Implementing a Process to Systematically Identify and Address Poor Medication Adherence in Pediatric Liver Transplant Recipients.

OBJECTIVES: Poor adherence to medication following pediatric liver transplantation remains a major challenge, with some estimates suggesting that 50% of adolescent liver transplant recipients exhibit reduced medication adherence. To date, no gold standard has emerged to address this challenge; however, system interventions are most likely to be successful. We sought to implement a system to identify and address adherence barriers in a liver transplant clinic. METHODS: Using structured quality improvement methods, including multiple plan-do-study-act cycles, we developed a system to screen for patients at risk of poor adherence, identify patient- and/or parent-reported barriers to adherence, and partner with patients to overcome identified barriers. We developed a process to track key outcomes, including the variability in tacrolimus trough levels and episodes of late acute cellular rejection. RESULTS: The practice saw a total of 85 patients over 6 months, and about half were females. Over this period, the improvement team implemented this system-level process with high reliability (>90% of patients received the bundle of interventions). The most commonly identified adherence barrier by patients and caregivers was "forgetting." The second most commonly identified adherence barrier by patients was that the medication "gets in the way of their activities," whereas by caregivers, it was "difficulty swallowing pills." DISCUSSION: We identified challenges and opportunities to screen for poor adherence and identify patient- and/or caregiver-reported barriers to immunosuppression adherence. Identifying such barriers and partnering with patients to overcome those barriers using patient-centered, barrier-specific interventions could improve long-term graft survival through improved medication adherence.

Assessing barriers to adherence in routine clinical care for pediatric kidney transplant patients.

Patient-identified barriers to immunosuppressive medications are associated with poor adherence and negative clinical outcomes in transplant patients. Assessment of adherence barriers is not part of routine post-transplant care, and studies regarding implementing such a process in a reliable way are lacking. Using the Model for Improvement and PDSA cycles, we implemented a system to identify adherence barriers, including patient-centered design of a barriers assessment tool, identification of eligible patients, clear roles for clinic staff, and creating a culture of non-judgmental discussion around adherence. We performed time-series analysis of our process measure. Secondary analyses examined the endorsement and concordance of adherence barriers between patient-caregiver dyads. After three methods of testing, the most reliable delivery system was an EHR-integrated tablet that alerted staff of patient eligibility for assessment. Barriers were endorsed by 35% of caregivers (n=85) and 43% of patients (n=60). The most frequently patient-endorsed barriers were forgetting, poor taste, and side effects. Caregivers endorsed forgetting and side effects. Concordance between patient-caregiver dyads was fair (k=0.299). Standardized adherence barriers assessment is feasible in the clinical care of pediatric kidney transplant patients. Features necessary for success included automation, redundant systems with designated staff to identify and mitigate failures, aligned reporting structures, and reliable measurement approaches. Future studies will examine whether barriers predict clinical outcomes (eg, organ rejection, graft loss).

Relationship between therapeutic effects on infarct size in acute myocardial infarction and therapeutic effects on 1-year outcomes: A patient-level analysis of randomized clinical trials.

BACKGROUND: While infarct size in patients with ST-segment elevation myocardial infarction (STEMI) has been generally associated with long-term prognosis, whether a therapeutic effect on infarct size has a corresponding therapeutic effect on long-term outcomes is unknown. METHODS: Using combined patient-level data from 10 randomized trials of primary percutaneous coronary intervention (PCI) for STEMI, we created multivariable Cox proportional hazard models for one-year heart failure hospitalization and all-cause mortality, which included clinical features and a variable representing treatment effect on infarct size. The trials included 2679 participants; infarct size was measured at a median 4 days post infarction. RESULTS: Mean infarct size among the control groups ranged from 16% to 35% of the left ventricle, and from 12% to 36% among treatment groups. There was a significant relationship between treatment effect on infarct size and treatment effect on 1-year heart failure hospitalization (HR 0.85, 95% CI 0.77-0.93, P=.0006), but not on one-year mortality (HR 0.97, 95% CI 0.89-1.06). The treatment effect between infarct size and heart failure hospitalization was stable in sensitivity analyses adjusting for time from STEMI onset to infarct size assessment, and when considering heart failure as the main outcome and death as a competing risk. CONCLUSIONS: We conclude that early treatment-induced effects on infarct size are related in direction and magnitude to treatment effects on heart failure hospitalizations. This finding enables consideration of using infarct size as a valid surrogate outcome measure in assessing new STEMI treatments.

Comparison of Propensity Score Methods and Covariate Adjustment: Evaluation in 4 Cardiovascular Studies.

Propensity scores (PS) are an increasingly popular method to adjust for confounding in observational studies. Propensity score methods have theoretical advantages over conventional covariate adjustment, but their relative performance in real-word scenarios is poorly characterized. We used datasets from 4 large-scale cardiovascular observational studies (PROMETHEUS, ADAPT-DES [the Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents], THIN [The Health Improvement Network], and CHARM [Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity]) to compare the performance of conventional covariate adjustment with 4 common PS methods: matching, stratification, inverse probability weighting, and use of PS as a covariate. We found that stratification performed poorly with few outcome events, and inverse probability weighting gave imprecise estimates of treatment effect and undue influence to a small number of observations when substantial confounding was present. Covariate adjustment and matching performed well in all of our examples, although matching tended to give less precise estimates in some cases. PS methods are not necessarily superior to conventional covariate adjustment, and care should be taken to select the most suitable method.

Relationship Between Infarct Size and Outcomes Following Primary PCI: Patient-Level Analysis From 10 Randomized Trials.

BACKGROUND: Prompt reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) reduces infarct size and improves survival. However, the intuitive link between infarct size and prognosis has not been convincingly demonstrated in the contemporary era. OBJECTIVES: This study sought to determine the strength of the relationship between infarct size assessed early after primary percutaneous coronary intervention (PCI) in STEMI and subsequent all-cause mortality, reinfarction, and hospitalization for heart failure. METHODS: We performed a pooled patient-level analysis from 10 randomized primary PCI trials (total 2,632 patients) in which infarct size was assessed within 1 month after randomization by either cardiac magnetic resonance (CMR) imaging or technetium-99m sestamibi single-photon emission computed tomography (SPECT), with clinical follow-up for ≥ 6 months. RESULTS: Infarct size was assessed by CMR in 1,889 patients (71.8%) and by SPECT in 743 patients (28.2%). Median (25th, 75th percentile) time to infarct size measurement was 4 days (3, 10 days) after STEMI. Median infarct size (% left ventricular myocardial mass) was 17.9% (8.0%, 29.8%), and median duration of clinical follow-up was 352 days (185, 371 days). The Kaplan-Meier estimated 1-year rates of all-cause mortality, reinfarction, and HF hospitalization were 2.2%, 2.5%, and 2.6%, respectively. A strong graded response was present between infarct size (per 5% increase) and subsequent mortality (Cox-adjusted hazard ratio: 1.19 [95% confidence interval: 1.18 to 1.20]; p < 0.0001) and hospitalization for heart failure (adjusted hazard ratio: 1.20 [95% confidence interval: 1.19 to 1.21]; p < 0.0001), independent of age, sex, diabetes, hypertension, hyperlipidemia, current smoking, left anterior descending versus non-left anterior descending infarct vessel, symptom-to-first device time, and baseline TIMI (Thrombolysis In Myocardial Infarction) flow 0/1 versus 2/3. Infarct size was not significantly related to subsequent reinfarction. CONCLUSIONS: Infarct size, measured by CMR or technetium-99m sestamibi SPECT within 1 month after primary PCI, is strongly associated with all-cause mortality and hospitalization for HF within 1 year. Infarct size may, therefore, be useful as an endpoint in clinical trials and as an important prognostic measure when caring for patients with STEMI.

Comparison of Stent Expansion Guided by Optical Coherence Tomography Versus Intravascular Ultrasound: The ILUMIEN II Study (Observational Study of Optical Coherence Tomography [OCT] in Patients Undergoing Fractional Flow Reserve [FFR] and Percutaneous Coronary Intervention).

OBJECTIVES: The present study sought to determine whether optical coherence tomography (OCT) guidance results in a degree of stent expansion comparable to that with intravascular ultrasound (IVUS) guidance. BACKGROUND: The most important predictor of adverse outcomes (thrombosis and restenosis) after stent implantation with IVUS guidance is the degree of stent expansion achieved. METHODS: We compared the relative degree of stent expansion (defined as the minimal stent area divided by the mean of the proximal and distal reference lumen areas) after OCT-guided stenting in patients in the ILUMIEN (Observational Study of Optical Coherence Tomography [OCT] in Patients Undergoing Fractional Flow Reserve [FFR] and Percutaneous Coronary Intervention) (N = 354) and IVUS-guided stenting in patients in the ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) study (N = 586). Stent expansion was examined in all 940 patients in a covariate-adjusted analysis as well as in 286 propensity-matched pairs (total N = 572). RESULTS: In the matched-pair analysis, the degree of stent expansion was not significantly different between OCT and IVUS guidance (median [first, third quartiles] = 72.8% [63.3, 81.3] vs. 70.6% [62.3, 78.8], respectively, p = 0.29). Similarly, after adjustment for baseline differences in the entire population, the degree of stent expansion was also not different between the 2 imaging modalities (p = 0.84). Although a higher prevalence of post-PCI stent malapposition, tissue protrusion, and edge dissections was detected by OCT, the rates of major malapposition, tissue protrusion, and dissections were similar after OCT- and IVUS-guided stenting. CONCLUSIONS: In the present post-hoc analysis of 2 prospective studies, OCT and IVUS guidance resulted in a comparable degree of stent expansion. Randomized trials are warranted to compare the outcomes of OCT- and IVUS-guided coronary stent implantation.

Prospective, multicenter, randomized, controlled pilot trial of peritoneal hypothermia in patients with ST-segment- elevation myocardial infarction.

BACKGROUND: Systemic hypothermia may reduce infarct size if established before reperfusion. The large surface area of the bowel may facilitate rapid hypothermia. We therefore examined the feasibility, safety, and efficacy of hypothermia induced by an automated peritoneal lavage system in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset were randomized to peritoneal hypothermia before and for 3 hours after percutaneous coronary intervention versus control. The primary safety end point was the 30-day composite rate of death, reinfarction, ischemia-driven target vessel revascularization, major bleeding, sepsis, pneumonia, peritonitis, severe arrhythmia, or renal failure. The primary efficacy end point was infarct size assessed by cardiac MRI on day 3 to 5. Fifty-four patients were randomized at 7 centers to hypothermia (n=28) versus control (n=26). Hypothermia was successfully initiated in 96.3% of patients, and median [interquartile range] temperature at first balloon inflation was 34.7 [34.0-34.9]°C. Median door-to-balloon times in the hypothermia and control groups were 62 [51-81] and 47 [37-55] minutes, respectively (P=0.007). The primary safety end point occurred in 6 (21.4%) and 0 (0%) patients in the hypothermia and control groups, respectively (P=0.01), including 3 versus 0 stent thrombosis events. Infarct size was 17.2% [15.1-20.6] and 16.1% [10.0-22.2] in the hypothermia and control groups, respectively (P=0.54). CONCLUSIONS: Peritoneal hypothermia is feasible and achieves rapid cooling with only a modest increase in treatment times in the setting of ST-segment-elevation myocardial infarction. However, in the present randomized trial, peritoneal hypothermia was associated with an increased rate of adverse events without reducing infarct size. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01655433.