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Background The Veterans Health Administration (VA) serves Veterans in the nation’s largest integrated healthcare system. VA seeks to provide high quality of healthcare to Veterans, but due to the VA Choice and MISSION Acts, VA increasingly pays for care outside of its system in the community. This systematic review compares care provided in VA and non-VA settings, and includes published studies from 2015 to 2023, updating 2 prior systematic reviews on this topic. Methods We searched PubMed, Web of Science, and PsychINFO from 2015 to 2023 for published literature comparing VA and non-VA care, including VA-paid community care. Records were included at the abstract or full-text level if they compared VA medical care with care provided in other healthcare systems, and included clinical quality, safety, access, patient experience, efficiency (cost), or equity outcomes. Data from included studies was abstracted by two independent reviewers, with disagreements resolved by consensus. Results were synthesized narratively and via graphical evidence maps. Results Thirty-seven studies were included after screening 2415 titles. Twelve studies compared VA and VA-paid community care. Most studies assessed clinical quality and safety, and studies of access were second most common. Only six studies assessed patient experience and six assessed cost or efficiency. Clinical quality and safety of VA care was better than or equal to non-VA care in most studies. Patient experience in VA care was better than or equal to experience in non-VA care in all studies, but access and cost/efficiency outcomes were mixed. Discussion VA care is consistently as good as or better than non-VA care in terms of clinical quality and safety. Access, cost/efficiency, and patient experience between the two systems are not well studied. Further research is needed on these outcomes and on services widely used by Veterans in VA-paid community care, like physical medicine and rehabilitation.

BACKGROUND: Well-defined, systematic, and transparent processes to identify health research gaps, needs, and priorities are vital to ensuring that available funds target areas with the greatest potential for impact. OBJECTIVE: The purpose of this review is to characterize methods conducted or supported by research funding organizations to identify health research gaps, needs, or priorities. METHOD: We searched MEDLINE, PsycINFO, and the Web of Science up to September 2019. Eligible studies reported on methods to identify health research gaps, needs, and priorities that had been conducted or supported by research funding organizations. Using a published protocol, we extracted data on the method, criteria, involvement of stakeholders, evaluations, and whether the method had been replicated (i.e., used in other studies). RESULTS: Among 10,832 citations, 167 studies were eligible for full data extraction. More than half of the studies employed methods to identify both needs and priorities, whereas about a quarter of studies focused singularly on identifying gaps (7%), needs (6%), or priorities (14%) only. The most frequently used methods were the convening of workshops or meetings (37%), quantitative methods (32%), and the James Lind Alliance approach, a multi-stakeholder research needs and priority setting process (28%). The most widely applied criteria were importance to stakeholders (72%), potential value (29%), and feasibility (18%). Stakeholder involvement was most prominent among clinicians (69%), researchers (66%), and patients and the public (59%). Stakeholders were identified through stakeholder organizations (51%) and purposive (26%) and convenience sampling (11%). Only 4% of studies evaluated the effectiveness of the methods and 37% employed methods that were reproducible and used in other studies. DISCUSSION: To ensure optimal targeting of funds to meet the greatest areas of need and maximize outcomes, a much more robust evidence base is needed to ascertain the effectiveness of methods used to identify research gaps, needs, and priorities. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-07064-1.

Although transitions between health care systems are common when patients move between jobs or insurers, they are especially difficult to navigate when patients with mental health conditions leave an integrated system, such as the Military Health System (MHS). The authors synthesize evidence from studies of interventions that facilitate transitions between mental health care systems, such as the transition from the MHS to the Veterans Health Administration (VHA). The authors searched multiple research databases, reference-mined bibliographies of existing reviews, and consulted with experts to identify existing evaluations of transition support interventions. Key informants helped identify pertinent populations of interest who are transitioning between health care systems. Seventeen studies evaluating different approaches met inclusion criteria. Studies reported on different outcomes, and few could be combined in aggregated analyses. Analyses showed that care transition interventions can increase outpatient mental health service use, but the overall body of evidence is limited.

Background Understanding the safety of vaccines is critical to inform decisions about vaccination. Our objective was to conduct a systematic review of the safety of vaccines recommended for children, adults, and pregnant women in the United States. Methods We searched the literature in November 2020 to update a 2014 Agency for Healthcare Research and Quality review by integrating newly available data. Studies of vaccines that used a comparator and reported the presence or absence of key adverse events were eligible. Adhering to Evidence-based Practice Center methodology, we assessed the strength of evidence (SoE) for all evidence statements. The systematic review is registered in PROSPERO (CRD42020180089). Results Of 56,603 reviewed citations, 338 studies reported in 518 publications met inclusion criteria. For children, SoE was high for no increased risk of autism following measles, mumps, and rubella (MMR) vaccine. SoE was high for increased risk of febrile seizures with MMR. There was no evidence of increased risk of intussusception with rotavirus vaccine at the latest follow-up (moderate SoE), nor of diabetes (high SoE). There was no evidence of increased risk or insufficient evidence for key adverse events for newer vaccines such as 9-valent human papillomavirus and meningococcal B vaccines. For adults, there was no evidence of increased risk (varied SoE) or insufficient evidence for key adverse events for the new adjuvanted inactivated influenza vaccine and recombinant adjuvanted zoster vaccine. We found no evidence of increased risk (varied SoE) for key adverse events among pregnant women following tetanus, diphtheria, and acellular pertussis vaccine, including stillbirth (moderate SoE). Conclusions Across a large body of research we found few associations of vaccines and serious key adverse events; however, rare events are challenging to study. Any adverse events should be weighed against the protective benefits that vaccines provide.

ObjectiveOne potential barrier to optimal healthcare may be provider burnout or occupational-related stress in the workplace. The objective of this study is to conduct a systematic review to identify the predictors of burnout among US. healthcare providers.DesignSystematic review using in-depth critical appraisal to assess risk of bias and present the quality of evidence in synthesised results from the prognostic studies.Data sourcesWe searched 11 databases, registries, existing reviews and contacted experts through 4 October 2021.Eligibility criteria for selecting studiesWe included all studies evaluating potential predictors and documenting the presence and absence of associations with burnout assessed as a multidimensional construct. We excluded studies that relied solely on a single continuous subscale of burnout. Data were abstracted from eligible studies and checked for accuracy by a content expert and a methodologist.Data extraction and synthesisTwo reviewers independently screened citations and full-text publications using predetermined eligibility criteria.ResultsThe 141 identified studies evaluated a range of burnout predictors. Findings for demographic characteristics were conflicting or show no association. Workplace factors, such as workload, work/life balance, job autonomy and perceived support from leadership, had stronger associations with risk for burnout. Mental health factors, such as anxiety, and physical health risks may increase the risk, although the direction of these associations is unclear as few prospective studies exist to address this question. Factors such as social support appear to have a protective effect.ConclusionWe found the most evidence for workplace, mental health and psychosocial factors in predicting burnout but limited evidence for other potential predictors. However, more prospective studies are needed to improve our understanding about how to prevent provider burnout.PROSPERO registration numberCRD4202014836.

Well-defined, systematic, and transparent processes to identify health research gaps, needs, and priorities are vital to ensuring that available funds target areas with the greatest potential for impact. This study documents a scoping review of published methods used for identifying health research gaps, establishing research needs, and determining research priorities and provides relevant information on 362 studies. Of the 362 studies, 167 were linked to funding decisionmaking and underwent a more detailed data abstraction process. The authors noted that most studies focused on physical health conditions, but few addressed psychological health conditions. The most frequent method for identifying research gaps, needs, and priorities was to convene workshops or conferences. One-third of studies employed quantitative methods, and nearly as many used the James Lind Alliance Priority Setting Partnerships approach. Other methods included literature reviews, qualitative methods, consensus methods, and reviews of source materials. The criterion most widely applied to determine health research gaps, needs, and priorities was the importance to stakeholders, followed by the potential value and feasibility of carrying out the research. The two largest stakeholder groups were researchers and clinicians. More than one-half the studies involved patients and the public as stakeholders. Very few studies have evaluated the impact of methods used to identify research gaps, needs, and priorities. This study provides a roadmap of methods used for identifying health research gaps, needs, and priorities, which may help accelerate progress toward validating methods that ensure the effective targeting of funds to meet the greatest areas of need and to maximize impact.

Posttraumatic stress disorder (PTSD) is a condition that can emerge after exposure to a traumatic event. It involves several symptoms, including distressing memories or dreams and/or dissociative reactions; psychological distress at exposure to trauma cues; physiologic reactions to cues; avoidance of stimuli associated with the event; negative alterations in cognitions and mood associated with the trauma; and alterations in arousal and reactivity, including sleep disturbance. The purpose of this systematic review is to synthesize the evidence from randomized controlled trials on the effects that interventions for adults with PTSD have on sleep outcomes. The authors searched research databases and bibliographies of existing systematic reviews to identify pertinent trials published in English; literature was identified by the searches using predetermined eligibility criteria. The primary outcome domain included sleep quality, insomnia, and nightmares. Secondary outcomes were PTSD symptoms and adverse events. Risk of bias and the quality of evidence were assessed for each outcome. The identified interventions addressed pharmacological, psychological, behavioral, complementary, and integrative medicine treatments aimed at improving sleep or lessening other PTSD symptoms. Interventions in general showed an effect on sleep. Interventions explicitly targeting sleep—particularly psychotherapy targeting sleep—showed larger effects on sleep than did interventions not targeting sleep. Heterogeneity was considerable, but sleep effect estimates were not systematically affected by trauma type, setting, or modality. Comparative effectiveness studies are needed to support the findings.

Objective In pandemics like COVID-19, the need for medical resources quickly outpaces available supply. policymakers need strategies to inform decisions about allocating scarce resources. Study design and setting We updated a systematic review on evidence-based approaches and searched databases through May 2020 for evaluation of strategies for policymakers. Results The 201 identified studies evaluated reducing demand for healthcare, optimizing existing resources, augmenting resources, and adopting crisis standards of care. Most research exists to reduce demand (n = 149); 39 higher quality studies reported benefits of contact tracing, school closures, travel restrictions, and mass vaccination. Of 28 strategies to augment resources, 6 higher quality studies reported effectiveness of establishing temporary facilities, use of volunteers, and decision support software. Of 23 strategies to optimize existing resources, 12 higher quality studies reported successful scope of work expansions and building on existing interagency agreements. Of 15 COVID-19 studies, 5 higher quality studies reported on combinations of policies and benefits of community-wide mask policies. Conclusion Despite the volume, the evidence base is limited; few strategies were empirically tested in robust study designs. The review provides a comprehensive overview of the effects of strategies to allocate resources and provides critical appraisal to identify the best available evidence.

ImportanceAcupuncture is a popular treatment that has been advocated for dozens of adult health conditions and has a vast evidence base.ObjectiveTo map the systematic reviews, conclusions, and certainty or quality of evidence for outcomes of acupuncture as a treatment for adult health conditions.Evidence ReviewComputerized search of PubMed and 4 other databases from 2013 to 2021. Systematic reviews of acupuncture (whole body, auricular, or electroacupuncture) for adult health conditions that formally rated the certainty, quality, or strength of evidence for conclusions. Studies of acupressure, fire acupuncture, laser acupuncture, or traditional Chinese medicine without mention of acupuncture were excluded. Health condition, number of included studies, type of acupuncture, type of comparison group, conclusions, and certainty or quality of evidence. Reviews with at least 1 conclusion rated as high-certainty evidence, reviews with at least 1 conclusion rated as moderate-certainty evidence, and reviews with all conclusions rated as low- or very low-certainty evidence; full list of all conclusions and certainty of evidence.FindingsA total of 434 systematic reviews of acupuncture for adult health conditions were found; of these, 127 reviews used a formal method to rate certainty or quality of evidence of their conclusions, and 82 reviews were mapped, covering 56 health conditions. Across these, there were 4 conclusions that were rated as high-certainty evidence, and 31 conclusions that were rated as moderate-certainty evidence. All remaining conclusions (>60) were rated as low- or very low-certainty evidence. Approximately 10% of conclusions rated as high or moderate-certainty were that acupuncture was no better than the comparator treatment, and approximately 75% of high- or moderate-certainty evidence conclusions were about acupuncture compared with a sham or no treatment.Conclusions and RelevanceDespite a vast number of randomized trials, systematic reviews of acupuncture for adult health conditions have rated only a minority of conclusions as high- or moderate-certainty evidence, and most of these were about comparisons with sham treatment or had conclusions of no benefit of acupuncture. Conclusions with moderate or high-certainty evidence that acupuncture is superior to other active therapies were rare.

ImportanceHousing insecurity—that is, difficulty with housing affordability and stability—is prevalent and results in increased risk for both homelessness and poor health. However, whether interventions that prevent housing insecurity upstream of homelessness improve health remains uncertain.ObjectiveTo review evidence characterizing associations of primary prevention strategies for housing insecurity with adult physical health, mental health, health-related behaviors, health care use, and health care access.Evidence ReviewPairs of independent reviewers systematically searched PubMed, Web of Science, EconLit, and the Social Interventions Research and Evaluation Network for quantitative studies published from 2005 to 2021 that evaluated interventions intended to directly improve housing affordability and/or stability either by supporting at-risk households (targeted primary prevention) or by enhancing community-level housing supply and affordability in partnership with the health sector (structural primary prevention). Risk of bias was appraised using validated tools, and the evidence was synthesized using modified Grading of Recommendations Assessment, Development, and Evaluation criteria.FindingsA total of 26 articles describing 3 randomized trials and 20 observational studies (16 longitudinal designs and 4 cross-sectional quasi–waiting list control designs) were included. Existing interventions have focused primarily on mitigating housing insecurity for the most vulnerable individuals rather than preventing housing insecurity outright. Moderate-certainty evidence was found that eviction moratoriums were associated with reduced COVID-19 cases and deaths. Certainty of evidence was low or very low for health associations of other targeted primary prevention interventions, including emergency rent assistance, legal assistance with waiting list priority for public housing, long-term rent subsidies, and homeownership assistance. No studies evaluated health system–partnered structural primary prevention strategies.Conclusions and RelevanceThis systematic review found mixed and mostly low-certainty evidence that interventions that promote housing affordability and stability were associated with improved adult health outcomes. Existing interventions may need to be paired with other efforts to address the structural determinants of health. As health care systems and insurers respond to increasing opportunities to invest in housing as a determinant of health, further research is needed to clarify where along the housing insecurity pathway interventions should focus for the most effective and equitable health impact.

Objective. This evidence report synthesizes the available evidence on radiation therapy for brain metastases. Data sources. We searched PubMed®, Embase®, Web of Science, Scopus, CINAHL®, clinicaltrials.gov, and published guidelines in July 2020; assessed independently submitted data; consulted with experts; and contacted authors. Review methods. The protocol was informed by Key Informants. The systematic review was supported by a Technical Expert Panel and is registered in PROSPERO (CRD42020168260). Two reviewers independently screened citations; data were abstracted by one reviewer and checked by an experienced reviewer. We included randomized controlled trials (RCTs) and large observational studies (for safety assessments), evaluating whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) alone or in combination, as initial or postoperative treatment, with or without systemic therapy for adults with brain metastases due to non-small cell lung cancer, breast cancer, or melanoma. Results. In total, 97 studies, reported in 190 publications, were identified, but the number of analyses was limited due to different intervention and comparator combinations as well as insufficient reporting of outcome data. Risk of bias varied; 25 trials were terminated early, predominantly due to poor accrual. Most studies evaluated WBRT, alone or in combination with SRS, as initial treatment; 10 RCTs reported on post-surgical interventions. The combination treatment SRS plus WBRT compared to SRS alone or WBRT alone showed no statistically significant difference in overall survival (hazard ratio [HR], 1.09; confidence interval [CI], 0.69 to 1.73; 4 RCTs; low strength of evidence [SoE]) or death due to brain metastases (relative risk [RR], 0.93; CI, 0.48 to 1.81; 3 RCTs; low SoE). Radiation therapy after surgery did not improve overall survival compared with surgery alone (HR, 0.98; CI, 0.76 to 1.26; 5 RCTs; moderate SoE). Data for quality of life, functional status, and cognitive effects were insufficient to determine effects of WBRT, SRS, or post-surgical interventions. We did not find systematic differences across interventions in serious adverse events radiation necrosis, fatigue, or seizures (all low or moderate SoE). WBRT plus systemic therapy (RR, 1.44; CI, 1.03 to 2.00; 14 studies; moderate SoE) was associated with increased risks for vomiting compared to WBRT alone. Conclusion. Despite the substantial research literature on radiation therapy, comparative effectiveness information is limited. There is a need for more data on patient-relevant outcomes such as quality of life, functional status, and cognitive effects.

Objective Ductal carcinoma in situ (DCIS) has the potential to progress to invasive carcinoma. The optimal management of DCIS and methods for individualizing treatment of DCIS are still being determined. This evidence map depicts the robustness and topical span of research on DCIS management choice on patient-centered and clinical outcomes. Methods We searched PubMed, EMBASE, PsycINFO, PubMed Health, PROSPERO, and clinical practice guideline sites to identify systematic reviews of DCIS management options and consulted with topic experts. A bubble plot visualizes the literature volume and research content for patient-centered outcomes. An online decision tree facilitates discussions with patients and guides through the available evidence. Results In total, 40 systematic reviews met inclusion criteria. The research syntheses addressed DCIS management options, including the role of magnetic resonance imaging, axillary surgery/sentinel lymph node biopsy, and excisional biopsy. The map shows existing evidence for mutually exclusive treatment options including active surveillance, breast-conserving surgery, nipple sparing mastectomy, and simple mastectomy. Research findings for intraoperative radiation, adjuvant radiation therapy, adjuvant hormone therapy, hypofractionation radiotherapy, accelerated partial breast irradiation, radiation therapy plus boost, and combined radiation and hormone therapy, as well as for breast reconstruction after mastectomy and surveillance mammography postsurgery are also displayed. The evidence map highlights a scarcity of robust evidence on patient-centered outcomes. Conclusions The evidence map provides an overview of DCIS research showing the range of management options and remaining decisional dilemmas that follow a diagnosis of DCIS. It maps the evidence in accessible tools to guide practice and future research. : Video Summary:http://links.lww.com/MENO/A448.

Objective. To conduct a systematic review of the literature on the safety of vaccines recommended for routine immunization in the United States, updating the 2014 Agency for Healthcare Research and Quality (AHRQ) report on the topic. Data sources. We searched MEDLINE®, Embase®, CINAHL®, Cochrane CENTRAL, Web of Science, and Scopus through November 9, 2020, building on the prior 2014 report; reviewed existing reviews, trial registries, and supplemental material submitted to AHRQ; and consulted with experts. Review methods. This report addressed three Key Questions (KQs) on the safety of vaccines currently in use in the United States and included in the Centers for Disease Control and Prevention’s (CDC) recommended immunization schedules for adults (KQ1), children and adolescents (KQ2), and pregnant women (KQ3). The systematic review was supported by a Technical Expert Panel that identified key adverse events of particular concern. Two reviewers independently screened publications; data were extracted by an experienced subject matter expert. Studies of vaccines that used a comparator and reported the presence or absence of adverse events were eligible. We documented observed rates and assessed the relative risks for key adverse events. We assessed the strength of evidence (SoE) across the existing findings from the prior 2014 report and the new evidence from this update. The systematic review is registered in PROSPERO (CRD42020180089). Results. A large body of evidence is available to evaluate adverse events following vaccination. Of 56,608 reviewed citations, 189 studies met inclusion criteria for this update, adding to data in the prior 2014 report, for a total of 338 included studies reported in 518 publications. Regarding vaccines recommended for adults (KQ1), we found either no new evidence of increased risk for key adverse events with varied SoE or insufficient evidence in this update, including for newer vaccines such as recombinant influenza vaccine, adjuvanted inactivated influenza vaccine, and recombinant adjuvanted zoster vaccine. The prior 2014 report noted a signal for anaphylaxis for hepatitis B vaccines in adults with yeast allergy and for tetanus, diphtheria, and acellular pertussis vaccines. Regarding vaccines recommended for children and adolescents (KQ2), we found either no new evidence of increased risk for key adverse events with varied SoE or insufficient evidence, including for newer vaccines such as 9-valent human papillomavirus vaccine and meningococcal B vaccine. The prior 2014 report noted signals for rare adverse events—such as anaphylaxis, idiopathic thrombocytopenic purpura, and febrile seizures—with some childhood vaccines. Regarding vaccines recommended for pregnant women (KQ3), we found no evidence of increased risk for key adverse events with varied SoE among either pregnant women or their infants following administration of tetanus, diphtheria, and acellular pertussis vaccines during pregnancy. Conclusion. Across this large body of research, we found no new evidence of increased risk since the prior 2014 report for key adverse events following administration of vaccines that are routinely recommended. Signals from the prior report remain unchanged for rare adverse events, which include anaphylaxis in adults and children, and febrile seizures and idiopathic thrombocytopenic purpura in children. There is no evidence of increased risk of adverse events for vaccines currently recommended in pregnant women. There remains insufficient evidence to draw conclusions about some rare potential adverse events.

Purpose This evidence report synthesizes the available evidence on radiation therapy for brain metastases. Methods and Materials The literature search included PubMed, EMBASE, Web of Science, Scopus, CINAHL, clinicaltrials.gov, and published guidelines in July 2020; independently submitted data, expert consultation, and contacting authors. Included studies were randomized controlled trials (RCTs) and large observational studies (for safety assessments), evaluating whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) alone or in combination, as initial or postoperative treatment, with or without systemic therapy for adults with brain metastases due to lung cancer, breast cancer, or melanoma. Results Ninety-seven studies reported in 189 publications were identified, but the number of analyses was limited owing to different intervention and comparator combinations as well as insufficient reporting of outcome data. Risk of bias varied, and 25 trials were terminated early, predominantly owing to poor accrual. The combination of SRS plus WBRT compared with SRS alone or WBRT alone showed no statistically significant difference in overall survival (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.69%-1.73%; 4 RCTs) or death owing to brain metastases (relative risk [RR], 0.93; 95% CI, 0.48%-1.81%; 3 RCTs). Radiation therapy after surgery did not improve overall survival compared with surgery alone (HR, 0.98; 95% CI, 0.76%-1.26%; 5 RCTs). Data for quality of life, functional status, and cognitive effects were insufficient to determine effects of WBRT, SRS, or postsurgery interventions. We did not find systematic differences across interventions in serious adverse events, number of adverse events, radiation necrosis, fatigue, or seizures. WBRT plus systemic therapy (RR 1.44; 95% CI, 1.03%-2.00%; 14 studies) was associated with increased risks for vomiting compared with WBRT alone. Conclusions Despite the substantial research literature on radiation therapy, comparative effectiveness information is limited. There is a need for more data on patient-relevant outcomes such as quality of life, functional status, and cognitive effects.

Chimeric antigen receptor (CAR)-T cell therapies appear to be promising treatments for non-Hodgkin's and B-cell lymphoma. However, several CAR-T therapies approved by the US Food and Drug Administration have only been tested for efficacy in relatively few single-arm clinical trials with small sample sizes. We sought to examine the differences between patients in these trials and the general population of patients with non-Hodgkin's and B-cell lymphoma. Five hundred and twenty-two patients from 15 CAR-T trials found in a systematic review and 417,492 patients from the Surveillance, Epidemiology, and End Results (SEER) Program database were compared. CAR-T study participants appeared to be younger (46.7% under 70 years old vs. 42.2%), more male (68.0% vs. 55.7%), and followed for a shorter period of time compared to patients in the SEER population (mean [M] 45.6 months, 95% confidence interval [CI] 17.7 to 63.3 months follow-up vs. M 57.1 months, 95% CI 57.0 to 57.3 months survival). CAR-T study participants may differ significantly from the general population of patients with non-Hodgkin's and B-cell lymphoma. Effectiveness of CAR-T therapies in the general population of lymphoma patients may differ from effectiveness demonstrated in trials. Newly created CAR-T patient registries are essential to establishing population-level effectiveness of the therapies.

Background Uncertainty remains regarding the effectiveness of treatments for patients diagnosed with both an alcohol use disorder (AUD) and depressive disorder. This study aimed to compare the effectiveness of clinical interventions for improving symptoms of adults with co-occurring AUDs and depressive disorders. Methods and findings We searched CINAHL, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Excerpta Medica Database, International Clinical Trials Registry Platform (ICTRP), PubMed, PsycINFO, and Web of Science from inception to December 2020. We included randomized controlled trials (RCTs) evaluating clinical interventions for adults with co-occurring AUDs and depressive disorders. Two independent reviewers extracted study-level information and outcome data. We assessed risk of bias using the Cochrane Risk of Bias tool, used frequentist random effects models for network meta-analyses, and rated our confidence in effect estimates using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Primary outcomes were remission from depression and alcohol use. Secondary outcomes were depressive symptoms, alcohol use, heavy drinking, health-related quality of life, functional status, and adverse events. We used standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes to estimate intervention effects. Overall, 36 RCTs with 2,729 participants evaluated 14 pharmacological and 4 psychological interventions adjunctive to treatment as usual (TAU). Studies were published from 1971 to 2019, conducted in 13 countries, and had a median sample size of 50 participants (range: 14 to 350 participants). We have very low confidence in all estimates of intervention effects on our primary outcomes (i.e., remission from depression and remission from alcohol use). We have moderate confidence that cognitive behavioral therapies (CBTs) demonstrated greater benefit than no additional treatment (SMD = −0.84; 95% confidence interval [CI], −1.05 to −0.63; p < 0.001) for depressive symptoms and low confidence (SMD = −0.25; 95% CI, −0.47 to −0.04; p = 0.021) for alcohol use. We have low confidence that tricyclic antidepressants (TCAs) demonstrated greater benefit than placebo (SMD = −0.37; 95% CI, −0.72 to −0.02, p = 0.038) for depressive symptoms. Compared with placebo, we have moderate confidence that selective serotonin reuptake inhibitors (SSRIs) demonstrated greater benefit for functional status (SMD = −0.92; 95% CI, −1.36 to −0.47, p < 0.001) and low confidence for alcohol use (SMD = −0.30; 95% CI, −0.59 to −0.02, p = 0.039). However, we have moderate confidence that patients receiving SSRIs also were more likely to experience an adverse event (OR = 2.20; 95% CI, 0.94 to 5.16, p = 0.07). We have very low confidence in all other effect estimates, and we did not have high confidence in any effect estimates. Limitations include the sparsity of evidence on intervention effects over the long term, risks of attrition bias, and heterogeneous definitions of adverse events in the evidence base. Conclusions We are very uncertain about the existence (or not) of any non-null effects for our primary outcomes of remission from depression and remission from alcohol use. The available evidence does suggest that CBTs likely reduced, and TCAs may have resulted in a slight reduction of depressive symptoms. SSRIs likely increased functional status, and SSRIs and CBTs may have resulted in a slight reduction of alcohol use. However, patients receiving SSRIs also likely had an increased risk of experiencing an adverse event. In addition, these conclusions only apply to postintervention and are not against active comparators, limiting the understanding of the efficacy of interventions in the long term as well as the comparative effectiveness of active treatments. As we did not have high confidence in any outcomes, additional studies are warranted to provide more conclusive evidence., Sean Grant and co-workers report on pharmacological and psychological treatments for patients with both alcohol-use and depressive disorders., Author summary Why was this study done? Alcohol use disorders (AUDs) and depressive disorders are prevalent behavioral health conditions among adult populations, often co-occur, and have significant personal, societal, and economic consequences. Existing systematic reviews and clinical practice guidelines often focus on either AUDs or depressive disorders, despite the prevalence and significance of their co-occurrence. The objective of this review is to examine the available evidence on the effectiveness of clinical interventions for adult patients with co-occurring AUD and depressive disorders. What did the researchers do and find? We conducted a systematic review and network meta-analysis (NMA) of 36 randomized controlled trials (RCTs) with 2,729 participants evaluating 14 pharmacological and 4 psychological interventions for adults with co-occurring AUDs and depressive disorders. We have very low confidence in all estimates of intervention effects on our primary outcomes (i.e., remission from depression and remission from alcohol use). We found that cognitive behavioral therapies (CBTs) likely reduced, and tricyclic antidepressants (TCAs) may have resulted in a slight reduction of depressive symptoms, selective serotonin reuptake inhibitors (SSRIs) likely increased functional status, SSRIs and CBTs may have resulted in a slight reduction of alcohol use, and SSRIs also likely resulted in an increased risk of experiencing an adverse event. We have very low confidence in all other effect estimates, and we did not have high confidence in any effect estimates. What do these findings mean? We did not have high confidence in any effect estimates, and we have very low confidence in the vast majority of estimates of intervention effects across all outcomes. For policy and practice, we are very uncertain about the existence (or not) of any non-null effects for our primary outcomes of remission from depression and remission from alcohol use. The available evidence does suggest potentially actionable benefits at postintervention of CBTs for depressive symptoms and alcohol use, TCAs for depressive symptoms, and SSRIs for alcohol use and functional status—although SSRIs also likely have higher risks of adverse events (including serious adverse events). For research, future trials are needed that are prospectively registered, adequately powered, fit for pragmatic purposes, comprehensively report study information and outcomes, and evaluate interventions discussed in clinical practice guidelines yet missing from the current body of evidence.

Background The objective was to conduct a systematic review of toolkit evaluations intended to spread interventions to improve healthcare quality. We aimed to determine the components, uptake, and effectiveness of publicly available toolkits. Methods We searched PubMed, CINAHL, and the Web of Science from 2005 to May 2018 for evaluations of publicly available toolkits, used a forward search of known toolkits, screened references, and contacted topic experts. Two independent reviewers screened publications for inclusion. One reviewer abstracted data and appraised the studies, checked by a second reviewer; reviewers resolved disagreements through discussion. Findings, summarized in comprehensive evidence tables and narrative synthesis addressed the uptake and utility, procedural and organizational outcomes, provider outcomes, and patient outcomes. Results In total, 77 studies evaluating 72 toolkits met inclusion criteria. Toolkits addressed a variety of quality improvement approaches and focused on clinical topics such as weight management, fall prevention, vaccination, hospital-acquired infections, pain management, and patient safety. Most toolkits included introductory and implementation material (e.g., research summaries) and healthcare provider tools (e.g., care plans), and two-thirds included material for patients (e.g., information leaflets). Pre-post studies were most common (55%); 10% were single hospital evaluations and the number of participating staff ranged from 17 to 704. Uptake data were limited and toolkit uptake was highly variable. Studies generally indicated high satisfaction with toolkits, but the perceived usefulness of individual tools varied. Across studies, 57% reported on adherence to clinical procedures and toolkit effects were positive. Provider data were reported in 40% of studies but were primarily self-reported changes. Only 29% reported patient data and, overall, results from robust study designs are missing from the evidence base. Conclusions The review documents publicly available toolkits and their components. Available uptake data are limited but indicate variability. High satisfaction with toolkits can be achieved but the usefulness of individual tools may vary. The existing evidence base on the effectiveness of toolkits remains limited. While emerging evidence indicates positive effects on clinical processes, more research on toolkit value and what affects it is needed, including linking toolkits to objective provider behavior measures and patient outcomes. Trial Registration PROSPERO registration number: PROSPERO 2014:CRD42014013930. Electronic supplementary material The online version of this article (10.1186/s13012-019-0929-8) contains supplementary material, which is available to authorized users.

RAND Europe conducted a study on the societal impact of early breast cancer. This study was divided into three interconnected phases, which together aim to enrich the evidence base on the broader health, societal and economic impacts of treatment of early breast cancer, using a mixed methods approach. The second phase was a systematic review on the non-clinical outcomes of recurrence after treatment of early breast cancer.

Objective Obesity is preventable and yet continues to be a major risk factor for chronic disease. Multiple prevention approaches have been proposed across multiple settings where people live, work, learn, worship, and play. This review searched the vast literature on obesity prevention interventions to assess their effects on daily energy consumed and energy expended. Methods This systematic review (PROSPERO registration CRD42017077083) searched seven databases for systematic reviews and studies reporting energy intake and expenditure. Two independent reviewers screened 5,977 citations; data abstraction supported an evidence map, comprehensive evidence tables, and meta-analysis; critical appraisal assessed risk of bias; and the quality of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results Hundreds of published reviews were identified. However, few studies reported on energy intake and expenditure to determine intervention success. Ninety-nine studies across all intervention domains were identified. Few areas demonstrated statistically significant effects across studies; school-based approaches and health care initiatives reduced energy consumed, education reduced energy consumed and increased energy expended, and social-group approaches increased energy expenditure. Conclusions Despite the amount of research on obesity prevention interventions, very few studies have provided relevant information on energy intake and expenditure, two factors determining weight gain. Future research needs to fill this gap to identify successful public health policies.

Purpose Patient-reported data are playing an increasing role in health care. In oncology, data from quality of life (QoL) assessment tools may be particularly important for those with limited survival prospects, where treatments aim to prolong survival while maintaining or improving QoL. This paper examines the use and impact of using QoL measures on health care of cancer patients within a clinical setting, particularly those with brain cancer. It also examines facilitators and challenges, and provides implications for policy and practice. Design We conducted a systematic literature review, 15 expert interviews and a consultation at an international summit. Results The systematic review found no relevant intervention studies specifically in brain cancer patients, and after expanding our search to include other cancers, 15 relevant studies were identified. The evidence on the effectiveness of using QoL tools was inconsistent for patient management, but somewhat more consistent in favour of improving patient–physician communication. Interviews identified unharnessed potential and growing interest in QoL tool use and associated challenges to address. Conclusion Our findings suggest that the use of QoL tools in cancer patients may improve patient–physician communication and have the potential to improve care, but the tools are not currently widely used in clinical practice (in brain cancer nor some other cancer contexts) although they are in clinical trials. There is a need for further research and stakeholder engagement on how QoL tools can achieve most impact across cancer and patient contexts. There is also a need for policy, health professional, research and patient communities to strengthen information exchange and debate, support awareness raising and provide training on tool design, use and interpretation. Electronic supplementary material The online version of this article (doi:10.1007/s11136-016-1278-6) contains supplementary material, which is available to authorized users.

ObjectivesGenetic therapies replace or inactivate disease-causing genes or introduce new or modified genes. These therapies have the potential to cure in a single application rather than treating symptoms through repeated administrations. This evidence map provides a broad overview of the genetic therapies that have been evaluated in randomised controlled trials (RCTs) for efficacy and safety.Eligibility criteriaTwo independent reviewers screened publications using predetermined eligibility criteria. Study details and data on safety and efficacy were abstracted from included trials. Results were visualised in an evidence map.Information sourcesWe searched PubMed, EMBASE, Web of Science, ClinicalTrials.gov and grey literature to November 2018.Risk of biasOnly RCTs were included in this review to reduce the risk of selection bias in the evaluation of genetic therapy safety and efficacy.Included studiesWe identified 119 RCTs evaluating genetic therapies for a variety of clinical conditions.Synthesis of resultsOn average, samples included 107 participants (range: 1–1022), and were followed for 15 months (range: 0–124). Interventions using adenoviruses (40%) to treat cardiovascular diseases (29%) were the most common.Description of the effectIn RCTs reporting safety and efficacy outcomes, in the majority (60%) genetic therapies were associated with improved symptoms but in nearly half (45%) serious adverse event (SAEs) were also reported. Improvement was reported in trials treating cancer, cardiovascular, ocular and muscular diseases. However, only 19 trials reported symptom improvement for at least 1 year.Strengths and limitations of evidenceThis is the first comprehensive evidence map of RCTs evaluating the safety and efficacy of genetic therapies. Evidence for long-term effectiveness and safety is still sparse. This lack of evidence has implications for the use, ethics, pricing and logistics of genetic therapies.InterpretationThis evidence map provides a broad overview of research studies that allow strong evidence statements regarding the safety and efficacy of genetic therapies. Most interventions improve symptoms, but SAE are also common. More research is needed to evaluate genetic therapies with regard to the potential to cure diseases.

Context Palliative care continues to be a rapidly growing field aimed at improving quality of life for patients and their caregivers. Objectives The purpose of this review was to provide a synthesis of the evidence in palliative care to inform the fourth edition of the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care. Methods Ten key review questions addressing eight content domains guided a systematic review focused on palliative care interventions. We searched eight databases in February 2018 for systematic reviews published in English from 2013, after the last edition of National Consensus Project guidelines was published, to present. Experienced literature reviewers screened, abstracted, and appraised data per a detailed protocol registered in PROSPERO. The quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations criteria. The review was supported by a technical expert panel. Results We identified 139 systematic reviews meeting inclusion criteria. Reviews addressed the structure and process of care (interdisciplinary team care, 13 reviews; care coordination, 18 reviews); physical aspects (48 reviews); psychological aspects (26 reviews); social aspects (two reviews); spiritual, religious, and existential aspects (11 reviews); cultural aspects (three reviews); care of the patient nearing the end of life (grief/bereavement programs, six reviews; final days of life, two reviews); ethical and legal aspects (36 reviews). Conclusion A substantial body of evidence exists to support clinical practice guidelines for quality palliative care, but the quality of evidence is limited.

Background Depression is a common mental health disorder for which clinical practice guidelines have been developed. Prior systematic reviews have identified complex organizational interventions, such as collaborative care, as effective for guideline implementation; yet, many healthcare delivery organizations are interested in less resource-intensive methods to increase provider adherence to guidelines and guideline-concordant practices. The objective of this systematic review was to assess the effectiveness of healthcare provider interventions that aim to increase adherence to evidence-based treatment of depression in routine clinical practice. Methods We searched five databases through August 2017 using a comprehensive search strategy to identify English-language randomized controlled trials (RCTs) in the quality improvement, implementation science, and behavior change literature that evaluated outpatient provider interventions, in the absence of practice redesign efforts, to increase adherence to treatment guidelines or guideline-concordant practices for depression. We used meta-analysis to summarize odds ratios, standardized mean differences, and incidence rate ratios, and assessed quality of evidence (QoE) using the GRADE approach. Results Twenty-two RCTs promoting adherence to clinical practice guidelines or guideline-concordant practices met inclusion criteria. Studies evaluated diverse provider interventions, including distributing guidelines to providers, education/training such as academic detailing, and combinations of education with other components such as targeting implementation barriers. Results were heterogeneous and analyses comparing provider interventions with usual clinical practice did not indicate a statistically significant difference in guideline adherence across studies. There was some evidence that provider interventions improved individual outcomes such as medication prescribing and indirect comparisons indicated more complex provider interventions may be associated with more favorable outcomes. We did not identify types of provider interventions that were consistently associated with improvements across indicators of adherence and across studies. Effects on patients’ health in these RCTs were inconsistent across studies and outcomes. Conclusions Existing RCTs describe a range of provider interventions to increase adherence to depression guidelines. Low QoE and lack of replication of specific intervention strategies across studies limited conclusions that can be drawn from the existing research. Continued efforts are needed to identify successful strategies to maximize the impact of provider interventions on increasing adherence to evidence-based treatment for depression. Trial registration PROSPERO record CRD42017060460 on 3/29/17 Electronic supplementary material The online version of this article (10.1186/s13012-018-0788-8) contains supplementary material, which is available to authorized users.

BackgroundLong-term conditions place a substantial burden on primary care services, with drug therapy a core aspect of clinical management. The ideal frequency for issuing of repeat prescriptions for these medications is unknown.AimTo examine the impact of longer duration versus shorter (28-day) duration prescriptions.Design and SettingSystematic review of primary care studies (PROSPERO: CRD42015027042)MethodScientific and grey literature databases were searched from inception up to 21/10/2015. Eligible studies were randomised controlled trials (RCTs) and observational studies that assessed longer prescriptions (range 2 to 4 months) compared with shorter prescriptions (around 28 days), in patients with stable, chronic conditions being treated in primary care. Outcomes of interest were: health outcomes, adverse events, medication adherence, medication wastage, professional administration time, pharmacists’ time/costs, patient experience, and patient out-of-pocket costs.ResultsModerate quality evidence from nine studies suggested that longer prescriptions are associated with increased medication adherence. Evidence from six studies suggested longer prescriptions may increase medication waste, but results were not always statistically significant and were of very low quality. No eligible studies were identified that measured any of the other outcomes of interest, including health outcomes and adverse events.ConclusionThere is insufficient evidence for the overall impact of differing prescription lengths on clinical and health service outcomes, although studies do suggest adherence may improve with longer prescriptions. Current UK recommendations to provide shorter prescriptions are not substantiated by the current evidence base. How this fits inLocal guidance from many health service commissioners, as well as the UK’s Pharmaceutical Services Negotiating Committee, encourages general practitioners (GPs) to issue shorter prescriptions, typically 28 days in length. This guidance is based on non-systematic review evidence, which was not substantiated by our systematic review. Longer prescriptions lengths for people with stable, chronic conditions could be potentially important to GPs in terms of reducing their workload. It also has the potential to have a positive impact for patients, including improving adherence and thus medication effectiveness, and reducing time, cost and inconvenience.

The objective of this systematic review was to synthesize the effectiveness of health care provider interventions that aim to increase the uptake of evidence-based treatment of depression in routine clinical practice. This study summarizes results of comprehensive searches in the quality improvement, implementation science, and behavior change literature. Studies evaluated diverse provider interventions such as sending out depression guidelines to providers, education and training such as academic detailing, and combinations of education with other components such as targeting implementation barriers. A detailed critical appraisal process assessed risk of bias and study quality. The body of evidence was graded using established evidence synthesis criteria. Twenty-two randomized controlled trials promoting uptake of clinical practice guidelines and guideline-concordant practices met inclusion criteria. Results were heterogeneous and analyses comparing interventions with usual clinical practice did not indicate a statistically significant difference in guideline adherence across studies. There was some evidence that interventions improved individual outcomes such as medication prescribing and indirect comparisons indicated that more complex interventions may be associated with more favorable outcomes. However, we did not identify types of interventions that were consistently associated with improvements across indicators of guideline adherence and across studies. Due to the small number of studies reporting team interventions or approaches tested in specialty care we did not identify robust evidence that effects vary by provider group or setting. Low quality of evidence and lack of replication of specific intervention strategies limited conclusions that can be drawn from the existing research.

The European Bathing Directive (2006/7/EC) stipulates water quality standards for recreational bathing waters based on specified limits of faecal indicator organisms (FIOs). Presence of FIOs above the limits is considered to be indicative of poor water quality and to present a risk to bathers' health. The European Bathing Directive (2006) is to be reviewed in 2020. We conducted a rapid evidence assessment on recreational bathing waters and gastrointestinal illness (GI) to identify the extent of the literature published since the previous review period in 2003 and to determine whether there is any new evidence which may indicate that a revision to the Directive would be justified. Overall, 21 papers (from 16 studies), including two RCTs, met the inclusion criteria; 12 were conducted in marine waters and four were conducted in freshwater. Considerable heterogeneity existed between study protocols and the majority had significant methodological limitations, including self-selection and misclassification biases. Moreover, there was limited variation in water quality among studies, providing a limited evidence base on which to assess the classification standards. Overall, there appears to be a consistent significant relationship between faecal indicator organisms and GI in freshwater, but not marine water studies. Given the apparent lack of relationship between GI and water quality, it is unclear whether the boundaries of the Bathing Waters Directive are supported by studies published in the post-2003 period. We suggest that more epidemiological evidence is needed to disprove or confirm the original work that was used to derive these boundaries for marine waters.

The Forces in Mind Trust commissioned RAND Europe to conduct a systematic review of literature on UK Service leaver families' into civilian life. The study examined the evidence base across four thematic areas: engagement with families, family breakdown, family housing and spousal employment. The review identifies areas where evidence is lacking and presents a series of recommendations for future research.

RAND Europe was commissioned by the Forces in Mind Trust to conduct a systematic review to develop a better understanding of the evidence base around four themes associated with the transition into civilian life for UK Service leaver families.

RAND Europe undertook a systematic review of the evidence of effectiveness and cost effectiveness on changing the public's risk related behaviour pertaining to antimicrobial use to inform the development of a NICE public health guideline aimed at delaying antimicrobial resistance (AMR). The review considered educational interventions targeting individuals, communities or the general public delivered via any mode. Specifically, it aimed to address: 1. Which educational interventions are effective and cost-effective in changing the public's behaviour to ensure they only ask for antimicrobials when appropriate and use them correctly? 2. Which educational interventions are effective and cost-effective in changing the public's behaviour to prevent infection and reduce the spread of antimicrobial resistance? Overall, 60 studies met the inclusion criteria; 29 related to research question 1, and 36 related to research question 2 (five studies were applicable to both). The key findings are summarised in "Evidence Statements" in accordance with NICE guidelines. Evidence Statements provide a high level overview of the key features of the evidence including: the number of studies, the quality of evidence, and the direction of the estimated effect followed by a brief summary of each of the supporting studies. Studies are grouped into Evidence Statements by setting and intervention.