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Background: Effective strategies are needed to facilitate the prompt diagnosis and treatment of tuberculosis in countries with a high burden of the disease.Methods: We conducted a cluster-randomized trial in which Ugandan community health centers were assigned to a multicomponent diagnostic strategy (on-site molecular testing for tuberculosis, guided restructuring of clinic workflows, and monthly feedback of quality metrics) or routine care (on-site sputum-smear microscopy and referral-based molecular testing). The primary outcome was the number of adults treated for confirmed tuberculosis within 14 days after presenting to the health center for evaluation during the 16-month intervention period. Secondary outcomes included completion of tuberculosis testing, same-day diagnosis, and same-day treatment. Outcomes were also assessed on the basis of proportions.Results: A total of 20 health centers underwent randomization, with 10 assigned to each group. Of 10,644 eligible adults (median age, 40 years) whose data were evaluated, 60.1% were women and 43.8% had human immunodeficiency virus infection. The intervention strategy led to a greater number of patients being treated for confirmed tuberculosis within 14 days after presentation (342 patients across 10 intervention health centers vs. 220 across 10 control health centers; adjusted rate ratio, 1.56; 95% confidence interval [CI], 1.21 to 2.01). More patients at intervention centers than at control centers completed tuberculosis testing (adjusted rate ratio, 1.85; 95% CI, 1.21 to 2.82), received a same-day diagnosis (adjusted rate ratio, 1.89; 95% CI, 1.39 to 2.56), and received same-day treatment for confirmed tuberculosis (adjusted rate ratio, 2.38; 95% CI, 1.57 to 3.61). Among 706 patients with confirmed tuberculosis, a higher proportion in the intervention group than in the control group were treated on the same day (adjusted rate ratio, 2.29; 95% CI, 1.23 to 4.25) or within 14 days after presentation (adjusted rate ratio, 1.22; 95% CI, 1.06 to 1.40).Conclusions: A multicomponent diagnostic strategy that included on-site molecular testing plus implementation supports to address barriers to delivery of high-quality tuberculosis evaluation services led to greater numbers of patients being tested, receiving a diagnosis, and being treated for confirmed tuberculosis. (Funded by the National Heart, Lung, and Blood Institute; XPEL-TB ClinicalTrials.gov number, NCT03044158.). [ABSTRACT FROM AUTHOR]

Background: In Vietnam and other global settings, men who have sex with men (MSM) have become the population at greatest risk of HIV infection. Although HIV pre-exposure prophylaxis (PrEP) has been implemented as a prevention strategy, PrEP outcomes may be affected by low persistence and adherence among MSM with unhealthy alcohol use. MSM have a high prevalence of unhealthy alcohol use in Vietnam, which may affect PrEP outcomes., Methods: Design: We will conduct a two-arm hybrid type 1 effectiveness-implementation randomized controlled trial of a brief alcohol intervention (BAI) compared to the standard of care (SOC) at the Sexual Health Promotion (SHP) clinic Hanoi, Vietnam., Participants: Sexually active MSM (n=564) who are newly initiating PrEP or re-initiating PrEP and have unhealthy alcohol use will be recruited and randomized 1:1 to the SOC or BAI arm. A subgroup of participants (n=20) in each arm will be selected for longitudinal qualitative interviews; an additional subset (n=48) in the BAI arm will complete brief quantitative and qualitative interviews after completion of the BAI to assess the acceptability of the intervention. Additional implementation outcomes will be assessed through interviews with clinic staff and stakeholders (n=35)., Intervention: Study participants in both arms will receive standard care for PrEP clients. In the BAI arm, each participant will receive two face-to-face intervention sessions and two brief booster phone sessions, based on cognitive behavioral therapy and delivered in motivational interviewing informed style, to address their unhealthy alcohol use., Outcomes: Effectiveness (PrEP and alcohol use) and cost-effectiveness outcomes will be compared between the two arms. Intervention implementation outcomes (acceptability, feasibility, adoption) will be assessed among MSM participants, clinic staff, and stakeholders., Discussion: This proposed trial will assess an alcohol intervention for MSM with unhealthy alcohol use who initiate or re-initiate PrEP, while simultaneously preparing for subsequent implementation. The study will measure the effectiveness of the BAI for increasing PrEP persistence through reducing unhealthy alcohol use in a setting where excessive alcohol consumption is a normative behavior. If effective, implementation-focused results will inform future scale-up of the BAI in similar settings., Trial Registration: NCT06094634 on clinicaltrials.gov. Registered 16 October 2023., (© 2024. The Author(s).)

Background: Evidence-based interventions (EBIs) often address normative behaviors. If a behavior is also common among clinicians, they may be skeptical about the necessity or effectiveness of an EBI. Alternatively, clinicians' attitudes and behaviors may be misaligned, or they may lack the knowledge and self-efficacy to deliver the EBI. Several EBIs address unhealthy alcohol use, a common and often culturally acceptable behavior. But unhealthy alcohol use may be particularly harmful to people with HIV (PWH). Here, we present an implementation trial using an experiential implementation strategy to address clinicians' knowledge, attitudes, and behaviors. Clinicians receive the experiential intervention before they begin delivering an evidence-based brief alcohol intervention (BAI) to PWH with unhealthy alcohol use., Methods: Design: In this hybrid type 3 implementation-effectiveness cluster randomized controlled trial, ART clinics (n = 30) will be randomized 1:1 to facilitation, a flexible strategy to address implementation barriers, or facilitation plus the experiential brief alcohol intervention (EBAI). In the EBAI arm, clinicians, irrespective of their alcohol use, will be offered the BAI as experiential learning. EBAI will address clinicians' alcohol-related attitudes and behaviors and increase their knowledge and confidence to deliver the BAI., Participants: ART clinic staff will be enrolled and assessed at pre-BAI training, post-BAI training, 3, 12, and 24 months. All PWH at the ART clinics who screen positive for unhealthy alcohol use will be offered the BAI. A subset of PWH (n = 810) will be enrolled and assessed at baseline, 3, and 12 months., Outcomes: We will compare implementation outcomes (acceptability, fidelity, penetration, costs, and sustainability) and effectiveness outcomes (viral suppression and alcohol use) between the two arms. We will assess the impact of site-level characteristics on scaling-up the BAI. We will also evaluate how experiencing the BAI affected clinical staff's alcohol use and clinic-level alcohol expectations in the EBAI arm., Discussion: This trial contributes to implementation science by testing a novel strategy to implement a behavior change intervention in a setting in which clinicians themselves may engage in the behavior. Experiential learning may be useful to address normative and difficult to change lifestyle behaviors that contribute to chronic diseases., Trial Registration: NCT06358885 (04/10/2024), https://clinicaltrials.gov/study/NCT06358885 ., (© 2024. The Author(s).)

Purpose: Statins are commonly prescribed medications with recognised side effects including muscle weakness. Despite this, little is known about their effect on the physical activity and falls risk in the older population. This paper aims to explore the relationship between statin use and the physical activity and falls risk in adults aged 65 and older., Methods: MEDLINE, Embase, CINAHL and PsycINFO were searched on 21/11/2022 to obtain relevant articles. Data considered appropriate included that relating to muscle strength, grip strength, gait speed, balance and falls incidence. Reference and citation searches were performed to identify further relevant papers, and all eligible articles were subject to a Critical Appraisal Skills Programme (CASP) to assess potential bias. With the data being highly heterogeneous, no attempt to measure effect size was made and a narrative synthesis approach was used. The review proposal was registered with PROSPERO: CRD42022366159., Results: Twenty articles were included. Data were inconsistent throughout, with the overall trend suggesting no significant negative effects of statins on the parameters of physical activity, or on falls risk. This was especially true in matched and adjusted cohorts, where potential confounders had been accounted for., Conclusion: This review did not identify a relationship between statin use and physical activity and falls risk in people aged 65 years and older. Ultimately, the risks and benefits of every medication should be considered in the context of each individual., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Evidence should be the foundation for a well-designed family planning (FP) program, but existing evidence is rarely aligned with and/or synthesized to speak directly to FP programmatic needs. Based on our experience cocreating FP research and learning agendas (FP RLAs) in Côte d'Ivoire, Malawi, Mozambique, Nepal, Niger, and Uganda, we argue that FP RLAs can drive the production of coordinated research that aligns with national priorities.To cocreate FP RLAs, stakeholders across 6 countries conducted desk reviews of 349 documents and 106 key informant interviews, organized consultation meetings in each country to prioritize evidence gaps and generate research and learning questions, and, ultimately, formed 6 FP RLAs comprising 190 unique questions. We outline the process for consensus-driven development of FP RLAs and communicate the results of an analysis of the questions in each FP RLA across 4 technical areas: self-care, equity, high impact practices, and youth. Each question was categorized as a learning versus research question, the former indicating an opportunity to synthesize existing evidence and the latter to conduct new research to answer the question. Themes emerging from the data shed light on shared evidence gaps across the 6 countries. We argue that similarities and differences in the questions in each FP RLA reflect the unique implementation experience and context, as well as each country's placement on the FP S-curve. Early uses of the FP RLAs include informing the development of FP costed implementation plans and FP2030 commitments. FP RLAs have also been discussed in multiple thematic working groups. For FP stakeholders, these FP RLAs represent a consensus-based agenda that can guide the generation and synthesis of evidence to answer each country's most pressing questions, ultimately driving progress toward increasingly evidence-based programming and policy., (© Brittingham et al.)

Background: Decentralised molecular testing for tuberculosis could reduce missed diagnoses and losses to follow-up in high-burden settings. The aim of this study was to evaluate the cost and cost-effectiveness of the Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) study strategy, a multicomponent strategy including decentralised molecular testing for tuberculosis, in Uganda., Methods: We conducted a costing and cost-effectiveness analysis nested in a pragmatic cluster-randomised trial of onsite (decentralised) versus hub-and-spoke (centralised) testing for tuberculosis with Xpert MTB/RIF Ultra (Xpert) in 20 community health centres in Uganda. We collected empirical data on the cost of the XPEL-TB strategy (decentralised Xpert testing, workflow redesign, and performance feedback) and routine tuberculosis testing (onsite smear microscopy with specimen transport for centralised Xpert testing) from the health system perspective. Time-and-motion studies were performed to estimate activity-based service costs. Cost-effectiveness was assessed as the incremental cost (2019 US$) per tuberculosis diagnosis and per 14-day treatment initiation., Findings: The XPEL-TB study ran from Oct 22, 2018, to March 1, 2020. Effectiveness and cost-effectiveness outcomes were assessed from Dec 1, 2018, to Nov 30, 2019 and included 4867 women and 3139 men. On a per-test basis, the cost of decentralised ($20·46, range $17·85-25·72) and centralised ($18·20, range $16·58-24·25) Xpert testing was similar. However, decentralised testing resulted in more patients receiving appropriate Xpert testing, so the per-patient cost of decentralised testing was higher: $20·28 (range $17·68-25·48) versus $9·59 (range $7·62-14·34). The XPEL-TB strategy was estimated to cost $1332 (95% uncertainty range $763-5558) per incremental tuberculosis diagnosis and $687 ($501-1207) per incremental patient initiating tuberculosis treatment within 14 days. Cost-effectiveness was reduced in sites performing fewer than 150-250 tests annually., Interpretation: The XPEL-TB strategy facilitated higher rates of Xpert testing for tuberculosis at a similar per-test cost and modest incremental cost per tuberculosis diagnosis and treatment initiation. Decentralised Xpert testing, with appropriate implementation supports, should be scaled up to clinics with sufficient testing volume to support a single-module device., Funding: The National Heart, Lung, and Blood Institute., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Funding for paediatric bilateral cochlear implantation became available in Ireland in 2014. Prior to this, children eligible for cochlear implantation received a unilateral implant., Objective: To examine the cohort of children who received a unilateral cochlear implant in the 4 year period following bilateral cochlear implantation funding becoming available., Methods: A clinical audit of all children implanted for the first time between July 2014 and July 2018. The unilaterally implanted children (n = 105) were divided into 3 groups according to whether they met the audiometric thresholds for implantation in neither ear (Group 1), one ear (Group 2) or both ears (Group 3). One year post operative functional outcomes were examined for all 3 groups., Results: All 3 groups showed significant improvements in functional outcomes at 1 year post op. To date, 20% of the unilaterally implanted children have proceeded to get a sequential CI, often where there was no change in audiological status., Conclusions: The number of children in Groups 1 and 2 highlighted how our decision making around cochlear implantation has changed in recent years. Unilateral cochlear implantation in certain circumstances is good practice, independent of the audiological profile when an experienced multi-disciplinary team (MDT) is involved in the decision making process. Decision making using a holistic model approach is key, including involving the parent/carer and, where appropriate, the child/teenager themselves. A staged bilateral cochlear implant is also a good option, where careful monitoring and support for the first implant has resulted in positive outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Digital adherence technologies like 99DOTS are increasingly considered as an alternative to directly observed therapy for tuberculosis (TB) treatment supervision. We evaluated the cost and cost-effectiveness of 99DOTS in a high-TB-burden setting., Methods: We assessed the costs of implementing 99DOTS in Uganda through a pragmatic, stepped-wedge randomized trial. We measured costs from the health system perspective at 5 of 18 study facilities. Self-reported service activity time data were used to assess activity-based service costs; other costs were captured from budgets and key informant discussions using standardized forms. We estimated costs and effectiveness considering the 8-month study period ("trial specific") and using a 5-year time horizon ("extended activities"), the latter including a "marginal clinic" expansion scenario that ignored above-site implementation costs. Cost-effectiveness was assessed as cost per patient successfully completing treatment, using Monte Carlo simulation, cost-effectiveness acceptability curves, and sensitivity analyses to evaluate uncertainty and robustness of results., Results: The total cost of implementing 99DOTS in the "trial-specific" scenario was $99 554 across 18 clinics (range $3771-$6238 per clinic). The cost per treatment success in the "trial-specific" scenario was $355 (range $229-$394), falling to $59 (range $50-$70) assuming "extended activities," and $49 (range $42-$57) in the "marginal clinic" scenario. The incremental cost-effectiveness of 99DOTS in the "extended-activity" scenario was $355 per incremental treatment success., Conclusions: Costs and cost-effectiveness of 99DOTS were influenced by the degree to which infrastructure is scaled over time. If sustained and scaled up, 99DOTS can be a cost-effective option for TB treatment adherence support in high-TB-burden settings like Uganda., (Copyright © 2021 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: To compare listening and spoken language outcomes after cochlear implantation for children born preterm and at term, and to examine patterns associated with additional disabilities or gestational age., Method: Children were included if they underwent cochlear implantation in 2013 or 2014 and had complete 5-year follow-up data available. An analysis of assessment data recorded annually was conducted, including outcomes as measured by the Category of Auditory Performance (CAP), the Speech Intelligibility Rating, Second Edition (SIR 2) scale, and the British Picture Vocabulary Scales, Third Edition (BPVS-3). Analyses were conducted to measure the impact of preterm birth and of additional causes of disability on these outcomes., Results: Eighty-two children (39 males, 43 females; median corrected age at first cochlear implantation 28.5mo [interquartile range 16.3-48.5]) were included in the study. Children who underwent cochlear implantation experienced significant improvements as measured by the CAP, SIR 2, and BPVS-3. Comparable improvements were seen in the groups born at term and preterm. Children with additional disabilities experienced significant improvement in all measures but performed less well than children without additional disabilities., Interpretation: Infants born preterm benefit from cochlear implantation to a degree comparable to their peers born at term. Additional disabilities may limit improvements in speech intelligibility, listening performance, and receptive vocabulary. Children with additional disabilities, nonetheless, derived significant benefit from cochlear implantation; additional benefits of cochlear implantation for this subgroup may go unmeasured by the outcome tools used in this study., (© 2021 Mac Keith Press.)

Introduction: Preventive therapy is essential for reducing tuberculosis (TB) burden among people living with HIV (PLWH) in high-burden settings. Short-course preventive therapy regimens, such as three-month weekly rifapentine and isoniazid (3HP) and one-month daily rifapentine and isoniazid (1HP), may help facilitate uptake of preventive therapy for latently infected patients, but the comparative cost-effectiveness of these regimens under different conditions is uncertain., Methods: We used a Markov state-transition model to estimate the incremental costs and effectiveness of 1HP versus 3HP in a simulated cohort of patients attending an HIV clinic in Uganda, as an example of a low-income, high-burden setting in which TB preventive therapy might be prescribed to PLWH. Our primary outcome was the incremental cost-effectiveness ratio, expressed as 2019 US dollars per disability-adjusted life year (DALY) averted. We estimated cost-effectiveness under different conditions of treatment completion and efficacy of 1HP versus 3HP, latent TB prevalence and rifapentine price., Results: Assuming equivalent clinical outcomes using 1HP and 3HP and a rifapentine price of $0.21 per 150 mg, 1HP would cost an additional $4.66 per patient treated. Assuming equivalent efficacy but 20% higher completion with 1HP versus 3HP, 1HP would cost $1,221 per DALY averted relative to 3HP. This could be reduced to $18 per DALY averted if 1HP had 5% greater efficacy than 3HP and the price of rifapentine were 50% lower. At a rifapentine price of $0.06 per 150 mg, 1HP would become cost-neutral relative to 3HP., Conclusions: 1HP has the potential to be cost-effective under many realistic circumstances. Cost-effectiveness depends on rifapentine price, relative completion and efficacy, prevalence of latent TB and local willingness-to-pay., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Delays in diagnosis and treatment of tuberculosis (TB) remain common in high-burden countries. To improve case detection, substantial investments have been made to scale-up Xpert MTB/RIF (Xpert), a cartridge-based nucleic acid amplification test that can detect TB within 2 hours, as a replacement for sputum smear microscopy. However, the optimal strategy for implementation of Xpert testing remains unclear., Methods: The Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial uses an ultra-pragmatic, hybrid type II effectiveness-implementation design to assess the effectiveness and implementation of a streamlined strategy for delivery of Xpert testing in real-world settings. Twenty health centers with TB microscopy units were selected to participate in the trial, with ten health centers randomized to the intervention strategy (onsite molecular testing using GeneXpert Edge, process redesign to facilitate same-day TB diagnosis and treatment, and performance feedback) or routine care (onsite sputum smear microscopy plus referral of sputum samples to Xpert testing sites). The primary outcome is the number of patients with microbiologically confirmed TB who were initiated on treatment within 14 days of presentation to the health center, which reflects successful completion of the TB diagnostic evaluation process. Secondary outcomes include health outcomes (6-month vital status), as well as measures of the reach, adoption, and implementation of the intervention strategy., Discussion: The design elements and implementation approach for the XPEL-TB trial were intentionally selected to minimize disruptions to routine care procedures, with the goal of limiting their influence on key primary and secondary outcomes. Trial findings may result in increased support and funding for rapid, onsite molecular testing as the standard-of-care for all patients being evaluated for TB., Trial Registration: US National Institutes of Health's ClinicalTrials.gov, NCT03044158. Registered 06 February 2017. Pan African Clinical Trials Registry, PACTR201610001763265. Registered 03 September 2016.