Daily Adherence Research Articles

Social Inequity and Structural Barriers to Completion of Ecological Momentary Assessments for Young Men Who Have Sex With Men and Trans Women Living With HIV in San Francisco.

BackgroundEcological momentary assessments (EMAs) administered via text messaging facilitate real-time data collection. With widespread cell phone access, EMAs are becoming more available to even the most disenfranchised communities, such as those living with HIV. However, structural barriers disproportionately burden young men who have sex with men (MSM) and trans women (TW) living with HIV and threaten participation in HIV research.ObjectiveWe aim to identify structural barriers to completing EMA text surveys nested within a digital HIV care intervention for young MSM and TW living with HIV in San Francisco.MethodsA total of 10,800 EMA text messages were delivered daily over 90 days to 120 participants enrolled in the Health eNav intervention (2017-2018) at the San Francisco Department of Public Health. EMA surveys inquired about participants’ daily affect, sexual behaviors, substance use, and treatment adherence. Survey completion was calculated after 30, 60, and 90 days of follow-up. We described characteristics of nonstarters (those who provided less than four complete responses to the first seven EMA surveys) and analyzed structural correlates of days to first weeklong or more EMA survey noncompletion using multivariable Cox proportional hazards regression. Qualitative interviews were used to evaluate the acceptability of EMA surveys.ResultsParticipants completed 4384 of 10,800 (40.59%) EMA surveys. Completion of 70% or more of EMA surveys was attained by 56 of 120 participants (46.7%) at 30 days of follow-up, 40/120 (33.3%) at 60 days of follow-up, and 30/120 (25.0%) by the end of the 90-day study period. Twenty-eight participants (23.3%) were identified as nonstarters, and were more likely to be recently incarcerated (prevalence ratio [PR] 2.3, 95% CI 1.3-4.4), forego basic needs for HIV medications (PR 2.4, 95% CI 1.3-4.5), and be diagnosed with HIV in the last year (PR 2.2, 95% CI 1.1-4.1). Adjusting for nonstarters, young MSM and TW living in temporary/transitional housing (adjusted hazard ratio [aHR] 1.8, 95% CI 1.1-3.0), foregoing HIV medications to afford basic needs (aHR 1.7, 95% CI 1.1-2.7), and having less than a college education (aHR 3.5, 95% CI 1.4-9.0) had greater hazard of weeklong or more EMA survey noncompletion. Overall, there was high acceptability of the EMA surveys.ConclusionsAlthough access to and use of technology is increasingly ubiquitous, this analysis demonstrates persisting gaps in EMA completion by socioeconomic factors such as incarceration, education level, housing, and competing needs for young MSM and TW living with HIV in San Francisco. Moreover, those recently diagnosed with HIV were more likely to experience an immediate drop-off in completing EMA surveys. EMAs are feasible for individuals not experiencing social inequity and structural barriers. HIV prevention technologies addressing these barriers and leveraging similar methodology may prove effective for young MSM and TW living with HIV.

Tenofovir-Diphosphate as a Marker of HIV Pre-exposure Prophylaxis Use Among East African Men and Women.

Background: Controlled pharmacokinetic (PK) studies in United States populations have defined categories of tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) for various pre-exposure prophylaxis (PrEP) adherence targets. It is unknown how these categories perform in other populations. Therefore, we evaluated the sensitivity and specificity of these PK-derived categories compared to daily medication electronic adherence monitoring (MEMS) data among East African men and women using daily PrEP.Methods: Participants were enrolled as members of HIV serodiscordant couples as part of an open-label PrEP study in Kenya and Uganda. Blood samples were taken at quarterly visits and stored as DBS, which were analyzed for TFV-DP concentrations.Results: Among 150 samples from 103 participants, MEMs data indicated that 87 (58%) took ≥4 doses and 62 (41%) took ≥6 per week consistently over the 4 weeks prior to sample collection. Sensitivities of DBS TFV-DP levels were 62% for the ≥4 doses/week category (≥700 fmol/punch TFV-DP) and 44% for the ≥6 doses/week category (≥1050 fmol/punch TFV-DP); specificities were 86 and 94%, respectively. There were no statistically significant differences in these sensitivities and specificities by gender.Conclusion: In this sample of East African PrEP users, categories of TFV-DP concentrations developed from directly observed PrEP use among United States populations had high specificity but lower than expected sensitivity. Sensitivity was lowest when MEMS data indicated high adherence (i.e., ≥6 doses/week). PrEP studies and implementation programs should carefully consider the sensitivity and specificity of the TFV-DP levels used for adherence feedback.

Measuring the Implementation of Lifestyle-Integrated Functional Exercise in Primary Care for Older Adults: Results of a Feasibility Study.

ABSTRACTOur pilot study evaluated the feasibility, effectiveness, and implementation of a group-based lifestyle-integrated functional exercise (Mi-LiFE) program for older adults in an interprofessional primary care practice. A physical therapist taught participants how to integrate strength and balance activities into daily routines during one individual and four group sessions, and two follow-up phone calls. Feasibility outcomes were recruitment, adherence, and retention over 6 months. Physical activity (PA) (accelerometer, International Physical Activity Questionnaire [IPAQ]), Short Physical Performance Battery (SPPB), and health-related quality of life (EuroQol Five-Dimensional Questionnaire with 3 Levels [EQ5D-3L]) were evaluated at baseline and 6 months. Of the 123 eligible individuals, 39 per cent participated and 61 per cent were not interested or unreachable. Forty-eight participants (mean ± standard deviation [SD] age = 81 ± 5 years; body mass index [BMI] = 28 ± 5 kg/m2; 60% women; moderate-to-vigorous PA = 49 ± 87 minutes/week) enrolled. Four participants withdrew prior to intervention. Thirty-two participants (67%) were retained at follow-up. Daily diary-documented adherence was 50 per cent at 6 months, and 77 per cent attended more than four sessions. No statistically significant changes in moderate-to-vigorous PA and SPPB outcomes were observed; yet self-reported strength and balance PA and quality of life significantly improved at follow-up. The Mi-LiFE program is feasible with acceptable recruitment and attendance rates alongside modifications to address retention and adherence challenges. These findings inform the feasibility of future pragmatic exercise programs in primary care for older adults.

Modeling lottery incentives for daily adherence.

Many health issues require adherence to recommended daily activities, such as taking medication to manage a chronic condition, walking a certain distance to promote weight loss, or measuring weights to assess fluid balance in heart failure. The cost of nonadherence can be high, with respect to both individual health outcomes and the healthcare system. Incentivizing adherence to daily activities can promote better health in patients and populations and potentially provide long‐term cost savings.Multiple incentive structures are possible. We focus here on a daily lottery incentive in which payment occurs when both the participant's lottery number matches the number drawn and the participant adheres to the targeted daily behavior.Our objective is to model the lottery's effect on participants' probability to complete the targeted task, particularly over the short term. We combine two procedures for analyzing such binary time series: a parameter‐driven regression model with an autocorrelated latent process and a comparative interrupted time series. We use the output of the regression model as the control generator for the comparative time series in order to create a quasi‐experimental design.

Quality Metrics for Antimicrobial Stewardship Programs.

Antimicrobial stewardship programs (ASPs) are targeted to optimize antimicrobial use. However, pediatric metrics used to measure outcomes of ASPs are not well established. Our aim for this project was to identify, refine, and develop consensus on standard metrics for pediatric ASPs. By using a modified Delphi process, 2 surveys were sent to experts and stakeholders to establish consensus on the utility of metrics. These were subdivided into 4 ASP domains: (1) antimicrobial consumption, (2) microbiologic outcomes, (3) clinical outcomes, and (4) process measures. Respondents were asked to rank the scientific merit, impact, feasibility, and accountability of each metric. Metrics with ≥75% agreement for scientific merit were included and metrics with ≤25% agreement were discarded. Consensus was finalized with a face-to-face meeting and final survey. Thirty-eight participants from 15 pediatric hospitals across Canada completed all 3 rounds of the Delphi survey. In the domain of antimicrobial consumption, the 2 selected metrics were (1) days of therapy per 1000 patient-days and (2) total antimicrobial days. The clinical and process outcomes chosen were (1) 30-day readmission rate and (2) adherence to ASP recommendations, respectively. A microbiologic outcome was felt to be important and feasible, but consensus could not be obtained on a measure. Several barriers to implementation of the metrics were identified, including information technology limitations at various centers. We obtained consensus on 4 metrics to evaluate pediatric antimicrobial stewardship activities in Canada. Adoption of these metrics by pediatric ASPs will facilitate measurement of outcomes nationally and internationally.

The Role of Pharmacy Refill Measures in Assessing Adherence and Predicting HIV Disease Markers in Youth with Perinatally-Acquired HIV (PHIV).

Antiretroviral (ARV) adherence is critical in monitoring disease response in youth with perinatally-acquired HIV (PHIV). We used pharmacy refill (PR) information for PHIV youth from the PHACS Memory Sub-study to calculate medication availability over 2, 4, and 6months. PR, a proxy of adherence, was compared with self-reported 7-day adherence in predicting suppressed viral load (SVL < 400copies/mL) and higher CD4% (≥ 25%). Among 159 PHIV youth, 79% were adherent by 7-day recall, and 62, 55, and 48% by PR over 2, 4, and 6months, respectively. Agreement between 7-day recall and PR adherence was weak (Kappa = 0.09-0.25). In adjusted logistic regression models, adherence showed associations with SVL for 7-day recall (OR 2.78, 95% CI 1.08, 7.15) and all PR coverage periods (6-month: OR 3.24, 95% CI 1.22, 8.65). Similar associations were observed with higher CD4%. PR measures were predictive of study retention. Findings suggest a possibly independent role of PR adherence measures.

HSR19-112: Qualitative Development of a Patient-Reported Outcome Measure of Symptom Burden in Breast Cancer

Background: The use of disease-specific patient-reported outcomes (PROs) is critical for facilitating individualized symptom monitoring and improving cancer patient outcomes. The MD Anderson Symptom Inventory (MDASI) is a PRO measure of symptom burden. The purpose of this study was to describe the patient experience and define the content domain for the MDASI module specific to breast cancer (MDASI-Br). Methods: 36 patients with breast cancer across the disease and treatment continuum described their experience in single qualitative interviews. Content analysis was used to define the symptom burden content domain. An expert panel scored the relevance on a 0–4 scale (4 = relevant) of the symptoms identified from the qualitative interviews. Symptoms were selected for inclusion in the MDASI-Br if they met at least 1 of the following criteria: (1) mean relevance rating of ≥3 by the expert panel, (2) described by ≥20% of patients in qualitative interviews, or (3) core MDASI items. Results: Participants had a mean age of 57.9 years, 86.1% had stage I–III, and 52.8% were on active treatment. 36 symptoms were identified, with 14 reported by ≥20% of participants. Symptoms varied among participants based on disease stage and treatment modality. Fatigue and distress were described by most women regardless of treatment, whereas arm swelling was reported only by women who had undergone surgery, and skin changes were reported primarily by women who received radiation therapy. Patients volunteered ways in which symptoms affected daily functioning. 21 symptoms were included in the MDASI-Br for psychometric testing, including 6 breast cancer-specific symptoms: breast changes, hot flashes, constipation, arm swelling, fingernail or toenail changes, and skin changes. Two additional symptoms, vaginal dryness and decrease in sexual interest or activity, were included because they are common to endocrine therapy. Conclusions: Patients with breast cancer experience numerous but distinct symptoms related to disease and treatment that may result in interference with daily activities, relationships, life plans, treatment adherence, and mood. Various treatments result in unique symptom burden. The content domain for a PRO symptom-burden measure of breast cancer encompasses the diversity, severity, and activity interference of common symptoms of breast cancer and its treatment.

Current opinion in ophthalmology: novel glaucoma devices in the pipeline.

Adherence to chronic use of topical intraocular pressure (IOP) lowering medications is a fundamental barrier to successful, long-term control in patients suffering from glaucoma. This has fueled innovation to create new vehicles for drug administration, new drug formulations with enhanced bioavailability, and minimally invasive glaucoma surgeries (MIGS) with improved risk-benefit profiles to enhance sustained IOP control. The present article is an overview of novel devices in the pipeline. Several new devices that promise to deliver sustained drug therapy and reduce dependence on daily patient adherence are currently being vetted through clinical trials. In addition, the pipeline for new MIGS devices that target sustained IOP control continues to grow. Alternative drug delivery approaches and novel MIGS devices broaden the treatment options for patients with glaucoma. This will allow the clinician to customize treatment by selecting specific approaches based on each patient's individual needs and coexisting ocular pathologies. Additional comprehensive, large-scale, clinical studies will help define the role that these options hold in a constantly evolving treatment paradigm.

Vulnerable Periods: Characterizing Patterns of Sexual Risk and Substance Use During Lapses in Adherence to HIV Pre-exposure Prophylaxis Among Men Who Have Sex With Men.

Pre-exposure prophylaxis (PrEP) is highly efficacious, but some groups of men who have sex with men may have difficulty adhering to daily dosing. Prevention-effective adherence suggests that PrEP's efficacy depends on adherence at the time of HIV exposure; yet, few studies have examined how exposures (ie, high-risk sex) overlap with periods of consecutive missed PrEP doses. Substance use may also play a role in these vulnerable periods. We used digital pill bottles to monitor the daily adherence of 40 PrEP-experienced patients recruited from an outpatient clinic in the Northeastern US over a six-month period. Participants also completed detailed online diaries every 2 weeks during this time that surveyed their sexual behavior and substance use each day. Daily adherence was high overall (M = 83.9%, SD = 18.0%), but 53% (N = 21) had a lapse of > 3 consecutive daily PrEP doses over 6 months. Participants' rate of engaging in high-risk condomless anal sex (CAS) did not differ across lapse days versus continuously adherent days. Alcohol use was not associated with engaging in CAS during a PrEP lapse. However, participants reported engaging in CAS significantly more often during a PrEP adherence lapse on days when they also used stimulant drugs. Men who have sex with men may have periodic difficulty adhering to PrEP at the specific times when they are at risk. Stimulant drug use could play an important role in increasing HIV risk specifically during adherence lapses.

Evaluation of an Incentive-based Intervention to Improve 90-day Adherence in PAP-Naive Patients

Evaluation of an Incentive-based Intervention to Improve 90-day Adherence in PAP-Naive Patients

Centers for Medicare and Medicaid Services Positive Airway Pressure Adherence Criteria May Limit Treatment to Many Medicare Beneficiaries.

Centers for Medicare and Medicaid Services (CMS) reimbursement for positive airway pressure (PAP) devices for obstructive sleep apnea treatment is dependent on patients meeting adherence expectations within the first 3 months on therapy. Adherence is defined as usage of the device for at least 4 hours per night on 70% of nights during a consecutive 30-day period. We hypothesize that the adherence pattern may be established beyond this initial period, which may limit the opportunity to treat many patients. Treatment and adherence data from PAP devices were monitored via wireless modems for 42 consecutive PAP-naïve military veterans who completed 1 year of nightly monitoring. Their baseline characteristics were as follows: age (mean ± standard deviation) 58.5 ± 12.5 years; body mass index 33.7 ± 5.7 kg/m2; diagnostic apnea-hypopnea index (pretreatment) 28.1 ± 18.5 events/h; apnea-hypopnea index on PAP: 4.3 ± 3.3 events/h. We examined daily, monthly, quarterly, semiannual, and annual reports, and the best 30-day adherence report for each quarter. In the first 3 months, 19 of 42 participants were adherent by CMS criteria, and 23 of 42 participants were not. Of the 19 adherent participants, 13 remained adherent and 6 became nonadherent or stopped PAP treatment for the remainder of the year. In the 23 initially nonadherent participants, 16 stopped PAP treatment, and 7 participants (30.4%) became adherent (using CMS criteria) during the rest of the year. Thus, PAP adherence during the first 3 months was predictive for the rest of the year in only 68.4%. PAP nonadherence during the first 3 months was predictive for further nonadherence in only 69.6% of the cases. Overall, this led to a 65% sensitivity and 72% specificity of using adherence at 3 months in predicting adherence at 1 year. CMS adherence criteria affecting PAP coverage are restrictive and can result in the withholding of therapy in many patients who otherwise might become adherent. Registry: ClinicalTrials.gov, Title: Remote Monitoring in Obstructive Sleep Apnea, Identifier: NCT01678560, URL: https:// clinicaltrials.gov/ct2/show/NCT01678560.

Home Care Program Increases the Engagement in Patients With Heart Failure

Heart failure patients seen in the outpatient home care setting and in cardiology clinics have repeated emergency department visits, hospital admissions, and readmissions despite receiving education about their medications diet and self-care interventions such as daily weights. The objective of this evidence-based practice change was to determine, in home care patients, whether the use of standardized teach-back methodology educational materials would improve their knowledge and confidence in the self-care of their chronic disease. Of the 22 patients enrolled, 15 were not readmitted to the hospital within 9 months of home care admission. The Self-Care of Heart Failure Index revealed an improvement in patient and caregiver contributions to heart failure self-care maintenance (daily adherence and symptom monitoring). The findings suggest that engaging patients by increasing their knowledge of their disease and their self-confidence can reduce hospitalizations and subsequent readmissions.

Practical implementation of noninvasive ventilation in Amyotrophic Lateral Sclerosis: lessons learned from a clinical case series.

PurposeNoninvasive ventilation (NIV) may improve survival and quality of life in Amyotrophic Lateral Sclerosis (ALS) patients. There is a surprising paucity of practical guidelines for office-based implementation and management of NIV outside of tertiary ALS centers. We saw the need for a clinical protocol to allow feasible and consistent NIV management in this patient population.MethodsWe created a clinical protocol for office-based initiation of NIV implemented on consecutive ALS patients referred from our regional ALS multidisciplinary clinic. The protocol provided initial empiric settings using a bilevel device in volume-assured pressure support mode. A respiratory therapist (RT) initiated NIV in an office setting and made adjustments according to patient tolerance and therapy targets outlined in the protocol. Later setting changes were performed at patient or provider request. We evaluated patient adherence and efficacy via device download at 30 days and 1 year.ResultsWe present data from a case series of the first 14 consecutive patients initiated on NIV over a 20-month period. Our protocol underwent iterative modification based on clinical experience and patient feedback. Early challenges included the significant time and resource burden required to coordinate device downloads and patient follow-up. Early 30-day NIV adherence was variable (median 20 out of 30 days), while 1-year NIV adherence was excellent (median 27.5 out of 30 days).ConclusionsOur RT-driven clinical NIV protocol was feasible but labor intensive. Achieving real-world adherence of NIV in our ALS patients required iterative protocol adjustment, significant RT provider time, and tele-based follow-up.

Gay and Bisexual Men's Strategies to Maintain Daily Adherence to Their HIV Pre-exposure Prophylaxis (PrEP) Medication: Results from a Qualitative Study.

Since FDA approval in 2012, HIV pre-exposure prophylaxis (PrEP) has been adopted by key populations, including gay and bisexual men (GBM), to reduce their HIV transmission risk. Given that PrEP is optimally effective when taken as prescribed, it is critical to understand the adherence strategies GBM use. We conducted one-on-one, semi-structured interviews with GBM taking PrEP in 2015-2016 (n = 103). Using thematic analysis, we identified six adherence strategies, with most participants (84.3%) utilizing multiple strategies to maintain adequate adherence: (1) integrating PrEP into part of a daily routine, (2) using a pillbox, (3) cognitive strategies/visual cues, (4) setting recurring smartphone alarms or reminders, (5) keeping medication on oneself at all times, and (6) partner or peer support for reminders and/or pill sharing. Overall, participants reported high PrEP adherence (M = 1.6 missed doses in the prior 30days), though nearly all described missing at least one dose unintentionally in the past. Participants credited their high levels of adherence in part to the strategies they adopted. Providers working with GBM prescribed PrEP, especially patients reporting difficulties with adherence, might consider recommending any or all of the six strategies described in this study.

Advancing HIV Biomedical Prevention Research for At-Risk Adolescents.

Despite significant additions to the HIV prevention toolbox, infection rates across the United States continue to rise among vulnerable adolescents and young adults. Access to these interventions by youth at risk for HIV is limited by the lack of data about their safety and use, compounding the myriad contextual barriers to effectively preventing HIV in this group. The NIH-funded Adolescent Trials Network implemented an innovative approach to the inclusion of adolescents at risk for HIV infection who consented for their own participation in the first adolescent study of HIV pre-exposure prophylaxis (PrEP). This model of mature minor consent was supported by state-based adolescent treatment statutes that extend an adolescent's ability to consent to participation in research with a sufficient prospect of clinical benefit from the intervention to justify the potential risks, and a balance of benefits and risks that is at least as favorable as available evidence-based alternatives. Important data on the safety and patterns of PrEP use by at-risk adolescents prompted the FDA to revise the label. The expanded indication of PrEP for HIV prevention in adolescents is hoped to inform clinical guidelines and provides a powerful tool to reduce new infections in the United States among vulnerable at-risk adolescents. Lessons learned from this years-long iterative endeavor have implications for improving access to the rapidly evolving landscape of HIV prevention modalities, including recently implemented studies of long-acting PrEP formulations designed to reduce the burden of daily adherence required by oral PrEP, a major clinical pitfall for adolescent clinicians and their patients.

Predictors of Daily Adherence to HIV Pre-exposure Prophylaxis in Gay/Bisexual Men in the PRELUDE Demonstration Project.

Adequate adherence to pre-exposure prophylaxis (PrEP) is critical to prevent HIV infection, but accurately measuring adherence remains challenging. We compared two biological [blood drug concentrations in plasma and peripheral blood mononuclear cells (PBMC)] and two self-reported measures (facilitated recall to clinicians and self-report in online surveys) and identified predictors of daily PrEP adherence among gay and bisexual men (GBM) in their first 12months on PRELUDE, an open-label, single-arm PrEP demonstration project in New South Wales, Australia. 327 participants were enrolled; 263 GBM attended their 12-month follow-up visit (81% retention). Overall, 91% of blood samples had plasma drug concentrations indicative of taking 7pills/week, and 99% had protective drug concentrations (≥ 4 pills/week). Facilitated recall to clinicians identified 99% of participants with protective adherence as measured by PBMC drug concentrations. Daily adherence measured by facilitated recall was associated with behavioural practices including group sex (aOR 1.33, 95% CI 1.15-1.53, p < 0.001). Retained participants maintained high adherence to daily PrEP over 12months, confirmed by four different measures. Facilitated recall to clinicians is a suitable measure for assessing PrEP adherence in populations engaged in care where there is established trust and rapport with patients. Trial registration: ClinicalTrials.gov NCT02206555.

Specific hypertension smartphone application to improve medication adherence in hypertension: a cluster-randomized trial

Introduction: Digital interventions, such as smartphone applications (apps), are becoming an increasingly common way to support medication adherence and self-management in chronic illness.Aim: To evaluate the effectiveness of the intervention in pharmacological therapeutic adherence in mild to moderate arterial hypertension (AHT), through an app installed on a mobile phone, as well as the degree of control reached by the patient with this tool.Methods: Prospective, randomized controlled trial, full study and multicenter study. Four primary care centers participated. One hundred and fifty-four hypertensive patients under antihypertensive treatment were included. Two groups were established: a control group (CG) with usual intervention (n = 77) and an intervention group (n = 77) (IG), targeting hypertensive people who owned and regularly used a mobile smartphone, specifically using the app called AlerHTA to promote health education and reminder of appointments. There were three visits: initial, 6 and 12 months. Drug adherence was measured by electronic monitors (MEMSs). The primary outcomes were average daily percentage adherence between 80 and 100%, and AHT control.Results: A total of 148 patients finished the study. Mean age was 57.5 ± 9.9. Global adherence was 77.02% (CI = 70.25–83.79) and daily adherence was 74.32% (CI = 67.29–81.35%). Daily adherence was 93.15% and 86.3% in IG, and 70.66% and 62.66% in CG after 6 and 12 months respectively (p < .05). The percentage of uncontrolled patients was 28.3% (CI = 21.05–35.55%). The control of high blood pressure at 12 months was 17.8% and 38.6% for IG and CG respectively (p < .05). The number of patients needed to treat to avoid non-adherence (NNT) was 4.23 patients.Conclusions: The intervention with an app installed on the mobile phones of hypertensive patients favors pharmacological therapeutic adherence and improves the percentage of hypertensive patient control.Trial registration: Spanish Agency of Medicine: EPA-SP UN-HTA-2015-01.

The Conundrum of Hydroxyurea Use and Health Care Utilization in Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is a chronic condition associated with a decreased lifespan. Studies in adult and pediatric SCD populations have shown that hydroxyurea (HU) reduces the frequency and intensity of SCD painful events and decreases morbidity. Follow-up studies of MSH patients also showed cost effectiveness and improved survival for HU user. Adequate dosing and continuous daily adherence to HU use are necessary to achieve these benefits. The NIH Consensus Statement on HU Treatment for SCD had identified non-adherence as a major barrier to the effectiveness of HU therapy.The overarching aim of the study wasto describe the pattern of HCU and health quality indicators (HQI) in a SCD population at different ages of the transition period-data submitted in another abstract-. Here we present data supporting patterns of HU utilization and cost in three different SCD patient age-groups.Methods: We conducted a retrospective data analysis of health insurance claims from a single health plan for service dates 04/01/2016 through 03/21/2017. Members meeting the claims-based definition of SCD (those with any sickle cell related ICD 9/10 CM diagnosis code on two or more separate encounters on distinct dates during the study period) with 12 months of continuous membership were included in the analysis. Only members ages 11-35 years were selected based on study aims and then stratified into three groups representing pre-transition (Group A: 11-18 yr.), transition (Group B: 19-26 yr.), and adult (Group C: 27-35 yr.). Data obtained include demographics, utilization patterns such as: number and cost of Emergency Room (ED) visits, ED reliance rate and total cost of care. Health quality indicators (HQI) such as: hydroxyurea (HU) use, calculated HU medication possession ratio (MPR), influenza (Flu) vaccination status, and total cost and number of visits for PCP and specialists were also obtained. An ED ratio reliance ratio above 0.33 was considered an indicator of excessive reliance. HU medication possession ratio (MPR) of 1.0 was considered complete adherenceResults: One hundred-fourty-four patients, 88 (61%) female, fit the inclusion criteria. Patient number was similarly distributed in all groups: A: 50, B: 48, and C: 46. Medicaid was the primary insurance for 123 (85%) patients, followed by Commercial 15 (10%), and Medicare 6 (5%). The % of HU prescription filled was less than 4 in all three groups, the younger patients -pre-transition group- had 37 % vs. 33% for each of the two group of older patients. HU medication possession ratio was similar and low for all three groups: A=.27, B=.26 and C=.28; 1.0. Those on HU independently of the age groups had a lower rates of both lower and Higher ED reliance rate than those not on HU. For those on HU, the older patients-group C- was the only one with increase of higher ED reliance with compared with those with lower ED reliance (A: 7 vs. 12; B: 5 vs. 7 and C: 9 vs. 4). The Total Cost of Care of the pre-transition group was similar ~$22,000 between those prescribed HU and those not on HU. The total cost of care was twice as much for those study subjects on HU than for those on group B and C ($44,941 and $42,633). Those not on HU in the groups B and C had the lower total care cost ($25,817 and $17,763).Conclusion: After 20 years of HU approval by the FDA as a disease modifying therapy for SCD, analysis of insurance data regarding HU use, adherence and cost of care in SCD patients before, during and after transition from Pediatric to adult care, still reveals poor adherence and higher overall total care cost but, and lower ED reliance. This Conundrum supports the needs further emphasis on increasing education towards use and adherence to HU therapy, while continuing to develop new therapeutic interventions towards disease modification and cure. DisclosuresNo relevant conflicts of interest to declare.

HIV Antiretroviral Pre-Exposure Prophylaxis: Development Challenges and Pipeline Promise.

The US Food and Drug Administration (FDA) approved oral daily tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis of human immunodeficiency virus (HIV) infection in 2012 on the basis of two randomized controlled trials (RCTs), one in men who have sex with men (MSM) and another in HIV serodiscordant heterosexual couples. Subsequently, even greater efficacy has been demonstrated in MSM with rapid population-level incidence reductions in some locations. In contrast, studies of antiretroviral pre-exposure prophylaxis (PrEP) in heterosexual women showed only modest or no efficacy, largely attributed to low adherence. The mixed results of antiretroviral-based PrEP bear witness to unique drug development challenges at this complicated intersection of sexual behavior, public health, and drug development. Multiple innovative methods and formulation strategies followed to address unmet medical needs of persons struggling with daily oral PrEP adherence or preference for nonsystemic PrEP options. Clinical pharmacology plays essential roles throughout this PrEP development process, especially in early product development and through pharmacologically informed enhancement and interpretation of clinical trials.

Smartphones for Real-time Assessment of Adherence Behavior and Symptom Exacerbation for High-Risk Youth with Asthma: Pilot Study

BackgroundYouth with asthma who have poor medication adherence, have limited access to care, and are frequently seen in the acute care setting are often termed “high risk.”ObjectiveThis study aimed to design and test the feasibility of using smartphone technology to assess contextual factors that may impact changes in daily medication adherence and to identify new symptom episodes among high-risk youth with asthma in their home environment.MethodsYouth aged 8-17 years with high-risk asthma from 2 children’s hospitals were eligible for the 2-month study. An app was downloaded on participants’ phones at enrollment. Daily text message (short message service) reminders were sent to complete ecological momentary assessment of asthma symptoms and other contextual factors such as emotional state using the app. Bluetooth inhaler devices were used to record timestamps of inhaler use with the ability to review and manually enter data. The acceptability was assessed with surveys, key informant interviews (KII), and frequency of days with asthma data. KII data were used in an iterative design approach to identify challenges, strengths, and suggestions for maximizing use. Generalized linear mixed modeling was used to preliminarily explore contextual factors associated with changes in daily adherence.ResultsWe enrolled 14 children aged 8-16 years (13/14, 93% were African Americans). Over the 2-month study period, participants reported coughing (42/110, 38%), wheezing (8/111, 7%), chest tightness (9/109, 8%), boredom (57/109, 52%), and 10 new asthma symptom episodes. The controller medication adherence was 30%, which increased significantly on days with asthma symptoms or boredom. Data were received on 89% (606/681) of study days. Surveys and KIIs suggest acceptability among youth and their caregivers. Challenges reported during the study included lost or damaged phones and available memory.ConclusionsYouth and their caregivers reported the acceptability of using smartphones for real-time asthma monitoring. Overall, the controller medication adherence was low but increased significantly on days with reported asthma symptoms or boredom, suggesting that daily contextual factors may be associated with a change in the adherence behavior.