed, particularly for conditions other than low back pain

Objectives: To assess the effectiveness and harms of opioid therapy for chronic noncancer pain; alternative opioid dosing strategies; and risk mitigation strategies

Objectives: Structured Abstract Background: Interventions to discourage use of tobacco products among children and adolescents may help decrease tobacco-related illness. Tobacco products for this review include electronic nicotine delivery systems, often referred to as e-cigarettes. Purpose: To systematically update the 2013 U.S. Preventive Services Task Force (USPSTF) review on primary care relevant interventions for tobacco use prevention and cessation in children and adolescents. Data Sources: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, PsycINFO, and EMBASE (September 1, 2012 to June 25, 2019) with surveillance through February 7, 2020. Study Selection: We selected primary care relevant studies based on inclusion and exclusion criteria developed for each key question. We included randomized and nonrandomized controlled trials of children and adolescents up to 18 years of age for cessation and 25 years of age for prevention. Trials that compared behavioral or pharmacological interventions with a no or minimal smoking intervention control group (e.g., usual care, attention control, wait list) were included. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): Twenty-six trials met inclusion criteria. Behavioral interventions were associated with decreased likelihood of smoking initiation compared with control interventions (k=13, n=21,700; 7.4% vs. 9.2%; relative risk [RR] 0.82, 95% confidence interval [CI] 0.73 to 0.92). In trials restricted to smokers, behavioral interventions had no effect on smoking prevalence (k=9, n=2,516, 80.7% vs. 84.1% continued smoking, RR 0.97, 95% CI, 0.93 to 1.01). Behavioral interventions were more effective than control interventions at decreasing smoking prevalence in trials of smokers and nonsmokers (k=7, n=10,533; 16.8% vs. 20.1%; RR 0.91, 95% CI, 0.83 to 0.995). However, these results were sensitive to inclusion of two trials of very intensive interventions. Two trials of bupropion and one trial of nicotine replacement therapy found no significant benefits of medication on likelihood of smoking cessation. One trial each found no evidence for a beneficial intervention effect on health outcomes or on adult smoking. Limitations: Few trials addressed the prevention or cessation of tobacco products other than cigarettes; no trials evaluated effects of interventions on e-cigarette use. Trials of pharmacotherapy were few and had small sample sizes. Conclusions: Behavioral interventions can reduce the likelihood of smoking initiation in nonsmoking youth and young adults. Research is needed to identify effective behavioral interventions for youth who smoke or who use other tobacco products and to understand the effectiveness of pharmacotherapy on cessation. Due to the rapid escalation of e-cigarette use among youth, both prevention and cessation trials that target and/or include e-cigarettes are imminently needed.

Objectives: Background: Prior reviews on hepatitis C (HCV) infection screening and treatment used by the U.S. Preventive Services Task Force (USPSTF) to inform its 2013 recommendation found interferon-containing antiviral therapies associated with sustained virologic response (SVR) rates of 68 percent to 78 percent and an association between SVR after antiviral therapy and improved clinical outcomes. Interferon-containing regimens were associated with a high rate of harms. Since the prior reviews, interferon-containing antiviral therapies have been replaced by all-oral direct acting antiviral (DAA) regimens. Purpose: To systematically review the evidence on screening for HCV infection in asymptomatic adults and adolescents, including effects of DAA regimens and interventions to prevent mother-to-child transmission. Data Sources: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Ovid MEDLINE and ClinicalTrials.gov through February 2019, manually reviewed reference lists, and conducted literature surveillance through November 22, 2019. Study Selection: Randomized controlled trials (RCTs), non-randomized trials, and cohort studies of HCV screening, antiviral therapy, and interventions to prevent mother-to-child transmission of HCV infection on SVR and clinical outcomes; and cohort studies on the association between an SVR after antiviral therapy versus no SVR and clinical outcomes. Treatment studies focused on populations without cirrhosis who are more likely to be asymptomatic and identified by screening. Data Extraction: One investigator abstracted data, and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): No study evaluated the benefits of HCV screening versus no screening, or the yield of repeat versus one-time screening. Previously reviewed studies found that HCV screening might be associated with negative psychological and social consequences, but had important methodological limitations; no new studies were identified. One new study found similar diagnostic yield of risk-based and birth cohort screening, but it was retrospective and assumed perfect implementation of risk-based screening. Ten trials reported improvements in some quality of life and functional outcomes following DAA treatment compared with prior to treatment, but differences were small, studies were open-label, and there was no non-DAA comparison group. Forty-nine trials found DAA regimens associated with pooled SVR rates that ranged from 95.5 percent to 98.9 percent across genotypes; rates of serious adverse events (1.9%) and withdrawal due to adverse events (0.4%) were low. Seven trials reported SVR rates in adolescents with DAA therapy similar to those observed in adults. An SVR after antiviral therapy was associated with decreased risk of all-cause mortality (13 studies, pooled hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.28 to 0.56), liver mortality (4 studies, pooled HR 0.11, 95% CI, 0.04 to 0.27), cirrhosis (4 cohorts in 3 studies, pooled HR 0.36, 95% CI, 0.33 to 0.40), and hepatocellular carcinoma (20 studies, pooled HR 0.29, 95% CI, 0.23 to 0.38) versus no SVR, after adjustment for potential confounders. New evidence on interventions to reduce the risk of mother-to-infant transmission was limited and did not change the conclusion from the prior review that no intervention has been clearly demonstrated to reduce risk. Limitations: Most DAA trials were not randomized and did not have a non-DAA comparison group, almost all DAA trials relied on SVR as the main efficacy outcome, observational studies varied in how well they adjusted for confounders, and few studies evaluated the effectiveness of DAA regimens in adolescents. Conclusions: The USPSTF previously determined that HCV screening is highly accurate. Currently recommended all-oral DAA regimens are associated with very high SVR rates (95.5% to 98.9% across genotypes) and few harms relative to older antiviral therapies. An SVR after antiviral therapy is associated with improved clinical outcomes compared with no SVR, after adjusting for potential confounders. Direct evidence on the benefits of HCV screening remains unavailable, and direct evidence on the effects of antiviral therapy on clinical outcomes remains limited but indicates improved long-term outcomes.

Objectives: A systematic review to assess the efficacy and comparative effectiveness of pharmacological interventions for pregnant and postpartum women with psychiatric disorders.

Objectives: Objective: In view of the development of hypoglycemic agents in recent years and the growth in the number of people with type 2 diabetes mellitus(T2DM), latest information is needed for clinicians and patients to make more reliable decisions. The objective of this systematic review database is to compare and summarize the effects of the current three new types of hypoglycemic agents: dipeptidyl peptidase-4 inhibitors (DPP-4Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-dependent glucose transporter 2 inhibition SGLT-2Is on outcomes of effectiveness, safety and economy. Methods: We searched the PubMed, Embase and Cochrane Library databases for original English-language articles, and collected unpublished studies’ data from clinicaltrial.org and other sources,we also manually search reference list of review literatures and grey literatures. We included all randomized controlled trials (RCTs) that any one of the three new types of hypoglycemic drugs (DPP-4Is, GLP-1RAs or SGLT-2Is) was applied in at least one comparative group in the RCT, alone or combined with other drugs. The searching process is now updated to March 2019, and will be updated every 1-2 years. Results: The numbers of RCTs we found completed and have reported outcomes were as follow: DPP-4Is 414, GLP-1RAs 338, SGLT-2Is 307. The total number of these literatures were 1059. After removing the duplicate literatures between the three types of hypoglycemic drugs, the total number of studies included in this systematic review database is now 930. The most common control group is placebo in this literature warehouse now. Other hypoglycemic drugs are also be compared as control, including: Biguanide, Sulfonylureas, Thiazolidinedione, Alpha-glucosidase inhibitor, insulin preparations, etc. Meanwhile, there are also comparisons between or within the three new types of hypoglycemic drugs. Significance: Till today, the existing results of original researches on the effectiveness and safety of three type of hypoglycemic drugs are diverse, and related systematic reviews are still incomplete. For example, study had shown that SGLT-2Is improve cardiovascular function in T2DM patients with coronary artery disease or chronic kidney dysfunction compared to DPP-4Is; DPP-4Is(sitagliptin)may exert a less potent effect on HbA1C, FPG, PPG, and weight reduction than GLP-1 receptor agonists in obese or overweight patients; There are also differences between different drugs in one single type. Observing the effects of hypoglycemic drugs requires studies with large samples and long term observation. Therefore, better evidences are needed to provide a compelling reason for their use in different situations and different population subgroups. A network evidence set of the three types of new hypoglycemic drugs can be constructed based on all the RCTs in this constantly updated database. With the help of real-world research partners, in-depth discussion on the differences of the three types of new hypoglycemic drugs in a single outcome (effectiveness, safety and economy) and multiple comprehensive outcomes can be conducted by network meta-analysis and IPD meta-analysis. After evaluating the quality of these above evidences, further summaries and recommendations can be made combining with the benefit-risk relationship based on different decision-making scenarios and expert opinions. We hope that more comprehensive and multi-dimensional evidences of the comparison of the three types of new hypoglycemic drugs will be obtained through this evidence-based evaluation research. These evidences will provide more reliable basis for clinicians when making decisions, provide reference for guideline makers and regulatory decision-making departments. It will enhance the accuracy and confidence when we make decisions, and actually bring the greatest health benefits to patients with T2DM, which also provide a reference for the evaluation of other drugs.

Objectives: The review aims to inform health care providers, policymakers, and a clinical practice guideline update from the American Academy of Child and Adolescent Psychiatry (AACAP) about the currently available evidence on interventions for adolescents to reduce or cease substance use. The review addresses both behavioral and pharmacological interventions used for adolescents or young adults with problematic substance use or a diagnosis of a substance use disorder (SUD), excluding tobacco.

Objectives: This systematic review will assess the prevention and treatment of primary headache during pregnancy, postpartum, and breastfeeding.

Objectives: Purpose of the Review The American College of Physicians (ACP) nominated the topic of management of acute diverticulitis to the Agency for Healthcare Research and Quality for systematic review. 45, 46 The ACP develops guidelines based on the needs of its members and the internal medicine community.47 The scope of the current systematic review was developed to support the ACP in its effort to create a new clinical practice guideline that will address diagnosis and staging of acute diverticulitis, nonsurgical treatment of acute diverticulitis, colorectal cancer screening in people with a history of diverticulitis, and interventions to prevent recurrence of acute diverticulitis. Specifically, (1) the systematic review will summarize existing systematic reviews on the test accuracy of CT imaging for diagnosis and staging of acute diverticulitis and conduct a de novo review of harms related to false positive, false negative, and incidental findings on CT imaging for suspected acute diverticulitis; (2) it will address effectiveness, comparative effectiveness, and harms of hospitalization for acute uncomplicated diverticulitis, antibiotics use for acute complicated or uncomplicated diverticulitis, and interventional radiology techniques for acute complicated diverticulitis; (3) it will review the benefits and harms of colonoscopy in people with a history of diverticulitis; and (4) it will evaluate pharmacologic, nonpharmacologic, and elective surgical interventions to prevent recurrent diverticulitis. Of note, this review will not evaluate the need for, or the choice of, surgery for the patient with acute diverticulitis. The intended audience includes guideline developers, clinicians and other providers of care for patients with diverticulitis, healthcare policy makers, and patients.

Objectives: Background: Medications to reduce breast cancer risk are an effective prevention intervention for women at increased risk, although medications also cause adverse effects. Purpose: To update the 2013 U.S. Preventive Services Task Force (USPSTF) systematic review on the use of medications to reduce the risk of primary breast cancer. Data Sources: Searches included the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE (January 1, 2013 to February 1, 2019); and manual review of reference lists. Studies published before 2013 were identified from prior systematic reviews for the USPSTF. Study Selection: Discriminatory accuracy studies of breast cancer risk assessment methods; double-blind, placebo-controlled or head-to-head randomized controlled trials (RCT) of tamoxifen, raloxifene, and aromatase inhibitors for primary prevention of breast cancer that enrolled women without preexisting breast cancer; and RCTs and observational studies of harms of medications. Data Extraction: One investigator abstracted data on study methods; setting; population characteristics; eligibility criteria; interventions; numbers enrolled and lost to followup; method of outcome ascertainment; and results for each outcome and a second investigator checked abstractions for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): Eighteen risk models evaluated in 25 studies had generally low discriminatory accuracy in predicting the probability of breast cancer in an individual (c-statistics 0.55 to 0.65). Most models performed only slightly better than age alone as a risk predictor. No studies evaluated optimal ages or frequencies of risk assessment. In placebo-controlled trials, tamoxifen (risk ratio [RR] 0.69; 95% confidence interval [CI], 0.59 to 0.84; 7 fewer cases per 1000 women over 5 years of use [95% CI, 4 to 12]; 4 trials), raloxifene (RR 0.44; 95% CI, 0.24 to 0.80; 9 fewer cases [95% CI, 3 to 15]; 2 trials), and the aromatase inhibitors exemestane and anastrozole (RR 0.45; 95% CI, 0.26 to 0.70; 16 fewer cases [95% CI, 8 to 24]; 2 trials) reduced invasive breast cancer. Risk for invasive breast cancer was higher for raloxifene than tamoxifen in the Study of Tamoxifen And Raloxifene (STAR) head-to-head trial (RR, 1.24; 95% CI, 1.05 to 1.47) after long-term followup. Effects did not differ by age of initiation or duration of use (3 to 5 years), although these effects were not directly compared. Risk reduction persisted at least 8 years after discontinuation in tamoxifen trials with long-term followup. All medications reduced estrogen receptor positive, but not estrogen receptor negative invasive breast cancer; tamoxifen reduced noninvasive cancer in two trials; and breast-cancer specific and all-cause mortality were not reduced. In placebo-controlled trials, raloxifene (RR 0.61; 95% CI, 0.53 to 0.73; 2 trials) reduced vertebral fractures; tamoxifen reduced nonvertebral fractures in the National Surgical Adjuvant Breast and Bowel Project (NSABP P-1) trial (RR 0.66; 95% CI, 0.45 to 0.98); while the aromatase inhibitors had no effect on fractures. Tamoxifen and raloxifene had similar effects on reducing fractures at multiple vertebral and nonvertebral sites in the STAR head-to-head trial. In placebo-controlled trials, tamoxifen (RR 1.93; 95% CI, 1.33 to 2.68; 4 trials) and raloxifene (RR 1.56; 95% CI, 1.11 to 2.60; 2 trials) increased thromboembolic events, while aromatase inhibitors did not. Raloxifene caused fewer thromboembolic events (RR 0.75; 95% CI, 0.60 to 0.93) than tamoxifen in the STAR head-to-head trial. Tamoxifen, raloxifene, and aromatase inhibitors did not increase coronary heart disease events or strokes. In placebo-controlled trials, tamoxifen increased endometrial cancer (RR 2.25; 95% CI, 1.17 to 4.41; 3 trials), while raloxifene and aromatase inhibitors did not. In the STAR head-to-head trial, raloxifene caused fewer cases of endometrial cancer (RR 0.55; 95% CI, 0.36 to 0.83) and endometrial hyperplasia (RR 0.19; 95% CI, 0.12 to 0.29), and fewer hysterectomies (RR 0.45; 95% CI, 0.37 to 0.54) than tamoxifen. Tamoxifen increased cataracts (RR 1.22; 95% CI, 1.08 to 1.48; 3 trials) and cataract surgery compared with placebo, while raloxifene and aromatase inhibitors did not. Risks for thromboembolic events and endometrial cancer with tamoxifen were higher for older compared with younger women and returned to normal after discontinuation. All medications caused adverse effects, such as vasomotor or musculoskeletal symptoms, that varied by medication. Risks for invasive cancer were generally reduced in all population subgroups evaluated based on menopausal status (pre and postmenopausal); family history of breast cancer; body mass index categories; modified Gail model risk categories; and age at menarche, parity, or age at first live birth, although results varied. Tamoxifen and anastrozole had larger effects in reducing invasive breast cancer in women with previous breast lesions (lobular carcinoma in situ, atypical ductal hyperplasia, or atypical lobular hyperplasia). Limitations: Trials were limited by clinical heterogeneity related to different medications, exposure durations, eligibility criteria, adherence, and ascertainment of outcomes. No trials compared timing and duration directly. Long-term followup data were lacking from most trials, and followup was particularly short for the aromatase inhibitors. Trials were not designed for subgroup comparisons and analysis of differences may be underpowered. Conclusions: Tamoxifen, raloxifene, and the aromatase inhibitors exemestane and anastrozole reduce invasive breast cancer in women without preexisting breast cancer, but also cause adverse effects that vary by medication. Tamoxifen and raloxifene increase thromboembolic events and tamoxifen increases endometrial cancer and cataracts. Identifying candidates for therapy is complicated by risk stratification methods that demonstrate low accuracy.

Objectives: Background: Pathogenic mutations in breast cancer susceptibility genes BRCA1 and BRCA2 increase risks for breast, ovarian, fallopian tube, and peritoneal cancer in women; interventions reduce risk in mutation carriers. Purpose: To update the 2013 U.S. Preventive Services Task Force review on benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA1/2-related cancer in women. Data Sources: Cochrane libraries; MEDLINE, PsycINFO, EMBASE (January 1, 2013 to March 6, 2019 for updates; January 1, 1994 to March 6, 2019 for new key questions and populations); reference lists. Study Selection: Discriminatory accuracy studies, randomized controlled trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer. Data Extraction: Data on study methods; setting; population characteristics; eligibility criteria; interventions; numbers enrolled and lost to followup; outcome ascertainment; and results were abstracted. Two reviewers independently assessed study quality. Data Synthesis (Results): 103 studies (110 articles) were included. No studies evaluated the effectiveness of risk assessment, genetic counseling, and genetic testing in reducing incidence and mortality of BRCA1/2-related cancer. Fourteen studies of 10 risk assessment tools to guide referrals to genetic counseling demonstrated moderate to high accuracy (area under the receiver operating characteristic curve 0.68 to 0.96). No studies determined optimal ages, frequencies, or harms of risk assessment. Twenty-eight studies indicated genetic counseling is associated with reduced breast cancer worry, anxiety, and depression; increased understanding of risk; and decreased intention for testing. A RCT showed that population-based testing of Ashkenazi Jews detected more BRCA1/2 mutations than family-history based testing, while measures of anxiety, depression, distress, uncertainty, and quality of life were similar between groups; clinical outcomes were not evaluated. Twenty studies indicated breast cancer worry and anxiety were higher after testing for women with positive results and lower for others, and understanding of risk was higher. No RCTs evaluated the effectiveness of intensive screening for breast or ovarian cancer in mutation carriers. In observational studies, false-positive rates, additional imaging, and benign biopsies were higher with magnetic resonance imaging than mammography. In eight RCTs, tamoxifen (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.59 to 0.84; 4 trials), raloxifene (RR, 0.44 95% CI, 0.24 to 0.80; 2 trials), and aromatase inhibitors (RR, 0.45 95% CI, 0.26 to 0.70; 2 trials) were associated with lower risks of invasive breast cancer compared with placebo; results were not specific to mutation carriers. Adverse effects included venous thromboembolic events for tamoxifen and raloxifene; endometrial cancer and cataracts for tamoxifen; and vasomotor, musculoskeletal, and other symptoms for all medications. In observational studies, mastectomy was associated with 90 to 100 percent reduction in breast cancer incidence and 81 to 100 percent reduction in breast cancer mortality; oophorectomy or salpingo-oophorectomy was associated with 69 to 100 percent reduction in ovarian cancer; complications were common with mastectomy. Limitations: Including only English-language articles and studies applicable to the United States; varying number, quality, and applicability of studies; and few studies of untested women previously treated for BRCA1/2-related cancer. Conclusions: Risk assessment, genetic counseling, and genetic testing to reduce BRCA1/2-cancer incidence and mortality as a prevention service has not been directly evaluated by current research. Risk assessment with familial risk tools accurately identifies high-risk women for genetic counseling. Genetic counseling reduces breast cancer worry, anxiety, and depression; increases understanding of risk; and decreases intention for mutation testing, while testing improves accuracy of understanding of risk. The effectiveness of intensive screening is not known, but it increases false-positive results and procedures. Risk-reducing medications and surgery are associated with reduced breast and ovarian cancer, but also have adverse effects. Evidence gaps relevant to prevention remain and additional studies are needed to better inform clinical practice.

Objectives: To summarize research on achieving health equity in ten preventive services for cancer, cardiovascular disease, and diabetes in adults for a National Institutes of Health Pathways to Prevention Workshop by identifying the effects of impediments and barriers that create disparities and the effectiveness of interventions to reduce them.

Objectives: Background: A 2012 systematic review on HIV screening for the U.S. Preventive Services Task Force (USPSTF) found strong evidence that antiretroviral therapy (ART) is associated with improved clinical outcomes in persons with CD4+ T helper cell (CD4) counts less than 500 cells/mm3 and substantially decreases risk of HIV transmission, with certain antiretroviral agents potentially associated with long-term cardiovascular harms. The USPSTF previously found HIV screening tests to be highly accurate. Purpose: To systematically update the 2012 USPSTF review on screening for HIV in adolescents and adults, focusing on research gaps identified in the prior review. Data Sources: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and MEDLINE (2012 to June 2018) and manually reviewed reference lists, with surveillance through January 2019. Study Selection: Randomized, controlled trials (RCTs) and controlled observational studies on benefits and harms of screening versus no screening and on the yield of screening at different intervals; the effects of earlier versus later initiation of ART; and long-term (≥2 years) harms of ART. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): We did not identify any studies on benefits or harms of HIV screening versus no screening, or on the yield of repeat versus one-time screening or of screening at different intervals. Two new RCTs conducted completely or partially in low-resource settings found initiation of ART in persons with CD4 counts greater than 500 cells/mm3 associated with lower risk of composite clinical outcomes (mortality, AIDS-defining events, or serious non-AIDS events) (relative risk [RR], 0.44 [95% confidence interval (CI), 0.31 to 0.63] and RR, 0.57 [95% CI, 0.35 to 0.95]); early initiation of ART was not associated with increased risk of cardiovascular events. A large observational study also found initiation of ART in persons in high-resource settings with CD4 counts greater than 500 cells/mm3 to be associated with reduced risk of mortality or AIDS events, although the magnitude of effect was smaller. New evidence regarding the association between abacavir use and increased risk of cardiovascular events was inconsistent, and certain antiretroviral regimens were associated with increased risk of long-term neuropsychiatric, renal, hepatic, and bone adverse events. Limitations: Only English-language articles were included. Observational studies were included. Studies conducted in resource-poor settings were included, which might limit applicability to general screening in the United States. Conclusions: New evidence extends effectiveness of ART to asymptomatic persons with CD4 counts greater than 500 cells/mm3. Certain ART regimens may be associated with long-term cardiovascular, neuropsychiatric, hepatic, renal, or bone harms, but early initiation of ART is not associated with increased risk of cardiovascular events. Research is needed to inform optimal screening intervals.

Objectives: Structured Abstract Background: A 2012 systematic review on HIV screening for the U.S. Preventive Services Task Force (USPSTF) found strong evidence that antiretroviral therapy (ART) greatly decreases the risk of mother-to-child HIV transmission but that use of ART may be associated with increased risk of preterm delivery. The USPSTF previously found HIV screening tests to be highly accurate. Purpose: To systematically update the 2012 USPSTF review on HIV screening in pregnancy, focusing on research gaps identified in the prior review. Data Sources: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and MEDLINE (2012 to June 2018) and manually reviewed reference lists, with surveillance through January 25, 2019. Study Selection: We selected randomized, controlled trials (RCTs) and cohort studies of pregnant women that reported risk of mother-to-child transmission or maternal or infant harms associated with prenatal HIV screening or ART during pregnancy. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): We identified no studies on the benefits or harms of prenatal HIV screening versus no screening, or on the yield of repeat versus one-time screening or screening at different intervals. One new RCT and five new cohort studies were consistent with the 2012 USPSTF review in finding combination ART highly effective at reducing the risk of mother-to-child transmission of HIV infection, especially if started early in pregnancy (rate of mother-to-child transmission <1%). As in the prior USPSTF review, one new RCT and several observational studies found certain ART regimens associated with increased risk of preterm delivery without increased risk of low birth weight. One RCT conducted in Africa found prenatal tenofovir-based ART associated with very preterm delivery and early infant death versus zidovudine-based ART, but the trial had methodological limitations. Prenatal exposure to most currently recommended ART drugs was not associated with increased risk of overall birth defects, but limited evidence found certain ART agents and regimens associated with increased risk of congenital abnormalities, cardiac anomalies, and echocardiographic changes, with no association with adverse neurodevelopmental outcomes. Evidence on long-term maternal harms associated with short-term exposure to ART during pregnancy remains limited, with some evidence of short-term harms. Limitations: Only English-language articles were included. Observational studies were included. Studies conducted in resource-poor settings were included, which might limit applicability to screening in the United States. Conclusions: Combination ART is highly effective at reducing risk of mother-to-child HIV transmission. The USPSTF previously determined that avoidance of breastfeeding and Caesarean delivery in women with HIV ribonucleic acid levels greater than 1,000 copies/mL near the time of delivery is also effective at reducing mother-to-child transmission, and that prenatal screening is accurate at diagnosing HIV infection. Use of certain ART regimens during pregnancy is associated with increased risk of preterm delivery and may be associated with other adverse pregnancy outcomes. Although more evidence is required to better understand short- and long-term maternal and infant harms, selection of ART regimens may help mitigate or reduce harms.

Objectives: Background: Effective prevention strategies for HIV infection are an important public health priority. Pre-exposure prophylaxis (PrEP) involves use of antiretroviral therapy (ART) regularly (e.g., daily) or before and after HIV exposure events to decrease the risk of acquiring HIV infection. Purpose: To synthesize evidence for the U.S. Preventive Services Task Force (USPSTF) on effects of PrEP on risk of HIV acquisition, mortality, harms, and other clinical outcomes; effects of adherence on PrEP-associated outcomes; and accuracy of methods for identifying potential candidates for PrEP. Data Sources: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, and Embase from inception to June 2018 and manually reviewed reference lists; additional surveillance for new literature was conducted through January 25, 2019. Study Selection: Randomized, controlled trials on the benefits and harms of PrEP versus placebo or no PrEP in adults without HIV infection at high risk of becoming infected; studies on the diagnostic accuracy of instruments for predicting incident HIV infection; studies on effects of adherence to PrEP on risk of HIV infection; and studies on rates of adherence to PrEP in U.S. populations. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): In populations at higher risk of acquiring HIV infection, PrEP was associated with decreased risk of HIV infection versus placebo or no PrEP (11 trials; relative risk [RR], 0.46 [95% confidence interval (CI), 0.33 to 0.66; I2=67%; absolute risk reduction, -2.0% [95% CI, -2.8% to -1.2%] after 4 months to 4 years). Effects were consistent across HIV risk categories and for PrEP with tenofovir disoproxil fumarate plus emtricitabine or tenofovir alone. There was a strong association between higher adherence and greater efficacy (adherence ≥70%: 6 trials; RR, 0.27 [95% CI, 0.19 to 0.39]; I2=0%; adherence >40% to <70%: 3 trials; RR, 0.51 [95% CI, 0.38 to 0.70]; I2=0%; and adherence ≤40%: 2 trials; RR, 0.93 [95% CI, 0.72 to 1.20]; I2=0%; p<0.00001 for interaction). No trial reported effects of nondaily dosing except for one trial of event-driven PrEP (RR, 0.14 [95% CI, 0.03 to 0.63]). There was no difference between PrEP and placebo or no PrEP in risk of serious adverse events (12 trials; RR, 0.93 [95% CI, 0.77 to 1.12]; I2=56%). PrEP was associated with increased risk of renal adverse events (12 trials; RR, 1.43 [95% CI, 1.18 to 1.75]; I2=0%; absolute risk difference, 0.56% [95% CI, 0.09% to 1.04%]) and gastrointestinal adverse events (12 trials; RR, 1.63 [95% CI, 1.26 to 2.11]; I2=43%; absolute risk difference, 1.95% [95% CI, 0.48% to 3.43%]); most adverse events were mild and resolved with discontinuation of PrEP or with longer therapy. The association between PrEP and fracture was not statistically significant (7 trials; RR, 1.23 [95% CI, 0.97 to 1.56]; I2=0%). There were no differences between PrEP and placebo in risk of sexually transmitted infections, but most trials were blinded. Among women who became pregnant in trials of PrEP, PrEP was not associated with increased risk of spontaneous abortion (3 trials; RR, 1.09 [95% CI, 0.79 to 1.50]; I2=0%) or other adverse pregnancy outcomes. Instruments for predicting risk of incident HIV infection had moderate discrimination and require further validation. Adherence to PrEP in U.S. populations of men who have sex with men varied from high to low. Limitations: Restricted to English language, statistical heterogeneity in some pooled analyses, most randomized trials were conducted in low-income settings, limited evidence on adherence in U.S. populations, and evidence lacking in adolescents and pregnant women. Conclusions: In adults at increased risk of HIV infection, oral PrEP with tenofovir or tenofovir disoproxil fumarate plus emtricitabine is associated with decreased risk of HIV infection compared with placebo or no PrEP, although effectiveness decreases with inadequate adherence. PrEP is associated with increased risk of renal and gastrointestinal adverse events. Evidence on the accuracy of instruments for identifying persons at high risk of HIV infection is limited, with further validation needed.

Objectives: Objective. To assess comparative effectiveness and harms of opioid and nonopioid analgesics administered by emergency medical services for treatment of moderate to severe acute pain in the prehospital setting. Data sources. MEDLINE®, Embase® and Cochrane Central from earliest date through May 9, 2019; hand searches of references of relevant studies and study registries. Review methods. Two investigators screened abstracts, reviewed full-text files, abstracted data and assessed study level risk of bias. We performed meta-analyses when appropriate and graded the strength of evidence (SOE) upon which conclusions were made for a priori determined comparisons and outcomes. We defined the following as clinically important differences: 2 points on a 0 to 10 pain scale, time to analgesia of 5 minutes, 10% absolute risk difference for any adverse event, and 5% absolute risk difference for hypotension, respiratory depression and mental status changes. Results. We included 52 randomized controlled trials and 13 observational studies. Due to the absence or insufficiency of prehospital evidence we based conclusions for initial analgesia on indirect evidence from the emergency department (ED) setting. As initial analgesics, we found no evidence of a clinically important difference in the change of pain scores with opioids versus ketamine administered primarily intravenously (IV) (low SOE), IV acetaminophen (APAP) (low SOE), or nonsteroidal anti-inflammatory drugs (NSAIDs) administered primarily IV (moderate SOE). The combined use of an opioid and ketamine, administered primarily IV, may reduce pain more than an opioid alone at 15 and 30 minutes (low SOE) but we found no evidence of a clinically important difference at 60 minutes (low SOE). We found no evidence of a clinically important difference in time-to-analgesia with opioids compared with APAP, both administered IV. Opioids may cause fewer adverse events than ketamine (low SOE), primarily administered intranasally (IN). Opioids cause less dizziness than ketamine (low SOE) but may increase the risk of respiratory depression compared with ketamine (low SOE), primarily administered IV. Opioids cause more dizziness (moderate SOE) and may cause more adverse events than APAP (low SOE), both administered IV, but we found no evidence of a clinically important difference in hypotension (low SOE). Opioids may cause more adverse events and more drowsiness than NSAIDs (low SOE), administered primarily IV. Evidence on comparative effects of nitrous oxide and on harms of combined opioid and ketamine is insufficient. For patients whose pain is not adequately reduced by IV morphine initially, we found that giving IV ketamine may reduce pain more and may be quicker than giving additional IV morphine (low SOE, insufficient evidence to determine comparative harms). Conclusion. As initial analgesia administered primarily IV, opioids are no different than ketamine, APAP and NSAIDs in reducing acute pain in the prehospital setting. Opioids may cause fewer total side effects than ketamine, but more than APAP or NSAIDs. Differences in specific side effects vary between analgesics and can further inform treatment decisions. Combined administration of an opioid and ketamine may reduce acute pain more than an opioid alone but comparative harms are uncertain. When initial morphine is inadequate in reducing pain, giving ketamine may provide greater and quicker acute pain relief than giving additional morphine, although comparative harms are uncertain. Due to indirectness, strength of evidence is generally low, and future research in the prehospital setting is needed.

Objectives: Background: In 2006, the United States Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against routine screening for elevated blood lead levels in asymptomatic children aged 1 to 5 who are at increased risk for lead poisoning (I recommendation), and recommended against routine screening for those at average risk (D recommendation). Purpose: To synthesize evidence on the effects of screening, testing, and treatment for elevated blood lead level in children aged five and under in the primary care setting, in order to update a prior USPSTF review on screening for elevated blood lead levels in childhood. Data Sources: Cochrane CENTRAL and Cochrane Database of Systematic Reviews (through June 2018), and Ovid MEDLINE (1946 to June 2018), reference lists, and surveillance through December 5, 2018. Study Selection: English-language trials and observational studies of screening effectiveness, test accuracy, benefits and harms of screening and interventions in asymptomatic children five and under. Data Extraction: One investigator abstracted details about study design, patient population, setting, screening method, follow up, and results. Two investigators independently applied pre specified criteria to rate study quality using methods developed by the USPSTF. Discrepancies were resolved through consensus. Data Synthesis (Results): A total of 22 studies were included in this review (N=10,449). No studies directly evaluated clinical benefits or harms of screening versus not screening children for elevated blood lead levels. More than one positive answer on the 5-item 1991 Centers for Disease Control and Prevention (CDC) screening questionnaire was associated with a pooled sensitivity of 48 percent (95% confidence interval [CI], 31.4 to 65.6%) and specificity of 58 percent (95% CI, 39.9 to 74.0%) for identifying children with a venous blood level >10µg/dL (5 studies, N = 2,265). Adapted versions of the CDC questionnaire did not demonstrate improved accuracy. Capillary blood lead testing demonstrated sensitivity of 87 percent to 91 percent and specificity >90 percent, compared with venous measurement (4 studies, N = 1,431). Counseling and nutritional interventions or residential lead hazard control techniques did not reduce blood lead concentrations in asymptomatic children, but studies were few and had methodological limitations (7 studies, N = 1,419). A trial of dimercaptosuccinic acid (DMSA) chelation therapy found reduced blood lead levels in children at one week to one year but not at 4.5 to 6 years (N = 780), while another trial found no effect at one- and six-months (N = 39). Seven-year followup assessments showed no effect on neuropsychological development; a small deficit in linear growth (height difference at 7 years in treated patients 1.17cm; 95% CI, 0.41 to 1.93); and poorer cognitive outcomes reported as the Attention and Executive Functions sub-score of the Developmental Neuropsychological Assessment (NEPSY) (unadjusted difference -1.8; 95% CI, -4.5 to 1.0, adjusted P = 0.045) in children treated with DMSA chelation. Limitations: Limited to English-language articles; quality and applicability of studies were limited due to study design, poor reporting of statistical outcomes, and loss to follow up. Studies were lacking on the effectiveness of screening or effectiveness of treatments in reducing elevated blood lead levels or improving health outcomes in children. There was no direct evidence on the harms of screening children for elevated blood lead levels. Conclusions: Evidence on the benefits and harms of screening children for elevated lead levels is lacking. Screening questionnaires are not accurate for identifying children with elevated blood lead levels. Capillary blood testing is slightly less accurate than venous blood levels for identification of elevated blood levels. Treatment studies of chelating agents, often combined with environmental or household interventions, were not associated with sustained effects on blood level levels but were associated with harms.

Objectives: Structured Abstract Background: In 2006, the United States Preventive Services Task Force (USPSTF) recommended against routine screening for elevated blood lead levels in asymptomatic pregnant women (D recommendation). Purpose: To synthesize evidence on the effects of screening, testing, and treatment for elevated blood lead level in pregnant women, in order to update a 2006 USPSTF systematic review. Data Sources: Cochrane CENTRAL and Cochrane Database of Systematic Reviews (through June 2018), and Ovid MEDLINE (1946 to June 2018), reference lists, and surveillance through December 5, 2018. Study Selection: English-language trials and observational studies of screening effectiveness, test accuracy, benefits and harms of screening and interventions in asymptomatic pregnant women. Data Extraction: One investigator abstracted details about study design, patient population, setting, screening method, follow up, and results. Two investigators independently applied prespecified criteria to rate study quality using methods developed by the USPSTF. Discrepancies were resolved through consensus. Data Synthesis: No studies directly evaluated clinical benefits and harms of screening pregnant women for elevated lead levels versus no screening, or how effectiveness of screening varies according to the gestational age at which screening is performed. One fair quality study (N = 314) evaluated the diagnostic accuracy of using a version of the CDC screening questionnaire for lead exposure in children, modified for identifying pregnant women with elevated lead levels. The study used four out of five of the questions from the CDC questionnaire and found a sensitivity of 75.7 percent and specificity of 46.2 percent. The most predictive single item was living in a home built before 1960. One fair quality RCT from Mexico found calcium supplementation in healthy pregnant women (N = 670; mean baseline lead levels ~ 4 µg/dL) associated with a reduction in serum lead levels compared with placebo (difference 11%, p=0.004). No studies reported health outcomes or harms associated with interventions to reduce blood levels in asymptomatic pregnant women. Limitations: Limited to English-language articles; quality and applicability of studies were limited due to flawed study design, poor reporting of statistical outcomes, and loss to follow up. Two studies addressed the key questions, with no evidence on effects of screening or interventions for elevated lead levels in pregnant women on health outcomes. Conclusions: Evidence on the benefits and harms of screening pregnant women for elevated blood lead levels is extremely limited, with no evidence on effects of screening or interventions for lowering elevated blood lead levels in pregnant women on health outcomes.

Objectives:

Objectives: Objective. To assess efficacy of intermittent inhaled corticosteroid (ICS) therapy in different populations (0 to 4 years old with recurrent wheezing, 5 years and older with persistent asthma, with or without long-acting beta agonist [LABA]), and to assess efficacy of added long-acting muscarinic antagonist (LAMA) in patients 12 years and older with uncontrolled, persistent asthma. Data sources. MEDLINE®, Embase®, Cochrane Central, and Cochrane Database of Systematic Reviews bibliographic databases from earliest date through March 23, 2017; hand searches of references of relevant studies; www.clinicaltrials.gov and the International Controlled Trials Registry Platform. Review methods. Two investigators screened abstracts of identified references for eligibility and subsequently reviewed full-text files. We abstracted data, performed meta-analyses when appropriate, assessed the risk of bias of each individual study, and graded the strength of evidence for each comparison and outcome. Outcomes for which data were extracted included exacerbations, mortality, asthma control composite scores, spirometry, asthma-specific quality of life, and rescue medication use. Results. We included 56 unique studies (54 randomized controlled trials, 2 observational studies) in this review. Compared to rescue short-acting beta-agonist (SABA) use, adding intermittent ICS reduces the risk of exacerbation requiring oral steroids and improves caregiver quality of life in children less than 5 years old with recurrent wheezing in the setting of a respiratory tract infection (RTI). In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence, leading to primarily low strength of evidence ratings. Using ICS and LABA as both a controller and quick relief therapy reduced the risk of exacerbations and improved symptom control in patients 12 years and older compared to ICS controller (with or without LABA). Data in patients 4 to 11 years old suggest lower risk of exacerbations with ICS and LABA controller and quick relief use, but with a lower strength of evidence than in the older population. In patients 12 years and older with uncontrolled, persistent asthma, LAMA versus placebo as add-on to ICS reduces the risk of exacerbations requiring systemic corticosteroids and improves lung function measure through spirometry. Current evidence does not suggest that a difference exists in the efficacy of LAMA versus LABA as add-on to ICS. Triple therapy of ICS, LAMA, and LABA improves lung function measured through spirometry, although the risk of exacerbation was not different versus ICS and LABA. Conclusions. Intermittent ICS added to SABA during an RTI provides benefit to patients less than 5 years of age with recurrent wheezing. In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence for this question. In patients 12 years and older with persistent asthma, using ICS and LABA as both a controller and quick relief therapy may be more effective at preventing exacerbations than ICS controller (with or without LABA). LAMA is effective in the management of uncontrolled, persistent asthma in patients 12 years of age and older, and current evidence does not suggest a difference between LAMA and LABA as add-on to ICS.

Objectives: Objective. To assess select adverse events of antidepressants in the treatment of major depressive disorder (MDD) in adults 65 years old or older. Antidepressants included in this review, as determined by expert opinion, are selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone and vortioxetine. Data sources. MEDLINE®, Embase®, Cochrane Central, and PsycINFO bibliographic databases from earliest date through May 15, 2018; hand searches of references of relevant studies; www.clinicaltrials.gov and the International Controlled Trials Registry Platform. Review methods. Two investigators screened abstracts and subsequently reviewed full-text files. We abstracted data, performed meta-analyses when appropriate, assessed the risk of bias of each individual study, and graded the strength of evidence (SOE) for each comparison and select outcomes. Number needed to harm (NNH) is reported for graded outcomes with statistically significant findings. Results. Nineteen RCTs and two observational studies reported in 41 articles were included. Studies mostly evaluated treatment of the acute phase (<12 weeks) of MDD which was of moderate severity in patients 65 years and older, required subjects to be free from uncontrolled medical comorbidities or psychological conditions, and relied on spontaneous reporting of adverse events. Evidence was scarce and conclusions (based on statistical significance) for a given comparison and outcome are based often on a single study; particularly for specific adverse events. None of the RCTs were powered or designed to capture adverse events and most RCTs studied low doses of antidepressants. Observational data were limited by residual confounding. SSRIs (escitalopram and fluoxetine, moderate SOE), vortioxetine (high SOE) and bupropion XR (moderate SOE) led to a statistically similar frequency of adverse events compared with placebo; whereas SNRIs (duloxetine and venlafaxine) were found to cause a greater number of adverse events (high SOE, NNH 10) compared with placebo during treatment of the acute phase of MDD. Both SSRIs (citalopram, escitalopram and fluoxetine) and SNRIs caused a greater number of withdrawals due to adverse events compared with placebo (SSRIs low SOE, NNH 11; SNRIs moderate SOE, NNH 17). Duloxetine led to a greater number of falls compared with placebo (moderate SOE, NNH 10) during 24 weeks treatment. A single observational study provided evidence on long term use of antidepressants (low SOE) and suggested increased risk of adverse events (SSRIs), falls (SSRIs, SNRI venlafaxine, mirtazapine, trazadone), fractures (SSRIs, SNRI venlafaxine, mirtazapine), and mortality (SSRIs, SNRI venlafaxine, mirtazapine, trazadone), compared to no antidepressant. Evidence for the comparative harms of different antidepressants was limited to single RCTs mostly studying treatment of the acute phase of MDD (<12 weeks). Comparing SSRIs to each other or SSRIs to SNRIs showed statistically similar rates of adverse events (moderate SOE). SSRIs (paroxetine, citalopram, sertraline) had fewer withdrawals due to adverse events compared with TCAs (amitriptyline or nortriptyline) (low SOE, NNT 13) as did mirtazapine compared with paroxetine (low SOE, NNT 9). Vortioxetine had fewer adverse events compared with duloxetine (high SOE, NNT 6 ). Increasing age was associated with greater incidence of serious adverse events with escitalopram (low SOE). The increased risk of falls on duloxetine may be associated with the presence of cardiopulmonary conditions (low SOE). Conclusions. In patients 65 years of age or older with MDD, treatment of the acute phase of MDD with SNRIs (duloxetine and venlafaxine) led to a greater number of adverse events compared with placebo while adverse events were statistically similar to placebo with SSRIs (escitalopram, fluoxetine), vortioxetine and bupropion. SSRIs (citalopram, escitalopram and fluoxetine) and SNRIs (duloxetine and venlafaxine) led to a greater number of study withdrawals due to adverse events compared with placebo and duloxetine increased the risk of falls. Further characterization of the comparative safety of antidepressants is difficult because few studies were identified, comparisons were based on statistical significance, trials were not powered to identify small difference in adverse events and observational studies may be confounded. Comparative, long-term, well-designed studies that report specific adverse events are needed to better inform decisionmaking in this population.

Objectives: Technical brief

Objectives: The objectives of this database are to: 1. Systematically compile and provide access to primary, English-language, peer-reviewed science linking dietary fiber intake in humans to one or more of 10 potential health benefits 2. Provide researchers with a tool to understand how different fibers are characterized in studies 3. Facilitate researchers in identifying gaps in the current research 4. Create a database to serve as a starting foundation of primary human literature for conducting evidence-based reviews and meta-analyses 5. Efficiently assist researchers in identifying fibers of interest. This database should serve as a foundation for future work. Specific inclusion and exclusion criteria, detailed in the user manual, were applied in determining database eligibility; thus, this database is not intended to serve as a sole source for identifying all possible fiber literature for the purposes of conducting a meta-analysis or systematic review. This database contains Population, Intervention, Comparator, and Outcome (PICO) data to help users formulate and narrow the focus of their research question. It is expected that secondary searches will be conducted to augment this database.

Objectives: Background. Posttraumatic stress disorder (PTSD) reduces quality of life and functioning. People with PTSD have symptoms such as intrusive thoughts, nightmares, flashbacks, avoidance of trauma-related stimuli, negative beliefs about oneself and/or others, and hypervigilance. The symptoms may be due to direct or indirect exposure to trauma, such as witnessing actual or threatened death, injury, or violence including sexual violence and threats of harm. Although recent clinical practice guidelines and reviews exist, providing a single, updatable source of PTSD treatment trials would be useful for clinicians, researchers, and policymakers. Purpose. To provide detailed information on PTSD treatment research, we systematically abstracted data from randomized controlled trials (RCTs) of PTSD interventions. The National Center for Posttraumatic Stress Disorder (NCPTSD) intends to use the data to develop a publicly available data repository. The NCPTSD is part of the U.S. Department of Veterans Affairs. Data Sources. We searched PTSDpubs (formerly PILOTS), Ovid® MEDLINE®, Cochrane CENTRAL, PsycINFO®, Embase®, CINAHL®, and Scopus® for eligible RCTs and reviewed reference lists of selected systematic reviews and clinical practice guidelines. Methods. In consultation with NCPTSD, we established inclusion criteria for RCTs and specific data elements to be abstracted. We dually reviewed citations from the literature search, and then the full text of potentially includable articles for eligibility, resolving any disagreements using consensus. One team member abstracted data from included RCTs into evidence tables, and a second reviewer checked abstracted data for accuracy and completeness. The primary publication for each RCT was abstracted; data and citations from any secondary publications (i.e., companion papers) appear in the same record. Findings. We identified 318 RCTs of PTSD interventions for abstraction (106 pharmacologic studies and 212 nonpharmacologic studies) published from 1988 to 2018, with a peak number of publications (31) in 2015. Psychotherapeutic interventions were the most commonly studied (55%), whereas 30 percent evaluated pharmacologic interventions. Most studies were conducted in the United States (61%), and most had sample sizes in the range of 25 to 100 participants (60% of studies) with a relatively small number of studies enrolling fewer than 25 participants (18%). More studies enrolled participants from a community population (57%) than from a military, veteran or other population, and the majority of studies were conducted in the outpatient setting (67%). Studies most often enrolled participants with a mix of trauma types (51%), followed by studies of participants with combat-related trauma (20%). Although there was wide variation, the most commonly used PTSD assessment methods were the Clinician-Administered PTSD Scale (CAPS) and the Structured Clinical Interview for DSM (SCID). Less than half of the studies reported loss of PTSD diagnosis or clinically meaningful response/remission of symptoms. Several other data elements were infrequently reported, including the number of participants with a history of traumatic brain injuries and the number of trauma types. Conclusions. The data abstracted from 318 RCTs of treatments for PTSD can be used to create a publicly available data repository. By identifying important gaps in the research, such a data repository can inform future study design and conduct.

Objectives: Objectives: This review evaluates the comparative effectiveness of different strategies for treating labor dystocia in women with otherwise uncomplicated pregnancies. Data Sources: We searched PubMed®, Embase®, CINAHL®, and the Cochrane Database of Systematic Reviews (CDSR), limiting the searches to studies in the English-language and comparative studies published from January 1, 2005, to February 15,2019. Review Methods: Two investigators screened each abstract and full-text article for inclusion, abstracted data, rated quality and applicability, and graded evidence. When possible, random-effects models were used to compute summary estimates of effects.

Objectives: Objective. Previous studies have demonstrated varying success for treatment of infertility. Much of this literature however does not focus on treatment of women with specific diagnoses. This systematic review evaluated the comparative effectiveness and safety of fertility treatment strategies for (a) women of reproductive age (18-44) who are infertile due to polycystic ovary syndrome (PCOS), endometriosis, unknown reasons, or tubal or peritoneal factors or (b) couples with male factor infertility; and evaluated short- and long-term health outcomes of gamete donors in infertility. Data sources. We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for English-language studies published from January 1, 2007, to October 3, 2018, that reported live birth rates, pregnancy and neonatal outcomes, time to pregnancy, and short-term and long-term adverse outcomes for mothers and children born after infertility treatment. For male and female donors, we searched for studies reporting short- and long-term adverse effects and quality-of-life outcomes. Review methods. Two investigators screened each abstract and full-text article for inclusion; abstracted data; and performed quality ratings, applicability ratings, and evidence grading. Where appropriate, random-effects models were used to compute summary estimates of effects.

Objectives: Objectives: To conduct a systematic review to identify and summarize the available evidence about the effectiveness of telehealth consultations and to explore using decision modeling techniques to supplement the review. Telehealth consultations are defined as the use of telehealth to facilitate collaboration between two or more providers, often involving a specialist, or among clinical team members, across time and/or distance. Consultations may focus on the prevention, assessment, diagnosis, and/or clinical management of acute or chronic conditions. Data Sources. We searched Ovid MEDLINE®, the Cochrane Central Register of Controlled Trials (CCRCT), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL®) to identify studies published from 1996 to May 2018. We also reviewed reference lists of identified studies and systematic reviews, and we solicited published or unpublished studies through an announcement in the Federal Register. Data for the model came both from studies identified via the systematic review and from other sources. Methods. We included comparative studies that provided data on clinical, cost, or intermediate outcomes associated with the use of any technology to facilitate consultations for inpatient, emergency, or outpatient care. We rated studies for risk of bias and extracted information about the study design, the telehealth interventions, and results. We assessed the strength of evidence and synthesized the findings using quantitative and qualitative methods. An exploratory decision model was developed to assess the potential economic impact of telehealth consultations for traumatic brain injuries in adults. Results. The search yielded 9,366 potentially relevant citations. Upon review, 8,356 were excluded and the full text of 1,010 articles was pulled for review. Of these, 233 articles met our criteria and were included—54 articles evaluated inpatient consultations, 73 emergency care, and 106 outpatient care. The overall results varied by setting and clinical topic, but generally the findings are that telehealth improved outcomes or that there was no difference between telehealth and the comparators. Remote intensive care unit (ICU) consultations likely reduce ICU and total hospital mortality with no significant difference in ICU or hospital length of stay; specialty telehealth consultations likely reduce the time patients spend in the emergency department; telehealth for emergency medical services likely reduces mortality for patients with heart attacks, and remote consultations for outpatient care likely improve access and a range of clinical outcomes (moderate strength of evidence in favor of telehealth). Findings with lower confidence are that inpatient telehealth consultations may reduce length of stay and costs; telehealth consultations in emergency care may improve outcomes and reduce costs due to fewer transfers and also may reduce outpatient visits and costs due to less travel (low strength of evidence in favor of telehealth). Current evidence reports no difference in clinical outcomes with inpatient telehealth specialty consultations, no difference in mortality but also no difference in harms with telestroke consultations, and no difference in satisfaction with outpatient telehealth consultations (low strength of evidence of no difference). Too few studies reported information on potential harms from outpatient telehealth consultations for conclusions to be drawn (insufficient evidence). An exploratory cost model underscores the importance of perspective and assumptions in using modeling to extend evidence and the need for more detailed data on costs and outcomes when telehealth is used for consultations. For example, a model comparing telehealth to transfers and in-person neurosurgical consultations for acute traumatic brain injury identified that the impact of telehealth on costs may depend on multiple factors including how alternatives are organized (e.g., if the telehealth and in-person options are part of the same health care system) and whether the cost of a telehealth versus an in-person consultation differ. Conclusions. In general, the evidence indicates that telehealth consultations are effective in improving outcomes or providing services with no difference in outcomes; however, the evidence is stronger for some applications, and less strong or insufficient for others. Exploring the use of a cost model underscored that the economic impact of telehealth consultations depends on the perspective used in the analysis. The increase in both interest and investment in telehealth suggests the need to develop a research agenda that emphasizes rigor and focuses on standardized outcome comparisons that can inform policy and practice decisions.

Objectives: Objective. To summarize evidence on outcomes of long-term osteoporosis drug therapy to prevent fractures, on continuing versus discontinuing osteoporosis drug therapy (i.e., placebo drug holidays), and on whether osteoporosis drug intervention effects vary as a function of patient, bone, or drug characteristics. Data sources. MEDLINE, Embase and Cochrane databases from 1995 to June 2018; ClinicalTrials.gov; bibliographies of relevant systematic reviews Review methods. Long-term osteoporosis drug therapy was defined as >3 years and drug holiday as osteoporosis drug discontinuation for ≥1 year after ≥1 year of prior osteoporosis drug use. Two reviewers independently rated risk of bias (ROB) and strength of evidence (SOE), resolving discrepancies by consensus. Included studies were English-language trials for incident fractures and harms and controlled observational studies for additional harms outcomes. For low or medium ROB studies, one reviewer extracted data and a second verified accuracy. Results. Of 56 eligible publications, 44 had low or medium ROB, including 32 publications of trials (7 unique studies) and 12 publications of observational studies (10 unique studies). Nearly all studies were comprised of postmenopausal women. Mean participant age was 72 years; all but 2 studies had a mean age <80 years. In postmenopausal women with osteoporosis, compared with placebo, 4 years of alendronate or raloxifene reduced risk of incident vertebral fractures (high SOE), 4 years of alendronate reduced risk of incident clinical fractures (moderate SOE). In postmenopausal women with past fractures, compared with placebo, both long-term estrogen and long-term estrogen/progestin reduced risk of incident clinical fractures and long-term estrogen reduced risk of incident hip fractures (all low SOE). Alendronate, denosumab and raloxifene for 4 years each significantly increased total hip and lumbar spine bone mineral density (BMD) versus placebo. Continuation versus discontinuation of alendronate after 5 years reduced risk of incident clinical vertebral fractures in one large trial (10 vs. 5 years, moderate SOE), but not in another smaller trial (7 vs. 5 years, low SOE). Continuation versus discontinuation of zoledronic acid (6 vs. 3 years) reduced risk of incident radiographic vertebral fractures (moderate SOE), but evidence was insufficient about risk of incident clinical vertebral fractures. Neither alendronate nor zoledronic acid continuation reduced risk of nonvertebral fractures (low SOE) versus discontinuation; for both, continuation was associated with generally stable hip BMD compared to small, but significant declines with discontinuation. Based primarily on observational studies, long-term bisphosphonates may increase risks of radiologically confirmed atypical femoral fractures (AFF), subtrochanteric or femoral shaft fractures without confirmed AFF features, and osteonecrosis of the jaw (ONJ). Limitations. Minimal data for men or individuals with comorbidities. Low power to assess risks of incident clinical fractures. No data compared long-term effects of sequential treatments (e.g., anabolic followed by anti-resorptive) or different durations of drug holidays. Analyses of possible treatment effect modifiers almost entirely post hoc. Observational studies used variable drug treatment and control exposures and harms definitions. Conclusions. For postmenopausal women with osteoporosis by BMD or past fractures, long-term alendronate and raloxifene reduced risk of incident vertebral fractures; long-term alendronate, estrogen, and estrogen/progestin reduced risk of clinical fractures; and long-term estrogen reduces risk of incident hip fractures. Longer-term use of bisphosphonates versus discontinuation may lower vertebral fracture risk and stabilize hip BMD, but doesn’t reduce nonvertebral fracture risk and may increase risk of AFF and ONJ. Long-term estrogen and estrogen/progestin increased risk of cardiovascular disease, and long-term estrogen increased risk of dementia and breast cancer. To address remaining knowledge gaps, future trials and observational studies should enroll diverse populations (sex, comorbidity), examine the effects of sequential treatments and compare drug holidays of different durations, be powered for clinical fractures, and use standard AFF and ONJ definitions. A priori analyses to examine whether treatment outcomes vary by patient, bone and drug treatment characteristics may inform individualized treatment decisions.

Objectives: The objectives of this database are to: 1. Systematically compile and provide access to primary, English-language, peer-reviewed science linking dietary fiber intake in humans to one or more of 10 potential health benefits 2. Provide researchers with a tool to understand how different fibers are characterized in studies 3. Facilitate researchers in identifying gaps in the current research 4. Create a database to serve as a starting foundation of primary human literature for conducting evidence-based reviews and meta-analyses 5. Efficiently assist researchers in identifying fibers of interest. This database should serve as a foundation for future work. Specific inclusion and exclusion criteria, detailed in the user manual, were applied in determining database eligibility; thus, this database is not intended to serve as a sole source for identifying all possible fiber literature for the purposes of conducting a meta-analysis or systematic review. This database contains Population, Intervention, Comparator, and Outcome (PICO) data to help users formulate and narrow the focus of their research question. It is expected that secondary searches will be conducted to augment this database.

Objectives: As part of our Center focusing on understanding Genetic Privacy and Identity in Community Settings, we conducted a systematic literature review of what is already known about people’s concerns about genetic privacy in clinical care and research. We discovered that the research to date has focused primarily on concerns about downstream data users, issues of control, and whether data is revealed. Only recently have people been asked under what circumstances they might be willing to give up some privacy for another purpose. Remarkably little has been reported regarding the sociocultural factors that influence individuals’ opinions and decisions, even though these are where concerns can be addressed. Filling these gaps will be a major focus of our group’s research agenda.

Objectives: Although a number of systematic reviews on corneal disease have been published, the reliability of these reviews remains unclear. We will characterize and appraise the methodological reliability of systematic reviews on interventions for corneal disease. The purpose of our study is to evaluate the current available evidence on interventions for corneal disease, state the strengths and limitations and formulate recommendations for improving future review conduct.

Objectives: This is a Methods Research project that catalogs the various projects with publicly available data on the SRDR Webpage.

Objectives: The purpose of this systematic review is to update the 2012 Comparative Effectiveness Review that evaluated the benefits and harms of drug therapies for adults with rheumatoid arthritis (RA). This updated review has a targeted scope focusing solely on patients with early RA, defined as no more than one year of diagnosed disease. This report is intended to help health care decision makers -- patients, and clinicians, health system leaders, and policymakers, among others -- make well-informed decisions regarding early RA and thereby improve the quality of health care services.

Objectives: Objectives: This review updates previous reviews regarding the optimal risk stratification tools for stroke and bleeding prediction and treatment options for stroke prevention. Data Sources: We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for relevant English-language comparative studies published from January 1, 2000, to February 14, 2018. Review Methods: Two investigators screened each abstract and full-text article for inclusion, abstracted data, rated quality and applicability, and graded evidence. When possible, random-effects models were used to compute summary estimates of effects.

Objectives: This proposed evidence mapping project will summarize the data related to Flavan-3-ols and its connection to vascular health outcomes and risk factors.

Objectives: Structured Abstract Objectives. Many interventions are available to manage chronic pain; understanding the durability of treatment effects may assist with treatment selection. We sought to assess which noninvasive, nonpharmacological treatment for selected chronic pain conditions are associated with persistent improvement in function and pain outcomes at least 1 month after the completion of treatment. Data sources. Electronic databases (Ovid MEDLINE®, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews), through November 2017, reference lists, and ClinicalTrials.gov. Review methods. Using predefined criteria, we selected randomized controlled trials of noninvasive, nonpharmacological treatments for five common chronic pain conditions (chronic low back pain, chronic neck pain, osteoarthritis of the knee, hip, or hand, fibromyalgia, and tension headache) that addressed efficacy or harms compared with usual care, no treatment, waitlist, placebo, or sham intervention; compared with pharmacological therapy; or compared with exercise. Study quality was assessed, data extracted, and results summarized for function and pain. Only trials reporting results for at least 1 month post-intervention were included. We focused on the persistence of effects at short term (1 to < 6 months following treatment completion), intermediate term (≥6 to <12 months), and long term (≥12 months). Results. 218 publications (202 trials) were included. Many included trials were small. Evidence on outcomes beyond 1 year after treatment completion was sparse. Most trials enrolled patients with moderate baseline pain intensity (e.g., >5 on a 0 to 10 point numeric rating scale) and duration of symptoms ranging from 3 months to >15 years. The most common comparison was against usual care. Chronic low back pain: At short term, massage, yoga, and psychological therapies (primarily cognitive behavioral therapy [CBT]) (Strength of evidence [SOE]: Moderate) and exercise, acupuncture, spinal manipulation, and multidisciplinary rehabilitation (SOE: Low) were associated with slight improvements in function compared with usual care or inactive controls. Except for spinal manipulation, these interventions also improved pain. Effects on intermediate term function were sustained for yoga, spinal manipulation, multidisciplinary rehabilitation (SOE: Low), and psychological therapies (SOE: Moderate). Improvements in pain continued into intermediate term for exercise, massage and yoga (moderate effect, SOE: Low), mindfulness-based stress reduction (small effect, SOE: Low), spinal manipulation, psychological therapies, and multidisciplinary rehabilitation (small effects, SOE: Moderate). For acupuncture, there was no difference in pain at intermediate term, but a slight improvement at long term (SOE: Low). Psychological therapies were associated with slightly greater improvement than usual care or an attention control on both function and pain at short-term, intermediate-term, and long-term followup (SOE: Moderate). At short and intermediate term, multidisciplinary rehabilitation slightly improved pain compared with exercise (SOE: Moderate). High-intensity multidisciplinary rehabilitation (≥20 hours/week or >80 hours total) was not clearly better than nonhigh-intensity programs. Chronic neck pain: At short- and intermediate-terms, acupuncture and Alexander Technique were associated with slightly improved function compared with usual care (both interventions), sham acupuncture, or sham laser (SOE: Low), but no improvement in pain was seen at any time (SOE: Low). Short-term, low-level laser therapy was associated with moderate improvement in function and pain (SOE: Moderate). Combination exercise (any 3 of the following: muscle performance, mobility, muscle re-education, aerobic) demonstrated a slight improvement in pain and function short and long-term (SOE: Low). Osteoarthritis: For knee osteoarthritis, at short-term exercise and ultrasound demonstrated small short-term improvements in function compared with usual care, an attention control or sham procedure (SOE: Moderate for exercise, Low for ultrasound), which persisted into the intermediate term only for exercise (SOE: Low). Exercise was also associated with moderate improvement in pain (SOE: Low). Long term, the small improvement in function seen with exercise persisted, but there was no clear effect on pain (SOE: Low). Evidence was sparse on interventions for hip and hand osteoarthritis. Exercise for hip osteoarthritis was associated with slightly greater function and pain improvement than usual care short term (SOE: Low). The effect on function was sustained intermediate term (SOE: Low). Fibromyalgia: In the short term, acupuncture (SOE: Moderate), CBT, tai chi, qigong, and exercise (SOE: Low) were associated with slight improvements in function compared with an attention control, sham, no treatment or usual care. Exercise (SOE: Moderate) and CBT improved pain slightly and tai chi and qigong (SOE: Low) improved pain moderately in the short term. At intermediate term for exercise (SOE: Moderate), acupuncture and CBT (SOE: Low), slight functional improvements persisted and were also seen for myofascial release massage and multidisciplinary rehabilitation (SOE: Low); pain was improved slightly with multidisciplinary rehabilitation in the intermediate-term (SOE: Low). In the long term, small improvements in function continued for multidisciplinary rehabilitation but not for exercise or massage (SOE: Low for all); massage (SOE: Low) improved long-term pain slightly but no clear impact on pain for exercise (SOE: Moderate) or multidisciplinary rehabilitation (SOE: Low) was seen. Short-term CBT was associated with a slight improvement in function but not pain compared with pregabalin. Chronic tension headache: Evidence was sparse and the majority of trials were of poor quality. Spinal manipulation slightly improved function and moderately improved pain short-term versus usual care and laser acupuncture was associated with slight pain improvement short term compared with sham (SOE Low). There was no evidence suggesting increased risk for serious treatment-related harms for any of the interventions, although data on harms were limited. Conclusions. Exercise, multidisciplinary rehabilitation, acupuncture, cognitive behavioral therapy, and mind-body practices were most consistently associated with durable slight to moderate improvements in function and pain for specific chronic pain conditions. Our findings provided some support for clinical strategies that focused on use of nonpharmacological therapies for specific chronic pain conditions. Additional comparative research on sustainability of effects beyond the immediate post-treatment period is needed, particularly for conditions other than low back pain.

Objectives: Objectives. To systematically identify and summarize evaluations of measures of circulatory and respiratory compromise, focusing on measures that can be used in field assessment by emergency medical services to inform decisions about the level of trauma care needed. We identified research on the ability of different measures to predict whether a patient was seriously injured and thus required transport to the highest level of trauma care available. Data sources. We searched Ovid MEDLINE®, CINAHL®, and the Cochrane databases from 1996 through August 2017. Reference lists of included articles were reviewed for additional relevant citations. Review methods. We included studies of individual measures and measures that combined circulatory, respiratory, and level of consciousness assessment. Evaluations included diagnostic accuracy (sensitivity and specificity) and area under the receiver operating characteristic curve (AUROC). We used data provided to calculate values that were not reported and pooled estimates across studies when feasible. Results. We identified and included 138 articles reporting results of 134 studies. Circulatory compromise measures evaluated in these studies included systolic blood pressure, heart rate, shock index, lactate, base deficit, and heart rate variability or complexity. The respiratory measures evaluated included respiration rate, oxygen saturation, partial pressure of carbon dioxide, and need for airway support. Many different combination measures were identified, but most were evaluated in only one or two studies. Pooled AUROCs from out-of-hospital data were 0.67 for systolic blood pressure (moderate strength of evidence); 0.67 for heart rate, 0.72 for shock index, 0.77 for lactate, 0.70 for respiratory rate, and 0.89 for Revised Trauma Score combination measure (all low strength of evidence); and were considered poor to fair. The only AUROC that reached a level considered excellent was for the Glasgow Coma Scale, age, and arterial pressure (GAP) combination measure (AUROC, 0.96; estimate based on emergency department data). All of the measures had low sensitivities and comparatively high specificities (e.g., sensitivities ranging from 13% to 74% and specificities ranging from 62% to 96% for out-of-hospital pooled estimates). Conclusions. Physiologic measures usable in triaging trauma patients have been evaluated in multiple studies; however, their predictive utilities are moderate and far from ideal. Overall, the measures have low sensitivities, high specificities, and AUROCs in the poor-to-fair range. Combination measures that include assessments of consciousness seem to perform better, but whether they are feasible and valuable for out-of-hospital use needs to be determined. Modification of triage measures for children or older adults is needed, given that the measures perform worse in these age groups; however, research has not yet conclusively identified modifications that result in better performance.

Objectives: This systematic review is an update of a 2013 report that evaluated psychological and pharmacological treatments of adults with posttraumatic stress disorder (PTSD). The purpose of this review is to update the earlier work, expand the range of treatments examined, address earlier uncertainties, identify ways to improve care for PTSD patients, and reduce variation in existing treatment guidelines.

Objectives: Objective. Assess the effect of drug and nondrug interventions for treating acute symptoms associated with bipolar disorder (BD) and preventing relapse. Data sources. Ovid MEDLINE® and PsychInfo, the Cochrane Central Register of Controlled Trials, and Ovid Embase® bibliographic databases; hand searches of references of relevant systematic reviews through May, 2017. Review methods. Eligible studies included randomized controlled trials and prospective cohorts with comparator arms enrolling adults with BD of any type with 3 weeks followup for acute mania, 3 months for depression, and 6 months for maintenance treatments. We excluded acute mania and depression studies with greater than 50 percent attrition. Results. We synthesized evidence from 181 unique studies, 117 studies for 28 drugs, 64 studies for nondrug interventions. All drug findings with at least low-strength evidence were based on studies almost exclusively enrolling adults with BD-I. Asenapine, cariprazine, quetiapine, and olanzapine improved acute mania symptoms compared to placebo (low-strength evidence). However, improvements were of modest clinical significance, with values that were less than the minimally important difference, but still large enough that a reasonable proportion of participants likely received a benefit. Unpooled evidence indicated an overall beneficial effect of risperidone and ziprasidone on acute mania symptoms compared to placebo (low-strength evidence). Participants using antipsychotics, except quetiapine, reported more extrapyramidal symptoms compared to placebo, and those using olanzapine reported more clinically significant weight gain. Lithium improved acute mania in the short-term and prolonged time to relapse in the long-term compared to placebo (low-strength evidence). No difference was found between olanzapine and divalproex/valproate (low-strength evidence). For drugs not approved for BD, paliperidone also improved acute mania compared to placebo (low-strength evidence), while topiramate and allopurinol showed no benefit (low-strength evidence). Further, lithium improved acute mania better than topiramate, although withdrawals for adverse events were lower for topiramate. Only lithium reached a minimally important difference. All other drug comparisons to placebo or active controls for acute mania, depression, and maintenance had insufficient evidence. For psychosocial interventions, cognitive behavioral training (CBT) was no better for depression or mania symptoms than psychoeducation or other active psychosocial comparators (low-strength evidence). Systematic/collaborative care had no effect on relapse compared to inactive comparators (low-strength evidence). Evidence was insufficient for all other nondrug interventions. Conclusions. We found no high- or moderate-strength evidence for any intervention to effectively treat any phase of any type of BD compared with placebo or an active comparator. Low-strength evidence showed improved mania symptoms for all FDA-approved antipsychotics, except aripiprazole, when compared with placebo for adults with BD-I. Low-strength evidence also showed benefit from lithium for acute mania in the short-term and resulted in longer periods of maintenance versus placebo in adults with BD-I. Participants using atypical antipsychotics, except quetiapine, reported more extrapyramidal symptoms compared with placebo, and those using olanzapine reported more clinically significant weight gain. Evidence was insufficient for most nondrug interventions. Low-strength evidence showed no benefit for CBT on mood symptoms compared with active controls or systematic/collaborative care compared with inactive controls on relapse. Information on harms was limited across all drug and nondrug studies. Future studies of BD treatments will require innovative ways to increase study completion rates.

Objectives: The objectives of this database are to: 1. Systematically compile and provide access to primary, English-language, peer-reviewed science linking dietary fiber intake in humans to one or more of 10 potential health benefits 2. Provide researchers with a tool to understand how different fibers are characterized in studies 3. Facilitate researchers in identifying gaps in the current research 4. Create a database to serve as a starting foundation of primary human literature for conducting evidence-based reviews and meta-analyses 5. Efficiently assist researchers in identifying fibers of interest. This database should serve as a foundation for future work. Specific inclusion and exclusion criteria, detailed in the user manual, were applied in determining database eligibility; thus, this database is not intended to serve as a sole source for identifying all possible fiber literature for the purposes of conducting a meta-analysis or systematic review. This database contains Population, Intervention, Comparator, and Outcome (PICO) data to help users formulate and narrow the focus of their research question. It is expected that secondary searches will be conducted to augment this database.

Objectives: The purpose of this technology assessment is to review the current definitions of treatment-resistant depression (TRD), to assess how closely current TRD treatment studies fit the most common definition, and to suggest how to improve TRD treatment research.

Objectives:

Objectives: This review assesses the role of bronchial thermoplasty (BT) in adults with asthma.

Objectives: To evaluate the clinical utility and diagnostic accuracy of fractional exhaled nitric oxide (FeNO) in people age 5 years and older with asthma; and the ability of FeNO measured at age 4 years or younger to predict a future diagnosis of asthma. PubMed ID:

Objectives: To evaluate the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in the treatment of allergic asthma

Objectives: Objective: To evaluate (1) the diagnostic accuracy of selected depression screening instruments and strategies versus a validated criterion standard in adult patients within 3 months of an acute coronary syndrome (ACS) event, and (2) the comparative safety and effectiveness of a broad range of pharmacologic and nonpharmacologic treatments for depression in adult patients who have received a criterion-based diagnosis of depression or had clinically important depressive symptoms using a validated depression scale, and who are within 3 months of an ACS event. Data Sources: We searched PubMed®, Embase®, PsycINFO®, CINAHL®, and the Cochrane Database of Systematic Reviews for English-language studies published from January 1, 2003, to April 27, 2017, that evaluated the accuracy of tools for diagnosing depression in patients after ACS or that evaluated interventions for treating post-ACS patients identified with depression. Review Methods: Two investigators individually screened each abstract and full-text article for inclusion; abstracted data; and rated quality, applicability, and strength of evidence. Where appropriate, random-effects models were used to compute summary estimates of effects.

Objectives: Objectives. Attention deficit hyperactivity disorder (ADHD) is a common pediatric neurobehavioral disorder often treated in the primary care setting. This systematic review updates and extends two previous systematic evidence reviews and focuses on the comparative effectiveness of methods to establish the diagnosis of ADHD, updates the comparative effectiveness of pharmacologic and nonpharmacologic treatments, and evaluates different monitoring strategies in the primary care setting for individuals from birth through 17 years of age. Data sources. We searched PubMed®, Embase®, PsycINFO® and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1, 2011, through November 7, 2016. Review methods. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects when sufficient data were available for meta-analysis.

Objectives: SR of nonsurgical interventions for stress, urgency, and mixed urinary incontinence in women (excluding neuropathic UI and children). Network meta-analysis of "urinary incontinence outcomes" ("cure", improvement, and satisfaction with the level of incontinence achieved). Qualitative review of quality of life outcomes. Summary of adverse events. This is an update of a 2012 review done by the Minnesota EPC. Available data from eligible studies included in the prior review are uploaded as separate files.

Objectives: Objectives. For patients with lower extremity chronic venous disease (LECVD), the optimal diagnostic testing and treatment for symptom relief, preservation of limb function, and improvement in quality of life is not known. This systematic review included a narrative review of diagnostic testing modalities and assessed the comparative effectiveness of exercise training, medical therapy, weight reduction, mechanical compression therapy, and invasive procedures (i.e., surgical and endovascular procedures) in patients with LECVD. Data sources. We searched PubMed®, Embase®, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1, 2000 to June 30, 2016. Review methods. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects. Results. A total of 111 studies contributed evidence, as follows: Diagnosis of LECVD: A narrative review was conducted due to the scant literature and availability of only 10 observational studies evaluating the comparative effectiveness of diagnostic testing modalities in a heterogeneous population of patients with LECVD. In addition to the history and physical exam, multiple physiologic and imaging modalities (plethysmography, duplex ultrasound, intravascular ultrasonography, magnetic resonance venography, computed tomography venography, and invasive venography) are useful to confirm LECVD and/or localize the disease and guide therapy. There was insufficient evidence to support or refute the recommendations from current clinical guidelines that duplex ultrasound should be used as the firstline diagnostic test for patients being evaluated for LECVD or for those for whom invasive treatment is planned. Treatment of lower extremity chronic venous insufficiency/incompetence/reflux: Ninety-three studies (87 randomized controlled trials, 6 observational) evaluated the comparative effectiveness of exercise training, medical therapy, weight reduction, mechanical compression therapy, surgical intervention, and endovenous intervention in patients with lower extremity chronic venous insufficiency/incompetence/reflux. There was no long-term difference in effectiveness between radiofrequency ablation (RFA) and high ligation plus stripping, but RFA was associated with less periprocedural pain, faster improvement in symptom scores and quality of life, and fewer adverse events. Among patients undergoing endovenous interventions, RFA, endovenous laser ablation (EVLA), and sclerotherapy demonstrated improvement in quality-of-life scores and standardized symptom scores. When compared with patients treated with EVLA, those treated with foam sclerotherapy had significantly less periprocedural pain but lower rates of vein occlusion and higher rates of repeat intervention, and patients treated with RFA had significantly less periprocedural pain but also less short-term improvement in Venous Clinical Severity Score. When compared with patients treated with placebo, those treated with foam sclerotherapy had statistically significant improvement in standardized symptom scores, occlusion rates, and quality of life. When compared with patients treated with placebo or no compression therapy, those treated with compression therapy had significant improvement in standardized symptom scores and quality of life. Treatment of lower extremity chronic venous obstruction/thrombosis: Eight studies (3 randomized controlled trials, 5 observational) evaluated the comparative effectiveness of exercise training, medical therapy, weight reduction, mechanical compression therapy, surgical intervention, and endovenous intervention in patients with lower extremity chronic venous obstruction/thrombosis. In patients with post-thrombotic syndrome, exercise training plus patient education and monthly phone follow-up resulted in improved quality of life but not improved symptom severity when compared with patient education and monthly phone follow-up. In patients with both May-Thurner Syndrome and superficial venous reflux who were treated with EVLA (with or without stent placement), there were fewer recurrent ulcerations, improvement in reflux severity and symptoms, and improvement in quality of life in long-term follow-up. In patients with chronic proximal iliac vein obstruction, treatment with catheter-directed urokinase at the time of endovenous stenting resulted in similar effectiveness but catheter-directed urokinase had higher technical failure rates and bleeding risk when compared with endovenous stenting alone. Very few studies evaluated modifiers of effectiveness in the study population. Conclusions. The available evidence for treatment of patients with LECVD is limited by heterogeneous studies that compared multiple treatment options, measured varied outcomes, and assessed disparate outcome timepoints. Very limited comparative effectiveness data have been generated to study new and existing diagnostic testing modalities for patients with LECVD. When compared with patients’ baseline measures, endovenous interventions (e.g. EVLA, sclerotherapy, and RFA) and surgical ligation demonstrated improvement in quality-of-life scores and Venous Clinical Severity Score at various timepoints after treatment; however, there were no statistically significant differences in outcomes between treatment groups (e.g. endovenous vs. endovenous; endovenous vs. surgical). Several advances in care in endovenous interventional therapy have not yet been rigorously tested, and there are very few studies on conservative measures (e.g., lifestyle modification, compression therapy, exercise training) in the literature published since 2000. Additionally, the potential additive effects of many of these therapies are unknown. The presence of significant clinical heterogeneity of these results makes conclusions for clinical outcomes uncertain and provides an impetus for further research to improve the care of patients with LECVD.

Objectives: To evaluate the comparative effectiveness and safety of treatments for childhood anxiety disorders, including panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, and separation anxiety. PubMed ID: Data were entered into this project retrospectively using a PDF format files, including studies characteristics, binary outcomes, continuous outcomes, withdraw outcomes and studies quality.

Objectives: Objectives. This systematic review (SR) provides evidence on pharmacological and psychosocial treatments for schizophrenia. Data sources. MEDLINE®, the Cochrane Library databases, PsycINFO® and included studies through February 2017. Study selection. We included studies comparing second generation antipsychotics (SGA) with each other or with a first generation antipsychotic (FGA) and studies comparing psychosocial interventions with usual care in adults with schizophrenia. Data extraction. We extracted study design, year, setting, country, sample size, eligibility criteria, population, clinical and intervention characteristics, results, and funding source. Results. We included one SR of 138 trials (N=47,189) and 24 trials (N=6,672) for SGAs versus SGAs, one SR of 111 trials (N=118,503) and five trials (N=1,055) for FGAs versus SGAs, and 13 SRs of 271 trials (N=25,050) and 27 trials (n=6,404) for psychosocial interventions. Trials were mostly fair quality and strength of evidence was low or moderate. For drug therapy, the majority of the head to head evidence was on older SGAs, with sparse data on SGAs approved in the last 10 years (asenapine, lurasidone, iloperidone, cariprazine, brexpiprazole), and recent long-acting injection [LAI] formulations of aripiprazole and paliperidone. Older SGAs were similar in measures of function, quality of life, mortality, and overall adverse events, except that risperidone LAI had better social function than quetiapine. Core illness symptoms were improved more with olanzapine and risperidone than asenapine, quetiapine, and ziprasidone and more with paliperidone than lurasidone and iloperidone; all were superior to placebo. Risperidone LAI and olanzapine had less withdrawal due to adverse events. Compared with olanzapine and risperidone, haloperidol, the most studied FGA, had similar improvement in core illness symptoms, negative symptoms, symptom response, and remission but greater incidence of adverse event outcomes. In comparison with usual care, most psychosocial interventions reviewed were more effective in improving intervention-targeted outcomes, including core illness symptoms. Various functional outcomes were improved more with assertive community care, cognitive behavioral therapy, family interventions, psychoeducation, social skills training, supported employment, and early interventions for first episode psychosis (FEP) than with usual care. Quality of life was improved more with cognitive behavioral therapy and early interventions for FEP than usual care. Relapse was reduced with family interventions, psychoeducation, illness self-management, family interventions, and early interventions for FEP. Conclusions. Most comparative evidence on pharmacotherapy relates to the older drugs, with clozapine, olanzapine, and risperidone superior on more outcomes than other SGAs. Older SGAs were similar to haloperidol on benefit outcomes but had fewer adverse event outcomes. Most psychosocial interventions improved functional outcomes, quality of life, and core illness symptoms, and several reduced relapse compared with usual care.

Objectives: Objectives. To compare different routes, doses, and dosing strategies of naloxone administration for suspected opioid overdose by emergency medical services (EMS) personnel in field settings, and to compare effects of transport to a health care facility versus nontransport following successful reversal of opioid overdose with naloxone. Methods. Four databases were searched through March 2017. Additional studies were identified from reference lists and technical experts. We included randomized controlled trials (RCTs) and cohort studies comparing different naloxone routes of administration, doses, or dosing strategies and on effects of transport or nontransport following successful reversal of opioid overdose with naloxone. Two investigators independently applied prespecified criteria to rate study quality. The strength of evidence was determined based on the overall risk of bias, consistency, directness, precision, and reporting bias. Results. Twelve studies met inclusion criteria. Three RCTs and four cohort studies compared different routes of administration. Two trials compared intranasal (IN) with intramuscular (IM) naloxone administration (strength of evidence [SOE] for all outcomes: low). While 2 mg of a higher-concentration formulation of IN naloxone (2 mg/1 mL) is similar in efficacy to 2 mg of IM naloxone, 2 mg of a lower-concentration formulation of IN naloxone (2 mg/5 mL formulation) is less effective than the same dose IM but associated with decreased risk of agitation and/or irritation. The 2 mg/5 mL formulation of IN naloxone studied in this trial is lower than concentrations used in the United States. In both trials, IN naloxone was associated with increased likelihood of rescue naloxone use. Although one RCT and two observational studies evaluated intravenous (IV) versus IN naloxone, evidence was insufficient to determine comparative benefits and harms, due to methodological limitations and poor applicability to U.S. EMS settings (SOE: insufficient). There was insufficient evidence from two observational studies to compare parenteral routes of administration (IM, IV, or subcutaneous [SQ]). No study compared outcomes of patients transported versus not transported following successful reversal of opioid overdose with naloxone. Five studies reported low rates of deaths and serious adverse events (0% to 1.25%) in patients not transported to a hospital after successful naloxone treatment, but used an uncontrolled design and had other methodological limitations (SOE: insufficient). Limitations. Few studies met inclusion criteria, all studies had methodological limitations, and no study evaluated naloxone auto-injectors or IN naloxone formulations recently approved by the US Food and Drug Administration (FDA). Conclusions. Low-strength evidence suggested that higher-concentration IN naloxone (2 mg/1 mL) is similar in efficacy to IM naloxone (2 mg), with no difference in adverse events. Research is needed on the comparative effectiveness of the FDA-approved naloxone auto-injectors (0.4 mg and 2 mg) and highly concentrated (4 mg/0.1 mL and 2 mg/0.1 mL) IN naloxone reformulation, different doses, and dosing strategies. Uncontrolled studies suggested that nontransport of patients following successful reversal of naloxone overdose might be associated with a low rate of serious harms, but patients were probably at low risk for such events, and there was insufficient evidence to determine risk of transport versus nontransport.

Objectives: Our objective is to determine the efficacy and adverse events profile of cryotherapy for the treatment of basal cell carcinoma compared to other therapeutic options or non intervention.

Objectives: We conducted a technology assessment to summarize and appraise the current evidence regarding the effectiveness and safety of bariatric surgery in the Medicare-eligible population.

Objectives: SR for AHRQ and CMS on psychometric properties of functional measures in lower limb amputees, heterogeneity of treatment effect of lower limb prostheses and components (LLP), and long term outcomes.

Objectives: Technical Brief

Objectives: Although a number of systematic reviews on dry eye have been published, the quality of these reviews remains unclear. We will characterize and appraise the methodological quality of systematic reviews on interventions for dry eye. The purpose of our study is to evaluate the current available evidence on interventions for dry eye, state the strengths and limitations and formulate recommendations for improving future review conduct.

Objectives: The objectives of this database are to: 1. Systematically compile and provide access to primary, English-language, peer-reviewed science linking dietary fiber intake in humans to one or more of 10 potential health benefits 2. Provide researchers with a tool to understand how different fibers are characterized in studies 3. Facilitate researchers in identifying gaps in the current research 4. Create a database to serve as a starting foundation of primary human literature for conducting evidence-based reviews and meta-analyses 5. Efficiently assist researchers in identifying fibers of interest. This database should serve as a foundation for future work. Specific inclusion and exclusion criteria, detailed in the user manual, were applied in determining database eligibility; thus, this database is not intended to serve as a sole source for identifying all possible fiber literature for the purposes of conducting a meta-analysis or systematic review. This database contains Population, Intervention, Comparator, and Outcome (PICO) data to help users formulate and narrow the focus of their research question. It is expected that secondary searches will be conducted to augment this database.

Objectives: This review assessed evidence for interventions aimed at preventing or delaying the onset of age-related cognitive decline, mild cognitive impairment (MCI), or clinical Alzheimer’s-type dementia (CATD).

Objectives: The objectives of this database are to: 1. Systematically compile and provide access to primary, English-language, peer-reviewed science linking dietary fiber intake in humans to one or more of 9 potential health benefits 2. Provide researchers with a tool to understand how different fibers are characterized in studies 3. Facilitate researchers in identifying gaps in the current research 4. Create a database to serve as a starting foundation of primary human literature for conducting evidence-based reviews and meta-analyses 5. Efficiently assist researchers in identifying fibers of interest. This database should serve as a foundation for future work. Specific inclusion and exclusion criteria, detailed in the user manual, were applied in determining database eligibility; thus, this database is not intended to serve as a sole source for identifying all possible fiber literature for the purposes of conducting a meta-analysis or systematic review. This database contains Population, Intervention, Comparator, and Outcome (PICO) data to help users formulate and narrow the focus of their research question. It is expected that secondary searches will be conducted to augment this database.

Objectives: This review was conducted to evaluate the effectiveness and safety of interventions targeting sensory challenges in children with Autism Spectrum Disorder (ASD). This report is a update on a previous report from 2011.

Objectives: This review was conducted to evaluate the comparative effectiveness and safety of medical interventions (defined broadly as interventions involving the administration of external substances to the body or use of external, non-behavioral procedures to treat symptoms of ASD) for children with Autism Spectrum Disorder (ASD). This report is a update on a previous report from 2011.

Objectives: Objectives. To assess the predictive utility, reliability, and ease of use of the total Glasgow Coma Scale (tGCS) versus the motor component of the Glasgow Coma Scale (mGCS) for field triage of trauma, as well as comparative effects on clinical decisionmaking and clinical outcomes. Data Sources. MEDLINE®, CINAHL, PsycINFO, HAPI (Health & Psychosocial Instruments), and the Cochrane Databases (January 1995 through June, 2016). Additional studies were identified from reference lists and technical experts. Study Selection. Studies on the predictive utility of the tGCS versus the mGCS or Simplified Motor Scale (SMS) (a simplified version of the mGCS), randomized trials and cohort studies on effects of the tGCS versus the mGCS on rates of over- or under-triage, and studies on interrater reliability and ease of use of the tGCS, mGCS, and/or SMS. Data Extraction. One investigator abstracted details about study characteristics and results; a second investigator checked data for accuracy. Two investigators independently applied prespecified criteria to rate study quality. Data on discrimination of tGCS versus mGCS and tGCS versus SMS were pooled using a random effects model. The strength of evidence was determined based on the overall risk of bias, consistency, directness, precision, and reporting bias. Results. 33 studies met inclusion criteria; 24 studies addressed predictive utility and 10 addressed interrater reliability or ease of use. No study assessed comparative effects on over- or under-triage or clinical outcomes. For in-hospital mortality, the tGCS is associated with slightly greater discrimination than the mGCS (pooled mean difference in area under the receiver operating characteristic curve [AUROC] 0.015, 95% confidence interval [CI] 0.009 to 0.022, I2=85%, 12 studies; strength of evidence [SOE]: Moderate) or the SMS (pooled mean difference in AUROC 0.030, 95% CI 0.024 to 0.036, I2=0%, 5 studies; SOE: Moderate). This means that for every 100 trauma patients, the tGCS is able to correctly discriminate 1 to 3 more cases of in-hospital mortality from cases without in-hospital mortality than the mGCS or the SMS . The tGCS is also associated with greater discrimination than the mGCS or SMS for receipt of neurosurgical interventions, severe brain injury, and emergency intubation (differences in AUROC ranged from 0.03 to 0.05; SOE: Moderate). Differences in discrimination between the mGCS versus the SMS were small (differences in the AUROC ranged from 0.000 to 0.01; SOE: Moderate). Findings were robust in sensitivity and subgroup analyses based on age, type of trauma, study years, assessment setting (out-of-hospital vs. emergency department), risk of bias assessment, and other factors. Differences between the tGCS, mGCS, and SMS in diagnostic accuracy (sensitivity, specificity) based on standard thresholds (scores of ≤15, ≤5, and ≤1) were small, based on limited evidence (SOE: Low). The interrater reliability of tGCS and mGCS appears to be high, but evidence was insufficient to determine if there were differences between scales (SOE: Insufficient). Three studies found the tGCS associated with a lower proportion of correct scores than the mGCS (differences in proportion of correct scores ranged from 6% to 27%), though the difference was statistically significant in only one study (SOE: Low). Limitations. Evidence on comparative predictive utility was primarily restricted to effects on discrimination. All studies on predictive utility were retrospective and the mGCS and SMS were taken from the tGCS rather than independently assessed. Most studies had methodological limitations. We restricted inclusion to English-language studies and were limited in our ability to assess publication bias. Studies on ease of use focused on scoring of video or written patient scenarios; field studies and studies on other measures of ease of use such as time required and assessor satisfaction were not available. Conclusions. The tGCS is associated with slightly greater discrimination than the mGCS or SMS for in-hospital mortality, receipt of neurosurgical interventions, severe brain injury, and emergency intubation. The clinical significance of small differences in discrimination is likely to be small, and could be offset by factors such as convenience and ease of use. Research is needed to understand how use of the tGCS versus the mGCS or SMS impacts clinical outcomes and risk of over- or under-triage.

Objectives: OBJECTIVES: The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP.

Objectives: OBJECTIVES: The objective of the review was to assess the effectiveness and safety of corticosteroids as adjunctive therapy for bacterial keratitis. Secondary objectives included evaluation of health economic outcomes and quality of life outcomes.

Objectives: Background: Primary congenital glaucoma (PCG) manifests within the first few years of a child's life and is not associated with any other systemic or ocular abnormalities. PCG results in considerable morbidity even in developed countries. Several surgical techniques for treating this condition, and lowering the intraocular pressure (IOP) associated with it, have been described. Objectives: To compare the effectiveness and safety of different surgical techniques for PCG.

Objectives: Background: Glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell death resulting in damage to the optic nerve head and the retinal nerve fiber layer. Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment epithelium (the densely pigmented posterior surface of the iris) that leads to dispersion of the pigment and its deposition on various structures within the eye. Pigmentary glaucoma is a specific form of open-angle glaucoma found in patients with pigment dispersion syndrome. Topcial medical therapy is usually the first-line treatment; however, peripheral laser iridotomy has been proposed as an alternate treatment. Peripheral laser iridotomy involves creating an opening in the iris tissue to allow drainage of fluid from the posterior chamber to the anterior chamber and vice versa. Equalizing the pressure within the eye may help to alleviate the friction that leads to pigment dispersion and prevent visual field deterioration. However, the effectiveness of peripheral laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown. Objectives: The objective of this review was to assess the effects of peripheral laser iridotomy compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no treatment, for pigment dispersion syndrome and pigmentary glaucoma.

Objectives: OBJECTIVES: To evaluate the effects of perioperative antibiotic prophylaxis for endophthalmitis following cataract surgery compared with no prophylaxis or other form of prophylaxis.

Objectives: Background: Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the commonest form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death. Objectives: To systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of OAG in adults.

Objectives: OBJECTIVES: To evaluate the relative effectiveness and safety of medical therapy for the treatment of AK.

Objectives: Background: Angle-closure glaucoma is characterized by obstruction to the outflow of aqueous humor and consequent rise in intraocular pressure. The obstruction may result from an anatomical predisposition of the eye or may be due to pathophysiologic processes in any part of the eye. The former is considered the primary form and the latter a secondary form of angle closure. Relative pupillary block obstructing free flow of aqueous from the posterior chamber of the eye to the anterior chamber is considered to be the most common mechanism of angle closure. Crowding of the angle is another mechanism, which often coexists with pupillary block. This can result from an anterior placement of the lens due to an increase in the thickness of the lens (as occurs with aging), anterior displacement by a posterior force (for example choroidal effusion), or laxity of the zonules. Objectives: The objective of this review was to assess the effectiveness of lens extraction for chronic primary angle-closure glaucoma compared with other interventions for the condition in people without past history of acute-angle closure attacks.

Objectives: OBJECTIVES: To assess the effects of interventions for trachomatous trichiasis for people living in endemic settings.

Objectives: OBJECTIVES: The objective of this review was to analyse the effects of various surgical and non-surgical treatments in randomised trials of participants with intermittent exotropia, and to report intervention criteria and determine the significance of factors such as age with respect to outcome.

Objectives: OBJECTIVES: To assess the comparative effectiveness of fornix- versus limbal-based conjunctival flaps in trabeculectomy for adult glaucoma, with a specific focus on intraocular pressure (IOP) control and complications (adverse effects).

Objectives: OBJECTIVES: The objective of this review was to assess the effects of face washing promotion for the prevention of active trachoma in endemic communities.

Objectives: OBJECTIVES: To assess the evidence for the effectiveness of environmental sanitary measures on the prevalence of active trachoma in endemic areas.

Objectives: OBJECTIVES: The primary aim of this review was to assess the effectiveness of doxycycline plus ivermectin versus ivermectin alone for prevention and treatment of onchocerciasis. The secondary aim was to assess the effectiveness of doxycycline plus ivermectin versus ivermectin alone for prevention and treatment of onchocercal ocular lesions in communities co-endemic for onchocerciasis and Loa loa (loiasis) infection.

Objectives: OBJECTIVES: To assess the relative effectiveness, primarily with respect to IOP control and safety, of the use of different devices as adjuncts to trabeculectomy compared with standard trabeculectomy in eyes with glaucoma.

Objectives: To determine the safety, efficacy, and evidence for halting disease progression for retinal prosthesis systems (RPSs) and the outcomes that are and could be assessed in future studies of these devices.

Objectives: OBJECTIVES: The objective of this review was to assess the effects of corticosteroids on visual recovery in eyes with acute optic neuritis.

Objectives: OBJECTIVES: To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis.

Objectives: OBJECTIVES To assess the relative effectiveness and safety of combined surgery versus cataract surgery (phacoemulsification) alone for co-existing cataract and glaucoma. The secondary objectives include cost analyses for different surgical techniques for co-existing cataract and glaucoma.

Objectives: OBJECTIVES: The aim of this review was to investigate interferon alfa as a treatment modality for neovascular age-related macular degeneration.

Objectives: To assess and compare the effectiveness and safety of intravitreal injections of aflibercept versus ranibizumab, bevacizumab, or sham for treatment of patients with neovascular AMD.

Objectives: Background: Glaucoma is a multifactorial optic neuropathy characterized by an acquired loss of retinal ganglion cells at levels beyond normal age-related loss and corresponding atrophy of the optic nerve. Although many treatments are available to manage glaucoma, glaucoma is a chronic condition. Some patients may seek complementary or alternative medicine approaches such as acupuncture to supplement their regular treatment. The underlying plausibility of acupuncture is that disorders related to the flow of Chi (the traditional Chinese concept translated as vital force or energy) can be prevented or treated by stimulating relevant points on the body surface. Objectives: The objective of this review was to assess the effectiveness and safety of acupuncture in people with glaucoma.

Objectives:

Objectives: We anticipate this report will be of primary value to organizations that develop guidelines for tonsillectomy, to clinicians who provide care for children with indications for tonsillectomy, and for families making treatment decisions. Children who are candidates for tonsillectomy may be treated by clinicians including pediatricians, otolaryngologists, sleep medicine physicians, allergists, family physicians, anesthesiologists, infectious disease physicians, nurse practitioners, physician assistants, and nurses. This report supplies practitioners and researchers up-to-date information about the current state of evidence and assesses the quality of studies that aim to determine the outcomes and safety of tonsillectomy.

Objectives: We assessed the evidence about management of uterine fibroids. Specifically, we sought to determine effectiveness of interventions, risks of harm, and whether individual or fibroid characteristics influence outcomes.

Objectives:

Objectives: Update of review of VTE thromboprophylaxis after total hip replacement, total knee replacement, and hip fracture surgery.

Objectives: Comparison of the benefits and harms of second-generation antidepressants (SGAs), psychological treatment options as first-step interventions for adult outpatients with acute -phase major depressive disorder (MDD), and as second-step interventions for patients with MDD who did not achieve remission after a first treatment attempt with SGAs.

Objectives: Resident safety issues are common in nursing homes. Relevant literature reports a range of poor clinical outcomes thought to be preventable if specific care processes were consistently implemented. The goal of this project was to summarize relevant literature, including identifying safety issues and contextual factors that affect safety in nursing homes; potential hospital safety interventions of relevance to nursing homes; literature on safety interventions evaluated in nursing homes; barriers and facilitators of interventions; and future directions for safety research in this setting.

Objectives: Comparison of the benefits and harms of second-generation antidepressants (SGAs), psychological treatment options as first-step interventions for adult outpatients with acute -phase major depressive disorder (MDD), and as second-step interventions for patients with MDD who did not achieve remission after a first treatment attempt with SGAs.

Objectives: Comparison of the benefits and harms of second-generation antidepressants (SGAs), psychological treatment options as first-step interventions for adult outpatients with acute -phase major depressive disorder (MDD), and as second-step interventions for patients with MDD who did not achieve remission after a first treatment attempt with SGAs.

Objectives:

Objectives: Background: The optimal blood pressure target in patients with chronic kidney disease (CKD) is unclear. Purpose: To summarize trials comparing lower versus higher blood pressure targets in adult patients with CKD and focus on proteinuria as an effect modifier.

Objectives: The objectives of this database are to: 1. Systematically compile and provide access to primary, English-language, peer-reviewed science linking dietary fiber intake in humans to one or more of 9 potential health benefits 2. Provide researchers with a tool to understand how different fibers are characterized in studies 3. Facilitate researchers in identifying gaps in the current research 4. Create a database to serve as a starting foundation of primary human literature for conducting evidence-based reviews and meta-analyses 5. Efficiently assist researchers in identifying fibers of interest This database should serve as a foundation for future work. Specific inclusion and exclusion criteria, detailed in the user manual, were applied in determining database eligibility; thus, this database is not intended to serve as a sole source for identifying all possible fiber literature for the purposes of conducting a meta-analysis or systematic review. This database contains Population, Intervention, Comparator, and Outcome (PICO) data to help users formulate and narrow the focus of their research question. It is expected that secondary searches will be conducted to augment this database.

Objectives:

Objectives: Adults with serious mental illness (SMI) often experience gaps in access to needed health care compared with other populations. Such disparities may be even more pronounced between certain groups of patients with SMI, differing by race, ethnicity, gender, economic disadvantage (including housing stability) and socioeconomic status, and geographic location (chiefly, rural versus urban residence); disparities arise as well for lesbian, gay, bisexual, and transgender (LGBT) individuals and those who have difficulty communicating in English (because it is a second language).

Objectives: Comparison of the benefits and harms of second-generation antidepressants (SGAs), psychological treatment options as first-step interventions for adult outpatients with acute -phase major depressive disorder (MDD), and as second-step interventions for patients with MDD who did not achieve remission after a first treatment attempt with SGAs.

Objectives:

Objectives: Objective. To assess the efficacy, comparative effectiveness, and adverse effects of drugs newly used (last 10 years) within several drug classes (i.e., alpha blockers – silodosin; antimuscarinics - tolterodine, solifenacin, fesoterodine; beta-3 adrenoceptor agonists – mirabegron; phosphodiesterase type 5 (PDE-5) inhibitors - tadalafil, sildenafil) to treat lower urinary tract symptoms attributed to BPH. Data sources. Ovid MEDLINE®, the Cochrane Central Register of Controlled Trials, and Ovid Embase bibliographic databases; hand searches of references of relevant studies. Review methods. We searched bibliographic databases from earliest electronic indexing through March 2015. Two investigators screened titles and abstracts of search results and full-text of relevant references for eligibility. Eligible studies included randomized controlled trials (RCTs) and long-term (>1 year duration) observational studies for long-term adverse effects. We assessed risk of bias for RCTs, extracted data, pooled data for analysis when appropriate and feasible and evaluated strength of evidence for comparisons and outcomes. Results. We searched bibliographic databases through July 2015 for studies testing specific drugs or combinations that included newly used drugs. We synthesized evidence from 57 unique trials and 7 observational studies. All trials lasted less than 3 months. Silodosin was more effective than placebo in improving LUTS, but was similar to tamsulosin, and there were more adverse effects with silodosin, including abnormal ejaculation. Solifenacin/alpha blocker (AB) combination therapy was better than placebo, but tolterodine/AB, solifenacin/AB, and fesoterodine/AB combination therapy were similar to AB monotherapy, and there was often evidence of higher adverse effects with combination therapy. Tadalafil improved LUTS more than placebo but had more adverse effects. Traditional ABs achieved better or similar outcomes than tadalafil; most evidence on comparative adverse effects was insufficient. We identified trials testing other drugs (mirabegron, oxybutynin, darifenacin, sildenafil, and vardenafil), but found the evidence insufficient to draw conclusions about efficacy, comparative effectiveness, or adverse effects. Evidence was insufficient on long-term effectiveness, other relevant outcomes (prevention of symptom progression, acute urinary retention or need for surgical intervention) or adverse effects. Conclusions. Several drugs newly used, along or in combination with traditional drugs, to treat LUTS attributed to BPH show some evidence of short-term symptom efficacy when compared to placebo. However, outcomes are similar to traditional alpha-blocker therapy and adverse effects are often higher with the newly used drugs or combination therapies. Data were not available to assess long-term maintenance, prevention of disease progression (including acute urinary retention or need for surgical intervention), and adverse effects.

Objectives: Objective. Update a 2011 review of differences in accuracy of diagnostic tests and the effects of interventions to prevent and treat C. difficile infection (CDI) in adults. Data sources. Medline, the Cochrane Clinical Trials Registry, EMBASE, from 2010 through April 2015 plus reference lists of included studies and recent systematic reviews. Methods. Two investigators screened abstracts and full texts of identified references for eligibility. Eligible studies included studies of sensitivity and specificity for diagnostic tests in patients at risk for CDI. We included randomized controlled trials or high quality cohort studies enrolling adult patients with CDI or suspected CDI for treatment interventions. Prevention studies also included adult patients at risk for CDI and observational study designs. Two investigators extracted data, assessed individual study risk of bias, and evaluated the strength of evidence for each comparison and outcome. Pooled estimates were analyzed to assess the efficacy and comparative effectiveness of a variety of treatments. Results. We identified 37 diagnostic studies and 56 studies evaluating prevention or treatment interventions to update the review. High-strength evidence showed nucleic amplification tests were sensitive and specific for CDI when using culture as the reference standard. Low-strength evidence found some institutional prevention interventions, such as antibiotic prescribing practices and transmission interruption (terminal room cleaning with hydrogen peroxide vapor and handwashing campaigns) reduces CDI incidence. Low-strength evidence also suggests prevention programs can be sustained over several years. For CDI treatment, vancomycin is more effective than metronidazole (high-strength evidence), and the effect does not vary by severity (moderate-strength evidence). Fidaxomicin remains noninferior to vancomycin for the initial cure of CDI (moderate-strength evidence), but is superior to vancomycin for prevention of recurrent CDI (now high-strength evidence). Although both FMT and probiotics were the subject of a significant number of new studies, the overall high risk of bias of many of these studies necessitated low-strength of evidence ratings. Specifically, low-strength evidence suggests that FMT may have a significant effect on reducing recurrent CDI. Similarly, low-strength evidence suggests that lactobaccilus strains and multiorganism probiotics also can reduce recurrent CDI. However, Saccharomyces boulardii was no more effective than placebo in preventing recurrent CDI. Evidence for FMT for refractory CDI was insufficient. Few studies reported adverse events; when reported, few events were noted. Conclusions. Research on diagnostic testing for and interventions to treat CDI expanded considerably in 4 years. Nucleic acid amplification tests have high sensitivity and specificity for CDI. Vancomycin is more effective than metronidazole for initial CDI, while fidaxomicin is more effective than vancomycin for the prevention of recurrent CDI. FMT and lactobacillus probiotics to restore colonic biodiversity and improve patient resistance to CDI or recurrence have low strength but relatively consistent positive evidence for efficacy.

Objectives: Objective. To examine existing system-, clinic-, provider-, and individual-level interventions to improve culturally appropriate health care for people with disabilities; lesbian, gay, bisexual, and transgender (LGBT) populations; and racial-ethnic minority populations. Data sources. Ovid MEDLINE®, PsycINFO®, Ovid Embase®, and the Cochrane EPOC; hand searches of references of relevant studies. Review methods. Two investigators screened abstracts and full-text articles of identified references for eligibility. Eligible studies included randomized controlled trials (RCTs), prospective cohort studies, and other observational studies with comparators that evaluated cultural competence interventions aimed at reducing health disparities in the formal healthcare system. Two investigators abstracted data and assessed risk of bias. Given the sparse and patchy literature that precluded pooling, a qualitative analysis is provided. Results. Over 37,000 nonduplicated, English language citations were reviewed; 56 unique studies were identified as of June, 2015: 20 RCTs and five observational studies for individuals with disabilities; five RCTs (six manuscripts) and six observational studies for LGBT populations; and 14 RCTs (15 manuscripts), four observational studies, and two systematic reviews for members of racial and ethnic minorities. Interventions fell into four broad categories: (1) provider trainings and education; (2) interventions providing alteration of an established protocol, or the delivery of an established protocol, to meet the needs of a target population; (3) interventions prompting patients to interact with the formal health care system or health care providers; and (4) interventions aimed at providing culturally competent care at the point of service. Educational programs and trainings to improve professional students’ and providers’ cultural competence behavior is the most prevalent type of cultural competence intervention. Two existing, high quality systematic reviews of provider educational interventions for racial/ethnic minority populations found low-strength evidence that cultural competence training had mixed effects for intermediate outcomes and no effect on treatment outcomes. Sixteen studies aimed at changing provider attitudes and beliefs through training or curricula were identified for the disability population. Eleven of these studies focused on reducing professional stigma toward people with serious or chronic mental illness; five focused on changing professional attitudes and beliefs about people with physical or intellectual disability. Three educational interventions were identified for the LGBT population. Several short-term effects were evaluated; however, long-term effects of provider training on provider cultural competence behavior in the clinical setting and subsequent patient health outcomes have not been evaluated for the disability and LGBT populations. Two included studies reported a potential harm from provider training, an increase in negative attitudes, or stigma resulting from intervention. Interventions providing alterations of an established protocol were concentrated in the racial/ethnic minority populations. The 12 studies of culturally tailored health care interventions for racial/ethnic minority populations focused primarily on treatment of chronic physical or mental health conditions (e.g., diabetes, depression, substance abuse). Two psychological interventions were also tailored for members of the LGBT population. Another common type of intervention was to provide additional resources to encourage or empower patients to interact with the formal health care system and/or health care providers. The stated aims of these types of interventions were to increase receipt of screenings for which disparities are well-documented (e.g., papanicolaou tests for people with mobility impairments or colorectal cancer screening among Latino immigrants), or to help patients engage in medical decisionmaking. These studies met inclusion criteria if the intervention was conducted by a medical professional in a formal health care system. One potential limitation of these types of interventions is that they rely on strong identification with a common culture. The population groups highlighted in this review are large and diverse. Creating an intervention for “African Americans” or “women who have sex with women” may be differentially effective for specific subpopulations. The most common culturally competent point of service interventions were documents, similar to a handheld medical record, that patients carried to their appointments to prompt providers to evaluate areas of known disparity for a specific population. These interventions may be coupled with provider notices or trainings. Virtual interventions were also considered culturally competent point of service interventions for some people with disabilities, as they create access in a unique way. These interventions are seen as conceptually parallel to infrastructure changes that improve access for people with physical disabilities. For the majority of included studies, the risk of bias was high. The most common methodological problems were: lack of randomization to treatment; lack of attention control; little or no followup; and failure to report unintended consequences. Large segments of vulnerable or disadvantaged populations, such as children with disabilities, people who may be gender nonconforming or transgender, or numerous racial or ethnic groups, including Native Americans or Alaskan Natives, remain essentially invisible in the cultural competence literature. This is compounded for people who are members of more than one priority population. Conclusions. None of the included studies measured the effect of cultural competence interventions on health care disparities. Most of the training interventions measured changes in professional attitudes toward the population of interest, but did not measure the downstream effect of changing provider beliefs on the care delivered to patients. Interventions that altered existing protocols, empowered patients to interact with the formal health care system, or prompted provider behavior at the point of care were more likely to measure patient-centered outcomes. The medium or high risk of bias of the included studies, the heterogeneity of populations, and the lack of measurement consensus prohibited pooling estimates or commenting about efficacy in a meaningful or responsible way. The term cultural competence is not well defined for the LGBT and disability populations, and is often conflated with patient-centered or individualized care. There are many gaps in the literature; many large subpopulations are not represented.

Objectives: Objective. To assess the efficacy, comparative effectiveness, and harms of treatments for insomnia disorder in the general adult population and older adults. Data sources. Ovid MEDLINE®, the Cochrane Central Register of Controlled Trials, Embase®, and PsycINFO®SYCINFO bibliographic databases; hand searches of references of relevant studies. Review methods. Two investigators screened abstracts and full-text articles of identified references for eligibility. Eligible studies included systematic reviews, randomized controlled trials (RCTs), and long-term observational pharmacologic studies enrolling participants with insomnia disorder. We analyzed data for global outcomes (measures that assess both sleep and daytime functioning associated with sleep), sleep parameters, and harms. We assessed risk of bias for RCTs, extracted data, assessed quality of relevant systematic reviews, and evaluated strength of evidence for comparisons and outcomes. Pooled estimates were analyzed to assess the efficacy and comparative effectiveness of treatments. Results. We searched bibliographic databases through January 2015 for studies evaluating psychological, pharmacologic, and complementary, and alternative medicine interventions for insomnia disorder. We synthesized evidence from 181 unique studies (data from 128 unique RCTs and 3 systematic reviews that( synthesizeing data from 42 unique RCTs) and 12 observational studies. Sample sizes and enrollment criteria varied; most trials were short in duration. Outcome reporting and intervention effect sizes varied, and a large placebo response was often observed. Cognitive behavioral therapy for insomnia (CBT-I) improved global outcomes and nearly all sleep parameters in the general adult population, older adults, and adults with pain. We found insufficient evidence on adverse effects of these interventions. Evidence was less robust for psychological interventions other than CBT-I, but low -strength evidence shows that some interventions improve some sleep outcomes. Low- to moderate -strength evidence indicated that the nonbenzodiazepine hypnotics, eszopiclone and zolpidem, and the orexin receptor antagonist, suvorexant, improved short-term global and sleep outcomes in general adult populations. Doxepin improved sleep outcomes. The absolute mean effect was small. Evidence for benzodiazepine hypnotics, melatonin agonists, and antidepressants in general populations and for most pharmacologic interventions in older adults was generally insufficient. Evidence on adverse effects from RCT data was generally insufficient or low strength. Observational studies suggest that hypnotics may be associated with dementia, fractures, and major injury. Food and Drug Administration (FDA) labels warn about cognitive and behavioral changes, including driving impairment, and other harms, and advise lower doses reduction in for females and older/debilitated adults. Evidence on complementary and alternative medicine was insufficient. Evidence was insufficient to compare hypnotic medications within or across classes or versus CBT-I. Conclusions. CBT-I or medical therapy with eszopiclone, zolpidem, and suvorexant improve global and sleep outcomes for insomnia disorder. Clinical significance, applicability, comparative effectiveness, and long-term efficacy, especially among older adults, are less well known. Effect sizes vary, and a large placebo response is sometimes observed. Observational studies suggest an association of hypnotics with infrequent but serious, harms. FDA labels provide specific warnings and precautions for drugs approved for insomnia.

Objectives: Objective. To assess the efficacy and comparative effectiveness of surgical and nonsurgical treatments for fecal incontinence (FI) in adults. Data sources. Ovid MEDLINE®, Embase®, PEDro®, CINAHL, AMED, and the Cochrane Central Register of Controlled Trials (CENTRAL), hand searches of systematic reviews. Methods. Two investigators screened abstracts of identified references for eligibility (examined treatments in adults with FI, published from 1980 to present, had a control/comparator group; case series were included for surgical interventions). Full-text articles were reviewed to identify patient-reported outcomes (FI episodes, FI severity, quality of life, urgency, pain, other). We extracted data, assessed risk of bias of individual studies, and evaluated strength of evidence for each comparison and outcome. Results. Sixty-three unique studies met inclusion criteria; an additional 53 surgical case series were examined for surgical adverse effects. Enrolled adults were mostly female with mixed FI etiologies. Most RCTs were nonsurgical (n=38); 13 examined pelvic floor muscle training (PFMT) and PFMT with biofeedback (PFMT-BF). Meta-analysis was not possible because numerous outcomes were used. Low strength evidence suggests that dietary fiber (psyllium) decreases FI episodes (-2.5 per week) at 1 month; clonidine has no effect; and PFMT-BF with electrostimulation is no more effective than PFMT-BF for FI severity and quality of life over 2 to 3 months. Low-strength evidence at 6 months suggests that dextranomer anal bulking injections are more effective than sham injections on FI quality of life, the number of FI-free days, and the percent of adults with at least 50 percent reduction from baseline in FI episodes; but no more effective than PFMT-BF with or without electrostimulation on FI severity (PFMT-BF -5.4 vs. dextranomer -4.6 point Vaizey score improvements) and quality of life; and no more effective than sham injection on FI severity (-2.5 versus -1.7 point sham improvement in Cleveland Clinic FI score [CCFIS]) or FI episode frequency. Moderate-strength evidence suggests that Durasphere® (off-label) bulking injections reduce FI severity up to 6 months (-4 to -5 points CCFIS) but gains diminish thereafter. Evidence was insufficient for all other surgical and nonsurgical comparisons. Surgical improvements varied. Noninvasive nonsurgical treatments had few minor adverse effects (AEs). Surgical treatments were associated with more frequent and more severe complications than nonsurgical interventions. AEs were most frequent for the artificial bowel sphincter (22-100 percent of adults). Surgical AEs ranged from minor to major (infection, bowel obstruction, perforation, fistula). Major surgical complications often required reoperation; fewer required permanent colostomy. Only 12 percent of randomized controlled trials (RCTs) were high quality. Conclusion. There is limited evidence to support any FI treatments beyond 3 to 6 months. It is difficult to compare the effectiveness of surgical to nonsurgical FI treatments because nonsurgical approaches generally precede surgery, and adults who undergo surgery have typically failed more nonsurgical treatment. Most current interventions show modest improvements in FI outcomes that meet minimal important differences (MID) in the short term, where MID is known. More invasive surgical procedures have substantial complications. Numerous outcome measures and lack of compliance with study reporting standards are modifiable impediments in the field. Future studies should focus on longer-term effects and attempt to identify subgroups of adults by FI etiology that might benefit from specific interventions.

Objectives: This small systematic review addresses interventions to prevent or de-escalate aggressive behavior and to reduce use of seclusion and restraint for aggressive behaviors. We focus on studies in acute health care settings, as to our knowledge no such review has been done using data from such settings.

Objectives: The calcineurin inhibitors (CNIs) tacrolimus and cyclosporine A (CsA) are effective immunosuppressive agents for renal transplantation, but they must be managed carefully to avoid toxicity. Routine therapeutic monitoring guides dosing, but uncertainty surrounds different monitoring methods and timepoints. Additionally, the effectiveness of strategies to reduce CNI exposure with lower therapeutic levels and other immunosuppressants is unclear. This systematic review evaluates the evidence for three Key Questions. Key Question 1 compares immunoassay analysis with liquid chromatographic or mass spectrometric analytical techniques for therapeutic monitoring of CNIs. Key Question 2 examines CsA monitoring timepoints. Key Question 3 evaluates alternatives to full-dose CNI regimens.

Objectives: The cleaning of hard surfaces in hospital rooms is essential for reducing the risk of healthcare-associated infections (HAIs). Many methods are available for cleaning and monitoring cleanliness, but their comparative effectiveness is not well understood. This Technical Brief summarizes the evidence base addressing environmental cleaning of high-touch surfaces in hospital rooms and highlights future research directions.

Objectives: The purpose of this review is to provide an evidence report that the National Institutes of Health, Office of Disease Prevention, Pathways to Prevention Workshop Program can use to inform a workshop focused on Total Worker Health® (TWH). TWH is defined as policies, programs, and practices that integrate protection from work-related safety and health hazards with promotion of injury and illness prevention efforts to advance worker well-being. This review describes the body of evidence evaluating TWH interventions, assesses the benefits and harms of interventions, and highlights research gaps and future research needs.

Objectives: Background: Genetics research in recent decades has discovered numerous genetic variants that help explain the etiology of developmental disabilities (DDs). Genetic tests (e.g., array comparative genomic hybridization, sequencing) are rapidly diffusing into clinical practice for diagnosing DDs or, more often, for determining their genetic etiology. An urgent need exists for a better understanding of these tests and their clinical utility. Purpose: This Technical Brief collects and summarizes information on genetic tests that are clinically available in the United States to detect genetic markers that predispose to DDs. It also identifies, but does not systematically review, existing evidence addressing the tests’ clinical utility. This Brief primarily focuses on patients with idiopathic or unexplained DDs, particularly intellectual disability, global developmental delay, and autism spectrum disorder. Several better-defined DD syndromes, including Angelman syndrome, fragile X syndrome, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Smith-Magenis syndrome, velocardiofacial syndrome, and Williams syndrome are also included. Patient-centered health outcomes (e.g., functional or symptomatic improvement) and intermediate outcomes (e.g., changes in clinical decisions or family reproductive decisions, the tests’ diagnostic accuracy and analytic validity) are examined. Methods: We sought input from nine Key Informants to identify important clinical, technology, and policy issues from different perspectives. We searched the National Center for Biotechnology Information’s Genetic Testing Registry (GTR) to identify genetic tests. A structured search of studies published since 2000 was performed to identify available evidence that addresses genetic tests’ clinical utility. Findings: Our search of the GTR database identified 672 laboratory-developed tests offered by 63 providers in 29 States. We also identified one test cleared by the U.S. Food and Drug Administration. Common genetic testing methods used include array comparative genomic hybridization, microarray, DNA sequencing (the Sanger method or next-generation sequencing), and polymerase chain reaction. We did not identify any studies that directly assessed the impact of genetic testing on health outcomes. Most of the clinical studies identified for indirect assessment of clinical utility are case series reporting on a test’s diagnostic yield.

Objectives: Objective. To assess the available evidence about home-based primary care (HBPC) interventions for adults with serious or disabling chronic conditions. Data sources. Articles from January 1998 through May 2015 were identified using Ovid MEDLINE, CINAHL, Clinical Trials.gov, Cochrane Database of Systematic Reviews, reference lists, and gray literature databases. Review methods. We included randomized controlled trials (RCTs) and observational studies of HBPC, including home visits by a primary care provider, longitudinal management, and comprehensive care. Study quality was assessed, data extracted, and results summarized qualitatively. Results. We identified 4,406 citations and reviewed 219 full-text articles; 19 studies were included. Two were RCTs while 17 were observational studies. The strongest evidence (moderate) was that HBPC reduces hospitalizations and hospital days. Reductions in emergency and specialty visits and in costs were supported by less strong evidence, while no or unclear effects were identified on hospital readmissions and nursing home days. Evidence about clinical outcomes was limited to studies that reported no significant differences in function or mortality. HBPC had a positive impact on patient and caregiver experience, including satisfaction, quality of life, and caregiver needs, but the strength of evidence for these outcomes was low. In studies that reported on the impact of patient characteristics, moderate evidence indicated frail or sicker patients are more likely to benefit from HBPC. No identified studies assessed the impact of organizational characteristics. No adverse events were reported. Only one study examined the potential for a negative impact; none was found. The services included in the HBPC interventions varied widely, and no identifiable combination was related to more positive outcomes. We did identify four studies that evaluated the addition of specific services. Combining palliative care and primary care home visits increased the likelihood of death at home (low strength of evidence), while studies on adding caregiver support (one study) or transitional care (one study) to HBPC were rated as insufficient evidence. Conclusions. Current research evidence is generally positive, providing moderate-strength evidence that HBPC reduces utilization of inpatient care, and providing low-strength evidence about its impact on utilization of other health services, costs, and patient and caregiver experience. Future research should focus on the content and organizational context of HBPC interventions so that experiences can be replicated or improved on by others. Additional research is also needed about which patients benefit most from HBPC and how HBPC can be best used in the continuum of care.

Objectives: Objectives. Low back pain is common and many pharmacological and nonpharmacological therapies are available. This review examines the evidence on the comparative benefits and harms of noninvasive treatments for low back pain. Data Sources. A prior systematic review (searches through October 2008), electronic databases (Ovid MEDLINE and the Cochrane Libraries, January 2008 to April 2015), reference lists, and clinical trials registries. Review Methods. Using predefined criteria, we selected systematic reviews of randomized trials of pharmacological treatments (acetaminophen, nonsteroidal anti-inflammatory drugs [NSAID]s, opioids, skeletal muscle relaxants, benzodiazepines, antidepressants, antiseizure medications, and systemic corticosteroids) and nonpharmacological treatments (psychological therapies, multidisciplinary rehabilitation, spinal manipulation, acupuncture, massage, exercise and related therapies, and various physical modalities) for nonradicular or radicular low back pain that addressed effectiveness or harms versus placebo, no treatment, usual care, a sham therapy, an inactive therapy, or another active therapy. We also included randomized trials that were not in systematic reviews. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively based on the totality of the evidence. Results. Of the 2,545 citations identified at the title and abstract level, a total of 156 publications were included. Most trials enrolled patients with pain symptoms of at least moderate intensity (e.g., >5 on a 0- to 10-point NRS for pain). Across interventions, pain intensity was the most commonly reported outcome, followed by back-specific function. When present, observed benefits for pain were generally in the small (5 to 10 points on a 0- to 100-point visual analogue scale [VAS] or 0.5 to 1.0 points on a 0- to 10-point numerical rating scale) to moderate (10 to 20 points) range. Effects on function were generally smaller than effects on pain; in some cases there were positive effects on pain but no effects on function, and fewer studies measured function than pain. Benefits were mostly measured at short-term followup. For acute low back pain, evidence suggested that NSAIDs (strength of evidence [SOE]: low to moderate), skeletal muscle relaxants (SOE: moderate), opioids (SOE: low), exercise (SOE: low), and superficial heat (SOE: moderate) are more effective than placebo, no intervention, or usual care and that acetaminophen (SOE: low) and systemic corticosteroids (SOE: low) are no more effective than placebo. For chronic low back pain, effective therapies versus placebo, sham, no treatment, usual care, or wait list are NSAIDs, opioids, tramadol, duloxetine, multidisciplinary rehabilitation, acupuncture, and exercise (SOE: moderate) and benzodiazepines, psychological therapies, massage, yoga, tai chi, and low-level laser therapy (SOE: low); spinal manipulation was as effective as other active interventions (SOE: moderate). Few trials evaluated the effectiveness of treatments for radicular low back pain, but the available evidence found that benzodiazepines, corticosteroids, traction, and spinal manipulation were not effective or associated with small effects (SOE: low). Relatively few trials directly compared the effectiveness of different medications, different nonpharmacological therapies, or compared pharmacological versus nonpharmacological therapies, and generally found no clear differences in effects. Pharmacological therapies were associated with increased risk of adverse events versus placebo (SOE: low to moderate). Trials were not designed or powered to detect serious harms from pharmacological therapies. Although rates appeared to be low, and there was not an increased risk of serious harms versus placebo, this does not rule out significant risk from some treatments. For nonpharmacological therapies, assessment of harms was suboptimal, but serious harms appeared rare (SOE: low). Conclusions. A number of pharmacological and nonpharmacological, noninvasive treatments for low back pain are associated with small to moderate, primarily short-term effects on pain versus placebo, sham, wait list, or no treatment. Effects on function were generally smaller than effects on pain. More research is needed to understand optimal selection of treatments, effective combinations and sequencing of treatments, effectiveness of treatments for radicular low back pain, and effectiveness on outcomes other than pain and function.

Objectives: Low-calorie sweeteners (LCS), also known as sugar substitutes, non-nutritive sweeteners, or artificial sweeteners, are ingredients added to foods and beverages to provide sweetness without adding a significant amount of calories. A large body of literature evidence exists on low-calorie sweeteners yet the health effects of LCS beyond body weight or composition remain unknown and have not been systematically reviewed. As evidence and interest on LCS continues to grow, there is the need to understand the potential effects of low-calorie sweeteners. LCS evidence map is a database that collects the features and characteristics of the LCS studies. (Paper PMID:26728979). LCS database includes data on study design (study design and duration), population (baseline health status, age, sample size, anthropometrics), intervention/comparison (type of LCS, comparisons or control groups, numbers of people analyzed, forms of administration), and outcomes/study endpoint. In addition, study aim/hypothesis and funding source were also collected. (LCS Manual and database Code book available through: http://static-content.springer.com/esm/art%3A10.1186%2Fs12874-015-0105-z/MediaObjects/12874_2015_105_MOESM2_ESM.docx). Outcomes were also coded into clinically and biologically relevant outcome groups, classified by the research team and a stakeholder panel, to better describe data in the map (See Outcome Groups Table in the codebook). Database Objectives • Provide a database of existing literature on LCS and health outcomes. • Index key features and characteristics for quick summary report generation. • Help identify LCS and health effect of interest and identify gaps in LCS research • Systematically collect information to support further evidence synthesis

Objectives: To systematically review evidence addressing the diagnosis and management of infantile hemangiomas (IH).

Objectives: 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.

Objectives: The objectives of this database are to: 1. Systematically compile and provide access to primary, English-language, peer-reviewed science linking dietary fiber intake in humans to one or more of 9 potential health benefits 2. Provide researchers with a tool to understand how different fibers are characterized in studies 3. Facilitate researchers in identifying gaps in the current research 4. Create a database to serve as a starting foundation of primary human literature for conducting evidence-based reviews and meta-analyses 5. Efficiently assist researchers in identifying fibers of interest This database should serve as a foundation for future work. Specific inclusion and exclusion criteria, detailed in the user manual, were applied in determining database eligibility; thus, this database is not intended to serve as a sole source for identifying all possible fiber literature for the purposes of conducting a meta-analysis or systematic review. This database contains Population, Intervention, Comparator, and Outcome (PICO) data to help users formulate and narrow the focus of their research question. It is expected that secondary searches will be conducted to augment this database.

Objectives: Objectives: This review sought to systematically review the available literature on health information exchange (HIE), the electronic sharing of clinical information across the boundaries of health care organizations. HIE has been promoted as an important application of technology in medicine that can improve the efficiency, cost-effectiveness, quality, and safety of health care delivery. However, HIE also requires considerable investment by sponsors, which have included governments as well as health care organizations. This review aims to synthesize the currently available research addressing HIE effectiveness, use, usability, barriers and facilitators to actual use, implementation; and sustainability, and to present this information as a foundation on which future implementation, expansion, and research can be based. Results: We included 136 studies overall, with 34 on effectiveness, 26 of which reported intermediate clinical, economic, or patient outcomes, and eight that reported on clinical perceptions of HIE. We also found 58 studies on the use of HIE, 22 on usability and other facilitators and barriers to actual use of HIE, 45 on facilitators or barriers to HIE implementation, and 17 on factors related to sustainability of HIE. No studies of HIE effectiveness reported impact on primary clinical outcomes (e.g., mortality and morbidity) or identified harms. Low-quality evidence somewhat supports the value of HIE for reducing duplicative laboratory and radiology test ordering, lowering emergency department costs, reducing hospital admissions (less so for readmissions), improving public health reporting, increasing ambulatory quality of care, and improving disability claims processing. In studies of clinician perceptions of HIE most respondents attributed positive changes to the HIE such as improvements in coordination, communication and knowledge about the patient. However in one study clinicians reported that the HIE did not save time and may not be worth the cost. Studies of HIE use found that HIE adoption has increased over time, with 76 percent of U.S. hospitals exchanging information in 2014, an 85 percent increase since 2008 and a 23 percent increase since 2013. HIE systems were used by 38 percent of office-based physicians in 2012 while use remains low, less than 1 percent, among long-term care providers. Within organizations with HIE, the number of users or the number of visits in which the HIE was used was generally very low. The degree of usability of an HIE was associated with increased rates of use, but not was not associated with effectiveness outcomes. The most commonly cited barriers to HIE use were lack of critical mass electronically exchanging data, inefficient workflow, and poorly designed interface and update features. Information was insufficient to allow us to assess usability by HIE function or architecture. Studies provided information on both external environmental and internal organizational characteristics that affect implementation and sustainability. General characteristics of the HIE organization (e.g. strong leadership) or specific characteristics of the HIE system were the most frequently cited facilitators while disincentives such as competition or lack of a business case for HIE were the most frequently identified barriers. Conclusions: The full impact of HIE on clinical outcomes and potential harms is inadequately studied, although evidence provides some support for benefit in reducing use of some specific resources and achieving improvements in quality of care measures. Use of HIE has risen over time and is highest in hospitals and lowest in long-term care settings. However, use of HIE within organizations that offer it is still low. Barriers to HIE use include lack of critical mass participating in the exchange, inefficient workflow, and poorly designed interface and update features. Studies have identified numerous facilitators and barriers to implementation and sustainability but the studies have not ranked or compared their impact. To advance our understanding of HIE, future studies need to address comprehensive questions, use more rigorous designs, use a standard for describing types of HIE, and be part of a coordinated, systematic approach to studying HIE.

Objectives: The purpose of this form is to abstract data from reports corresponding to a study included in a systematic review.

Objectives:

Objectives: 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.

Objectives: Structured Abstract Objectives. Low back pain is common and injections with corticosteroids are a frequently used treatment option. This report reviews the current evidence on effectiveness and harms of epidural, facet joint, and sacroiliac corticosteroid injections for low back pain conditions. Data Sources. A prior systematic review (searches through July 2008), electronic databases (Ovid MEDLINE, Scopus, and the Cochrane Libraries from January 2008 through October 2014), reference lists, and clinical trials registries. Review Methods. Using predefined criteria, we selected randomized trials of patients with lumbosacral radiculopathy, spinal stenosis, nonradicular back pain, or chronic postsurgical back pain that compared effectiveness or harms of epidural, facet joint, or sacroiliac corticosteroid injections versus placebo or other interventions. We also included randomized trials that compared different injection techniques and large (sample sizes >1000) observational studies of back injections that reported harms. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively and using meta-analysis on outcomes stratified by immediate- (1 week to <2 weeks), short- (2 weeks to <3 months), intermediate- (3 months to <1 year), and long-term (>1 year) followup. Results. Seventy-eight randomized trials of epidural injections, 13 trials of facet joint injections, and one trial of sacroiliac injections were included. For epidural corticosteroid injections versus placebo interventions for radiculopathy, the only statistically significant effects were on mean improvement in pain at immediate-term followup (weighted mean difference [WMD] ‒7.55 on a 0 to 100 scale, 95% CI ‒11.4 to ‒3.74) (strength of evidence [SOE]: moderate), mean improvement in function at immediate-term followup when an outlier trial was excluded (standardized mean difference [SMD] ‒0.33, 95% CI ‒0.56 to ‒0.09) (SOE: low), and risk of surgery at short-term followup (relative risk [RR] 0.62, 95% CI 0.41 to 0.92) (SOE: low). The magnitude of effects on pain and function was small, did not meet predefined thresholds for minimum clinically important differences, and there were no differences on outcomes at longer-term followup. Evidence on effects of different injection techniques, patient characteristics, or comparator interventions estimates was limited and did not show clear effects. Trials of epidural corticosteroid injections for radiculopathy versus nonplacebo interventions did not clearly demonstrate effectiveness (SOE: insufficient to low). Evidence was limited for epidural corticosteroid injections versus placebo interventions for spinal stenosis (SOE: low to moderate) or nonradicular back pain (SOE: low), but showed no differences in pain, function, or likelihood of surgery. Studies found no clear differences between various facet joint corticosteroid injections (intra-articular, extra-articular [peri-capsular], or medial branch) and placebo interventions (SOE: low to moderate). There was insufficient evidence from one very small trial to determine effects of peri-articular sacroiliac joint corticosteroid injections injection (SOE: insufficient). Serious harms from injections were rare in randomized trials and observational studies, but harms reporting was suboptimal (SOE: low). Conclusions: Epidural corticosteroid injections for radiculopathy were associated with immediate improvements in pain and might be associated with immediate improvements in function, but benefits were small and not sustained, and there was no effect on long-term risk of surgery. Evidence did not suggest that effectiveness varies based on injection technique, corticosteroid, dose, or comparator. Limited evidence suggested that epidural corticosteroid injections are not effective for spinal stenosis or nonradicular back pain and that facet joint corticosteroid injections are not effective for presumed facet joint pain. There was insufficient evidence to evaluate effectiveness of sacroiliac joint corticosteroid injections.

Objectives: The objective of this project is to systematically review and quantitatively evaluate randomized controlled trials and prospective cohort studies, separately, that examined the relationship between low-calorie sweeteners and body weight and composition.

Objectives: To increase knowledge about the effectiveness of quality improvement (QI), implementation, and dissemination strategies that seek to improve the mental health care of children and adolescents; to examine harms associated with these strategies; and to determine whether effectiveness or harms vary in subgroups based on system, organizational, practitioner, or patient characteristics.

Objectives: Background: Repeated psychiatric hospitalizations, affecting primarily those individuals with a serious mental illness, are a substantial problem. Little is known about the effectiveness of different lengths of hospital stay for these patients, transition support services after discharge, or short- or long-term alternatives to psychiatric hospitalization. Purpose: To describe and compare four core management strategies to reduce psychiatric readmissions—length of stay for inpatient care, transition support services (i.e., care provided as the individual moves to outpatient care), short-term alternatives to psychiatric hospitalizations (i.e., short-term outpatient care provided in place of psychiatric hospitalization for those not at significant risk of harm to self or others), and long-term alternatives to psychiatric hospitalization—for patients at high risk of psychiatric readmission. Methods: We searched published and unpublished sources for information about the effectiveness of these strategies. We also interviewed key informants, representing mental health providers, health services researchers, policymakers, payers, and patient advocacy groups, to confirm and augment our findings. Findings: Other than Assertive Community Treatment (ACT), an alternative to psychiatric hospitalization, we did not identify an overall theoretical model that identified key intervention components. Components of the various strategies overlap and are likely interdependent. Evidence suggests that the most commonly measured outcome, psychiatric readmissions, probably undercounts true readmission rates; other measures of well-being and functioning need to be measured. Of the 63 studies that assessed the link between a management strategy and readmission, two addressed LOS, five addressed transition support services, four addressed short-term alternatives to psychiatric hospitalization, and 52 addressed long-term alternatives to psychiatric hospitalization. The bulk of these studies address two interventions: intensive case management (a transitional support service) and ACT. The availability and implementation of the various management strategies can vary substantially across the country. Conclusions: Important next steps include determining (1) the key components, or packages of components, that are most effective in keeping those at high risk of psychiatric rehospitalization functioning in the community; (2) how to accurately measure the most meaningful outcomes; and (3) how to most efficiently apply effective strategies to areas with varying resources.

Objectives:

Objectives: 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.

Objectives: Objective: To compare the prevalence of PCOS phenotypes and obesity of PCOS women seen in the clinical (referred) setting vs. those identified in general population.

Objectives: 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.

Objectives:

Objectives: Objectives: Given the number of medications available for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices. The objective of this review was to summarize the benefits and harms of medications (metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 [DPP- 4] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists), as monotherapy and in combination, for the treatment of adults with type 2 diabetes; Data Sources: We searched the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases from inception through April 2010 for original English-language articles and sought unpublished data from the Food and Drug Administration and others; Review Methods: Two reviewers independently screened titles to identify studies that assessed intermediate outcomes (e.g., hemoglobin A1c [HbA1c]), long-term clinical outcomes (e.g., mortality), and harms (e.g., hypoglycemia) in head-to-head monotherapy or combination therapy comparisons. Two reviewers serially extracted data for each article using standardized protocols, assessed applicability, and independently evaluated study quality; Results: The review included 140 randomized controlled trials and 26 observational studies. We graded evidence as low or insufficient for long-term clinical outcomes of all-cause mortality, cardiovascular disease, nephropathy, and neuropathy. Most medications lowered HbA1c on average by 1 absolute percentage point, but metformin was more efficacious than the DPP-4 inhibitors. Two-drug combinations had similar HbA1c reduction. Compared with metformin, thiazolidinediones and sulfonylureas had a more unfavorable effect on weight (mean difference of +2.6 kg). Metformin decreased low density lipoprotein cholesterol relative to pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a fourfold higher risk of mild/moderate hypoglycemia compared with metformin alone, and, in combination with metformin, had more than a fivefold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones had an increased risk of congestive heart failure relative to sulfonylureas and bone fractures relative to metformin. Diarrhea occurred more often for metformin compared with thiazolidinedione users; Conclusions: Comprehensive information comparing benefits and harms of diabetes medications can facilitate personalized treatment choices for patients. Although the long-term benefits and harms of diabetes medications remain unclear, the evidence supports use of metformin as a first- line agent. Comparisons of two-drug combinations showed little to no difference in HbA1c reduction, but some combinations increased risk for hypoglycemia and other adverse events.

Objectives: The objective of this study was to systematically review studies of early intensive behavioral and developmental approaches that may improve outcomes for children with ASD.

Objectives: 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.

Objectives: The effect and association of omega−3 fatty acids (n-3 FA) intake and biomarker levels with cardiovascular (CV) clinical and intermediate outcomes remains controversial. We update prior Evidence Reports of n-3 FA and clinical and intermediate CV disease (CVD) outcomes.

Objectives: 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.

Objectives: An update of the 2006 and 2007 CERs comparing medical treatment, angioplasty+-stenting, and open vascular procedures for atherosclerotic renal artery stenosis. The update reviews only angioplasty with stenting (not an update of angioplasty without stenting).

Objectives: 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.

Objectives: 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.

Objectives: Objectives: Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage or debridement. Data Sources: We abstracted data from: 42 randomized, controlled trials (RCTs) of viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on arthroscopy. The search included foreign-language studies and relevant conference proceedings. Review Methods: The review methods were defined prospectively in a written protocol. We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract. Where randomized trials were few, we sought other study designs. We independently assessed the quality of all primary studies. Results: Viscosupplementation trials generally report positive effects on pain and function scores compared to placebo, but the evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large (n=1,583), high- quality, National Institutes of Health-funded, multicenter RCT showed no significant difference compared to placebo. Glucosamine sulfate has been reported to be more effective than glucosamine hydrochloride, which was used in GAIT, but the evidence is not sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose metabolism are short term, or if longer (e.g., 3 years), excluded patients with metabolic disorders. The best available evidence for arthroscopy, a single sham-controlled RCT (n=180), showed that arthroscopic lavage with or without debridement was equivalent to placebo. The main limitations of this trial are the use of a single surgeon and enrollment of patients at a single Veterans Affairs Medical Center. No studies reported separately on patients with secondary OA of the knee. The only comparative study was an underpowered, poor-quality trial comparing viscosupplementation to arthroscopy with debridement. Conclusions: Osteoarthritis of the knee is a common condition. The three interventions reviewed in this report are widely used in the treatment of OA of the knee, yet the best available evidence does not clearly demonstrate clinical benefit. Uncertainty regarding clinical benefit can be resolved only by rigorous, multicenter RCTs. In addition, given the public health impact of OA of the knee, research on new approaches to prevention and treatment should be given high priority.

Objectives: Systematic review of imaging tests for diagnosis, staging, and/or screening of pancreatic adenocarcinoma

Objectives: Background: Depressive disorders such as major depressive disorder (MDD), dysthymia, and subsyndromal depression may be serious disabling illnesses. MDD affects more than 16 percent of adults at some point during their lifetimes. Second-generation antidepressants dominate the medical management of depressive disorders. These drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and other drugs with related mechanisms of action that selectively target neurotransmitters. Objectives: The objective of this report was to compare the benefits and harms of bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine for the treatment of depressive disorders, including variations of effects in patients with accompanying symptoms and patient subgroups. Data Sources: We updated a comparative effectiveness review published in 2007 by the Agency for Healthcare Research and Quality searching PubMed, Embase, The Cochrane Library, and International Pharmaceutical Abstracts up to January 2011. Review Methods: Two people independently reviewed the literature, abstracted data, and rated the risk of bias. If data were sufficient, we conducted meta-analyses of head-to-head trials of the relative benefit of response to treatment. In addition, we conducted mixed treatment comparisons to derive indirect estimates of the comparative efficacy among all second-generation antidepressants. Results: From a total of 3,722 citations, we identified 248 studies of good or fair quality. Overall, no substantial differences in efficacy could be detected among second-generation antidepressants for the treatment of acute-phase MDD. Statistically significant differences in response rates between some drugs are small and likely not clinically relevant. No differences in efficacy were apparent in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbidities, although evidence within these subpopulations was limited. Differences exist in the incidence of specific adverse events and the onset of action. Venlafaxine leads to higher rates of nausea and vomiting, sertraline to higher rates of diarrhea, and mirtazapine to higher rates of weight gain than comparator drugs. Bupropion causes lower rates of sexual dysfunction than other antidepressants. The evidence is insufficient to draw conclusions about the comparative efficacy and effectiveness for the treatment of dysthymia and subsyndromal depression. Conclusions: Our findings indicate that the existing evidence does not warrant the choice of one second-generation antidepressant over another based on greater efficacy and effectiveness. Differences with respect to onset of action and adverse events may be taken into consideration for the choice of a medication.

Objectives: Systematic Review for AHRQ EPC Program

Objectives: Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm of the liver, and accurate diagnosis and staging of HCC are important for guiding treatment and other clinical decisions. A number of imaging modalities are available for detection of HCC in surveillance and non-surveillance settings, evaluation of focal liver lesions to identify HCC, and staging of HCC. The purpose of this review is to compare the effectiveness of imaging techniques for HCC on test performance, clinical decisionmaking, clinical outcomes, and harms.

Objectives: 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.

Objectives: The purpose of this technical brief is to understand current utilization of metastatic breast imaging modalities for treatment evaluation in the United States, both in order to summarize the current state of the science and to inform future research on this topic.

Objectives: This systematic review will assess the surgical breast reconstruction options for women who are undergoing (or have undergone) mastectomy for breast cancer. Specifically, the review will address: (1) the (comparative) benefits and harms of IBR and AR (Key Question [KQ] 1) (2) the (comparative) benefits and harms of timing of IBR and AR in relation to chemotherapy and radiation therapy (KQ 2) (3) the (comparative) benefits and harms of various options for IBR (KQs 3, 4, and 5) (4) the (comparative) benefits and harms of various flap types for AR (KQ 6).

Objectives: Descriptive systematic literature review from epidemiologic perspective of studies assessing influence of environmental and meteorological factors on COVID-19 transmission and severity.

Objectives: 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.

Objectives: A systematic review focusing on the effectiveness of behavioral programs for type 1 diabetes (T1DM), and identifying factors contributing to program effectiveness for type 2 diabetes (T2DM).

Objectives: 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.

Objectives: Purpose: We aimed to update and expand previous syntheses of evidence- and consensus-based guidance on decision and simulation modeling using a systematic review-driven stakeholder-led process.

Objectives: Breast implants are medical devices used to reconstruct the breast following mastectomy, to augment breast size, or to correct a congenital abnormality.1 Breast implants consist of a silicone outer shell and a filler (most commonly silicone gel or saline). In the US about half of implants are silicone gel-filled implants. Recently, the Food and Drug Administration (FDA) has recommended the creation of a surveillance registry to monitor for potential adverse events associated with silicone gel breast implants. However, a clinical registry that can provide meaningful data on the long-term safety requires a large number of patients and rigorous patient follow-up, both of which have been difficult for breast implant companies to achieve. The American Society of Plastic Surgeons (ASPS®) and the Plastic Surgery Foundation (PSF) has solicited this systematic review (SR) to summarize the state of the literature on safety outcomes in women with silicone gel breast implants for the purpose of informing the development of the registry.

Objectives: Objectives: To conduct a systematic review and synthesize the evidence for the effects of surgical treatments for subcapital and intertrochanteric/subtrochanteric hip fractures on patient-focused outcomes for elderly patients. Data Sources: MEDLINE®, Cochrane databases, Scirus, and ClinicalTrials.gov, and expert consultants. We also manually searched reference lists from relevant systematic reviews. Review Methods: High quality quasi-experimental design studies were used to examine relationships between patient characteristics, type of fracture, and patient outcomes. Randomized controlled trials were used to examine relationships between type of surgical treatment and patient outcomes. Patient mortality was examined with Forest plots. Narrative analysis was used for pain, quality of life (QoL), and functional outcomes due to inconsistently measured and reported outcomes. Results: Mortality does not appear to differ by device class, or by devices within a class. Nor, on the whole, do pain, functioning, and QoL. Some internal fixation devices may confer earlier return to functioning over others for some patients, but such gains are very short lived. Very limited results suggest that subcapital hip fracture patients with total hip replacements have improved patient outcomes over internal fixation, but it is unclear whether these results would continue to hold if the analyses included the full complement of relevant covariates. Age, gender, prefracture functioning, and cognitive impairment appear to be related to mortality and functional outcomes. Fracture type does not appear to be independently related to patient outcomes. Again, however, the observational literature does not include the full complement of potential covariates and it is uncertain if these results would hold. Conclusions: Several factors limit our ability to definitively answer the key questions posed in this study using the existing literature. Limited perspectives lead to incomplete sets of independent variables included in analyses. Specific populations are poorly defined and separated for comparative study. Fractures with widely varying biomechanical problems are often lumped together. Outcome variables are inconsistently measured and reported, making it very difficult to aggregate or even compare results. If future high quality trials continue to support the evidence that differences in devices are short term at best, within the first few weeks to few months of recovery, policy implications involve establishing the value of a shorter recovery relative to the cost of the new device. As the literature generally focuses on community dwelling elderly patients, more attention needs to be directed toward understanding implications of surgical treatment choices for the nursing home population.

Objectives: 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.

Objectives: The Vanderbilt Evidence-based Practice Center systematically reviewed evidence on therapies for children ages 2 to 12 with autism spectrum disorders (ASDs). We focused on treatment outcomes, modifiers of treatment effectiveness, evidence for generalization of outcomes to other contexts, and evidence to support treatment decisions in children ages 0-2 at risk for an ASD diagnosis.

Objectives: To comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines.

Objectives: Background: Many health decisions about screening and treatment for cancers involve uncertainty or tradeoffs between the expected benefits and harms. Patient decision aids have been developed to help health care consumers and their providers identify the available alternatives and choose the one that aligns with their values. It is unclear whether the effectiveness of decision aids for decisions related to cancers differs by people’s average risk of cancer or by the content and format of the decision aid.; Objectives: We sought to appraise and synthesize the evidence assessing the effectiveness of decision aids targeting health care consumers who face decisions about cancer screening or prevention, or early cancer treatment (Key Question 1), particularly with regard to decision aid or patient characteristics that might function as effect modifiers. We also reviewed interventions targeting providers for promotion of shared decision making using decision aids (Key Question 2).; Data sources: We searched MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO®, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL®) from inception to the end of June 2014.; Review methods: For Key Question 1, we included randomized controlled trials comparing decision aid interventions among themselves or with a control. We included trials of previously developed decision aids that were delivered at the point of the actual decision. We predefined three population groups of interest based on risk or presence of cancer (average cancer risk, high cancer risk, early cancer). The assessed outcomes pertained to measurements of decisional quality and cognition (e.g., knowledge scores), attributes of the decision-making process (e.g., Decisional Conflict Scale), emotion and quality of life (e.g., decisional regret), and process and system-level attributes. We assessed for effect modification by population group, by the delivery format or content of the decision aid or other attributes, or by methodological characteristics of the studies. For Key Question 2, we included studies of any intervention to promote patient decision aid use, regardless of study design and outcomes assessed.; Results: Of the 16,669 screened citations, 87 publications were eligible, corresponding to 83 (68 trials; 25,337 participants) and 5 reports for Key Questions 1 and 2, respectively. Regarding the evolution of the decision aid format and content over time, more recent trials increasingly studied decision aids that were more practical to deliver (e.g., over the Internet or without human mediation) and more often clarified preferences explicitly. Overall, participants using decision aids had higher knowledge scores compared with those not using decision aids (standardized mean difference, 0.23; 95% credible interval [CrI], 0.09 to 0.35; 42 comparison strata with 12,484 participants). Compared with not using decision aids, using decision aids resulted in slightly lower decisional conflict scores (weighted mean difference of -5.3 units [CrI, -8.9 to - 1.8] on the 0-100 Decisional Conflict Scale; 28 comparison strata; 7,923 participants). There was no difference in State-Trait Anxiety Inventory scores (weighted mean difference = 0.1; 95% CrI, -1.0 to 0.7 on a 20-80 scale; 16 comparison strata; 2,958 participants). Qualitative synthesis suggested that patients using decision aids are more likely to make informed decisions and have accurate risk perceptions; further, they may make choices that best agree with their values and may be less likely to remain undecided. Because there was insufficient, sparse, or no information about effects of decision aids on patient-provider communication, patient satisfaction with decision-making process, resource use, consultation length, costs, or litigation rates, a quantitative synthesis was not done. There was no evidence for effect modification by population group, by the delivery format or content of the decision aid or other attributes, or by methodological characteristics of the studies. Data on Key Question 2 were very limited.; Conclusions: Cancer-related decision aids have evolved over time, and there is considerable diversity in both format and available evidence. We found strong evidence that cancer-related decision aids increase knowledge without adverse impact on decisional conflict or anxiety. We found moderate- or low-strength evidence that patients using decision aids are more likely to make informed decisions, have accurate risk perceptions, make choices that best agree with their values, and not remain undecided. This review adds to the literature that the effectiveness of cancer-related decision aids does not appear to be modified by specific attributes of decision aid delivery format, content, or other characteristics of their development and implementation. Very limited information was available on other outcomes or on the effectiveness of interventions that target providers to promote shared decision making by means of decision aids.

Objectives: This evidence map on sugars and health outcomes was developed using an iterative process. Evidence Map data are being used to support a stakeholders ‘ decision-making on refining research questions and topic prioritization. The goal of this Future Research Needs project is to characterize the available evidence regarding the intake of sugars and health outcomes and identify priority areas where additional research needs remain.

Objectives: Objectives: We focused on four questions: (1) What are the risks and benefits of an oral diabetes agent (i.e., glyburide), as compared to all types of insulin, for gestational diabetes? (2) What is the evidence that elective labor induction, cesarean delivery, or timing of induction is associated with benefits or harm to the mother and neonate? (3) What risk factors are associated with the development of type 2 diabetes after gestational diabetes? (4) What are the performance characteristics of diagnostic tests for type 2 diabetes in women with gestational diabetes? Data Sources: We searched electronic databases for studies published through January 2007. Additional articles were identified by searching the table of contents of 13 journals for relevant citations from August 2006 to January 2007 and reviewing the references in eligible articles and selected review articles. Review Methods: Paired investigators reviewed abstracts and full articles. We included studies that were written in English, reported on human subjects, contained original data, and evaluated women with appropriately diagnosed gestational diabetes. Paired reviewers performed serial abstraction of data from each eligible study. Study quality was assessed independently by each reviewer. Main Results: The search identified 45 relevant articles. The evidence indicated that (1) maternal glucose levels do not differ substantially in those treated with insulin versus insulin analogues or oral agents; (2) average infant birth weight may be lower in mothers treated with insulin than with glyburide; (3) induction at 38 weeks may reduce the macrosomia rate, with no increase in cesarean delivery rates; (4) anthropometric measures, fasting blood glucose (FBG), and 2-hour glucose value are the strongest risk factors associated with development of type 2 diabetes; (5) FBG had high specificity, but variable sensitivity, when compared to the 75-gm oral glucose tolerance test (OGTT) in the diagnosis of type 2 diabetes after delivery. Conclusions: The evidence suggests that benefits and a low likelihood of harm are associated with the treatment of gestational diabetes with an oral diabetes agent or insulin. The effect of induction or elective cesarean on outcomes is unclear. The evidence is consistent that anthropometry identifies women at risk of developing subsequent type 2 diabetes; however, no evidence suggested the FBG out-performs the 75-gm OGTT in diagnosing type 2 diabetes after delivery.

Objectives: Evidence mapping for topic development of diet and physical activity promotion programs systematic review. Most data are derived from abstracts, not full text articles.

Objectives: Objectives: Preoperative testing is used to guide the action plan for patients undergoing surgical and other procedures that require anesthesia and to predict potential postoperative complications. There is uncertainty whether routine or per-protocol testing in the absence of a specific indication prevents complications and improves outcomes, or whether it causes unnecessary delays, costs, and harms due to false-positive results. Data sources: We searched MEDLINE® and Ovid Healthstar® (from inception to July 22, 2013), as well as Cochrane Central Trials Registry and Cochrane Database of Systematic Reviews. Review methods: We included comparative and cohort studies of both adults and children undergoing surgical and other procedures requiring either anesthesia or sedation (excluding local anesthesia). We included all preoperative tests that were likely to be conducted routinely (in all patients) or on a per-protocol basis (in selected patients). For comparative studies, the comparator of interest was either no testing or ad hoc testing done at the discretion of the clinician. We also looked for studies that compared routine and per-protocol testing. The outcomes of interest were mortality, perioperative events, complications, patient satisfaction, resource utilization, and harms related to testing. Results: Fifty-seven studies (14 comparative and 43 cohort) met inclusion criteria for the review. Well-conducted randomized controlled trials (RCTs) of cataract surgeries suggested that routine testing with electrocardiography, complete blood count, and/or a basic metabolic panel did not affect procedure cancellations (2 RCTs, relative risks [RRs] of 1.00 or 0.97), and there was no clinically important difference for total complications (3 RCTs, RR = 0.99; 95% confidence interval, 0.86 to 1.14). Two RCTs and six nonrandomized comparative studies of general elective surgeries in adults varied greatly in the surgeries and patients included, along with the routine or per-protocol tests used. They also mostly had high risk of bias due to lack of adjustment for patient and clinician factors, making their results unreliable. Therefore, they yielded insufficient evidence regarding the effect of routine or per-protocol testing on complications and other outcomes. There was also insufficient evidence for patients undergoing other procedures. No studies reported on quality of life, patient satisfaction, or harms related to testing. Conclusions: There is high strength of evidence that, for patients scheduled for cataract surgery, routine preoperative testing has no effect on total perioperative complications or procedure cancellation. There is insufficient evidence for all other procedures and insufficient evidence comparing routine and per-protocol testing. There is no evidence regarding quality of life or satisfaction, resource utilization, or harms of testing and no evidence regarding other factors that may affect the balance of benefits and harms. The findings of the cataract surgery studies are not reliably applicable to other patients undergoing other higher risk procedures. Except arguably for cataract surgery, numerous future adequately powered RCTs or well-conducted and analyzed observational comparative studies are needed to evaluate the benefits and harms of routine preoperative testing in specific groups of patients with different risk factors for surgical and anesthetic complications undergoing specific types of procedures and types of anesthesia.

Objectives:

Objectives: The SR compares use of different slings versus other surgical interventions to treat stress urinary incontinence in women.

Objectives: 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.

Objectives: Systematic review of diagnostic accuracy and clinical impact of PET and PET-CT used for surveillance in several cancer types