Emmanuel Coker-Schwimmer

Interventions to Improve Adherence to Self-administered Medications for Chronic Diseases in the United States: A Systematic Review

BACKGROUND Suboptimum medication adherence is common in the United States and leads to serious negative health consequences but may respond to intervention. PURPOSE To assess the comparative effectiveness of patient, provider, systems, and policy interventions that aim to improve medication adherence for chronic health conditions in the United States. DATA SOURCES Eligible peer-reviewed publications from MEDLINE and the Cochrane Library indexed through 4 June 2012 and additional studies from reference lists and technical experts. STUDY SELECTION Randomized, controlled trials of patient, provider, or systems interventions to improve adherence to long-term medications and nonrandomized studies of policy interventions to improve medication adherence. DATA EXTRACTION Two investigators independently selected, extracted data from, and rated the risk of bias of relevant studies. DATA SYNTHESIS The evidence was synthesized separately for each clinical condition; within each condition, the type of intervention was synthesized. Two reviewers graded the strength of evidence by using established criteria. From 4124 eligible abstracts, 62 trials of patient-, provider-, or systems-level interventions evaluated 18 types of interventions; another 4 observational studies and 1 trial of policy interventions evaluated the effect of reduced medication copayments or improved prescription drug coverage. Clinical conditions amenable to multiple approaches to improving adherence include hypertension, heart failure, depression, and asthma. Interventions that improve adherence across multiple clinical conditions include policy interventions to reduce copayments or improve prescription drug coverage, systems interventions to offer case management, and patient-level educational interventions with behavioral support. LIMITATIONS Studies were limited to adults with chronic conditions (excluding HIV, AIDS, severe mental illness, and substance abuse) in the United States. Clinical and methodological heterogeneity hindered quantitative data pooling. CONCLUSION Reduced out-of-pocket expenses, case management, and patient education with behavioral support all improved medication adherence for more than 1 condition. Evidence is limited on whether these approaches are broadly applicable or affect longterm medication adherence and health outcomes. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Transitional care interventions to prevent readmissions for persons with heart failure: a systematic review and meta-analysis.

Heart failure (HF) is a leading cause of hospitalization and health care costs in the United States (1). Up to 25% of patients hospitalized with HF are readmitted within 30 days (25). Readmissions after an index hospitalization for HF are related to various conditions. An analysis of Medicare claims data from 2007 to 2009 found that 35% of readmissions within 30 days were for HF; the remainder were for diverse indications (for example, renal disorders, pneumonia, and arrhythmias) (2). To reduce rehospitalization of Medicare patients, in October 2012, the Centers for Medicare & Medicaid Services began decreasing reimbursements to hospitals with excessive risk-standardized readmission (6). This policy incentivizes hospitals to develop programs to reduce readmission rates for persons with HF. Despite advances in the quality of acute and chronic HF disease management, knowledge gaps remain about effective interventions to support the transition of care for persons with HF. Interventions designed to prevent readmissions among populations transitioning from one care setting to another are often called transitional care interventions (7, 8). They aim to avoid poor outcomes caused by uncoordinated care, such as preventable readmissions (9). Although no clear set of components defines transitional care interventions, they focus on patient or caregiver education, medication reconciliation, and coordination among health professionals involved in the transition. We conducted a systematic review of transitional care interventions for persons with HF for the Effective Health Care Program of the Agency for Healthcare Research and Quality (AHRQ) (10). We included a broad range of intervention types (Table 1) applicable to adults transitioning from hospital to home that aimed to prevent readmissions. Although 30-day readmissions are the focus of quality measures, we also included readmissions measured over 3 to 6 months because these are common, costly, and potentially preventable (5). The full technical report addressed 5 questions (Appendix Table 1). For this article, we focused on readmission and mortality outcomes. Table 1. Transitional Care Interventions Appendix Table 1. Scope and Key Questions* Methods We developed and followed a standard protocol. A technical report that details methods and includes complete search strategies and additional evidence tables is available at www.effectivehealthcare.ahrq.gov/reports/final.cfm. Data Sources and Searches We searched MEDLINE, the Cochrane Library, and CINAHL for English-language and human-only studies published from 1 July 2007 to late October 2013, and we used a previous technology assessment on a similar topic to identify randomized, controlled trials (RCTs) published before 1 July 2007 (11). An experienced Evidence-based Practice Center librarian conducted the searches, and a second librarian reviewed them. We manually searched reference lists of pertinent reviews, included trials, and background articles on this topic to look for relevant citations our searches might have missed. We searched for relevant unpublished studies using ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. Study Selection We developed inclusion and exclusion criteria with respect to populations, interventions, comparators, outcomes, timing, settings, and study designs (Appendix Table 2). We included studies of adults recruited during or within 1 week of an index hospitalization for HF that compared a transitional care intervention with another eligible intervention or with usual care (that is, routine or standard care, as defined by the primary studies). We required that interventions include 1 or more of the following components: education of patient or caregiver delivered before or after discharge, planned or scheduled outpatient clinic visits (primary care or multidisciplinary heart failure [MDS-HF] clinic), home visits, telemonitoring, structured telephone support (STS), transition coach or case management, or interventions to increase provider continuity. We required studies to report a readmission rate, mortality rate, or the composite outcome (all-cause readmission or mortality). In the full report, we also assessed emergency department visits, acute care visits, hospital days of subsequent readmissions, quality of life, functional status, and caregiver or self-care burden (10). Appendix Table 2. Inclusion and Exclusion Criteria for Studies of Transitional Care Interventions for Patients Hospitalized for HF Data Extraction and Risk-of-Bias Assessment One team member extracted relevant data from each article, and a second team member reviewed all data extractions for completeness and accuracy. We used predefined criteria based on the AHRQ Methods Guide for Comparative Effectiveness Reviews (12) to rate studies as having low, medium, high, or unclear risk of bias. Two reviewers independently assessed risk of bias for each study, and disagreements were resolved by consensus. Data Synthesis and Analysis We categorized intervention types primarily on the basis of the method and environment of delivery, as defined in Table 1. One investigator categorized the intervention, and a second team member reviewed the categorization. Disagreements were resolved by consensus. Given heterogeneity of the clinic-based interventions, we subcategorized these by clinic setting: MDS-HF, nurse-led HF, or primary care. We used DerSimonianLaird random-effects models (13) for meta-analyses of outcomes reported by multiple studies that were sufficiently similar to justify combining results. We ran meta-analyses of trials that reported the number of deaths or number of persons readmitted in each group (and not total readmissions per group). When only the total number of readmissions per group was available, we contacted authors for additional data. When we could not obtain the number of persons readmitted, we did not include the results in meta-analyses; instead, we included the results in qualitative syntheses and considered them when grading the strength of evidence (SOE). For readmission and mortality rates, we calculated risk ratios (RRs). We stratified analyses for each intervention category by outcome timing and separated rates reported at 30 days from those after 30 days (that is, rates reported over 3 to 6 months were combined). We did not include studies rated as high or unclear risk of bias in our main analyses but included them in sensitivity analyses, which are available in the technical report (10); we describe them here only when they differed from primary analyses. We assessed statistical heterogeneity using the chi-square and I 2 statistics (14, 15). We calculated the number needed to treat (NNT) for readmission and mortality outcomes when we had statistically significant findings based on our primary analyses of trials rated as low or medium risk of bias, and we found at least low SOE for benefit. The NNT was derived from the RR and median usual care event rate using methods described in the Cochrane Handbook (16). We conducted meta-analyses using Stata, version 11.1 (StataCorp, College Station, Texas). We did meta-analysis stratified by intensity in each intervention category when variation existed. The results of these subgroup analyses are available in the main report (10); we describe them here only when we found a difference in efficacy based on level of intensity. Given the heterogeneity of included interventions, we could not develop a single measure of intensity that could be applied to all intervention categories. For most interventions, we defined intensity as the duration, frequency, or periodicity of patient contact and categorized each intervention as low-, medium-, or high-intensity. We reserved the low-intensity category for interventions that included 1 episode of patient contact or few resources. We graded SOE as high, moderate, low, or insufficient based on guidance established for the Evidence-based Practice Center program (17). The approach incorporates 4 key domains: risk of bias, consistency, directness, and precision. When only 1 study reported an outcome of interest, we usually graded the SOE as insufficient (primarily due to unknown consistency and imprecision); however, when similar interventions had consistent results at other time points, we graded the SOE as low. Two reviewers assessed each domain for each outcome, and differences were resolved by consensus. Role of the Funding Source The AHRQ funded this review, and AHRQ staff participated in the development of the scope of the work and reviewed draft manuscripts. Approval from AHRQ was required before the manuscript could be submitted for publication, but the authors are solely responsible for the content and the decision to submit it for publication. Results Searches of all sources identified 2419 potentially relevant citations. We included 47 RCTs (Appendix Figure 1). Trial characteristics are shown in Appendix Table 3. Most trials compared a transitional care intervention with usual care; 2 directly compared more than 1 intervention (both rated high risk of bias) (18, 19). In general, trials included adults with a mean age of 70 years who were hospitalized with a primary diagnosis of HF. Most reported HF disease severity based on the New York Heart Association classification and included persons with moderate to severe HF. Twenty-nine trials reported mean ejection fraction. Of these, 27 enrolled persons with a mean ejection fraction less than 0.50 and 7 trials specified a reduced ejection fraction as an inclusion criterion. Across most trials, the majority of patients were prescribed an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. The percentages of patients who were prescribed -blockers at discharge varied widely across trials. Trials were conducted in a range of settings: academic medical centers, Department of Veterans Affairs hospitals,

Medication Therapy Management Interventions in Outpatient Settings A Systematic Review and Meta-analysis

IMPORTANCE Medication therapy management (MTM) services (also called clinical pharmacy services) aim to reduce medication-related problems and their downstream outcomes. OBJECTIVE To assess the effect of MTM interventions among outpatients with chronic illnesses. DATA SOURCES MEDLINE, Cochrane Library, and International Pharmaceutical Abstracts through January 9, 2014. STUDY SELECTION Two reviewers selected studies with comparators and eligible outcomes of ambulatory adults. DATA EXTRACTION AND SYNTHESIS Dual review of titles, abstracts, full-text, extractions, risk of bias, and strength of evidence grading. We conducted meta-analyses using random-effects models. MAIN OUTCOMES AND MEASURES Medication-related problems, morbidity, mortality, quality of life, health care use, costs, and harms. RESULTS Forty-four studies met the inclusion criteria. The evidence was insufficient to determine the effect of MTM interventions on most evaluated outcomes (eg, drug therapy problems, adverse drug events, disease-specific morbidity, disease-specific or all-cause mortality, and harms). The interventions improved a few measures of medication-related problems and health care use and costs (low strength of evidence) when compared with usual care. Specifically, MTM interventions improved medication appropriateness (4.9 vs 0.9 points on the medication appropriateness index, P < .001), adherence (approximately 4.6%), and percentage of patients achieving a threshold adherence level (odds ratios [ORs] ranged from 0.99 to 5.98) and reduced medication dosing (mean difference, -2.2 doses; 95% CI, -3.738 to -0.662). Medication therapy management interventions reduced health plan expenditures on medication costs, although the studies reported wide CIs. For patients with diabetes mellitus or heart failure, MTM interventions lowered the odds of hospitalization (diabetes: OR, 0.91 to 0.93 based on type of insurance; adjusted hazard rate for heart failure: 0.55; 95% CI, 0.39 to 0.77) and hospitalization costs (mean differences ranged from -

Interventions to prevent post-traumatic stress disorder: a systematic review.

363.45 to -

Review and special articleInterventions to Prevent Post-Traumatic Stress Disorder: A Systematic Review

398.98). The interventions conferred no benefit for patient satisfaction and most measures of health-related quality of life (low strength). CONCLUSIONS AND RELEVANCE We graded the evidence as insufficient for most outcomes because of inconsistency and imprecision that stem in part from underlying heterogeneity in populations and interventions. Medication therapy management interventions may reduce the frequency of some medication-related problems, including nonadherence, and lower some health care use and costs, but the evidence is insufficient with respect to improvement in health outcomes.

Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis

CONTEXT Traumatic events are prevalent worldwide; trauma victims seek help in numerous clinical and emergency settings. Using effective interventions to prevent post-traumatic stress disorder (PTSD) is increasingly important. This review assessed the efficacy, comparative effectiveness, and harms of psychological, pharmacologic, and emerging interventions to prevent PTSD. EVIDENCE ACQUISITION The following sources were searched for research on interventions to be included in the review: MEDLINE; Cochrane Library; CINAHL; EMBASE; PILOTS (Published International Literature on Traumatic Stress); International Pharmaceutical Abstracts; PsycINFO; Web of Science; reference lists of published literature; and unpublished literature (January 1, 1980 to July 30, 2012). Two reviewers independently selected studies, extracted data or checked accuracy, assessed study risk of bias, and graded strength of evidence. All data synthesis occurred between January and September 2012. EVIDENCE SYNTHESIS Nineteen studies covered various populations, traumas, and interventions. In meta-analyses of three trials (from the same team) for people with acute stress disorder, brief trauma-focused cognitive behavioral therapy was more effective than supportive counseling in reducing the severity of PTSD symptoms (moderate-strength); these two interventions had similar results for incidence of PTSD (low-strength); depression severity (low-strength); and anxiety severity (moderate-strength). PTSD symptom severity after injury decreased more with collaborative care than usual care (single study; low-strength). Debriefing did not reduce incidence or severity of PTSD or psychological symptoms in civilian traumas (low-strength). Evidence about relevant outcomes was unavailable for many interventions or was insufficient owing to methodologic shortcomings. CONCLUSIONS Evidence is very limited regarding best practices to treat trauma-exposed individuals. Brief cognitive behavioral therapy may reduce PTSD symptom severity in people with acute stress disorder; collaborative care may help decrease symptom severity post-injury.

Folic acid supplementation for the prevention of neural tube defects: An updated evidence report and systematic review for the US Preventive Services Task Force

CONTEXT Traumatic events are prevalent worldwide; trauma victims seek help in numerous clinical and emergency settings. Using effective interventions to prevent post-traumatic stress disorder (PTSD) is increasingly important. This review assessed the efficacy, comparative effectiveness, and harms of psychological, pharmacologic, and emerging interventions to prevent PTSD. EVIDENCE ACQUISITION The following sources were searched for research on interventions to be included in the review: MEDLINE; Cochrane Library; CINAHL; EMBASE; PILOTS (Published International Literature on Traumatic Stress); International Pharmaceutical Abstracts; PsycINFO; Web of Science; reference lists of published literature; and unpublished literature (January 1, 1980 to July 30, 2012). Two reviewers independently selected studies, extracted data or checked accuracy, assessed study risk of bias, and graded strength of evidence. All data synthesis occurred between January and September 2012. EVIDENCE SYNTHESIS Nineteen studies covered various populations, traumas, and interventions. In meta-analyses of three trials (from the same team) for people with acute stress disorder, brief trauma-focused cognitive behavioral therapy was more effective than supportive counseling in reducing the severity of PTSD symptoms (moderate-strength); these two interventions had similar results for incidence of PTSD (low-strength); depression severity (low-strength); and anxiety severity (moderate-strength). PTSD symptom severity after injury decreased more with collaborative care than usual care (single study; low-strength). Debriefing did not reduce incidence or severity of PTSD or psychological symptoms in civilian traumas (low-strength). Evidence about relevant outcomes was unavailable for many interventions or was insufficient owing to methodologic shortcomings. CONCLUSIONS Evidence is very limited regarding best practices to treat trauma-exposed individuals. Brief cognitive behavioral therapy may reduce PTSD symptom severity in people with acute stress disorder; collaborative care may help decrease symptom severity post-injury.

A comparative effectiveness review of parenting and trauma-focused interventions for children exposed to maltreatment.

Study question What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults? Methods This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT. Summary answer and limitations Meta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, −0.38, −2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of the findings. What this study adds Second generation antidepressants and CBT have evidence bases of benefits and harms in major depressive disorder. Available evidence suggests no difference in treatment effects of second generation antidepressants and CBT, either alone or in combination, although small numbers may preclude detection of small but clinically meaningful differences. Funding, competing interests, data sharing This project was funded under contract from the Agency for Healthcare Research and Quality by the RTI-UNC Evidence-based Practice Center. Detailed methods and additional information are available in the full report, available at http://effectivehealthcare.ahrq.gov/.

Comparative benefits and harms of complementary and alternative medicine therapies for initial treatment of major depressive disorder: Systematic review and meta-analysis

Importance Neural tube defects are among the most common congenital anomalies in the United States. Periconceptional folic acid supplementation is a primary care–relevant preventive intervention. Objective To review the evidence on folic acid supplementation for preventing neural tube defects to inform the US Preventive Services Task Force for an updated Recommendation Statement. Data Sources MEDLINE, Cochrane Library, EMBASE, and trial registries through January 28, 2016, with ongoing surveillance through November 11, 2016; references; experts. Study Selection English-language studies of folic acid supplementation in women. Excluded were poor-quality studies; studies of prepubertal girls, men, women without the potential for childbearing, and neural tube defect recurrence; and studies conducted in developing countries. Data Extraction and Synthesis Two investigators independently reviewed abstracts, full-text articles, and risk of bias of included studies. One investigator extracted data and a second checked accuracy. Because of heterogeneity, data were not pooled. Main Outcomes and Measures Neural tube defects, harms of treatment (twinning, respiratory outcomes). Results A total of 24 studies (N > 58 860) were included. In 1 randomized clinical trial from Hungary initiated in 1984, incidence of neural tube defects for folic acid supplementation compared with trace element supplementation was 0% vs 0.25% (Peto odds ratio [OR], 0.13 [95% CI, 0.03-0.65]; n = 4862). Odds ratios from cohort studies recruiting participants between 1984 and 1996 demonstrated beneficial associations and ranged from 0.11 to 0.27 (n = 19 982). Three of 4 case-control studies with data from 1976 through 1998 reported ORs ranging from 0.6 to 0.7 (n > 7121). Evidence of benefit led to food fortification in the United States beginning in 1998, after which no new prospective studies have been conducted. More recent case-control studies drawing from data collected after 1998 have not demonstrated a protective association consistently with folic acid supplementation, with ORs ranging from 0.93 to 1.4 and confidence intervals spanning the null (n > 13 990). Regarding harms, 1 trial (OR, 1.40 [95% CI, 0.89-2.21]; n = 4767) and 1 cohort study (OR, 1.04 [95% CI, 0.91-1.18]; n = 2620) found no statistically significant increased risk of twinning. Three systematic reviews found no consistent evidence of increased risk of asthma (OR, 1.06 [95% CI, 0.99-1.14]; n = 14 438), wheezing, or allergy. Conclusions and Relevance In studies conducted before the initiation of food fortification in the United States in 1998, folic acid supplementation provided protection against neural tube defects. Newer postfortification studies have not demonstrated a protective association but have the potential for misclassification and recall bias, which can attenuate the measured association of folic acid supplementation with neural tube defects.

Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review

Objective: To systematically review the comparative effectiveness evidence for interventions to ameliorate the negative sequelae of maltreatment exposure in children ages birth to 14 years. Methods: We assessed the research on pharmacological and psychosocial interventions (parent-mediated approaches or trauma-focused treatments) reporting mental and behavioral health, caregiver-child relationship, and developmental and/or school functioning outcomes. We conducted focused searches of MEDLINE (through PubMed), Social Sciences Citation Index, PsycINFO, and the Cochrane Library (1990–2012). Reviewer pairs independently evaluated the studies for eligibility using predetermined inclusion/exclusion criteria, evaluated studies for risk of bias, extracted data, and graded the strength of evidence (SOE) for each comparison and each outcome based on predetermined criteria. Results: Based on our review of 6282 unduplicated citations, we found 17 trials eligible for inclusion. Although several interventions show promising comparative benefit for child well-being outcomes, the SOE for all but one of these interventions was low. The results highlight numerous substantive and methodological gaps to address in the future research. Conclusions: It is too early to make strong treatment recommendations, as comparative research remains relatively nascent in the child maltreatment arena. These gaps reflect, in large part, the Herculean demands on researchers involved in conducting high-quality clinical studies with this highly vulnerable population. The National Child Traumatic Stress Network and the Developmental-Behavioral Pediatrics Research Network (DBPNet) are two potentially powerful platforms to conduct large rigorous trials needed to move the field forward. More broadly, a paradigm shift among researchers and funders alike is needed to galvanize the commitment and resources necessary for conducting collaborative clinical trials with this highly vulnerable population.