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Introduction: The ACCESS trial showed that those who received a copayment elimination benefit had a modest improvement in their adherence to medications, but no improvement in clinical outcomes. This is consistent with other studies that have demonstrated that time-limited copayment elimination was welcomed by participants. However, the removal of such benefits can be problematic, as participants may have become accustomed to receiving the benefit, and made changes to their spending that would need to be reconsidered. We aimed to explore participants' experience with resuming cost sharing for their medications at the end of the ACCESS trial and if this experience influenced their willingness to participate in future trials like ACCESS. Methods: We conducted semi-structured interviews with 21 former participants of the ACCESS trial who were receiving the copayment elimination intervention, with discussions focused on the loss of the copayment elimination. The interviews were recorded, transcribed, and analyzed in duplicate using thematic analysis. Results: Four primary themes emerged from the analysis, including emotionality regarding loss of benefits; notification of benefit termination, describing tangible losses from coverage ending, but resistance to acknowledging negative impacts; and acceptability of receiving a temporary financial benefit. Many participants described negative emotions around the loss of coverage and concern about affording care for their chronic diseases. Despite negative emotions about the end of their study benefit, participants generally had a positive view of the study and would participate again in a future study of this nature. Conclusion: The positive tangible and emotional benefits of the copayment elimination over 3 years outweighed the negative emotions and impacts associated with having to become reaccustomed to life without it. Patient and public contribution: Within the ACCESS trial, participants were involved in the design, modification, and implementation of the program using multiple focus groups. The current study aimed to engage patients to provide input on their experience and engagement with the copayment elimination program. [ABSTRACT FROM AUTHOR]

Background: Hypertension is the most common cardiovascular disease in Peru despite the availability of cost-effective, evidence-based treatment. Here we describe the rationale and study design for a hybrid type 2 randomized controlled trial to test the implementation and effectiveness of a community health worker (CHW)-led hypertension control program within the national primary care system in Puno, Peru. Methods: We will recruit 1068 adult participants with hypertension aged ≥ 18 years in Puno, Peru, via facility-based enrollment and community health fairs. Participants will be individually randomized (1:1) to either continue with usual care or participate in a 12-month CHW-led home-based hypertension control program consisting of blood pressure monitoring, medication adherence support, and healthy lifestyle counseling. Outcome development and reporting are guided by the Consolidated Framework for Implementation Research (CFIR), the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, and the Proctor et al. framework. Clinical effectiveness outcomes include mean change in systolic blood pressure (primary outcome), diastolic blood pressure, and HbA1C. Implementation outcomes include fidelity (i.e., CHW protocol adherence and dose), reach, adoption, sustainability, acceptability, and cost-effectiveness. Discussion: The ANDES trial is testing the first CHW-led multicomponent strategy for hypertension and type 2 diabetes management in Peru. This type 2 hybrid trial will provide critical insights into the individual, community, and system-level factors necessary for successful implementation and effectiveness. These data can inform the future adaptation and scaling of the ANDES strategy in Peru and other LMICs, as well as influence policies at the system level to support this transition. Furthermore, by addressing both hypertension and diabetes, the ANDES strategy supports integrated care approaches advocated by the WHO HEARTS technical package, ultimately enhancing health outcomes and reducing morbidity and mortality in the region. Trial registration: ClinicalTrials.gov, ID: NCT05524987, Addressing Hypertension and Diabetes through Community-Engaged Systems in Puno, Peru (ANDES study), prospectively registered on September 1, 2021. [ABSTRACT FROM AUTHOR]

Background: Patient education is a crucial strategy for promoting prevention and diabetes self-management since glycemic control achievement involves taking medications, medical nutrition therapy, physical exercise, and behavior changes. However, patient education programs are still barely implemented in low- and middle-income countries. This trial aims to investigate whether a lifestyle education intervention added to physical exercising is superior to sole physical exercising regarding functional capacity, disease-related knowledge, health behaviors, cardiometabolic health parameters, quality of life, depression, and diet quality in individuals with prediabetes or diabetes. Methods: Multicenter double-blinded randomized controlled trial with two parallel arms involving 12-week intervention and 6-month follow-up. The eligible individuals (≥ 18 years, living with prediabetes or diabetes, literate, no clinical decompensation and/or physical and/or mental limitations that contraindicate physical exercising, written physician permission for exercise, no cognitive impairment, no vision limitations for reading, no confirmed diagnosis of unstable coronary disease or heart failure, no pacemaker and/or implantable cardioverter-defibrillator, no complex ventricular arrhythmias, no intermittent claudication, no recent cardiovascular event or cardiac surgery, and no currently enrolled in a structured exercise program) were recruited from two Brazilian cities and randomized to either (1) an Exercise and Lifestyle Education Program (ExLE) or (2) an Exercise Program (Ex), which can be delivered on-site or remotely based on the participants' internet access and technology literacy. The primary outcomes will be changes in functional capacity and disease-related knowledge. The secondary outcomes will involve changes in health behaviors (health literacy, physical activity level, exercise self-efficacy, and medication adherence) and cardiometabolic health parameters (glycemic control, anthropometric measures, and cardiac autonomic control). Program adherence, satisfaction with the program, diabetes-related morbidity, and changes in quality of life, depression, and diet quality will be the tertiary outcomes. Assessments will occur at baseline, post-intervention, and after 6-month follow-up. Discussion: If superior effectiveness of ExLE compared to Ex program to improve the outcomes measures is found, this program could be delivered broadly in the Brazilian health system, especially in the primary care facilities where most individuals living with prediabetes and diabetes in our country are assisted. Trial registration: ClinicalTrials.gov, NCT03914924. Registered on April 16, 2019. [ABSTRACT FROM AUTHOR]

Background: Use of antibiotics is the main driver of antimicrobial resistance which is considered one of the biggest threats to human health. In Denmark, most antibiotics are prescribed in general practice. Acute lower respiratory tract infections, including community-acquired pneumonia (CAP), are among the most frequent indications for antibiotic prescribing. Phenoxymethylpenicillin is established as first-line treatment in general practice in Denmark. However, the treatment duration with phenoxymethylpenicillin is mostly based on traditions. Both 5 and 7 days of treatment is recommended in Danish guidelines, and when asking the general practitioners about what treatment duration, they prescribe the variation is even bigger. Several hospital-based studies have proven short course (≤ 6 days) antibiotic treatment non-inferior to long course (≥ 7 days) treatment of CAP. No evidence exists on the optimal treatment duration for CAP in non-hospitalised patients. This randomised controlled trial aim to investigate the optimal treatment duration with phenoxymethylpenicillin for CAP in adults diagnosed in general practice in Denmark. Methods: This is an open-label, pragmatic, randomised controlled, five-arm DURATIONS trial. Participants will be recruited from at least 24 general practices in Denmark. Eligible participants are adults, with no pre-existing lung disease, presenting with symptoms of CAP, and in whom the general practitioner finds it relevant to treat with antibiotics. The study will compare treatment with phenoxymethylpenicillin 1.2 MIE q.i.d. in 3, 4, 5, 6, and 7 days. Discussion: This study will provide evidence for the optimal antibiotic treatment duration of CAP in general practice and inform future guidelines on CAP in all countries using phenoxymethylpenicillin for the treatment of acute respiratory tract infections in adults. The results of this study might also be used to guide treatment recommendations in other countries using phenoxymethylpenicillin. Moreover, a (potential) reduction in antibiotic use might lower the development of antimicrobial resistance, increase patient treatment adherence, reduce risks of adverse events, and lower the economical exp Trial registration: ClinicalTrials.gov: NCT06295120. Registered 28 February 2024. The Scientific Ethics Committee for the North Denmark Region: N-20230039. [ABSTRACT FROM AUTHOR]

Background: Recent literature suggests that ADHD is a risk factor for the development of antisocial behavior that is more severe and persistent than in community and other psychiatric populations. The combination of stimulant medication and psychotherapy (particularly cognitive behavioral therapy, CBT) is considered an evidence-based intervention for adults with ADHD. In contrast, few studies have evaluated the efficacy of medication in adult prisoners with ADHD, and the literature on the efficacy of psychotherapy is virtually nonexistent. Therefore, this article presents the protocol of a trial that will assess the efficacy of a formulation-based CBT program for inmates with ADHD. Methods: The study has a multicenter randomized controlled trial design. After screening and recruitment, participants will be randomly assigned to the CBT intervention, a general offender treatment program, or a waitlist. Pre- and post-treatment self-report and clinician-report assessments, as well as 6- and 12-month follow-up assessments will be conducted. These will include both clinical (e.g., ADHD symptoms, depression and anxiety symptoms, self-esteem, alcohol/drug abuse, treatment adherence, quality of life) and criminological (e.g., recidivism and risk of recidivism) measures. Linear mixed models will be used to assess differences between groups. Discussion: This study may be the first to evaluate the efficacy of a psychotherapy intervention in adult inmates with ADHD. It is expected that addressing the specific needs of ADHD would not only result in the previously reported clinical improvements (e.g., reduction in ADHD and comorbidity symptoms), but also reduce the risk and rate of recidivism compared to the general intervention or no intervention. However, the design may be limited by the difficulties inherent in the prison setting and in following up the sample after release. Trial registration: ClinicalTrials.gov NCT06080373. Registered on October 12, 2023. [ABSTRACT FROM AUTHOR]

Background: The distinction between normal and high blood pressure remains a debated topic, with varying guidelines on when to start medication. Contemporary guidelines advocate for the initiation of antihypertensive therapy in individuals who present with high-normal blood pressure, particularly those exhibiting elevated 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores. Despite these recommendations, there is a notable lack of direct evidence supporting the efficacy of treating high-normal blood pressure to prevent major adverse cardiovascular events (MACE). Methods: The PRINT-TAHA9 trial, a unicentric, randomized, open-label, controlled, parallel clinical study, seeks to explore the effects of intensive blood pressure control on MACE in participants with high-normal blood pressure. We will enroll 1620 adults aged 18 years and above with a systolic blood pressure range of 130–140 mmHg, diastolic blood pressure under 90 mmHg, and atherosclerotic cardiovascular disease (ASCVD) risk score exceeding 7.5%. The study will be executed in five distinct phases, with each phase enrolling between 300 and 400 participants. Participants will be randomly assigned to either the treatment group receiving antihypertensive medication (amlodipine/valsartan) and a low-salt/low-fat diet or to the control group receiving a similar diet. Follow-up visits are scheduled every 6 months over a 3-year period to monitor blood pressure, evaluate medication adherence, document any adverse events, and adjust the intervention as necessary. Cox proportional hazards regression analysis will be employed to examine the disparities between the two arms. Discussion: Despite guidelines promoting early treatment of elevated blood pressure, the debate continues due to insufficient evidence that such interventions significantly reduce the occurrence of MACE. This trial seeks to address this critical evidence gap. Trial registration: The PRINT-TAHA9 trial was registered in October 2019 with the Iranian Registry of Clinical Trials (IRCT.ir) under the registration number IRCT20191002044961N1. https://irct.behdasht.gov.ir/trial/43092. [ABSTRACT FROM AUTHOR]

Background: Low back pain is one of the most common symptoms of osteoporosis. The pain can seriously affect patients' mood and quality of life; it can also further aggravate bone loss, causing a serious social burden. Minodronate is an oral bisphosphonate that needs to be administered daily. It significantly reduces levels of bone turnover markers (BTMs) and rapidly improves symptoms of low back pain in patients with osteoporosis. Osteoporosis requires long-term treatment, and daily dosing reduces patient compliance. Minodronate has a better safety profile than other bisphosphonates. The objective of the trial is to explore the efficacy and safety of minodronate in the treatment of low back pain in postmenopausal osteoporosis patients. Methods: This is a single-centre, randomized, open-label controlled trial with a 24-week duration. Seventy-two eligible patients will be randomly divided into 4 groups. Subjects will be randomized at a 1:1 ratio to receive either minodronate (1 mg/day) or alendronate (10 mg/day) every day; senior women (≥ 75 years old) and older women (< 75 years old) will be at a ratio of 1:2. The primary outcome is the time required for the visual analogue scale (VAS) score to decline by ≥ 10 from baseline. The secondary outcome is the changes in VAS scores from baseline, the frequency and dosage of rescue medication, BTMs, bone mineral density (BMD), and variations in upper gastrointestinal (GI) symptom scores from baseline (including heartburn, pain, and bloating). Discussion: This study will provide objective evidence for the efficiency and safety of minodronate. Furthermore, it will be helpful to evaluate the quantitative relationship between BTMs and BMD in patients with osteoporosis under different ages. Trial registration: This study protocol has been registered with ClinicalTrials.gov ID NCT05645289 (https://clinicaltrials.gov/search?term=NCT05645289) on December 8, 2022. The registry name is Peking University Third Hospital. This study protocol was reviewed and approved by the Peking University Third Hospital Medical Science Research Ethics Committee (M2022465, 2022.08.09, V2.0). The results will be published in scientific peer-reviewed journals. Trial status: The protocol was registered at ClinicalTrials.gov (registration number: NCT05645289). Recruitment has started in January 2023 and is still ongoing. [ABSTRACT FROM AUTHOR]

Background: Digital technologies, such as wearable devices and smartphone applications (apps), can enable the decentralisation of clinical trials by measuring endpoints in people's chosen locations rather than in traditional clinical settings. Digital endpoints can allow high-frequency and sensitive measurements of health outcomes compared to visit-based endpoints which provide an episodic snapshot of a person's health. However, there are underexplored challenges in this emerging space that require interdisciplinary and cross-sector collaboration. A multi-stakeholder Knowledge Exchange event was organised to facilitate conversations across silos within this research ecosystem. Methods: A survey was sent to an initial list of stakeholders to identify potential discussion topics. Additional stakeholders were identified through iterative discussions on perspectives that needed representation. Co-design meetings with attendees were held to discuss the scope, format and ethos of the event. The event itself featured a cross-disciplinary selection of talks, a panel discussion, small-group discussions facilitated via a rolling seating plan and audience participation via Slido. A transcript was generated from the day, which, together with the output from Slido, provided a record of the day's discussions. Finally, meetings were held following the event to identify the key challenges for digital endpoints which emerged and reflections and recommendations for dissemination. Results: Several challenges for digital endpoints were identified in the following areas: patient adherence and acceptability; algorithms and software for devices; design, analysis and conduct of clinical trials with digital endpoints; the environmental impact of digital endpoints; and the need for ongoing ethical support. Learnings taken for next generation events include the need to include additional stakeholder perspectives, such as those of funders and regulators, and the need for additional resources and facilitation to allow patient and public contributors to engage meaningfully during the event. Conclusions: The event emphasised the importance of consortium building and highlighted the critical role that collaborative, multi-disciplinary, and cross-sector efforts play in driving innovation in research design and strategic partnership building moving forward. This necessitates enhanced recognition by funders to support multi-stakeholder projects with patient involvement, standardised terminology, and the utilisation of open-source software. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and at present, India has the highest burden of acute coronary syndrome and ST-elevation myocardial infarction (MI). A key reason for poor outcomes is non-adherence to medication. Methods: The intervention is a 2 × 2 factorial design trial applying two interventions individually and in combination with 1:1 allocation ratio: (i) ASHA-led medication adherence initiative comprising of home visits and (ii) m-health intervention using reminders and self-reporting of medication use. This design will lead to four potential experimental conditions: (i) ASHA-led intervention, (ii) m-health intervention, (iii) ASHA and m-health intervention combination, (iv) standard of care. The cluster randomized trial has been chosen as it randomizes communities instead of individuals, avoiding contamination between participants. Subcenters are a natural subset of the health system, and they will be considered as the cluster/unit. The factorial cluster randomized controlled trial (cRCT) will also incorporate a nested health economic evaluation to assess the cost-effectiveness and return on investment (ROI) of the interventions on medication adherence among patients with CVDs. The sample size has been calculated to be 393 individuals per arm with 4–5 subcenters in each arm. A process evaluation to understand the effect of the intervention in terms of acceptability, adoption (uptake), appropriateness, costs, feasibility, fidelity, penetration (integration of a practice within a specific setting), and sustainability will be done. Discussion: The effect of different types of intervention alone and in combination will be assessed using a cluster randomized design involving 18 subcenter areas. The trial will explore local knowledge and perceptions and empower people by shifting the onus onto themselves for their medication adherence. The proposal is aligned to the WHO-NCD aims of improving the availability of the affordable basic technologies and essential medicines, training the health workforce and strengthening the capacity of at the primary care level, to address the control of NCDs. The proposal also helps expand the use of digital technologies to increase health service access and efficacy for NCD treatment and may help reduce cost of treatment. Trial registration: The trial has been registered with the Clinical Trial Registry of India (CTRI), reference number CTRI/2023/10/059095. [ABSTRACT FROM AUTHOR]

Background: Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after gastrectomy. However, there is no consistent evidence supporting the beneficial effects of ONS on BWL, muscle strength and health-related quality of life (HRQoL). This study aimed to evaluate the effects of ONS formulated primarily with carbohydrate and protein on BWL, muscle strength, and HRQoL. Methods: This will be a multicenter, open-label, parallel, randomized controlled trial in patients with gastric cancer who will undergo gastrectomy. A total of 120 patients who will undergo gastrectomy will be randomly assigned to the ONS group or usual care (control) group in a 1:1 ratio. The stratification factors will be the clinical stage (I or ≥ II) and surgical procedures (total gastrectomy or other procedure). In the ONS group, the patients will receive 400 kcal (400 ml)/day of ONS from postoperative day 5 to 7, and the intervention will continue postoperatively for 8 weeks. The control group patients will be given a regular diet. The primary outcome will be the percentage of BWL (%BWL) from baseline to 8 weeks postoperatively. The secondary outcomes will be muscle strength (handgrip strength), HRQoL (EORTC QLQ-C30, QLQ-OG25, EQ-5D-5L), nutritional status (hemoglobin, lymphocyte count, albumin), and dietary intake. All analyses will be performed on an intention-to-treat basis. Discussion: This study will provide evidence showing whether or not ONS with simple nutritional ingredients can improve patient adherence and HRQoL by reducing BWL after gastrectomy. If supported by the study results, nutritional support with simple nutrients will be recommended to patients after gastrectomy for gastric cancer. Trial registration: jRCTs051230012; Japan Registry of Clinical Trails. Registered on Apr. 13, 2023. [ABSTRACT FROM AUTHOR]

Background: There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. Methods: This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18–65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. Discussion: This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022. [ABSTRACT FROM AUTHOR]

Background: Multimorbid and frail elderly patients often carry a high burden of treatment. Hospitalization due to the onset of an acute illness can disrupt the fragile balance, resulting in further readmissions after hospital discharge. Current models of care in Germany do not meet the needs of this patient group. Rather lack of coordination and integration of care combined with a lack of interdisciplinary approaches result in fragmented and inadequate care and increase the burden of treatment even more. Methods: eliPfad is a randomized controlled trial conducted in 6 hospitals in Germany. Multimorbid elderly patients aged 55 or older are randomly assigned to the intervention or control group. Patients in the intervention group receive the eliPfad intervention additional to standard care. The core components of eliPfad are: Early assessment of patients' individual treatment burden and support through a specially trained case manager Involvement of the patient's general practitioner (GP) right from the beginning of the hospital stay Preparation of an individual, cross-sectoral treatment plan through the interdisciplinary hospital team with the involvement of the patient's GP Establishment of a cross-sectoral electronic patient record (e-ePA) for documentation and cross-sectoral exchange Support/Promote patient adherence Tailored early rehabilitation during the hospital stay, which is continued at home Close-tele-monitoring of medically meaningful vital parameters through the use of tablets, digital devices, and personal contacts in the home environment The intervention period begins in the hospital and continues 6 weeks after discharge. Patients in the control group will be treated according to standard clinical care and discharged according to current discharge management. The primary aim is the prevention/reduction of readmissions in the first 6 months after discharge. In addition, the impact on health-related quality of life, the burden of treatment, survival, self-management, medication prescription, health literacy, patient-centered care, cost-effectiveness, and process evaluation will be examined. Nine hundred forty-eight patients will be randomized 1:1 to intervention and control group. Discussion: If eliPfad leads to fewer readmissions, proves (cost-)effective, and lowers the treatment burden, it should be introduced as a new standard of care in the German healthcare system. Trial registration: The trial was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) on 08/14/2023 under the ID DRKS00031500. [ABSTRACT FROM AUTHOR]

Introduction: A substantial proportion of patients with bipolar disorder experience daily subsyndromal mood swings, and the term "mood instability" reflecting the variability in mood seems associated with poor prognostic factors, including impaired functioning, and increased risk of hospitalization and relapse. During the last decade, we have developed and tested a smartphone-based system for monitoring bipolar disorder. The present SmartBipolar randomized controlled trial (RCT) aims to investigate whether (1) daily smartphone-based outpatient monitoring and treatment including clinical feedback versus (2) daily smartphone-based monitoring without clinical feedback or (3) daily smartphone-based mood monitoring only improves mood instability and other clinically relevant patient-related outcomes in patients with bipolar disorder. Methods and analysis: The SmartBipolar trial is a pragmatic randomized controlled parallel-group trial. Patients with bipolar disorder are invited to participate as part of their specialized outpatient treatment for patients with bipolar disorder in Mental Health Services in the Capital Region of Denmark. The included patients will be randomized to (1) daily smartphone-based monitoring and treatment including a clinical feedback loop (intervention group) or (2) daily smartphone-based monitoring without a clinical feedback loop (control group) or (3) daily smartphone-based mood monitoring only (control group). All patients receive specialized outpatient treatment for bipolar disorder in the Mental Health Services in the Capital Region of Denmark. The trial started in March 2021 and has currently included 150 patients. The outcomes are (1) mood instability (primary), (2) quality of life, self-rated depressive symptoms, self-rated manic symptoms, perceived stress, satisfaction with care, cumulated number and duration of psychiatric hospitalizations, and medication (secondary), and (3) smartphone-based measures per month of stress, anxiety, irritability, activity, and sleep as well as the percentage of days with presence of mixed mood, days with adherence to medication and adherence to smartphone-based self-monitoring. A total of 201 patients with bipolar disorder will be included in the SmartBipolar trial. Ethics and dissemination: The SmartBipolar trial is funded by the Capital Region of Denmark and the Independent Research Fund Denmark. Ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248) as well as data permission (journal number: P-2019–809). The results will be published in peer-reviewed academic journals, presented at scientific meetings, and disseminated to patients' organizations and media outlets. Trial registration: Trial registration number: NCT04230421. Date March 1, 2021. Version 1. [ABSTRACT FROM AUTHOR]

Background: In the USA, the primary cause of death and morbidity continues to be cardiovascular disease (CVD). Numerous trials have shown that statin medication reduces the likelihood of CVD events; it is a cornerstone of CVD prevention. However, studies have also indicated that up to 60% of the estimated 26.8 million Americans prescribed primary prevention statin treatment are nonadherent during the first year. Multi-component behavioral change technique (BCT) therapies have shown moderate promise in improving medication adherence as well as other positive health behaviors (such as physical activity). However, no research has looked at the duration of multi-component BCT intervention needed to result in a clinically significant improvement in statin adherence behaviors. This study aims to determine the necessary dose of a multi-component BCT intervention (defined as duration in weeks) to promote adherence to statin medication among those on primary prevention statin treatment by utilizing the modified time-to-event continuous reassessment method (TiTE-CRM). Methods and design: The study will utilize the modified TiTE-CRM in 42 participants, recruited in 14 cohorts of 3 participants each. The goal of this analysis is to identify the minimum effective dose (MED) of a multi-behavior change technique (BCT) intervention required to increase adherence to statins by 20% between baseline and follow-up periods. Using the TiTE-CRM method, the dose of the behavior intervention in weeks will be assigned to each cohort based on the performance of the prior cohort. At the end of the study, the intervention dose that has been found to be associated with a 20% increase in statin adherence among 80% of participants assigned to that dose will be identified as the MED. Discussion: If successful, the current trial will provide additional guidance to researchers and clinicians seeking to increase statin medication adherence using a BCT intervention by identifying the dose (i.e., the duration) of an intervention required to meaningfully increase adherence. Trial registration: ClinicalTrials.gov NCT05273736. Registered on March 10, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05273736 [ABSTRACT FROM AUTHOR]

Background: Dysphagia can lead to serious complications such as aspiration and aspiration pneumonia, timely and effective rehabilitation training can improve the swallowing function of patients. However, the conventional rehabilitation training methods used in clinical settings have shortcomings such as poor adherence of patients. We present the study design of a randomized controlled trial that evaluated whether video-game based swallowing rehabilitation training can effectively improve swallowing in patients with dysphagia and whether it has additional benefits compared with conventional training methods to improve swallowing function and training compliance among patients with dysphagia. Methods: A randomized controlled trial with 4 weeks of intervention and 4 weeks of follow-up will be conducted in a rehabilitation center in Beijing, China. We will enroll 78 patients aged 18–80 years with dysphagia. Participants will be randomly assigned to the experimental group (video-game based swallowing function training) and the control group (conventional swallowing function training). All participants will receive 30 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcome is swallowing function. Secondary outcomes include patients' quality of life, training compliance, and training satisfaction. Outcomes are assessed at baseline (pre-treatment), 4 weeks of treatment (post-treatment), and 8 weeks (follow-up), and the assessor is not aware of the participants' grouping. Discussion: The protocol describes a new rehabilitation training method for dysphagia, which involves participant eligibility recruitment, recruitment strategies, and data analysis plan. The results of the study will inform the rehabilitation training and clinical care management of swallowing function in patients with dysphagia. Trial registration: ClinicalTrials.gov, NCT05978700. Registered on 28 July 2023. [ABSTRACT FROM AUTHOR]

Introduction: The rising prevalence of knee osteoarthritis is placing a considerable strain on the global healthcare system. To address this issue, telemedicine-supported multicomponent exercise therapy has emerged as a promising approach. This therapy combines exercise, patient education, and health coaching to empower knee osteoarthritis patients to manage their condition from the comfort of their homes. Nevertheless, there are some existing limitations in the current research on this approach, including challenges related to patient compliance and the absence of objective evaluation methods. Methods and analysis: Patients diagnosed with knee osteoarthritis, who have not undergone knee surgery in the past year, will be recruited for a randomized controlled trial. The trial will include an intervention group and a control group. The intervention group will receive an mHealth app-based multicomponent exercise therapy, consisting of exercise therapy, patient education, and health coaching. Meanwhile, the control group will receive usual care, involving drug therapy and patient education. The primary outcome of the trial will be the measurement of pain intensity, assessed using a visual analog scale at baseline and at 4, 8, and 12 weeks of the post-intervention. To analyze the data, a two-factor, four-level repeated measures ANOVA will be used if the assumptions of homogeneity of variance and sphericity are met. If not, a mixed effects model will be employed. Discussion: The aim of the study is to evaluate the effectiveness of multicomponent exercise therapy aimed at enhancing pain self-management for knee osteoarthritis patients in the comfort of their own homes. The intervention incorporate wearable devices equipped with advanced deep learning systems to monitor patients' adherence to the prescribed at-home exercise regimen, as well as to track changes in outcomes before and after the exercise sessions. The findings from this trial have the potential to enhance both the accessibility and quality of care provided to knee osteoarthritis patients, offering valuable insights for future improvements in their treatment and management. Trial registration: Chinese Clinical Trials Registry, ChiCTR2300073688. Registered on 19 July 2023, https://www.chictr.org.cn/bin/project/edit?pid=199707. World Health Organization International Clinical Trials Registry Platform, https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2300073688. [ABSTRACT FROM AUTHOR]

Background: Australia persistently has one of the highest rates of colorectal cancer (CRC) in the world. Australia's National Bowel Cancer Screening Program (NBCSP) sends a biennial Faecal Immunochemical Test (FIT)—the 'NBCSP kit'—to everyone eligible for the programme between 50 and 74 years old; however, participation in the programme is low, especially in the 50- to 60-year-old age group. Our previous efficacy trial ('SMARTscreen') demonstrated an absolute increase in uptake of 16.5% (95% confidence interval = 2.02–30.9%) for people sent an SMS with motivational and instructional videos, from their general practice prior to receiving their NBCSP kit, compared to those receiving usual care. Building on the strengths of the SMARTscreen trial and addressing limitations, the 'SMARTERscreen' trial will test the effect on participation in the NBCSP of sending either an SMS only or an SMS with online video material to general practice patients due to receive their NBCSP compared to 'usual care'. Methods: SMARTERscreen is a three-arm stratified cluster randomised controlled trial involving 63 general practices in two states in Australia. Eligible patients are patients who are aged 49–60 years and due to receive their NBCSP kit within the next 2 weeks during the intervention period. General practices will be equally randomised to three trial arms (21:21:21, estimated average 260 patients/practice). The two interventions include (i) an SMS with an encouraging message from their general practice or (ii) the same SMS with weblinks to additional motivational and instructional videos. The control arm will receive 'usual care'. Using the intention-to-treat approach, primary analysis will estimate the three pair-wise between-arm differences in the proportion of eligible patients who participate in the NBCSP within 6 months of when their kit is sent, utilising screening data from the Australian National Cancer Screening Register (NCSR). Patient intervention adherence to the interventions will also be evaluated. Findings will be incorporated into the Policy1-Bowel microsimulation model to estimate the long-term health benefits and cost-effectiveness of the interventions. Discussion: SMARTERscreen will provide high-level evidence determining whether an SMS or an SMS with web-based material sent to general practice patients prior to receiving their NBCSP kit increases participation in bowel cancer screening. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12623000036617. Registered on 13 January 2023. Trial URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385119&isClinicalTrial=False [ABSTRACT FROM AUTHOR]

Background: Physical activity is an effective management strategy for heart failure with reduced ejection fraction, but patients' compliance is challenging. Walking is a suitable form of physical activity due to its convenience and sustainability, and it can potentially improve functional capacity in heart failure patients. Objectives: The WATCHFUL trial aims to determine whether a pedometer-based walking intervention combined with face-to-face sessions and regular telephone contact improves functional capacity in heart failure patients. Methods: The WATCHFUL trial is a 6-month multicenter, parallel-group, randomized, controlled, superiority trial with a 6-month follow-up. A total of 202 patients were recruited for the trial. The primary analysis will evaluate the change in distance walked during the 6-min walk test from baseline to 6 months based on the intention-to-treat population; the analysis will be performed using a linear mixed-effect model adjusted for baseline values. Missing data will be imputed using multiple imputations, and the impact of missing data will be assessed using a sensitivity analysis. Adverse events are monitored and recorded throughout the trial period. Discussion: The trial has been designed as a pragmatic trial with a scalable intervention that could be easily translated into routine clinical care. The trial has been affected by the COVID-19 pandemic, which slowed patients' recruitment and impacted their physical activity patterns. Conclusions: The present publication provides details of the planned statistical analyses for the WATCHFUL trial to reduce the risks of reporting bias and erroneous data-driven results. Trial registration: ClinicalTrials.gov (identifier: NCT03041610, registered: 3/2/2017). [ABSTRACT FROM AUTHOR]

Background: Mechanical hyperinflation maneuver (MHM) is a technique known for optimizing bronchial hygiene and respiratory mechanics; however, its effects on intracranial compliance are not known. Methods: Sixty patients aged ≥ 18 years, with clinical diagnosis of acute stroke, confirmed by neuroimaging examination, with onset of symptoms within 72 h, under mechanical ventilation through tracheal tube, will participate in this study. Participants will be randomly allocated into 2 groups: experimental group (n = 30)—MHM plus tracheal aspiration—and control group (n = 30)—tracheal aspiration only. Intracranial compliance will be measured by a non-invasive technique using Brain4care BcMM-R-2000 sensor. This will be the primary outcome. Results will be recorded at 5 times: T0 (start of monitoring), T1 (moment before MHM), T2 (moment after the MHM and before tracheal aspiration), T3 (moment after tracheal aspiration), T4, and T5 (monitoring 10 and 20 min after T3). Secondary outcomes are respiratory mechanics and hemodynamic parameters. Discussion: This study will be the first clinical trial to examine the effects and safety of MHM on intracranial compliance measured by non-invasive monitoring. Limitation includes the impossibility of blinding the physical therapist who will supervise the interventions. It is expected with this study to demonstrate that MHM can improve respiratory mechanics and hemodynamic parameters and provide a safe intervention with no changes in intracranial compliance in stroke patients. [ABSTRACT FROM AUTHOR]

Background: Adherence is key to the treatment success of multi-drug resistant tuberculosis (MDR-TB) and prevention of community transmission. Directly observed therapy (DOT) is the recommended approach for the management of patients with MDR-TB. Uganda implements a health facility-based DOT approach where all patients diagnosed with MDR-TB report to the nearest private or public health facility for daily observation of ingesting their medicines by a health care provider. Directly observed therapy is very costly for both the patient and health care system. It follows the assumption that MDR TB patients have a history of poor adherence to TB treatment. But only 21% of MDR-TB patients notified globally and 1.4–12% notified in Uganda had been previously treated for TB. The shift to all oral treatment regimen for MDR-TB provides an opportunity for the exploration of self-administered therapy for this group of patients even with use of remotely operated adherence technology. We are conducting a non-inferiority open-label randomized controlled trial to compare adherence to MDR-TB treatment among patients on self-administered therapy (measured by Medication Events Monitoring System (MEMS) technology) with a control group on DOT. Methods: We plan to enrol 164 newly diagnosed MDR-TB patients aged ≥ 8 years from three regional hospitals based in rural and urban Uganda. Patients with conditions that affect their dexterity and ability to operate the MEMS-operated medicine equipment will not be eligible to participate in the trial. Patients are randomized to either of the two study arms: self-administered therapy with adherence being monitored using MEMS technology (intervention arm) or health facility-based DOT (control arm) and will be followed up monthly. Adherence is measured by the number of days the medicine bottle is open to access medication as recorded by the MEMS software in the intervention arm and treatment complaint days as recorded in the TB treatment card in the control arm. The primary outcome is the comparison of adherence rates between the two study arms. Discussion: The evaluation of self-administered therapy for patients with MDR-TB is important to inform cost-effective management strategies for these patients. The approval of all oral regimens for the treatment of MDR-TB provides an opportunity for innovations such as MEMS technology to support sustainable options for MDR-TB treatment adherence support in low-resource settings. Trial registration: Pan African Clinical Trials Registry, Cochrane #PACTR202205876377808. Retrospectively registered on 13 May 2022 [ABSTRACT FROM AUTHOR]

Background: Tuberculosis remains a leading infectious cause of death in resource-limited settings. Effective treatment is the cornerstone of tuberculosis control, reducing mortality, recurrence and transmission. Supporting treatment adherence through facility-based observations of medication taking can be costly to providers and patients. Digital adherence technologies (DATs) may facilitate treatment monitoring and differentiated care. The ASCENT-Ethiopia study is a three-arm cluster randomised trial assessing two DATs with differentiated care for supporting tuberculosis treatment adherence in Ethiopia. This study is part of the ASCENT consortium, assessing DATs in South Africa, the Philippines, Ukraine, Tanzania and Ethiopia. The aim of this study is to determine the costs, cost-effectiveness and equity impact of implementing DATs in Ethiopia. Methods and design: A total of 78 health facilities have been randomised (1:1:1) into one of two intervention arms or a standard-of-care arm. Approximately 50 participants from each health facility will be enrolled on the trial. Participants in facilities randomised to the intervention arms are offered a DAT linked to the ASCENT adherence platform for daily adherence monitoring and differentiated response for those who have missed doses. Participants at standard-of-care facilities receive routine care. Treatment outcomes and resource utilisation will be measured for each participant. The primary effectiveness outcome is a composite index of unfavourable end-of-treatment outcomes (lost to follow-up, death or treatment failure) or treatment recurrence within 6 months of end-of-treatment. For the cost-effectiveness analysis, end-of-treatment outcomes will be used to estimate disability-adjusted life years (DALYs) averted. Provider and patient cost data will be collected from a subsample of 5 health facilities per study arm, 10 participants per facility (n = 150). We will conduct a societal cost-effectiveness analysis using Bayesian hierarchical models that account for the individual-level correlation between costs and outcomes as well as intra-cluster correlation. An equity impact analysis will be conducted to summarise equity efficiency trade-offs. Discussion: Trial enrolment is ongoing. This paper follows the published trial protocol and describes the protocol and analysis plan for the health economics work package of the ASCENT-Ethiopia trial. This analysis will generate economic evidence to inform the implementation of DATs in Ethiopia and globally. Trial registration: Pan African Clinical Trial Registry (PACTR) PACTR202008776694999. Registered on 11 August 2020, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=12241. [ABSTRACT FROM AUTHOR]

Background: Adherence to antiretroviral (ARV) treatment for HIV infection is challenging because of many factors. The World Health Organization (WHO) has recommended using digital adherence technologies (DATs). However, there is limited evidence on how DATs improve adherence. Wisepill® is an internet-enabled medication dispenser found feasible and acceptable in several studies. However, limited evidence is available on its effectiveness in improving ART adherence, specifically among children and adolescents. Furthermore, DATs are often developed without involving the target groups. We propose a two-stage project consisting of a formative study to customize an existing Wisepill DAT intervention and a randomized clinical trial to investigate the effectiveness of DAT combined with reminder cues and tailored feedback on adherence to ARV treatment among children and adolescents living with HIV and retention in care among breastfeeding women living with HIV in Kilimanjaro and Arusha Region, Tanzania. Methods: We will conduct a formative mixed-methods study and three sub-trials in Kilimanjaro and Arusha Regions among (1) children aged 0–14 years and their caregivers, (2) adolescents aged 15–19 years and (3) breastfeeding women and their HIV-negative infants. In the formative study, we will collect and analyse data on needs and contents for DATs, including the contents of short message service (SMS) texts and tailored feedback. The results will inform the customization of the DAT to be tested in the sub-trials. In the trials, participants will be randomized in the intervention arm, where the DAT will be implemented or the control arm, where standard care will be followed. Participants in the intervention arm will take their medication from the Wisepill box and receive daily reminder texts and tailored feedback during clinic visits. Discussion: If the intervention improves adherence to ART and the devices are acceptable, accurate and sustainable, the intervention can be scaled up within the National Aids Control Programmes. Trial registration: PACTR202301844164954, date 27 January 2023. [ABSTRACT FROM AUTHOR]

Background: Buprenorphine-naloxone is a medication shown to improve outcomes for individuals seeking treatment for opioid use disorder (OUD); however, outcomes are limited by low medication adherence rates. This is especially true during the early stages of treatment. Methods: The present study proposes to utilize a sequential multiple assignment randomized trial design to compare two psychological interventions targeting buprenorphine-naloxone adherence: (1) contingency management (CM) and (2) brief motivational interviewing plus substance-free activities session plus mindfulness (BSM). Participants will be N = 280 adults who present to a university-based addictions clinic seeking treatment for OUD. Participants will be randomized to condition to receive 4 sessions of their assigned intervention (CM or BSM). Participants who are adherent, defined as attending physician appointments and having buprenorphine present in urine toxicology, will enter maintenance intervention for an additional 6 months. Those who are not adherent will be re-randomized to receive either the other intervention or both interventions. Follow-up will occur at 8 months post-randomization. Conclusions: This novel design will examine the benefit of sequential treatment decisions following non-adherence. The primary outcome of this study is buprenorphine-naloxone medication adherence, as assessed by physician visit attendance and presence of buprenorphine in urine. Results will elicit the relative efficacy of CM and BSM compared to one another and whether keeping the initial treatment approach when adding the alternative approach for initially non-adherent individuals is beneficial. Trial registration: ClinicalTrials.gov NCT04080180 [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that Internet-based cognitive behavioral therapy (ICBT) is as effective as a stand-alone treatment and helps facilitating access to treatment. Given the complexity of the treatment, we argue that the effect of ICBT could be even greater if guided by a therapist, as this could increase treatment adherence. We modified an established and well-evaluated treatment approach and developed a mobile application for treating social anxiety disorder (SAD). In the present study, we compare the efficacy of app use alone (APP) with video-based, therapist-guided app use (TG-APP) and with a wait-list control group (WLC) in terms of symptom reduction, and various secondary outcomes such as increase in quality of life or decrease of general psychological distress. Methods/design: A within-between interaction design with randomization to one of three conditions will be used. In the APP condition, patients receive only the app without any additional contact with therapists, while in the TG-APP condition, therapists provide 8 sessions of video-based treatment in addition to using the app. The study will be conducted in two university outpatient treatment centers with reliably diagnosed SAD patients. The primary outcome will be defined as change in SAD symptoms, as measured by the Liebowitz Social Anxiety Scale (expert rating). Furthermore, a wide range of self-reports and clinician ratings for other symptoms (depression, general psychopathology) or quality of life will be used. A simulation-based power analysis for a 3 × 2 interaction effect (group × time) on the primary outcome in a linear mixed model resulted in a total sample size of N = 165. Discussion: The present study will be one of the first to examine the additional benefit of therapist-guided video sessions regarding the use of an app treating SAD. Study results are pivotal to future treatment application in SAD. [ABSTRACT FROM AUTHOR]

Background: Foot complications occur in conjunction with poorly controlled diabetes. Plantar forefoot ulceration contributes to partial amputation in unstable diabetics, and the risk increases with concomitant neuropathy. Reducing peak plantar forefoot pressure reduces ulcer occurrence and recurrence. Footwear and insoles are used to offload the neuropathic foot, but the success of offloading is dependent on patient adherence. This study aims to determine which design and modification features of footwear and insoles improve forefoot plantar pressure offloading and adherence in people with diabetes and neuropathy. Methods: This study, involving a series of N-of-1 trials, included 21 participants who had a history of neuropathic plantar forefoot ulcers. Participants were recruited from two public hospitals and one private podiatry clinic in Sydney, New South Wales, Australia. This trial is non-randomised and unblinded. Participants will be recruited from three sites, including two high-risk foot services and a private podiatry clinic in Sydney, Australia. Mobilemat™ and F-Scan® plantar pressure mapping systems by TekScan® (Boston, USA) will be used to measure barefoot and in-shoe plantar pressures. Participants' self-reports will be used to quantify the wearing period over a certain period of between 2 and 4 weeks during the trial. Participant preference toward footwear, insole design and quality-of-life-related information will be collected and analysed. The descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics (version 27). And the software NVivo (version 12) will be utilised for the qualitative data analysis. Discussion: This is the first trial assessing footwear and insole interventions in people with diabetes by using a series of N-of-1 trials. Reporting self-declared wearing periods and participants' preferences on footwear style and aesthetics are the important approaches for this trial. Patient-centric device designs are the key to therapeutic outcomes, and this study is designed with that strategy in mind. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000699965p. Registered on June 23, 2020 [ABSTRACT FROM AUTHOR]

Background: Self-management support is increasingly viewed as an integral part of chronic condition management in adolescence. It is well recognized that markers of chronic illness control deteriorate during adolescence. Due to the increasing prevalence of long-term chronic health conditions in childhood and improved survival rates of previously life-limiting conditions in children and adolescents, significant numbers of adolescents are having to manage their chronic condition effectively as they transition to adult health care. Therapy adherence has been identified as a major challenge for young people living with a chronic condition such as cystic fibrosis, diabetes, or asthma requiring long-term pharmacological therapy and/or lifestyle modifications. Most systematic reviews on self-management interventions address adult populations. Very few intervention studies are directed at adolescents with a chronic condition who are transitioning to adult health services. This protocol describes a prospective randomized controlled trial of a standardized self-management intervention program delivered to adolescents aged 15-18 years prior to their transfer to adult care. This study has been designed to provide evidence regarding self-management programs for adolescents and is the first study to use the Flinders Program with this important, under-researched age group.Methods: A randomized controlled trial is used to investigate the effectiveness of a modified adolescent-friendly version of an adult self-management program. This program is directed at improving self-management in an adolescent cohort 15-18 years of age with a chronic condition being treated in a specialist pediatric hospital. Participants will be randomized to either usual care or the modified Flinders Program plus usual care. Data collection will include measures of specific illness control, unscheduled hospital admissions, and questionnaires to record self-management competencies, quality of life, self-efficacy, and outcome measures specific to the chronic condition at baseline, 3 months, 6 months, and 12 months after delivery.Discussion: This study will provide a better understanding of the elements required for effective self-management programs in adolescents with a chronic condition and address some important knowledge gaps in current literature. The study will be carried out in collaboration with the Discipline of Behavioural Health at Flinders University, Adelaide, Australia, in order to inform the development of an adolescent version of the successful and validated Flinders Program™.Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12621000390886). Registered on April 8, 2021. [ABSTRACT FROM AUTHOR]

Background: Medication non-adherence is a prevalent health problem in people with type 2 diabetes mellitus (T2DM). Interventions have previously been developed to improve medication adherence, but inconsistent outcomes have been reported. A potential explanation for this inconsistency is a 'one size fits all' approach, with interventions not tailored to the needs and preferences of individuals. Therefore, the aim of this study is to evaluate the effectiveness of a personalised intervention programme aimed at improving adherence to oral antidiabetic and/or antihypertensive medication in people with T2DM.Methods: A parallel-group randomised controlled trial will be conducted in 40-50 community pharmacies in the Netherlands and the United Kingdom (UK). A total of 300 participants will be included and followed up for a period of 6 months. Participants will be people with T2DM identified as non-adherent to oral antidiabetic and/or antihypertensive medication, aged 35-75 years and mobile phone users. The intervention group will receive a personalised intervention programme that is based on one or more of the participants' pre-defined non-adherence profile(s), namely (I) Knowledge and perceptions, (II) Practical problems, (III) Side effects and (IV) Negative mood and beliefs. The intervention comprises of one or more supporting modules, namely (I) Brief messaging, (II) Clinical medication review, (III) Medication schedule, (IV) Reminding messaging, (V) Medication dispensing systems, (VI) Smart messaging, (VII) Referral to general practitioner and (VIII) Unguided web-based Self Help Application for low mood. The control group will receive usual care including access to a publicly available informative diabetes website. The primary study outcome is medication adherence measured with a telephone pill count. Secondary outcomes are systolic blood pressure, HbA1c level, self-reported medication adherence, attitude and beliefs toward medication, satisfaction with diabetes treatment, health status and medical consumption and productivity cost. In addition, a process evaluation will be undertaken to establish the fidelity, reach and the extent to which intervention delivery is normalised in the daily practice of community pharmacy teams.Discussion: The study can lead to a personalised intervention programme that improves medication adherence in people with T2DM that are non-adherent to oral antidiabetic and/or antihypertensive medication.Trial Registration: Dutch Trial Register, Trial NL8747 , registered 02 July, 2020; ISRCTN Registry, ISRCTN36009809 , registered 05 February, 2020. [ABSTRACT FROM AUTHOR]

Background: Despite nationwide improvements in cardiovascular disease (CVD) mortality and morbidity, CVD deaths in adults with type 2 diabetes (T2DM) are 2-4 times higher than among those without T2DM. A key contributor to these poor health outcomes is medication non-adherence. Twenty-one to 42% of T2DM patients do not take blood sugar, blood pressure (BP), or statin medications as prescribed. Interventions that foster and reinforce patient-centered communication show promise in improving health outcomes. However, they have not been widely implemented, in part due to a lack of compelling evidence for their effectiveness in real-life primary care settings.Methods: This pragmatic cluster-randomized trial randomizes 17 teams in 12 Federally Qualified Healthcare Centers (FQHCs) to two experimental groups: intervention (group 1): Office-Gap + Texting vs. control (group 2): Texting only. Office-GAP (Office-Guidelines Applied to Practice) is a patient activation intervention to improve communication and patient-provider partnerships through brief patient and provider training in shared decision-making (SDM) and use of a guideline-based checklist. The texting intervention (Way2Health) is a cell phone messaging service that informs and encourages patients to adhere to goals, adhere to medication use and improve communication. After recruitment, patients in groups 1 and 2 will both attend (1) one scheduled group visit, (90-120 min) conducted by trained research assistants, and (2) follow-up visits with their providers after group visit at 0-1, 3, 6, 9, and 12 months. Data will be collected over 12-month intervention period. Our primary outcome is medication adherence measured using eCAP electronic monitoring and self-report. Secondary outcomes are (a) diabetes-specific 5-year CVD risk as measured with the UK Prospective Diabetes Study (UKPDS) Engine score, (b) provider engagement as measured by the CollaboRATE Shared-Decision Making measure, and (c) patient activation measures (PAM).Discussion: This study will provide a rigorous pragmatic evaluation of the effectiveness of combined mHealth, and patient activation interventions compared to mHealth alone, targeting patients and healthcare providers in safety net health centers, in improving medication adherence and decreasing CVD risk. Given that 20-50% of adults with chronic illness demonstrate medication non-adherence, increasing adherence is essential to improve CVD outcomes as well as healthcare cost savings.Trial Registration: The ClinicalTrials.gov registration number is NCT04874116. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Improving medication adherence among persons with cardiovascular disease through m-health and community health worker-led interventions in Kerala; protocol for a type II effectiveness-implementation research-(SHRADDHA-ENDIRA)." The correction addresses an error in the spelling of the 12th author's name. The correct name is Ravivarman Lakshmanasamy, not Ravivarman Lakshmanaswamy. The original article has been corrected. The authors of the article are Jaideep C. Menon, Denny John, Aswathy Sreedevi, Chandrasekhar Janakiram, R Akshaya, S Sumithra, M. S Aravind, Mathews Numpeli, Bipin Gopal, B. A Renjini, P. K Sajeev, Ravivarman Lakshmanasamy, and Abhishek Kunwar. [Extracted from the article]

Background: Over 80% of the morbidity and mortality related to non-communicable diseases (NCDs) occurs in low-income and middle-income countries (LMICs). Community health workers (CHWs) may improve disease control and medication adherence among patients with NCDs in LMICs, particularly in sub-Saharan African settings. In Uganda, and the majority of LMICs, management of uncontrolled hypertension remains limited in constrained health systems. Intervening at the primary care level, using CHWs to improve medical treatment outcomes has not been well studied. We aim to determine the effectiveness of a CHW-led intervention in blood pressure control among confirmed hypertensive patients and patient-related factors associated with uncontrolled hypertension.Methods: We will conduct a stepped-wedge cluster randomized controlled trial study of 869 adult patients with hypertension attending two NCD clinics to test the effectiveness, acceptability, and fidelity of a CHW-led intervention. The multi-component intervention will be centered on monthly household visits by trained CHWs for a period of 1 year, consisting of the following: (1) blood pressure and sugar monitoring, (2) BMI monitoring, (3) cardiovascular disease risk assessment, (4) using checklists to guide monitoring and referral to clinics, and (5) healthy lifestyle counseling and education. During home visits, CHWs will remind patients of follow-up visits. We will measure blood pressure at baseline and 3-monthly for the entire cohort. We will conduct individual-level mixed effects analyses of study data, adjusting for time and clustering by patient and community.Conclusion: The results of this study will inform community delivered HTN management across a range of LMIC settings.Trial Registration: ClinicalTrials.gov NCT05068505 . Registered on October 6, 2021. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is one of the most common cardiac arrhythmia diseases. Thromboembolic prophylaxis plays an essential role in AF therapy, but at present, general practitioners (GPs) are presumed to lack the knowledge and enthusiasm for AF management. Clinical decision support systems (CDSS), assisted by artificial intelligence, help primary care providers (PCPs) make quick, individualized, and correct clinical decisions. This primary aim of the study is to identify whether the promotion of the CDSS would improve the primary care provided to patients with AF. The secondary objectives are mainly to assess the health-economic and clinical benefits from using the CDSS, and the improvement of GPs' AF management capability.Methods: This study will be a prospective cluster randomized controlled trial, conducted among 14 community health centers in Shanghai which were randomized as the intervention group and control group in a ratio of 1:1. The intervention group will use the CDSS in the consultation of patients with AF and the control group will maintain their usual care. The trial will include 498 patients with AF and the follow-up period will be 12 months. The primary outcome is set as the proportion of antithrombotic treatment prescriptions in agreement with recommendations in the latest China's AF-related guidelines. The secondary outcomes are the frequency of consultation, the compliance rate of international normalized ratio (INR) in patients with warfarin, stroke morbidity, treatment compliance, medication satisfaction, and the cost-benefit analysis. Per-protocol (PP) analysis and the intention-to-treat (ITT) analysis will be conducted.Discussion: This study aims to identify whether the application of CDSS to manage patients with AF in China's community health centers would bring benefits for patients, physicians, and health economics.Trial Registration: Registry name: AI (Development and promotion of an AI-assisted tool for NVAF management in primary care); registry number: ChiCTR2100052307; registration date: Nov. 22nd, 2021; http://www.chictr.org.cn/showproj.aspx?proj=133849 . [ABSTRACT FROM AUTHOR]

Background: Millions of people in Germany suffer from chronic pain, in which course and intensity are multifactorial. Besides physical injuries, certain psychosocial risk factors are involved in the disease process. The national health care guidelines for the diagnosis and treatment of non-specific low back pain recommend the screening of psychosocial risk factors as early as possible, to be able to adapt the therapy to patient needs (e.g., unimodal or multimodal). However, such a procedure has been difficult to implement in practice and has not yet been integrated into the rehabilitation care structures across the country.Methods: The aim of this study is to implement an individualized therapy and aftercare program within the rehabilitation offer of the German Pension Insurance in the area of orthopedics and to examine its success and sustainability in comparison to the previous standard aftercare program. The study is a multicenter randomized controlled trial including 1204 patients from six orthopedic rehabilitation clinics. A 2:1 allocation ratio to intervention (individualized and home-based rehabilitation aftercare) versus the control group (regular outpatient rehabilitation aftercare) is set. Upon admission to the rehabilitation clinic, participants in the intervention group will be screened according to their psychosocial risk profile. They could then receive either unimodal or multimodal, together with an individualized training program. The program is instructed in the clinic (approximately 3 weeks) and will continue independently at home afterwards for 3 months. The success of the program is examined by means of a total of four surveys. The co-primary outcomes are the Characteristic Pain Intensity and Disability Score assessed by the German version of the Chronic Pain Grade questionnaire (CPG).Discussion: An improvement in terms of pain, work ability, patient compliance, and acceptance in our intervention program compared to the standard aftercare is expected. The study contributes to provide individualized care also to patients living far away from clinical centers.Trial Registration: DRKS, DRKS00020373 . Registered on 15 April 2020. [ABSTRACT FROM AUTHOR]

Background: People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings.Hypothesis: Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers.Design: Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years.Entry Criteria: South Asian, men or women, age 40-70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0-6.4% inclusive).Exclusion Criteria: known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness.Endpoints: The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance.Intervention: Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker.Results: We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum).Conclusion: The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group.Irb Approval: 16/WM/0171 TRIAL REGISTRATION: EudraCT 2016-001350-18 . Registered on 14 April 2016. ClinicalTrials.gov NCT02949739 . Registered on 31 October 2016, First posted on 31/10/2016. [ABSTRACT FROM AUTHOR]

Objective: Medication adherence in gout is suboptimal, and the lack of effective interventions to address it presents a huge challenge. Medication adherence and gout outcomes are worse in racial/ethnic minorities. The objective of this paper was to provide the details of the study protocol for randomized, controlled trial (RCT) in African Americans (AAs) with gout that will test the effectiveness of a culturally appropriate gout storytelling intervention.Methods: The SToRytelliing to Improve Disease outcomes in Gout (STRIDE-GO) study will be a 12-month, multicenter, open-label RCT that will assess the effect of a culturally appropriate gout storytelling in at least 300 AA veterans with gout. Participants will be randomized to gout-storytelling intervention vs. a stress reduction video in a 1:1 ratio. The primary outcome is urate-lowering therapy (ULT) adherence measured with MEMSCap™, an electronic monitoring system (efficacy, 6 months; sustenance of efficacy, 12 months). Secondary outcomes include gout flares, serum urate (SU), gout-specific health-related quality of life [HRQOL], self-reported ULT adherence, patient satisfaction with treatment, and patient understanding of the intervention. AA veterans with gout who met the 1977 Preliminary American College of Rheumatology (ACR) classification criteria for gout, currently prescribed an oral ULT medication (allopurinol or febuxostat) for at least 6 months, and not using a pillbox to redistribute their medications, will be invited to an in-person study visit. After the study coordinators obtain informed consent, and ensure that participants meet the inclusion criteria, the eligible participants will be provided with their current ULT in a MEMSCap™ bottle for the 1-month run-in period and asked to return to the clinic in 1 month. ULT adherence with MEMSCap™ will be recorded at a 1-month return visit. Interested participants will complete the baseline assessments, randomized using the computerized system to either gout-storytelling intervention or a stress reduction intervention video arm and watch the respective video in-clinic. Patients will be interviewed on the phone at 2 and 4 months regarding the viewing of the videos at home at each time. Participants will be assessed in-clinic at 3, 6, 9, and 12 months; MEMSCap™ data and patient surveys will be captured at each visit. For any missed visit, assessments will be completed on the phone and MEMSCap™ data captured at the next in-clinic visit.Discussion: The study will assess the efficacy of a behavioral intervention to improve ULT adherence in minority populations with gout.Trial Registration: ClinicalTrials.gov NCT02741700. Registered on 14 September 2018. [ABSTRACT FROM AUTHOR]

Abstract Background Oral hygiene is of paramount importance for the preservation of oral health, and for patients affected by periodontal disease establishing an effective oral hygiene routine is the first step of therapy. Several clinical frameworks have been developed to foster behavior change, such as motivational interviewing. However, two obstacles can be identified. First, patients tend to forget the advice they were given during the consultation. Second, it is hard to maintain motivation in the long term, thus leading to relapse. An innovative eHealth solution was designed with the aim to tackle both obstacles and supplement the current clinical standard of care. The primary objective is to compare the full mouth plaque scores of study groups (eHealth plus standard of care versus standard of care only) at 8 weeks of follow up. The main secondary objective is to compare the full mouth bleeding score at 8 weeks of follow up. Methods/design The “GoPerio” study is a multicenter, randomized, controlled trial assessing the impact of a novel eHealth concept for oral hygiene motivation (personalized video of oral hygiene routine available for the patient via a cloud server plus interactive text messages) in addition to the current standard of care (motivational interviewing plus tooth scaling and polishing). The minimum sample size required is 86 patients. Participants will be randomized (allocation ratio 1:1): test group (eHealth plus standard of care) versus control group (standard of care only). The primary outcome is oral hygiene as measured by the full mouth (six sites per tooth) plaque control record (PCR) index. The main secondary outcome is gingival inflammation as measured by the full mouth (six sites per tooth) bleeding on probing (BOP) index. Both the primary and the main secondary outcomes are evaluated by blinded and calibrated examiners at 8 weeks of follow up. The other secondary outcomes are patient satisfaction and patient behavior change and motivation. Discussion The study will investigate the value of an innovative eHealth approach to strengthen patient motivation for oral hygiene. If proven effective, such an approach would supplement the current clinical standard of care, resulting in improved clinical outcomes with negligible impact on productivity in a dental practice. Trial registration ClinicalTrials.gov, NCT03109808. Registered on 12 April 2017. Sponsor: Hospices Civils de Lyon. BP 2251, 3 quai des Célestins, 69,229 Lyon cedex 02. Protocol version: 1.0 as of 21 September 2016.

Background: Nowadays, the main challenge of transplantation is the improvement of long-term care, aiming at reducing treatment-related complications and at decreasing rejection rates. Patients' adherence to both treatment and hygienic-dietary measures is mandatory to achieve these objectives. Adherence to immunosuppressive drugs is estimated to be only 70%. We hypothesized that the implementation of a personalized pharmaceutical plan (PPP) would increase adherence and therefore graft survival.Methods/design: This study is a stepped-wedge cluster randomized trial with transplantation units defining clusters. Twelve clusters from 10 university hospitals were recruited. All centres started on the same day in the control phase. Every 7 weeks, one centre will switch to the intervention phase and remain there until the end of inclusions. We plan to recruit 1716 kidney and/or liver transplant patients. The intervention phase consists in setting up the PPP: development of the patient's hospital and community pharmaceutical follow-up. In the hospital, the pharmacist will carry out drug reconciliation upon admission, daily pharmaceutical follow-up of prescriptions and pharmaceutical interviews with the patient in order to explain the modalities of taking immunosuppressive drugs and hygienic-dietary measures. After hospitalization, during the post-transplantation year, pharmaceutical meetings will take place, prior to medical consultations in order to check the patient's understanding of the prescription, his adherence, to remind them of hygienic-dietary measures and to look for adverse effects. The hospital pharmacist will also be in charge of establishing a close link with the community pharmacist (CP) and general practitioner, especially providing discharge medication reconciliation, an e-learning and a checklist. Moreover, prior to each pharmaceutical consultation, the hospital pharmacist will contact the CP to discuss patient adherence. The primary outcome is adherence to immunosuppressive treatments 1 year post-transplantation assessed by using the BAASIS questionnaire and the health insurance data from the national health data system. A medico-economic study will measure the efficiency of this plan.Discussion: GRePH aims to increase adherence of liver and/or kidney transplant patients to their immunosuppressive therapies in order to reduce transplant rejections. To this end, a new clinical pharmacy model, the PPP, will be set up in 10 university hospitals.Trial Registration: ClinicalTrials.gov NCT04295928 . Registered on 5 March 2020. [ABSTRACT FROM AUTHOR]

Background: Psoriasis affects 2-4% of the Western adult population and is a socio-economic burden for patients and society. Topical drugs are recommended as first-line treatment for mild-to-moderate psoriasis, but low adherence is a barrier to treatment success. Psoriasis patients require support, in order to improve their long-term use of topical drugs. The project aims to test whether a patient-supporting intervention delivered by dermatology nurses can reduce the severity of psoriasis, improve the use of topical drugs, and is cost-effective compared to standard procedure.Methods: The intervention consists of improved support delivered to patients by three experienced dermatology nurses, who will support patients on a regular basis by consultations with a focus on providing reminder systems, accountability, reinforcement, and building trust in the treatment. Each patient will be supported by the same dermatology nurse throughout the entire study period. The effect will be compared with standard procedure. The intervention will be tested in a randomized controlled trial during a 48-week period. A group of patients with moderate-to-severe psoriasis (psoriasis affecting ≥ 4% of the total body surface area) and 18-85 years of age who are prescribed topical treatment will be randomized to a non-intervention (n ≈ 57) or intervention group (n ≈ 57). Participants in both arms will be prescribed topical preparations containing corticosteroid and/or calcipotriol. The primary outcome will be a change in the severity of psoriasis, measured as reduction in the Lattice-System Physician's Global Assessment. Secondary outcomes will include changes in health-related quality of life (measured by disease specific and generic questionnaires), primary adherence (i.e., proportion of filled prescriptions), and secondary adherence by objective measure (rate of topical drug consumption (obtained by weighing medication packages) compared to estimated recommended consumption). A health economic evaluation is planned to run alongside the trial. Participants' total health costs will be estimated on the basis of health costs reported to the national health registries and costs spent on the intervention, after which a cost-utility and cost-effectiveness analysis will be carried out.Discussion: If the intervention can reduce the severity of psoriasis in a significant manner and is economically favorable compared to standard treatment, there is potential for implementing the intervention in dermatology clinics.Trial Registration: Clinicaltrials.gov NCT04220554 . Registered on January 7, 2020. Study results, either positive, negative, or inconclusive, will be published on www.clinicaltrials.gov . Trial registration no. with the Danish Regional Committee on Health Research Ethics, registration no. 72613. [ABSTRACT FROM AUTHOR]

Background: Financial toxicity, the material and psychological burden of the cost of treatment, affects 30-50% of people with cancer, even those with health insurance. The burden of treatment cost can affect treatment adherence and, ultimately, mortality. Financial toxicity is a health equity issue, disproportionately affecting patients who are racial/ethnic minorities, have lower incomes, and are < 65 years old. Patient education about treatment cost and patient-oncologist cost discussions are recommended as ways to address financial toxicity; however, research shows cost discussions occur infrequently (Altice et al. J Natl Cancer Inst 109:djw205, 2017; Schnipper et al. J Clin Oncol 34:2925-34, 2016; Zafar et al. Oncologist 18:381-90, 2013; American Cancer Society Cancer Action Network 2010). Our overall goal is to address the burden of financial toxicity and work toward health equity through a tailorable education and communication intervention, the DISCO App. The aim of this longitudinal randomized controlled trial is to test the effectiveness of the DISCO App on the outcomes in a population of economically and racially/ethnically diverse cancer patients from all age groups.Methods: Patients diagnosed with breast, lung, colorectal, or prostate cancer at a NCI-designated comprehensive cancer center in Detroit, MI, will be randomized to one of three study arms: one usual care arm (arm 1) and two intervention arms (arms 2 and 3). All intervention patients (arms 2 and 3) will receive the DISCO App before the second interaction with their oncologist, and patients in arm 3 will receive an intervention booster. The DISCO App, presented on an iPad, includes an educational video about treatment costs, ways to manage them, and the importance of discussing them with oncologists. Patients enter socio-demographic information (e.g., employment, insurance status) and indicate their financial concerns. They then receive a tailored list of questions to consider asking their oncologist. All patients will have up to two interactions with their oncologist video recorded and complete measures at baseline, after the recorded interactions and at 1, 3, 6, and 12 months after the second interaction. Outcome measures will assess discussions of cost, communication quality, knowledge of treatment costs, self-efficacy for treatment cost management, referrals for support, short- and longer-term financial toxicity, and treatment adherence.Discussion: If effective, this intervention will improve awareness of and discussions of treatment cost and alleviate the burden of financial toxicity. It may be especially helpful to groups disproportionately affected by financial toxicity, helping to achieve health equity.Trial Registration: ClinicalTrials.gov NCT04766190. Registered on February 23, 2021. [ABSTRACT FROM AUTHOR]

Background: Nearly half of patients do not take their cardiovascular medications as prescribed, resulting in increased morbidity, mortality, and healthcare costs. Mobile and digital technologies for health promotion and disease self-management offer an opportunity to adapt behavioral "nudges" using ubiquitous mobile phone technology to facilitate medication adherence. The Nudge pragmatic clinical trial uses population-level pharmacy data to deliver nudges via mobile phone text messaging and an artificial intelligent interactive chat bot with the goal of improving medication adherence and patient outcomes in three integrated healthcare delivery systems.Methods: The Theory of mHealth, the Expanded RE-AIM/PRISM, and the PRECIS-2 frameworks were used for program planning, implementation, and evaluation, along with a focus on dissemination and cost considerations. During the planning phase, the Nudge study team developed and piloted a technology-based nudge message and chat bot of optimized interactive content libraries for a range of diverse patients. Inclusion criteria are very broad and include patients in one of three diverse health systems who take medications to treat hypertension, atrial fibrillation, coronary artery disease, diabetes, or hyperlipidemia. A target of approximately 10,000 participants will be randomized to one of 4 study arms: usual care (no intervention), generic nudge (text reminder), optimized nudge, and optimized nudge plus interactive AI chat bot. The PRECIS-2 tool indicated that the study protocol is very pragmatic, although there is variability across PRECIS-2 dimensions.Discussion: The primary effectiveness outcome is medication adherence defined by the proportion of days covered (PDC) using pharmacy refill data. Implementation outcomes are assessed using the RE-AIM framework, with a particular focus on reach, consistency of implementation, adaptations, cost, and maintenance/sustainability. The project has limitations including limited power to detect some subgroup effects, medication complications (bleeding), and longer-term outcomes (myocardial infarction). Strengths of the study include the diverse healthcare systems, a feasible and generalizable intervention, transparent reporting using established pragmatic research and implementation science frameworks, strong stakeholder engagement, and planning for dissemination and sustainment.Trial Registration: ClinicalTrials.gov NCT03973931 . Registered on 4 June 2019. The study was funded by the NIH; grant number is 4UH3HL144163-02 issued 4/5/19. [ABSTRACT FROM AUTHOR]

Background: Self-management of hypertension is of great significance given its increasing incidence and its associated disabilities. In view of the increased use of mobile health in medicine, the present study evaluated the effect of a self-management application on patient adherence to hypertension treatment.Methods: This clinical trial was performed on 120 hypertensive patients who were provided with a mobile intervention for 8 weeks and followed up until the 24th week. Data on the primary outcome (adherence to treatment) and secondary outcomes (adherence to the DASH diet, regular monitoring of blood pressure, and physical activity) were collected using a questionnaire and a mobile application, respectively. The inter-group change difference over time was analyzed using repeated measures ANOVA (general linear model).Results: The treatment adherence score increased by an average of 5.9 (95% CI 5.0-6.7) in the intervention group compared to the control group. The scores of "adherence to the low-fat and low-salt diet plans" were 1.7 (95% CI 1.3-2.1) and 1.5 (95% CI 1.2-1.9), respectively. Moreover, moderate physical activity increased to 100.0 min (95% CI 61.7-138.3) per week in the intervention group.Conclusion: The treatment and control of blood pressure require a multifaceted approach given its complexity and multifactorial nature. Considering the widespread use of smartphones, mHealth interventions can be effective in self-management and better patient adherence to treatments. Our results showed that this application can be used as a successful tool for hypertension self-management in patients attending public hospitals in developing countries.Trial Registration: Iran Randomized Clinical Trial Center IRCT2015111712211N2 . Registered on 1 January 2016. [ABSTRACT FROM AUTHOR]

Background: For patients with early breast cancer considered at very-low risk of local relapse, risks of radiotherapy may outweigh the benefits. Decisions regarding treatment omission can lead to patient uncertainty (decisional conflict), which may be lessened with patient decision aids (PDA). PRIMETIME (ISRCTN 41579286) is a UK-led biomarker-directed study evaluating omission of adjuvant radiotherapy in breast cancer; an embedded Study Within A Trial (SWAT) investigated whether PDA reduces decisional conflict using a cluster stepped-wedge trial design.Methods: PDA diagrams and a video explaining risks and benefits of radiotherapy were developed in close collaboration between patient advocates and PRIMETIME trialists. The SWAT used a cluster stepped-wedge trial design, where each cluster represented the radiotherapy centre and referring peripheral centres. All clusters began in the standard information group (patient information and diagrams) and were randomised to cross-over to the enhanced information group (standard information plus video) at 2, 4 or 6 months. Primary endpoint was the decisional conflict scale (0-100, higher scores indicating greater conflict) which was assessed on an individual participant level. Multilevel mixed effects models used a random effect for cluster and a fixed effect for each step to adjust for calendar time and clustering. Robust standard errors were also adjusted for the clustering effect.Results: Five hundred twenty-one evaluable questionnaires were returned from 809 eligible patients (64%) in 24 clusters between April 2018 and October 2019. Mean decisional conflict scores in the standard group (N = 184) were 10.88 (SD 11.82) and 8.99 (SD 11.82) in the enhanced group (N = 337), with no statistically significant difference [mean difference - 1.78, 95%CI - 3.82-0.25, p = 0.09]. Compliance with patient information and diagrams was high in both groups although in the enhanced group only 121/337 (36%) reported watching the video.Conclusion: The low levels of decisional conflict in PRIMETIME are reassuring and may reflect the high-quality information provision, such that not everyone required the video. This reinforces the importance of working with patients as partners in clinical trials especially in the development of patient-centred information and decision aids. [ABSTRACT FROM AUTHOR]

Background: South Africa has achieved drug-susceptible TB (DS-TB) treatment success of only 77% among people with new and previously treated TB. Alternative approaches are required to improve medication adherence and treatment completion to limit transmission, TB relapse and the development of resistance. This study aims to implement and evaluate the use of adherence medication monitors (Wisepill evriMED 1000) with a differentiated response to patient care, among DS-TB patients in three provinces of South Africa.Methods: In total, 18 public health clinics across three provinces were selected. Clinics were randomised to intervention or standard of care clinics. In each clinic, approximately 145 DS-TB patients are being enrolled to reach a total of 2610. All patients have their daily adherence monitored using medication monitors. In the intervention arm, patients are receiving medication monitor reminders and differentiated care in response to adherence data. This weekly review of daily real-time monitoring will be undertaken from a central database. The differentiated care model includes automated SMS reminders with a missed dose, research staff-initiated phone call to the patient with a second or third missed dose, a home visit if four or more doses are missed, and motivational counselling if four or more doses are missed repeatedly. Fidelity of the intervention will be measured through process evaluation. Patients in control clinics will receive medication monitors for adherence tracking, standard of care TB education, and normal clinic follow-up procedures. The primary outcome is the proportion of patients by arm with >80% adherence, as measured by the medication monitor. The feasibility and acceptability of the intervention will be assessed by in-depth interviews with patients, stakeholders, and study staff. A cost effectiveness analysis of the intervention and standard of care clinics will be conducted.Significance: This trial will provide evidence for the use of an intervention, including medication monitors and differentiated care package, to improve adherence to TB treatment. Improved adherence should also improve TB treatment completion rates, thus reducing loss to follow-up rates, and TB relapse among people with TB. The intervention is intended to ultimately improve overall TB control and reduce TB transmission in South Africa.Trial Registration: Pan African Trial Registry PACTR201902681157721 . Registered on 11 February 2019. [ABSTRACT FROM AUTHOR]

Background: Regular supervision of patients with type-2 diabetes mellitus (T2DM) by healthcare providers is essential to optimise their glycaemic control but is challenging to achieve in current care models. Telemonitoring is postulated to bridge this gap by leveraging on internet-of-things and mobile-health technology. This study aims to determine the effectiveness of a novel telemonitoring system (OPTIMUM) in improving the glycaemic control of patients with T2DM compared with standard of care alone.Methods: This mixed-method study comprises an initial randomised controlled trial involving 330 Asian adults with T2DM, aged 26-65 years old with an HbA1c of 7.5-10%, with 115 in the intervention and control arms each. Those in the intervention arm will use standardised Bluetooth-enabled devices to transmit their capillary glucose, blood pressure and weight measurements to the OPTIMUM system. Primary care physicians and nurses will remotely supervise them according to an embedded management algorithm for 6 months, including tele-education via weekly videos over 8 weeks and asynchronous tele-consultation if abnormal or absent parameters are detected. Patients in both arms will be assessed at baseline, 6, 12 and 24 months post-recruitment. The primary outcome will be their HbA1c difference between both arms at baseline and 6 months. Blood pressure and weight control; quality of life, medication adherence, confidence in self-management, diabetic literacy and related distress and healthcare utilisation using validated questionnaires; and incident retinal, renal, cardiac and cerebrovascular complications will be compared between the two arms as secondary outcomes at stipulated time-points. Intervention arm patients will be interviewed using qualitative research methods to understand their experience, acceptance and perceived usefulness of the OPTIMUM system.Discussion: Overall, this study seeks to evaluate the effectiveness of cultural-adapted telemonitoring system in improving glycaemic control of Asians with type-2 diabetes mellitus compared to standard of care. The results of this trial will better inform policy makers in adopting telemedicine for population health management.Trial Registration: ClinicalTrials.gov NCT04306770 . Registered on March 13, 2020. [ABSTRACT FROM AUTHOR]

Background: Symptomatic knee osteoarthritis (KOA) is common in China. Pharmacological therapy is not the first recommendation because of its safety issues. Nonpharmacological therapy, such as lifestyle adjustments, weight loss, muscle strengthening, and aerobic exercise programs, is strongly recommended for KOA. However, these approaches may fail due to poor patient compliance. There is a lack of high-quality randomized controlled trials of acupotomy, an effective treatment for KOA. This study was designed to investigate the efficacy of acupotomy in patients with KOA.Methods: A total of 136 patients will be enrolled at the First Affiliated Hospital of Guangzhou University of Chinese Medicine and assigned to the acupotomy group or sham acupotomy group according to the block randomization scheme. Patients in the acupotomy group will receive 2 sessions of acupotomy for 2 weeks (once a week). Patients in the sham group will receive 2 sessions of sham stimulation for 2 weeks (once a week). All patients will use indomethacin cream externally. The primary outcome will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the secondary outcomes will be the visual analog scale (VAS) score, plantar pressure distribution test result, X-ray examination findings, musculoskeletal ultrasound findings, maximum knee circumference, joint mobility, and quality of life. Measurements will be taken at baseline, 1 week after the end of treatment, and at the 3- and 6-month follow-ups.Discussion: To the best of our knowledge, this will be the first single-blind, sham-controlled study of acupotomy. The outcome assessors will also be blinded. The aim of this work is to demonstrate the efficacy of acupotomy in treating KOA.Trial Registration: Chinese Clinical Trial Registry ChiCTR2000033047 . Registered on 18 May 2020. [ABSTRACT FROM AUTHOR]

Background: Degenerative lumbar spinal stenosis (DLSS) is a common condition secondary to degenerative changes. Acupuncture may be effective for treating DLSS. However, there is a lack of sufficient evidence showing the efficacy of acupuncture. The aim of this study is to assess the efficacy and safety of acupuncture for relieving neurogenic claudication in patients with DLSS.Methods: A total of 196 patients will be randomly assigned to an acupuncture group or a sham acupuncture group at a ratio of 1:1. Patients will receive 18 sessions of treatment for 6 continuous weeks. The primary outcome will be the change in the Modified Roland-Morris Disability Questionnaire score from baseline to week 6. The secondary outcomes will include the change in the scores from baseline for the Numerical Rating Scale, Swiss Spinal Stenosis Questionnaire, and Anxiety and Depression Scale. Additionally, the expectancy of acupuncture, blinding, and safety will also be assessed. All analysis will be performed based on intention-to-treat.Discussion: The aim of this study is to evaluate the efficacy and safety of acupuncture for the treatment of neurogenic claudication in patients with DLSS. A limitation of this study is that acupuncturists cannot be blinded according to the characteristics of acupuncture, which may introduce some bias.Trial Registration: ClinicalTrials.gov NCT03784729 and protocol ID 2018-161-KY. Registered on 18 December 2018. [ABSTRACT FROM AUTHOR]

Background: An estimand defines the target of estimation for a clinical trial through specification of the treatment, target population, variable, population-level summary and of the strategies for intercurrent events. A carefully defined estimand aligns the clinical trial design and analysis with the scientific question of interest and adequately accounts for so-called intercurrent events. The ICH E9(R1) addendum suggests five estimand strategies. We evaluated to what extent current practice in drug development and regulatory assessment fits in the estimand framework.Methods: We systematically evaluated what estimands, especially what strategies for intercurrent events are advised in European Medicines Agency disease guidelines, used in sponsors' trials and additionally requested by the European Medicines Agency in assessment dossiers. We selected four therapeutic areas: nervous system, oncology, cardiovascular diseases and respiratory diseases. For each, we evaluated all disease guidelines with approved drugs, the dossiers of the most recently approved drugs matching the guidelines and corresponding regulatory questions.Results: Strategies for intercurrent events were present in 18 (53%) of 34 guidelines, in all 34 sponsor documentations and in 15 (44%) of 34 sets of regulatory questions. Treatment policy was advised in 13 (38%) guidelines and was applied in 9 corresponding sponsor documentations. Of these 9, it was the sole strategy in 4 cases and accompanied by another strategy in 5 cases. Hypothetical strategy was not advised in guidelines. However, it was the leading strategy applied in 25 (74%) sponsor documentations. Composite strategy was advised in 3 (9%) guidelines and applied accompanied by another strategy in 2 corresponding sponsor documentations. While on treatment strategy was not advised in guidelines, but was applied in 2 sponsor documentations. Principal stratum strategy was advised in 2 guidelines but not applied in corresponding sponsor documentations. Of the regulatory questions, treatment policy was present in 2 cases (6%), hypothetical in 6 cases (18%), composite in 6 cases (18%) and while on treatment in 1 case (3%).Conclusions: Estimand attributes are present in guidelines, sponsor documentations and regulatory questions, but not described as estimands. Treatment policy was most often advised in guidelines, but hypothetical was the leading strategy applied in sponsor documentations. Thus, results indicate not a full concordance between the regulatory target of estimation and what is actually estimated. The lack of concordance was mostly due to limitations in collection of intercurrent events data to enable a treatment policy strategy. There is, therefore, a need to better define estimands at the design stage and throughout the applications dossiers and assessment reports. [ABSTRACT FROM AUTHOR]

Background: Treatment fidelity, defined as ensuring that the recipient receives the intended intervention, is a critical component for accurate estimation of treatment efficacy. Ensuring fidelity and protocol adherence in behavioral trials requires careful planning during the design phase and implementation during the trial. The Tinnitus Retraining Therapy Trial (TRTT) randomized individuals with severe tinnitus to tinnitus retraining therapy (TRT, comprised of tinnitus-specific educational counseling (TC) and sound therapy (ST) using conventional sound generators (SGs)); Partial TRT (TC and placebo SGs); or standard of care (SOC), using a patient-centered care approach. Study audiologists administered both types of counseling in the TRTT, creating a challenge for managing protocol adherence.Methods: We developed methods to enhance treatment fidelity including training, competency assessment, scripts, visual aids, and fidelity monitoring. Protocol monitors identified critical topics and content to be addressed for each type of counseling session, prepared corresponding scripts, and developed training aids and treatment-specific checklists covering those topics. Study audiologists' competency assessment required submission and review by the protocol monitors of an audiotape of one TC and one SOC counseling session. Treatment-specific aids included scripts, a 3-D model of the ear, handouts, and for TC, an illustrated flip-chart with talking points that followed the scripted content. During the trial, audiologists completed treatment-specific checklists during each counseling session, indicating topics covered/discussed and submitted audiotapes of counseling sessions. Protocol monitors reviewed audiotapes using corresponding treatment-specific checklists. Results for individual checklist items were tabulated and proportions calculated.Results: Twenty-five audiologists were certified for TC and/or SOC counseling and 24 completed at least one counseling session. Adherence to each of 33 critical items on the TC checklist as assessed by the protocol monitor ranged from 70 to 100% across 37 counseling sessions (median 97%), with no difference between adherence for TRT (median, 97%) and partial TRT (median, 100%). Adherence to each of 44 critical items on the SOC checklist across 30 SOC counseling sessions ranged from 42 to 100% (median, 87.5%).Conclusion: The TRTT used multiple methods to address treatment fidelity. The close adherence to each treatment type was critical for evaluating the efficacy of the study interventions in this randomized trial.Trial Registration: clinicaltrials.gov NCT01177137 . Registered on 5 August 2010. [ABSTRACT FROM AUTHOR]

Background: Despite its proven efficacy in reducing recurrence and improving survival, adherence to endocrine therapy (ET) is suboptimal in women with breast cancer (BC). Health-related quality of life (HRQoL) in BC has been widely studied and many positive effects have been highlighted. Recently, a link between HRQoL and compliance with ET has been suggested, which would suggest a potential role for HRQoL assessment in improving compliance with ET. With the advent of digital technologies, electronic collection of HRQoL on a tablet is now possible. Thus, we hypothesize that systematic HRQoL assessment (using a tablet, prior to each consultation, with presentation of scores to clinicians) coupled with therapeutic information could have an impact on 12-month compliance with ET in patients with non-metastatic BC.Methods: In this study, we will include 342 women with non-metastatic hormone receptor-positive BC with an indication for treatment with ET. Patients will be randomly assigned 1:1 by minimization and stratified by age, stage, type of ET prescribed, and presence of comorbidities (or not) in two arms. The intervention will consist of numerical HRQoL assessment using the CHES (Computer-based Health Evaluation System) software before each consultation (with delivery of scores to clinicians) coupled with therapeutic information. Therapeutic information will consist of three workshops related to understanding the prescription, nutrition, and fatigue. A reminder letter will be sent to patients every month. Patients in the control group will follow standard care. HRQoL will be assessed using a classic "paper-pencil" collection at baseline in both arms to ensure comparability between arms and at 12 months. The primary endpoint is 12-month compliance with ET. Patient satisfaction with care and the clinicians' perception of the usefulness of routine HRQoL assessment will also be assessed.Discussion: This study will allow clinicians to identify and better understand the areas in which patients who receive ET have difficulties and thus it will assist clinicians with patient management. Systematic evaluation of HRQoL could provide an additional endpoint for measuring patients' health status and treatment-related symptoms, including ET. If the results of this study are positive, this intervention could be proposed as an integral part of daily clinical practice in patients who receive ET.Trial Registration: ClinicalTrials.govNCT04176809. Registered Nov. 25, 2019. [ABSTRACT FROM AUTHOR]

Background: This study aimed to test the feasibility and titration methods used to achieve specific blood pressure (BP) control targets in hypertensive patients of rural China.Methods: A randomized, controlled, open-label trial was conducted in Rongcheng, China. We enrolled 105 hypertensive participants aged over 60 years, and who had no history of stroke or cardiovascular disease. The patients were randomly assigned to one of three systolic-BP target groups: standard: 140 to < 150 mmHg; moderately intensive: 130 to < 140 mmHg; and intensive: < 130 mmHg. The patients were followed for 6 months.Discussion: The optimal target for systolic blood pressure (SBP) lowering is still uncertain worldwide and such information is critically needed, especially in China. However, in China the rates of awareness, treatment and control are only 46.9%, 40.7%, and 15.3%, respectively. It is challenging to achieve BP control in the real world and it is very important to develop population-specific BP-control protocols that fully consider the population's characteristics, such as age, sex, socio-economic status, compliance with medication, education level, and lifestyle. This randomized trial showed the feasibility and safety of the titration protocol to achieve desirable SBP targets (< 150, < 140, and < 130 mmHg) in a sample of rural, Chinese hypertensive patients. The three BP target groups had similar baseline characteristics. After 6 months of treatment, the mean SBP measured at an office visit was 137.2 mmHg, 131.1 mmHg, and 124.2 mmHg, respectively, in the three groups. Home BP and central aortic BP measurements were also obtained. At 6 months, home BP measurements (2 h after drug administration) showed a mean SBP of 130.9 mmHg in the standard group, 124.9 mmHg in the moderately intensive group, and 119.7 mmHg in the intensive group. No serious adverse events were recorded over the 6-month study period. Rates of adverse events, including dry cough, palpitations, and arthralgia, were low and showed no significant differences between the three groups. This trial provided real-world experience and laid the foundation for a future, large-scale, BP target study.Trial Registration: Feasibility Study of the Intensive Systolic Blood Pressure Control; ClinicalTrials.gov, ID: NCT02817503. Registered retrospectively on 29 June 2016. [ABSTRACT FROM AUTHOR]

Background: Patient adherence to treatment is a key determinant of outcome for healthcare interventions. Whilst non-adherence has been well evidenced in settings such as drug therapy, information regarding patient adherence to orthoses, particularly in the acute setting, is lacking. The aim of this systematic review was to identify, summarise, and critically appraise reported methods for assessing adherence to removable orthoses in adults following acute injury or surgery.Methods: Comprehensive searches of the Ovid versions of MEDLINE, Embase, AMED, CINAHL, Central, the Cochrane Database of Systematic Reviews, and SPORTDiscus identified complete papers published in English between 1990 and September 2018 reporting measurement of adherence to orthoses in adults following surgery or trauma to the appendicular skeleton. Only primary studies with reference to adherence in the title/abstract were included to maintain the focus of the review. Data extraction included study design, sample size, study population, orthosis studied, and instructions for use. Details of methods for assessing adherence were extracted, including instrument/method used, frequency of completion, number of items (if applicable), and score (if any) used to evaluate adherence overall. Validity and reliability of identified methods were assessed together with any conclusions drawn between adherence and outcomes in the study.Results: Seventeen papers (5 randomised trials, 10 cohort studies, and 2 case series) were included covering upper (n = 13) and lower (n = 4) limb conditions. A variety of methods for assessing adherence were identified, including questionnaires (n = 10) with single (n = 3) or multiple items (n = 7), home diaries (n = 4), and discussions with the patient (n = 3). There was no consistency in the target behaviour assessed or in the timing or frequency of assessment or the scoring systems used. None of the measures was validated for use in the target population.Conclusions: Measurement and reporting of adherence to orthosis use is currently inconsistent. Further research is required to develop a measurement tool that provides a rigorous and reproducible assessment of adherence in this acute population.Trial Registration: PROSPERO: CRD42016048462. Registered on 17/10/2016. [ABSTRACT FROM AUTHOR]