Tuberculosis Medication Research Articles

Magnitude of undernutrition and associated factors among adult tuberculosis patients attending public health facilities in Haramaya District, Eastern Ethiopia

BackgroundTuberculosis is one of the top ten causes of illness, death, and disability throughout the world. Undernutrition reduces immunity, which makes latent tuberculosis more likely to become active tuberculosis. Tuberculosis makes these conditions worse. The body of a person suffering from TB has an increased demand for energy, which often causes a TB patient to lose a significant amount of weight and this can worsen acute undernutrition. The aim of this study was to assess the magnitude of undernutrition and its associated factors among adult TB patients in public health facilities in Haramaya district, eastern Ethiopia.MethodsInstitution-based cross-sectional study was conducted among 330 adult tuberculosis patients on follow-up in public health facility of Haramaya District, eastern Ethiopia from January 10, 2021 to February 20, 2021. An anthropometric assessment was done after a face-to-face interview using a pretested structured questionnaire. SPSS 24 was used to analyze the data. Bivariable and multivariable logistic regression model was used to identify factors associated with undernutrition.ResultsThe overall prevalence of undernutrition was 43.6% (95% CI 38.2–49.1%). Proportion of severe, moderate and mild undernutrition was 11.8%, 12.4%, and 19.4%, respectively. Age group of 18–24 years (AOR = 4.12; 95% CI 1.36–12.51), not have formal education (AOR = 1.76; 95% CI 1.01–3.08), having large family size (AOR = 2.62; 95% CI 1.43–4.82), low dietary diversity (AOR = 2.96; 95% CI 1.75–4.99), lack of latrine (AOR = 2.14; 95% CI 1.26–3.65), history of TB treatment (AOR = 2.56; 95% CI 1.19–5.54) and taking intensive phase of anti-TB drugs (AOR = 3.18; 95% CI 1.62–6.25) were factors found significantly associated with under nutrition.ConclusionThe prevalence of undernutrition was high. Age, educational status, family size, dietary diversity, toilet facility, history of tuberculosis medication and intensive phase of anti-TB drugs were found significantly associated with undernutrition. The nutritional derangement could call for fast nutritional intervention in the management of pulmonary tuberculosis patients.

Hepatotoxicity and tuberculosis treatment outcomes in chronic liver disease.

The treatment of tuberculosis (TB) is known to cause liver injury, however, there is limited data to guide optimal treatment for patients with chronic liver disease. We undertook a retrospective case series of patients with chronic liver disease and TB disease. The primary objective was to determine if there was a difference in the incidence of drug-induced liver injury (DILI) in patients with cirrhosis versus those with chronic hepatitis. Additionally, we sought to compare TB treatment outcomes, type and duration of therapy, and incidence of adverse events. We included 56 patients (chronic hepatitis 40; cirrhosis 16). There were 33 patients (58.9%) who experienced DILI requiring treatment modification, with no significant difference between groups (65% versus 43.8%, p = 0.23). Patients with chronic hepatitis were more likely to receive treatment with standard first-line intensive phase therapy that included a combination of rifampin (RIF), isoniazid, and pyrazinamide (80.8% versus 19.2%, p = 0.03) and any regimen than included isoniazid (92.5% versus 68.8%, p = 0.04). The risk of DILI was higher when more hepatotoxic TB medications were used. Overall treatment success in this cohort was low (55.4%), with no significant difference between groups (62.5% versus 37.5%, p = 0.14). Most patients with treatment success (97%) were able to tolerate a rifamycin. The risk of DILI is high, especially with the use of isoniazid, in patients with TB and chronic liver disease. This risk can be effectively mitigated with no difference in treatment outcomes in the presence of cirrhosis.

Patient-reported usability and satisfaction with electronic medication event reminder and monitor device for tuberculosis: a multicentre, randomised controlled trial

The success of a tuberculosis digital adherence technology relies on patients' satisfaction with and the usability of the technology. This study aimed to evaluate treatment satisfaction and usability of a digital medication event reminder and monitor (MERM) device for patients with tuberculosis to address the prespecified secondary endpoint of the SELFTB trial. In this multicenter, randomised controlled trial, adults (≥18 years) with new or previously treated, bacteriologically-confirmed, drug-sensitive pulmonary tuberculosis who were eligible to start anti-tuberculosis therapy were recruited from 10 healthcare facilities in Ethiopia. With a computer-generated random number sequence, participants were randomly assigned 1:1 to receive a 15-day tuberculosis medication supply dispensed with an evriMED500® MERM device to self-administer and return every 15 days or the standard in-person DOT. Both arms were followed throughout the standard two-month intensive treatment phase. Treatment was based on the WHO-recommended two-month fixed-dose-combination of first-line anti-tuberculosis drug delivered as a single daily dose (2RHZE). Treatment Satisfaction Questionnaire for Medication version 4 (TSQM 1.4©) was used to measure and compare treatment satisfaction between arms. Adapted System Usability Scale (SUS) was used to assess the usability of the device, with emphasis on ease of use, challenges, benefits, motivation, popularity, and recommendation. The findings were correlated with adherence and clinical endpoints including sputum smear conversion and IsoScreen urine isoniazid test results. This trial is registered with ClinicalTrials.gov, NCT04216420. Between June 2, 2020, and June 15, 2021, 337 patients were screened for eligibility, of whom 109 participants enrolled and completed the satisfaction [control (n=57) and intervention (n=52) arms] and usability [intervention arm (n=52)] questionnaires. TSQM 1.4© geometric mean scores were: Effectiveness 73.25 [geometric standard deviation (GSD) 1.28], Side Effects 100, Convenience 63.31 (GSD 1.45), and Global Satisfaction 77.29 (GSD 1.25). TSQM score was significantly higher in the intervention vs the control: Effectiveness [85.78 vs 63.43, 95% CI 1.35 (1.26-1.45), p<0.001], Convenience [85.41 vs 48.18, 95% CI 1.77 (1.63-1.93), p<0.001], and Global Satisfaction [90.19 vs 67.11, 95% CI 1.34 (1.26-1.43), p<0.001]. There were significant associations between Global Satisfaction and medication adherence (p=0.017). Average SUS score was 97.45%, which was close to the best imaginable SUS value of 100%. Likelihood to Recommend (LTR) value was ≥9, on a scale of 0-10, for 90.4% of MERM users, yielding higher net promoters. There was no significant association between usability and medication adherence (p=0.691). Our findings suggested that treatment satisfaction scores were superior in the intervention vs control arms and across the domains of Effectiveness, Convenience, and Global Satisfaction. There was excellent usability of the MERM device and a significantly higher number of users likely to promote the device. High tuberculosis burden countries may transform patient-centered care through ongoing evaluation and scale-up of digital health innovations. U.S. National Institute of Health (NIH) Fogarty International Center and National Institute of Allergy and Infectious Diseases (D43 TW009127) and the Emory Center for AIDS Research (P30 AI050409).

Examining Drug-Resistant Tuberculosis Stigma Among Health Care Workers Toward the Development of a Stigma-Reduction Intervention: Protocol for a Scoping Review

Drug-resistant tuberculosis (DRTB) is an increasing threat to human health and economic security worldwide. Exacerbating the severity of DRTB is the low rate of service delivery, leading to increased community transmission of the disease, further amplified by stigma. Health workers are on the front line of service delivery; their efforts in all areas of disease control are suspected of having resulted in stigmatization, impacting patient-centered care. As a growing concern, attention to addressing the DRTB stigma confronting health workers is required. However, little is known about stigma among health workers delivering services to patients with DRTB. This scoping review will provide an overview that could help inform appropriate responses toward stigma-reduction interventions for these health workers. This scoping review protocol articulates a methodology that will examine the facets of DRTB-related stigma confronting health workers in high TB- and DRTB-burdened countries. This scoping review will (1) summarize stigma barriers and facilitators contributing to stigmatization among health workers delivering services to patients with DRTB, (2) identify the most common stigma barrier and facilitator, and (3) summarize the stigma-reduction intervention recommendations in the studies. Guided by Arksey and O'Malley's framework and the recommendations of Munn et al, we will conduct a scoping review of relevant literature providing evidence of DRTB-related stigma among health workers from countries with a high burden of tuberculosis (TB) and DRTB. We will search published articles written in English from 2010 onward in electronic databases using Medical Subject Headings and keywords. Our search will apply a 3-step search strategy and use software tools to manage references and facilitate the entire scoping review process. The findings of our review will be presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews checklist. Our study is registered with Open Science Framework Registries. This scoping review is part of a bigger project that will critically investigate stigma among health workers delivering services to patients resistant to TB medications. This study began in November 2021 and is expected to finish in 2023. The study has retrieved 593 abstracts out of 12,138 articles searched since February 2022 from the identified databases. The findings of this study will be published in a peer-reviewed journal. This review will provide an outline of the aspects of DRTB-related stigma confronting health workers. The findings of this review could help inform appropriate responses toward stigma-reduction interventions for these health workers. This is significant because interventions addressing related TB (and DRTB) stigma in the workplace are lacking. DERR1-10.2196/43084.

Parents Knowledge and Experiences of Child TB Patients about Medicine Administration in the Intensive Phase

BACKGROUND: Children with pulmonary tuberculosis (TB) who are undergoing intensive phase of treatment often experience negative things, resulting in disobedience in taking medication. Exploration of the experiences of pediatric TB patients in the treatment process needs to be known as information for management from the aspect of drug adherence. The role of parents in overcoming these problems is very important, so it is necessary to know the extent of their knowledge about pulmonary TB disease. METHODS: A qualitative study to explore the experiences of pediatric TB patients was conducted by interviewing 15 patients aged 8–12 years. In addition, a questionnaire was filled out to assess the knowledge about TB of the patient’s parents. The results of the recorded interviews were written and analyzed using the thematic method, while the results of the questionnaire from parents were analyzed descriptively. RESULTS: The results of the questionnaire showed that as many as ten respondents (66.6%) had a sufficient level of knowledge with 9 (60%). Analysis of the data using the Spearman rank test obtained a significance value (p) of 0.11 where p &lt; 0.05, which means there is no relationship between adherence to medication for pulmonary tuberculosis in children and the knowledge of parents in the intensive phase. CONCLUSION: Parental knowledge is sufficient or good does not guarantee that it can change the behavior of individuals or children in complying with the treatment in the intensive phase, although knowledge plays an important role in increasing adherence to taking medication in the intensive phase, there may be other factors that influence so that there is no relationship.

Roadblocks and resilience: A qualitative study of the impact of pediatric tuberculosis on Tanzanian households and solutions from caregivers

ABSTRACT Distinct from quantifying the economic sequelae of tuberculosis (TB) in adults, data are scarce regarding lived experiences of youth and their caregivers seeking and sustaining TB treatment in low income communities. Children ages 4–17 diagnosed with TB and their caregivers were recruited from rural and semi-urban northern Tanzania. Using a grounded theory approach, a qualitative interview guide was developed, informed by exploratory research. Twenty-four interviews were conducted in Kiswahili, audio-recorded and analyzed for emerging and consistent themes. Dominant themes found were socioemotional impacts of TB on households, including adverse effects on work productivity, and facilitators and obstacles to TB care, including general financial hardship and transportation challenges. The median percentage of household monthly income spent to attend a TB clinic visit was 34% (minimum: 1%, maximum: 220%). The most common solutions identified by caregivers to mitigate adverse impacts were transportation assistance and nutrition supplementation. To end TB, healthcare systems must acknowledge the total financial burden shouldered by low wealth families seeking pediatric TB care, provide consultations and medications locally, and increase access to TB-specific communal funds to mitigate burdens such as inadequate nutrition. Trial registration: planned sub-study of the registered prospective study, NCT05283967. Trial registration: ClinicalTrials.gov identifier: NCT05283967.

A Study to Determine The Incidence of Pulmonary Tuberculosis in Urban Slum Areas of Ram Nagar (North Belagavi) - An Observational Study

Background Tuberculosis is one of most prominent mycobacterium diseases. It kills more people than any other infectious disease in the world. The worldwide mortality rate of tuberculosis is around 2 million per year and nearly 0.5 million people die from it. Low socio-economic status is considered a significant risk factor for tuberculosis. Objectives To determine the incidence of pulmonary tuberculosis in urban slum areas of Ram Nagar North Belagavi.Methods This observational study included 70 families 325 subjects of both sexes and all age groups in urban slum areas of Ram Nagar Belagavi. Subjects were interrogated with a self-structured questionnaire related to symptoms of pulmonary tuberculosis and categorized into three parameters i.e. positive cases suspected cases and cases already on tuberculosis medication. Results The study revealed that out of 325 interrogated subjects seven were suspected of tuberculosis. Out of seven suspected cases three were found to be tuberculosis-positive and out of the three positive cases one subject was already taking medication. Conclusion In this study 2ndash3 of people were suspected of tuberculosis. This shows the relation between low socio-economic status and tuberculosis as reported in slum areas of Ram Nagar Belagavi. Therefore preventive programs are necessary to tackle such rising tubercular infections.

Tuberculosis and Pulmonary Co-Infections: Clinical Profiles and Management Strategies

Tuberculosis (TB) along with pulmonary co-infections in patients became a grave concern to public health complicating the disease diagnosis, treatment, and prognosis. It became a challenge to healthcare professionals urging to develop new diagnostic tools and treatment regimens. This paper reviews the complex interplay and management strategies for Tuberculosis patients with co-infections. It encompasses antimicrobial therapy tailored to particular pathogens, including their susceptibility profiles to antibiotics, and understanding the potential implications of drug interactions with anti- Tuberculosis medications. In cases of co-infection between Tuberculosis and Human Immuno-Deficiency Virus (HIV), a particular focus is placed on the significance of synergistic methods and treatment duration. Moreover, immunomodulatory drugs, immunotherapies, cellular treatments, adjunct therapies, and immunomodulatory agents that are customised to the patient's immunological status and co-infecting pathogens emerge as a crucial component. Mitigating the transmission of pulmonary co-infections requires the implementation of infection control measures in both healthcare settings and communities. A strong barrier against the spread of tuberculosis and related illnesses is formed by administrative, engineering, and personal protective measures combined with screening, education, isolation, and contact tracking. Prospective approaches underscore the necessity for enhanced diagnostic instruments, promoting cutting-edge technologies including molecular diagnostics, immunological tests, radiological imaging, biosensors, and point-of-care diagnostics. Comprehensive management is emphasised through multidisciplinary care comprising pulmonologists, infectious disease experts, microbiologists, and immunologists. Priorities for research include combination medications, new therapeutic approaches, personalised medicine, and developing diagnostic techniques to improve knowledge of and treatments for pulmonary co-infections.

SCREENING OF ASHITABA (ANGELICA KEISKEI K.) COMPOUNDS AS POTENTIAL MYCOBACTERIUM TUBERCULOSIS KASA INHIBITORS

Objective: Tuberculosis (TB) is a major global issue, mainly owing to the emergence of antibiotic-resistant strains of the disease's causative agent, Mycobacterium tuberculosis. The current standard of treatment for tuberculosis entails a prolonged course of antibiotics with toxic side effects and is accompanied by low patient compliance. Therefore, developing and discovering TB medications is critical to obtaining TB drugs that are more effective and sensitive to Mycobacterium tuberculosis. Ashitaba (Angelica keiskei K.) has reported that Ashitaba extract and chalcone have anti-TB properties, but the responsible compound has not been reported yet. This study aimed to identify the profile metabolites present in Ashitaba and their interaction with Mycobacterium tuberculosis KasA.&#x0D; Methods: To suggest these, we used molecular docking and molecular dynamic to predict the interactions of 40 selected compounds from the Ashitaba against Mycobacterium tuberculosis KasA (PDB ID 2WGE).&#x0D; Results: The results of molecular docking identified the top two compounds as xanthoangelol I (XAI) and (2E)-1-[4-hydroxy-2-(2-hydroxy-2-propanyl)-2,3-dihydro-1-benzofuran-7-yl]-3-(4-hydroxyphenyl)-2-propen-1-one (4HH), with bond free energies of-12.03 and-11.87 kcal/mol, respectively. Based on the results of molecular dynamics simulations, the XAI was stronger than 4HH in stabilizing complexes with 2WGE with total energy (ΔGbind, MMGBSA) of-54.8512 and-37.8836 kcal/mol, respectively.&#x0D; Conclusion: It can be concluded that xanthoangelol I (XAI) have the most potent inhibitor of Mycobacterium tuberculosis KasA.

Renal tuberculosis mimics renal cell carcinoma

The prevalence of renal tuberculosis (TB) in Thailand is high, but few reports have been published with regard to this issue. This report concerns the case of a 34-year-old Thai female with large masses in the right kidney, liver, and an enlarged lymph node in the abdominal cavity. The renal mass appeared to resemble the end stage of a carcinoma, but the pathology report of renal tissue indicated suspected tuberculosis. The patient was treated with TB medication for 6 months. A computerized tomography scan of the abdominal cavity after 6 months showed that there was no evidence of disease remaining

Improving Tuberculosis Medication Adherence: The Potential of Integrating Digital Technology and Health Belief Model.

Tuberculosis (TB) is a significant public health concern. Globally, TB is among the top 10 and the leading cause of death due to a single infectious agent. Providing standard anti-TB therapy for at least 6 months is recommended as one of the crucial strategies to control the TB epidemic. However, the long duration of TB treatment raised the issue of non-adherence. Non-adherence to TB therapy could negatively affect clinical and public health outcomes. Thus, directly observed therapy (DOT) has been introduced as a standard strategy to improve anti-TB medication adherence. Nonetheless, the DOT approach has been criticized due to inconvenience, stigma, reduced economic productivity, and reduced quality of life, which ultimately could complicate adherence issues. Apart from that, its effectiveness in improving anti-TB adherence is debatable. Therefore, digital technology could be an essential tool to enhance the implementation of DOT. Incorporating the health belief model (HBM) into digital technology can further increase its effectiveness in changing behavior and improving medication adherence. This article aimed to review the latest evidence regarding TB medication non-adherence, its associated factors, DOT's efficacy and its alternatives, and the use of digital technology and HBM in improving medication adherence. This paper used the narrative review methodology to analyze related articles to address the study objectives. Conventional DOT has several disadvantages in TB management. Integrating HBM in digital technology development is potentially effective in improving medication adherence. Digital technology provides an opportunity to improve medication adherence to overcome various issues related to DOT implementation.

Tuberculosis Monitoring Encouragement Adherence Drive (TMEAD): Toward improving the adherence of the patients with drug-sensitive tuberculosis in Nashik, Maharashtra.

Adherence to tuberculosis (TB) medication is one of the critical challenges to tuberculosis elimination in India. Digital adherence technologies (DAT) have the potential to facilitate medication adherence and monitor it remotely. Tuberculosis Monitoring Encouragement Adherence Drive (TMEAD) is one such DAT piloted in Nasik, Maharashtra, from April 2020 to December 2021. The study aims to assess the adherence and cost-effectiveness of TMEAD compared to the standard of care among patients with drug-sensitive tuberculosis (DSTB) residing in the urban areas of Nasik, Maharashtra, India. A quasi-experimental study was conducted among new cases of TB as per the National TB Elimination Programme (NTEP) residing in the urban geography of Nasik. The intervention and control arms were purposively selected from non-contaminating TB units (TUs). A total of 400 DSTB patients (200 in the intervention group and 200 in the control group) were enrolled. After enrolment, patients in the intervention arm were provided with the TMEAD device and followed for 24 weeks to assess treatment outcomes. Adherence was measured as those patients who have completed 80% of prescribed doses, as reported during patient follow-up, and further validated by analyzing the trace of rifampicin in urine among 20% of patients from both arms. A budget impact analysis was done to assess the impact of the TMEAD program on the overall state health budget. Out of 400 enrolled DSTB patients, 261 patients completed treatment, 108 patients were on treatment, 15 patients died, and 16 patients were defaulters over the study period. The study reported overall treatment adherence of 94% among those who completed treatment. Patient reports indicated high levels of treatment adherence in the intervention group (99%) as compared to the control group (90%). Adherence assessed through analyzing trace of rifampicin in the urine sample for the intervention arm was 84% compared to the control arm (80%). Per beneficiary (discounted) cost for TMEAD was Indian rupees (INR) 6,573 (USD 83). The incremental cost-effectiveness ratio of the intervention is INR 11,599 (USD 146), which shows that the intervention is highly cost-effective. This study revealed that patient-reported treatment adherence was high in TMEAD when compared to standard therapy of care for DSTB patients and the intervention is cost-effective. TMEAD could complement the national strategy to end TB by improving adherence to the treatment regimen in India.

1269. End HIV with DOT: Maybe?

Abstract Background Directly observed Therapy (DOT) has proven to be a valuable asset used in ascertaining adherence to tuberculosis (TB) medications, methadone, psychiatric medications and HIV medications. Both HIV and TB share the need of adherence to treatment to avoid resistance. However, unlike TB, HIV treatment must be taken for life. Argus Community (Argus DOT) provides Directly Observed Therapy to assist with medication adherence to HIV positive patients with medication adherence barriers who are not virally suppressed as long as the patient is from an affiliated medical provider network which includes St. Barnabas Designated AIDS Center (SBH DAC). Methods SBH DAC started referring patients who have not been virally suppressed to Argus DOT March 2021 to help reach our goal of 90% virally suppressed rate (viral load &amp;lt; 200 copies/ml) by the end of 2021. Those who agreed to DOT were referred, accepted and enrolled in Argus. Argus DOT calls patients daily Monday to Friday to remind them to take their medications. We performed a retrospective chart review of SBH DAC/Argus DOT patients to see if this intervention improved our suppression rate from March 2021 to December 2021 and if there were any barriers for our patients in regards to receiving these benefits. Results 18 patients were approached by the DAC team to enroll in Argus DOT; of those 15 originally agreed to the program. 3 patients declined the enrollment. Of the 15 patients who agreed to the program, 6 patients discontinued the program and none of these 6 patients achieved viral load suppression. Results of 9 patients who stayed with Argus DOT: 8 out of 9 patients achieved a viral load &amp;lt; 200 copies/ml and one achieved 230 copies/ml from 2200 copies/ml. 2 patients achieve a viral load &amp;lt; 20 copies/ml (undetectable). Conclusion This small study shows Argus DOT as valuable asset in achieving decrease HIV viral load in patients with medication adherence barriers. 50% accepting and staying with the program achieved 89% viral suppression; close to the 90% needed to End the Epidemic. 9 out of 18 who did not agree or discontinued Argus DOT due to uncontrolled psychiatric, substance use, nonworking phones and distrust did not achieve viral suppression. Co-located psychiatric, substance use as well as in-house SBH DOT personnel is needed to achieve viral load suppression. Disclosures All Authors: No reported disclosures.

Factors of medication adherence among adult patients with tuberculosis: A literature review

Introduction: Medication adherence is a critical factor in the success of tuberculosis (TB) therapy. Many factors are related to TB medication adherence among TB patients in clinical and community services. This study aimed to identify the factors of TB medication adherence based on the Social-Ecological Model. Methods: A literature review was carried out for this study. Articles published between 2016 and 2021 in three databases were included in this study.

Construction and application of tuberculosis medical and nursing integration cooperation model.

To explore the clinical effect of the tuberculosis (TB) doctor-nurse integration management model METHODS: This study is a retrospective historical cohort study. The clinical data of 180 patients with TB in our hospital from 2019 to 2020 were analyzed retrospectively. In a control group, 90 cases were treated with the traditional medical care model. An observation group of 90 cases received clinical diagnoses, treatments, and nursing under a doctor-nurse integration management model. Comparative analyses between the two groups were conducted on various aspects, including the awareness level of TB prevention and control, medication compliance and patient satisfaction. Comparisons between the two groups were evaluated using independent-sample t-tests or Chi-squared tests RESULTS: Compared with the control group, the knowledge awareness levels of TB prevention and medication compliance in the observation group were significantly higher (p <.05). The appointment waiting times and hospitalization times in the observation group were significantly lower than in the control group (p<.05). The total average satisfaction score of the patients in the observation group was significantly higher than in the control group (p<.05). Compared with the control group, the patients in the observation group were significantly more satisfied with their nursing methods, operating techniques, psychological techniques, service attitudes, and ward management (p<.05). In addition, in the observation group, medical-nursing relationships and doctor-patient communication were better than in the control group; additionally, the satisfaction of doctors with nursing work was also higher than in the control group, which was a statistically significant difference (p<.05) CONCLUSION: The implementation of an integrated medical-nursing cooperation model for TB will help increase the awareness of health knowledge in patients with TB, improve patient medication compliance and enhance patient satisfaction.

Effectiveness of a digital medication event reminder and monitor device for patients with tuberculosis (SELFTB): a multicenter randomized controlled trial

BackgroundTuberculosis remains the leading cause of death from a single infectious disease worldwide. Trials evaluating digital adherence technologies for tuberculosis in low- and middle-income countries are urgently needed. We aimed to assess whether a digital medication event reminder and monitor (MERM) device-observed self-administered therapy improves adherence and treatment outcomes in patients with tuberculosis compared with the standard in-person directly observed therapy (DOT).MethodsWe did a two-arm, attention-controlled, effectiveness-implementation type 2 hybrid, randomized controlled trial in ten healthcare facilities in Addis Ababa, Ethiopia. We included adults with new or previously treated, bacteriologically confirmed, drug-sensitive pulmonary tuberculosis who were eligible to start anti-tuberculosis therapy. Participants were randomly assigned (1:1) to receive a 15-day tuberculosis medication supply in the evriMED500® MERM device to self-administer and return every 15 days (intervention arm) or visit the healthcare facilities each day to swallow their daily dose with DOT by healthcare providers (control arm). Both arms were followed throughout the standard two-month intensive treatment phase (2RHZE). For control participants, some provider-approved take-home doses might be allowed for extenuating circumstances in real-world practice. Data were collected on patient information (demographic, socioeconomic, behavioral, social, and clinical information), medication adherence measures (MERM vs. DOT records, IsoScreenTM urine colorimetric isoniazid test, and adherence self-report), and clinical measures (pre-post treatment sputum Xpert MTB/RIF assay or microscopy, and adverse treatment outcomes). The intention-to-treat (ITT) primary endpoints were (1) individual-level percentage adherence over the two-month intensive phase measured by adherence records compiled from MERM device vs. DOT records that also considered all take-home doses as having been ingested and (2) sputum smear conversion following the standard two-month intensive phase treatment. Secondary endpoints were (1) individual-level percentage adherence over the two-month intensive phase measured by adherence records compiled from the MERM device vs. DOT records that considered all take-home doses as not ingested, (2) negative IsoScreen urine isoniazid test, (3) adverse treatment outcome (having at least one of the three events: treatment not completed; death; or loss to follow-up), and (4) self-reported adherence. The MERM device has an electronic module and a medication container that records adherence, stores medication, emits audible and visual on-board alarms to remind patients to take their medications on time and refill, and enables providers to download the data and monitor adherence.ResultsParticipants were enrolled into the study between 02 June 2020 and 15 June 2021, with the last participant completing follow-up on 15 August 2021. A total of 337 patients were screened for eligibility, of whom 114 were randomly assigned and included in the final analysis [57 control and 57 intervention participants]. Participants were 64.9% male, 15% with HIV, 10.5% retreatment, and 5.3% homeless. Adherence to TB medication was comparable between the intervention arm [geometric mean percentage (GM%) 99.01%, geometric standard deviation (GSD) 1.02] and the control arm [GM% 98.97%, GSD 1.04] and was within the prespecified margin for non-inferiority [mean ratio (MR) 1.00 (95% CI 0.99–1.01); p = 0.954]. The intervention arm was significantly superior to the control arm in the secondary analysis that considered all take-home doses in the control were not ingested [control GM% 77.71 (GSD 1.57), MR 1.27 (95% CI 1.33–1.43)]. Urine isoniazid testing was done on 443 (97%) samples from 114 participants; 13 participants had at least one negative result; a negative test was significantly more common among the control group compared with the intervention group [11/57 (19.3%) vs 2/57 (3.5%); p = 0.008]. There was no significant difference between the control and intervention arms for smear conversion [55 (98.2%) vs 52 (100%); p>0.999], adverse treatment outcomes [0 vs 1 (1.9%); p = 0.48], and self-report non-adherence [5 (8.9%) vs 1 (1.9%); p = 0.21].ConclusionsIn this randomized trial of patients with drug-sensitive pulmonary tuberculosis, medication adherence among participants assigned to MERM-observed self-administered therapy was non-inferior and superior by some measures when compared with the standard in-person DOT. Further research is needed to understand whether adherence in the intervention is primarily driven by allowing self-administered therapy which reduced challenges of repeated clinic visits or by the adherence support provided by the MERM system. To avoid contributing to patient barriers with DOT, tuberculosis medical programs should consider alternatives such as medication event monitors.Trial registrationClinicalTrials.gov, NCT04216420.

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

Little is known about whether digital adherence technologies are economical for patients with tuberculosis (TB) in resource-constrained settings. 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). 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. 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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT04216420.

Design, development, and testing of a voice-text mobile health application to support Tuberculosis medication adherence in Uganda.

BackgroundTuberculosis (TB) continues to persist with a high disease burden globally. Non-adherence to treatment remains a major problem to TB control. In Uganda, one in every four TB patients does not adhere to their TB medication. The purpose of this study was to design, develop and assess implementation of a voice-text-based mobile application to support TB patients’ adherence to medication.MethodsDesign science research methodology (DSRM) was utilized to develop a voice-text-based mobile health application. Agile software methodology was used to achieve steps of DSRM that are; design and development. Focus group discussions (FGDs) and Key informant interviews (KIIs) were conducted and data analysed using thematic content analysis.ResultsDuring problem identification, Stigma, transport costs, being asymptomatic, drug side effects, lack of family support were identified as challenges affecting adherence. Technologies identified and used for the development of the voice-text application included; extensible mark-up language (XML) File, Apache server, Ubuntu Server, Hypertext Pre-processor, and jQuery. In the pilot study, 27 voice messages were broadcasted, 85.2% were delivered, 103 text messages were sent and 92.2% were delivered to the intended recipients.ConclusionsVoice-text message mobile health application can be used to reach a wider patient population and it has the capability of addressing some of the challenges affecting TB medication adherence.

Quantifying the Magnitude and Composition of Out-of-Pocket Expenditure on Medicines in India2014 to 2017-18: A Repeated Cross-Sectional Analysis

Introduction: More than 60% of healthcare expenditure by households in India is paid as out-of-pocket expenditure and expenditure on medicines is the single largest component of these payments. Increasing longevity and rising incidence of chronic conditions is expected to further increase the utilization of medicines and aggravate the associated financial burden. Objectives: This paper quantifies the magnitude of out-of-pocket expenditure on medicines and changes there in, between 2014 and 2017-18. The paper looks at the expenditure across, states, types of providers and ailments. Method: Repeated cross-sectional analysis using two rounds of health surveys by National Sample Survey Organization has been used. Results: The mean out-of-pocket expenditure on medicines per episode fell from ₹ 4386 to ₹ 3857 for inpatient care and from ₹ 459 to ₹ 418, in constant prices, for outpatient care. Despite the decline in the magnitude of expenditure, its share in total out-of-pocket expenditure has remained high at 49%. The out-of-pocket expenditure on medicines for private provider was higher than that for public provider. Medication for cancer and tuberculosis have the highest expenditure and show an upward trend. A high percentage of people incur out-of-pocket expenditure on medicines for fever, respiratory and musculo-skeletal diseases. The percentage of people incurring expenditure on medication for cardio-vascular diseases and diabetes has increased. Conclusion: The mean out-of-pocket expenditure on medicines per episode has fallen, yet the expenditure remains high. People rely on utilization of medicines at private providers and pharmacies. Supply side and demand side policies needed to further reduce out-of-pocket expenditure on medicines.

Spatiotemporal Variation and Predictors of Unsuppressed Viral Load among HIV-Positive Men and Women in Rural and Peri-Urban KwaZulu-Natal, South Africa.

Unsuppressed HIV viral load is an important marker of sustained HIV transmission. We investigated the prevalence, predictors, and high-risk areas of unsuppressed HIV viral load among HIV-positive men and women. Unsuppressed HIV viral load was defined as viral load of ≥400 copies/mL. Data from the HIV Incidence District Surveillance System (HIPSS), a longitudinal study undertaken between June 2014 to June 2016 among men and women aged 15–49 years in rural and peri-urban KwaZulu-Natal, South Africa, were analysed. A Bayesian geoadditive regression model which includes a spatial effect for a small enumeration area was applied using an integrated nested Laplace approximation (INLA) function while accounting for unobserved factors, non-linear effects of selected continuous variables, and spatial autocorrelation. The prevalence of unsuppressed HIV viral load was 46.1% [95% CI: 44.3–47.8]. Predictors of unsuppressed HIV viral load were incomplete high school education, being away from home for more than a month, alcohol consumption, no prior knowledge of HIV status, not ever tested for HIV, not on antiretroviral therapy (ART), on tuberculosis (TB) medication, having two or more sexual partners in the last 12 months, and having a CD4 cell count of <350 cells/μL. A positive non-linear effect of age, household size, and the number of lifetime HIV tests was identified. The higher-risk pattern of unsuppressed HIV viral load occurred in the northwest and northeast of the study area. Identifying predictors of unsuppressed viral load in a localized geographic area and information from spatial risk maps are important for targeted prevention and treatment programs to reduce the transmission of HIV.