Engaging Patients and Other Non-Researchers in Health Research: Defining Research Engagement.

With the increase in patient and consumer activism through the late twentieth century and into this century, patient roles in research evolved into a new model of research engagement, with patients serving as active advisors and co-leading or leading clinical research. By requiring active engagement of patients and other stakeholders, several government research funders have advanced this model, particularly in Canada, the United States (US), United Kingdom (UK), and Australia. A consortium of individuals from these countries formed a Multi-Stakeholder Engagement (MuSE) consortium to examine critical issues in engaged research, establish consensus on definitions, and provide guidance for the field, beginning with an overview of how to involve stakeholders in health research (Concannon et al. J Gen Intern Med. 2019;34(3):458-463) and continuing here with an examination of definitions of research engagement. The political and advocacy roots of engaged research are reflected in definitions. Engagement is conceptualized with reference to research project goals, from informing specific clinical decisions to informing health-system level decisions. Political and cultural differences across countries are evident. Some of these government funders focus on empirical rather than ethical rationales. In countries with centralized health technology assessment, the link between societal values and engaged research is explicit. Ethical rationales for engagement are explicit in most of the published literature on research engagement. Harmonization of definitions is recommended so that research engagement elements, methods, and outcomes and impacts can be clearly examined and understood, and so that the field of research engagement can proceed from a clear conceptual foundation. Specific recommendations for terminology definitions are provided. Placing engaged research on a continuum from specific clinical decisions to more global public and social justice concerns clarifies the type of engaged research, supports appropriate comparisons, and improves the rigor of engaged research methods. The results help identify knowledge gaps in this growing field.

Testing small study effects in multivariate meta-analysis.

Small study effects occur when smaller studies show different, often larger, treatment effects than large ones, which may threaten the validity of systematic reviews and meta-analyses. The most well-known reasons for small study effects include publication bias, outcome reporting bias, and clinical heterogeneity. Methods to account for small study effects in univariate meta-analysis have been extensively studied. However, detecting small study effects in a multivariate meta-analysis setting remains an untouched research area. One of the complications is that different types of selection processes can be involved in the reporting of multivariate outcomes. For example, some studies may be completely unpublished while others may selectively report multiple outcomes. In this paper, we propose a score test as an overall test of small study effects in multivariate meta-analysis. Two detailed case studies are given to demonstrate the advantage of the proposed test over various naive applications of univariate tests in practice. Through simulation studies, the proposed test is found to retain nominal Type I error rates with considerable power in moderate sample size settings. Finally, we also evaluate the concordance between the proposed tests with the naive application of univariate tests by evaluating 44 systematic reviews with multiple outcomes from the Cochrane Database.

Challenges encountered in the conduct of Optimal Health: A patient-centered comparative effectiveness study of interventions for adults with serious mental illness.

BACKGROUND: The aim of patient-centered comparative effectiveness research is to conduct stakeholder-driven investigations that identify which interventions are most effective for which patients under specific circumstances. Conducting this research in real-world settings comes with unique experiences and challenges. We provide the study design, challenges confronted, and the solutions we devised for Optimal Health, a stakeholder-informed patient-centered comparative effectiveness study focused on the needs of seriously mentally ill individuals receiving case management services in community mental health centers across Pennsylvania. METHODS: Optimal Health, supported by the Patient-Centered Outcomes Research Institute, is a cluster-randomized trial of two evidence-based interventions for improving health and wellness across 11 provider sites. Participants were followed for 18-24 months, with repeated measurements of self-reported health status and activation in care and administrative measurements of primary and specialty health service utilization. Health-related quality of life, engagement in care, and service utilization are to be compared via random effects mixed models. Stakeholders were, and continue to be, engaged via focus groups, interviews, and stakeholder advisory board meetings. A learning collaborative model was used to support shared learning and implementation fidelity across provider sites. RESULTS: From 1 November 2013 through 15 July 2014, we recruited 1229 adults with serious mental illness, representing 85.1% of those eligible for study participation. Of these, 713 are in the Provider-Supported arm of the study and 516 in Patient Self-Directed Care. Across five data collection time points, we retained 86% and 83% of the participants in the Provider-Supported and Self-Directed arms, respectively. LESSONS LEARNED: Lessons learned relate to estimation of the size of our study population, the value of multiple data sources, and intervention training and implementation. The use of historical claims data can lead to an overestimation of eligible participants and, subsequently, a reduced study sample and an imbalance between intervention arms. Disruptions in continuity of care in real-world settings can pose challenges to on-site self-report data collection, although the inclusion of multiple data sources in study design can improve data completeness. Geographic dispersion of rural provider sites and staff turnover can lead to training and intervention fidelity challenges that can be overcome with the use of a "train-the-trainer" model, "wellness champions," and the use of a Learning Collaborative approach. Stakeholder engagement in mitigating these challenges proved to be critical to study progress. CONCLUSION: Conducting real-world patient-centered comparative effectiveness research in healthcare systems that care for seriously mentally ill persons is an important yet challenging undertaking, one which requires flexibility in identifying potential adaptations within all major study phases. Advice from a wide range of stakeholders is critical in development of successful strategies.

Association of Spinal Manipulative Therapy With Clinical Benefit and Harm for Acute Low Back Pain: Systematic Review and Meta-analysis.

IMPORTANCE: Acute low back pain is common and spinal manipulative therapy (SMT) is a treatment option. Randomized clinical trials (RCTs) and meta-analyses have reported different conclusions about the effectiveness of SMT. OBJECTIVE: To systematically review studies of the effectiveness and harms of SMT for acute (≤6 weeks) low back pain. DATA SOURCES: Search of MEDLINE, Cochrane Database of Systematic Reviews, EMBASE, and Current Nursing and Allied Health Literature from January 1, 2011, through February 6, 2017, as well as identified systematic reviews and RCTs, for RCTs of adults with low back pain treated in ambulatory settings with SMT compared with sham or alternative treatments, and that measured pain or function outcomes for up to 6 weeks. Observational studies were included to assess harms. DATA EXTRACTION AND SYNTHESIS: Data extraction was done in duplicate. Study quality was assessed using the Cochrane Back and Neck (CBN) Risk of Bias tool. This tool has 11 items in the following domains: randomization, concealment, baseline differences, blinding (patient), blinding (care provider [care provider is a specific quality metric used by the CBN Risk of Bias tool]), blinding (outcome), co-interventions, compliance, dropouts, timing, and intention to treat. Prior research has shown the CBN Risk of Bias tool identifies studies at an increased risk of bias using a threshold of 5 or 6 as a summary score. The evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. MAIN OUTCOMES AND MEASURES: Pain (measured by either the 100-mm visual analog scale, 11-point numeric rating scale, or other numeric pain scale), function (measured by the 24-point Roland Morris Disability Questionnaire or Oswestry Disability Index [range, 0-100]), or any harms measured within 6 weeks. FINDINGS: Of 26 eligible RCTs identified, 15 RCTs (1711 patients) provided moderate-quality evidence that SMT has a statistically significant association with improvements in pain (pooled mean improvement in the 100-mm visual analog pain scale, -9.95 [95% CI, -15.6 to -4.3]). Twelve RCTs (1381 patients) produced moderate-quality evidence that SMT has a statistically significant association with improvements in function (pooled mean effect size, -0.39 [95% CI, -0.71 to -0.07]). Heterogeneity was not explained by type of clinician performing SMT, type of manipulation, study quality, or whether SMT was given alone or as part of a package of therapies. No RCT reported any serious adverse event. Minor transient adverse events such as increased pain, muscle stiffness, and headache were reported 50% to 67% of the time in large case series of patients treated with SMT. CONCLUSIONS AND RELEVANCE: Among patients with acute low back pain, spinal manipulative therapy was associated with modest improvements in pain and function at up to 6 weeks, with transient minor musculoskeletal harms. However, heterogeneity in study results was large.

Association Between Palliative Care and Patient and Caregiver Outcomes: A Systematic Review and Meta-analysis.

Importance: The use of palliative care programs and the number of trials assessing their effectiveness have increased. Objective: To determine the association of palliative care with quality of life (QOL), symptom burden, survival, and other outcomes for people with life-limiting illness and for their caregivers. Data Sources: MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL to July 2016. Study Selection: Randomized clinical trials of palliative care interventions in adults with life-limiting illness. Data Extraction and Synthesis: Two reviewers independently extracted data. Narrative synthesis was conducted for all trials. Quality of life, symptom burden, and survival were analyzed using random-effects meta-analysis, with estimates of QOL translated to units of the Functional Assessment of Chronic Illness Therapy-palliative care scale (FACIT-Pal) instrument (range, 0-184 [worst-best]; minimal clinically important difference [MCID], 9 points); and symptom burden translated to the Edmonton Symptom Assessment Scale (ESAS) (range, 0-90 [best-worst]; MCID, 5.7 points). Main Outcomes and Measures: Quality of life, symptom burden, survival, mood, advance care planning, site of death, health care satisfaction, resource utilization, and health care expenditures. Results: Forty-three RCTs provided data on 12 731 patients (mean age, 67 years) and 2479 caregivers. Thirty-five trials used usual care as the control, and 14 took place in the ambulatory setting. In the meta-analysis, palliative care was associated with statistically and clinically significant improvements in patient QOL at the 1- to 3-month follow-up (standardized mean difference, 0.46; 95% CI, 0.08 to 0.83; FACIT-Pal mean difference, 11.36] and symptom burden at the 1- to 3-month follow-up (standardized mean difference, -0.66; 95% CI, -1.25 to -0.07; ESAS mean difference, -10.30). When analyses were limited to trials at low risk of bias (n = 5), the association between palliative care and QOL was attenuated but remained statistically significant (standardized mean difference, 0.20; 95% CI, 0.06 to 0.34; FACIT-Pal mean difference, 4.94), whereas the association with symptom burden was not statistically significant (standardized mean difference, -0.21; 95% CI, -0.42 to 0.00; ESAS mean difference, -3.28). There was no association between palliative care and survival (hazard ratio, 0.90; 95% CI, 0.69 to 1.17). Palliative care was associated consistently with improvements in advance care planning, patient and caregiver satisfaction, and lower health care utilization. Evidence of associations with other outcomes was mixed. Conclusions and Relevance: In this meta-analysis, palliative care interventions were associated with improvements in patient QOL and symptom burden. Findings for caregiver outcomes were inconsistent. However, many associations were no longer significant when limited to trials at low risk of bias, and there was no significant association between palliative care and survival.

Evaluating site-of-care-related racial disparities in kidney graft failure using a novel federated learning framework.

OBJECTIVES: Racial disparities in kidney transplant access and posttransplant outcomes exist between non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients in the United States, with the site of care being a key contributor. Using multi-site data to examine the effect of site of care on racial disparities, the key challenge is the dilemma in sharing patient-level data due to regulations for protecting patients' privacy. MATERIALS AND METHODS: We developed a federated learning framework, named dGEM-disparity (decentralized algorithm for Generalized linear mixed Effect Model for disparity quantification). Consisting of 2 modules, dGEM-disparity first provides accurately estimated common effects and calibrated hospital-specific effects by requiring only aggregated data from each center and then adopts a counterfactual modeling approach to assess whether the graft failure rates differ if NHB patients had been admitted at transplant centers in the same distribution as NHW patients were admitted. RESULTS: Utilizing United States Renal Data System data from 39 043 adult patients across 73 transplant centers over 10 years, we found that if NHB patients had followed the distribution of NHW patients in admissions, there would be 38 fewer deaths or graft failures per 10 000 NHB patients (95% CI, 35-40) within 1 year of receiving a kidney transplant on average. DISCUSSION: The proposed framework facilitates efficient collaborations in clinical research networks. Additionally, the framework, by using counterfactual modeling to calculate the event rate, allows us to investigate contributions to racial disparities that may occur at the level of site of care. CONCLUSIONS: Our framework is broadly applicable to other decentralized datasets and disparities research related to differential access to care. Ultimately, our proposed framework will advance equity in human health by identifying and addressing hospital-level racial disparities.

WITHDRAWN: Spinal manipulative therapy for low-back pain.

BACKGROUND: Low-back pain is a costly illness for which spinal manipulative therapy is commonly recommended. Previous systematic reviews and practice guidelines have reached discordant results on the effectiveness of this therapy for low-back pain. OBJECTIVES: To resolve the discrepancies related to the use of spinal manipulative therapy and to update previous estimates of effectiveness, by comparing spinal manipulative therapy with other therapies and then incorporating data from recent high-quality randomized, controlled trials (RCTs) into the analysis. SEARCH METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL were electronically searched from their respective beginning to January 2000, using the Back Group search strategy; references from previous systematic reviews were also screened. SELECTION CRITERIA: Randomized, controlled trials (RCT) that evaluated spinal manipulative therapy for patients with low-back pain, with at least one day of follow-up, and at least one clinically-relevant outcome measure. DATA COLLECTION AND ANALYSIS: Two authors, who served as the authors for all stages of the meta-analysis, independently extracted data from unmasked articles. Comparison treatments were classified into the following seven categories: sham, conventional general practitioner care, analgesics, physical therapy, exercises, back school, or a collection of therapies judged to be ineffective or even harmful (traction, corset, bed rest, home care, topical gel, no treatment, diathermy, and minimal massage). MAIN RESULTS: Thirty-nine RCTs were identified. Meta-regression models were developed for acute or chronic pain and short-term and long-term pain and function. For patients with acute low-back pain, spinal manipulative therapy was superior only to sham therapy (10-mm difference [95% CI, 2 to 17 mm] on a 100-mm visual analogue scale) or therapies judged to be ineffective or even harmful. Spinal manipulative therapy had no statistically or clinically significant advantage over general practitioner care, analgesics, physical therapy, exercises, or back school. Results for patients with chronic low-back pain were similar. Radiation of pain, study quality, profession of manipulator, and use of manipulation alone or in combination with other therapies did not affect these results. AUTHORS' CONCLUSIONS: There is no evidence that spinal manipulative therapy is superior to other standard treatments for patients with acute or chronic low-back pain.

Infusion of statistical science in comparative effectiveness research.

PURPOSE: We present a general introduction to comparative effectiveness research (CER) from a statistician's viewpoint and focus on how statisticians can contribute to the methodology of CER. CONCLUSIONS: The statistical science community needs to determine the priorities for methodological research in CER, in collaboration with our colleagues in the aligned medical fields. CER requires that we apply a new paradigm - a focus on the patient. The emphasis on the patient is driven by patients themselves, the federal government, and private payers, in addition to the fact that there is a rising chronic disease burden that is making patient populations more heterogeneous. The availability of new technology and data sources introduces not only complexity but also opportunity. Statistical scientists should rise to meet these new demands and develop optimal, statistically valid approaches to CER, just as they have in agriculture and clinical trials.

Learning from local to global: An efficient distributed algorithm for modeling time-to-event data.

OBJECTIVE: We developed and evaluated a privacy-preserving One-shot Distributed Algorithm to fit a multicenter Cox proportional hazards model (ODAC) without sharing patient-level information across sites. MATERIALS AND METHODS: Using patient-level data from a single site combined with only aggregated information from other sites, we constructed a surrogate likelihood function, approximating the Cox partial likelihood function obtained using patient-level data from all sites. By maximizing the surrogate likelihood function, each site obtained a local estimate of the model parameter, and the ODAC estimator was constructed as a weighted average of all the local estimates. We evaluated the performance of ODAC with (1) a simulation study and (2) a real-world use case study using 4 datasets from the Observational Health Data Sciences and Informatics network. RESULTS: On the one hand, our simulation study showed that ODAC provided estimates nearly the same as the estimator obtained by analyzing, in a single dataset, the combined patient-level data from all sites (ie, the pooled estimator). The relative bias was <0.1% across all scenarios. The accuracy of ODAC remained high across different sample sizes and event rates. On the other hand, the meta-analysis estimator, which was obtained by the inverse variance weighted average of the site-specific estimates, had substantial bias when the event rate is <5%, with the relative bias reaching 20% when the event rate is 1%. In the Observational Health Data Sciences and Informatics network application, the ODAC estimates have a relative bias <5% for 15 out of 16 log hazard ratios, whereas the meta-analysis estimates had substantially higher bias than ODAC. CONCLUSIONS: ODAC is a privacy-preserving and noniterative method for implementing time-to-event analyses across multiple sites. It provides estimates on par with the pooled estimator and substantially outperforms the meta-analysis estimator when the event is uncommon, making it extremely suitable for studying rare events and diseases in a distributed manner.

Evidence for improving palliative care at the end of life: a systematic review.

BACKGROUND: Many persons and their families are burdened by serious chronic illness in late life. How to best support quality of life is an important consideration for care. PURPOSE: To assess evidence about interventions to improve palliative and end-of-life care. DATA SOURCES: English-language citations (January 1990 to November 2005) from MEDLINE, the Database of Abstracts of Reviews of Effects, the National Consensus Project for Quality Palliative Care bibliography, and November 2005 to January 2007 updates from expert reviews and literature surveillance. STUDY SELECTION: Systematic reviews that addressed "end of life," including terminal illness (for example, advanced cancer) and chronic, eventually fatal illness with ambiguous prognosis (for example, advanced dementia), and intervention studies (randomized and nonrandomized designs) that addressed pain, dyspnea, depression, advance care planning, continuity, and caregiving. DATA EXTRACTION: Single reviewers screened 24,423 titles to find 6381 relevant abstracts and reviewed 1274 articles in detail to identify 33 high-quality systematic reviews and 89 relevant intervention studies. They synthesized the evidence by using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) classification. DATA SYNTHESIS: Strong evidence supports treating cancer pain with opioids, nonsteroidals, radionuclides, and radiotherapy; dyspnea from chronic lung disease with short-term opioids; and cancer-associated depression with psychotherapy, tricyclics, and selective serotonin reuptake inhibitors. Strong evidence supports multi component interventions to improve continuity in heart failure. Moderate evidence supports advance care planning led by skilled facilitators who engage key decision makers and interventions to alleviate caregiver burden. Weak evidence addresses cancer-related dyspnea management, and no evidence addresses noncancer pain, symptomatic dyspnea management in advanced heart failure, or short-acting antidepressants in terminal illness. No direct evidence addresses improving continuity for patients with dementia. Evidence was weak for improving caregiver burdens in cancer and was absent for heart failure. LIMITATIONS: Variable literature indexing for advanced chronic illness and end of life limited the comprehensiveness of searches, and heterogeneity was too great to do meta-analysis. CONCLUSION: Strong to moderate evidence supports interventions to improve important aspects of end-of-life care. Future research should quantify these effects and address the generalizability of insights across the conditions and settings of the last part of life. Many critical issues lack high-quality evidence.

Comparative Clinical Effectiveness of Nonsurgical Treatment Methods in Patients With Lumbar Spinal Stenosis: A Randomized Clinical Trial.

Importance: Lumbar spinal stenosis (LSS) is the most common reason for spine surgery in older US adults. There is an evidence gap about nonsurgical LSS treatment options. Objective: To explore the comparative clinical effectiveness of 3 nonsurgical interventions for patients with LSS. Design, Setting, and Participants: Three-arm randomized clinical trial of 3 years' duration (November 2013 to June 2016). Analysis began in August 2016. All interventions were delivered during 6 weeks with follow-up at 2 months and 6 months at an outpatient research clinic. Patients older than 60 years with LSS were recruited from the general public. Eligibility required anatomical evidence of central canal and/or lateral recess stenosis (magnetic resonance imaging/computed tomography) and clinical symptoms associated with LSS (neurogenic claudication; less symptoms with flexion). Analysis was intention to treat. Interventions: Medical care, group exercise, and manual therapy/individualized exercise. Medical care consisted of medications and/or epidural injections provided by a physiatrist. Group exercise classes were supervised by fitness instructors in senior community centers. Manual therapy/individualized exercise consisted of spinal mobilization, stretches, and strength training provided by chiropractors and physical therapists. Main Outcomes and Measures: Primary outcomes were between-group differences at 2 months in self-reported symptoms and physical function measured by the Swiss Spinal Stenosis questionnaire (score range, 12-55) and a measure of walking capacity using the self-paced walking test (meters walked for 0 to 30 minutes). Results: A total of 259 participants (mean [SD] age, 72.4 [7.8] years; 137 women [52.9%]) were allocated to medical care (88 [34.0%]), group exercise (84 [32.4%]), or manual therapy/individualized exercise (87 [33.6%]). Adjusted between-group analyses at 2 months showed manual therapy/individualized exercise had greater improvement of symptoms and physical function compared with medical care (-2.0; 95% CI, -3.6 to -0.4) or group exercise (-2.4; 95% CI, -4.1 to -0.8). Manual therapy/individualized exercise had a greater proportion of responders (≥30% improvement) in symptoms and physical function (20%) and walking capacity (65.3%) at 2 months compared with medical care (7.6% and 48.7%, respectively) or group exercise (3.0% and 46.2%, respectively). At 6 months, there were no between-group differences in mean outcome scores or responder rates. Conclusions and Relevance: A combination of manual therapy/individualized exercise provides greater short-term improvement in symptoms and physical function and walking capacity than medical care or group exercises, although all 3 interventions were associated with improvements in long-term walking capacity. Trial Registration: ClinicalTrials.gov Identifier: NCT01943435.

A Payer-Guided Approach To Widespread Diffusion Of Behavioral Health Homes In Real-World Settings.

People with serious mental illness experience decreased life expectancy related to co-occurring medical conditions. A nonprofit behavioral health managed care organization implemented an innovative behavioral health home, in partnership with community mental health providers, to build a culture of wellness among all staff members, with a focus on prevention and holistic (that is, behavioral, social, and physical) health. The behavioral health home added one of two distinct care approaches, one patient driven and the other provider driven. The innovative approaches were implemented at eleven community mental health providers: Six delivered patient-driven care, and five delivered provider-driven care. We studied outcomes in the period October 2013-January 2016. Multiple diffusion strategies were utilized to encourage uptake. Our results revealed that both approaches significantly increased patient activation in care (more quickly in provider-supported care), engagement in primary and specialty care, and perceived mental health status. The success of this behavioral health home in improving important outcomes and the use of novel diffusion strategies led to its dissemination to forty-three additional providers across Pennsylvania.

Economic Evaluation of Quality Improvement Interventions Designed to Improve Glycemic Control in Diabetes: A Systematic Review and Weighted Regression Analysis.

OBJECTIVE: Quality improvement (QI) interventions can improve glycemic control, but little is known about their value. We systematically reviewed economic evaluations of QI interventions for glycemic control among adults with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: We used English-language studies from high-income countries that evaluated organizational changes and reported program and utilization-related costs, chosen from PubMed, EconLit, Centre for Reviews and Dissemination, New York Academy of Medicine's Grey Literature Report, and WorldCat (January 2004 to August 2016). We extracted data regarding intervention, study design, change in HbA1c, time horizon, perspective, incremental net cost (studies lasting ≤3 years), incremental cost-effectiveness ratio (ICER) (studies lasting ≥20 years), and study quality. Weighted least-squares regression analysis was used to estimate mean changes in HbA1c and incremental net cost. RESULTS: Of 3,646 records, 46 unique studies were eligible. Across 19 randomized controlled trials (RCTs), HbA1c declined by 0.26% (95% CI 0.17-0.35) or 3 mmol/mol (2 to 4) relative to usual care. In 8 RCTs lasting ≤3 years, incremental net costs were $116 (95% CI -$612 to $843) per patient annually. Long-term ICERs were $100,000-$115,000/quality-adjusted life year (QALY) in 3 RCTs, $50,000-$99,999/QALY in 1 RCT, $0-$49,999/QALY in 4 RCTs, and dominant in 1 RCT. Results were more favorable in non-RCTs. Our limitations include the fact that the studies had diverse designs and involved moderate risk of bias. CONCLUSIONS: Diverse multifaceted QI interventions that lower HbA1c appear to be a fair-to-good value relative to usual care, depending on society's willingness to pay for improvements in health.

A model for a smallpox-vaccination policy.

BACKGROUND: The new reality of biologic terrorism and warfare has ignited a debate about whether to reintroduce smallpox vaccination. METHODS: We developed scenarios of smallpox attacks and built a stochastic model of outcomes under various control policies. We conducted a systematic literature review and estimated model parameters on the basis of European and North American outbreaks since World War II. We assessed the trade-offs between vaccine-related harms and benefits. RESULTS: Nations or terrorists possessing a smallpox weapon could feasibly mount attacks that vary with respect to tactical complexity and target size, and patterns of spread can be expected to vary according to whether index patients are hospitalized early. For acceptable results, vaccination of contacts must be accompanied by effective isolation. Vaccination of contacts plus isolation is expected to result in 7 deaths (from vaccine or smallpox) in a scenario involving the release of variola virus from a laboratory, 19 deaths in a human-vector scenario, 300 deaths in a building-attack scenario, 2735 deaths in a scenario involving a low-impact airport attack, and 54,729 deaths in a scenario involving a high-impact airport attack. Immediate vaccination of the public in an attacked region would provide little additional benefit. Prior vaccination of health care workers, who would be disproportionately affected, would save lives in large local or national attacks but would cause 25 deaths nationally. Prior vaccination of health care workers and the public would save lives in a national attack but would cause 482 deaths nationally. The expected net benefits of vaccination depend on the assessed probability of an attack. Prior vaccination of health care workers would be expected to save lives if the probability of a building attack exceeded 0.22 or if the probability of a high-impact airport attack exceeded 0.002. The probability would have to be much higher to make vaccination of the public life-saving. CONCLUSIONS: The analysis favors prior vaccination of health care workers unless the likelihood of any attack is very low, but it favors vaccination of the public only if the likelihood of a national attack or of multiple attacks is high.

A systematic review of measures of end-of-life care and its outcomes.

OBJECTIVE: To identify psychometrically sound measures of outcomes in end-of-life care and to characterize their use in intervention studies. DATA SOURCES: English language articles from 1990 to November 2005 describing measures with published psychometric data and intervention studies of end-of-life care. STUDY DESIGN: Systematic review of end-of-life care literature. EXTRACTION METHODS: Two reviewers organized identified measures into 10 major domains. Eight reviewers extracted and characterized measures from intervention studies. PRINCIPAL FINDINGS: Of 24,423 citations, we extracted 200 articles that described 261 measures, accepting 99 measures. In addition to 35 measures recommended in a prior systematic review, we identified an additional 64 measures of the end-of-life experience. The most robust measures were in the areas of symptoms, quality of life, and satisfaction; significant gaps existed in continuity of care, advance care planning, spirituality, and caregiver well-being. We also reviewed 84 intervention studies in which 135 patient-centered outcomes were assessed by 97 separate measures. Of these, 80 were used only once and only eight measures were used in more than two studies. CONCLUSIONS: In general, most measures have not undergone rigorous development and testing. Measure development in end-of-life care should focus on areas with identified gaps, and testing should be done to facilitate comparability across the care settings, populations, and clinical conditions. Intervention research should use robust measures that adhere to these standards.

Systematic review: impact of health information technology on quality, efficiency, and costs of medical care.

BACKGROUND: Experts consider health information technology key to improving efficiency and quality of health care. PURPOSE: To systematically review evidence on the effect of health information technology on quality, efficiency, and costs of health care. DATA SOURCES: The authors systematically searched the English-language literature indexed in MEDLINE (1995 to January 2004), the Cochrane Central Register of Controlled Trials, the Cochrane Database of Abstracts of Reviews of Effects, and the Periodical Abstracts Database. We also added studies identified by experts up to April 2005. STUDY SELECTION: Descriptive and comparative studies and systematic reviews of health information technology. DATA EXTRACTION: Two reviewers independently extracted information on system capabilities, design, effects on quality, system acquisition, implementation context, and costs. DATA SYNTHESIS: 257 studies met the inclusion criteria. Most studies addressed decision support systems or electronic health records. Approximately 25% of the studies were from 4 academic institutions that implemented internally developed systems; only 9 studies evaluated multifunctional, commercially developed systems. Three major benefits on quality were demonstrated: increased adherence to guideline-based care, enhanced surveillance and monitoring, and decreased medication errors. The primary domain of improvement was preventive health. The major efficiency benefit shown was decreased utilization of care. Data on another efficiency measure, time utilization, were mixed. Empirical cost data were limited. LIMITATIONS: Available quantitative research was limited and was done by a small number of institutions. Systems were heterogeneous and sometimes incompletely described. Available financial and contextual data were limited. CONCLUSIONS: Four benchmark institutions have demonstrated the efficacy of health information technologies in improving quality and efficiency. Whether and how other institutions can achieve similar benefits, and at what costs, are unclear.

Caregiver Integration During Discharge Planning for Older Adults to Reduce Resource Use: A Metaanalysis.

OBJECTIVES: To determine the effect of integrating informal caregivers into discharge planning on postdischarge cost and resource use in older adults. DESIGN: A systematic review and metaanalysis of randomized controlled trials that examine the effect of discharge planning with caregiver integration begun before discharge on healthcare cost and resource use outcomes. MEDLINE, EMBASE, and the Cochrane Library databases were searched for all English-language articles published between 1990 and April 2016. SETTING: Hospital or skilled nursing facility. PARTICIPANTS: Older adults with informal caregivers discharged to a community setting. MEASUREMENTS: Readmission rates, length of and time to post-discharge rehospitalizations, costs of postdischarge care. RESULTS: Of 10,715 abstracts identified, 15 studies met the inclusion criteria. Eleven studies provided sufficient detail to calculate readmission rates for treatment and control participants. Discharge planning interventions with caregiver integration were associated with a 25% fewer readmissions at 90 days (relative risk (RR) = 0.75, 95% confidence interval (CI) = 0.62-0.91) and 24% fewer readmissions at 180 days (RR = 0.76, 95% CI = 0.64-0.90). The majority of studies reported statistically significant shorter time to readmission, shorter rehospitalization, and lower costs of postdischarge care among discharge planning interventions with caregiver integration. CONCLUSION: For older adults discharged to a community setting, the integration of caregivers into the discharge planning process reduces the risk of hospital readmission.

AHRQ series on complex intervention systematic reviews-paper 5: advanced analytic methods.

BACKGROUND AND OBJECTIVE: Advanced analytic methods for synthesizing evidence about complex interventions continue to be developed. In this paper, we emphasize that the specific research question posed in the review should be used as a guide for choosing the appropriate analytic method. METHODS: We present advanced analytic approaches that address four common questions that guide reviews of complex interventions: (1) How effective is the intervention? (2) For whom does the intervention work and in what contexts? (3) What happens when the intervention is implemented? and (4) What decisions are possible given the results of the synthesis? CONCLUSION: The analytic approaches presented in this paper are particularly useful when each primary study differs in components, mechanisms of action, context, implementation, timing, and many other domains.

AHRQ series on complex intervention systematic reviews-paper 4: selecting analytic approaches.

BACKGROUND: Systematic reviews of complex interventions can vary widely in purpose, data availability and heterogeneity, and stakeholder expectations. RATIONALE: This article addresses the uncertainty that systematic reviewers face in selecting methods for reviews of complex interventions. Specifically, it lays out parameters for systematic reviewers to consider when selecting analytic approaches that best answer the questions at hand and suggests analytic techniques that may be appropriate in different circumstances. DISCUSSION: Systematic reviews of complex interventions comprising multiple questions may use multiple analytic approaches. Parameters to consider when choosing analytic methods for complex interventions include nature and timing of the decision (clinical practice guideline, policy, or other); purpose of the review; extent of existing evidence; logistic factors such as the timeline, process, and resources for deciding the scope of the review; and value of information to be obtained from choosing specific systematic review methods. Reviewers may elect to revise their analytic approach based on new or changing considerations during the course of the review but should guard against bias through transparency of reporting.