Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study.

Variable pharmacokinetics of rifampin in tuberculosis (TB) treatment can lead to poor outcomes. Urine spectrophotometry is simpler and more accessible than recommended serum-based drug monitoring, but its optimal efficacy in predicting serum rifampin underexposure in adults with TB remains uncertain. Adult TB patients in New Jersey and Virginia receiving rifampin-containing regimens were enrolled. Serum and urine samples were collected over 24 h. Rifampin serum concentrations were measured using validated liquid chromatography-tandem mass spectrometry, and total exposure (area under the concentration-time curve) over 24 h (AUC0-24) was determined through noncompartmental analysis. The Sunahara method was used to extract total rifamycins, and rifampin urine excretion was measured by spectrophotometry. An analysis of 58 eligible participants, including 15 (26%) with type 2 diabetes mellitus, demonstrated that urine spectrophotometry accurately identified subtarget rifampin AUC0-24 at 0-4, 0-8, and 0-24 h. The area under the receiver operator characteristic curve (AUC ROC) values were 0.80 (95% CI 0.67-0.90), 0.84 (95% CI 0.72-0.94), and 0.83 (95% CI 0.72-0.93), respectively. These values were comparable to the AUC ROC of 2 h serum concentrations commonly used for therapeutic monitoring (0.82 [95% CI 0.71-0.92], P = 0.6). Diabetes status did not significantly affect the AUC ROCs for urine in predicting subtarget rifampin serum exposure (P = 0.67-0.92). Spectrophotometric measurement of urine rifampin excretion within the first 4 or 8 h after dosing is a simple and cost-effective test that accurately predicts rifampin underexposure. This test provides critical information for optimizing tuberculosis treatment outcomes by facilitating appropriate dose adjustments.

Optimizing usability of a mobile health intervention for Spanish-speaking Latinx people with HIV through user-centered design: a post-implementation study.

Objective: Latinx people comprise 30% of all new human immunodeficiency virus (HIV) infections in the United States and face many challenges to accessing and engaging with HIV care. To bridge these gaps in care, a Spanish-language mobile health (mHealth) intervention known as ConexionesPositivas (CP) was adapted from an established English-language platform called PositiveLinks (PL) to help improve engagement in care and reduce viral nonsuppression among its users. We aimed to determine how CP can address the challenges that Latinx people with HIV (PWH) in the United States face. Materials and methods: We conducted a post-implementation study of the CP mHealth platform, guided by principles of user-centered design. We enrolled 20 Spanish-speaking CP users in the study, who completed the previously validated System Usability Scale (SUS) and semistructured interviews. Interviews were transcribed and translated for analysis. We performed thematic coding of interview transcripts in Dedoose. Results: The SUS composite score was 75, which is within the range of good usability. Four categories of themes were identified in the interviews: client context, strengths of CP, barriers to use and dislikes, and suggestions to improve CP. Positive impacts included encouraging self-monitoring of medication adherence, mood and stress, connection to professional care, and development of a support system for PWH. Discussion: While CP is an effective and easy-to-use application, participants expressed a desire for improved personalization and interactivity, which will guide further iteration. Conclusion: This study highlights the importance of tailoring mHealth interventions to improve equity of access, especially for populations with limited English proficiency.

Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study.

OBJECTIVE: Pharmacokinetic variability drives tuberculosis (TB) treatment outcomes but measurement of serum drug concentrations for personalised dosing is inaccessible for children in TB-endemic settings. We compared rifampin urine excretion for prediction of a serum target associated with treatment outcome. DESIGN: Prospective diagnostic accuracy study. SETTING: Inpatient wards and outpatient clinics, northern Tanzania. PATIENTS: Children aged 4-17 years were consecutively recruited on initiation of WHO-approved treatment regimens. INTERVENTIONS: Samples were collected after directly observed therapy at least 2 weeks after initiation in the intensive phase: serum at pre-dose and 1, 2 and 6 hours post-dose, later analysed by liquid chromatography-tandem mass spectrometry for calculation of rifampin total exposure or area under the concentration time curve (AUC0-24); urine at post-dose intervals of 0-4, 4-8 and 8-24 hours, with rifampin excretion amount measured onsite by spectrophotometry. MAIN OUTCOME MEASURES: Receiver operating characteristic (ROC) curve for percentage of rifampin dose excreted in urine measured by spectrophotometry to predict serum rifampin AUC0-24 target of 31.7 mg*hour/L. RESULTS: 89 children, 52 (58%) female, with median age of 9.1 years, had both serum and urine collection. Only 59 (66%) reached the serum AUC0-24 target, reflected by a range of urine excretion patterns. Area under the ROC curve for percentage of rifampin dose excreted in urine over 24 hours predicting serum AUC0-24 target was 69.3% (95% CI 56.7% to 81.8%), p=0.007. CONCLUSIONS: Urine spectrophotometry correlated with a clinically relevant serum target for rifampin, representing a step toward personalised dosing for children in TB-endemic settings.

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

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.

Duration of Symptoms Prior to Pediatric and Adolescent Tuberculosis Diagnosis and Its Impact on Schooling in Tanzania: A Mixed Methods Study.

At least a third of tuberculosis (TB) cases remain undiagnosed, disproportionately so in children and adolescents, which is hampering global elimination goals. Prolonged symptom duration presents a high-risk scenario for childhood TB in endemic areas, but the prolonged period of symptoms and its impact on educational attainment are rarely documented. Using a mixed method approach, we aimed to quantify the duration of respiratory symptoms and describe their impact on education among children from a rural area of Tanzania. We used data from a prospectively enrolled cohort of children and adolescents aged 4-17 years in rural Tanzania at the start of active TB treatment. We report on the cohort's baseline characteristics and explore the correlation between duration of symptoms and other variables. In-depth qualitative interviews were designed on the basis of a grounded theory approach to explore the impact of TB on educational attainment among school-aged children. In this cohort, children and adolescents diagnosed with TB experienced symptoms for a median of 85 days (interquartile range: 30, 231 days) prior to treatment initiation. In addition, 56 participants (65%) had a TB exposure in the household. Of the 16 families with school-aged children who were interviewed, 15 (94%) reported a significant negative impact of TB on the schooling of their children. Children in this cohort experienced a long duration of TB symptoms; the extent of illness impacted absenteeism at school. Screening initiatives for households affected by TB may lead to a shortened duration of symptoms and may minimize the impact on school attendance.

Convalescent Plasma for Preventing Critical Illness in COVID-19: a Phase 2 Trial and Immune Profile.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion. In a single-arm phase II study, patients >18 years-old with respiratory symptoms with confirmed COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 h of admission. Levels of SARS-CoV-2 detected by PCR in the respiratory tract and circulating anti-SARS-CoV-2 antibody titers were sequentially measured before and after CIP transfusion. Twenty-nine patients were transfused high titer CIP and 48 contemporaneous comparable controls were identified. All classes of antibodies to the three SARS-CoV-2 target proteins were significantly increased at days 7 and 14 post-transfusion compared with baseline (P < 0.01). Anti-nucleocapsid IgA levels were reduced at day 28, suggesting that the initial rise may have been due to the contribution of CIP. The groups were well-balanced, without statistically significant differences in demographics or co-morbidities or use of remdesivir or dexamethasone. In participants transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). IMPORTANCE Transfusion of high-titer CIP to non-critically ill patients early after admission with COVID-19 respiratory disease was associated with significantly increased anti-SARS-CoV-2 specific antibodies (compared to baseline) and a non-significant reduction in ICU transfer and death (compared to controls). This prospective phase II trial provides a suggestion that the antiviral effects of CIP from early in the COVID-19 pandemic may delay progression to critical illness and death in specific patient populations. This study informs the optimal timing and potential population of use for CIP in COVID-19, particularly in settings without access to other interventions, or in planning for future coronavirus pandemics.

Adapting an m-Health Intervention for Spanish-Speaking Latinx People Living with HIV in the Nonurban Southern United States.

Background: Latinx people in the United States are disproportionately diagnosed with HIV and are more likely to experience worse HIV-related health outcomes. Although m-health has demonstrated success in improving HIV care, a gap remains in the development of m-health platforms tailored to Latinx populations. Methods: We conducted formative study to guide the adaptation of an evidence-based m-health intervention, PositiveLinks (PL), for Spanish-speaking Latinx people living with HIV (PLWH). Spanish-speaking Latinx PLWH in the nonurban Southern United States completed semistructured interviews and viewed a demo version of the m-health intervention. Qualitative analysis was performed using a grounded theory approach. Emerging themes were identified in four topic areas: (1) prior experiences with technology, (2) desired m-health features, (3) experiences with prototype app, and (4) iteration of prototype. Results: All PLWH who participated (n = 22) were born outside the continental United States. Participants included 10 men, 10 women, and 2 transgender participants. Mean age was 41.1 years (standard deviation 11.6 years). Participants expressed concerns about privacy, a need for reliable information, and interest in practical m-health features such as appointment and medication reminders. After trialing the Spanish-language PL prototype, participants reported that peer support and positive reinforcement were strong motivators to use the app. The ability to individualize the app to meet one's own needs was also considered important. Conclusion: This formative study provides baseline attitudes about m-health among Latinx PLWH as well as desired m-health features. m-Health interventions are acceptable to Spanish-speaking PLWH and involving the target population in a user-centered formative process led to improvements in app accessibility and usability.

Beyond Interpretation: The Unmet Need for Linguistically and Culturally Competent Care for Latinx People Living with HIV in a Southern Region with a Low Density of Spanish Speakers.

Latinx people living with HIV (PLWH) experience disparities in health outcomes and face unique barriers to care related to language, intersectional stigma, and immigration status. We aimed to explore the lived experience of Spanish-speaking Latinx PLWH in the nonurban South to better understand how to improve care for this minority language population. We conducted semistructured interviews with 22 participants (10 men, 10 women, 2 transgender women) who were recruited from a Ryan White HIV/AIDS program (RWHAP) and a community-based organization. Almost all participants were foreign born. Emerging themes included language barriers, cultural differences, inadequate interpreter services, HIV-related and intersectional stigma, isolation, and relationships as a source of support. These barriers may contribute to disparities in outcomes for Latinx PLWH. New interventions are needed to overcome barriers, foster community, and ensure culturally tailored models of care. Potential clinic-level interventions include the development of specialized training for RWHAP interpreters and inclusion of interpreters in care teams.