Low Strength Of Evidence Research Articles

Long-Term Drug Therapy and Drug Discontinuations and Holidays for Osteoporosis Fracture Prevention: A Systematic Review.

Optimal long-term osteoporosis drug treatment (ODT) is uncertain. To summarize the effects of long-term ODT and ODT discontinuation and holidays. Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies. 48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB). Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy. Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE). No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays. Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms. National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).

Pharmacologic and Nonpharmacologic Treatments for Urinary Incontinence in Women: A Systematic Review and Network Meta-analysis of Clinical Outcomes.

Urinary incontinence (UI), a common malady in women, most often is classified as stress, urgency, or mixed. To compare the effectiveness of pharmacologic and nonpharmacologic interventions to improve or cure stress, urgency, or mixed UI in nonpregnant women. MEDLINE, Cochrane Central Register of Controlled Trials (Wiley), Cochrane Database of Systematic Reviews (Wiley), EMBASE (Elsevier), CINAHL (EBSCO), and PsycINFO (American Psychological Association) from inception through 10 August 2018. 84 randomized trials that evaluated 14 categories of interventions and reported categorical cure or improvement outcomes. 1 researcher extracted study characteristics, results, and study-level risk of bias, with verification by another independent researcher. The research team collaborated to assess strength of evidence (SoE) across studies. 84 studies reported cure or improvement outcomes (32 in stress UI, 16 in urgency UI, 4 in mixed UI, and 32 in any or unspecified UI type). The most commonly evaluated active intervention types included behavioral therapies, anticholinergics, and neuromodulation. Network meta-analysis showed that all interventions, except hormones and periurethral bulking agents (variable SoE), were more effective than no treatment in achieving at least 1 favorable UI outcome. Among treatments used specifically for stress UI, behavioral therapy was more effective than either α-agonists or hormones in achieving cure or improvement (moderate SoE); α-agonists were more effective than hormones in achieving improvement (moderate SoE); and neuromodulation was more effective than no treatment for cure, improvement, and satisfaction (high SoE). Among treatments used specifically for urgency UI, behavioral therapy was statistically significantly more effective than anticholinergics in achieving cure or improvement (high SoE), both neuromodulation and onabotulinum toxin A (BTX) were more effective than no treatment (high SoE), and BTX may have been more effective than neuromodulation in achieving cure (low SoE). Scarce direct (head-to-head trial) evidence and population heterogeneity based on UI type, UI severity, and history of prior treatment. Most nonpharmacologic and pharmacologic interventions are more likely than no treatment to improve UI outcomes. Behavioral therapy, alone or in combination with other interventions, is generally more effective than pharmacologic therapies alone in treating both stress and urgency UI. Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069903).

Vitamin B12 in Relation to Oxidative Stress: A Systematic Review.

The triage theory posits that modest micronutrient deficiencies may induce reallocation of nutrients to processes necessary for immediate survival at the expense of long-term health. Neglected processes could in time contribute to the onset of age-related diseases, in which oxidative stress is believed to be a major factor. Vitamin B12 (B12) appears to possess antioxidant properties. This review aims to summarise the potential antioxidant mechanisms of B12 and investigate B12 status in relation to oxidative stress markers. A systematic query-based search of PubMed was performed to identify eligible publications. The potential antioxidant properties of B12 include: (1) direct scavenging of reactive oxygen species (ROS), particularly superoxide; (2) indirect stimulation of ROS scavenging by preservation of glutathione; (3) modulation of cytokine and growth factor production to offer protection from immune response-induced oxidative stress; (4) reduction of homocysteine-induced oxidative stress; and (5) reduction of oxidative stress caused by advanced glycation end products. Some evidence appears to suggest that lower B12 status is related to increased pro-oxidant and decreased antioxidant status, both overall and for subclinically deficient individuals compared to those with normal B12 status. However, there is a lack of randomised controlled trials and prospective studies focusing specifically on the relation between B12 and oxidative stress in humans, resulting in a low strength of evidence. Further work is warranted.

The effect of mindfulness meditation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.

There is a growing interest in the effectiveness of mindfulness meditation for sleep disturbed populations. Our study sought to evaluate the effect of mindfulness meditation interventions on sleep quality. To assess for relative efficacy, comparator groups were restricted to specific active controls (such as evidenced-based sleep treatments) and nonspecific active controls (such as time/attention-matched interventions to control for placebo effects), which were analyzed separately. From 3303 total records, 18 trials with 1654 participants were included. We determined the strength of evidence using four domains (risk of bias, directness of outcome measures, consistency of results, and precision of results). At posttreatment and follow-up, there was low strength of evidence that mindfulness meditation interventions had no effect on sleep quality compared with specific active controls (ES 0.03 (95% CI -0.43 to 0.49)) and (ES -0.14 (95% CI -0.62 to 0.34)), respectively. Additionally, there was moderate strength of evidence that mindfulness meditation interventions significantly improved sleep quality compared with nonspecific active controls at postintervention (ES 0.33 (95% CI 0.17-0.48)) and at follow-up (ES 0.54 (95% CI 0.24-0.84)). These preliminary findings suggest that mindfulness meditation may be effective in treating some aspects of sleep disturbance. Further research is warranted.

Comparative effectiveness and harms of intravitreal antivascular endothelial growth factor agents for three retinal conditions: a systematic review and meta-analysis.

Intravitreal antivascular endothelial growth factor (VEGF) agents are widely used to treat ocular conditions but the benefits and harms of these treatments are uncertain. We conducted a systematic review to compare the effects of aflibercept, bevacizumab and ranibizumab on best-corrected visual acuity (BCVA) changes, quality of life and ocular or systemic adverse events in patients with neovascular age-related macular degeneration (NVAMD), diabetic macular oedema (DME) and central or branch retinal vein occlusion (RVO). We searched published and unpublished literature sources to February 2017 for randomised controlled trials and cohort or modelling studies reporting comparative costs in the USA. Two reviewers extracted data and graded the strength of the evidence using established methods. Of 17 included trials, none reported a clinically important difference (≥ 5 letters) in visual acuity gains between agents. Nine trials provide high-strength evidence of no difference between bevacizumab and ranibizumab for NVAMD. Three trials provide moderate-strength evidence of no difference between bevacizumab and ranibizumab for DME. There was low-strength evidence of similar effects between aflibercept and ranibizumab for NVAMD, aflibercept and bevacizumab for RVO and all three agents for DME. There was insufficient evidence to compare bevacizumab and ranibizumab for RVO. Rates of ocular adverse events were low, and systemic harms were generally similar between groups, although 1 DME trial reported more arterial thrombotic events with ranibizumab versus aflibercept. Overall, no agent had a clear advantage over another for effectiveness or safety. Aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials. Systematic review registration number: CRD42016034076.

Clinical Outcomes Associated With Sickle Cell Trait: A Systematic Review.

Although sickle cell trait (SCT) is largely a benign carrier state, it may increase risk for certain clinical outcomes. To evaluate associations between SCT and clinical outcomes in children and adults. English-language searches of PubMed, CINAHL, the Cochrane Library, Current Contents Connect, Scopus, and Embase (1 January 1970 to 30 June 2018) and bibliographies of review articles. Observational controlled studies (published in English) in children or adults that examined an association between SCT and any of 24 clinical outcomes specified a priori in the following 6 categories: exertion-related injury; renal, vascular, pediatric, and surgery- or trauma-related outcomes; and overall mortality. A single reviewer extracted study data, which was checked by another; 2 reviewers independently assessed study quality; and strength of evidence was assessed by consensus. Of 7083 screened studies, 41 met inclusion criteria. High-strength evidence supported a positive association between SCT and risk for pulmonary embolism, proteinuria, and chronic kidney disease. Moderate-strength evidence supported a positive association between SCT and exertional rhabdomyolysis and a null association between SCT and deep venous thrombosis, heart failure or cardiomyopathy, stroke, and pediatric height or weight. Absolute risks for thromboembolism and rhabdomyolysis were small. For the remaining 15 clinical outcomes, data were insufficient or strength of evidence was low. Publication bias was possible, and high-quality evidence was scant. Sickle cell trait is a risk factor for a few adverse health outcomes, such as pulmonary embolism, kidney disease, and exertional rhabdomyolysis, but does not seem to be associated with such complications as heart failure and stroke. Insufficient data or low-strength evidence exists for most speculated complications of SCT. National Human Genome Research Institute.

A3824 Effectiveness of Home Blood Pressure Telemonitoring

Objectives: To summarize evidence about the effectiveness of home blood pressure telemonitoring (HBPT) and identify the key components of intervention. Methods: We comprehensively searched PubMed, EMBASE and the Cochrane Library for relevant studies. The authors were contacted for additional information. Two authors independently extracted the data and assessed the risk of bias. Results: 46 randomized controlled trials (RCTs) including a total of 13 875 cases were identified. Compared to usual care, HBPT improved office systolic blood pressure (BP) and diastolic BP by 3.99 mmHg (95% CI: 5.06 to 2.93; p < 0.001) and 1.99 mmHg (95% CI: −2.60 to −1.39; p < 0.001), respectively. A larger proportion of patients achieved BP normalization in the intervention group (RR: 1.16; 95% CI: 1.08 to 1.25; p < 0.001). For HBPT plus additional support (including counseling, education, behavioral management, medication management with decision, adherence contracts, etc.) versus HBPT alone (or plus less intense additional support), the mean changes in systolic and diastolic BP were 2.44 mm Hg (95%Cl, 4.88 to 0.00 mm Hg; p = 0.05) and 1.12 mm Hg (95% CI, −2.34 to 0.1 mm Hg; p = 0.07), respectively. For those surrogate outcomes, low strength evidence failed to show difference. In subgroup analysis, high strength evidence supported a lower BP with HBPT that lasted for 6 or 12 months and was accompanied with counseling support from study personnel. Conclusion: HBPT can improve BP control in the hypertensive patients. It may be more efficacious when a proactive additional support is provided during the intervention process.

Effectiveness of Policies and Programs to Combat Adult Obesity: a Systematic Review.

This systematic review identifies programs, policies, and built-environment changes targeting prevention and control of adult obesity and evaluates their effectiveness. We searched PubMed, CINAHL, PsycINFO, and EconLit from January 2000 to March 2018. We included natural experiment studies evaluating a program, policy, or built-environment change targeting adult obesity and reporting weight/body mass index (BMI). Studies were categorized by primary intervention target: physical activity/built environment, food/beverage, messaging, or multiple. Two reviewers independently assessed the risk of bias for each study using the Effective Public Health Practice Project tool. Of 158 natural experiments targeting obesity, 17 reported adult weight/BMI outcomes. Four of 9 studies reporting on physical activity/built environment demonstrated reduced weight/BMI, although effect sizes were small with low strength of evidence and high risk of bias. None of the 5 studies targeting the food/beverage environment decreased weight/BMI; strength of evidence was low, and 2 studies were rated high risk of bias. We identified few natural experiments reporting on the effectiveness of programs, policies, and built-environment changes on adult obesity. Overall, we found no evidence that policies intending to promote physical activity and healthy eating had beneficial effects on weight/BMI and most studies had a high risk of bias. Limitations include few studies met our inclusion criteria; excluded studies in children and those not reporting on weight/BMI outcomes; weight/BMI reporting was very heterogeneous. More high-quality research, including natural experiments studies, is critical for informing the population-level effectiveness of obesity prevention and control initiatives in adults.

Efficacy and safety of allergen immunotherapy in patients with allergy to molds: A systematic review.

Allergen immunotherapy (AIT) with mould extracts has been performed for many years but the final demonstration of its clinical efficacy is still missing, due to the small number of studies and their inconsistent results. To systematically review efficacy and safety of AIT for the treatment of respiratory allergies to moulds. The primary outcomes were safety and reduction of symptoms (Symptom Score, SS) and medication use (Medication Score, MS) in patients treated with AIT compared to controls. The strength of the evidence was graded based on the risk of bias, consistency and magnitude of effect, according to the GRADE Working Group's guide. Medline, Web of Science and the Cochrane Library (through September 2017) supplemented with manual searches of reference lists. Randomized studies of intervention comparing AIT to placebo/pharmacotherapy. Studies not reporting on our outcome of interest or without a control population were excluded. Nine studies (168 children, 99 adults; median sample size, 27) met the inclusion criteria. The risk of bias was moderate-to-high in all but one study. Low strength evidence supports the assumption that AIT is effective in reducing symptoms and medication use, with only four of nine studies reporting higher benefit of AIT vs. comparators. The highest benefit of AIT compared to pharmacotherapy/placebo was reported in studies with a longer follow-up (SMD for MS from -3.96 to -3.97 in favour of AIT) and low risk of bias (VAS for SS: 66.3±13 in AIT group; 186.6±39 in comparators; P<0.05). No difference was reported with respect to study sample size, route of administration, age of participants. Generalised adverse reactions were reported in 12.5% of participants treated with sublingual immunotherapy, and 37.2% of participants treated with subcutaneous immunotherapy. Low strength evidence suggests that mould AIT is efficacious for the treatment of respiratory allergies. High-quality studies with an adequate sample size are needed.

Interventional Therapy Versus Medical Therapy for Secundum Atrial Septal Defect: A Systematic Review (Part 2) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Secundum atrial septal defect (ASD) is the most common adult congenital heart defect and can present with wide variation in clinical findings. With the intention of preventing morbidity and mortality associated with late presentation of ASD, consensus guidelines have recommended surgical or percutaneous ASD closure in adults with right heart enlargement, with or without symptoms. The aim of the present analysis was to determine if the protective effect of secundum ASD closure in adults could be qualified by pooling data from published studies. A systematic review and meta-analysis were performed by using EMBASE, MEDLINE (through PubMed), and the Cochrane Library databases to assess the effect of secundum ASD percutaneous or surgical closure in unoperated adults ≥18 years of age. Data were pooled across studies with the DerSimonian-Laird random-effects model or a Bayesian meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. Bias assessment was performed with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. A total of 11 nonrandomized studies met the inclusion criteria, contributing 603 patients. Pooled analysis showed a protective effect of ASD closure on New York Heart Association functional class and on right ventricular systolic pressure, volumes, and dimensions. Two additional studies comprising 652 patients were reviewed separately for mortality outcome and primary outcome of interest because they did not meet the inclusion criteria. Those studies showed that ASD closure was associated with a weak protective effect on adjusted mortality rate but no significant impact on atrial arrhythmias in patients >50 years of age. Across all studies, there was significant heterogeneity between studies for nearly all clinical outcomes. The overall body of evidence was limited to observational cohort studies, the limitations of which make for low-strength evidence. Even within the parameters of the included studies, quality of evidence was further diminished by the lack of well-defined clinical outcomes. In conclusion, pooled data analysis on the impact of secundum ASD closure in adults was notably limited because of the lack of randomized controlled trials in patients with only secundum ASD. The few cohort studies in this population demonstrated improvement in functional status and right ventricular size and function as shown by echocardiogram. However, our findings suggest that at the time of this publication, insufficient data are available to determine the impact of ASD repair on mortality rate in adults.

Evidence Review-Social Determinants of Health for Veterans.

Veterans Health Administration (VHA) is committed to providing high-quality care and addressing health disparities for vulnerable Veterans. To meet these goals, VA policymakers need guidance on how to address social determinants in operations planning and day-to-day clinical care for Veterans. MEDLINE (OVID), CINAHL, PsycINFO, and Sociological Abstracts were searched from inception to January 2017. Additional articles were suggested by peer reviewers and/or found through search of work associated with US and VA cohorts. Eligible articles compared Veterans vs non-Veterans, and/or Veterans engaged with those not engaged in VA healthcare. Our evidence maps summarized study characteristics, social determinant(s) addressed, and whether health behaviors, health services utilization, and/or health outcomes were examined. Qualitative syntheses and quality assessment were performed for articles on rurality, trauma exposure, and sexual orientation. We screened 7242 citations and found 131 eligible articles-99 compared Veterans vs non-Veterans, and 40 included engaged vs non-engaged Veterans. Most articles were cross-sectional and addressed socioeconomic factors (e.g., education and income). Fewer articles addressed rurality (N = 20), trauma exposure (N = 17), or sexual orientation (N = 2); none examined gender identity. We found no differences in rural residence between Veterans and non-Veterans, nor between engaged and non-engaged Veterans (moderate strength evidence). There was insufficient evidence for role of rurality in health behaviors, health services utilization, or health outcomes. Trauma exposures, including from events preceding military service, were more prevalent for Veterans vs non-Veterans and for engaged vs non-engaged Veterans (low-strength evidence); exposures were associated with smoking (low-strength evidence). Little published literature exists on some emerging social determinants. We found no differences in rural residence between our groups of interest, but trauma exposure was higher in Veterans (vs non-Veterans) and engaged (vs non-engaged). We recommend consistent measures for social determinants, clear conceptual frameworks, and analytic strategies that account for the complex relationships between social determinants and health.

Marijuana Use, Respiratory Symptoms, and Pulmonary Function: A Systematic Review and Meta-analysis.

The health effects of smoking marijuana are not well-understood. To examine the association between marijuana use and respiratory symptoms, pulmonary function, and obstructive lung disease among adolescents and adults. PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library from 1 January 1973 to 30 April 2018. Observational and interventional studies published in English that reported pulmonary outcomes of adolescents and adults who used marijuana. Four reviewers independently extracted study characteristics and assessed risk of bias. Three reviewers assessed strength of evidence. Studies of similar design with low or moderate risk of bias and sufficient data were pooled. Twenty-two studies were included. A pooled analysis of 2 prospective studies showed that marijuana use was associated with an increased risk for cough (risk ratio [RR], 2.04 [95% CI, 1.02 to 4.06]) and sputum production (RR, 3.84 [CI, 1.62 to 9.07]). Pooled analysis of cross-sectional studies (1 low and 3 moderate risk of bias) showed that marijuana use was associated with cough (RR, 4.37 [CI, 1.71 to 11.19]), sputum production (RR, 3.40 [CI, 1.99 to 5.79]), wheezing (RR, 2.83 [CI, 1.89 to 4.23]), and dyspnea (RR, 1.56 [CI, 1.33 to 1.83]). Data on pulmonary function and obstructive lung disease were insufficient. Few studies were at low risk of bias, marijuana exposure was limited in the population studied, cohorts were young overall, assessment of marijuana exposure was not uniform, and study designs varied. Low-strength evidence suggests that smoking marijuana is associated with cough, sputum production, and wheezing. Evidence on the association between marijuana use and obstructive lung disease and pulmonary function is insufficient. None. (PROSPERO: CRD42017059224).

Interventions to reduce inappropriate prescribing of antibiotics for acute respiratory tract infections: summary and update of a systematic review.

ObjectiveAntibiotic overuse contributes to antibiotic resistance and adverse consequences. Acute respiratory tract infections (RTIs) are the most common reason for antibiotic prescribing in primary care, but such infections often do not require antibiotics. We summarized and updated a previously performed systematic review of interventions to reduce inappropriate use of antibiotics for acute RTIs.MethodsTo update the review, we searched MEDLINE®, the Cochrane Library (until January 2018), and reference lists. Two reviewers selected the studies, extracted the study data, and assessed the quality and strength of evidence.ResultsTwenty-six interventions were evaluated in 95 mostly fair-quality studies. The following four interventions had moderate-strength evidence of improved/reduced antibiotic prescribing and low-strength evidence of no adverse consequences: parent education (21% reduction, no increase return visits), combined patient/clinician education (7% reduction, no change in complications/satisfaction), procalcitonin testing for adults with RTIs of the lower respiratory tract (12%–72% reduction, no increased adverse consequences), and electronic decision support systems (24%–47% improvement in appropriate prescribing, 5%–9% reduction, no increased complications).ConclusionsThe best evidence supports use of specific educational interventions, procalcitonin testing in adults, and electronic decision support to reduce inappropriate antibiotic prescribing for acute RTIs without causing adverse consequences.

Role of sublingual immunotherapy in the treatment of asthma: An updated systematic review.

The purpose of the systematic review is to evaluate the efficacy and safety of sublingual immunotherapy (SLIT) for the treatment of allergic asthma. PubMed, Embase, and CENTRAL databases were searched, updating an earlier review (January 1, 2005 through May 8, 2017). Randomized, controlled studies (RCTs) were included, which reported one of the prespecified outcomes: asthma symptoms measured by control composite scores; quality of life; medication use; pulmonary physiology; and health-care utilization. For safety outcomes, RCTs and observational studies were included. Two independent reviewers extracted data, assessed risk of bias, and graded strength of evidence (SOE) for each outcome. Fourteen RCTs (n = 2585) assessed the efficacy of SLIT for asthma. The RCTs utilized house dust mite (HDM), birch, or grass allergen. SLIT improved asthma symptoms (high SOE), decreased use of long-term control medication, and improved forced expiratory volume in 1 second (FEV1 ) (moderate SOE). SLIT may decrease quick-relief medication use, and improve disease-specific quality of life (low SOE). For safety, 20 RCTs and 10 observational studies (n = 3621) were identified. Local (risk differences ranged from -0.03 to +0.765) and systemic allergic reactions (risk differences ranged from -0.03 to +0.06) were a common occurrence in SLIT and control groups. Life-threatening reactions were uncommon, with 3 cases of anaphylaxis and no deaths reported. There is moderate-to-high strength evidence that SLIT improves allergic asthma symptoms, reduces long-term control medication use, and improves FEV1 based on studies of HDM, birch, and grass. SLIT rarely is associated with life-threatening adverse events.

Association Between Prescription Drug Monitoring Programs and Nonfatal and Fatal Drug Overdoses: A Systematic Review.

Prescription drug monitoring programs (PDMPs) are a key component of the president's Prescription Drug Abuse Prevention Plan to prevent opioid overdoses in the United States. To examine whether PDMP implementation is associated with changes in nonfatal and fatal overdoses; identify features of programs differentially associated with those outcomes; and investigate any potential unintended consequences of the programs. Eligible publications from MEDLINE, Current Contents Connect (Clarivate Analytics), Science Citation Index (Clarivate Analytics), Social Sciences Citation Index (Clarivate Analytics), and ProQuest Dissertations indexed through 27 December 2017 and additional studies from reference lists. Observational studies (published in English) from U.S. states that examined an association between PDMP implementation and nonfatal or fatal overdoses. 2 investigators independently extracted data from and rated the risk of bias (ROB) of studies by using established criteria. Consensus determinations involving all investigators were used to grade strength of evidence for each intervention. Of 2661 records, 17 articles met the inclusion criteria. These articles examined PDMP implementation only (n= 8), program features only (n= 2), PDMP implementation and program features (n= 5), PDMP implementation with mandated provider review combined with pain clinic laws (n= 1), and PDMP robustness (n= 1). Evidence from 3 studies was insufficient to draw conclusions regarding an association between PDMP implementation and nonfatal overdoses. Low-strength evidence from 10 studies suggested a reduction in fatal overdoses with PDMP implementation. Program features associated with a decrease in overdose deaths included mandatory provider review, provider authorization to access PDMP data, frequency of reports, and monitoring of nonscheduled drugs. Three of 6 studies found an increase in heroin overdoses after PDMP implementation. Few studies, high ROB, and heterogeneous analytic methods and outcome measurement. Evidence that PDMP implementation either increases or decreases nonfatal or fatal overdoses is largely insufficient, as is evidence regarding positive associations between specific administrative features and successful programs. Some evidence showed unintended consequences. Research is needed to identify a set of "best practices" and complementary initiatives to address these consequences. National Institute on Drug Abuse and Bureau of Justice Assistance.

PMH6 - Psychosocial and Other Non-Drug Treatments for Bipolar Disorder in Adults: A Systematic Review

Assess the effect of psychosocial and other non-drug interventions for treating acute symptoms (depression, mania, and lack of function) associated with bipolar disorder (BD) and preventing relapse. We searched Ovid MEDLINE®, Embase®, PsychInfo, the Cochrane Central Register of Controlled Trials, and hand searched references of relevant systematic reviews through May 2017. Eligible studies included randomized controlled trials and prospective cohorts with comparator arms enrolling adults with BD of any type with 3 weeks follow-up for acute mania, 3 months for depression, and 6 months for maintenance treatments. We excluded studies with greater than 50 percent attrition. We examined studies by both intervention category and comparator type (inactive and active). We qualitatively synthesized evidence from 63 publications reporting 48 unique studies. A further 6 studies were excluded for high attrition. Clinical states of enrolled subjects and interventions within categories varied greatly. Cognitive behavioral training 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 interventions and outcomes. We were generally unable to draw conclusions about the effect of non-drug interventions for bipolar disorders, largely due to population and intervention heterogeneity. While excluding 12.5 percent of unique studies due to high attrition limited the evidence base, the findings from these studies were of questionable validity. Psychosocial interventions may provide benefits not measured in the reviewed literature. Many of the interventions included components of disease education, discussion of triggers, and coping mechanisms. Providing such information may help patients accept their diagnosis, which can provide benefits in terms of other outcomes such as adherence to pharmacological treatment.

Allergen-Specific Immunotherapy in the Treatment of Pediatric Asthma: A Systematic Review.

Treatment options for allergic asthma include allergen avoidance, pharmacotherapy, and allergen immunotherapy. Summarize and update current evidence for the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in pediatric allergic asthma. PubMed, Embase, Cochrane Central Register of Controlled Trials (January 1, 2005, through May 8, 2017), ClinicalTrials.gov, and the US Food and Drug Administration Adverse Event Reporting System. We reevaluated trials from our 2013 systematic review. We included studies with children ≤18 years of age in which researchers reported on prespecified outcomes and had an intervention arm receiving aeroallergen SCIT or SLIT. Only randomized controlled trials (RCTs) were included for efficacy. RCTs and non-RCTs were included for safety outcomes. Two reviewers extracted data. We included 40 studies (17 SCIT trials, 11 SLIT trials, 8 non-RCTs for SCIT safety, and 4 non-RCTs for SLIT safety). We found moderate-strength evidence that SCIT reduces long-term asthma medication use. We found low-strength evidence that SCIT improves asthma-related quality of life and forced expiratory volume in 1 second. There was also low-strength evidence that SLIT improves medication use and forced expiratory volume in 1 second. There was insufficient evidence on asthma symptoms and health care use. There were no trials in which researchers evaluated asthma symptoms using a validated tool. Study characteristics and outcomes were reported heterogeneously. In children with allergic asthma, SCIT may reduce long-term asthma medication use. Local and systemic allergic reactions are common, but anaphylaxis is reported rarely.

Benefits and Harms of Cranial Electrical Stimulation for Chronic Painful Conditions, Depression, Anxiety, and Insomnia: A Systematic Review.

Cranial electrical stimulation (CES) is increasingly popular as a treatment, yet its clinical benefit is unclear. To review evidence about the benefits and harms of CES for adult patients with chronic painful conditions, depression, anxiety, and insomnia. Several databases from inception to 10 October 2017 without language restrictions and references from experts, prior reviews, and manufacturers. Randomized controlled trials of CES versus usual care or sham CES that reported pain, depression, anxiety, or sleep outcomes in any language. Single-reviewer extraction checked by another; dual independent quality assessment; strength-of-evidence grading by the first author with subsequent group discussion. Twenty-eight articles from 26 randomized trials met eligibility criteria. The 2 trials that compared CES with usual care were small, and neither reported a statistically significant benefit in pain or anxiety outcomes for patients with fibromyalgia or anxiety, respectively. Fourteen trials with sham or placebo controls involving patients with painful conditions, such as headache, neuromuscular pain, or musculoskeletal pain, had conflicting results. Four trials done more than 40 years ago and 1 from 2014 provided low-strength evidence of a possible modest benefit compared with sham treatments in patients with anxiety and depression. Trials in patients with insomnia (n= 2), insomnia and anxiety (n= 1), or depression (n= 3) had inconclusive or conflicting results. Low-strength evidence suggested that CES does not cause serious side effects. Most trials had small sample sizes and short durations; all had high risk of bias due to inadequate blinding. Evidence is insufficient that CES has clinically important effects on fibromyalgia, headache, neuromusculoskeletal pain, degenerative joint pain, depression, or insomnia; low-strength evidence suggests modest benefit in patients with anxiety and depression. Veterans Affairs Quality Enhancement Research Initiative. (PROSPERO: CRD42016023951).

Provider Types and Outcomes in Obstructive Sleep Apnea Case Finding and Treatment: A Systematic Review.

Obstructive sleep apnea (OSA) diagnosis and care models rely on sleep specialist physicians (SSPs) and can be expensive and inefficient. To assess OSA case-finding accuracy and comparative effectiveness of care by non-sleep specialists (NSSs) and SSPs. MEDLINE and CINAHL from January 2000 through July 2017. English-language trials or observational studies comparing case finding or care by SSPs versus providers not specifically trained as SSPs (NSSs) for adults with suspected or diagnosed OSA. One investigator extracted data and assessed risk of bias and strength of evidence, with confirmation by a second investigator. Primary outcomes were patient-centered (mortality, access to care, quality of life, patient satisfaction, adherence, symptom scores, and adverse events). Intermediate outcomes included resource use, costs, time to initiation of treatment, and case finding. Four observational studies (n= 580; mean age, 52 years; 77% male) reported good agreement between NSSs and SSPs on appropriate diagnostic testing and classification of OSA severity (low-strength evidence). Five randomized trials and 3 observational studies (n= 1515; mean age, 52 years; 68% male) found that care provided by NSSs and SSPs resulted in similar quality of life, adherence, and symptom scores (low-strength evidence). Evidence was insufficient for access to care and adverse events. Many outcomes were reported infrequently or not at all. Many NSSs had extensive training or experience in sleep medicine, which limits generalizability of findings to providers with less experience. Care by NSSs and SSPs resulted in similar outcomes in adults with known or suspected OSA. Studies are needed to determine care model implementation and reproducibility of results in nonacademic settings and among less experienced NSSs. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO: CRD42016036810 [full Veterans Affairs Evidence-based Synthesis Program report]).

Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

Optimal treatment to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia is uncertain. To summarize current evidence on the efficacy and harms of pharmacologic interventions to prevent or delay cognitive decline, MCI, or dementia in adults with normal cognition or MCI. Several electronic databases from January 2009 to July 2017, bibliographies, and expert recommendations. English-language trials of at least 6 months' duration enrolling adults without dementia and comparing pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes. Two reviewers independently rated risk of bias and strength of evidence; 1 extracted data, and a second checked accuracy. Fifty-one unique trials were rated as having low to moderate risk of bias (including 3 that studied dementia medications, 16 antihypertensives, 4 diabetes medications, 2 nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin, 17 hormones, and 7 lipid-lowering agents). In persons with normal cognition, estrogen and estrogen-progestin increased risk for dementia or a combined outcome of MCI or dementia (1 trial, low strength of evidence); high-dose raloxifene decreased risk for MCI but not for dementia (1 trial, low strength of evidence); and antihypertensives (4 trials), NSAIDs (1 trial), and statins (1 trial) did not alter dementia risk (low to insufficient strength of evidence). In persons with MCI, cholinesterase inhibitors did not reduce dementia risk (1 trial, low strength of evidence). In persons with normal cognition and those with MCI, these pharmacologic treatments neither improved nor slowed decline in cognitive test performance (low to insufficient strength of evidence). Adverse events were inconsistently reported but were increased for estrogen (stroke), estrogen-progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism). High attrition, short follow-up, inconsistent cognitive outcomes, and possible selective reporting and publication. Evidence does not support use of the studied pharmacologic treatments for cognitive protection in persons with normal cognition or MCI. Agency for Healthcare Research and Quality.