Longitudinal Adherence Research Articles

Hepatocellular Carcinoma Surveillance among Individuals with Cirrhosis: Trends by Payer, Etiology, and Calendar Year, from a Statewide, Multi-Payer Dataset, 2010-2018.

Hepatocellular carcinoma (HCC) surveillance is underutilized, with <25% of individuals with cirrhosis receiving surveillance exams as recommended. The epidemiology of cirrhosis and HCC in the United States has also shifted in recent years, but little is known about recent trends in surveillance utilization. We characterized patterns of HCC surveillance by payer, cirrhosis etiology, and calendar year in insured individuals with cirrhosis. We conducted a retrospective cohort study of individuals with cirrhosis using claims data from Medicare, Medicaid, and private insurance plans in North Carolina. We included individuals ≥ 18 years with a first occurrence of an ICD-9/10 code for cirrhosis between January 1, 2010, and June 30, 2018. The outcome was HCC surveillance by abdominal ultrasound, CT, or MRI. We estimated 1- and 2-year cumulative incidences for HCC surveillance and assessed longitudinal adherence to surveillance by computing the proportion of time covered (PTC). Among 46,052 individuals, 71% were enrolled through Medicare, 15% through Medicaid, and 14% through private insurance. The overall 1-year cumulative incidence of HCC surveillance was 49% and the 2-year cumulative incidence was 55%. For those with an initial screen in the first 6 months of their cirrhosis diagnosis, the median 2-year PTC was 67% (Q1, 38%; Q3, 100%). HCC surveillance initiation after cirrhosis diagnosis remains low, though it has improved slightly over time, particularly among individuals with Medicaid. This study provides insight into recent trends in HCC surveillance and highlights areas to target for future interventions, particularly among patients with nonviral etiologies.

Risk prediction for advanced neoplasia using longitudinal adherence measures to fecal immunochemical test-based colorectal cancer screening programs

BackgroundPatterns of longitudinal adherence may predict advanced neoplasia (AN) detection in subsequent rounds of colorectal cancer (CRC) screening. However, after more than five rounds, it is important to obtain a simplified measure. The aim was to determine the best simplified measure of longitudinal adherence to predict AN detection in CRC screening. MethodsIndividuals with four invitations from a Dutch Fecal immunochemical testing (FIT-)based pilot study and two Italian FIT-based CRC screening programs were included. We calculated AN detection in the fourth round, stratified by prior adherence. Five simplified measures were compared to full information (permutations) using chi-squared goodness-of-fit: adherence previous invitation, consistency, frequency, frequency + adherence previous invitation, and proportion of invitations covered. ResultsAN detection in the fourth round was highly dependent on prior adherence behavior. For inconsistent adherence, detection in the fourth round was strongly dependent on frequency and time since last participation. The performance of the simplified measures to capture this variation differed considerably. ‘Adherence previous invitation’ scored worst in predicting AN detection. ‘Frequency+adherence previous invitation’ had lowest chi-squared goodness-of-fit. DiscussionThe simplified measure ‘frequency+adherence previous invitation’ is the best measure to reflect patterns of longitudinal adherence and could be used to emphasize to individuals the importance of CRC screening.

High PrEP uptake and objective longitudinal adherence among HIV-exposed women with personal or partner plans for pregnancy in rural Uganda: A cohort study.

In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. We enrolled HIV-negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure ("high" adherence when pillbox was opened ≥80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not; concentrations TFV ≥40 ng/mL and TFV-DP ≥600 fmol/punch were categorized as "high." Women who became pregnant were initially exited from the cohort by design; from March 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion who initiated PrEP); and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI: 27.8 to 29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N = 118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI: 83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% [95% CI: 43%, 62%]) and 1 HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N = 17) was 98% (95% CI: 97%, 99%). Study design limitations include lack of a control group. Women in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment; serial measures of TFV-DP in whole blood suggest 41% to 47% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics. Future iterations of this work should compare the outcomes to current standard of care. ClinicalTrials.gov Identifier: NCT03832530 https://clinicaltrials.gov/ct2/show/NCT03832530?term=lynn+matthews&cond=hiv&cntry=UG&draw=2&rank=1.

Participation and adherence to mammography screening in the Capital Region of Denmark: The importance of age over time.

Mammography screening's effectiveness depends on high participation levels. Understanding adherence patterns over time is important for more accurately predicting future effectiveness. This study analyzed longitudinal adherence to the biennial invitations in the Capital Region of Denmark from 2008-2017. We analyzed participation rates for five-year age groups along with their percent changes in each invitation round using linear regressions. Participation in the mammography screening program increased from 73.1% to 83.1% from 2008-2017. The participation rate among all age groups increased from the first to the fifth round, with the oldest age group having the largest increase (average percent change = 3.66; p-value = 0.03).

Adherence to Canadian 24-Hour Movement Guidelines among infants and associations with development: a longitudinal study

BackgroundTo examine: 1) longitudinal adherence to the Canadian 24-Hour Movement Guidelines in a sample of infants and 2) associations between adherence to the guidelines over time and development.MethodsParticipants were 250 parent-infant dyads from the Early Movers project in Edmonton, Alberta. At 2, 4, and 6 months of age, physical activity, sedentary behaviour, sleep, and development were measured with a parental questionnaire that included items from the Ages & Stages Questionnaire (ASQ-3). Parents also reported the dates six major gross motor milestones were acquired during the first 18 months of life according to World Health Organization criteria. In a sub-sample (n = 93), movement behaviours were also measured with a time-use diary at 2, 4, and 6 months and gross motor development was measured by a physiotherapist using the Alberta Infant Motor Scale (AIMS) at 6 months. Guideline adherence was defined as: 1) ≥ 30 min/day of tummy time, 2) no screen time, some reading time, no restrained bouts > 1 h (time-use diary only), and 3) 14–17 h (2 months) or 12–16 h (4 and 6 months) of sleep per 24-h period. Generalized estimating equations were conducted as well as linear mixed models and linear regression models that adjusted for demographic characteristics.ResultsFew infants met the guidelines at all time-points (questionnaire: 2%; time-use diary: 0%). Infants that met a recommendation at 2 months, compared to those that did not, were 1.8–8.2 times more likely to meet that recommendation at subsequent time-points. Meeting more recommendations across time-points, according to both measures, was associated with a higher mean ASQ-3 gross motor score. Each additional time-point of tummy time recommendation adherence (questionnaire-measured) was associated with a 5–11-day earlier acquisition of independent sitting, crawling, and independent standing milestones. In the sub-sample, each additional time-point of guideline adherence was associated with a 16% higher AIMS score at 6 months.ConclusionsGuideline adherence was low across the first 6 months of infancy. Overall, meeting more recommendations over this period appeared important for gross motor development. Parents and caregivers should be targeted as early as possible with guideline dissemination and activation strategies to promote healthy infant development.

Examining nonadherence in the treatment of tuberculosis: The patterns that lead to failure.

Adherence has been shown to be a major predictor of tuberculosis treatment failure and relapse. The current adherence metrics can be improved to provide higher resolution of adherence patterns and identify patients in need of alternative treatment interventions. We investigated how adherence patterns affect treatment outcomes, when adherence is likely to decrease during treatment and which patients are at risk of being nonadherent. Individual-level data were pooled from 3 clinical trials (n =3724) for treatment of drug susceptible tuberculosis where monthly or weekly adherence patterns were collected and adherence patterns were quantified to assess the impact of clustered missed doses vs. randomly missed doses on tuberculosis treatment outcomes. Significance was determined through univariate and multivariate cox regression models. Patients who miss doses in clusters have an increased hazard risk for unfavourable outcomes and missing as little as 4 treatment days in 1 month resulted in 61% higher risk of unfavourable outcomes compared to patients who missed no treatment days (P < .01). Patients older than 50 years, and patients who experienced an adverse event were associated with lower adherence. Our results show that the pattern in which patients miss their drugs is important to their overall outcomes and missing treatment days in clusters rather than randomly increases the risk of poor outcomes. In the future more intensive and longitudinal adherence measurements will be valuable for clinical trials and regimen design and interpretation.

Longitudinal Adherence to Diabetes Quality Indicators and Cardiac Disease: A Nationwide Population-Based Historical Cohort Study of Patients With Pharmacologically Treated Diabetes.

Background Evidence of the cardiovascular benefits of adherence to quality indicators in diabetes care over a period of years is lacking. Methods and Results We conducted a population-based, historical cohort study of 105 656 people aged 45 to 80 with pharmacologically treated diabetes and who were free of cardiac disease in 2010. Data were retrieved from electronic medical records of the 4 Israeli health maintenance organizations. The association between level of adherence to national quality indicators (2006-2010: adherence assessment) and incidence of cardiac outcome; ischemic heart disease or heart failure (2011-2016: outcome assessment) was estimated using Cox proportional hazards models. During 529 551 person-years of follow-up, 19 246 patients experienced cardiac disease. An inverse dose-response association between the level of adherence and risk of cardiac morbidity was shown for most of the quality indicators. The associations were modified by age, with stronger associations among younger patients (<65 years). Low adherence to low-density lipoprotein cholesterol testing (≤2 years) during the first 5 years was associated with 41% increased risk of cardiac morbidity among younger patients. Patients who had uncontrolled low-density lipoprotein cholesterol in all first 5 years had hazard ratios of 1.60 (95% CI, 1.49-1.72) and 1.23 (95% CI, 1.14-1.32), among patients aged <65 and ≥65 years, respectively, compared with those who achieved target level. Patients who failed to achieve target levels of glycated hemoglobin or blood pressure had an increased risk (hazard ratios, 1.50-1.69) for cardiac outcomes. Conclusions Longitudinal adherence to quality indicators in diabetes care is associated with reduced risk of cardiac morbidity. Implementation of programs that measure and enhance quality of care may improve the health outcomes of people with diabetes.

Invited Commentary: Learning about Breast Cancer Outcomes in Asian Women to Close the Health Equity Gap.

Invited Commentary: Learning about Breast Cancer Outcomes in Asian Women to Close the Health Equity Gap.

Mobile health adherence for the detection of recurrent recent-onset atrial fibrillation

ObjectiveThe Rate Control versus Electrical Cardioversion Trial 7–Acute Cardioversion versus Wait and See trial compared early to delayed cardioversion for patients with recent-onset symptomatic atrial fibrillation (AF). This study aims...

Guidance for setting international standards on reporting longitudinal adherence to stool-based colorectal cancer screening

Longitudinal adherence to colorectal cancer (CRC) screening is reported using different summarizing measures, which hampers international comparison. We provide evidence to guide recommendations on which longitudinal adherence measure to report.Using adherence data over four stool-based CRC screening rounds in three countries, we calculated six summarizing adherence measures; adherence over all rounds, adherence per round, rescreening, full programme adherence (yes/no), regularity (never/inconsistent/consistent screenees) and number of times participated. For each measure, we calculated the accuracy in capturing the observed adherence patterns. Using the ASCCA model, we predicted screening effectiveness when using summarizing measures as model input versus the observed adherence patterns.Adherence over all rounds in the Italian, Spanish and Dutch cohorts was 64.9%, 42.8% and 61.5%, respectively, and the proportion of consistent screenees was 50.9%, 26.3% and 45.7%. Number of times participated and regularity were most accurate and resulted in similar model-predicted screening effectiveness as simulating the observed adherence patterns of Italy, Spain and the Netherlands (mortality reductions: 24.4%, 16.9% and 23.5%). Adherence over all rounds and adherence per round were least accurate. Screening effectiveness was overestimated when using adherence over all rounds (mortality reductions: 26.8%, 19.4% and 25.7%) and adherence per round (mortality reductions: 26.8%, 19.5% and 25.9%).To conclude, number of times participated and regularity were most accurate and resulted in similar model-predicted screening effectiveness as using the observed adherence patterns. However they require longitudinal data. To facilitate international comparison of CRC screening programme performance, consensus on an accurate adherence measure to report should be reached.

Adherence to professional society guidelines among women with stress or mixed urinary incontinence.

AimsThe objective of this analysis was to describe longitudinal adherence with recommended urinary incontinence (UI) evaluation and treatment guidelines over a 2‐year period in patients newly diagnosed with stress (SUI) or mixed UI (MUI), and average 2‐year cost associated with initial treatment.MethodsA retrospective claims analysis using the IBM MarketScan database was conducted. Women diagnosed with SUI/MUI between July 1, 2014 and June 30, 2016 were identified using the International Classification of Diseases (ICD) 9 and 10 codes for SUI or MUI. Newly diagnosed SUI/MUI patients who did not have a UI‐related diagnosis for at least 1 year before their index date were assessed.Results103 813 patients with newly diagnosed SUI or MUI were identified. Of those, 96.15% (99 821/103 813) received an initial evaluation in accordance with professional guidelines (e.g., patient history, physical examination, urinalysis). Only 6.8% (5086/74 925) and 7.7% (2229/28 888) of patients with SUI and MUI, respectively, received a first‐line behavioral treatment (e.g., pelvic floor muscle exercises, bladder training), according to guidelines. The 2‐year average UI‐related medical costs associated with guideline adherence for SUI were $5770.93 ± $9454.81 and for MUI, $4416.16 ± $7401.53. Nonadherence was observed in 59.2% (44 382/74 925) of SUI and 64.1% (18 530/28 888) of MUI patients. Two‐year average UI‐related medical costs for the nonadherent group were $8568.00 ± $11 275.52 for SUI and $6986.66 ± $10 765.55 for MUI, significantly more than the adherent group (p < 0.0001).ConclusionThe majority of SUI or MUI patients do not receive a documented behavioral intervention as their first‐line treatment, which is a recommendation by professional society guidelines. This was found to affect the cost burden for payers; those that were nonadherent had significantly higher costs 2‐year postindex.

Impaired Human Sexual and Erectile Function Affecting Semen Quality, in Obstructive Sleep Apnea: A Pilot Study.

Obstructive sleep apnea (OSA) is a rising problem, with important implications for public health. Recent evidence has revealed a link between OSA and reduced male fertility. We investigated the association between OSA and sexual and erectile function, as well as semen quality, and the effect of treatment by continuous positive airway pressure (CPAP). A total of 41 male subjects, who underwent polysomnography for suspected OSA, participated in the study. Erectile and sexual function were assessed with the 15-item International Index of Erectile Function (IIEF-15) questionnaire, blood samples, and sperm analysis. OSA patients after the initiation of CPAP treatment were followed for a period of 1 year. Thirty-two patients were diagnosed with OSA, and nine subjects without OSA were used as a control group. OSA patients demonstrated significantly impaired erectile function, reduced testosterone levels, and lower semen quality. Multivariable regression analysis showed that BMI and IIEF score were independent determinants of AHI. Sexual function improved after a year of CPAP therapy in OSA patients. This study provides further evidence regarding the association between OSA and erectile function impairment, as well as semen quality. Longitudinal adherence to CPAP treatment has a beneficial effect on erectile function.

Characterizing HIV-Preventive, Plasma Tenofovir Concentrations-A Pooled Participant-level Data Analysis From Human Immunodeficiency Virus Preexposure Prophylaxis Clinical Trials.

Daily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration. Participant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models. Around 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels. Using the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.

Time Trend Analysis of Tuberculosis Treatment While Using Digital Adherence Technologies-An Individual Patient Data Meta-Analysis of Eleven Projects across Ten High Tuberculosis-Burden Countries.

Worldwide, non-adherence to tuberculosis (TB) treatment is problematic. Digital adherence technologies (DATs) offer a person-centered approach to support and monitor treatment. We explored adherence over time while using DATs. We conducted a meta-analysis on anonymized longitudinal adherence data for drug-susceptible (DS) TB (n = 4515) and drug-resistant (DR) TB (n = 473) populations from 11 DAT projects. Using Tobit regression, we assessed adherence for six months of treatment across sex, age, project enrolment phase, DAT-type, health care facility (HCF), and project. We found that DATs recorded high levels of adherence throughout treatment: 80% to 71% of DS-TB patients had ≥90% adherence in month 1 and 6, respectively, and 73% to 75% for DR-TB patients. Adherence increased between month 1 and 2 (DS-TB and DR-TB populations), then decreased (DS-TB). Males displayed lower adherence and steeper decreases than females (DS-TB). DS-TB patients aged 15–34 years compared to those >50 years displayed steeper decreases. Adherence was correlated within HCFs and differed between projects. TB treatment adherence decreased over time and differed between subgroups, suggesting that over time, some patients are at risk for non-adherence. The real-time monitoring of medication adherence using DATs provides opportunities for health care workers to identify patients who need greater levels of adherence support.

Adherence to contemporary antiretroviral treatment regimens and impact on immunological and virologic outcomes in a US healthcare system

Only a few recent reports have examined longitudinal adherence patterns in US clinics and its impact on immunological and virological outcomes among large cohorts initiating contemporary antiretroviral therapy (ART) in US clinics. We followed all persons with HIV (PLWH) in a California clinic population initiating ART between 2010 and 2017. We estimated longitudinal adherence for each PLWH by calculating the medication possession ratio within multiple 6-month intervals using pharmacy refill records. During the study, 2315 PWLH were followed for a median time of 210.8 weeks and only 179 (7.7%) were lost-to-follow-up. The mean adherence was 84.9%. Age (Hazard Ratio (HR): (95% confidence interval): 1.25 (1.20-1.31) per 10-year increase) and Black race (HR: 0.62 (0.53-0.73) vs. White) were associated with adherence in the cohort. A 10% percent increase in adherence increased the odds of being virally suppressed by 37% (OR and 95% CI: 1.37 [1.33-1.41]) and was associated with an increase in mean CD4 count by 8.54 cells/ul in the next 6-month interval (p-value <0.0001). Our study shows that despite large improvements in retention in care, demographic disparities in adherence to ART persist. Adherence was lower among younger patients and black patients. Our study confirmed the strong association between adherence to ART and viral suppression but could only establish a weak association between adherence and CD4 count. These findings reaffirm the importance of adherence and retention in care and further highlight the need for tailored patient-centered HIV Care Models as a strategy to improve PLWH's outcomes.

Longitudinal Adherence to Inhaled Corticosteroids in Pediatric Patients with Difficult to Control Asthma

The purpose of this study is to examine adherence to inhaled corticosteroids in children with difficult-to-treat (DTT) asthma, in whom poor adherence is known to lead to poor outcomes. Participants received multi-modal treatment strategy including a digital adherence intervention.

Three Sides to the Story: Adherence Trajectories During the First Year of SGLT2 Inhibitor Therapy Among Medicare Beneficiaries.

We aimed to understand the factors associated with sodium-glucose cotransporter 2 inhibitor (SGLT2i) adherence and longitudinal adherence trajectories in older adults with type 2 diabetes. Using Medicare claims data (April 2013-December 2017), we identified 83,675 new SGLT2i users ≥66 years old with type 2 diabetes. We measured SGLT2i adherence as the proportion of days covered (PDC) during the first year of SGLT2i therapy. We used linear regression to assess the association between baseline covariates and PDC. Then we used group-based trajectory modeling to identify distinct longitudinal SGLT2i adherence groups and used a multivariable logistic regression model to examine the association between baseline covariates and membership in these adherence groups. Unadjusted mean PDC was 63%. Previous adherence to statins had the strongest positive association with PDC (regression coefficient 6.00% [95% CI 5.50, 6.50]), whereas female sex (-5.51% [-6.02, -5.00]), and Black race/ethnicity (-5.06% [-6.03, -4.09]) had the strongest negative association. We identified three adherence trajectory groups: low (23% of patients, mean PDC 17%), moderate (32%, mean PDC 50%), and high (45%, mean PDC 96%) adherence. More patients in the high adherence group were previously adherent to statins (odds ratio 1.43 [95% CI 1.39, 1.48]), and more women (1.28 [1.23, 1.32]) and Black patients (1.31 [1.23, 1.40]) were in the low adherence group. In a large population of older patients with type 2 diabetes, 45% were highly adherent during the first year of SGLT2i treatment. Female sex and Black race/ethnicity were most strongly associated with low adherence.

Long-term Mammography Adherence among Uninsured Women Enrolled in the Breast Screening and Patient Navigation (BSPAN) Program.

The Breast Screening and Patient Navigation (BSPAN) Program provides access to no-cost breast cancer screening services to uninsured women in North Texas. Using data from the longitudinal BSPAN program (2012-2019), we assessed prevalence and correlates of (i) baseline adherence and (ii) longitudinal adherence to screening mammograms. Outcomes were baseline adherence (adherent if women received second mammogram 9-30 months after the index mammogram) and longitudinal adherence (assessed among baseline adherent women and defined as being adherent 39 months from the index mammogram). We used multivariable logistic regression and multivariable Cox proportional hazards model to assess associations of sociodemographic and clinical characteristics with baseline and longitudinal adherence, respectively. Of 19,292 women, only 5,382 (27.9%) were baseline adherent. Baseline adherence was more likely among women who were partnered, preferred speaking Spanish, had poor reading ability, had prior Papanicolaou (PAP) testing, and prior screening mammograms, compared with women who were non-partnered, preferred speaking English, had good reading ability, had no prior PAP testing, and no prior screening mammograms, respectively. Of those who were baseline adherent, 4,364 (81.1%) women demonstrated longitudinal adherence. Correlates of longitudinal adherence were similar to those from baseline adherence. A large proportion of baseline adherent women (>80%) achieved longitudinal adherence, which highlights the importance of concentrating resources during the second mammogram in the progression toward continued adherence. Results from our unique dataset provide realistic mammography adherence rates and may be generalizable to other areas introducing no-cost screening to low-income women, independent of any regular patient-centered medical home.

Mammography adherence in relation to function-related indicators in older women

Prior studies of screening mammography patterns by functional status in older women show inconsistent results. We used Breast Cancer Surveillance Consortium-Medicare linked data (1999–2014) to investigate the association of functional limitations with adherence to screening mammography in 145,478 women aged 66–74 years. Functional limitation was represented by a claims-based function-related indicator (FRI) score which incorporated 16 items reflecting functional status. Baseline adherence was defined as mammography utilization 9–30 months after the index screening mammography. Longitudinal adherence was examined among women adherent at baseline and defined as time from the index mammography to end of the first 30-month gap in mammography. Multivariable logistic regression and Cox proportional hazards models were used to investigate baseline and longitudinal adherence, respectively. Subgroup analyses were conducted by age (66–70 vs. 71–74 years). Overall, 69.6% of participants had no substantial functional limitation (FRI score 0), 23.5% had some substantial limitations (FRI score 1), and 6.8% had serious limitations (FRI score ≥ 2). Mean age at baseline was 68.5 years (SD = 2.6), 85.3% of participants were white, and 77.1% were adherent to screening mammography at baseline. Women with a higher FRI score were more likely to be non-adherent at baseline (FRI ≥ 2 vs. 0: aOR = 1.13, 95% CI = 1.06, 1.20, p-trend < 0.01). Similarly, a higher FRI score was associated with longitudinal non-adherence (FRI ≥ 2 vs. 0: aHR = 1.16, 95% CI = 1.11, 1.22, p-trend < 0.01). Effect measures of FRI did not differ substantially by age categories. Older women with a higher burden of functional limitations are less likely to be adherent to screening mammography recommendations.

Adherence Trajectories of Extended Direct-Acting Oral Anticoagulants and Risk of Recurrent Venous Thromboembolism and Major Bleeding: A Retrospective Cohort Study

▪Introduction: The optimal duration of extended oral anticoagulant treatment for patients with venous thromboembolism (VTE) beyond the initial 3 to 6 months of the treatment remains undetermined. Group-based trajectory modeling (GBTM) is a data-driven method that can categorize patients with similar longitudinal adherence patterns over time into distinct subgroups. This study identified distinct patient subgroups with similar adherence trajectories of extended treatment of direct-acting oral anticoagulants (DOACs), and then examined the association between adherence trajectories and the risk of recurrent VTE and major bleeding among patients with VTE.Methods: We identified patients ≥18 years with a diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) from inpatient claims using 2013-2019 Truven Commercial and Medicare Supplemental database. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy-defined as ≥83% proportion days covered (PDC) with oral anticoagulants during the initial 6-month treatment period, and had extended treatment with any DOACs or no extended therapy. Based on the monthly PDC as the DOAC adherence measure, we used GBTM to identify DOAC adherence trajectories during 6 months of the extended treatment. The final trajectory model was chosen by assessing the Bayesian information criteria, Nagin's criteria, and having at least 10% of patients in each trajectory group for improving clinical utility. We compared recurrent VTE and major bleeding among adherence trajectory subgroups. Patients were followed up from the initiation of the extended treatment until the occurrence of the study outcomes, discontinuation of DOACs, switching to warfarin, end of study period, or end of enrollment, whichever occurred first. Cox proportional hazard modeling with inverse probability treatment weighting (IPTW) was used to obtain hazard ratios (HR) and 95% confidence intervals (95% CI).Results: The study cohort (mean age=58.7 years and 51.1% males) consisted of 10,960 patients with extended treatment of DOACs (4,294 apixaban, 6,409 rivaroxaban, 238 dabigatran, and 19 edoxaban users) with a mean treatment duration of 7.7 months and 5,133 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The final GBTM models identified four distinct adherence trajectories for extended therapy including (1) patients with consistent adherence (group 1, 40.7%), (2) patients with gradually declining adherence (group 2, 14.3%), (3) patients with rapidly declining adherence (group 3, 13.1%), and (4) patients with no extended treatment (reference group, 31.9%) (Figure 1). The incidence rates of recurrent VTE were 18.6, 46.9, 84.1, and 160.7 per 10,000 person-years, and those of major bleeding were 61.0, 125.1, 168.3, and 48.7 per 10,000 person-years in group 1, group 2, group 3, and the reference group, respectively. After IPTW, demographics and clinical characteristics (e.g., HAS-BLED bleeding risk score, provoked VTE) were comparable across the four trajectory groups with <0.1 of the standardized mean difference for each pairwise comparison. Compared to the reference group, group 1 (HR=0.09, 95% CI=0.05-0.17) and group 2 (HR=0.16, 95% CI=0.04-0.58) had decreased risk of recurrent VTE without increasing risk of major bleeding (HR=1.26, 95% CI=0.76-2.10 in group 1, HR=2.28, 95% CI=0.96-5.36 in group 2). There was no difference in the risk of recurrent VTE (HR=0.32, 95% CI=0.09-1.16) in group 3 but they had an increased risk of major bleeding (HR=2.69, 95% CI=1.00-7.23). The findings were consistent across different types of DOACs, suggesting a class effect of DOACs as extended therapy.Conclusions: We identified 4 distinct trajectories of DOAC adherence during the 6 months of extended therapy among patients who completed 6 months of initial treatment. Compared to no extended treatment, persistent use of DOACs during extended treatment was associated with a lower risk of recurrent VTE without increasing major bleeding risk, whereas a rapid decline in adherence was associated with an increased risk of major bleeding with no difference in the risk of recurrence. Our findings provide evidence on the benefits of continuing and being adherent to extended anticoagulant treatment in patients with VTE without increasing the risk of major bleeding. [Display omitted] DisclosuresKang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Jones: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; MERCK: Research Funding. DeRemer: BMS advisory board attendee: Honoraria; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. Park: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding.