Background: Opioid treatment programs (OTPs) permit patients to ingest daily methadone doses unsupervised and away from the clinic, a strategy that enhances treatment access and convenience but has the potential for mismanagement.Objective: This retrospective review, conducted during the COVID-19 pandemic (5/2020-1/2022), evaluates the feasibility and acceptability of a commercially available electronic pillbox to safely administer methadone take-home tablets in a large community-based OTP (census >500 people).Methods: Study participants (n = 24; 54% male, 46% female; M age = 63 years) had recently received more take-homes per visit to support national social distancing directives, and were instructed that they could maintain these privileges by agreeing to use the pillbox.Results: Results demonstrate good demand feasibility as most participants (71%) agreed to use the pillbox. Good implementation feasibility was observed through safe and reliable delivery of most take-home tablets, with a staff support line to resolve technical issues. Acceptability was modest as six participants (25%) requested to return the pillbox despite losing some take-home privileges.Conclusion: Results support continued use and study of the electronic pillbox to safely deliver and increase access to methadone take-home doses.

Patients usually deviate from prescribed medication schedules and show reduced adherence. Even when the adherence is sufficient, there are conditions where the medication schedule should be modified. Crucial drug-drug, food-drug, and supplement-drug interactions can lead to treatment failure. We present the development of an internet of medical things (IoMT) platform to improve medication adherence and enable remote treatment modifications. Based on photos of food and supplements provided by the patient, using a camera integrated to a portable 3D-printed low-power pillbox, dangerous interactions with treatment medicines can be detected and prevented. We compare the medication adherence of 14 participants following a complex medication schedule using a functional prototype that automatically receives remote adjustments, to a dummy pillbox where the adjustments are sent with text messages. The system usability scale (SUS) score was 86.79, which denotes excellent user acceptance. Total errors (wrong/no pill) between the functional prototype and the dummy pillbox did not demonstrate any statistically significant difference (p = 0.57), but the total delay of the intake time was higher (p = 0.03) during dummy pillbox use. Thus, the proposed low-cost IoMT pillbox improves medication adherence even with a complex regimen while supporting remote dose adjustment.

Pill count is used to assess drug adherence in people living with HIV (PLHIV). Carrying a pillbox is associated with fear of concealment and stigma and might indicate poor adherence and predict someone who will be lost to follow-up (LTFU). We therefore assessed the association between pillbox return and being LTFU in rural Tanzania.
This is a nested study of the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). We included PLHIV aged ≥ 18 years enrolled in KIULARCO between January 2013 and March 2019 with follow-up through January 2020, who were on antiretroviral treatment (ART) for ≥ 6 months. Baseline was defined as the latest ART initiation or KIULARCO enrolment. We determined the association between time-dependent failed pillbox return updated at every visit and LTFU using Kaplan-Meier estimation and Cox models.
Among 2552 PLHIV included in the study, 1735 (68.0%) were female, 959 (40.3%) had a WHO stage III/IV and 1487 (66.4%) had a CD4 cell count < 350 cells/µL. The median age was 38.4 years [interquartile range (IQR): 31.7-46.2]. During a median follow-up of 33.1 months (IQR: 17.5-52.4), 909 (35.6%) participants were LTFU, 43 (1.7%) died and 194 (7.6%) had transferred to another clinic. The probability of being LTFU was higher among PLHIV with failed pillbox return than among those who returned their pillbox [30.0%, 95% confidence interval (CI): 26.8-33.2% vs. 19.4%, 95% CI: 17.4-21.6%, respectively, at 24 months (hazard ratio = 1.67, 95% CI: 1.46-1.90; p < 0.001)].
Failed pillbox return was associated with a higher risk of being LTFU and could be used as a simple tool to identify PLHIV for appropriate interventions to reduce their chance of being LTFU.

OBJECTIVE: Nonadherence to a long-term therapy, including diabetes mellitus, is one of the global problems that need to be overcome. This study aims to determine the effect of pillbox use and education by pharmacists toward medication adherence in patients with diabetes mellitus in a Primary Health Care Center in Mataram.
METHODS: This research was an experimental research design with pretest-posttest with control group design. The study was conducted from October to December 2019 at Tanjung Karang Primary Health Care Center, Mataram. Measurement of adherence was done using the Adherence to Refill and Medication Scale questionnaire. The higher the score, the more nonadherence the patients. Patients were divided into three groups, which were the control group, educational intervention group, and pillbox and educational intervention group. Each group consisted of 11 patients.
RESULTS: Patients\' medication adherence increased from 19.54 (SD 4.37) to 15.18 (SD 2.64) in the education and pillbox intervention group (p=0.004). Whereas, in the education and control group, the adherence did not provide a significant change (p>0.05). Based on the difference in adherence scores, it was known that what contributed to changes in compliance was refilling medicine and intentional nonadherence in taking medicine subscale (p=0.024).
CONCLUSIONS: Providing education and pillbox done by pharmacists at the Primary Health Care Center can increase adherence to the therapy of diabetes mellitus patients. Pharmacists at the Primary Health Care Center can use the intervention model to improve the level of adherence of patients with chronic illness.

BACKGROUND: To address the multifaceted challenges associated with tuberculosis (TB) in-person directly observed therapy (DOT), the World Health Organization recently recommended that countries maximize the use of digital adherence technologies. Sub-Saharan Africa needs to investigate the effectiveness of such technologies in local contexts and proactively contribute to global decisions around patient-centered TB care. This study aims to evaluate the effectiveness of pillbox-enabled self-administered therapy (SAT) compared to standard DOT on adherence to TB medication and treatment outcomes in Ethiopia. It also aims to assess the usability, acceptability, and cost-effectiveness of the intervention from the patient and provider perspectives.
METHODS: This is a multicenter, randomized, controlled, open-label, superiority, effectiveness-implementation hybrid, mixed-methods, two-arm trial. The study is designed to enroll 144 outpatients with new or previously treated, bacteriologically confirmed, drug-sensitive pulmonary TB who are eligible to start the standard 6-month first-line anti-TB regimen. Participants in the intervention arm (n = 72) will receive 15 days of HRZE-isoniazid, rifampicin, pyrazinamide, and ethambutol-fixed-dose combination therapy in the evriMED500 medication event reminder monitor device for self-administration. When returned, providers will count any remaining tablets in the device, download the pill-taking data, and refill based on preset criteria. Participants can consult the provider in cases of illness or adverse events outside of scheduled visits. Providers will handle participants in the control arm (n = 72) according to the standard in-person DOT. Both arms will be followed up throughout the 2-month intensive phase. The primary outcomes will be medication adherence and sputum conversion. Adherence to medication will be calculated as the proportion of patients who missed doses in the intervention (pill count) versus DOT (direct observation) arms, confirmed further by IsoScreen urine isoniazid test and a self-report of adherence on eight-item Morisky Medication Adherence Scale. Sputum conversion is defined as the proportion of patients with smear conversion following the intensive phase in intervention versus DOT arms, confirmed further by pre-post intensive phase BACTEC MGIT TB liquid culture. Pre-post treatment MGIT drug susceptibility testing will determine whether resistance to anti-TB drugs could have impacted culture conversion. Secondary outcomes will include other clinical outcomes (treatment not completed, death, or loss to follow-up), cost-effectiveness-individual and societal costs with quality-adjusted life years-and acceptability and usability of the intervention by patients and providers.
CONCLUSIONS: This study will be the first in Ethiopia, and of the first three in sub-Saharan Africa, to determine whether electronic pillbox-enabled SAT improves adherence to TB medication and treatment outcomes, all without affecting the inherent dignity and economic wellbeing of patients with TB.
BACKGROUND: ClinicalTrials.gov, NCT04216420. Registered on 2 January 2020.

This study aims to evaluate the potential role of pillboxes used for the preparation and delivery of individual daily medical treatments in the drug circuit of the Military Instruction Hospital (France) as reservoirs of bacterial contaminants. Samples were obtained from 32 pillboxes after decontamination (T1), after preparation in the pharmacy (T2), after use in two different medical units (T3), and again after usual mechanical washing (T4). Qualitative (identification and antibiotic susceptibility) and quantitative (contamination rate and number of colony forming units-CFUs) bacteriological tests were performed. Susceptible and resistant strains of environmental saprophytes were identified. The pillbox contamination rate was relatively low at T1 (13%). It was significantly increased at T2 (63%, p = 0.001 vs. T1), again at T3 (88%, p < 0.05 vs. T2, p < 0.001 vs. T1), and finally decreased dramatically at T4 (31%, p < 0.001 vs. T3, p > 0.05 vs. T1). The number of CFUs was significantly increased at T2 compared with that of T1 (36.7 ± 13.4 and 5.36 ± 3.64, respectively, p < 0.001) and again at T3 (84.4 ± 19.4, p < 0.001 vs. T1 and T2) and was significantly reduced at T4 (7.0 ± 2.0 vs. T3, p < 0.001) to a level that was not significantly different from that at T1. So, the use of pillboxes to deliver individual medications to patients in the hospital is a potential risk factor for bacterial cross-contamination.

An appropriate medication management depends on executive system integrity, which can be affected by aging. Previous studies showed that seniors commit frequent errors when having to fill in a pillbox. Nevertheless, to the best of our knowledge, no study has really considered the absence of cognitive disorders in the studied sample. The present study aimed to investigate pillbox filling in cognitively healthy elderly (specially focusing on executive system preservation) for whom no cognitive deterioration neither any depressive episode had occurred during a one year period. The filling task has been completed using a weekly pillbox and eight fictitious drugs. The selection of the 27 seniors aged from 71 to 90 years has been based on their results to neuropsychological tests (Trail making test, Stroop Victoria, Tower of London, Montreal cognitive assessment) and a depression assessment scale (Short geriatric depression scale). Results showed that 67% of the participants committed at least one error when filling the pillbox and 56% at least 3. The maximal number of errors was 38. Further, the errors analysis showed that 85% of the errors had been repeated (e.g. reproduced on several days). Finally, the more complex the drug prescriptions are, the higher the error rate is. No other variable (age, gender, level education, habit of filling a pillbox) had any effect on the number of errors. So, the pillbox filing task can be considered as a complex task associated with a high risk of errors. Moreover, the absence of cognitive disorders is not a success factor to the task. A prospect for the future should be to try to limit the error rate by developing, for instance, an external support helping to the filling of the pillbox and a learning process for the use of this support.

OBJECTIVE: To compare patient cognition measured by Medi-Cog, a tool to assess cognitive literacy and pillbox skills, with pillbox concordance using two scoring methods, Pillbox Fill (PBF) and Prospective Pill Count (PPC).
METHODS: Prospective, descriptive, cross-sectional study.
METHODS: Primary care.
METHODS: Multiethnic participants with type 2 diabetes with sufficient vision and dexterity to load a pillbox.
METHODS: Medi-Cog scores were correlated with ability to fill a pillbox based on both the PPC and the PBF scoring methods. Variables were analyzed by multivariate linear and logistic regression.
METHODS: To determine whether there is a difference between PBF and PPC scoring methods relative to Medi-Cog prediction of pillbox concordance.
RESULTS: Sixty-four participants loaded an average of 5.2 medications. Mean Medi-Cog score for five patients who failed PBF but passed PPC were lower than the entire cohort (5.6 compared with 6.2). Correlation between PBF and PPC methods was 0.978; P = 0.01. Regression values for Medi-Cog\'s ability to predict PBF and PPC scores were r = 0.668 and r2 = 0.446, and r = 0.660 and r2 = 0.436; P < 0.01 for all.
CONCLUSIONS: Compared with PPC, PBF proved to be a more conservative scoring method and captured an additional five patients who scored less-well on the Medi-Cog. Future studies are needed to explore the value of using pillbox assessments as well as cognitive screening prior to recommending pillbox use.