Adherence Threshold Research Articles

The effect of cognitive emotion regulation on direct-acting antivirals adherence in patients with hepatitis C

IntroductionAdherence to direct-acting antivirals (DAAs) could be a predictor of chronic viral hepatitis C (HCV) therapeutic failure. We examined the perceptions of patients receiving DAAs to determine how cognitive factors influence their decision to maintain adherence. Also, we explored the threshold of DAAs adherence for obtaining sustained virologic response (SVR) among patients with HCV, in order to better implement a strategy that improves the DAAs adherence in the future clinical practice.MethodsA single-arm prospective study was performed. Patients with HCV that started and completed DAAs treatment in the County Hospital of Craiova, Dolj, Romania, were enrolled. Patients’ medication adherence was assessed using the HCV-AD10 questionnaire, and the cognitive emotion regulation was measured with CERQ questionnaire (five positive/adaptive cognitive emotion-regulation domains and four negative/maladaptive domains). Spearman correlation analysis was conducted to explore the relationships between adherence and different factors. ROC-curves were used to evaluate the adherence threshold to achieve SVR. A linear regression model was performed to analyze the primary outcome (DAAs adherence) to be the target variable based on given independent variables (age, treatment duration, severity of HCV, the nine adaptive and maladaptive strategies).Results368 patients (mean age: 61 years) with HCV diagnosed 4.05 ± 6.38 (average) years ago were enrolled. Mean (±SD) adherence via HCV-AD10 was 91.51 ± 8.34, and the proportion of the participants achieving SVR was 96%. Patients with an adherence less than 84% (5 patients, 1.36%) was considered nonadherent and they have a high probability of not achieving response (sensitivity and specificity of 83% and 80%, respectively). We obtained significantly higher values of three adaptive strategies between adherent and nonadherent patients following DAAs treatment: in positive refocusing (p-value = 0.044), refocus on planning (p-value = 0.037), and positive reappraisal (p-value = 0.047).DiscussionThe interplay between the three adaptive strategies of the cognitive emotion regulation and the enhancement of DAAs adherence contributes to a more holistic comprehension of patient behavior in the context of HCV treatment. Increasing refocusing and planning using goal setting and assisting patients in establishing specific, achievable goals can be crucial strategies for clinicians aiming to improve adherence among their patients.

Medication adherence to inhalation therapy and the risk of COPD exacerbations: a systematic review with meta-analysis

BackgroundAssessing medication adherence is crucial in chronic obstructive pulmonary disease (COPD) management to prevent exacerbations. However, it is unclear whether this association between adherence and exacerbations is influenced by the...

Estimating the economic impact of blister-packaging on medication adherence and health care costs for a Medicare Advantage health plan.

Medication nonadherence is a persistent challenge in the United States, leading to increased health care resource utilization (HCRU) and health care costs and worsened health outcomes. Medicare Star Ratings is a program developed by the Centers for Medicare and Medicaid Services (CMS) to evaluate Medicare health plan quality and performance. Three of the Medicare Part D Star Ratings quality measures assess medication adherence, showing the importance CMS places on improving medication adherence in older adults. Although a variety of medication adherence-enhancing interventions are available to help promote adherence among patients, one intervention that has shown success historically is blister-packaging. To model the potential impact of blister-packaging chronic medications on HCRU and health care costs in the Medicare population. An economic model was developed to assess the potential impact of blister-packaging the 3 Medicare Star Ratings adherence measure medication classes: renin-angiotensin system antagonists (RASAs), statins, and noninsulin antidiabetics. The model perspective was that of a hypothetical Medicare Advantage health plan with a plan size of 100,000 members. A 12-month time horizon was used in the model. The dichotomous adherence threshold in the model was set at 80% or greater of the proportion of days covered (PDC). Literature-based references were used to inform both the impact of blister-packaging on the number of patients who become adherent as well as the impact of medication adherence on HCRU and health care costs for each of the medication classes. One-way sensitivity analyses and several scenario analyses were conducted to assess model uncertainty. Owing to increased adherence from the blister-packaging intervention, the hypothetical health plan in the analysis saw 776 additional members adherent to RASAs, 1,651 additional members adherent to statins, and 414 additional members adherent to oral antidiabetics. Although medication expenditure increased for all 3 medication classes (RASAs: $274,963; statins: $730,083; oral antidiabetics: $100,529), medical costs decreased across all classes (RASAs: -$4,098,848; statins: -$5,549,699; oral antidiabetics: -$917,968). Total net health care costs decreased by $3,823,885 for RASAs (-$3.19 per member per month [PMPM]), $4,819,616 for statins (-$4.02 PMPM), and $817,438 for oral antidiabetics (-$0.68 PMPM). The entire Medicare Advantage population scenario analysis saw reductions in total health care costs of $1,081,394,737 for RASAs, $1,362,987,376 for statins, and $231,171,496 for oral antidiabetics. Dispensing chronic medications with blister-packaging for Medicare Advantage health plan patients was modeled to reduce HCRU and health care costs. Future studies are needed to assess whether the impact of blister-packaging medications is tied to reductions in HCRU and health care costs in real-world settings.

Estimation of optimal adherence threshold for tumor necrosis factor inhibitors in rheumatoid arthritis

IntroductionOptimal adherence thresholds can vary across medications and disease states. The objective of the study was to determine the optimal threshold of the proportion of days covered (PDC) for tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA).MethodsPatients with RA initiating self-administered TNF inhibitors were identified using 2012–18 Medicare fee-for-service claims. Time-varying PDC was calculated every day for the preceding 90 days during follow-up. Oral and injected glucocorticoid use, hospitalizations, emergency room (ER) visits, serious infections, and a composite of these were measured as outcomes. Time to first occurrence of each outcome as a function of time-varying PDC for TNF inhibitors was evaluated using Cox regression. Incident/dynamic time-dependent receiver operating characteristic curves and Youden’s J index were used to obtain the optimal PDC threshold for outcomes at 365 days.ResultsOf the 1190 patients who met the study inclusion criteria, almost 75% (865 patients) experienced at least one of the outcomes. Increasing PDC by 10% was significantly associated with decreased risks of the composite outcome (HR 0.98, 95% CI 0.96–1.00), oral glucocorticoid use (HR 0.93, 95% CI 0.91–0.96), and hospitalization (HR 0.96, 95% CI 0.94–0.99) but an increased risk of ER visits (HR 1.04, 95% 1.01–1.07). Optimal PDC thresholds for the composite outcome, oral glucocorticoid use, and hospitalization were 0.64, 0.59, and 0.56, respectively.ConclusionsIncreased PDC was associated with a decreased risk of adverse outcomes, except ER visits. The optimal PDC for TNF inhibitors in Medicare patients with RA based on clinical outcomes was about 60%.Key Points• The optimal proportion of days covered threshold for tumor necrosis factor inhibitors at 365 days based on clinical outcomes was found to be about 60%, which is lower than the traditional 80% used to define adherence.• Increased adherence was associated with decreased risks of oral glucocorticoid use, hospitalization, and the composite outcome. However, it was also associated with an increased risk of emergency room visits.• The mean time-varying 90-day proportion of days covered decreased throughout the study starting 92% at day 1 of follow-up to 62% at day 365.

#2160 Ketosis moderates the effect on kidney volume in dietary interventions for ADPKD—more insights on the KETO ADPKD trial

Abstract Background and Aims Autosomal-dominant polycystic kidney disease (ADPKD) is the most common monogenic disease leading to kidney failure. Tolvaptan, the only approved targeted treatment strategy, comes with adverse events such as hepatotoxicity and massive polyuria, limiting its use. Novel treatment strategies are urgently needed. Cyst-lining epithelial cells are glucose-dependent and metabolically inflexible. Evidence from polycystic kidney disease (PKD) animal models show that ketogenic dietary interventions (KDI) can ameliorate cyst growth and loss of kidney function. To enable clinical translation of these findings, our group set up a series of trials—from small cohorts and proof of principle studies to our most recent trial KETO-ADPKD, showing that KDIs are feasible and can work as a treatment for ADPKD [1]. This has received a lot of attention. With this post-hoc analyses, we aim to share further in-depth analyses of the factors moderating the effects we see on ADPKD. Method KETO-ADPKD is an exploratory randomized and controlled clinical trial (NCT04680780). Sixty-six patients were randomized to 3 months dietary intervention (ketogenic diet [KD] or water fasting [WF]) or the control group. Here, we explore correlations between biochemical readout parameters of ketosis and markers of disease progression. Results The KD group shows a promising, yet statistically not significant decline in height-adjusted total kidney volume (htTKV). Patients reaching high biochemical thresholds of ketosis however significantly reduced their htTKV in comparison with the control group (KD −16.3 ml/m, CG + 14.8 ml/m, p-value 0.049). This becomes even clearer when higher thresholds for adherence are administered: In a smaller group requiring not only beta-hydroxybutyrate (BHB) levels ≥0.5 mmol/l but breath acetone ≥5 ppm on 75% of daily measurements, htTKV could be reduced by −17.6 ml/m (KD) vs +14.8 ml/m (CG), p-value 0.026. The significant reduction of liver volume upon KD is not influenced by the level of ketosis. Beneficial effects on estimated glomerular filtration rate (eGFR) can be equally observed in all subsets. Weight loss ≥5% was nor associated with a more significant loss of kidney nor liver volume. Conclusion Subgroup analyses of the KETO-ADPKD trial show stronger impact of the dietary intervention with higher ketone body levels. In particular, ketogenesis as a marker of metabolic reprogramming strongly moderates the effects we see on kidney volume. The assessment of renal cyst fractions could further enlighten the effects on cyst burden. This is in line with preclinical data showing that ketosis rather than caloric intake is responsible for the amelioration of disease progression [2].

Using wearable technology data to explain recreational running injury: A prospective longitudinal feasibility study

ObjectivesInvestigate 1) if collecting and analysing wristwatch inertial measurement unit (IMU) and global positioning system (GPS) data using a commercially-available training platform was feasible in recreational runners and 2) which variables were associated with subsequent injury. DesignProspective longitudinal cohort. ParticipantsHealthy recreational runners. Main outcome measuresWe set a priori feasibility thresholds for recruitment (maximum six-months), acceptance (minimum 80%), adherence (minimum 70%), and data collection (minimum 80%). Participants completed three patient-reported outcome measures (PROMS) detailing their psychological health, sleep quality, and intrinsic motivation to run. We extracted baseline anthropometric, biomechanical, metabolic, and training load data from their IMU/GPS wristwatch for analysis. Participants completed a weekly injury status surveillance questionnaire over the next 12-weeks. Feasibility outcomes were analysed descriptively and injured versus non-injured group differences with 95% confidence intervals were calculated for PROM/IMU/GPS data. Results149 participants consented; 86 participants completed (55 men, 31 women); 21 developed an injury (0.46 injuries/1000km). Feasibility outcomes were satisfied (recruitment = 47 days; acceptance = 133/149 [89%]; adherence = 93/133 [70%]; data collection = 86/93 [92%]). Acute load by calculated effort was associated with subsequent injury (mean difference −562.14, 95% CI -1019.42, −21.53). ConclusionCollecting and analysing wristwatch IMU/GPS data using a commercially-available training platform was feasible in recreational runners.

Culturally Relevant Africultural Coping Moderates the Association Between Discrimination and Antiretroviral Adherence Among Sexual Minority Black Americans Living with HIV

Exposure to discrimination has been linked to lower HIV antiretroviral therapy (ART) adherence and poor HIV care outcomes among Black Americans. Coping has been shown to mitigate the harmful effects of discrimination on health behaviors, but the use of cultural relevant Africultural coping strategies is understudied as a moderator of the association between intersectional discrimination and ART adherence among Black Americans. We used adjusted logistic regression to test whether Africultural coping strategies (cognitive/emotional debriefing; collective; spiritual-centered; ritual-centered) moderated associations between multiple forms of discrimination (HIV, sexual orientation, race) and good ART adherence (minimum of 75% or 85% of prescribed doses taken, as measured by electronic monitoring in separate analyses) among 92 sexual minority Black Americans living with HIV. Mean adherence was 66.5% in month 8 after baseline (36% ≥ 85% adherence; 49% ≥ 75% adherence). Ritual-centered coping moderated the relationship between each of the three types of discrimination at baseline and good ART adherence in month 8 (regardless of the minimum threshold for good adherence); when use of ritual coping was low, the association between discrimination and adherence was statistically significant. The other three coping scales each moderated the association between racial discrimination and good ART adherence (defined by the 75% threshold); cognitive/emotional debriefing was also a moderator for both HIV- and race-related discrimination at the 85% adherence threshold. These findings support the benefits of Africultural coping, particularly ritual-centered coping, to help sexual minority Black Americans manage stressors associated with discrimination and to adhere well to ART.

Patterns of Nonadherence to Hydroxyurea in Pediatric Sickle Cell Disease

Background: Sickle cell disease (SCD) affects an estimated 100,000 American children and adults (CDC, 2017). Hydroxyurea is the first-line disease-modifying treatment for SCD. Daily oral hydroxyurea significantly reduces the frequency of pain and serious medical complications associated with SCD, including dactylitis and acute chest syndrome (Wang et al., 2011). However, adherence to hydroxyurea is less than optimal at 74% among pediatric patients, with 20% of children who are prescribed hydroxyurea taking less than 50% of their prescribed doses (Louiselle et al., 2016). Suboptimal hydroxyurea adherence is associated with increased risk for medical complications, diminished quality of life, and higher health care costs and utilization (e.g., Badawy et al., 2017; Thornburg et al., 2010). Factors associated with hydroxyurea nonadherence in pediatric SCD include female sex, older age, more adherence barriers (e.g., difficulty obtaining refills), lower socioeconomic status, and lower parent treatment knowledge. Purpose: This study aims to characterize trajectories of pediatric hydroxyurea adherence to identify subgroups that may be at highest risk for hydroxyurea nonadherence (e.g., sociodemographic factors), critical time periods for adherence support interventions (e.g., adolescence), and minimal adherence thresholds to optimize hydroxyurea efficacy. Methods: Retrospective chart review across two institutions (i.e., Cincinnati Children's Hospital Medical Center and Nemours Children's Hospital, Delaware) are ongoing. Participants will include patients with SCD ages 2 to 21 years who were prescribed hydroxyurea from March 2007 to February 2017. Researchers are extracting the following data from patient electronic medical records (EMRs) to estimate hydroxyurea adherence: hemoglobin F levels (HbF), mean corpuscular volume (MCV), and absolute neutrophil count (ANC). Additional clinical information will be extracted from patient EMRs including demographic information, SCD genotype, SCD complications, acute care utilization, medical and social complexity, and concomitant medication use. Descriptive statistics will be used to summarize demographic and clinical characteristics of the sample. MCV will be the primary measure of hydroxyurea adherence and Hgb F and ANC will be secondary measures. If the final sample size is sufficiently large, we will conduct group-based trajectory modeling (GBTM) to analyze patterns of hydroxyurea adherence changes over time and identify hydroxyurea adherence trajectory subgroups. Multinomial logistic regression analyses will be used to analyze potential predictors of hydroxyurea adherence trajectory subgroup membership. Results: Preliminary results revealed that as of February 2017, 88% of eligible patients (based on age) were prescribed hydroxyurea.Data from the first 30 completed chart reviews indicates that half of the sample was female (sex assigned at birth), all identified as Black or African American, all but two participants had HbSS, and the mean age 13.0 years ( SD=8.0, range=2.47 to 26.81). Average MCV across an average of 21 time points ( SD=14.2, range=5-74) was 94.3 ( SD=11.2, range=58.4-114.2). As of February 2017, 53% of individuals had MCV values at or above 100. Specifically, 60% of 5-9 year olds, 47% of 10-15 year olds, and 46% of 16+ year olds had MCV values at or above 100. Average Hgb F across an average of 21 time points ( SD=15.3, range=3-81) was 22.9 ( SD=9.3, range=2.6-44.8). As of February 2017, 50% of individuals had HbF values at or above 20.0. Specifically, 55% of 5-9 year olds, 32% of 10-15 year olds, and 55% of 16+ year olds had HbF values at or above 20.0. Average ANC (at non-ill visits) across an average of 20.0 time points ( SD=13.6, range=5-71) was 3,965 ( SD=1,227; range=1,600-6,910). As of February 2017, 31% of individuals had ANC values less than 3,000. Specifically, 20% of 5-9 year olds, 34% of 10-15 year olds, and 30% of 16+ year olds had ANC values less than 3,000. Discussion:Results from this study have the potential to help researchers and clinicians better understand patterns and correlates of hydroxyurea adherence in pediatric SCD patients that can be targeted in future interventions.

Optimal adherence threshold to non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation to reduce the risk of thromboembolism and death

Abstract Background Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effects of NOACs is currently unknown. Purpose To investigate thresholds of NOAC adherence in association with thromboembolic and mortality risks. Methods Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 NOAC prescription claim between January 1st, 2013 and January 1st, 2019 were identified. Patients were followed from NOAC initiation until the first occurrence of the investigated outcome, treatment discontinuation (>60-day supply gap), switch to VKAs, death, emigration or end of the study period. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability weighted Cox regression (adjusting for 39 confounding covariates) was used to investigate outcomes (identified using International Classification of Diseases-coded hospital discharge diagnoses and medical procedure codes) between NOAC users with a one-year PDC of 100% (reference group) and NOAC users with lower PDCs. Results A total of 92,111 newly-treated AF patients were included during a mean follow-up of 2.7 ± 1.4 years (250,750 person-years of on-treatment follow-up). The proportions of persistent NOAC users with a PDC of 100%, 95-99%, 90-94%, 85-89%, 80-84% and <80% after one year of treatment were 62.7%, 17.4%, 9.5%, 5.1%, 2.8% and 2.5%, respectively. Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and <80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)) after multivariable adjustment. Significantly higher risks of all-cause mortality (aHR 1.09, 95%CI (1.01-1.17) and major or clinically relevant non-major bleeding (aHR 1.10, 95%CI (1.04-1.16) were observed with decreasing levels of NOAC adherence, starting from NOAC users with a one-year PDC of 90-94% versus 100%. Findings were similar with once-daily and twice-daily dosed NOACs. Conclusion Lower adherence to NOAC treatment is associated with increased risks of thromboembolism, all-cause mortality and bleeding. For adequate stroke prevention in AF, the optimal adherence threshold to NOAC treatment should be at least 90%, irrespective of the dosing regimen of NOACs.Figure 1

Pilot study of remote electronic patient-reported outcomes (ePRO) symptom monitoring of palliative care needs among outpatients with advanced solid cancers.

250 Background: Early specialty palliative care for patients with advanced cancer is an evidence-based practice that improves health outcomes, yet patients do not receive timely referrals. ePRO symptom monitoring provides a ready care delivery platform to monitor patients for unmet palliative care needs and direct palliative care referral based on patient report. This study sought to obtain feasibility data for ePRO symptom monitoring of palliative care needs. Methods: We conducted a single-arm pilot study of longitudinal ePRO symptom monitoring of multidimensional palliative care needs among outpatients with advanced breast, gastrointestinal, and gynecologic cancers at an academic oncology practice. Adult patients on active treatment with a prognosis > 6 months were approached consecutively. Patients completed baseline measures and enrolled on a third-party symptom monitoring platform for 12 weeks. Patients received weekly monitoring of 14 common symptoms using the National Cancer Institute's PRO version of the common terminology criteria for adverse events (PRO-CTCAEs). Patients received monthly monitoring of palliative needs using 11 PRO items from validated measures and a clinician-developed item for patient request for palliative care. Weekly symptom alerts and monthly palliative care PRO assessments were reported to the primary oncology team for interdisciplinary clinical management. Acceptability and appropriateness of the intervention were assessed using the Acceptability of Intervention Measure (AIM) and Intervention Appropriateness Measure (IAM). Results: From May 2022 to April 2023, 29 of 37 eligible patients (78%) consented to the study, of which 25 completed baseline measures and enrolled on the platform (68% enrollment rate; most common reason for refusal was not enough time). Median age was 53 years (range 29-77), 18 (72%) female, 12 (48%) non-Hispanic White, 32% reported an ECOG-PRO score 2-3. 96% of patients met pre-defined ePRO adherence thresholds and 92% completed study end measures (1 patient censored for death). Completion of the palliative PRO items was > 94% for 9 of 11 items. Two PRO items for spiritual distress screening were skipped most often. 80% of patients reported a severe score for at least one palliative PRO symptom during the study period. Mean AIM and IAM scores were 3.92 and 4.26, respectively (range 3.25 – 5; best possible total score 5). Conclusions: Expanding evidence-based ePRO symptom monitoring to include monthly palliative care needs assessment is highly feasible, acceptable, and appropriate to patients. Adherence to PRO items was high, and most patients had at least one area of need. Future work will refine the ePRO palliative assessment with attention to spiritual distress screening and determine severity thresholds to develop a PRO-directed referral system to specialty palliative care.

CPAP adherence after ambulatory and in-hospital management in patients aged 65 years and older

ABSTRACT Objectives The aims of this study are to evaluate the early adherence to CPAP treatment in patients aged 65 years and older and to compare ambulatory (ACPAP) and in-hospital (HCPAP) management in starting CPAP treatment. Methods Adherence to CPAP therapy at 3 months was retrospectively studied in patients on whom CPAP therapy was initiated between 1 January 2020 and 31 December 2021. Patients in the ACPAP group were selected based on the current Belgian reimbursement criteria (OAHI ≥30/h and few comorbidities). Results 146 patients were studied (median OAHI 43.35/h [32.02; 57.40]; median age 69 [67.0; 73.0]): 116 (79.5%) patients in the HCPAP and 30 (20.5%) in the ACPAP group. Based on an adherence threshold of average CPAP use of ≥ 4 hours per day, 120 (82%) patients were adherent to the treatment; 94 (81%) patients in the HCPAP and 26 (86.7%) in the ACPAP group. The median CPAP use for the total population was 6.4 h/day [4.89; 7.34], reaching 6.3 h/d [4.79; 7.15] for the HCPAP group and 6.8 h/d [6.21; 8.06] for the ACPAP group (p = 0.019). Insomnia was a significant risk factor for non-adherence (OR 5.16 [1.64; 16.08], p = 0.0043) but the ACPAP method was not (OR 0.66 [0.18; 1.91], p = 0.4748). Conclusion Early CPAP adherence in patients ≥ 65 years old was good in terms of average use per day and proportion of adherent patients. ACPAP method was not a risk factor for lower CPAP adherence in patients presenting severe OSAS (OAHI ≥30/h) and few comorbidities.

Minimal Adherence Threshold to Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation to Reduce the Risk of Thromboembolism and Death: A Nationwide Cohort Study.

Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effect of NOACs is currently unknown. Therefore, we investigated thresholds of NOAC adherence in association with thromboembolic and mortality risks. Patients with AF initiating NOACs between 2013 and 2019 were identified in Belgian nationwide data. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability of treatment weighted Cox regression was used to investigate outcomes. 92,111 persons were included (250,750 person-years). Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and < 80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)). Significantly higher risks of all-cause mortality were observed with decreasing levels of NOAC adherence, which were already higher among NOAC users with a one-year PDC of 90-94% versus 100% (aHR 1.09, 95%CI (1.01-1.17)). Findings were similar with once-daily and twice-daily dosed NOACs. Poor adherence to NOACs is associated with increased risks of thromboembolism and all-cause mortality. The minimal adherence threshold should be ≥ 90%, preferably even ≥ 95%.

0434 Long-Term Positive Airway Pressure Usage Disparities in Black or Hispanic of any Race Adults with OSA

Abstract Introduction Black or African American and Hispanic of any race (B/H) adults are disproportionately affected by obstructive sleep apnea (OSA). Positive Airway Pressure (PAP) treatment may reduce disparities, but short-term PAP outcomes are worse among under-represented minority (URM) adults compared to other, mainly White, adults. No studies have examined if adherence disparities persist/worsen long-term. We evaluated disparities in PAP usage between B/H adults and other race/ethnicities. Methods We defined a clinical cohort of adults with moderate-severe OSA (apnea-hypopnea index [AHI]≥15 events/h) that underwent diagnostic sleep studies and initiated PAP between 01/2015-03/2018. Logistic regression was used to examine differences in the likelihood of still using PAP or meeting adherence threshold of ≥4 hours/night at 18-24 months. We performed mixed model for repeated measures to examine differences in h/night of PAP use over two years. Analyses were controlled for age, sex, BMI, AHI, and 3-month PAP usage to understand whether disparities emerged independent of short-term differences. Results Analyses included 1,518 individuals (694 [45.7%] B/H) with PAP usage at 3 months, who were middle-aged (53.4±14.1 years-old), majority men (64.4%), obese (38.2±9.8 kg/m2) and had severe OSA (46.6±30.2 events/h). B/H adults had 70% higher odds (OR [95% CI] = 1.70 [1.33-2.17]) of no longer using PAP 18-24 months after initiation. B/H adults using PAP had ~2 hours/night less usage than other race/ethnicities at 18-24 months (2.72 [2.49-2.97] vs. 4.52 [4.31-4.73] hours/night; p&amp;lt; 0.0001). This difference was attenuated but remained significant after accounting for 3-month usage (mean [95% CI] difference = -0.64 [-0.92, -0.37] hours/night). B/H adults using PAP were also 3-times more likely to be non-adherent at 18-24 months (OR [95% CI] = 3.00 [2.28-2.95]), and remained 2-times more likely to be non-adherent controlling for 3-month usage (2.14 [1.56-2.92]). Conclusion At 18-24 months, Black or Hispanic of any race adults with moderate-severe OSA were less likely to use PAP, had less usage when still using PAP, and were less likely to achieve adherence thresholds. Long-term PAP disparities exist, even after accounting for short-term differences. Promoting longer-term PAP adherence for URM is a priority to reduce these disparities and address healthcare inequities. Support (if any) AHA (20CDA35310360), NIH P01 HL094307, AHRQ K12HS026372

0552 Predictive Characteristics of Run-In Period Adherence in a Randomized Controlled Trial

Abstract Introduction The run-in period has been used in randomized controlled trials in obstructive sleep apnea (OSA) to assess continuous positive airway pressure (CPAP) adherence. We hypothesize that there are differences in participant characteristics and PAP adherence between those excluded after the run-in period and those included in the final analytic sample of the Sleep Apnea Stress Study (SASS, NCT00607893), a trial designed to examine effect of PAP treatment on intermediate cardiovascular outcomes. Methods The SASS trial was designed to include a 2-week run-in period with a 1-month wash-out period. Patients with CPAP adherence &amp;gt;4 hours of CPAP use for 70% of run-in period nights were randomized. Demographic factors were compared among groups using analysis of variance (ANOVA) or Kruskal-Wallis test in continuous variables, Pearson’s chi-square test or Fisher’s exact test was used for categorical variables. Bonferroni correction was applied for pairwise comparisons. SAS version 9.4 (The SAS Institute Cary, NC) was used to perform all analyses. Results Fifty-nine participants(30.8%) who did not meet PAP adherence threshold were excluded after run-in period and compared to Sham and CPAP treatment group(n=74 in each group). Results are presented as excluded vs sham treatment vs CPAP treatment. Participants excluded after the run-in period were more likely to be female than those who proceeded to randomization: 66% vs. 47% vs. 45%,p=0.031 and of Black race:73% vs. 42% vs. 47%, p=0.002. Participants excluded after the run-in period and those non-adherent to treatment in sham and CPAP were younger than adherent participants: excluded: 48.9±12.0, sham non-adherent 49.7±12.3, CPAP non-adherent 47.7 ± 13.2, sham adherent 58.3±9.3, CPAP non-adherent 54.3 ± 9.4, p=0.014. In the run-in period, participants who were excluded had the median of number of days using the device 12 (IQR 7-15), mean of average daily use 2.8±2.1 hours and median percent of days with 4+ hours use 18.2% (IQR 0-57.1%). Conclusion We identify that age and race are predictors of run-in period non-adherence to PAP therapy underscoring the need to develop pre-randomization PAP adherence optimization strategies specific to these subgroups to ensure representation in the trial. Support (if any) This work was supported by NIH HL079114-02.

The Medication Possession Ratio as a Predictor of Longitudinal HIV-1 Viral Suppression.

Antiretroviral adherence is essential to achieve viral suppression and limit HIV-related morbidity and mortality; however, antiretroviral adherence thresholds to achieve viral suppression in clinical practice have not been fully characterized using administrative claims data. The purpose of this study was to assess the relationship between medication adherence and viral suppression among adult persons with HIV/AIDS (PWH) receiving antiretroviral therapy (ART) for ≥6 months. This historical cohort, real-world investigation assessed maintenance of viral load suppression and viral load area-under-the-curve (vAUC) in PWH ≥18 years of age based on ART adherence. A marginal effects model was used to determine the predicted probabilities of final plasma HIV-1 RNA <50 copies/mL or vAUC <1,000 copy-days/mL according to the medication possession ratio (MPR), estimated using a Jackknife model variance estimator and a delta-method for marginal effects standard error. Tests for statistical significance used a Šidák method to correct for multiple comparisons. The mean MPR for ART was 86.7% (95% CI: 85.0%-88.4%) for the 372 PWH included in the study. The marginal effects analysis indicated that an MPR ≥82% was associated with a predicted probability of viral suppression <50 copies/mL (P < 0.05). Significant predicted probabilities for vAUC <1,000 copy-days/mL were observed with an MPR ≥90% (P < 0.05). Medication possession ratio as a proxy for drug exposure was significantly and consistently associated with viral suppression using a longitudinal measure of HIV viremia. These findings can aid clinicians in the clinical management of PWH and inform future studies of adherence-viral suppression relationships with contemporary antiretroviral regimens.

Inaxaplin for Proteinuric Kidney Disease in Persons with Two APOL1 Variants

BackgroundPersons with toxic gain-of-function variants in the gene encoding apolipoprotein L1 (APOL1) are at greater risk for the development of rapidly progressive, proteinuric nephropathy. Despite the known genetic cause, therapies targeting proteinuric kidney disease in persons with two APOL1 variants (G1 or G2) are lacking.MethodsWe used tetracycline-inducible APOL1 human embryonic kidney (HEK293) cells to assess the ability of a small-molecule compound, inaxaplin, to inhibit APOL1 channel function. An APOL1 G2–homologous transgenic mouse model of proteinuric kidney disease was used to assess inaxaplin treatment for proteinuria. We then conducted a single-group, open-label, phase 2a clinical study in which inaxaplin was administered to participants who had two APOL1 variants, biopsy-proven focal segmental glomerulosclerosis, and proteinuria (urinary protein-to-creatinine ratio of ≥0.7 to <10 [with protein and creatinine both measured in grams] and an estimated glomerular filtration rate of ≥27 ml per minute per 1.73 m2 of body-surface area). Participants received inaxaplin daily for 13 weeks (15 mg for 2 weeks and 45 mg for 11 weeks) along with standard care. The primary outcome was the percent change from the baseline urinary protein-to-creatinine ratio at week 13 in participants who had at least 80% adherence to inaxaplin therapy. Safety was also assessed.ResultsIn preclinical studies, inaxaplin selectively inhibited APOL1 channel function in vitro and reduced proteinuria in the mouse model. Sixteen participants were enrolled in the phase 2a study. Among the 13 participants who were treated with inaxaplin and met the adherence threshold, the mean change from the baseline urinary protein-to-creatinine ratio at week 13 was −47.6% (95% confidence interval, −60.0 to −31.3). In an analysis that included all the participants regardless of adherence to inaxaplin therapy, reductions similar to those in the primary analysis were observed in all but 1 participant. Adverse events were mild or moderate in severity; none led to study discontinuation.ConclusionsTargeted inhibition of APOL1 channel function with inaxaplin reduced proteinuria in participants with two APOL1 variants and focal segmental glomerulosclerosis. (Funded by Vertex Pharmaceuticals; VX19-147-101 ClinicalTrials.gov number, NCT04340362.)

Community pharmacist intervention to optimize statin adherence in diabetes care: The GuIDE-S study

BackgroundStatin use in people with type 2 diabetes (T2D) reduces cardiovascular events, yet adherence remains suboptimal. ObjectiveThis study evaluated the impact of a community pharmacist intervention on statin adherence in new users with T2D. MethodsAs part of a quasi-experimental study, community pharmacy staff proactively identified adult patients with T2D who were not prescribed a statin. When appropriate, the pharmacist prescribed a statin via a collaborative practice agreement or facilitated acquisition of a prescription from another prescriber. Patients received individualized education and follow-up and monitoring for 1 year. Adherence was defined as the proportion of days covered (PDC) by a statin over 12 months. Linear and logistic regression were used to compare the effect of the intervention on continuous and a binary adherence threshold, defined as PDC ≥ 80%, respectively. ResultsOverall, 185 patients started statin therapy and were matched to 370 control patients for analysis. Adjusted average PDC was 3.1% higher in the intervention group (95% CI −0.037 to 0.098). Patients in the intervention group were 21.2% more likely to have PDC ≥ 80% (95% CI 0.828–1.774). ConclusionThe intervention resulted in higher statin adherence than usual care; however, the differences were not statistically significant.

Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement.

Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. Methods: An inter-professional, multidisciplinary, international committee with various stakeholders was formed. Three working groups (the historical policy origins, impact of current policy, and international PAP coverage models) met and performed literature reviews and discussions. Using surveys and an iterative discussion-based consensus process, the policy statement recommendations were created. Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities.

A Novel Algorithm to Improve PrEP Adherence Monitoring Using Dried Blood Spots.

Tenofovir diphosphate (TFVdp; an active metabolite of oral HIV pre-exposure prophylaxis (PrEP)) is measured in dried blood spots (DBS) to estimate adherence. However, TFVdp's long half-life in whole blood may lead to misclassification following a recent change in adherence. PrEP's other metabolite, emtricitabine triphosphate (FTCtp), has a shorter half-life in whole blood but adherence thresholds are undefined. We characterized DBS TFVdp and FTCtp concentrations across many dosing scenarios. Population pharmacokinetic models were fit to TFVdp and FTCtp DBS concentrations from a directly observed therapy study (NCT03218592). Concentrations were simulated for 90 days of daily dosing followed by 90 days of 1 to 7 doses/week and for event-driven PrEP (edPrEP) scenarios. Thresholds of 1,000 and 200 fmol/punch, for TFVdp and FTCtp, respectively, were reflective of taking 4 doses/week (a minimum target for effective PrEP in men). TFVdp was < 1,000 fmol/punch for 17 days after initiating daily PrEP and > 1,000 fmol/punch for 62 days after decreasing to 3 doses/week. Respectively, FTCtp was < 200 fmol/punch for 4 days and > 200 fmol/punch for 6 days. Accuracy of edPrEP adherence classification depended on duration between last sex act and DBS sampling for both measures with misclassification ranging from 9-100%. These data demonstrate adherence misclassification by DBS TFVdp for 2 months following a decline in adherence, elucidating the need for FTCtp to estimate recent adherence. We provide proof of principle that individualized interpretation is needed to support edPrEP adherence monitoring. Our collective approach facilitates clinicians' ability to interpret DBS results and administer patient-centric interventions.

Updating the Adherence-Response for Oral Emtricitabine/Tenofovir Disoproxil Fumarate for Human Immunodeficiency Virus Pre-Exposure Prophylaxis Among Cisgender Women.

Using intraerythrocytic tenofovir-diphosphate data from the emtricitabine/tenofovir disoproxil fumarate arms of HIV Prevention Trials Network (HPTN) 083 (men) and HPTN 084 (women), approximately 99% efficacy was achieved at a lower adherence threshold in HPTN 083 (≥2 doses/week) compared with HPTN 084 (daily), suggesting higher adherence is necessary for women vs men.