Effectiveness and cost-effectiveness of community-based directly observed treatment (DOT) versus health facility-based DOT of tuberculosis in Africa: protocol for a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) remains a significant global health challenge, especially prevalent in the WHO African region. The WHO's End TB Strategy emphasises effective treatment approaches such as directly observed therapy (DOT), yet the optimal implementation of DOT, whether through health facility-based (HF DOT) or community-based (CB DOT) approaches, remains uncertain. OBJECTIVE: To conduct a systematic comparison of the effectiveness and cost-effectiveness of Community-Based Directly Observed Treatment (CB DOT) versus Health Facility-Based Directly Observed Treatment (HF DOT) for tuberculosis (TB) treatment in African settings. METHODS: We will conduct a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search PubMed, Embase, Web of Science, Scopus and the Cochrane Library for articles published up to 30 March 2023, without date restrictions. Eligible studies must be full economic evaluations conducted in African countries, comparing CB DOT to HF DOT regarding treatment outcomes and costs. Exclusion criteria include non-English, non-peer-reviewed or studies lacking caregiver involvement in CB DOT, health facility-based DOT comparison, direct comparability between CB DOT and HF DOT, significant selection bias or non-economic evaluations. Data extraction will be performed independently by reviewers, and meta-analyses will use STATA software. To pool the data, a random-effect model will be applied, and quality assessment of the studies will be conducted. ETHICS AND DISSEMINATION: Ethical approval is not required as the study will use previously published articles available publicly. Findings will be presented at international and national conferences and published in open-access, peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023443260.

Results From a Pilot Study of an Automated Directly Observed Therapy Intervention Using Artificial Intelligence With Conditional Economic Incentives Among Young Adults With HIV.

BACKGROUND: Despite improvements in antiretroviral therapy (ART) availability, suboptimal adherence is common among youth with HIV (YWH) and can increase drug resistance and poor clinical outcomes. Our study examined an innovative mobile app-based intervention that used automated directly observed therapy (aDOT) using artificial intelligence, along with conditional economic incentives (CEIs) to improve ART adherence and enhance viral suppression among YWH. SETTING: We conducted a pilot study of the aDOT-CEI intervention, informed by the operant framework of Key Principles in Contingency Management Implementation, to improve ART adherence among YWH (18-29) in California and Florida who had an unsuppressed HIV viral load. METHODS: We recruited 28 virally unsuppressed YWH from AIDS Healthcare Foundation clinics, who used the aDOT platform for 3 months. Study outcomes included feasibility and acceptability, self-reported ART adherence, and HIV viral load. RESULTS: Participants reported high satisfaction with the app (91%), and 82% said that it helped them take their medication. Comfort with the security and privacy of the app was moderate (55%), and 59% indicated the incentives helped improve daily adherence. CONCLUSIONS: Acceptability and feasibility of the aDOT-CEI intervention were high with potential to improve viral suppression, although some a priori metrics were not met. Pilot results suggest refinements which may improve intervention outcomes, including increased incentive amounts, provision of additional information, and reassurance about app privacy and security. Additional research is recommended to test the efficacy of the aDOT-CEI intervention to improve viral suppression in a larger sample.

Costs of Digital Adherence Technologies for Tuberculosis Treatment Support, 2018-2021.

Digital adherence technologies are increasingly used to support tuberculosis (TB) treatment adherence. Using microcosting, we estimated healthcare system costs (in 2022 US dollars) of 2 digital adherence technologies, 99DOTS medication sleeves and video-observed therapy (VOT), implemented in demonstration projects during 2018-2021. We also obtained cost estimates for standard directly observed therapy (DOT). Estimated per-person costs of 99DOTS for drug-sensitive TB were $98 in Bangladesh (n = 719), $119 in the Philippines (n = 396), and $174 in Tanzania (n = 976). Estimated per-person costs of VOT were $1,154 in Haiti (87 drug-sensitive), $304 in Moldova (173 drug-sensitive), $452 in Moldova (135 drug-resistant), and $661 in the Philippines (110 drug-resistant). 99DOTS costs may be similar to or less expensive than standard DOT. VOT is more expensive, although in some settings, labor cost offsets or economies of scale may yield savings. 99DOTS and VOT may yield savings to local programs if donors cover infrastructure costs.

Youth Ending the HIV Epidemic (YEHE): Protocol for a pilot of an automated directly observed therapy intervention with conditional economic incentives among young adults with HIV.

BACKGROUND: Young adults have a disproportionately high rate of HIV infection, high rates of attrition at all stages of the HIV care continuum, and an elevated probability of disease progression and transmission. Tracking and monitoring objective measures of antiretroviral therapy (ART) adherence in real time is critical to bolster the accuracy of research data, support adherence, and improve clinical outcomes. However, adherence monitoring often relies on self-reported and retrospective data or requires additional effort from providers to understand individual adherence patterns. In this study, we will monitor medication-taking using a real-time objective measure of adherence that does not rely on self-report or healthcare providers for measurement. METHODS: The Youth Ending the HIV Epidemic (YEHE) study will pilot a novel automated directly observed therapy-conditional economic incentive (aDOT-CEI) intervention to improve ART adherence among youth with HIV (YWH) in California and Florida who have an unsuppressed HIV viral load. The aDOT app uses facial recognition to record adherence each day, and then economic incentives are given based on a participant's confirmed adherence. We will enroll participants in a 3-month pilot study to assess the feasibility and acceptability of the aDOT-CEI intervention using predefined metrics. During and after the trial, a subsample of the pilot participants and staff/providers from participating AIDS Healthcare Foundation (AHF) clinics will participate in individual in-depth interviews to explore intervention and implementation facilitators and barriers. DISCUSSION: YEHE will provide data on the use of an aDOT-CEI intervention to improve adherence among YWH who are not virologically suppressed. The YEHE study will document the feasibility and acceptability and will explore preliminary data to inform a trial to test the efficacy of aDOT-CEI. This intervention has the potential to effectively improve ART adherence and virologic suppression among a key population experiencing health disparities. TRIAL REGISTRATION: The trial registration number is NCT05789875.

Cost of digital technologies and family-observed DOT for a shorter MDR-TB regimen: a modelling study in Ethiopia, India and Uganda.

BACKGROUND: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO's 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB. METHODS: A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters. RESULTS: Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients' direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses. CONCLUSIONS: While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients.

Estimated Costs of 4-Month Pulmonary Tuberculosis Treatment Regimen, United States.

We estimated direct costs of a 4-month or 6-month regimen for drug-susceptible pulmonary tuberculosis treatment in the United States. Costs were $23,000 per person treated. Actual treatment costs will vary depending on examination and medication charges, as well as expenses associated with directly observed therapy.

Effect of Digital Medication Event Reminder and Monitor-Observed Therapy vs Standard Directly Observed Therapy on Health-Related Quality of Life and Catastrophic Costs in Patients With Tuberculosis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Little is known about whether digital adherence technologies are economical for patients with tuberculosis (TB) in resource-constrained settings. Objective: To test the hypothesis that for patients with TB, a digital medication event reminder monitor (MERM)-observed therapy provides higher health-related quality of life (HRQoL) and lower catastrophic costs compared with standard directly observed therapy (DOT). Design, Setting, and Participants: This study was a secondary analysis of a randomized, 2-arm, open-label trial conducted in 10 health care facilities in Ethiopia. Eligible participants were adults with new or previously treated, bacteriologically confirmed, drug-sensitive pulmonary TB who were eligible to start first-line anti-TB therapy. Participants were enrolled between June 2, 2020, and June 15, 2021, with the last participant completing follow-up on August 15, 2021. Interventions: Participants were randomly assigned (1:1) to receive a 15-day TB medication supply dispensed with a MERM device to self-administer and return every 15 days (intervention arm) or the standard in-person DOT (control arm). Both groups were observed throughout the standard 2-month intensive treatment phase. Main Outcomes and Measures: Prespecified secondary end points of the original trial were HRQoL using the EuroQoL 5-dimension 5-level (EQ-5D-5L) tool and catastrophic costs, direct (out-of-pocket) and indirect (guardian and coping) costs from the individual patient perspective using the World Health Organization's Tool to Estimate Patient Costs, and common factors associated with lower HRQoL and higher catastrophic costs. Results: Among 337 patients screened for eligibility, 114 were randomly assigned, and 109 were included in the final complete-case intention-to-treat analysis (57 control and 52 intervention participants). The mean (SD) age was 33.1 (11.1) years; 72 participants (66.1%) were men, and 15 (13.9%) had HIV coinfection. EQ-5D-5L overall median (IQR) index value was 0.964 (0.907-1). The median (IQR) value was significantly higher in intervention (1 [0.974-1]) vs control (.908 [0.891-0.964]) (P < .001). EQ-5D-5L minimum and maximum health state utility values in intervention were 0.906 and 1 vs 0.832 and 1 in control. Patients' overall median (IQR) postdiagnosis cost was Ethiopian birr (ETB) 80 (ETB 16-ETB 480) (US $1.53). The median cost was significantly lower in intervention (ETB 24 [ETB 16-ETB 48]) vs control (ETB 432 [ETB 210-ETB 1980]) (P < .001), with median possible cost savings of ETB 336 (ETB 156-ETB 1339) (US $6.44) vs the control arm. Overall, 42 participants (38.5%; 95% CI, 29.4%-48.3%) faced catastrophic costs, and this was significantly lower in the intervention group (11 participants [21.2%]; 95% CI, 11.1%-34.7%) vs control (31 participants [54.4%]; 95% CI, 40.7%-67.6%) (P < .001). Trial arm was the single most important factor in low HRQoL (adjusted risk ratio [ARR], 1.49; 95% CI, 1.35-1.65; P < .001), while trial arm (ARR, 2.55; 95% CI, 1.58-4.13; P < .001), occupation (ARR, 2.58; 95% CI, 1.68-3.97; P < .001), number of cohabitants (ARR, 0.64; 95% CI, 0.43-0.95; P = .03), and smoking (ARR, 2.71; 95% CI, 1.01-7.28; P = .048) were the most important factors in catastrophic cost. Conclusions and Relevance: In patients with TB, MERM-observed therapy was associated with higher HRQoL and lower catastrophic costs compared with standard DOT. Patient-centered digital health technologies could have the potential overcoming structural barriers to anti-TB therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT04216420.

Tuberculosis treatment management in primary healthcare sectors: a mixed-methods study investigating delivery status and barriers from organisational and patient perspectives.

OBJECTIVE: Tuberculosis (TB) treatment management services (TTMSs) are crucial for improving patient treatment adherence. Under the TB integrated control model in China, healthcare workers (HCWs) in the primary healthcare (PHC) sectors are responsible for TTMS delivery. This mixed-method study aimed to explore the status of and barriers to TTMS delivery faced by HCWs in PHC sectors from the health organisational and patient perspectives. DESIGN: We completed a questionnaire survey of 261 TB healthcare workers (TB HCWs) and 459 patients with TB in the PHC sector and conducted 20 semistructured interviews with health organisational leaders, TB HCWs and patients with TB. SPSS V.22.0 and the framework approach were used for data analysis. SETTING: PHC sectors in Southwest China. RESULTS: Our results showed that TTMS delivery rate by HCWs in PHC sectors was <90% (88.4%) on average, and the delivery rates of intensive and continuation phase directly observed therapy (DOT) were only 54.7% and 53.0%, respectively. HCWs with high work satisfaction and junior titles were more likely to deliver first-time home visits and DOT services. Our results suggest that barriers to TTMS delivery at the organisational level include limited patient-centred approaches, inadequate resources and incentives, insufficient training, poor cross-sectional coordination, and strict performance assessment. At the patient level, barriers include low socioeconomic status, poor health literacy and TB-related social stigma. CONCLUSION: TTMSs in Southwest China still need further improvement, and this study highlighted specific barriers to TTMS delivery in the PHC sector. Comprehensive measures are urgently needed to address these barriers at the organisational and patient levels to promote TB control in Southwest China.

Global economic costs due to vivax malaria and the potential impact of its radical cure: A modelling study.

BACKGROUND: In 2017, an estimated 14 million cases of Plasmodium vivax malaria were reported from Asia, Central and South America, and the Horn of Africa. The clinical burden of vivax malaria is largely driven by its ability to form dormant liver stages (hypnozoites) that can reactivate to cause recurrent episodes of malaria. Elimination of both the blood and liver stages of the parasites ("radical cure") is required to achieve a sustained clinical response and prevent ongoing transmission of the parasite. Novel treatment options and point-of-care diagnostics are now available to ensure that radical cure can be administered safely and effectively. We quantified the global economic cost of vivax malaria and estimated the potential cost benefit of a policy of radical cure after testing patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency. METHODS AND FINDINGS: Estimates of the healthcare provider and household costs due to vivax malaria were collated and combined with national case estimates for 44 endemic countries in 2017. These provider and household costs were compared with those that would be incurred under 2 scenarios for radical cure following G6PD screening: (1) complete adherence following daily supervised primaquine therapy and (2) unsupervised treatment with an assumed 40% effectiveness. A probabilistic sensitivity analysis generated credible intervals (CrIs) for the estimates. Globally, the annual cost of vivax malaria was US$359 million (95% CrI: US$222 to 563 million), attributable to 14.2 million cases of vivax malaria in 2017. From a societal perspective, adopting a policy of G6PD deficiency screening and supervision of primaquine to all eligible patients would prevent 6.1 million cases and reduce the global cost of vivax malaria to US$266 million (95% CrI: US$161 to 415 million), although healthcare provider costs would increase by US$39 million. If perfect adherence could be achieved with a single visit, then the global cost would fall further to US$225 million, equivalent to $135 million in cost savings from the baseline global costs. A policy of unsupervised primaquine reduced the cost to US$342 million (95% CrI: US$209 to 532 million) while preventing 2.1 million cases. Limitations of the study include partial availability of country-level cost data and parameter uncertainty for the proportion of patients prescribed primaquine, patient adherence to a full course of primaquine, and effectiveness of primaquine when unsupervised. CONCLUSIONS: Our modelling study highlights a substantial global economic burden of vivax malaria that could be reduced through investment in safe and effective radical cure achieved by routine screening for G6PD deficiency and supervision of treatment. Novel, low-cost interventions for improving adherence to primaquine to ensure effective radical cure and widespread access to screening for G6PD deficiency will be critical to achieving the timely global elimination of P. vivax.

Family Health Strategy and determinants of directly observed treatment for tuberculosis in Brazil: a cross-sectional study with surveillance system data, 2014-2016. / Estratégia Saúde da Família e determinantes para o tratamento diretamente observado da tuberculose no Brasil: estudo transversal com dados do sistema de vigilância, 2014-2016.

OBJECTIVE: To assess the association between tuberculosis determinants and performance of directly observed treatment (DOT) under different levels of Family Health Strategy (FHS) coverage in Brazil. METHODS: This was a cross-sectional study using data on tuberculosis cases notified between 2014 and 2016 on the Notifiable Health Conditions Information System, as well as data on FHS coverage in the municipality of residence. Logistic regression was used. RESULTS: 177,626 individuals were included; being an alcohol user (odds ratio (OR) 1.09 - 95% confidence interval % [95%CI] 1.03;1.16), being deprived of liberty (OR=1.21 - 95%CI 1.12;1.32) and positive sputum smear microscopy (OR=1.15 - 95%CI 1.10;1.21) increased the chances of DOT being performed . When stratified by FHS coverage, these associations became weak in the highest stratum of coverage. CONCLUSION: DOT being performed was associated with determinants of tuberculosis. However, association was not confirmed among residents in municipalities with higher FHS coverage.

Patient-perceived treatment burden of tuberculosis treatment.

BACKGROUND: Treatment for tuberculosis lasts for a minimum of 6 months. The treatment burden experienced by patients in a low-incidence setting where directly observed therapy is the standard of care is not well-known. METHODS: Patients receiving tuberculosis treatment through the chest clinic at a tertiary hospital in Sydney, Australia, participated in a semi-structured interview. The interviews explored the treatment burden experienced by patients and possible solutions to ameliorate this burden. Interviews were conducted until data saturation was achieved. They were recorded, transcribed and analysed using NVivo 12 software. RESULTS: Twenty participants (80% male, mean age 40 years) with pulmonary (n = 13) and extra-pulmonary (n = 7) tuberculosis were interviewed. Participants experienced healthcare, financial, social and medication burdens along with lifestyle changes due to treatment. Medication intake was challenging due to the high number of pills, and 55% (n = 11) of patients experienced fatigue amongst other side effects. Patients found clinic-based directly observed therapy inconvenient, especially those working and/or studying. Suggestions to lessen treatment burden included reducing medication burden and better access to health services. CONCLUSION: Tuberculosis treatment is associated with substantial treatment burden for patients. Measures to reduce treatment burden including alternative treatment delivery methods which are more accommodating to patients than clinic-based directly observed therapy, such as video directly observed therapy or partially self -administered treatment, should be considered on a case-by-case basis.

Cost of Tuberculosis Therapy Directly Observed on Video for Health Departments and Patients in New York City; San Francisco, California; and Rhode Island (2017-2018).

Objectives. To assess costs of video and traditional in-person directly observed therapy (DOT) for tuberculosis (TB) treatment to health departments and patients in New York City, Rhode Island, and San Francisco, California.Methods. We collected health department costs for video DOT (VDOT; live and recorded), and in-person DOT (field- and clinic-based). Time-motion surveys estimated provider time and cost. A separate survey collected patient costs. We used a regression model to estimate cost by DOT type.Results. Between August 2017 and June 2018, 343 DOT sessions were captured from 225 patients; 87 completed a survey. Patient costs were lowest for VDOT live ($1.01) and highest for clinic DOT ($34.53). The societal (health department + patient) costs of VDOT live and recorded ($6.65 and $12.64, respectively) were less than field and clinic DOT ($21.40 and $46.11, respectively). VDOT recorded health department cost was not statistically different from field DOT cost in Rhode Island.Conclusions. Among the 4 different modalities, both types of VDOT were associated with lower societal costs when compared with traditional forms of DOT.Public Health Implications. VDOT was associated with lower costs from the societal perspective and may reduce public health costs when TB incidence is high.

Drones and digital adherence monitoring for community-based tuberculosis control in remote Madagascar: A cost-effectiveness analysis.

BACKGROUND: Continuing tuberculosis control with current approaches is unlikely to reach the World Health Organization's objective to eliminate TB by 2035. Innovative interventions such as unmanned aerial vehicles (or drones) and digital adherence monitoring technologies have the potential to enhance patient-centric quality tuberculosis care and help challenged National Tuberculosis Programs leapfrog over the impediments of conventional Directly Observed Therapy (DOTS) implementation. A bundle of innovative interventions referred to for its delivery technology as the Drone Observed Therapy System (DrOTS) was implemented in remote Madagascar. Given the potentially increased cost these interventions represent for health systems, a cost-effectiveness analysis was indicated. METHODS: A decision analysis model was created to calculate the incremental cost-effectiveness of the DrOTS strategy compared to DOTS, the standard of care, in a study population of 200,000 inhabitants in rural Madagascar with tuberculosis disease prevalence of 250/100,000. A mixed top-down and bottom-up costing approach was used to identify costs associated with both models, and net costs were calculated accounting for resulting TB treatment costs. Net cost per disability-adjusted life years averted was calculated. Sensitivity analyses were performed for key input variables to identify main drivers of health and cost outcomes, and cost-effectiveness. FINDINGS: Net cost per TB patient identified within DOTS and DrOTS were, respectively, $282 and $1,172. The incremental cost per additional TB patient diagnosed in DrOTS was $2,631 and the incremental cost-effectiveness ratio of DrOTS compared to DOTS was $177 per DALY averted. Analyses suggest that integrating drones with interventions ensuring highly sensitive laboratory testing and high treatment adherence optimizes cost-effectiveness. CONCLUSION: Innovative technology packages including drones, digital adherence monitoring technologies, and molecular diagnostics for TB case finding and retention within the cascade of care can be cost effective. Their integration with other interventions within health systems may further lower costs and support access to universal health coverage.

Transmission and prevalence of drug-resistant tuberculosis in a Brazilian setting under a directly observed therapy short-course strategy.

INTRODUCTION: We aimed to estimate the prevalence and transmission of drug-resistant tuberculosis in a high-burden Brazilian setting under directly observed therapy short-course strategy. METHODS: Isolates of culture-confirmed pulmonary tuberculosis patients from Guarulhos, Brazil, diagnosed in October 2007-2011 were subjected to drug susceptibility and IS6110-restriction fragment length polymorphism testing. RESULTS: The overall resistance prevalence was 11.5% and the multi-drug resistance rate was 4.2%. Twenty-six (43.3%) of 60 drug-resistant isolates were clustered. Epidemiological relationships were identified in 11 (42.3%) patients; 30.8% of the cases were transmitted in households. CONCLUSIONS: Drug-resistant tuberculosis was relatively low and transmitted in households and the community.

Electronic pillbox-enabled self-administered therapy versus standard directly observed therapy for tuberculosis medication adherence and treatment outcomes in Ethiopia (SELFTB): protocol for a multicenter randomized controlled trial.

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

Transmission and prevalence of drug-resistant tuberculosis in a Brazilian setting under a directly observed therapy short-course strategy

Abstract INTRODUCTION: We aimed to estimate the prevalence and transmission of drug-resistant tuberculosis in a high-burden Brazilian setting under directly observed therapy short-course strategy. METHODS: Isolates of culture-confirmed pulmonary tuberculosis patients from Guarulhos, Brazil, diagnosed in October 2007-2011 were subjected to drug susceptibility and IS6110-restriction fragment length polymorphism testing. RESULTS: The overall resistance prevalence was 11.5% and the multi-drug resistance rate was 4.2%. Twenty-six (43.3%) of 60 drug-resistant isolates were clustered. Epidemiological relationships were identified in 11 (42.3%) patients; 30.8% of the cases were transmitted in households. CONCLUSIONS: Drug-resistant tuberculosis was relatively low and transmitted in households and the community.

Estratégia Saúde da Família e determinantes para o tratamento diretamente observado da tuberculose no Brasil: estudo transversal com dados do sistema de vigilância, 2014-2016 / Estrategia Salud Familiar y determinantes para el tratamiento directamente observado de la tuberculosis en Brasil: un estudio transversal con datos del Sistema de Vigilancia, 2014-2016 / Family Health Strategy and determinants of directly observed treatment for tuberculosis in Brazil: a cross-sectional study with surveillance system data, 2014-2016

Objetivo: Analisar a associação entre determinantes da tuberculose e a realização do tratamento diretamente observado (TDO), sob diferentes níveis de cobertura da Estratégia Saúde da Família (ESF) no Brasil. Métodos: Estudo transversal, com dados dos casos de tuberculose notificados no Sistema de Informação de Agravos de Notificação entre 2014 e 2016, e da cobertura da ESF no município de residência. Empregou-se regressão logística. Resultados: Foram incluídos 177.626 indivíduos; ser etilista (odds ratio [OR] de 1,09 - intervalo de confiança de 95% [IC95%] de 1,03 a 1,16), estar privado de liberdade (OR=1,21 - IC95% 1,12;1,32) e apresentar baciloscopia positiva (OR=1,15 - IC95% 1,10;1,21) aumentaram as chances de realização do TDO. Quando estratificadas por cobertura da ESF, essas associações viram-se enfraquecidas no maior estrato de cobertura. Conclusão: A realização do TDO associou-se a determinantes da tuberculose; contudo, a associação não se confirmou entre residentes de municípios com maiores coberturas da ESF.

Objetivo: Analizar la asociación entre los determinantes de la tuberculosis y el desempeño del Tratamiento Directamente Observado (TDO) en diferentes coberturas de la Estrategia de Salud Familiar (ESF) en Brasil. Métodos: Estudio transversal con casos de tuberculosis notificados entre 2014 y 2016 en el Sistema de Información de Enfermedades de Notificación y cobertura de la Estrategia de Salud Familiar en el municipio de residencia. Se utilizó regresión logística. Resultados: Se incluyeron 177,626 individuos. Tener alcoholismo (odds ratio (OR) 1,09 - intervalo de confianza del 95% (IC95%) 1,03; 1,16), estar privados de libertad (OR=1.21 - IC95% 1,12;1.32) y tener baciloscopia positiva (OR=1,15 - IC95%1,10;1,21) aumentó las posibilidades de realizar el TDO. Cuando se estratificó por cobertura de ESF, estas asociaciones disminuyen en el estrato de mayor cobertura. Conclusión: El TDO se asoció a determinantes de la tuberculosis, sin embargo, no se confirmó entre los residentes en municipios con mayor cobertura de ESF.

Objective: To assess the association between tuberculosis determinants and performance of directly observed treatment (DOT) under different levels of Family Health Strategy (FHS) coverage in Brazil. Methods: This was a cross-sectional study using data on tuberculosis cases notified between 2014 and 2016 on the Notifiable Health Conditions Information System, as well as data on FHS coverage in the municipality of residence. Logistic regression was used. Results: 177,626 individuals were included; being an alcohol user (odds ratio (OR) 1.09 - 95% confidence interval % [95%CI] 1.03;1.16), being deprived of liberty (OR=1.21 - 95%CI 1.12;1.32) and positive sputum smear microscopy (OR=1.15 - 95%CI 1.10;1.21) increased the chances of DOT being performed . When stratified by FHS coverage, these associations became weak in the highest stratum of coverage. Conclusion: DOT being performed was associated with determinants of tuberculosis. However, association was not confirmed among residents in municipalities with higher FHS coverage.

Revisión sistemática: costo-efectividad, acceso y adherencia a programas de ejercicio supervisado en pacientes con claudicación intermitente / Systematic review: cost-effectiveness, access and adherence to supervised exercise programs in patients with intermittent claudication

OBJETIVO: Determinar las razones de la escasa derivación, acceso, y adherencia a programas de ejercicio supervisado (PES) en pacientes con claudicación intermitente (CI) y la costo-efectividad de estos programas a nivel Internacional. MÉTODOS: Se utilizaron las fuentes de datos de PubMed y ScienceDirect. Se incluyeron revisiones con acceso completo, publicados desde el año 2010, que incluían como mínimo 3 artículos de tipo cuantitativo. RESULTADOS: Se incluyeron 5 Revisiones asociadas a los resultados del ejercicio supervisado, su costo-efectividad, la baja derivación y adherencia a PES de los pacientes con CI. En cuanto a la costo-efectividad los resultados indican que los PES fueron rentables con un ICER de £711 a £1.608 por QALY ganado al compararlos con ejercicio no supervisado, y al compararlos con la cirugía de revascularización (CR) no hay diferencia significativa en QALY ganados, sin embargo, el costo por QALY fue €381.694 más alto para la CR. Por otro lado, las principales razones de la subutilización de los PES, es que los pacientes se resisten a asistir, ya que involucra un esfuerzo y responsabilidad, además de tener problemas de reembolso, teniendo baja adherencia. Sumado a esto, el interés personal de los médicos por realizar intervenciones que involucran pago por servicio produce una baja derivación (45% de cirujanos en Europa refieren menos del 50% de sus pacientes). CONCLUSIÓN: Las principales dificultades para adoptar los PES serían una carencia en la destinación de recursos, falta de centros, dificultad de traslado, falta de tiempo, o de interés por parte de los pacientes, además de incentivos financieros a otras alternativas de tratamiento por sobre PES lo que limita su derivación.

OBJECTIVE: To determine the reasons for the limited derivation, access and adherence to supervised exercise programs (SEP) in patients with intermittent claudication (IC) and the cost-effectiveness of these programs internationally. METHODS: PubMed and ScienceDirect databases were searched. Revisions with full access, published since 2010, which included at least 3 quantitative type articles. RESULTS: 5 reviews were included, these were associated with the results of the supervised exercise, its cost-effectiveness, the low referral and adherence to programs of patients with IC. Regarding cost-effectiveness, the results indicated that SEP were more cost-effective with an ICER of £711 to £1.608 per QALY gained when compared with unsupervised exercise, and that when compared with revascularization surgery (RC) there was no significant difference in QALYs, however the cost per QALY was € 381.694 higher for the RC. On the other hand, the main reasons for the underutilization of SEP are that patients are reluctant to attend, since it involves effort and responsibility, in addition to having reimbursement problems, therefore having low adherence. Added to this, the personal interest of doctors in performing interventions that involve payment for service produce a low referral (45% of surgeons in Europe refer less than 50% of their patients) CONCLUSION: The main difficulties in adopting the SEP would be a lack in the allocation of resources, lack of centers, difficulty of transportation, lack of time or lack of interest from patients, in addition to financial incentives to other treatment alternatives over SEP, which limits their referral.

Cost savings associated with video directly observed therapy for treatment of tuberculosis.

OBJECTIVE: To calculate the per-session and annual direct program costs to implement directly observed therapy (DOT) for tuberculosis treatment and to conduct a cost attribution analysis under varying proportions of DOT utilization for four DOT types.DESIGN: Program data covering the study period from September 2014 to August 2015 in New York City (NYC) were used to conduct a retrospective bottom-up micro-costing economic evaluation. For each DOT type, potential per-session and annual program savings were estimated as the cost averted by adopting a uniform distribution of DOT alternatives. Sensitivity analyses explored aggregate cost impacts of unequal distributions.RESULTS: There was a total of 38 035 unique DOT visits, of which 12 002 (32%) were clinic-based (CDOT); 15 483 (41%) were field-based (FDOT); 7185 (19%) were live-video (LVDOT); and 3365 (9%) were recorded-video (RVDOT). The per-session direct costs (in 2016 $US) for DOT services delivered during the study period were $8.46 for CDOT; $19.83 for FDOT; $6.54 for LVDOT; and $5.35 for RVDOT. Sensitivity analyses supported the main findings.CONCLUSIONS: Significant cost savings were estimated with increased utilization of VDOT. Assuming equivalent treatment adherence, duration, completion, and adverse events across DOT types, RVDOT was the modality that most minimized cost.

Rationale and design of a randomized pragmatic trial of patient-centered models of hepatitis C treatment for people who inject drugs: The HERO study.

BACKGROUND: Although people who inject drugs (PWID) having the highest incidence and prevalence of hepatitis C virus (HCV) in the US, HCV treatment is rarely provided to PWID due to assumptions about poor adherence and reinfection risk. As direct-acting antiviral agents (DAAs) have achieved sustained virologic response (SVR) rates of 95% or more, evidence-based strategies are urgently needed to demonstrate real-world effectiveness in marginalized patient populations such as PWID. The objectives of this study are: 1) to determine whether either of two patient-centered treatment models - patient navigation (PN) or modified directly observed therapy (mDOT) - results in more forward movement along the HCV care cascade including treatment initiation, adherence, and SVR; 2) using quantitative and qualitative methods, to understand factors associated with lack of treatment uptake, poor adherence (<80%), failure to achieve SVR, DAA resistance, and HCV reinfection. METHODS: The HERO study is a multi-site, pragmatic randomized clinical trial conducted in eight states where 754 HCV-infected PWID were randomly assigned to either PN or mDOT. CONCLUSIONS: This study addresses an urgent need for timely and accurate information on optimal models of care to promote HCV treatment initiation, adherence, treatment completion and SVR among PWID, as well as rates and factors associated with reinfection and resistance after treatment. This clinical trial has the potential to provide valuable information on how to reduce the burden of the HCV epidemic in PWID.