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Background Studies of implementation strategies range in rigor, design, and evaluated outcomes, presenting interpretation challenges for practitioners and researchers. This systematic review aimed to describe the body of research evidence testing implementation strategies across diverse settings and domains, using the Expert Recommendations for Implementing Change (ERIC) taxonomy to classify strategies and the Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM) framework to classify outcomes. Methods We conducted a systematic review of studies examining implementation strategies from 2010-2022 and registered with PROSPERO (CRD42021235592). We searched databases using terms “implementation strategy”, “intervention”, “bundle”, “support”, and their variants. We also solicited study recommendations from implementation science experts and mined existing systematic reviews. We included studies that quantitatively assessed the impact of at least one implementation strategy to improve health or health care using an outcome that could be mapped to the five evaluation dimensions of RE-AIM. Only studies meeting prespecified methodologic standards were included. We described the characteristics of studies and frequency of implementation strategy use across study arms. We also examined common strategy pairings and cooccurrence with significant outcomes. Findings Our search resulted in 16,605 studies; 129 met inclusion criteria. Studies tested an average of 6.73 strategies (0-20 range). The most assessed outcomes were Effectiveness ( n =82; 64%) and Implementation ( n =73; 56%). The implementation strategies most frequently occurring in the experimental arm were Distribute Educational Materials ( n =99), Conduct Educational Meetings ( n =96), Audit and Provide Feedback ( n =76), and External Facilitation ( n =59). These strategies were often used in combination. Nineteen implementation strategies were frequently tested and associated with significantly improved outcomes. However, many strategies were not tested sufficiently to draw conclusions. Conclusion This review of 129 methodologically rigorous studies built upon prior implementation science data syntheses to identify implementation strategies that had been experimentally tested and summarized their impact on outcomes across diverse outcomes and clinical settings. We present recommendations for improving future similar efforts.

The Veterans Health Administration (VA) is the largest integrated healthcare organization in the US and cares for the largest cohort of individuals with hepatitis C (HCV). A national HCV population management dashboard enabled rapid identification and treatment uptake with direct acting antiviral agents across VA hospitals. We describe the HCV dashboard (HCVDB) and evaluate its use and user experience. A user-centered design approach created the HCVDB to include reports based on the HCV care continuum: 1) 1945-1965 birth cohort high-risk screening, 2) linkage to care and treatment of chronic HCV, 3) treatment monitoring, 4) post-treatment to confirm cure (i.e., sustained virologic response), and 5) special populations of unstably housed Veterans. We evaluated frequency of usage and user experience with the System Usability Score (SUS) and Unified Theory of Acceptance and Use of Technology 2 (UTAUT2) instruments. Between November 2016 and July 2021, 1302 unique users accessed the HCVDB a total of 163,836 times. The linkage report was used most frequently (71%), followed by screening (13%), sustained virologic response (11%), on-treatment (4%), and special populations (<1%). Based on user feedback (n = 105), the mean SUS score was 73±16, indicating a good user experience. Overall acceptability was high with the following UTAUT2 rated from highest to least: Price Value, Performance Expectancy, Social Influence, and Facilitating Conditions. The HCVDB had rapid and widespread uptake, met provider needs, and scored highly on user experience measures. Collaboration between clinicians, clinical informatics, and population health experts was essential for dashboard design and sustained use. Population health management tools have the potential for large-scale impacts on care timeliness and efficiency.

Background Practical and feasible methods for matching implementation strategies to diagnosed barriers of evidence-based interventions in real-world contexts are lacking. This evaluation compared actual implementation strategies applied with those recommended by an expert opinion-based tool to improve guideline-concordant cirrhosis care in a Veterans Health Administration national learning collaborative effort. Methods This convergent parallel mixed-methods study aimed to (1) identify pre-implementation Consolidated Framework for Implementation Research (CFIR) barriers to cirrhosis care through focus groups with frontline providers, (2) generate 20 recommended strategies using focus group identified barriers entered into the CFIR-Expert Recommendations for Implementing Change (ERIC) Implementation Strategy Matching Tool, (3) survey providers over two consecutive years on the actual use of 73 ERIC strategies and determine strategy effectiveness, (4) compare actual versus recommended strategy use, and (5) compare actual versus expected barriers by reverse applying the CFIR-ERIC Matching Tool. Results Eighteen semi-structured focus groups were conducted with 197 providers representing 95 VA sites to identify barriers to quality improvement, including cirrhosis care complexity, clarity of national goals, and local leadership support. The CFIR-ERIC Matching Tool recommended strategies such as assessing for readiness and needs, promoting adaptability, building local groups, preparing champions, and working with opinion leaders and early adopters. Subsequent strategy surveys found that sites used the top 20 “recommended” strategies no more frequently than other strategies. However, 14 (70%) of the top recommended strategies were significantly positively associated with cirrhosis care compared to 48% of actual strategies. Reverse CFIR-ERIC matching found that the strategies most used in the first year corresponded to the following barriers: opinion leaders, access to knowledge and information, and resources. The strategies most frequently employed in the second year addressed barriers such as champions, cosmopolitanism, readiness for implementation, relative priority, and patient needs and resources. Strategies used in both years were those that addressed adaptability, trialability, and compatibility. Conclusions This study is among the first to empirically evaluate the relationship between CFIR-ERIC Matching Tool recommended strategies and actual strategy selection and effectiveness in the real world. We found closer connections between recommended strategies and strategy effectiveness compared to strategy frequency, suggesting validity of barrier identification, and application of the expert-informed tool.

Chronic liver disease (CLD) is among the strongest risk factors for adverse prescription opioid-related events. Yet, the current prevalence and factors associated with high-risk opioid prescribing in patients with chronic liver disease (CLD) remain unclear, making it challenging to address opioid safety in this population. Therefore, we aimed to characterize opioid prescribing patterns among patients with CLD. This retrospective cohort study included patients with CLD identified at a single medical center and followed for one year from 10/1/2015-9/30/2016. Multivariable, multinomial regression was used identify the patient characteristics, including demographics, medical conditions, and liver-related factors, that were associated with opioid prescriptions and high-risk prescriptions (≥90mg morphine equivalents per day [MME/day] or co-prescribed with benzodiazepines). Nearly half (47%) of 12,425 patients with CLD were prescribed opioids over a one-year period, with 17% of these receiving high-risk prescriptions. The baseline factors significantly associated with high-risk opioid prescriptions included female gender (adjusted incident rate ratio, AIRR = 1.32, 95% CI = 1.14-1.53), Medicaid insurance (AIRR = 1.68, 95% CI = 1.36-2.06), cirrhosis (AIRR = 1.22, 95% CI = 1.04-1.43) and baseline chronic pain (AIRR = 3.40, 95% CI = 2.94-4.01), depression (AIRR = 1.93, 95% CI = 1.60-2.32), anxiety (AIRR = 1.84, 95% CI = 1.53-2.22), substance use disorder (AIRR = 2.16, 95% CI = 1.67-2.79), and Charlson comorbidity score (AIRR = 1.27, 95% CI = 1.22-1.32). Non-alcoholic fatty liver disease was associated with decreased high-risk opioid prescriptions (AIRR = 0.56, 95% CI = 0.47-0.66). Opioid medications continue to be prescribed to nearly half of patients with CLD, despite efforts to curtail opioid prescribing due to known adverse events in this population.

Previous studies have demonstrated that opioids are often prescribed and associated with complications in outpatients with cirrhosis. Less is known about opioids among hospitalized patients with cirrhosis. We aimed to describe the patterns and complications of opioid use among inpatients with cirrhosis. This retrospective cohort study included adult patients with cirrhosis admitted to a single hospital system from 4/4/2014 to 9/30/2015. We excluded hospitalizations with a surgery, invasive procedure, or palliative care/hospice consult in order to understand opioid use that may be avoidable. We determined the frequency, dosage, and type of opioids given during hospitalization. Using bivariable and multivariable analyses, we assessed length of stay, intensive care unit transfer, and in-hospital mortality by opioid use. Of 217 inpatients with cirrhosis, 118 (54.4%) received opioids during hospitalization, including 41.7% of patients without prior outpatient opioid prescriptions. Benzodiazepines or hypnotic sleep aids were given to 28.8% of opioid recipients. In the multivariable model, younger age and outpatient opioid prescription were associated with inpatient opioids. Hospitalization was longer among opioid recipients (median 3.9 vs 3.0 days, p = 0.002) and this difference remained after adjusting for age, cirrhosis severity, and medical comorbidities. There was no difference in intensive care unit transfers and no deaths occurred. At discharge, 22 patients were newly started on opioids of whom 10 (45.5%) had opioid prescriptions at 90 days post-discharge. In non-surgical inpatients with cirrhosis, opioid prescribing was common and associated with prolonged length of stay. A high proportion of patients newly discharged with opioid prescriptions had ongoing prescriptions at 90 days post-discharge.

Depression after liver transplantation has been associated with decreased survival, but the effects of pre-transplant depression on early and late post-transplant outcomes remain incompletely evaluated. We assessed all patients who had undergone single-organ liver transplantation at a single center over the prior 10 years. A diagnosis of pre-transplant depression, covariates, and the outcomes of interest were extracted from the electronic medical record. Potential covariates included demographics, etiology and severity of liver disease, comorbidities, donor age, graft type, immunosuppression, and ischemic times. In multivariable models adjusting for these factors, we evaluated the effect of pre-transplant depression on transplant length of stay (LOS), discharge disposition (home vs. facility) and long-term survival. Among 1115 transplant recipients with a median follow-up time of 5 years, the average age was 56±11 and MELD was 12±9. Nineteen percent of the study population had a history of pre-transplant depression. Pre-transplant depression was associated with longer LOS (median = 19 vs. 14 days, IRR = 1.25, CI = 1.13,1.39), discharge to a facility (36% vs. 25%, OR 1.70,CI = 1.18,2.45), and decreased survival (HR = 1.54,CI = 1.14,2.08) in this cohort, accounting for other potential confounders. In conclusion, pre-transplant depression was significantly associated with longer transplant length of stay, discharge to a facility, and mortality in this cohort.

Background While few countries and healthcare systems are on track to meet the World Health Organization’s hepatitis C virus (HCV) elimination goals, the US Veterans Health Administration (VHA) has been a leader in these efforts. We aimed to determine which implementation strategies were associated with successful national viral elimination implementation within the VHA. Methods We conducted a five-year, longitudinal cohort study of the VHA Hepatic Innovation Team (HIT) Collaborative between October 2015 and September 2019. Participants from 130 VHA medical centers treating HCV were sent annual electronic surveys about their use of 73 implementation strategies, organized into nine clusters as described by the Expert Recommendations for Implementing Change taxonomy. Descriptive and nonparametric analyses assessed strategy use over time, strategy attribution to the HIT, and strategy associations with site HCV treatment volume and rate of adoption, following the Theory of Diffusion of Innovations. Results Between 58 and 109 medical centers provided responses in each year, including 127 (98%) responding at least once, and 54 (42%) responding in all four implementation years. A median of 13–27 strategies were endorsed per year, and 8–36 individual strategies were significantly associated with treatment volume per year. Data warehousing, tailoring, and patient-facing strategies were most commonly endorsed. One strategy—“identify early adopters to learn from their experiences”—was significantly associated with HCV treatment volume in each year. Peak implementation year was associated with revising professional roles, providing local technical assistance, using data warehousing (i.e., dashboard population management), and identifying and preparing champions. Many of the strategies were driven by a national learning collaborative, which was instrumental in successful HCV elimination. Conclusions VHA’s tremendous success in rapidly treating nearly all Veterans with HCV can provide a roadmap for other HCV elimination initiatives.

Background Alcohol cessation is the cornerstone of treatment for alcohol-related cirrhosis. This study evaluated associations between medical conversations about alcohol use disorder (AUD) treatment, AUD treatment engagement, and mortality. Methods This retrospective cohort study included all patients with ICD-10 diagnosis codes for cirrhosis and AUD who were engaged in hepatology care in a single healthcare system in 2015. Baseline demographic, medical, liver disease, and AUD treatment data were assessed. AUD treatment discussions and initiation, alcohol cessation, and subsequent 5-year mortality were collected. Multivariable models were used to assess the factors associated with subsequent AUD treatment and 5-year mortality. Results Among 436 patients with cirrhosis due to alcohol, 65 patients (15%) received AUD treatment at baseline, including 48 (11%) receiving behavioral therapy alone, 11 (2%) receiving pharmacotherapy alone, and 6 (1%) receiving both. Over the first year after a baseline hepatology visit, 37 patients engaged in AUD treatment, 51 were retained in treatment, and 14 stopped treatment. Thirty percent of patients had hepatology-documented AUD treatment recommendations and 26% had primary care-documented AUD treatment recommendations. Most hepatology (86%) and primary care (88%) recommendations discussed behavioral therapy alone. Among patients with ongoing alcohol use at baseline, AUD treatment one year later was significantly, independently associated with AUD treatment discussions with hepatology (adjusted odds ratio (aOR): 3.23, 95% confidence interval (CI): 1.58, 6.89) or primary care (aOR: 2.95; 95% CI: 1.44, 6.15) and negatively associated with having Medicaid insurance (aOR: 0.43, 95% CI: 0.18, 0.93). When treatment was discussed in both settings, high rates of treatment ensued (aOR: 10.72, 95% CI: 3.89, 33.52). Over a 5-year follow-up period, 152 (35%) patients died. Ongoing alcohol use, age, hepatic decompensation, and hepatocellular carcinoma were significantly associated with mortality in the final survival model. Conclusion AUD treatment discussions were documented in less than half of hepatology and primary care encounters in patients with alcohol-related cirrhosis, though such discussions were significantly associated with receipt of AUD treatment.

The Veterans Health Administration (VA) cares for over 80,000 Veterans with cirrhosis annually. Given the importance of understanding patient reported outcomes in this complex population, we aimed to assess the associations between attitudes towards care, disease knowledge, and health related quality of life (HRQoL) in a national sample. In this cross-sectional study, we mailed paper surveys to a random sample of Veterans with cirrhosis, oversampling those with decompensated disease. Surveys included the Veterans RAND 12-Item Health Survey (measuring HRQoL) and questions about demographics, characteristics of care, satisfaction with care (\"attitudes towards care\"), and symptoms of cirrhosis. Those who reported being \"unsure\" about whether they had decompensation events were defined as \"unsure about cirrhosis symptoms\" (\"disease knowledge\"). We used multivariable regression models to assess the factors associated with HRQoL. Of 1374 surveys, 551 (40%) completed surveys were included for analysis. Most Veterans (63%) were \"satisfied\" or \"very satisfied\" with VA liver care. Patients often self-reported being unsure about whether they had experienced hepatic decompensation events (34%). Overall average physical (PCS) and mental (MCS) component scores of HRQoL were 30±11 and 41±12. In multivariable regression models, hepatic decompensation (PCS:[beta] = -3.8, MCS:[beta] = -2.2), medical comorbidities ([beta] = --2.0, [beta] = -1.7), and being unsure about cirrhosis symptoms ([beta] = -1.9, [beta] = -3.3) were associated with worse HRQoL, while age ([beta] = 0.1, [beta] = 0.2) and satisfaction with care ([beta] = 0.6; [beta] = 1.6) were associated with significantly better HRQoL. Hepatic decompensation, lower satisfaction with care, and being unsure about cirrhosis symptoms were associated with reduced QOL scores in this national cohort.

Hospital readmission rate is receiving increasing regulatory scrutiny. Patients with cirrhosis have high hospital readmissions rates but the relationship between frequent readmissions and barriers to transplantation remains unexplored. The goal of this study was to determine risk factors for frequent readmissions among patients with cirrhosis and identify barriers to transplantation in this population. We retrospectively reviewed medical records of 587 patients with a confirmed diagnosis of cirrhosis admitted to a large tertiary care center between May 1, 2008 and May 1, 2009. Demographics, clinical factors, and outcomes were recorded. Multivariate logistic regression was performed to identify risk factors for high readmission rates. Transplant-related factors were assessed for patients in the high readmission group. The 587 patients included in the study had 1557 admissions during the study period. A subset of 87 (15%) patients with 5 or more admissions accounted for 672 (43%) admissions. The factors associated with frequent admissions were non-white race (OR = 2.45, p = 0.01), diabetes (OR = 2.04, p = 0.01), higher Model for End-Stage Liver Disease (MELD) score (OR = 35.10, p<0.0001 for MELD>30) and younger age (OR = 0.98, p = 0.02). Among the 87 patients with ≥5 admissions, only 14 (16%) underwent liver transplantation during the study period. Substance abuse, medical co-morbidities, and low (<15) MELD scores were barriers to transplantation in this group. A small group of patients with cirrhosis account for a disproportionately high number of hospital admissions. Interventions targeting this high-risk group may decrease frequent hospital readmissions and increase access to transplantation.