Cost analysis of acute care resource utilization among individuals with sickle cell disease in a middle-income country

Background The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC). We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea in a specialized hematology center in Brazil. Methods The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. The reasons for acute hospital visits were grouped as: 1) vaso-occlusive (VOC) pain, 2) infection, 3) anemia exacerbation, and 4) chronic organ damage complications. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period. Results In total, 1144 patients, median age 17 years (range 0–70), 903 (78.9%) with HbSS/HbSβ0-thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions. Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2176.40/visit). Compared with other genotypes, individuals with HbSS/HbSβ0-thalassemia were admitted more often (79% versus 21%, p < 0.0001), and their admission costs were higher ($1677.18 versus $1224.47/visit, p = 0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs. Costs of ED visits not resulting in admissions were lower among HbSS/HbSβ0-thalassemia individuals with hydroxyurea MPR ≥65% compared with visits by patients with MPR <65% ($98.16/visit versus $182.46/visit, p = 0.0007). No difference in admission costs were observed relative to hydroxyurea use. Discussion In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Hydroxyurea may reduce ED costs among individuals with HbSS/HbSβ0-thalassemia but is dependent on adherence level.

Three-step matching algorithm to enhance between-group comparability and minimize confounding in comparative effectiveness studies

We developed a three-step matching algorithm to enhance the between-group comparability for comparative drug effect studies involving prevalent new-users of the newer study drug versus older comparator drug(s). The three-step matching scheme is to match on: (1) index date of initiating the newer study drug to align the cohort entry time between study groups, (2) medication possession ratio measures that consider prior exposure to all older comparator drugs, and (3) propensity scores estimated from potential confounders. Our approach is illustrated with a comparative cardiovascular safety study of glucagon-like peptide-1 receptor agonist (GLP-1ra) versus sulfonylurea (SU) in type 2 diabetes patients using Taiwan’s National Health Insurance Research Database 2003–2015. 66% of 3195 GLP-1ra users had previously exposed to SU. The between-group comparability was well-achieved after implementing the matching algorithm (i.e., standardized mean difference < 0.2 for all baseline patient characteristics). Compared to SU, the use of GLP-1ra yielded a significantly reduced risk of the primary composite cardiovascular events (hazard ratio [95% confidence interval]: 0.71 [0.54–0.95], p = 0.022). Our matching scheme can enhance the between-group comparability in prevalent new-user cohort designs to minimize time-related bias, improve confounder adjustment, and ensure the reliability and validity of study findings.

Delta T, a Useful Indicator for Pharmacy Dispensing Data to Monitor Medication Adherence

Introduction: Calculating patients’ medication availability from dispensing or refill data is a common method to estimate adherence. The most often used measures, such as the medication possession ratio (MPR), average medication supplies over an arbitrary period. Averaging masks the variability of refill behavior over time. Goal: To derive a new absolute adherence estimate from dispensing data. Method: Dispensing histories of patients with 19 refills of direct oral anticoagulants (DOAC) between 1 January 2008 and 31 December 2017 were extracted from 39 community pharmacies in Switzerland. The difference between the calculated and effective refill day (ΔT) was determined for each refill event. We graphed ΔT and its dichotomized version (dΔT) against the MPR, calculated mean ΔT and mean dΔT per refill, and applied cluster analysis. Results: We characterized 2204 refill events from 116 DOAC patients. MPR was high (0.975 ± 0.129) and showed a positive correlation with mean ΔT. Refills occurred on average 17.8 ± 27.9 days “too early”, with a mean of 75.8 ± 20.2 refills being “on time”. Four refill behavior patterns were identified including constant gaps within or at the end of the observation period, which were critical. Conclusion: We introduce a new absolute adherence estimate ΔT that characterizes every refill event and shows that the refill behavior of DOAC patients is dynamic.

Trajectories of Adherence to Biologic Disease-Modifying Anti-Rheumatic Drugs in Tuscan Administrative Databases: The Pathfinder Study

Scanty information on clustering longitudinal real-world data is available in the medical literature about the adherence implementation phase in rheumatoid arthritis (RA). To identify and characterize trajectories by analyzing the implementation phase of adherence to biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), we conducted a retrospective cohort drug-utilization study using Tuscan administrative databases. RA patients were identified by a validated algorithm, including the first biologic DMARD supply from 2010 to 2015, RA specialist visit in the year before or after the first supply date and RA diagnosis in the five years before or in the year after the first supply date. We observed users for three years or until death, neoplasia, or pregnancy. We evaluated adherence quarterly through the Medication Possession Ratio. Firstly, we identified adherence trajectories and described the baseline characteristics; then, we focused on the trajectory most populated to distinguish the related sub-trajectories. We identified 952 first ever-biologic DMARD users in RA (712 females, mean age 52.7 years old, standard deviation 18.8). The biologic DMARD mostly supplied was etanercept (387 users) followed by adalimumab (233). Among 935 users with at least 3 adherence values, we identified 49 fully-adherent users, 829 continuous users, and 57 early-discontinuing users. Significant differences were observed among the index drugs. After focusing on the continuous users, three sub-trajectories were identified: continuous-steady users (556), continuous-alternate users (207), and continuous-declining users (66). No relevant differences emerged at the baseline. The majority of first ever-biologic DMARD users showed a continuous adherence behavior in RA. The role of adherence potential predictors and the association with effectiveness and safety outcomes should be explored by further studies.

Access to HIV Antiretroviral Therapy among People Living with HIV in Melbourne during the COVID-19 Pandemic

The social measures taken to control the COVID-19 pandemic can potentially disrupt the management of HIV. The objective of this study was to examine the impact of the Australian COVID-19 lockdown restrictions on access to antiretroviral therapy (ART) for people living with HIV in Melbourne. Using data from the Melbourne Sexual Health Centre (MSHC), we assessed the changes in rates of ART postal delivery, controlled viral load, and ART dispensing from 2018 to 2020. The percentage of ART delivered by postage from the MSHC pharmacy was calculated weekly. The percentage of people living with HIV with a controlled viral load (≤200 copies/mL) was calculated monthly. We calculated a yearly Medication Possession Ratio (MPR). The average percentage of HIV ART dispensed through postage for the years 2018, 2019, and 2020 was 3.7% (371/10,023), 3.6% (380/10,685), and 14% (1478/10,765), respectively (Ptrend < 0.0001). Of the 3115 people living with HIV, the average MPR for 2018, 2019, and 2020 was 1.05, 1.06, and 1.14, respectively (Ptrend = 0.28). The average percentage of people with an HIV viral load of <200 copies/mL for the years 2018, 2019, and 2020 was 97.6% (2271/2327), 98.0% (2390/2438), and 99.2% (2048/2064), respectively (Ptrend < 0.0001). This study found that the proportion of controlled viral load and access to ART of people living with HIV in Melbourne was largely unaffected by the COVID-19 lockdown restrictions. This suggests that some of the services provided by the MSHC during the pandemic, such as HIV ART postal delivery, may assist long-term HIV management.

Self-reported health literacy and medication adherence in older adults: a systematic review

ObjectivesTo give an overview over the associations between self-reported health literacy and medication adherence in older adults.DesignA systematic literature review of quantitative studies published in English and German.Data sourcesMEDLINE via PubMed, CINAHL, Cochrane Library, Epistemonikos and LIVIVO were searched.Eligibility criteriaIncluded studies had to examine the associations between self-reported health literacy and medication adherence in the elderly (samples including ≥66% of ≥60 years old) and had to use a quantitative methodology and had to be written in English or German.Data extraction and synthesisAll studies were screened for inclusion criteria by two independent reviewers. A narrative synthesis was applied to analyse all included studies thematically. Quality assessment was conducted using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.ResultsWe found 2313 studies, of which nine publications from eight studies were included in this review. Five studies reported a majority of participants with limited health literacy, one study reported a majority of participants with adequate health literacy, and three publications from two studies only reported mean levels of health literacy. Eight publications from seven studies used self-reports to measure medication adherence, while one study used the medication possession ratio. Overall, six publications from five studies reported significantly positive associations between health literacy and medication adherence while two studies reported positive but non-significant associations between both constructs and one study reported mixed results.ConclusionIn this review, associations between self-reported health literacy and medication adherence are rather consistent, indicating positive associations between both constructs in older adults. However, concepts and measures of health literacy and medication adherence applied in the included studies still show a noteworthy amount of heterogeneity (eg, different use of cutoffs). These results reveal the need for more differentiated research in this area.PROSPERO registration numberCRD42019141028.

Validation of a Virtual Assistant for Improving Medication Adherence in Patients with Comorbid Type 2 Diabetes Mellitus and Depressive Disorder

Virtual assistants are programs that interact with users through text or voice messages simulating a human-based conversation. The development of healthcare virtual assistants that use messaging platforms is rapidly increasing. Still, there is a lack of validation of these assistants. In particular, this work aimed to validate the effectiveness of a healthcare virtual assistant, integrated within messaging platforms, with the aim of improving medication adherence in patients with comorbid type 2 diabetes mellitus and depressive disorder. For this purpose, a nine-month pilot study was designed and subsequently conducted. The virtual assistant reminds patients about their medication and provides healthcare professionals with the ability to monitor their patients. We analyzed the medication possession ratio (MPR), measured the level of glycosylated hemoglobin (HbA1c), and obtained the patient health questionnaire (PHQ-9) score in the patients before and after the study. We also conducted interviews with all participants. A total of thirteen patients and five nurses used and evaluated the proposed virtual assistant using the messaging platform Signal. Results showed that on average, the medication adherence improved. In the final interview, 69% of the patients agreed with the idea of continuing to use the virtual assistant after the study.

Protective Effects of Angiotensin Receptor Blockers on the Incidence of Dementia in Patients with Chronic Kidney Disease: A Population-Based Nationwide Study

Chronic kidney disease (CKD) is associated with dementia. Angiotensin receptor blockers (ARBs) have been widely used for delaying CKD progression; however, their effect on dementia prevention in patients with CKD remains unclear. We designed a retrospective cohort study to investigate the effects of ARBs on the incidence of dementia in patients with CKD. We selected 21,208 patients from the Taiwan nationwide database from 1 January 2006 to 31 December 2006. We identified ARB users (n = 17,466) and ARB non-users (n = 3742) and their medication possession ratio (MPR). The Cox proportional hazard model was used to estimate hazard ratios (HRs) for the incidence of dementia in ARB users in the CKD population. During the 11-year follow-up period, 2207 dementia events were recorded; multivariate-adjusted hazard ratios for dementia by ARB usage and ARB usage per MPR were 0.578 (95% CI: 0.52–0.643) and 0.996 (95% CI: 0.995–0.998), respectively. This association was observed in almost all subgroups. Dose frequency effect of ARBs was noted; patients with higher MPRs of ARBs generally had higher protection from dementia. Patients with hypertension and CKD who received ARBs had a decreased risk of dementia. Protective effects of ARBs on dementia increased with the frequency of ARB use.

Real-world evidence on the strategy of olmesartan-based triple single-pill combination in Korean hypertensive patients: a prospective, multicenter, observational study (RESOLVE-PRO)

Background In this prospective, multicenter, non-comparative observational study, the effectiveness and safety of the triple single-pill combination (SPC) of olmesartan/amlodipine/hydrochlorothiazide (OM/AML/HCTZ) were evaluated in a real clinical practice setting in Korean patients with essential hypertension. Methods A total of 3752 patients were enrolled and followed for 12 months after administration of OM/AML/HCTZ. Primary endpoint was change from baseline to month 6 in the mean systolic blood pressure (SBP). Secondary endpoints included changes from baseline in the mean SBP at month 3, 9, 12 and the mean diastolic blood pressure (DBP) at month 3, 6, 9, 12; changes in the mean SBP/DBP according to age and underlying risk factors; and blood pressure control rate (%) at different time points. Adherence to and satisfaction with OM/AML/HCTZ treatment among patients and physicians were assessed by medication possession ratio (MPR) and numeric rating scale, respectively, as exploratory endpoints. Safety was evaluated by the incidence and severity of adverse events (AEs) as well as the discontinuation rate due to AEs. Results OM/AML/HCTZ administration led to significant reductions in the mean SBP/DBP by 11.5/6.6, 12.3/7.0, 12.3/7.2, and 12.8/7.4 mmHg from baseline to month 3, 6, 9 and 12, respectively (P < 0.0001). The BP reductions were maintained throughout the 1-year observation period in all patients with different age groups and risk factors (diabetes mellitus, cardiovascular disease, and renal disease). The BP control rate (%) of < 140/90 mmHg was 65.9, 67.9, 68.9, and 70.6% at month 3, 6, 9, and 12, respectively. The mean MPR during the observation period was 0.96. The safety results were consistent with the previously reported safety profile of OM/AML/HCTZ. Conclusions Treatment with the triple SPC of OM/AML/HCTZ demonstrated significant effectiveness in reducing SBP/DBP and achieving target BP control with high adherence over the 1-year observation period in Korean hypertensive patients and was well-tolerated. Trial registration CRIS, KCT0002196, Registered 3 May 2016.

52. PrEP Adherence and Discontinuation at a Pharmacy-Supported PrEP Program in Atlanta, GA

Background Pre-exposure prophylaxis (PrEP) is a highly effective biomedical strategy to decrease Human Immunodeficiency Virus (HIV) acquisition. Effectiveness of oral PrEP is linked to medication adherence. In 2018, Grady Health System (GHS) launched a PrEP program to increase PrEP access among un- and underinsured individuals living in metro Atlanta, Georgia. The purpose of this study is to determine PrEP medication adherence, PrEP discontinuation rates, and associated individual factors of patients enrolled during the first 18 months of the program’s implementation. Methods A single-center, retrospective chart review was conducted on patients enrolled in the GHS PrEP program between June 1, 2018 and February 29, 2020 who received more than one monthly PrEP prescription. Adherence was estimated using the medication possession ratio (MPR). The primary outcome was mean adherence to PrEP. Secondary outcomes include rate of high percent adherence (MPR &gt; 80%), median time of engagement in care, PrEP discontinuation rates, rates of PrEP re-engagement, and individual factors associated with PrEP discontinuation and low adherence. Results This study included 154 patients, 70.8% of them were Black, 62.3% were cisgender men, 59.1% were uninsured, and the mean age was 34. The majority of patients identified as men who have sex with men (51.9%). Mean PrEP adherence was 89.2%; 77.3% of patients demonstrated a high rate of adherence. No individual or social factors were associated with low adherence, but younger age was associated with higher rates of PrEP discontinuation (p&lt; 0.0061). At the end of the follow up period on October 30, 2020, 53.8% of patients were active in the program and 12.7% of those who discontinued had re-engaged with the program. The average length of program engagement was 9.8 months. Table 1. Baseline socio-demographic characteristics (N=154) Table 2. PrEP Adherence and Discontinuation at the GHS PrEP Program from 2018 to 2020 (N=154) Table 4. Multivariate analysis of individual factors associated with PrEP discontinuation and low adherence Conclusion Mean PrEP adherence at a safety net PrEP program in Atlanta was high and PrEP discontinuation rates were comparable to other PrEP clinics nationwide. We found no association with individual factors previously linked to lower adherence, including Black race, younger age, and insurance status. Program-related factors that may have impacted these findings need to be investigated. Other future areas of research include strategies to optimize engagement in care in younger patients. Disclosures Bradley L. Smith, Pharm.D., AAHIVP, Gilead Sciences, Inc (Advisor or Review Panel member)