Using Participatory Implementation Science to Advance Health Equity.

Participatory approaches to implementation science (IS) offer an inclusive, collaborative, and iterative perspective on implementing and sustaining evidence-based interventions (EBIs) to advance health equity. This review provides guidance on the principles and practice of participatory IS, which enables academic researchers, community members, implementers, and other actors to collaboratively integrate practice-, community-, and research-based evidence into public health and health care services. With a foundational focus on supporting academics in coproducing knowledge and action, participatory IS seeks to improve health, reduce inequity, and create transformational change. The three main sections of this review provide (a) a rationale for participatory approaches to research in implementation science, (b) a framework for integrating participatory approaches in research utilizing IS theory and methods, and (c) critical considerations for optimizing the practice and impact of participatory IS. Ultimately, participatory approaches can move IS activities beyond efforts to make EBIs work within harmful systems toward transformative solutions that reshape these systems to center equity.

Medication Safety in Clinical Trials: Role of the Pharmacist in Optimizing Practice, Collaboration, and Education to Reduce Errors.

Standardized safety practices for investigational drugs in clinical research protocols are limited and the vast majority of research pharmacists have concerns regarding its safety. Identified areas for medication safety risks include protocol complexity, medication ordering, and the processes for packaging, storage, and dispensing investigational medications. Inclusion of a pharmacist creates multiple mechanisms to promote safety and improve the quality of clinical research. This is accomplished through collaborating in the development of a research protocol, reviewing as a member of an advisory committee, developing mechanisms that contribute to safety, and assuring compliance with local and national regulations and standards. Ultimately, the profession of pharmacy has foundational responsibility for assuring the safe and effective use of medications, including investigational drugs in clinical research. It is through multidisciplinary collaboration that a research study will attain the highest standards for safety and maximize the quality and effectiveness of the data obtained in the clinical trial.

Impact of Inpatient Automatic Therapeutic Substitutions on Postdischarge Medication Prescribing.

Background: Automatic therapeutic substitution (ATS) is the act of therapeutic interchange, in which patients are transitioned from a nonformulary preadmission medication to an equivalent formulary medication upon admission. ATS protocols are able to provide several benefits; however, if medications are unreconciled at the time of discharge, then use may lead to duplication or omission resulting in adverse outcomes. The objective was to assess the impact of preidentified ATS protocol use during admission on duplication and omission postdischarge. Methods: This study included adults who received a preidentified ATS upon admission. The primary outcome was the incidence of duplication or omission at the time of discharge. The secondary outcome was the incidence of duplication or omission at the time of discharge in moderate-to-high readmission risk patients with completed transitions of care (TOC) services compared with incomplete TOC services. Results: A total of 689 encounters were assessed for appropriate reconciliation, duplication, or omission at time of discharge. The incidence of duplication or omission at the time of discharge was 9% (n = 62). Of the 689 encounters, 287 were assessed for the secondary outcome. The rate of duplication or omission at the time of discharge was 10% (n = 19) in the complete TOC services group and 8% (n = 8) in the incomplete TOC services group (P = .6763). Conclusion: This study identified a high rate of appropriate reconciliation of ATS protocols at the time of discharge, which illustrates ATS protocols are a safe medication use management strategy if implemented as intended.

Financial Effect of a Drug Distribution Model Change on a Health System.

Background: Drug manufacturers change distribution models based on patient safety and product integrity needs. These model changes can limit health-system access to medications, and the financial impact on health systems can be significant. Objective: The primary aim of this study was to determine the health-system financial impact of a manufacturer's change from open to limited distribution for bevacizumab (Avastin), rituximab (Rituxan), and trastuzumab (Herceptin). The secondary aim was to identify opportunities to shift administration to outpatient settings to support formulary change. Methods: To assess the financial impact on the health system, the cost minus discount was applied to total drug expenditure during a 1-year period after the distribution model change. The opportunity analysis was conducted for three institutions within the health system through chart review of each inpatient administration. Opportunity cost was the sum of the inpatient administration cost and outpatient administration margin. Results: The total drug expenditure for the study period was $26 427 263. By applying the cost minus discount, the financial effect of the distribution model change was $1 393 606. A total of 387 administrations were determined to be opportunities to be shifted to the outpatient setting. During the study period, the total opportunity cost was $1 766 049. Conclusion: Drug expenditure increased for the health system due to the drug distribution model change and loss of cost minus discount. The opportunity cost of shifting inpatient administrations could offset the increase in expenditure. It is recommended to restrict bevacizumab, rituximab, and trastuzumab through Pharmacy & Therapeutics Committees to outpatient use where clinically appropriate.

Do no harm: the impact of implementing cancer prevention strategies on other preventive health measures.

BACKGROUND: Translational efforts to increase uptake of evidence-based practices typically look at those outcomes in isolation of their impact on other aspects of care delivery. If we are in fact to "do no harm", we must consider the possible negative impact of improving use of one practice on other quality measures. Alternatively, a focus on one practice could lead to spread of effective strategies to other practices, which would be highly beneficial. We studied the impact of a colorectal cancer (CRC) screening initiative on delivery of other preventive care measures. METHODS: We used an interrupted time series design with implementation year as the interruption point. The initiative was conducted between 2015 and 2020, with three staggered cohorts. Main outcomes were quality measures for colorectal cancer screening, cervical cancer screening, hypertension management, diabetes management, weight screening and follow-up, tobacco use screening and cessation treatment, and depression screening and follow-up. RESULTS: The initiative was associated with an increase in CRC screening (OR = 1.67, p ≤ 0.01; average marginal effect = 12.2% points), and did not reduce performance on other quality measures in the year of CRC program implementation or a change in their respective secular trends. CONCLUSIONS: The initiative led to a clinically meaningful increase in CRC screening and was not associated with reductions in delivery of six other preventive services. Quality improvement (QI) initiatives typically approach implementation with an eye towards reducing unintended impact and leveraging existing staff and resources. Implementation research studies may benefit from considering how QI initiatives factor in the local context in implementation efforts.

Leveraging an implementation science partnership network to understand how Federally Qualified Health Centers operationalize and address health equity.

Health equity-focused implementation research requires using definitions and approaches that are relevant and meaningful to implementation partners. We examined how health equity was operationalized and addressed at Federally Qualified Health Centers (FQHCs). We conducted semi-structured interviews with leadership (n = 19) and staff (n = 12) at 10 FQHCs in an implementation science partnership network for cancer control equity to understand how they operationalized and addressed health equity. We performed rapid qualitative analysis and shared findings with a larger group of 13 community health centers (including the 10 FQHCs) at an Implementation Learning Community (ILC) to identify action areas for research and practice, followed by a second phase of synthesizing qualitative codes into themes and mapping themes onto a framework for advancing health equity in healthcare organizations. Participants defined health equity as central to the mission of FQHCs, and identified barriers (e.g. financing models) and facilitators (e.g. interpreter services) to advancing health equity at FQHCs. These findings resonated with ILC participants who emphasized the challenge of addressing root cause social determinants of inequities using limited available resources in FQHCs and the importance of developing meaningful collaboration with communities for data collection, data interpretation, data use, and data ownership. Themes captured recommendations to advance health equity in daily work at FQHCs, including investments in staffing, training, and resources. Mapping qualitative themes from health equity-centered interviews with FQHC partners onto a framework for advancing health equity in healthcare organizations can provide clear, context-specific direction for actions aimed at improving health and healthcare equity.

Health equity-focused implementation research requires using definitions and approaches that are relevant and meaningful to implementation partners. Toward this goal, our research team asked leadership and staff at Federally Qualified Health Centers (FQHCs) to share how they defined and addressed health equity at their practice settings. FQHC participants defined health equity as the essential mission of FQHCs as safety net organizations delivering care to medically underserved populations. In addition, key informants identified barriers (e.g. financing models) and facilitators (e.g. interpreter services) to advancing health equity at FQHCs. We presented these findings to a larger group of FQHC stakeholders who recommended that future implementation research and practice consider how FQHCs are challenged to address the root causes of healthcare inequities with limited resources. They also highlighted the importance of meaningful collaboration among researchers, FQHCs, and communities for data collection, data interpretation, data use, and data ownership to advance health equity. Conducting research to understand the perspectives and experiences of FQHC partners can provide clear, context-specific direction for actions to improve health equity and can inform future approaches to health equity-focused implementation research that ismeaningful to FQHC partners and the communities they serve.

A Systematic Review Evaluating Disparities in State-Run Quitline Utilization and Effectiveness in the U.S.

Context: Cigarette smoking is a public health problem in the U.S. and is marked by pervasive sociodemographic disparities. State-run quitlines may offer greater access to cessation services that could in turn help to reduce smoking disparities. The aim of this review was to synthesize the body of literature regarding sociodemographic disparities in the utilization and effectiveness of state-run quitlines. Evidence acquisition: The PRISMA guidelines were followed in conducting this review. Included articles were published between January 1, 1992 and May 28, 2019 and sourced from PubMed and Web of Science. Studies that evaluated state-run quitline utilization or effectiveness (cessation) by sex, race/ethnicity, sexual or gender identity, or SES (income, education, insurance) were included. Evidence synthesis: Our search yielded 2,091 unique articles, 17 of which met the criteria for inclusion. This review found that quitline utilization was higher among Black and Asian/Pacific Islander individuals than among White individuals and among people with lower income and lower education than among people with higher income and higher education. Quitline use was associated with less smoking cessation among females than among males, among American Indian/Alaskan Native individuals than among individuals from all other races and ethnicities, and among individuals of lower than among those of higher income and education. Conclusions: This review found that although communities disproportionately affected by smoking utilize quitlines more commonly than their White and more affluent peers, disparities in cessation persist for American Indian/Alaskan Native and individuals from lower SES groups who use quitlines.

Similar skills, different frames: a thematic analysis exploring conceptualizations held by community-based organization practitioners and academics regarding skills to use evidence-based interventions to address cancer inequities.

BACKGROUND: Community-based organizations (CBOs) are critical partners in delivering evidence-based interventions (EBIs) to address cancer inequities. However, CBO practitioners do not typically have access to opportunities to build the necessary capacity (skills, knowledge, motivation, and resources) for using EBIs. Although capacity-building interventions can offer a solution, inconsistent definitions and measurements of capacity limit the ability to develop and evaluate such efforts. We explored how and why conceptualizations of core skills for EBI use differ between practitioners and academics addressing cancer and other health inequities. We anchored the inquiry with a commonly used set of target skills for EBI capacity-building efforts. METHODS: The study was conducted by an interdisciplinary team of academic researchers and CBO practitioners. We gathered data through semi-structured, hour-long interviews with practitioners and academics working to address cancer and other health inequities (n = 19). After hearing a brief vignette about a CBO addressing cervical cancer inequities, participants considered a widely accepted list of skills for EBI use that included assessing needs, engaging stakeholders, and selecting, adapting, implementing, evaluating, and sustaining the EBI. We used a team-based, reflexive thematic analysis approach grounded in critical and constructivist perspectives. RESULTS: Overall, the original list resonated with practitioners and academics and they added new skills to the list (cultural humility and systems change). Practitioners' responses described skills from the reference point of addressing broader community needs and context and achieving change over the long term, emphasizing aspects of health promotion in their descriptions. Academics offered a mix of perspectives, with some focused on addressing community needs (and related flexibility regarding EBIs) but more emphasized skills needed to deliver a specific EBI to achieve a focused set of health and equity outcomes. CONCLUSIONS: There is a significant opportunity to leverage complementary expertise and perspectives held by practitioners and academics addressing cancer inequities. However, the different frames utilized suggest proactive efforts will be required to find alignment across groups, particularly in valuing diverse contributions and identifying relevant outcomes of interest for each group. Such alignment is critical to designing effective capacity-building interventions and supporting the routine utilization of EBIs to address cancer inequities.

Priority skills for equity-focused, evidence-based cancer control in community-based organizations: A group concept mapping analysis with academics and practitioners.

Introduction: Community-based organizations (CBOs) are important equity-promoting delivery channels for evidence-based interventions (EBIs). However, CBO practitioners often cannot access needed support to build EBI skills. Additionally, the capacity-building literature is hindered by inconsistent definitions, limited use of validated measures, and an emphasis on the perspectives of EBI developers versus implementers. To address these gaps, we explored commonalities and differences between CBO practitioners and academics in conceptualizing and prioritizing core EBI skills. Methods: We utilized Group Concept Mapping, a mixed-methods approach connecting qualitative data (e.g., regarding the range of critical EBI skills) and quantitative data (e.g., sorting and ranking data regarding unique skills) to create conceptual maps integrating perspectives from diverse participants. A total of 34 practitioners and 30 academics working with cancer inequities participated in the study. Results: Participants nominated 581 core skills for EBI use, and our team (including practitioners and academics) identified 98 unique skills from this list. Participants sorted them into conceptual groups, yielding five clusters: (1) using data and evaluation, (2) selecting and adapting EBIs, (3) connecting with community members, (4) building diverse and equitable partnerships, and (5) managing EBI implementation. The ordering of importance and presence of skill clusters were similar across groups. Overall, importance was rated higher than presence, suggesting capacity gaps. Conclusions: There are helpful commonalities between practitioners' and academics' views of core EBI skills in CBOs and apparent capacity gaps. However, underlying patterns suggest that differences between the groups' perceptions warrant further exploration.

Identifying Core Domains to Assess the "Quality of Death": A Scoping Review.

CONTEXT: There is growing recognition of the value to patients, families, society, and health systems in providing healthcare, including end-of-life care, that is consistent with both patient preferences and clinical guidelines. OBJECTIVES: Identify the core domains and subdomains that can be used to evaluate the performance of end-of-life care within and across health systems. METHODS: PubMed/MEDLINE (NCBI), PsycINFO (ProQuest), and CINAHL (EBSCO) databases were searched for peer-reviewed journal articles published prior to February 22, 2020. The SPIDER tool was used to determine search terms. A priori criteria were followed with independent review to identify relevant articles. RESULTS: A total of 309 eligible articles were identified out of 2728 discrete results. The articles represent perspectives from the broader health system (11), patients (70), family and informal caregivers (65), healthcare professionals (43), multiple viewpoints (110), and others (10). The most common condition of focus was cancer (103) and the majority (245) of the studies concentrated on high-income country contexts. The review identified five domains and 11 subdomains focused on structural factors relevant to end-of-life care at the broader health system level, and two domains and 22 subdomains focused on experiential aspects of end-of-life care from the patient and family perspectives. The structural health system domains were: 1) stewardship and governance, 2) resource generation, 3) financing and financial protection, 4) service provision, and 5) access to care. The experiential domains were: 1) quality of care, and 2) quality of communication. CONCLUSION: The review affirms the need for a people-centered approach to managing the delicate process and period of accepting and preparing for the end of life. The identified structural and experiential factors pertinent to the "quality of death" will prove invaluable for future efforts aimed to quantify health system performance in the end-of-life period.

Impact of clinical decision support therapeutic interchanges on hospital discharge medication omissions and duplications.

PURPOSE: Automatic therapeutic substitution (ATS) protocols are formulary tools that allow for provider-selected interchange from a nonformulary preadmission medication to a formulary equivalent. Previous studies have demonstrated that the application of clinical decision support (CDS) tools to ATS can decrease ATS errors at admission, but there are limited data describing the impact of CDS on discharge errors. The objective of this study was to describe the impact of CDS-supported interchanges on discharge prescription duplications or omissions. METHODS: This was a single-center, retrospective cohort study conducted at an academic medical center. Patients admitted between June 2017 and August 2019 were included if they were 18 years or older at admission, underwent an ATS protocol-approved interchange for 1 of the 9 included medication classes, and had a completed discharge medication reconciliation. The primary outcome was difference in incidence of therapeutic duplication or omission at discharge between the periods before and after CDS implementation. RESULTS: A total of 737 preimplementation encounters and 733 postimplementation encounters were included. CDS did not significantly decrease the incidence of discharge duplications or omissions (12.1% vs 11.2%; 95% confidence interval [CI], -2.3% to 4.2%) nor the incidence of admission duplication or inappropriate reconciliation (21.4% vs 20.7%; 95% CI, -3.4% to 4.8%) when comparing the pre- and postimplementation periods. Inappropriate reconciliation was the primary cause of discharge medication errors for both groups. CONCLUSION: CDS implementation was not associated with a decrease in discharge omissions, duplications, or inappropriate reconciliation. Findings highlight the need for thoughtful medication reconciliation at the point of discharge.

The Biosimilar Nocebo Effect? A Systematic Review of Double-Blinded Versus Open-Label Studies.

BACKGROUND: Several authors have hypothesized that adverse drug events (ADEs) upon switching from reference biologics to biosimilar products are related to the nocebo effect. However, a thorough and current review of the existing literature has not been conducted. OBJECTIVE: To evaluate if patient and/or physician knowledge of a switch from a reference biologic product to a biosimilar product was associated with an increase in ADEs likely to be susceptible to the nocebo effect. METHODS: Studies reporting efficacy and safety outcomes of a switch from a reference product to a biosimilar product were reviewed. Biologics with FDA-approved biosimilars in the United States were considered for review, including adalimumab, bevacizumab, etanercept, and infliximab. Studies were identified by searching controlled vocabulary (e.g., MeSH terms) and keywords within MEDLINE (via PubMed) and Embase. Descriptive statistics were used to quantify subjective and objective complications in double-blinded and single-blinded or open-label studies. RESULTS: Thirty-one trials including 3,271 patients were reviewed in the full analysis. Median discontinuation rates for any reason were 14.3% (range = 0.0-33.3) in open-label studies compared with 6.95% (range = 5.2-11.0) in double-blinded studies. Discontinuation rates for ADEs were 5.6% (range = 0.0-24.2) in open-label studies versus 3.1% (range = 2.0-5.2) in double-blinded studies, suggesting the nocebo effect does affect biosimilar adoption. Subgroup analyses of antidrug antibody (ADA) development and infusion reactions were similar between infliximab open-label and double-blinded studies. Discontinuation rates for any reason, for ADEs, and for lack of efficacy were generally higher in infliximab open-label trials compared with double-blinded trials. Etanercept biosimilar discontinuation rates for any reason were similar between study designs; however, incidences of injection site reactions and discontinuation rates for ADEs were higher in double-blinded compared with open-label study designs. CONCLUSIONS: Current evidence is insufficient to confirm a biosimilar nocebo effect, although higher discontinuation rates in infliximab biosimilar open-label studies support this theory. Further studies are needed to evaluate the existence of a biosimilar nocebo effect. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to disclose.

Safety risks with investigational drugs: Pharmacy practices and perceptions in the veterans affairs health system.

OBJECTIVES: Rigorous practices for safe dispensing of investigational drugs are not standardized. This investigation sought to identify error-prevention processes utilized in the provision of investigational drug services (IDS) and to characterize pharmacists' perceptions about safety risks posed by investigational drugs. METHODS: An electronic questionnaire was distributed to an audience of IDS pharmacists within the Veteran Affairs Health System. Multiple facets were examined including demographics, perceptions of medication safety, and standard processes used to support investigational drug protocols. RESULTS: Twenty-one respondents (32.8% response rate) from the Northeast, Midwest, South, West, and Non-contiguous United States participated. The mean number of pharmacist full-time equivalents (FTEs) dedicated to the IDS was 0.77 per site with 0.2 technician FTEs. The mean number of active protocols was 22. Seventeen respondents (81%) indicated some level of concern for safety risks. Concerns related to the packaging of medications were expressed, most notably lack of product differentiation, expiration dating, barcodes, and choice of font size or color. Regarding medication safety practices, the majority of sites had specific procedures in place for storing and securing drug supply, temperature monitoring, and prescription labeling. Repackaging bulk items and proactive error-identification strategies were less common. Sixty-seven percent of respondents reported that an independent double check was not routinely performed. CONCLUSIONS: Medication safety concerns exist among pharmacists in an investigational drug service; however, a variety of measures have been employed to improve medication safety practices. Best practices for the safe dispensing of investigational medications should be developed in order to standardize these error-prevention strategies.

Use of erythropoiesis-stimulating agents in the treatment of anemia in patients with systolic heart failure.

OBJECTIVE: To determine the efficacy and safety of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in patients with systolic heart failure. DATA SOURCES: A search of MEDLINE (1946-January 2014) and EMBASE (1947-January 2014) was conducted using the search terms erythropoietin and systolic heart failure. In addition, bibliographies of relevant articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: All English language randomized controlled trials evaluating clinical outcomes or adverse events when using ESAs in the setting of systolic heart failure were included. DATA SYNTHESIS: A total of 9 studies were reviewed. All studies examining hematological parameters found a statistically significant increase in hemoglobin levels with active treatment versus placebo. Of the 7 trials evaluating exercise tolerance or capacity, only 4 demonstrated statistically significant improvement in these measures in patients receiving ESAs, whereas the remainder showed no clinical benefit. Four studies examined quality-of-life measures. Although numerical improvements were observed in most trials, statistical significance was reached in only 2 trials. A nonsignificant trend for decreased mortality in patients treated with darbepoetin with a similar adverse event profile compared to placebo was shown in one study; however, the largest trial to date showed no benefit in all-cause mortality or heart failure-related hospitalizations with the use of ESAs. Additionally, a statistically significant increase in the number of cerebrovascular events and thrombotic events was found. CONCLUSION: There is inconclusive evidence to suggest that the use of ESAs in treating anemia in patients with heart failure is beneficial. Although ESAs demonstrated a clear ability for increasing hemoglobin levels, the data regarding clinical outcomes such as exercise parameters, quality of life, and hospitalizations are conflicting. In addition, a mortality benefit has not been shown; therefore, the potential for improved symptomatology must be weighed against the potential for adverse events.

The effect of angiotensin II receptor blockers on hyperuricemia.

The objective of this review was to explore the efficacy of angiotensin II receptor blockers (ARBs) for the treatment of hyperuricemia in individuals diagnosed with gout or hyperuricemia defined as ⩾7 mg/dl at baseline. A literature search of MEDLINE (1946 to June 2015) and EMBASE (1947 to June 2015) was conducted. The following search terms were used: 'uric acid', 'urate transporter', 'gout', 'angiotensin II receptor blockers', 'hyperuricemia' and the names for individual ARBs, as well as any combinations of these terms. Studies were excluded that did not explore fractional excretion or serum uric acid as an endpoint, if patients did not have a diagnosis of gout or hyperuricemia at baseline, or if they were non-English language. A total of eight studies met the inclusion criteria. Of the eight studies identified, six explored ARB monotherapy and two studies investigated ARBs as adjunct therapy. Losartan demonstrated statistically significant reductions in serum uric acid levels or increases in fractional excretion of uric acid in all studies, whereas no other ARB reached statistical benefit. The effect of ARBs on the occurrence of gout attacks or other clinical outcomes were not represented. Four studies evaluated safety effects of these agents indicating abnormalities such as minor changes in lab values. In conclusion, losartan is the only ARB that has consistently demonstrated a significant reduction in serum uric acid levels, although the significance of impacting clinical outcomes remains unknown. Losartan appears to be a safe and efficacious agent to lower serum uric acid levels in patients with hyperuricemia.

Retrospective evaluation of the clinical use of prothrombin complex concentrate for the reversal of anticoagulation with vitamin K antagonists.

Anticoagulation reversal is a time-sensitive intervention for the prevention of life-threatening hemorrhagic events occurring with bleeding or surgery. Recommendations for the most effective and well tolerated reversal agent in these settings remain controversial. Several clinical guidelines for the management of intracerebral hemorrhage support use of prothrombin complex concentrates (PCCs) for the rapid reversal of warfarin-associated coagulopathy despite limited clinical data. The purpose of this investigation was to evaluate the efficacy and safety of PCC for the rapid reversal of anticoagulation by vitamin K antagonists for life-threatening bleeding or emergent surgery and to assess adherence to a hospital-based protocol. A retrospective chart review was conducted of adult patients receiving PCC for the reversal of anticoagulation. Patients were assessed according to indication for anticoagulation reversal. The primary outcome measure was adequacy of international normalized ratio reversal. Other outcomes included cessation of bleeding, thrombotic complications, and adherence to an institutional-based guideline for the use of PCC. ICU and hospital length of stay and 30-day mortality was assessed. There were 70 patients included in this study. Mean international normalized ratio was reduced from 3.1 to 1.6 following administration of at least one dose of PCC. Cessation of bleeding occurred in 65.7% of patients. Clinical assessment was unclear in 18.6%. Thrombotic complications were observed in 7.1% of patients. The 30-day mortality rate was found to be 14.3%. These data demonstrate that PCC is a well tolerated and effective method for anticoagulation reversal associated with a relatively high 30-day survival rate.

The emerging role of tacrolimus in myasthenia gravis.

OBJECTIVE: To describe and evaluate the available evidence assessing the role of tacrolimus in the management of patients with myasthenia gravis (MG). DATA SOURCES: A literature search of MEDLINE (1946 to September 2014) and EMBASE (1947 to September 2014) was performed using the terms 'tacrolimus' and 'myasthenia gravis'. Citations of retrieved articles were examined for relevance. STUDY SELECTION AND DATA EXTRACTION: The search was limited to prospective clinical trials focused on clinical outcomes in patients with generalized MG. Case reports, retrospective evaluations and non-English articles were excluded. DATA SYNTHESIS: A total of 12 studies met inclusion criteria, of which seven articles evaluated tacrolimus in steroid-dependent patients and two examined the utility of tacrolimus in patients failing corticosteroids and cyclosporine. Other studies evaluated early initiation of tacrolimus after thymectomy, effectiveness of tacrolimus in de novo MG and the effectiveness of tacrolimus post-thymectomy in thymoma patients versus nonthymoma. A total of eight trials showed statistically significant improvements in quantitative MG score (QMGS) and postintervention status criteria - Myasthenia Gravis Foundation of America (PSC-MGFA). Of the trials examining steroid reduction with tacrolimus, two reported high rates of complete withdrawal; however, the most robust trial was unable to detect a difference in mean steroid dose. Long-term effects of tacrolimus (up to 5 years) were assessed in eight trials, which consistently showed positive effects on QMGS or reduction in adjunct therapies. CONCLUSIONS: There is limited yet promising information to suggest a beneficial role for tacrolimus in reducing QMGS and corticosteroid burden in patients with refractory symptoms or new-onset MG. Long-term use appears to be safe in this population.