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Background Despite accumulating evidence of the important health benefits of bariatric surgery in morbidly obese patients in general, bariatric surgery outcomes are less clear in higher-risk, high-priority populations of patients with BMI ≥ 50 kg/m 2 . To help the Department of Veterans Affairs (VA) Health Services Research & Development Service (HSR&D) develop a research agenda, we conducted a rapid evidence review to better understand bariatric surgery outcomes in adults with BMI ≥ 50 kg/m 2 . Methods We searched MEDLINE ® , the Cochrane Database of Systematic Reviews, the Cochrane Central Registry of Controlled Trials, and ClinicalTrials.gov through June 2016. We included trials and observational studies. We used pre-specified criteria to select studies, abstract data, and rate internal validity and strength of the evidence (PROSPERO registration number CRD42015025348). All decisions were completed by one reviewer and checked by another. Results Among 1892 citations, we included 23 studies in this rapid review. Compared with usual care, one large retrospective VA study provided limited evidence that bariatric surgery can lead to increased mortality in the first year, but decreased mortality long-term among super obese veterans. Studies that compared different bariatric surgical approaches suggested some differences in weight loss and complications. Laparoscopic gastric bypass generally resulted in greater short-term proportion of excess weight loss than did other procedures. Duodenal switch led to greater long-term weight loss than did gastric bypass, but with more complications. Conclusions The published literature that separates the super obese is insufficient for determining the precise balance of benefits and harms of bariatric surgery in this high-risk subgroup. Future studies should evaluate a more complete set of key outcomes with longer follow-up in larger samples of more broadly representative adults.

ObjectiveTo identify and describe evidence on brief emergency department (ED)-delivered behavioural and care process interventions among patients presenting with suicide attempt or acute ideation, substance overdose or psychosis.DesignWe employed a scoping review design and searched multiple data sources, clinical trial registries and references lists through March 2023. We included English-language trials and rigorously designed observational studies. In alignment with scoping review guidelines, we did not assess the quality of included studies or rate the strength of evidence of intervention effectiveness.PopulationOur population of interest was adults presenting to the ED with suicidality (eg, attempt or acute ideation), any substance overdose or acute psychosis from a primary mental health condition.InterventionWe included studies of brief behavioural or care process interventions delivered in the ED.Outcome measuresHealth outcomes (eg, symptom reduction), healthcare utilisation and harms.ResultsOur search identified 2034 potentially relevant articles. We included 40 studies: 3 systematic reviews and 39 primary studies. Most studies (n=34) examined ED interventions in patients with suicide attempt or suicidal ideation, while eight studies examined interventions in patients with opioid overdose. No studies examined ED interventions in patients with acute psychosis. Most suicide prevention studies reported that brief psychological, psychosocial or screening and triage interventions reduce suicide and suicide attempt following an ED visit. Most clinical trial interventions were multicomponent and included at least one follow-up. All substance overdose studies focused on opioids. These studies often contained medication and referral or consultation components. Multiple studies reported increases in substance use disorder treatment utilisation; evidence on repeat overdose events was limited.ConclusionsA wide range of multicomponent ED-delivered behavioural health interventions for suicidality and opioid use disorder show short-term improvement on primary outcomes such as suicide reattempt. Few studies on non-opioid substances and psychosis are available.

Development of resistance against current antimalarial drugs necessitates the search for novel drugs that interact with different targets and have distinct mechanisms of action. Malaria parasites depend upon high levels of glucose uptake followed by inefficient metabolic utilization via the glycolytic pathway, and the Plasmodium falciparum hexose transporter PfHT, which mediates uptake of glucose, has thus been recognized as a promising drug target. This transporter is highly divergent from mammalian hexose transporters, and it appears to be a permease that is essential for parasite viability in intra-erythrocytic, mosquito, and liver stages of the parasite life cycle. An assay was developed that is appropriate for high throughput screening against PfHT based upon heterologous expression of PfHT in Leishmania mexicana parasites that are null mutants for their endogenous hexose transporters. Screening of two focused libraries of antimalarial compounds identified two such compounds that are high potency selective inhibitors of PfHT compared to human GLUT1. Additionally, 7 other compounds were identified that are lower potency and lower specificity PfHT inhibitors but might nonetheless serve as starting points for identification of analogs with more selective properties. These results further support the potential of PfHT as a novel drug target.

Background Despite evidence that medications to treat opioid use disorder (OUD) are effective, most people who could benefit from this treatment do not receive it. This rapid review synthesizes evidence on current barriers and facilitators to buprenorphine/naloxone and naltrexone at the patient, provider, and system levels to inform future interventions aimed at expanding treatment. Methods We systematically searched numerous bibliographic databases through May 2020 and selected studies published since 2014. Study selection, data abstraction, coding of barriers and facilitators, and quality assessment were first completed by one reviewer and checked by a second. Results We included 40 studies of buprenorphine (5 also discussed naltrexone). Four types of patient and provider-level barriers to OUD medication use emerged—stigma related to OUD medications, treatment experiences and beliefs (positive or negative), logistical issues (time and costs as well as insurance and regulatory requirements), and knowledge (high or low) of OUD and the role of medications. Stigma was the most common barrier among patients, while logistical issues were the most common barriers among providers. Facilitators for both patients and providers included peer supports. Most administrator-identified or system-level barriers and facilitators fit into the category of logistical issues. We have moderate confidence in buprenorphine findings but low confidence in naltrexone findings due to the small number of studies. Discussion Stigma, treatment experiences, logistical issues, and knowledge gaps are the main barriers associated with low utilization of OUD medications. These barriers can overlap and mutually reinforce each other, but given that, it is plausible that reducing one barrier may lead to reductions in others. The highest priority for future research is to evaluate interventions to reduce stigma. Other priorities for future research include better identification of barriers and facilitators for specific populations, such as those with OUD related to prescription opioids, and for naltrexone use. Protocol Registration PROSPERO; CRD42019133394

An exponential increase in the number of systematic reviews published, and constrained resources for new reviews, means that there is an urgent need for guidance on explicitly and transparently integrating existing reviews into new systematic reviews. The objectives of this paper are: 1) to identify areas where existing guidance may be adopted or adapted, and 2) to suggest areas for future guidance development. We searched documents and websites from healthcare focused systematic review organizations to identify and, where available, to summarize relevant guidance on the use of existing systematic reviews. We conducted informational interviews with members of Evidence-based Practice Centers (EPCs) to gather experiences in integrating existing systematic reviews, including common issues and challenges, as well as potential solutions. There was consensus among systematic review organizations and the EPCs about some aspects of incorporating existing systematic reviews into new reviews. Current guidance may be used in assessing the relevance of prior reviews and in scanning references of prior reviews to identify studies for a new review. However, areas of challenge remain. Areas in need of guidance include how to synthesize, grade the strength of, and present bodies of evidence composed of primary studies and existing systematic reviews. For instance, empiric evidence is needed regarding how to quality check data abstraction and when and how to use study-level risk of bias assessments from prior reviews. There remain areas of uncertainty for how to integrate existing systematic reviews into new reviews. Methods research and consensus processes among systematic review organizations are needed to develop guidance to address these challenges.

Background Many clinicians are reevaluating the use of long-term opioid therapy (LTOT) for chronic pain in response to the opioid crisis and calls from organizations including the Centers for Disease Control & Prevention to limit prescribing of high-dose opioids. However, this practice change is occurring largely in the absence of data regarding patient outcomes. A 2017 systematic review found inconclusive evidence on the impact of LTOT dose reduction and discontinuation on pain severity and function, quality of life, withdrawal symptoms, substance abuse, and adverse effects. This rapid systematic review provides an updated evidence synthesis of patient outcomes following LTOT dose reduction including serious harms such as overdose and suicide. Methods We systematically searched numerous bibliographic databases from January 2017 (the end search date of the 2017 systematic review) through May 2020. One reviewer used prespecified criteria to assess articles for inclusion, evaluate study quality, abstract data, and grade strength of evidence, with a second reviewer checking. Results We included 49 studies—1 systematic review, 34 studies included in that systematic review, and 14 new studies. We prioritized evidence synthesis of 19 studies with the most applicability to the Veteran population and outpatient settings. Among these studies, improvements in mean pain scores were common among patients tapering opioids while participating in intensive multimodal pain interventions and mostly unchanged with less intensive or nonspecific co-interventions. Our confidence in these findings is low due to methodological limitations of the studies. Observational data suggests that serious harms such as opioid overdose and suicidal ideation can occur following opioid dose reduction or discontinuation, but the incidence of these harms at the population level is unknown. Discussion The net balance of benefits and harms of LTOT dose reduction for patients with chronic pain is unclear. Clinicians should closely monitor patients during the tapering process given the potential for harm.

Continued racial/ethnic health disparities were recently described as \"the most serious and shameful health care issue of our time.\" Although the 2014 US Affordable Care Act-mandated national insurance coverage expansion has led to significant improvements in health care coverage and access, its effects on life expectancy are not yet known. The Veterans Health Administration (VHA), the largest US integrated health care system, has a sustained commitment to health equity that addresses all 3 stages of health disparities research: detection, understanding determinants, and reduction or elimination. Despite this, racial disparities still exist in the VHA across a wide range of clinical areas and service types. To inform the health equity research agenda, we synthesized evidence on racial/ethnic mortality disparities in the VHA. Our research librarian searched MEDLINE and Cochrane Central Registry of Controlled Trials from October 2006 through February 2017 using terms for racial groups and disparities. We included studies if they compared mortality between any racial/ethnic minority and nonminority veteran groups or between different minority groups in the VHA (PROSPERO# CRD42015015974). We made study selection decisions on the basis of prespecified eligibility criteria. They were first made by 1 reviewer and checked by a second and disagreements were resolved by consensus (sequential review). Two reviewers sequentially abstracted data on prespecified population, outcome, setting, and study design characteristics. Two reviewers sequentially graded the strength of evidence using prespecified criteria on the basis of 5 key domains: study limitations (study design and internal validity), consistency, directness, precision of the evidence, and reporting biases. We synthesized the evidence qualitatively by grouping studies first by racial/ethnic minority group and then by clinical area. For areas with multiple studies in the same population and outcome, we pooled their reported hazard ratios (HRs) using random effects models (StatsDirect version 2.8.0; StatsDirect Ltd., Altrincham, England). We created an evidence map using a bubble plot format to represent the evidence base in 5 dimensions: odds ratio or HR of mortality for racial/ethnic minority group versus Whites, clinical area, strength of evidence, statistical significance, and racial group. From 2840 citations, we included 25 studies. Studies were large (n ≥ 10 000) and involved nationally representative cohorts, and the majority were of fair quality. Most studies compared mortality between Black and White veterans and found similar or lower mortality for Black veterans. However, we found modest mortality disparities (HR or OR = 1.07, 1.52) for Black veterans with stage 4 chronic kidney disease, colon cancer, diabetes, HIV, rectal cancer, or stroke; for American Indian and Alaska Native veterans undergoing noncardiac major surgery; and for Hispanic veterans with HIV or traumatic brain injury (most low strength). Although the VHA's equal access health care system has reduced many racial/ethnic mortality disparities present in the private sector, our review identified mortality disparities that have persisted mainly for Black veterans in several clinical areas. However, because most mortality disparities were supported by single studies with imprecise findings, we could not draw strong conclusions about this evidence. More disparities research is needed for American Indian and Alaska Native, Asian, and Hispanic veterans overall and for more of the largest life expectancy gaps. Public Health Implications. Because of the relatively high prevalence of diabetes in Black veterans, further research to better understand and reduce this mortality disparity may be prioritized as having the greatest potential impact. However, other mortality disparities affect thousands of veterans and cannot be ignored.

Background Primary care providers (PCPs) face many system- and patient-level challenges in providing multimodal care for patients with complex chronic pain as recommended in some pain management guidelines. Several models have been developed to improve the delivery of multimodal chronic pain care. These models vary in their key components, and work is needed to identify which have the strongest evidence of clinically-important improvements in pain and function. Our objective was to determine which primary care-based multimodal chronic pain care models provide clinically relevant benefits, define key elements of these models, and identify patients who are most likely to benefit. Methods To identify studies, we searched MEDLINE® (1996 to October 2016), CINAHL, reference lists, and numerous other sources and consulted with experts. We used predefined criteria for study selection, data abstraction, internal validity assessment, and strength of evidence grading. Results We identified nine models, evaluated in mostly randomized controlled trials (RCTs). The RCTs included 3816 individuals primarily from the USA. The most common pain location was the back. Five models primarily coupling a decision-support component—most commonly algorithm-guided treatment and/or stepped care—with proactive ongoing treatment monitoring have the best evidence of providing clinically relevant improvement in pain intensity and pain-related function over 9 to 12 months (NNT range, 4 to 13) and variable improvement in quality of life, depression, anxiety, and sleep. The strength of the evidence was generally low, as each model was only supported by a single RCT with imprecise findings. Discussion Multimodal chronic pain care delivery models coupling decision support with proactive treatment monitoring consistently provide clinically relevant improvement in pain and function. Wider implementation of these models should be accompanied by further evaluation of clinical and implementation effectiveness.

Background Multicomponent, interdisciplinary intensive primary care programs target complex patients with the goal of preventing hospitalizations, but programs vary, and their effectiveness is not clear. In this study, we systematically reviewed the impact of intensive primary care programs on all-cause mortality, hospitalization, and emergency department use. Methods We searched PubMed, CINAHL, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Reviews of Effects from inception to March 2017. Additional studies were identified from reference lists, hand searching, and consultation with content experts. We included systematic reviews, randomized controlled trials (RCTs), and observational studies of multicomponent, interdisciplinary intensive primary care programs targeting complex patients at high risk of hospitalization or death, with a comparison to usual primary care. Two investigators identified studies and abstracted data using a predefined protocol. Study quality was assessed using the Cochrane risk of bias tool. Results A total of 18 studies (379,745 participants) were included. Three major intensive primary care program types were identified: primary care replacement (home-based; three RCTs, one observational study, N  = 367,681), primary care replacement (clinic-based; three RCTs, two observational studies, N  = 9561), and primary care augmentation, in which an interdisciplinary team was added to existing primary care (five RCTs, three observational studies, N  = 2503). Most studies showed no impact of intensive primary care on mortality or emergency department use, and the effectiveness in reducing hospitalizations varied. There were no adverse effects reported. Discussion Intensive primary care interventions demonstrated varying effectiveness in reducing hospitalizations, and there was limited evidence that these interventions were associated with changes in mortality. While interventions could be grouped into categories, there was still substantial overlap between intervention approaches. Further work is needed to identify program features that may be associated with improved outcomes.

Objective This study aims to conduct an evidence review of the effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment for major depressive disorder. Methods We searched MEDLINE®, the Cochrane Central Registry of Controlled Trials, and PsycINFO through February 2017. We used prespecified criteria to select studies, abstract data, and rate internal validity and strength of the evidence (PROSPERO number CRD42016036358). Results We included two randomized trials (RCT), five controlled cohort studies, and six modeling studies of mostly women in their mid-40s with few comorbidities. CNSDose (ABCB1, ABCC1, CYP2C19, CYP2D6, UGT1A1) is the only pharmacogenomics test that significantly improved remission (one additional remitting patient in 12 weeks per three genotyped, 95% CI 1.7 to 3.5) and reduced intolerability in an RCT. ABCB1 genotyping leads to one additional remitting patient in 5 weeks per three genotyped (95% CI 3 to 20), but tolerability was not reported. In an RCT, GeneSight (CYP2D6, CYPC19, CYP1A2, SLC6A4, HTR2A) did not statistically significantly improve remission, and evidence is inconclusive about its tolerability. Evidence is generally low strength because RCTs were few and underpowered. Cost-effectiveness is unclear due to lack of directly observed cost-effectiveness outcomes. We found no studies that evaluated whether pharmacogenomics shortens time to optimal treatment, whether improvements were due to switches to genetically congruent medication, or whether effectiveness varies based on test and patient characteristics. Conclusions Certain pharmacogenomics tools show promise of improving short-term remission rates in women in their mid-40s with few comorbidities. But, important evidence limitations preclude recommending their widespread use and indicate a need for further research.