Background Tuberculosis (TB) is an urgent global health threat and the world’s deadliest infectious disease despite being largely curable. A critical challenge is to ensure that patients adhere to the full course of treatment to prevent the continued spread of the disease and development of drug-resistant disease. Mobile health interventions hold promise to provide the required adherence support to improve TB treatment outcomes. Objective This study aims to evaluate the effectiveness of the TB treatment support tools (TB-TSTs) intervention on treatment outcomes (success and default) and to assess patient and provider perceptions of the facilitators and barriers to TB-TSTs implementation. Methods The TB-TSTs study is an open-label, randomized controlled trial with 2 parallel groups in which 400 adult patients newly diagnosed with TB will be randomly assigned to receive usual care or usual care plus TB-TSTs. Participants will be recruited on a rolling basis from 4 clinical sites in Argentina. The intervention consists of a smartphone progressive web app, a treatment supporter (eg, TB nurse, physician, or social worker), and a direct adherence test strip engineered for home use. Intervention group participants will report treatment progress and interact with a treatment supporter using the app and metabolite urine test strip. The primary outcome will be treatment success. Secondary outcomes will include treatment default rates, self-reported adherence, technology use, and usability. We will assess patients’ and providers’ perceptions of barriers to implementation and synthesize lessons learned. We hypothesize that the TB-TSTs intervention will be more effective because it allows patients and TB supporters to monitor and address issues in real time and provide tailored support. We will share the results with stakeholders and policy makers. Results Enrollment began in November 2020, with a delayed start due to the COVID-19 pandemic, and complete enrollment is expected by approximately July 2022. Data collection and follow-up are expected to be completed 6 months after the last patient is enrolled. Results from the analyses based on the primary end points are expected to be submitted for publication within a year of data collection completion. Conclusions To our knowledge, this randomized controlled trial will be the first study to evaluate a patient-centered remote treatment support strategy using a mobile tool and a home-based direct drug metabolite test. The results will provide robust scientific evidence on the effectiveness, implementation, and adoption of mobile health tools. The findings have broader implications not only for TB adherence but also more generally for chronic disease management and will improve our understanding of how to support patients facing challenging treatment regimens. Trial Registration ClinicalTrials.gov NCT04221789; https://clinicaltrials.gov/ct2/show/NCT04221789. International Registered Report Identifier (IRRID) DERR1-10.2196/28094

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The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pump is responsible for the transport of Ca2+ from the cytosol into the sarcoplasmic reticulum at the expense of ATP, making it a regulator of both muscle relaxation and muscle-based energy expenditure. Neurogranin (Ng) is a small protein that negatively regulates calcineurin signaling. Calcineurin is Ca2+/calmodulin dependent phosphatase that promotes the oxidative fibre type in skeletal muscle and regulates muscle-based energy expenditure. A recent study has shown that calcineurin activation reduces SERCA Ca2+ transport efficiency, ultimately raising energy expenditure. Since the biomedical view of obesity states that it arises as an imbalance between energy intake and expenditure which favors the former, we questioned whether heterozygous Ng deletion (Ng+/-) would reduce SERCA efficiency and increase energy expenditure in female mice fed a high-fat diet (HFD). Young (3–4-month-old) female wild type (WT) and Ng+/- mice were fed a HFD for 12 weeks with their metabolic profile being analyzed using metabolic cages and DXA scanning, while soleus SERCA efficiency was measured using SERCA specific Ca2+ uptake and ATPase activity assays. Ng+/- mice showed significantly less cage ambulation compared to WT mice but this did not lead to any added weight gain nor changes in daily energy expenditure, glucose or insulin tolerance despite a similar level of food intake. Furthermore, we observed significant reductions in SERCA’s apparent coupling ratio which were associated with significant reductions in SERCA1 and phospholamban content. Thus, our results show that Ng regulates SERCA pump efficiency, and future studies should further investigate the potential cellular mechanisms.

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BACKGROUND Tuberculosis (TB) is an urgent global health threat and the world’s deadliest infectious disease despite it being largely curable. A critical challenge is to ensure that patients adhere to the full course of treatment to prevent the continued spread of disease and the development of drug resistant disease. Mobile health (mHealth) interventions hold promise to provide the needed adherence support to improve TB treatment outcomes. OBJECTIVE To evaluate the effectiveness of the TB treatment support tools (TB-TSTs) intervention on treatment outcomes (success, default) and to assess patient and provider perceptions of the facilitators and barriers to TB-TST implementation. METHODS The TB-TSTs study is a randomized controlled trial (RCT) with two parallel groups in which 400 adult patients newly diagnosed with TB will be randomly assigned to receive usual care or usual care plus TB-TSTs. Intervention group participants will report treatment progress and interact with a treatment supporter using an innovative interactive smartphone App and a paper-based drug metabolite urine test strip engineered for home use. The primary outcome will be treatment success. Secondary outcomes will include treatment default rates, self-reported adherence, technology use, and usability. We will assess patient and provider perceptions of barriers to implementation and synthesize lessons learned. We hypothesize that the TB-TSTs intervention will be more effective because it allows patients and TB supporters to monitor and address issues in real time and provide tailored support. We will share results with stakeholders and policymakers. RESULTS We anticipated the start of enrollment in November 2020, a delayed start due to the COVID-19 pandemic and complete enrollment by approximately July 2022. Data collection and follow-up is expected to be completed six months after the last patient is enrolled. Results from the analyses based on the primary endpoints are expected to be submitted for publication within a year of data collection completion. CONCLUSIONS This RCT will be the first to our knowledge to evaluate a patient centered remote treatment support strategy using a mobile tool and a home-based direct drug metabolite test. The results will provide robust scientific evidence on effectiveness, implementation, and adoption of the mHealth tools. Findings have broader implications not only for TB adherence but also chronic disease management more generally and will improve our understanding of how to support patients facing challenging treatment regimens. CLINICALTRIAL ClinicalTrials.gov NCT04221789; https://clinicaltrials.gov/ct2/show/NCT04221789