Interprofessional Medication Adherence Program for Patients With Diabetic Kidney Disease: Protocol for a Randomized Controlled and Qualitative Study (PANDIA-IRIS)

Background Despite effective treatments, more than 30% of patients with diabetes will present with diabetic kidney disease (DKD) at some point. Patients with DKD are among the most complex as their care is multifactorial and involves different groups of health care providers. Suboptimal adherence to polypharmacy is frequent and contributes to poor outcomes. As self-management is one of the keys to clinical success, structured medication adherence programs are crucial. The PANDIA-IRIS (patients diabétiques et insuffisants rénaux: un programme interdisciplinaire de soutien à l’adhésion thérapeutique) study is based on a routine medication adherence program led by pharmacists. Objective The aim of this study is to define the impact of the duration of this medication adherence program on long-term adherence and clinical outcomes in patients with DKD. Methods This monocentric adherence program consists of short, repeated motivational interviews focused on patients’ medication behaviors combined with the use of electronic monitors containing patients’ medications. When patients open the electronic monitor cap to take their medication, the date and hour at each opening are registered. In total, 73 patients are randomized as 1:1 in 2 parallel groups; the adherence program will last 6 months in the first group versus 12 months in the second group. After the intervention phases, patients continue using their electronic monitors for a total of 24 months but without receiving feedback. Electronic monitors and pill counts are used to assess medication adherence. Persistence and implementation will be described using Kaplan-Meier curves and generalized estimating equation multimodeling, respectively. Longitudinal adherence will be presented as the product of persistence and implementation and modelized by generalized estimating equation multimodeling. The evolution of the ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron Modified-Release Controlled Evaluation) and UKPDS (United Kingdom Prospective Diabetes Study) clinical scores based on medication adherence will be analyzed with generalized estimating equation multimodeling. Patients’ satisfaction with this study will be assessed through qualitative interviews, which will be transcribed verbatim, coded, and analyzed for the main themes. Results This study was approved by the local ethics committee (Vaud, Switzerland) in November 2015. Since then, 2 amendments to the protocol have been approved in June 2017 and October 2019. Patients’ recruitment began in April 2016 and ended in October 2020. This study was introduced to all consecutive eligible patients (n=275). Among them, 73 accepted to participate (26.5%) and 202 (73.5%) refused. Data collection is ongoing and data analysis is planned for 2022. Conclusions The PANDIA-IRIS study will provide crucial information about the impact of the medication adherence program on the adherence and clinical outcomes of patients with DKD. Monitoring medication adherence during the postintervention phase is innovative and will shed light on the duration of the intervention on medication adherence. Trial Registration Clinicaltrials.gov NCT04190251_PANDIA IRIS; https://clinicaltrials.gov/ct2/show/NCT04190251 International Registered Report Identifier (IRRID) DERR1-10.2196/25966

Self-titration of inhaled corticosteroid and β2-agonist in response to symptoms in mild asthma: a pre-specified analysis from the PRACTICAL randomised controlled trial

IntroductionIn mild asthma, as-needed budesonide–formoterol is superior or noninferior to maintenance budesonide plus as-needed short-acting β2-agonist in reducing severe exacerbations. In this pre-specified analysis, we investigated patterns of inhaled corticosteroid (ICS) and β2-agonist use in PRACTICAL, a randomised controlled trial.MethodsParticipants were randomised 1:1 to as-needed budesonide–formoterol (200/6 μg Turbuhaler, one actuation) or maintenance budesonide (200 μg Turbuhaler, one actuation twice a day) with as-needed terbutaline (250 μg, two actuations) for 52 weeks. 110 participants had electronic monitors attached to their study inhalers which captured the time and date of every actuation. Key outcome measures were patterns of ICS and β2-agonist use. One actuation of budesonide–formoterol was considered to be an equivalent bronchodilator dose as two actuations of terbutaline.ResultsParticipants randomised to as-needed budesonide–formoterol had more days with no ICS use compared with maintenance budesonide (median total days of no use 156 versus 22 days, respectively), lower median daily budesonide dose (164 versus 328 μg, respectively) and a greater median number of days of ≥4 budesonide actuations (4 versus 1 days, respectively). Participants randomised to as-needed budesonide–formoterol took higher equivalent doses of β2-agonist both overall (median number of actuations 0.8 versus 0.3 per day, respectively) and in response to worsening asthma (total number of “overuse days” of >8 or >16 actuations of budesonide–formoterol or terbutaline 33 versus 10 days, respectively).ConclusionsThe timing of ICS dose when self-titrated to β2-agonist use is more important than total ICS dose in reducing severe exacerbation risk in mild asthma, when associated with greater overall use of as-needed β2-agonist.

Protocol for a randomised controlled trial to evaluate the effectiveness of improving tuberculosis patients’ treatment adherence via electronic monitors and an app versus usual care in Tibet

Background: Treatment non-adherence is a serious challenge to effective tuberculosis (TB) control in Tibet. In this study we will pilot and evaluate the effectiveness of using new electronic monitors (e-monitors) and a smartphone app to improve treatment adherence among new pulmonary TB patients in Tibet. Methods: We will use a multicentre, parallel-group, individually-randomized controlled superiority trial with blinded outcome evaluation and unblinded treatment. We will randomise new pulmonary TB outpatients (aged ≥15 years old and free from communication impairment) from Shigatse, Tibet to either the intervention or control arm in a 1:1 ratio at the time of their diagnosis. All patients will be treated according to the World Health Organisation standard 6-month TB treatment regimen and the China National TB programme guidelines. Intervention arm patients will be given their medication via e-monitors that have automatic voice reminders, and record medication adherence data and share it with health staff via cloud connection. Intervention patients will also be encouraged of receiving smartphone-based video observed treatment if their adherence is problematic. Control arm patients will receive their medication in e-monitors that will collect medication adherence history, but will have their reminder function deactivated and are not linked to the app. The primary outcome is the rate of poor adherence, measured monthly during treatment as a binary indicator where poor adherence means missing ≥20% doses in a month. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and an analysis of the long-term effects of the intervention on TB control. Discussion: Our study is one of the first trials to evaluate the use of e-monitors and smartphone apps for customised treatment support in low- and middle-income countries (LMICs). All intervention activities are designed to be embedded into routine TB care with strong local ownership. Through the trial we intend to understand the feasibility of our intervention, its effectiveness, its cost-effectiveness and its long-term impacts to inform future scale-up in remote areas of China and other LMICs. Trial registration: Current Controlled Trials ISRCTN52132803, registered on 9 November 2018.

Protocol for a pragmatic randomised controlled trial to evaluate the effectiveness of improving tuberculosis patients’ treatment adherence via electronic monitors and an app versus usual care in Tibet

Background: Treatment non-adherence is a serious challenge to effective tuberculosis (TB) control in Tibet. In this study, we will pilot and evaluate the effectiveness of using new technologies, including electronic monitors (e-monitors) and a smartphone app, to improve treatment adherence among new pulmonary TB patients in Tibet, China. Methods: This is a prospective, pragmatic, multicentre, individual-randomized trial with blinded evaluation of outcomes and data analysis, and unblinded treatment. New pulmonary TB patients of Shigatse, Tibet will be randomized to either the intervention or control arm in a 1:1 ration at the time of their diagnoses. All patients will be treated according to the WHO standard TB treatment regimens and China National TB program guidelines. In the control arm, patients will receive their medicines in e-monitors that are deactivated for its reminder function but are able to collect medication adherence history. In the intervention arm, patients will take medications in e-monitors that will record their medication adherence and share with health staff via a smartphone app. Patients will be opted to receive video observed treatment when adherence is problematic. The primary outcome is the rate of poor adherence measured per month during their treatment. It will be calculated from monthly-level data for each patient indicating the number of doses missed per month, with poor monthly adherence defined as the patient having missed ≥20% of doses per month. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, a cost-effectiveness analysis and long-term effects on TB control. Discussion: Our study is one of the first trials to evaluate the use of e-monitors and smartphone app to improve communications between TB patients and health staff in low-and-middle income countries (LMICs). All intervention activities are designed to be embedded into routine practice of TB care with strong local ownership. Through the trial, we intend to understand the effectiveness of our intervention, as well as its feasibility, cost-effectiveness and long-term impact to inform future scale-up in remote areas of China and LMICs. Trial Registration: Current Controlled Trials ISRCTN52132803, registered on 9 November 2018. Keywords: Tuberculosis, treatment adherence, mhealth, randomised controlled trial, Tibet

The Presence of Human Immunodeficiency Virus-Associated Neurocognitive Disorders Is Associated With a Lower Adherence to Combined Antiretroviral Treatment

Background Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) are defined according to their diagnostic degrees as follows: asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia. Because high adherence to combined antiretroviral therapy (cART) is required to maintain viral suppression among HIV-infected patients, it is important to investigate the impact of HAND on medication adherence. Our study hypothesis was that patients with HAND had a lower medication adherence than patients who did not have HAND. Methods This was an observational, exploratory, 2-center pilot study of patients who had a state-of-the-art neurocognitive assessment performed between January 2011 and June 2015 while also being followed at their respective adherence clinics. Adherence was measured with electronic monitors. Patients’ sociodemographic characteristics, HIV viral load, and CD4 counts were retrieved from the Swiss HIV Cohort Study database. At each time t, adherence was computed as the proportion of patients taking medication as prescribed at that time. Results We included 59 patients, with a median (Q1, Q3) age of 53 years (47–58) and 39 (66%) were male participants. Twenty-two patients (35%) had no neurocognitive deficits, 16 (27%) patients had HAND, and 21 (35%) patients had non-HAND (mostly depression). Implementation over 3 years showed a significant decline (50%) in medication adherence among patients diagnosed with HAND in comparison with patients who had a normal neuropsychological status or a non-HIV-related cognitive deficit (implementation stayed 90% during follow-up). Conclusions Our findings support the hypothesis that HAND is associated with reduced cART adherence.

A review of behavioral tailoring strategies for improving medication adherence in serious mental illness

Nonadherence to psychopharmacological treatments poses a significant challenge to treatment success in individuals with serious mental illness, with upwards of 60% of people not taking their psychiatric medications as prescribed. Nonadherence is associated with adverse outcomes, including exacerbation of psychiatric symptoms, impaired functioning, increased hospitalizations and emergency room use, and increased health care costs. Whereas interventions using psychoeducation or cognitive approaches, such as motivational interviewing, have largely proven ineffective in improving adherence, approaches employing behavioral tailoring that incorporate medication taking into the daily routine and/or use environmental supports have shown promise. Recently, adherence-enhancing behavioral tailoring interventions that utilize novel technologies, such as electronic monitors and mobile phones, have been developed. Although interventions utilizing these platforms have the potential for widespread dissemination to a broad range of individuals, most require further empirical testing. This paper reviews selected behavioral tailoring strategies that aim to improve medication adherence and other functional outcomes among individuals with serious mental illness.