Gaps in TB preventive therapy for persons initiating antiretroviral therapy in Uganda: an explanatory sequential cascade analysis.

BACKGROUND: The WHO recommends TB symptom screening and TB preventive therapy (TPT) for latent TB infection (LTBI) in persons living with HIV (PLWH). However, TPT uptake remains limited. We aimed to characterize and contextualize gaps in the TPT care cascade among persons enrolling for antiretroviral therapy (ART).SETTING: Four PEPFAR-supported facilities in Uganda.METHODS: We studied a proportionate stratified random sample of persons registering for ART when TPT was available. Patient-level data on eligibility, initiation, and completion were obtained from registers to determine proportion of eligible patients completing each cascade step. We interviewed providers and administrators and used content analysis to identify barriers to guideline-concordant TPT practices.RESULTS: Of 399 study persons, 309 (77%) were women. Median age was 29 (IQR 25-34), CD4 count 405 cells/µL (IQR 222-573), and body mass 23 kg/m² (IQR 21-25). Of 390 (98%) screened, 372 (93%) were TPT-eligible. Only 62 (17%) eligible PLWH initiated and 36 (58%) of 62 completed TPT. Providers reported hesitating to prescribe TPT because they lacked confidence excluding TB by symptom screening alone and feared promoting drug resistance. Although isoniazid was available, past experience of irregular supply discouraged TPT initiation. Providers pointed to insufficient TB-dedicated staff, speculated that patients discounted TB risk, and worried TPT pill burden and side effects depressed ART adherence.CONCLUSIONS: While screening was nearly universal, most eligible PLWH did not initiate TPT. Only about half of those who initiated completed treatment. Providers feared promoting drug resistance, harbored uncertainty about continued availability, and worried TPT could antagonize ART adherence. Our findings suggest urgent need for stakeholder engagement in TPT provision.

Clinical and cost-effectiveness of bracing in symptomatic knee osteoarthritis management: protocol for a multicentre, primary care, randomised, parallel-group, superiority trial.

BACKGROUND: Brace effectiveness for knee osteoarthritis (OA) remains unclear and international guidelines offer conflicting recommendations. Our trial will determine the clinical and cost-effectiveness of adding knee bracing (matched to patients' clinical and radiographic presentation and with adherence support) to a package of advice, written information and exercise instruction delivered by physiotherapists. METHODS AND ANALYSIS: A multicentre, pragmatic, two-parallel group, single-blind, superiority, randomised controlled trial with internal pilot and nested qualitative study. 434 eligible participants with symptomatic knee OA identified from general practice, physiotherapy referrals and self-referral will be randomised 1:1 to advice, written information and exercise instruction and knee brace versus advice, written information and exercise instruction alone. The primary analysis will be intention-to-treat comparing treatment arms on the primary outcome (Knee Osteoarthritis Outcomes Score (KOOS)-5) (composite knee score) at the primary endpoint (6 months) adjusted for prespecified covariates. Secondary analysis of KOOS subscales (pain, other symptoms, activities of daily living, function in sport and recreation, knee-related quality of life), self-reported pain, instability (buckling), treatment response, physical activity, social participation, self-efficacy and treatment acceptability will occur at 3, 6, and 12 months postrandomisation. Analysis of covariance and logistic regression will model continuous and dichotomous outcomes, respectively. Treatment effect estimates will be presented as mean differences or ORs with 95% CIs. Economic evaluation will estimate cost-effectiveness. Semistructured interviews to explore acceptability and experiences of trial interventions will be conducted with participants and physiotherapists delivering interventions. ETHICS AND DISSEMINATION: North West Preston Research Ethics Committee, the Health Research Authority and Health and Care Research in Wales approved the study (REC Reference: 19/NW/0183; IRAS Reference: 247370). This protocol has been coproduced with stakeholders including patients and public. Findings will be disseminated to patients and a range of stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN28555470.