Urban scaling of opioid analgesic sales in the United States

Opioid misuse is a public health crisis in the United States. The origin of this crisis is associated with a sharp increase in opioid analgesic prescribing. We used the urban scaling framework to analyze opioid prescribing patterns in US commuting zones (CZs), i.e., groups of counties based on commuting patterns. The urban scaling framework postulates that a set of scaling relations can be used to predict health outcomes and behaviors in cities. We used data from the Drug Enforcement Administration’s Automated Reports and Consolidated Ordering System (ARCOS) to calculate counts of oxycodone/hydrocodone pills distributed to 607 CZs in the continental US from 2006 to 2014. We estimated the scaling coefficient of opioid pill counts by regressing log(pills) on log(population) using a piecewise linear spline with a single knot at 82,363. Our results show that CZs with populations below the knot scaled superlinearly (β = 1.36), i.e., larger CZs had disproportionally larger pill counts compared to smaller CZs. On the other hand, CZs with populations above the knot scaled sublinearly (β = 0.92), i.e., larger CZs had disproportionally smaller pill counts compared to smaller CZs. This dual scaling pattern was consistent across US census regions. For CZs with population below the knot, the superlinear scaling of pills is consistent with the explanation that an increased number of successful matches between prescribers and users will lead to higher prescribing rates. The non-linear scaling behavior observed could be the result of a combination of factors, including stronger health care systems and prescribing regulation in largely populated commuting zones, as well as high availability of other opioids such as heroin in these commuting zones. Future research should explore potential mechanisms for the non-linearity of prescription opioid pills.

Identifying Poor Adherence in Outpatients with Bipolar Disorder: A Comparison of Different Measures

Objective Unlike schizophrenia, comparisons of different methods of estimating inadequate adherence in bipolar disorder (BD) are scarce. This study compared four methods of identifying inadequate adherence among outpatients with BD. Materials and Methods Two self-reports, the Morisky Medication Adherence Questionnaire (MAQ) and the Drug Attitude Inventory (DAI-10), clinician ratings employing the Compliance Rating Scale (CRS), mood-stabilizer levels, and clinic-based pill counts were compared at intake in 106 outpatients with BD and after 6 months of follow-up (n = 75). Statistical Analysis Rates of nonadherence were determined for each method. The ability to detect inadequate adherence was based on sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR positive and LR negative). Correlation coefficients and Cohen's kappa values were used to determine the agreement between measures. Correlation coefficients were also used to evaluate the determinants of inadequate adherence Results The MAQ and the DAI-10 (cut-off score of two) yielded higher rates of nonadherence (35–47%) than the other methods. They were better at detecting adherence (specificity, 34–42%; PPV, 40–44%; and LR negative, 0.70–0.96) than other measures and had moderate ability to identify nonadherence compared with them (sensitivity, 63–73%; NPV, 54–70%; and LR positive, 1.02–1.16). They were associated with several established predictors of nonadherence. The MAQ and DAI-10 scores and the MAQ and CRS scores were modestly correlated. Multivariate analysis showed that 20% of the variance in the DAI-10 scores was explained by the MAQ scores. Despite their low yield, serum levels had a high sensitivity (88%) and higher accuracy (55%) in identifying inadequate adherence. CRS ratings and pill counts had high sensitivity but low specificity to detect inadequate adherence. Conclusion Self-reports appeared to be the most efficient method of ascertaining inadequate adherence among outpatients with BD. However, since none of the measures were adequate by themselves, a combination of different measures is more likely to maximize the chances of identifying inadequate adherence among these patients.

Evaluating the role of baseline geriatric assessment in predicting adherence to oral targeted therapies and outcomes in older adults with non-Hodgkin lymphoma.

12043 Background: Oral targeted therapies (OTT) have transformed the treatment landscape of Non-Hodgkin lymphoma (NHL). However, measuring, defining and optimizing adherence to OTT remains a challenge. Prior studies have reported variable adherence rates (12-100%) to OTT in cancer patients (pts), with suboptimal adherence associated with inferior outcomes. In older adults (OA), geriatric syndromes (GS) such as polypharmacy and cognitive impairment can impact adherence. While geriatric assessment (GA) can predict chemotherapy-related toxicity in OA, its utility in NHL pts on OTT is unknown. In this pilot study, we evaluate the role of GA in predicting adherence and outcomes in NHL pts on OTT. We also report the feasibility of using MEMS Cap, an electronic event monitoring system, to measure adherence in this population. Methods: Pts ≥70 years (yrs) with NHL, initiating/receiving OTT were included. A GA was performed at baseline; pt, disease, and OTT characteristics were recorded. Pts were followed monthly for the first 3 months (mos), then every 3 mos for 1 year. Primary endpoint was treatment adherence rate, measured using both subjective [brief adherence rating scale (BARS)] and objective (pill counts and MEMS cap) methods. Progression free survival (PFS) was measured from time of therapy initiation to disease progression or death. Results: Of the 54 pts screened, 25 were enrolled. Median age was 77 yrs (71-93 yrs), 21 pts had chronic lymphocytic leukemia, 3 had mantle cell lymphoma and 1 had marginal zone lymphoma. Most frequently used OTT were ibrutinib (n = 17) and venetoclax (n = 5). Most pts (72%) were on OTT at study entry. Median time on therapy was 16.4 mos (1.9-44.6 mos). GS included cognitive impairment (28%), depression (24%), polypharmacy (92%) and recent falls (12%); 48% pts had ≥2 GS. Nine pts (36%) had impaired 4-meter gait speed and/or timed-up-and-go; 20 pts (80%) had an adjusted CIRS-G score of ≥6. So far, pts have completed a median follow up of 3.3 mos. BARS was the most consistent measure of adherence used (63/63 visits, 100%). MEMS Cap and pill counts were used at 13% and 8% visits respectively. Only 5 pts used the MEMS Cap, mostly due to packaging incompatibility (44%-pill box, 32%-blister packs). Median adherence was 100% (range, 70%-100%) with no pts missing > 7 days of prescribed doses. Five pts (20%) required dose interruptions, mostly due to adverse events. Six pts discontinued therapy and 2 pts died of unrelated causes. Median PFS was not reached. Chronological age and presence of a GS were not associated with adherence rate or outcomes. Conclusions: Despite presence of ≥2 geriatric syndromes in 48% of older adults with NHL on OTT, self-reported adherence remains high ( > 99%) in this group. The MEMS Cap device has poor applicability in measuring adherence to OTT due to pill package incompatibility and increasing use of virtual/tele visits.

Effects of Pharmaceutical Pictograms on Medication Adherence in Elderly Patients with Chronic Diseases at Primary Health Care Center in Hat Yai, Songkhla

Objective: To compare drug adherence with or without pharmaceutical pictograms in the elderly with chronic diseases. Materials and Methods: The present study was a randomized controlled trial conducted between April 2019 and June 2019 at a primary health care center in Hat Yai, Songkhla, Thailand. The elderly patients with chronic diseases were randomly allocated to the experimental group (n=25) and the control group (n=25). The experimental group received pictogram labels, text labels, and verbal information on the consumption of medications from the pharmacist. The control group received text labels and verbal information from the pharmacist. Both groups received follow-up home visits two weeks later. Results: The present study results showed that medication adherence using pill counts in the experimental group was significantly higher than in the control group. The median medication adherence scores from pill counts was (interquartile range, IQR) 100 (100, 100) versus 95.56 (90.25, 100), respectively, p=0.011. The medication adherence with the medication taking behavior measure for Thai patients (MTB-Thai) significantly increased in the experimental group (100.0%) compared with the control group (45.8%) (p=0.0002). Conclusion: The present study showed that medication adherence is greatly improved when the medication instruction is supplemented with pictograms. Therefore, medication should include pictograms on labels to better convey medical instructions to elderly patients with chronic diseases. Keywords: Pharmaceutical pictograms, Medication adherence, Chronic disease, Elderly patients

Predictors of suboptimal adherence to isoniazid preventive therapy among adolescents and children living with HIV

This study identified factors associated with adherence to a 6-month isoniazid preventive therapy (IPT) course among adolescents and children living with HIV. Forty adolescents living with HIV and 48 primary caregivers of children living with HIV completed a Likert-based survey to measure respondent opinions regarding access to care, quality of care, preferred regimens, perceived stigma, and confidence in self-efficacy. Sociodemographic data were collected and adherence measured as the average of pill counts obtained while on IPT. The rates of suboptimal adherence (< 95% adherent) were 22.5% among adolescents and 37.5% among the children of primary caregivers. Univariate logistic regression was used to model the change in the odds of suboptimal adherence. Independent factors associated with suboptimal adherence among adolescents included age, education level, the cost of coming to clinic, stigma from community members, and two variables relating to self-efficacy. Among primary caregivers, child age, concerns about stigma, and location preference for meeting a community-health worker were associated with suboptimal adherence. To determine whether these combined factors contributed different information to the prediction of suboptimal adherence, a risk score containing these predictors was constructed for each group. The risk score had an AUC of 0.87 (95% CI: 0.76, 0.99) among adolescents and an AUC of 0.76 (95% CI: 0.62, 0.90), among primary caregivers suggesting that these variables may have complementary predictive utility. The heterogeneous scope and associations of these variables in different populations suggests that interventions aiming to increase optimal adherence will need to be tailored to specific populations and multifaceted in nature. Ideally interventions should address both long-established barriers to adherence such as cost of transportation to attend clinic and more nuanced psychosocial barriers such as perceived community stigma and confidence in self-efficacy.

Teaching Nurse Practitioner Students About Polypharmacy Through a Lived Experience

Polypharmacy (typically defined as the concomitant use of 5 or more medications) affects 40-50% of older adults in the U.S., and is associated with geriatric syndromes, a higher risk of medication non-adherence, and adverse drug events. Medication non-adherence is a common frustrating clinical issue for clinicians who provide care for older adult patients. Simultaneously, patients often find medication regimens to be complicated and confusing. This may contribute to medication non-adherence, which may further lead to adverse drug events and/or negative health outcomes. The more medications a patient is taking, the higher the risk for non-adherence. Thirty-eight students enrolled in an adult-gerontology primary care nurse practitioner program were given a bag of five mock medications that are commonly prescribed for older adults. Students were instructed to follow the directions on each of the bottles for approximately one month. A private messaging system was available for students if refills were needed or if they had questions about their medications. A debriefing session for this month-long, ungraded simulation was held, at which time students returned medication bottles. Pill counts were not analyzed, but all returned bottles contained mock medications. Approximately 52.6% of students estimated adhering to the medication regimen 0-24% of the time, whereas 26.3% reported an adherence rate of 25-50%. The most commonly cited barrier to adherence (55.3%) was “forgetfulness”. Nearly all students (89.5%) reported that the exercise “very much” increased their awareness of challenges patients face when managing medications, and 97% cited an increased awareness of ways to improve medication adherence.

Adherence to Antihypertensive Therapy: A Systematic Review of Russian Prospective Studies from 2000 to 2019

Russia belongs to countries with a high prevalence of arterial hypertension (AH), which is the main cause of premature death in the Russian population. The level of blood pressure (BP) is controlled in less than a third of patients, which may be due to poor adherence to medical recommendations and irregular medication. The manuscript provides a review of studies evaluating the effectiveness of measures to improve adherence to antihypertensive therapy (AHT).Aim. To prepare a systematic review of Russian studies to assess the effectiveness of measures to increase adherence to AHT, to determine/describe the main directions of the intervention and the methodological level.Material and methods. The search for full-text articles on adherence to AHT published in Russian in the period from 2000 to 2019 was carried out in the main Russian and international electronic databases eLIBRARY.ru, Embase, Russian Medicine, MEDLINE. Of the 563 publications found, 20 were included in the review.Results. In 14 studies, adherence was assessed using the 4-item Morisky Medication Adherence Scale (MMAS-4), other studies used bespoke questionnaires or pill counts. Two studies examined factors associated with adherence. The observation period was up 6 weeks to 12 months, the number of participants is 30-2435 people. A higher adherence was noted in women, people over 50 years old, with higher education, working, with concomitant diabetes mellitus and a history of myocardial infarction. Patient education was effective interventions to improve adherence (in particular, in studies, improvement on the MMAS-4 from 1.8 to 3.9 points, p=0.0002 or from 2.80 to 3.79 points, p<0.0001), telephone reminders (p<0.0001), training in self-measurement of blood pressure (p<0.05) and fixed combinations of drugs (p<0.05).Conclusion. The most effective ways to improve adherence are patient education and the use of drugs fixed combinations. In most studies, subjective methods of adherence assessing were used.

Role of community pharmacists in improving adherence and clinical outcomes after acute coronary syndromes (IM-ADHERENCE): six month-results

Background Acute coronary syndromes (ACS) are the leading cause of death from cardiovascular diseases (CVD) and are responsible for 8% of deaths in Italy. Available data evaluating patient long-term adherence show that about 20–30% of patients interrupts medical therapy within first six months from the index event. Although several strategies have been developed to improve adherence, there are few data evaluating the role of community pharmacist on patient adherence and its impact on clinical outcomes Purpose Our aim was to evaluate if involving community pharmacists could improve patients' adherence to medical prescriptions after ACS, reducing the rate of re-admissions due to CVD and related costs (IM-ADHERENCE study). We report the results of the first six months of the study. Methods Patients discharged for ACS from February to September 2018 in three main hospitals of our city area, in active therapy with at least one of the recommended drugs for secondary prevention (ASA, P2Y12, statin), were identified by a cardiologist to be included in the interventional arm. Patient's drug reconciliation was obtained by the hospital pharmacist before discharge. An adherence plan assessment was performed by the referral community pharmacist at 30 days, 3, 6, 9 and 12 months after discharge with 3 kinds of interventions: counseling, pill counts and self-administered questionnaire on adherence. The cardiologist also identified patients discharged within 6 months before the study beginning as historical control arm. The investigators collected the data from pill counts, questionnaire results on adherence (interventional arm) and administrative databases throughout 6 months from hospital discharge. Main outcome was the rate of adherent patients after 6 months, defined as a value of Proportion of Days Covered (PDC) &gt;80% (chi square test; p&lt;0.05). Secondary outcomes concerned re-admission rates due to CV events and related costs. Results A total of 128 patients were identified, 61 patients were enrolled in the interventional arm (age 68±12,3; 87% male; 15 drop-out included in the analysis). The interventional and control arms had the same sample size and were comparable. At 6 months, the interventional arm compared with control had a higher rate of adherent patients (51% vs 33%, p=0.046) and a lower rate of re-admission to hospital for CV events (46% vs 69%, p=0.01). A significant reduction in health costs was obtained as lower rate of hospitalizations (about € 207.501 in 6 months). Conclusions The intervention of community pharmacist in patient drug adherence after ACS reduced re-hospitalizations and health costs at 6 months from index event. This study was an opportunity to integrate hospital and community pharmacists with cardiologist work in treatment and outcome of ACS patients, achieving medication reconciliation and a higher drug adherence, with less re-hospitalizations. These data are waiting to be confirmed at 1-year analysis. Funding Acknowledgement Type of funding source: None

Returning of antiretroviral medication dispensed over a period of 8 months suggests non-adherence despite full adherence according to real time medication monitoring

Real-time medication monitoring (RTMM) may potentially enhance adherence to antiretroviral treatment (ART). We describe a participant in an ongoing trial who, shortly after completing trial participation, died of cryptococcal meningitis despite high levels of adherence according to self-report, pill-counts and RTMM (> 99%). However, she evidenced consistently high HIV viral load throughout the 48-week study follow-up. Subsequently, her relatives unsolicitedly returned eight months’ dispensed ART medication that she was supposed to have taken. This brief report illustrates the challenges of adherence measurements including RTMM, and reinforces the need to combine adherence assessments with viral load monitoring in HIV care.

Simultaneous Use of Two Different Tools to Assess Compliance with Antiepileptic Drugs: Experience in A Community-Based Study

Objective Antiepileptic drug (AED) therapy remains the primary form of treatment for epilepsy, noncompliance to which can result in breakthrough seizure, emergency department visits, fractures, head injuries, and increased mortality. Various tools like self-report measures, pill-counts, medication refills, and frequency of seizures can assess compliance with varying extent. Thus, assessment of compliance with AEDs is crucial to be studied. Materials and Methods Compliance was assessed using pill-count and Morisky medication adherence scale (MMAS) during home visits. A pill-count (pills dispensed–pills remaining)/(pills to be consumed between two visits) value of 0.85 to ≤1.15 was recorded as appropriate compliance. Underdose (<0.85) and overdose (>1.15) was labeled as noncompliance. Score of 1 was given to each positive answer in MMAS. Score of ≥1 was labeled as noncompliance.Statistical analysis: Relationship of demographic factors between compliant and noncompliant patients was analyzed using Chi-square test (SPSS version 21.0, IBM). Rest of the data was analyzed with the help of descriptive statistics using Microsoft Excel. p< 0.05 was considered statistically significant. Results Out of 105 patients, 54 patients were noncompliant with both pill-count and MMAS. 10 patients were noncompliant with pill-count only, while 10 were noncompliant with MMAS. Conclusion Both tools complement each other when used in combination, as use of a single tool was not able to completely detect compliance.