Smartphone-enabled video-observed versus directly observed treatment for tuberculosis: a multicentre, analyst-blinded, randomised, controlled superiority trial.

BACKGROUND: Directly observed treatment (DOT) has been the standard of care for tuberculosis since the early 1990s, but it is inconvenient for patients and service providers. Video-observed therapy (VOT) has been conditionally recommended by WHO as an alternative to DOT. We tested whether levels of treatment observation were improved with VOT. METHODS: We did a multicentre, analyst-blinded, randomised controlled superiority trial in 22 clinics in England (UK). Eligible participants were patients aged at least 16 years with active pulmonary or non-pulmonary tuberculosis who were eligible for DOT according to local guidance. Exclusion criteria included patients who did not have access to charging a smartphone. We randomly assigned participants to either VOT (daily remote observation using a smartphone app) or DOT (observations done three to five times per week in the home, community, or clinic settings). Randomisation was done by the SealedEnvelope service using minimisation. DOT involved treatment observation by a health-care or lay worker, with any remaining daily doses self-administered. VOT was provided by a centralised service in London. Patients were trained to record and send videos of every dose ingested 7 days per week using a smartphone app. Trained treatment observers viewed these videos through a password-protected website. Patients were also encouraged to report adverse drug events on the videos. Smartphones and data plans were provided free of charge by study investigators. DOT or VOT observation records were completed by observers until treatment or study end. The primary outcome was completion of 80% or more scheduled treatment observations over the first 2 months following enrolment. Intention-to-treat (ITT) and restricted (including only patients completing at least 1 week of observation on allocated arm) analyses were done. Superiority was determined by a 15% difference in the proportion of patients with the primary outcome (60% vs 75%). This trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN26184967. FINDINGS: Between Sept 1, 2014, and Oct 1, 2016, we randomly assigned 226 patients; 112 to VOT and 114 to DOT. Overall, 131 (58%) patients had a history of homelessness, imprisonment, drug use, alcohol problems or mental health problems. In the ITT analysis, 78 (70%) of 112 patients on VOT achieved ≥80% scheduled observations successfully completed during the first 2 months compared with 35 (31%) of 114 on DOT (adjusted odds ratio [OR] 5·48, 95% CI 3·10-9·68; p<0·0001). In the restricted analysis, 78 (77%) of 101 patients on VOT achieved the primary outcome compared with 35 (63%) of 56 on DOT (adjusted OR 2·52; 95% CI 1·17-5·54; p=0·017). Stomach pain, nausea, and vomiting were the most common adverse events reported (in 16 [14%] of 112 on VOT and nine [8%] of 114 on DOT). INTERPRETATION: VOT was a more effective approach to observation of tuberculosis treatment than DOT. VOT is likely to be preferable to DOT for many patients across a broad range of settings, providing a more acceptable, effective, and cheaper option for supervision of daily and multiple daily doses than DOT. FUNDING: National Institute for Health Research.

Explaining the successes and failures of tuberculosis treatment programs; a tale of two regions in rural eastern Uganda.

BACKGROUND: Optimally performing tuberculosis (TB) programs are characterized by treatment success rate (TSR) of at least 90%. In rural eastern Uganda, and elsewhere in sub Saharan Africa, TSR varies considerably across district TB programs and the reasons for the differences are unclear. This study explored factors associated with the low and high TSR across four districts in rural eastern Uganda. METHODS: We interviewed District TB and Leprosy Supervisors, Laboratory focal persons, and health facility TB focal persons from four districts in eastern Uganda as key informants. Interviews were audio recorded, transcribed verbatim, and imported into ATLAs.ti where thematic content analysis was performed and results were summarized into themes. RESULTS: The emerging themes were categorized as either facilitators of or barriers to treatment success. The emerging facilitators prevailing in the districts with high rates of treatment success were using data to make decisions and design interventions, continuous quality improvement, capacity building, and prioritization of better management of people with TB. The barriers common in districts with low rates of treatment success included lack of motivated and dedicated TB focal persons, scarce or no funding for implementing TB activities, and a poor implementation of community-based directly observed therapy short course. CONCLUSION: This study shows that several factors are associated with the differing rates of treatment success in rural eastern Uganda. These factors should be the focus for TB control programs in Uganda and similar settings in order to improve rates of treatment success.

High Completion Rate for 12 Weekly Doses of Isoniazid and Rifapentine as Treatment for Latent Mycobacterium tuberculosis Infection in the Federal Bureau of Prisons.

CONTEXT: Correctional facilities provide unique opportunities to diagnose and treat persons with latent tuberculosis infection (LTBI). Studies have shown that 12 weekly doses of isoniazid and rifapentine (INH-RPT) to treat LTBI resulted in high completion rates with good tolerability. OBJECTIVE: To evaluate completion rates and clinical signs or reported symptoms associated with discontinuation of 12 weekly doses of INH-RPT for LTBI treatment. SETTING/PARTICIPANTS: During July 2012 to February 2015, 7 Federal Bureau of Prisons facilities participated in an assessment of 12 weekly doses of INH-RPT for LTBI treatment among 463 inmates. MAIN OUTCOME MEASURES: Fisher exact test was used to assess the associations between patient sociodemographic characteristics and clinical signs or symptoms with discontinuation of treatment. RESULTS: Of 463 inmates treated with INH-RPT, 424 (92%) completed treatment. Reasons for discontinuation of treatment for 39 (8%) inmates included the following: 17 (44%) signs/symptoms, 9 (23%) transfer or release, 8 (21%) treatment refusal, and 5 (13%) provider error. A total of 229 (49.5%) inmates reported experiencing at least 1 sign or symptom during treatment; most frequently reported were fatigue (16%), nausea (13%), and abdominal pain (7%). Among these 229 inmates, signs/symptoms significantly associated with discontinuation of treatment included abdominal pain (P < .001), appetite loss (P = .02), fever/chills (P = .01), nausea (P = .03), sore muscles (P = .002), and elevation of liver transaminases 5× upper limits of normal or greater (P = .03). CONCLUSIONS: The LTBI completion rates were high for the INH-RPT regimen, with few inmates discontinuing because of signs or symptoms related to treatment. This regimen also has practical advantages to aid in treatment completion in the correctional setting and can be considered a viable alternative to standard LTBI regimens.

A National Survey on the Use of Electronic Directly Observed Therapy for Treatment of Tuberculosis.

CONTEXT: An increasing number of tuberculosis (TB) programs are adopting electronic directly observed therapy (eDOT), the use of technology to supervise patient adherence remotely. Pilot studies show that treatment adherence and completion were similar with eDOT compared with the standard in-person DOT. OBJECTIVE: In December 2015, the National Tuberculosis Controllers Association administered an online survey to determine the extent to which eDOT is used in the United States. PARTICIPANTS: Sixty-eight Centers for Disease Control and Prevention (CDC)-funded health department TB programs across the United States and a convenient sample of local health department TB programs. RESULTS: Fifty-six (82%) of 68 CDC-funded health department TB programs and an additional 57 local TB programs responded to the survey. Forty-seven (42%) of 113 TB programs are currently using eDOT, 41 (36%) are planning to implement it in the next year, and 25 (22%) have no plans to implement eDOT. Of the 47 TB programs using eDOT, 31 (66%) use synchronous video DOT, 4 (9%) asynchronous video DOT, 11 (23%) a combination of both, and 1 (2%) ingestible sensor to conduct electronic observations. Forty-one (87%) indicated that treatment adherence and 40 (85%) indicated that treatment completion were about the same or higher than in-person DOT. More than 80% indicated that eDOT resulted in program cost savings, and almost all (91%) reported benefits in patient and staff satisfaction. However, 25 (53%) of the 47 TB programs that use eDOT encountered technical challenges and 37 (79%) offer eDOT to less than a third of their patients. CONCLUSIONS: Results from this survey indicate that eDOT is a promising tool that can be utilized to efficiently and effectively manage TB treatment. Findings will inform other TB programs interested in implementing eDOT. However, further evaluation is needed to assess eDOT acceptability to understand barriers to eDOT implementation from the patient and provider perspectives.

A New Method to Directly Observe Tuberculosis Treatment: Skype Observed Therapy, a Patient-Centered Approach.

CONTEXT: Tuberculosis (TB) treatment completion is in part determined by patient's adherence to long-term drug regimens. To best ensure compliance, directly observed therapy (DOT) is considered the standard of practice. Nassau County Department of Health TB Control is responsible for providing DOT to patients with TB. OBJECTIVE: Tuberculosis Control sought to use and evaluate Skype Observed Therapy (SOT) as an alternative to DOT for eligible patients. DESIGN: The evaluation included analysis of patient's acceptance and adherence to drug regimen using SOT. Tuberculosis Control assessed staff efficiency and cost savings for this program. MAIN OUTCOME MEASURES: Percentages of SOT of patients and successful SOT visits, mileage, and travel time savings. RESULTS: Twenty percent of the caseload used SOT and 100% of patients who were eligible opted in. Average SOT success was 79%. Total mileage savings and time saved were $9,929.07 and 614 hours. CONCLUSIONS: Because SOT saves cost and time and is a suitable alternative to DOT for patients, it should be considered as part of new policies and practices in TB control programs.

Legal briefing: coerced treatment and involuntary confinement for contagious disease.

This issue's "Legal Briefing" column covers recent legal developments involving coerced treatment and involuntary confinement for contagious disease. Recent high profile court cases involving measles, tuberculosis, human immunodeficiency virus, and especially Ebola, have thrust this topic back into the bioethics and public spotlights. This has reignited debates over how best to balance individual liberty and public health. For example, the Presidential Commission for the Study of Bioethical Issues has officially requested public comments, held open hearings, and published a 90-page report on "ethical considerations and implications" raised by "U.S. public policies that restrict association or movement (such as quarantine)." Broadly related articles have been published in previous issues of The Journal of Clinical Ethics. We categorize recent legal developments on coerced treatment and involuntary confinement into the following six categories: 1. Most Public Health Confinement Is Voluntary 2. Legal Requirements for Involuntary Confinement 3. New State Laws Authorizing Involuntary Confinement 4. Quarantine Must Be as Least Restrictive as Necessary 5. Isolation Is Justified Only as a Last Resort 6. Coerced Treatment after Persistent Noncompliance.

Raising standards in UK TB control: introducing cohort review.

Cohort review has been used internationally to support tuberculosis (TB) control. We describe its first use in the UK by a London TB service. Improvements were noted in case management and contact tracing, weaknesses identified and important service changes put in place. Key areas of impact were directly observed therapy (DOT) provision (a greater proportion of cases offered DOT, and in response to low uptake resources diverted to create posts responsible for patient-centred DOT delivery), and contact tracing (more contacts per case screened and assessed). Cohort review enables whole system review and improvement. It has subsequently been adopted across the UK.

[Performance evaluation of primary care services for the treatment of tuberculosis]. / Avaliação de desempenho de serviços da atenção básica para o tratamento da tuberculose.

OBJECTIVE: Evaluating the performance of primary care services for the treatment of tuberculosis according to the assessment referential of health services (structure/process) in Cabedelo, a port city in the state of Paraíba. METHOD: An evaluation quantitative, cross-sectional study, in which were carried out 117 interviews with health professionals using a structured instrument. The analysis was based on the construction of indicators using a standardized value for the reduced variable (z=1). RESULTS: The structural indicators showed regular performance for the following variables: professional training, access to record instruments and coordination with other services. The process indicators related to external actions and information about the disease had unsatisfactory performance. The directly observed treatment and the flows of reference/counter-reference had regular performance. CONCLUSION: The focused professional qualification, the fragmentation of practices and the unsystematic home care constitute obstacles for carrying out actions aimed at providing expanded, continuous and resolute care.



[Nursing performance in the policy transfer of directly observed treatment of tuberculosis]. / Atuação da Enfermagem na transferência da política d otratamento diretamente observado da tuberculose.

OBJECTIVE: Analyzing the policy transfer of directly observed treatment of tuberculosis from the perspective of nursing. METHOD: This is a descriptive study with qualitative approach, which had 10 nurses of the Family Health Strategy in São Paulo as subjects. The interviews were carried out between May and June 2013, and were adopted the technique of thematic content analysis and the referential of policy transfer. RESULTS: On the signification of this treatment, are related the senses of disciplinary monitoring, the bond and approximation to the context of patients' lives. Operationally, nurses, community health agents and nursing technicians stand out as agents of implementation of this policy, developing multiple actions of user embracement. The nurse is evidenced as an educator in health, leader in the family health team, and capable of creating emotional bond with users. CONCLUSION: It was found that the innovations proposed in the treatment are incipient in the daily work of nurses.

Estimation of the contribution of private providers in tuberculosis case notification and treatment outcome in Pakistan.

To improve involvement of the private sector in the national tuberculosis (TB) programme in Pakistan various public-private mix projects were set up between 2004 and 2009. A retrospective analysis of data was made to study 6 different public-private mix models for TB control in Pakistan and estimate the contribution of the various private providers to TB case notification and treatment outcome. The number of TB cases notified through the private sector increased significantly from 77 cases in 2004 to 37,656 in 2009. Among the models, the nongovernmental organization model made the greatest contribution to case notification (58.3%), followed by the hospital-based model (18.9%). Treatment success was highest for the district-led model (94.1%) and lowest for the hospital-based model (74.2%). The private sector made an important contribution to the national data through the various public-private mix projects. Issues of sustainability and the lack of treatment supporters are discussed as reasons for lack of success of some projects.

Diagnostic delay amongst tuberculosis patients in Jogjakarta Province, Indonesia is related to the quality of services in DOTS facilities.

OBJECTIVES: To understand determinants of care-seeking patterns and diagnostic delay amongst tuberculosis (TB) patients diagnosed at direct observed treatment short course (DOTS) facilities in Jogjakarta, Indonesia. METHODS: Cross-sectional survey amongst newly diagnosed TB patients in 89 DOTS facilities whose history of care-seeking was reconstructed through retrospective interviews gathering data on socio-demographic determinants, onset of TB symptoms, type of health facilities visited, duration of each care-seeking action were recorded. RESULTS: Two hundred and fifty-three TB patients were included in the study whose median duration of patients' delay was 1 week and whose total duration of diagnostic delay was 5.4 weeks. The median number of visits was 4. Many of the patients' socio-demographic determinants were not associated with the care-seeking patterns, and no socio-demographic determinants were associated with the duration of diagnostic delay. More than 60% of TB patients started their care-seeking processes outside DOTS facilities, but the number of visits in DOTS facilities was greater during the overall care-seeking process. Surprisingly, patient's immediate visits to a DOTS facility did not correspond to shorter diagnostic delay. CONCLUSION: Diagnostic delay in Jogjakarta province was not associated with patients' socio demographic factors, but rather with the health system providing DOTS services. This suggests that strengthening the health system and improving diagnostic quality within DOTS services is now a more rational strategy than expanding the TB programme to engage more providers.

Structural and qualitative evaluation of microscopy and directly observed treatment centers under revised national tuberculosis control programme in Nanded city of Maharashtra.

Structural and qualitative evaluation of Revised National Tuberculosis Control Programme (RNTCP) is important to determine actual status of the programme in the field settings and to uncover the concealed gaps. The present cross-sectional study assessed the infrastructural facilities and quality of services provided through microscopy and directly observed treatment (DOT) centers at Nanded city of Maharashtra. The investigator made on spot observation on the activities at microscopy and DOT centers and assessed the infrastructural facilities using an observational checklist. Expert microbiologist cross checked the microscopy report done by the laboratory technicians. It revealed that retrieval mechanism was not functioning in more than half of the DOT centers. Only 5 DOT providers were trained in RNTCP. Stock of sputum containers, methylene blue, and carbol fuchsin was found to be inadequate at some microscopy centers. Half of the laboratory technicians reported high false positive result in spite of being trained. Improvement of infrastructural and logistic support along with the refreshing training for the workers are needed for effective implementation of RNTCP.

Missed opportunity for standardized diagnosis and treatment among adult tuberculosis patients in hospitals involved in Public-Private Mix for Directly Observed Treatment Short-Course strategy in Indonesia: a cross-sectional study.

BACKGROUND: The engagement of hospitals in Public-Private Mix (PPM) for Directly Observed Treatment Short-Course (DOTS) strategy has increased rapidly internationally - including in Indonesia. In view of the rapid global scaling-up of hospital engagement, we aimed to estimate the proportion of outpatient adult Tuberculosis patients who received standardized diagnosis and treatment at outpatients units of hospitals involved in the PPM-DOTS strategy. METHODS: A cross-sectional study using morbidity reports for outpatients, laboratory registers and Tuberculosis patient registers from 1 January 2005 to 31 December 2005. By quota sampling, 62 hospitals were selected. Post-stratification analysis was conducted to estimate the proportion of Tuberculosis cases receiving standardized management according to the DOTS strategy. RESULT: Nineteen to 53% of Tuberculosis cases and 4-18% of sputum smear positive Tuberculosis cases in hospitals that participated in the PPM-DOTS strategy were not treated with standardized diagnosis and treatment as in DOTS. CONCLUSION: This study found that a substantial proportion of TB patients cared for at PPM-DOTS hospitals are not managed under the DOTS strategy. This represents a missed opportunity for standardized diagnoses and treatment. A combination of strong individual commitment of health professionals, organizational supports, leadership, and relevant policy in hospital and National Tuberculosis Programme may be required to strengthen DOTS implementation in hospitals.

[Medication non adherence - predictive factors and diagnostics]. / Medikamentöse Nicht-Adhärenz - Prädiktive Faktoren und Diagnostik.

There are many complex reasons for medication non adherence and a gold standard to assess medication non adherence does not exist. We present factors associated with medication non adherence using the five adherence dimensions suggested by the World Health Organization as well as the subjective appraisal regarding medication intake of the patient as suggested by the National Institute of Health and Clinical Excellence in the UK. Based on current research based knowledge, we suggest a two step adherence assessment for the clinical setting: 1) a routine assessment (screening) using patient self-report complemented by non adherence evidence from other methods; 2) in-depth adherence assessment for patients with positive non adherence evidence via interview. The adherence assessment turns then into adherence support. Adherence is the result of a skilled collaborative partnership between patients and health professionals. In complex cases adherence has to be regarded as an aim to be achieved in several stages.

Social incentives for adherence to tuberculosis treatment.

OBJECTIVE: To analyze the influence of social incentives for adherence to tuberculosis (TB) treatment. METHOD: Qualitative study, in which 26 primary health care professionals of São Paulo were interviewed in 2015.Their testimonies were submitted to the speech analysis technique. The theoretical reference was the social determination of the health-disease process. Ethical procedures were observed. RESULTS: TB is related to precarious living conditions. Incentives such as the basic food basket and transportation stipends are relevant for patients' adherence to treatment, as well as to the create bonds between the patient and the health team. FINAL CONSIDERATIONS: The incentives strengthened adherence to TB treatment. However, interventions in the context of public measures must transcend the remedial dimension and be guided towards the transformation of the TB situation, which means supporting processes that modify living conditions.

Global monitoring of collaborative TB-HIV activities.

Tuberculosis (TB) and human immunodeficiency virus (HIV) programs are increasingly working together towards providing universal access to integrated TB and HIV prevention, treatment, care and support services. To monitor progress we need to measure the delivery and impact of these services; however, the lack of investment in monitoring and evaluation and the added complexity of sharing data between two vertical programs, makes monitoring and evaluation of collaborative TB-HIV activities especially challenging. We describe the global system to record, report and analyse data on collaborative TB-HIV activities and summarize results to date. Although the data suggest that there is a steady increase in collaborative TB-HIV activities in many high-burden countries over time, we are already falling behind the globally agreed implementation milestones. This is due to a combination of slow implementation and lack of necessary tools and systems for capturing activity data. In particular, data from HIV program monitoring of TB screening, TB preventive treatments and TB infection control for people living with HIV is lacking. Much remains to be done by both programs to improve the implementation, monitoring and evaluation of collaborative TB-HIV activities and to optimize prevention, treatment and care for people infected with both TB and HIV, especially in areas at high risk of drug-resistant TB.

Revising the tuberculosis recording and reporting information system.

OBJECTIVE: The tuberculosis recording and reporting information system (TB R&R), one of the five pillars of the DOTS strategy, has undergone a revision to comply with the new elements of the Stop TB Strategy and to ensure standardisation of essential TB information. DESIGN: An expert group on TB R&R, including the main technical partners, held a series of consultations with the Stop TB Working Groups and countries. Draft revised forms were field tested by countries with the participation of technical partners. A survey was conducted by the World Health Organization (WHO) in 105 countries. RESULT: The main changes in the TB R&R are the inclusion of TB-HIV activities (the leading reason for change at the country level), smear examinations and culture for settings performing this test routinely and the management of patient drug kits. The revised forms help monitor contributions from all care providers and community workers. The package of forms is presented in three sets: 1) essential data, 2) setting with routine culture and 3) additional data. CONCLUSION: The revised R&R forms were endorsed by the WHO, the KNCV Tuberculosis Foundation, the International Union Against Tuberculosis and Lung Disease and the US Centers for Disease Control and Prevention in 2007. They are now available in English, French and Spanish, and are adopted in most countries.

Adapting a generic tuberculosis control operational guideline and scaling it up in China: a qualitative case study.

BACKGROUND: The TB operational guideline (the deskguide) is a detailed action guide for county TB doctors aiming to improve the quality of DOTS, while the China national TB policy guide is a guide to TB control that is comprehensive but lacks operational usability for frontline TB doctors. This study reports the process of deskguide adaptation, its scale-up and lessons learnt for policy implications. METHODS: The deskguide was translated, reviewed, and revised in a working group process. Details of the eight adaptation steps are reported here. An operational study was embedded in the adaptation process. Two comparable prefectures were chosen as pilot and control sites in each of two participating provinces. In the pilot sites, the deskguide was used with the national policy guide in routine in-service training and supervisory trips; while in the control sites, only the national policy guide was used. In-depth interviews and focus groups were conducted with 16 county TB doctors, 16 township doctors, 17 village doctors, 63 TB patients and 57 patient family members. Following piloting, the deskguide was incorporated into the national TB guidelines for county TB dispensary use. RESULTS: Qualitative research identified that the deskguide was useful in the daily practice of county TB doctors. Patients in the pilot sites had a better knowledge of TB and better treatment support compared with those in the control sites. CONCLUSION: The adaptation process highlighted a number of general strategies to adapt generic guidelines into country specific ones: 1) local policy-makers and practitioners should have a leading role; 2) a systematic working process should be employed with capable focal persons; and 3) the guideline should be embedded within the current programmes so it is sustainable and replicable for further scale-up.

[The performance of health services in providing DOTs in households to control tuberculosis]. / Desempenho de serviços de saúde no Tratamento Diretamente Observado no domicílio para controle da tuberculose.

Exploratory study of qualitative and quantitative nature that evaluates the performance of the health services in providing DOT in households of a big city in Brazil. For the quantitative analysis, indexes were created to evaluate the optimization of material/human resources and the observation of the medicine ingestion. It was observed that performance of services is influenced by the availability of human/material resources, the internal organization of services and the absence of the ill person in the household. For the qualitative analysis it was used the content analysis, thematic modality. The main factors influencing the performance of the health service were found to be its insufficiency of material and human resources and the ill person's social-cultural and economic context. Concluding, it is necessary permanent managerial, organizational and techno-assistance qualification of the health professionals in the TB control.