Respiratory symptoms and lung function in patients treated for pulmonary tuberculosis in Malawi: a prospective cohort study

RationalePulmonary tuberculosis (PTB) can cause post-TB lung disease (PTLD) associated with respiratory symptoms, spirometric and radiological abnormalities. Understanding of the predictors and natural history of PTLD is limited.ObjectivesTo describe the symptoms and lung function of Malawian adults up to 3 years following PTB-treatment completion, and to determine the evolution of PTLD over this period.MethodsAdults successfully completing PTB treatment in Blantyre, Malawi were followed up for 3 years and assessed using questionnaires, post-bronchodilator spirometry, 6 min walk tests, chest X-ray and high-resolution CT. Predictors of lung function at 3 years were identified by mixed effects regression modelling.Measurement and main resultsWe recruited 405 participants of whom 301 completed 3 years follow-up (mean (SD) age 35 years (10.2); 66.6% males; 60.4% HIV-positive). At 3 years, 59/301 (19.6%) reported respiratory symptoms and 76/272 (27.9%) had abnormal spirometry. The proportions with low FVC fell from 57/285 (20.0%) at TB treatment completion to 33/272 (12.1%), while obstruction increased from and 41/285 (14.4%) to 43/272 (15.8%) at 3 years. Absolute FEV1 and FVC increased by mean 0.03 L and 0.1 L over this period, but FEV1 decline of more than 0.1 L was seen in 73/246 (29.7%). Higher spirometry values at 3 years were associated with higher body mass index and HIV coinfection at TB-treatment completion.ConclusionSpirometric measures improved over the 3 years following treatment, mostly in the first year. However, a third of PTB survivors experienced ongoing respiratory symptoms and abnormal spirometry (with accelerated FEV1 decline). Effective interventions are needed to improve the care of this group of patients.

Completion of isoniazid–rifapentine (3HP) for tuberculosis prevention among people living with HIV: Interim analysis of a hybrid type 3 effectiveness–implementation randomized trial

Background Scaling up shorter regimens for tuberculosis (TB) prevention such as once weekly isoniazid–rifapentine (3HP) taken for 3 months is a key priority for achieving targets set forth in the World Health Organization’s (WHO) END TB Strategy. However, there are few data on 3HP patient acceptance and completion in the context of routine HIV care in sub-Saharan Africa. Methods and findings The 3HP Options Trial is a pragmatic, parallel type 3 effectiveness–implementation randomized trial comparing 3 optimized strategies for delivering 3HP—facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between DOT and SAT using a shared decision-making aid—to people receiving care at a large urban HIV clinic in Kampala, Uganda. Participants and healthcare providers were not blinded to arm assignment due to the nature of the 3HP delivery strategies. We conducted an interim analysis of participants who were enrolled and exited the 3HP treatment period between July 13, 2020 and April 30, 2021. The primary outcome, which was aggregated across trial arms for this interim analysis, was the proportion who accepted and completed 3HP (≥11 of 12 doses within 16 weeks of randomization). We used Bayesian inference analysis to estimate the posterior probability that this proportion would exceed 80% under at least 1 of the 3HP delivery strategies, a coprimary hypothesis of the trial. Through April 2021, 684 participants have been enrolled, and 479 (70%) have exited the treatment period. Of these 479 participants, 309 (65%) were women, mean age was 41.9 years (standard deviation (SD): 9.2), and mean time on antiretroviral therapy (ART) was 7.8 years (SD: 4.3). In total, 445 of them (92.9%, 95% confidence interval (CI): [90.2 to 94.9]) accepted and completed 3HP treatment. There were no differences in treatment acceptance and completion by sex, age, or time on ART. Treatment was discontinued due to a documented adverse event (AE) in 8 (1.7%) patients. The probability that treatment acceptance and completion exceeds 80% under at least 1 of the three 3HP delivery strategies was greater than 99%. The main limitations are that the trial was conducted at a single site, and the interim analysis focused on aggregate outcome data to maintain blinding of investigators to arm-specific outcomes. Conclusions The 3HP was widely accepted by people living with HIV (PLHIV) in Uganda, and very high levels of treatment completion were achieved in a programmatic setting. These findings show that 3HP can enable effective scale-up of tuberculosis preventive therapy (TPT) in high-burden countries, particularly when delivery strategies are tailored to target known barriers to treatment completion. Trial registration ClinicalTrials.gov NCT03934931.

Expanding the Reach of an Evidence-Based, System-Level, Racial Equity Intervention: Translating ACCURE to the Maternal Healthcare and Education Systems

The abundance of literature documenting the impact of racism on health disparities requires additional theoretical, statistical, and conceptual contributions to illustrate how anti-racist interventions can be an important strategy to reduce racial inequities and improve population health. Accountability for Cancer Care through Undoing Racism and Equity (ACCURE) was an NIH-funded intervention that utilized an antiracism lens and community-based participatory research (CBPR) approaches to address Black-White disparities in cancer treatment completion. ACCURE emphasized change at the institutional level of healthcare systems through two primary principles of antiracism organizing: transparency and accountability. ACCURE was successful in eliminating the treatment completion disparity and improved completion rates for breast and lung cancer for all participants in the study. The structural nature of the ACCURE intervention creates an opportunity for applications in other health outcomes, as well as within educational institutions that represent social determinants of health. We are focusing on the maternal healthcare and K-12 education systems in particular because of the dire racial inequities faced by pregnant people and school-aged children. In this article, we hypothesize cross-systems translation of a system-level intervention exploring how key characteristics of ACCURE can be implemented in different institutions. Using core elements of ACCURE (i.e., community partners, milestone tracker, navigator, champion, and racial equity training), we present a framework that extends ACCURE's approach to the maternal healthcare and K-12 school systems. This framework provides practical, evidence-based antiracism strategies that can be applied and evaluated in other systems to address widespread structural inequities.

Differentiating transient from persistent diabetic range hyperglycemia in a cohort of people completing tuberculosis treatment in Dhaka, Bangladesh

Background In recent non-pandemic periods, tuberculosis (TB) has been the leading killer worldwide from a single infectious disease. Patients with DM are three times more likely to develop active TB and poor treatment outcomes. Single glycemic measurements at TB diagnosis may inaccurately diagnose or mischaracterize DM severity. Data are limited regarding glycemic dynamics from TB diagnosis through treatment. Methods Prospective study of glycemia dynamics in response to TB treatment measured glycosylated haemoglobin (HbA1c) in patients presenting to TB screening centres in Bangladesh to determine the prevalence and risk factors of hyperglycemia before and at TB treatment completion. Results 429 adults with active TB disease were enrolled and divided into groups based on history of DM and initial HbA1c range: normoglycemia, prediabetes, and DM. DM was diagnosed in 37%. At treatment completion,14(6%) patients from the normoglycemia and prediabetes groups had HbA1c>6.5%, thus increasing the prevalence of DM to 39%. The number needed to screen to diagnose one new case of DM at TB diagnosis was 5.7 and 16 at treatment completion in the groups without DM. Weight gain>5% at treatment completion significantly increased the risk of hyperglycemia in the groups without DM at TB diagnosis (95% CI 1.23–26.04, p<0.05). Conclusion HbA1c testing prior to and at TB treatment completion found a high prevalence of prediabetes and DM, including a proportion found at treatment completion and commonly in people with a higher percentage of weight gain. Further longitudinal research is needed to understand the effects of TB disease and treatment on insulin resistance and DM complications.

Outcome of drug resistant tuberculosis in Indian children

We aimed to determine the outcome of bacteriologically confirmed drug-resistant (DR) tuberculosis (TB) in 174 children. We found that DR-TB infected children have nonetheless a high treatment completion rate with a low incidence of fatality and treatment failure. Reversible adverse drug reactions are common during therapy.

Utility Estimation of Rituximab Versus Bendamustine-Rituximab Induction in Indolent Non-Hodgkin Lymphomas Using Patient-Reported Quality of Life Survey Data

Background Rituximab induction (RI) and bendamustine-rituximab (BR) induction are both options for the frontline management of indolent non-Hodgkin lymphomas (NHLs). Although BR induces longer progression-free survival than RI, BR confers more toxicity and a longer duration of initial induction than RI. The effects of RI versus BR on health-related quality of life (HRQoL) after induction treatment, and the implications on patient utility and quality-adjusted life-years (QALYs), have not been previously studied. We conducted a cost-utility analysis of RI versus BR utilizing patient-reported HRQoL survey data. Methods Patient-reported utility data were collected from the Hoogland Lymphoma Biobank, which enrolls patients with lymphoma at the University of Chicago and prospectively administers serial patient-level HRQoL surveys utilizing the Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Lymphoma (FACT-LYM) instruments. Patients with indolent NHLs (follicular lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma) who were treated with frontline RI (4 doses of weekly rituximab) or BR (6 months of monthly BR) and who had completed HRQoL surveys at both of the following timepoints were included: within 6 months of treatment completion (timepoint 1) and 6-12 months after treatment completion (timepoint 2). Individual FACT-G scores were converted into EQ-5D utility index scores using a United States-based validated mapping algorithm (Teckle et al., Health Qual Life Outcomes, 2013). Cost-utility analysis was performed by trial-based methodology in which patient-level QALYs are estimated using area-under-the-curve (AUC) between timepoints 1 and 2. Incremental cost utility ratio (ICUR) was calculated utilizing cost and life years gained inputs of RI and BR from previous cost-effectiveness literature. All HRQoL scores for RI versus BR at both timepoints were compared with unpaired two-tailed t-tests. Results There were 19 patients treated with RI and 13 patients treated with BR (Table 1). At timepoint 1, the BR cohort had significantly worse physical and emotional wellbeing on the FACT-G compared to the RI cohort, with emotional wellbeing significantly worse in the BR cohort at timepoint 2 (Table 2). EQ-5D utility index was stable at both timepoints for the RI cohort, and was initially lower in the BR cohort at timepoint 1 compared to RI but improved by timepoint 2 (Table 2). During the initial 12-month observation period after treatment completion, quality of life was higher for RI compared to BR (+0.02); however, when accounting for life years gained, the BR cohort had more QALYs (+1.53) (Table 3). Compared with RI, BR had an ICUR of $37,442. Conclusions Although HRQoL was inferior in the BR cohort in the first year after treatment completion, particularly in the emotional wellbeing domain on FACT-G, BR induction conferred higher QALYs owing to more life years gained as compared to RI induction. Given a cost-effectiveness threshold of $100,000 in the United States (Vanness et al., Ann Intern Med, 2021), BR induction is likely to be cost effective when considering patient-reported HRQoL over the first year after treatment completion. The present analysis is limited by the small number of patients from which utility values at each timepoint were derived; however, calculation of QALYs using a database of prospectively-collected HRQoL data is feasible. Further incorporation of patient-reported outcomes into cost-utility analysis is warranted, particularly with larger datasets. Figure 1 Figure 1. Disclosures Smith: Alexion, AstraZeneca Rare Disease: Other: Study investigator; Celgene, Genetech, AbbVie: Consultancy.