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Background: Care coordination is crucial to avoid potential risks of care fragmentation in people with complex care needs. While there are many empirical and conceptual approaches to measuring and improving care coordination, use of theory is limited by its complexity and the wide variability of available frameworks. We systematically identified and categorized existing care coordination theoretical frameworks in new ways to make the theory-to-practice link more accessible., Methods: To identify relevant frameworks, we searched MEDLINE®, Cochrane, CINAHL, PsycINFO, and SocINDEX from 2010 to May 2018, and various other nonbibliographic sources. We summarized framework characteristics and organized them using categories from the Sustainable intEgrated chronic care modeLs for multi-morbidity: delivery, FInancing, and performancE (SELFIE) framework. Based on expert input, we then categorized available frameworks on consideration of whether they addressed contextual factors, what locus they addressed, and their design elements. We used predefined criteria for study selection and data abstraction., Results: Among 4389 citations, we identified 37 widely diverse frameworks, including 16 recent frameworks unidentified by previous reviews. Few led to development of measures (39%) or initiatives (6%). We identified 5 that are most relevant to primary care. The 2018 framework by Weaver et al., describing relationships between a wide range of primary care-specific domains, may be the most useful to those investigating the effectiveness of primary care coordination approaches. We also identified 3 frameworks focused on locus and design features of implementation that could prove especially useful to those responsible for implementing care coordination., Discussion: This review identified the most comprehensive frameworks and their main emphases for several general practice-relevant applications. Greater application of these frameworks in the design and evaluation of coordination approaches may increase their consistent implementation and measurement. Future research should emphasize implementation-focused frameworks that better identify factors and mechanisms through which an initiative achieves impact.

Objective Antibiotic 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. Methods To 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. Results Twenty-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). Conclusions The 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.

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: 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., Objectives: To inform the health equity research agenda, we synthesized evidence on racial/ethnic mortality disparities in the VHA., Search Methods: 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., Selection Criteria: 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)., Data Collection and Analysis: 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., Main Results: 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)., Author's Conclusions: 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: 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.

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.

Background: To provide evidence synthesis for faster-paced healthcare decision-making, rapid reviews have emerged as a streamlined alternative to standard systematic reviews. In 2012, the Veterans Affairs Evidence-based Synthesis Program (VA ESP) added rapid reviews to support Veterans Health Administration (VHA) operational partners' more urgent decision-making needs. VHA operational partners play a substantial role in dissemination of ESP rapid reviews through a variety of routes, including posting on the VA ESP's public website ( http://www.hsrd., Research: va.gov/publications/esp/ ). As demand for rapid reviews rises, much progress has been made in characterizing methods and practices. However, evidence synthesis organizations still seek to better understand how and when rapid reviews are being used., Methods: The VA ESP administered an online survey to rapid review operational partners. The survey assessed the nature of decision-making needs, overall perception of review content, resulting actions, and implementation timeframe. We use descriptive statistics and narrative methods to summarize findings., Results: Between October 2011 and April 2015, we completed 12 rapid reviews for 35 operational partners. Operational partners were primarily non-academic subject matter experts with VA operations' decision-making authority. The most common topic categories reviewed were policy or system (50 %) or process of care (42 %) initiatives. Median report completion time was 14.5 weeks. Survey response rate was 46 %, with at least one operational partner responding for 92 % of reports. Reviews served multiple purposes including policy directive or regulation (72 %), supporting program development and evaluation (55 %), identifying future research needs (45 %), and determining implementation strategy (45 %). Overall, operational partners' perception of report content was positive. A majority of rapid reviews were used immediately and informed actions ranking high on the Institute of Medicine's Degrees of Impact framework: 45.4 % effected change, 18.2 % inspired action, 18.2 % informed the field, 9.1 % received recognition, and 9.1 % spread a message., Conclusions: VA ESP rapid reviews have increased the VHA's uptake of evidence to inform time-sensitive system-level decision-making. Key areas of interest for future evaluation include assessing user perception of our streamlined methods and the quality of our efforts to inform users of these methods, as well as comparing the usability and impact of our rapid and standard systematic reviews.

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of cholesterol-lowering medications that provide significant reductions in lipids but at a large cost relative to statins. With 2 such drugs now on the market, alirocumab and evolocumab, comparing the evidence base for these drugs is necessary for informed decision making., Objective: To compare the benefits and harms of the PCSK9 inhibitors alirocumab and evolocumab., Methods: The databases Ovid MEDLINE, Cochrane Library, SCOPUS, and ClinicalTrials.gov were used to search for randomized controlled trials of alirocumab or evolocumab with any relevant comparator reporting health outcomes, lipid outcomes, or harms through September 2015, and information was requested from manufacturers. Results were reviewed according to standard review methods., Results: The database searches revealed 17 fair- and good-quality trials; however, none had primary health outcomes or directly compared PCSK9 inhibitors. Alirocumab (75 mg to 150 mg subcutaneously every 2 weeks) resulted in significantly greater reductions in low-density lipoprotein cholesterol (LDL-C; -8% to -67%) at 12-24 weeks in patients with (a) heterozygous familial hypercholesterolemia and (b) patients at high or varied cardiovascular (CV) risk who were not at LDL-C goals with statin therapy. The highest strength evidence was for patients with high CV risk not at LDL-C goals. Alirocumab also resulted in high-density lipoprotein cholesterol (HDL-C) increases of 6%-12%. Low- and moderate-strength evidence for adjudicated CV events at 52-78 weeks for a priori analyses indicated no benefit. Low- and moderate-strength evidence also found no differences in harms except possibly slightly more injection-site reactions. Evolocumab (120 mg subcutaneously every 2 weeks to 420 mg every 4 weeks) resulted in significantly greater reductions in LDL-C (-32% to -71%) at 12-52 weeks in patients with heterozygous or homozygous familial hypercholesterolemia, patients intolerant of statins, and patients with varied CV risk not at LDL-C goal with statin therapy. The highest strength evidence was for heterozygous familial hypercholesterolemia and patients not at LDL-C goals. Moderate-strength evidence showed HDL-C increases in the range of 4.5%-6.8%. Harms were not different between groups, except possibly slightly greater overall adverse event reporting. Evidence on adjudicated CV outcomes was insufficient to draw conclusions because of sparseness of events, study limitations, and inability to assess consistency of findings., Conclusions: Alirocumab and evolocumab have evidence of large improvements in lipid levels. The strength of the evidence is greater for alirocumab than evolocumab in patients with high CV risk who were not at LDL-C target goals, while evidence for evolocumab is stronger in patients with heterogeneous familial hypercholesterolemia and patients with varied CV risk who were not at LDL-C target goals. Evidence on adjudicated CV outcomes for a priori analyses is unable to show benefit for alirocumab and is insufficient to draw conclusions for evolocumab. Important questions remain about the comparative effects on long-term health outcomes., Disclosures: This project was funded by The Drug Effectiveness Review Project. Project participants reviewed the manuscript but had no role in conducting the work or writing the manuscript. Any comments received from the participants during the course of the review were taken at the discretion of the authors independently. All authors had access to the data and a role in writing the manuscript. McDonagh, Peterson, and Holzhammer declare no conflict of interest or financial interest in any therapy discussed in this article. Fazio declares receiving compensation from Sanofi for a presentation on his science to a group of their advisors and has served as a consultant to MSD, BASF, NHP, Sanofi, Ionis Pharmaceuticals, and Kowa. Study concept and design were primarily contributed by McDonagh, along with Peterson and Holzhammer, with assistance from Fazio. Holzhammer took the lead in data collection, with assistance from McDonagh and Peterson. Data interpretation was performed by McDonagh, Peterson, and Fazio. The manuscript was written by McDonagh, Peterson, and Fazio, with assistance from Holzhammer, and revised by all the authors.

Objectives: To evaluate the benefits and harms of pharmacological therapy for depression in women during pregnancy or the postpartum period., Data Sources: Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, Scopus, ClinicalTrials.gov, and Scientific Information Packets from pharmaceutical manufacturers. Databases were searched from their inception to July 2013.., Review Methods: We included studies comparing pharmacological treatments for depression during or after pregnancy with each other, with nonpharmacological treatments, or with usual care or no treatment. Outcomes included both maternal and infant or child benefits and harms. Dual review was used for study inclusion, data abstraction, and quality assessment. We assessed study quality using methods of the Drug Effectiveness Review Project. We graded the strength of the body of evidence according to the methods of the Effective Health Care Program. Direct evidence comprised studies that compared interventions of interest in the population of interest (i.e., depressed women) and measured the outcomes of interest. Studies comparing groups of depressed women with control groups with no evidence of depression were considered indirect., Results: We included 15 observational studies that provided direct evidence on benefits and harms of antidepressants for depression during pregnancy. We included six randomized controlled trials and two observational studies of antidepressant treatment for depression in postpartum women. Studies of depressed pregnant women primarily compared antidepressant treatment with no treatment, and studies of postpartum women also compared antidepressants alone with combination antidepressant-nonpharmacological treatments. This evidence was insufficient to draw conclusions on the comparative benefits or harms of antidepressants for the outcomes of maternal depression symptoms, functional capacity, breastfeeding, mother-infant dyad interactions, and infant and child development for either pregnant or postpartum women with depression. Low-strength evidence suggests that neonates of women with depression taking selective serotonin reuptake inhibitors (SSRIs) during pregnancy had higher risk of respiratory distress than neonates of untreated women but that risk of preterm birth or neonatal convulsions does not differ between these groups. Direct evidence on the risk of major malformations and neonatal development with exposure to antidepressants in utero was insufficient to draw conclusions. For postpartum women with depression, evidence was insufficient to evaluate the full range of benefits and harms of treatment. Low-strength evidence was unable to show a benefit of adding brief psychotherapy or cognitive behavioral therapy to SSRIs., To address gaps in the direct evidence, we included an additional 109 observational studies of pregnant women receiving antidepressants for mixed or unreported reasons compared with pregnant women not taking antidepressants whose depression status was unknown. Signals from this indirect evidence suggest that future research should focus on the comparative risk of congenital anomalies and neonatal motor developmental delays. Although the absolute increased risk of autism spectrum disorder or attention-deficit hyperactivity disorder in the child associated with antidepressant use for depression in pregnancy may be very small, this issue also merits attention in future research. Future research should compare available treatments in groups of women with depression and have adequate sample sizes. Investigations should also take into account potential confounding, including age, race, parity, other exposures (e.g., alcohol, smoking, and other potential teratogens), and the impact of dose, severity of depression, timing of diagnosis, or prior depressive episodes., Conclusions: Evidence about the comparative benefits and harms of pharmacological treatment of depression in pregnant and postpartum women was largely inadequate to allow well-informed decisions about treatment. For pregnant women, this was mainly because comparison groups were not exclusively depressed women. For postpartum women, the lack of evidence arose chiefly from a scarcity of studies. These are major limitations, as depression is known to be associated with serious adverse outcomes. Given the prevalence of depression and its impact on the lives of pregnant women, new mothers, and children, new research to fill this informational gap is essential., Competing Interests: None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report., (This publication is in the public domain.)