Search

Introduction The large reservoir of tuberculosis (TB) infections is one of the main reasons for the persistent incidence of TB. Accurate diagnostic tests are crucial to correctly identify and treat people with TB infection, which is vital to eliminate TB globally. The rdESAT-6 and rCFP-10 (Cy-Tb) injection (‘Cy-Tb’), a TB-specific antigen skin test and STANDARD F TB-Feron FIA (‘Standard F TB’) measuring interferon-gamma by fluorescence immunoassay assay are two novel tools for the diagnosis of TB infection which offer advantages compared with current tests in low-resource settings and reduced costs to both health systems and TB-affected people. The proposed study aims to evaluate the diagnostic accuracy of these two new tests for TB infection diagnosis.Methods and analysis This cross-sectional study aims to assess the diagnostic accuracy for TB infection of the Cy-Tb skin test and Standard F TB assay (investigational tests) compared with the QuantiFERON-TB Gold Plus (QFT-Plus) assay as the immunological reference standard. Three different cohorts of study participants will be recruited at the Vietnam National Lung Hospital: adults with bacteriologically confirmed pulmonary TB (n=100), household contacts of people with TB (n=200) and people without TB infection (n=50). All consenting participants will undergo simultaneous testing with Cy-Tb, Standard F TB and QFT-Plus. The primary endpoint is the diagnostic accuracy of the Cy-Tb skin test and Standard F TB assay, expressed as sensitivity and specificity against the reference standard.Ethics and dissemination Ethical approval was granted by the Vietnam National Lung Hospital Institutional Review Board (65/23/CN-HDDD-BVPTU) and the Swedish Ethical Review Authority (Dnr 2023-04271-01). Study results will be disseminated to the scientific community and policymakers through scientific publications.Trial registration number NCT06221735.

Introduction The health and economic burden of tuberculosis (TB) in urban Viet Nam is high. Social protection and support interventions can improve treatment outcomes and reduce costs. However, evidence regarding optimal strategies in this context is lacking. This study aimed to increase understanding of what people with TB and healthcare providers (HCPs) perceive as important to improve TB treatment outcomes and reduce costs.Methods We conducted qualitative focus group discussions (seven groups, n=30) and key informant interviews (n=4) with people with drug-susceptible and multidrug-resistant TB and HCPs in Ha Noi and Ho Chi Minh City. Topic guides covered perspectives on and prioritisation of different forms of social protection and support. Data were analysed using reflexive thematic analysis and interpreted using a Framework for Transformative Social Protection.Results We identified three themes and seven subthemes. The first theme, ‘Existing financial safety nets are essential, but could go further to support people affected by TB’, highlights that support to meet the medical costs of TB treatment and flexible cash transfers are a priority for people with TB and HCPs. The second, ‘It is important to promote “physical and spiritual health” during TB treatment’, demonstrates that extended psychosocial and nutritional support would encourage people with TB during their treatment. The third, ‘Accessibility and acceptability are critical in designing social support interventions for people with TB’, shows the importance of ensuring that support is accessible and proportional to the needs of people with TB and their families.Conclusions Accessible interventions that incorporate financial risk protection, nutritional and psychosocial support matter most to people with TB and HCPs in urban Viet Nam to improve their treatment outcomes and reduce catastrophic costs. This study can inform the design of stronger person-centred interventions to advance progress towards the goals of the WHO’s End TB Strategy.

Objective Many children in low-income and middle-income countries are disadvantaged in achieving early developmental potential in childhood as they lack the necessary support from their surroundings, including from parents and caregivers. Digital technologies, such as smartphone apps, coupled with iterative codesign to engage end-users in the technology-delivered content development stages, can help overcome gaps in early child development (ECD). We describe the iterative codesign and quality improvement process that informs the development of content for the Thrive by Five International Program, localised for nine countries in Asia and Africa.Design Between 2021 and 2022, an average of six codesign workshops in each country were conducted in Afghanistan, Indonesia, Kyrgyzstan, Uzbekistan, Cameroon, the Democratic Republic of the Congo, Ethiopia, Kenya and Namibia.ParticipantsA total of 174 parents and caregivers and 58 in-country subject matter experts participated and provided feedback to refine and inform the cultural appropriateness of the Thrive by Five app and its content. Detailed notes from the workshops and written feedback were coded and analysed using established thematic techniques.Results Four themes emerged from the codesign workshops: local realities, barriers to positive parenting, child development and lessons learnt about the cultural context. These themes, as well as various subthemes, informed content development and refinement. For example, childrearing activities were requested and developed to promote inclusion of families from diverse backgrounds, encourage best parenting practices, increase engagement of fathers in ECD, address parents’ mental well-being, educate children about cultural values and help bereaved children with grief and loss. Also, content that did not align with the laws or culture of any country were removed.Conclusions The iterative codesign process informed the development of a culturally relevant app for parents and caregivers of children in the early years. Further evaluation is required to assess user experience and impact in real world settings.

Objectives To evaluate the performance of point-of-care C-reactive protein (CRP) as a screening tool for tuberculosis (TB) using a threshold of 10 mg/L in both people living with HIV (PLHIV) and HIV-negative individuals and compare it to symptom screening using a composite reference for bacteriological confirmation of TB.Methods Prospective cross-sectional study.Setting A primary healthcare facility in Lusaka, Zambia.Participants Consecutive adults (≥18 years) presenting for routine outpatient healthcare were enrolled. Of the 816 individuals approached to participate in the study, 804 eligible consenting adults were enrolled into the study, of which 783 were included in the analysis.Primary outcome measures Sensitivity, specificity, positive predictive value and negative predictive value (NPV) of CRP and symptom screening.Results Overall, sensitivity of WHO-recommended four-symptom screen (W4SS) and CRP were 87.2% (80.0–92.5) and 86.6% (79.6–91.8) while specificity was 30.3% (26.7–34.1) and 34.8% (31.2–38.6), respectively. Among PLHIV, sensitivity of W4SS and CRP was 92.2% (81.1–97.8) and 94.8% (85.6–98.9) while specificity was 37.0% (31.3–43.0) and 27.5% (22.4–33.1), respectively. Among those with CD4≥350, the NPV for CRP was 100% (92.9–100). In the HIV negative, sensitivity of W4SS and CRP was 83.8% (73.4–91.3) and 80.3% (69.5–88.5) while specificity was 25.4% (20.9–30.2) and 40.5% (35.3–45.6), respectively. Parallel use of CRP and W4SS yielded a sensitivity and NPV of 100% (93.8–100) and 100% (91.6–100) among PLHIV and 93.3% (85.1–97.8) and 90.0% (78.2–96.7) among the HIV negatives, respectively.Conclusion Sensitivity and specificity of CRP were similar to symptom screening in HIV-positive outpatients. Independent use of CRP offered limited additional benefit in the HIV negative. CRP can independently accurately rule out TB in PLHIV with CD4≥350. Parallel use of CRP and W4SS improves sensitivity irrespective of HIV status and can accurately rule out TB in PLHIV, irrespective of CD4 count.

Objectives To end tuberculosis (TB), the vast reservoir of 1.7–2.3 billion TB infections (TBIs) must be addressed, but achieving global TB preventive therapy (TPT) targets seems unlikely. This study assessed the feasibility of using interferon-γ release assays (IGRAs) at lower healthcare levels and the comparative performance of 3-month and 9-month daily TPT regimens (3HR/9H).Design, setting, participants and intervention This cohort study was implemented in two provinces of Viet Nam from May 2019 to September 2020. Participants included household contacts (HHCs), vulnerable community members and healthcare workers (HCWs) recruited at community-based TB screening events or HHC investigations at primary care centres, who were followed up throughout TPT.Primary and secondary outcomes We constructed TBI care cascades describing indeterminate and positivity rates to assess feasibility, and initiation and completion rates to assess performance. We fitted mixed-effects logistic and stratified Cox models to identify factors associated with IGRA positivity and loss to follow-up (LTFU).Results Among 5837 participants, the indeterminate rate was 0.8%, and 30.7% were IGRA positive. TPT initiation and completion rates were 63.3% (3HR=61.2% vs 9H=63.6%; p=0.147) and 80.6% (3HR=85.7% vs 9H=80.0%; p=0.522), respectively. Being male (adjusted OR=1.51; 95% CI: 1.28 to 1.78; p

Introduction Metformin is a medication likely to improve measures of cardiometabolic disturbance in young people with mental illness. Evidence also suggests metformin may improve depressive symptoms. This 52-week double-blind randomised control trial (RCT) aims to investigate the efficacy of metformin pharmacotherapy as an adjunct to a healthy lifestyle behavioural intervention in improving cardiometabolic outcomes, and depressive, anxiety and psychotic symptoms in youth with clinically diagnosed major mood syndromes.Methods and analysis At least 266 young people aged 16–25 presenting for mental healthcare for major mood syndromes who are also at risk for poor cardiometabolic outcomes will be invited to participate in this study. All participants will engage in a 12-week sleep–wake, activity and metabolically focused behavioural intervention programme. As an adjunctive intervention, participants will receive either metformin (500–1000 mg) or placebo pharmacotherapy for 52 weeks.Participants will undergo a series of assessments including: (1) self-report and clinician-administered assessments; (2) blood tests; (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) actigraphy. Univariate and multivariate tests (generalised mixed-effects models) will be used to examine changes in primary and secondary outcomes (and associations with predetermined predictor variables).Ethics and dissemination This study has been approved by the Sydney Local Health District Research Ethics and Governance Office (X22-0017). The results of this double-blind RCT will be disseminated into the scientific and broader community through peer-reviewed journals, conference presentations, social media and university websites.Trial registration number Australian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12619001559101p, 12 November 2019.

Objectives Our objective was to evaluate the impact of a service delivery model led by membership-based associations called Iddirs formed by women on tuberculosis preventive treatment (TPT) initiation and completion rates among children.Design Comparative, before-and-after study design.Setting Three intervention and two control districts in Ethiopia.Participants Children who had a history of close contact with adults with infectious forms of tuberculosis (TB). Child contacts in whom active TB and contraindications to TPT regimens were excluded were considered eligible for TPT.Interventions Between July 2020 and June 2021, trained women Iddir members visited households of index TB patients, screened child household contacts for TB, provided education and information on the benefits of TPT, linked them to the nearby health centre and followed them at home for TPT adherence and side effects. Two control zones received the standard of care, which comprised of facility-based provision of TPT to children. We analysed quarterly TPT data for treatment initiation and completion and compared intervention and control zones before and after the interventions and tested for statistical significance using Poisson regression.Primary and secondary outcome measures There were two primary outcome measures: proportion of eligible children initiated TPT and proportion completed treatment out of those eligible.Results TPT initiation rate among eligible under-15-year-old children (U15C) increased from 28.7% to 63.5% in the intervention zones, while it increased from 34.6% to 43.2% in the control zones, and the difference was statistically significant (p

Objectives Despite WHO guidelines recommending household contact investigation, and studies showing the impact of active screening, most tuberculosis (TB) programmes in resource-limited settings only carry out passive contact investigation. The cost of such strategies is often cited as barriers to their implementation. However, little data are available for the additional costs required to implement this strategy. We aimed to estimate the cost and cost-effectiveness of active contact investigation as compared with passive contact investigation in urban Pakistan.Methods We estimated the cost-effectiveness of ‘enhanced’ (passive with follow-up) and ‘active’ (household visit) contact investigations compared with standard ‘passive’ contact investigation from providers and the programme’s perspective using a simple decision tree. Costs were collected in Pakistan from a TB clinic performing passive contact investigation and from studies of active contact tracing interventions conducted. The effectiveness was based on the number of patients with TB identified among household contacts screened.Results The addition of enhanced contact investigation to the existing passive mode detected 3.8 times more cases of TB per index patient compared with passive contact investigation alone. The incremental cost was US$30 per index patient, which yielded an incremental cost of US$120 per incremental patient identified with TB. The active contact investigation was 1.5 times more effective than enhanced contact investigation with an incremental cost of US$238 per incremental patient with TB identified.Conclusion Our results show that enhanced and active approaches to contact investigation effectively identify additional patients with TB among household contacts at a relatively modest cost. These strategies can be added to the passive contact investigation in a high burden setting to find the people with TB who are missed and meet the End TB strategy goals.

Introduction Approximately 75% of major mental illness occurs before the age of 25 years. Despite this, our capacity to provide effective, early and personalised interventions is limited by insufficient evidence for characterising early-stage, and less specific, presentations of major mental disorders in youth populations. This article describes the protocol for setting up a large-scale database that will collect longitudinal, prospective data that incorporate clinical, social and occupational function, neuropsychological, circadian, metabolic, family history and genetic metrics. By collecting data in a research-purposed, standardised manner, the ‘Neurobiology Youth Follow-up Study’ should improve identification, characterisation and profiling of youth attending mental healthcare, to better inform diagnosis and treatment at critical time points. The overall goal is enhanced long-term clinical and functional outcomes.Methods and analysis This longitudinal clinical cohort study will invite participation from youth (12–30 years) who seek help for mental health-related issues at an early intervention service (headspace Camperdown) and linked services. Participants will be prospectively tracked over 3 years with a series of standardised multimodal assessments at baseline, 6, 12, 24 and 36 months. Evaluations will include: (1) clinician-administered and self-report assessments determining clinical stage, pathophysiological pathways to illness, diagnosis, symptomatology, social and occupational function; (2) neuropsychological profile; (3) sleep–wake patterns and circadian rhythms; (4) metabolic markers and (5) genetics. These data will be used to: (1) model the impact of demographic, phenomenological and treatment variables, on clinical and functional outcomes; (2) map neurobiological profiles and changes onto a transdiagnostic clinical stage and pathophysiological mechanisms framework.Ethics and dissemination This study protocol has been approved by the Human Research Ethics Committee of the Sydney Local Health District (2020/ETH01272, protocol V.1.3, 14 October 2020). Research findings will be disseminated through peer-reviewed journals and presentations at scientific conferences and to user and advocacy groups. Participant data will be de-identified.

Introduction In Canada, deceased organ donation provides over 80% of transplanted organs. At the time of death, families, friends or others assume responsibility as substitute decision-makers (SDMs) to consent to organ donation. Despite their central role in this process, little is known about what barriers, enablers and beliefs influence decision-making among SDMs. This study aims to explore the experiences and perspectives of SDMs involved in making decisions around the withdrawal of life-sustaining therapies, end-of-life care and deceased organ donation.Methods and analysis SDMs of 60 patients admitted to intensive care units will be enrolled for this study. Ten hospitals across five provinces in Canada in a prospective multicentre qualitative cohort study. We will conduct semistructured telephone interviews in English or French with SDMs between 6 and 8 weeks after the patient’s death. Our sampling frame will stratify SDMs into three groups: SDMs who were not approached for organ donation; SDMs who were approached and consented to donate and SDMs who were approached but did not consent to donate. We will use two complementary theoretical frameworks—the Common-Sense Self-Regulation Model and the Theoretical Domains Framework— to inform our interview guide. Interview data will be analysed using deductive directed content analysis and inductive thematic analysis.Ethics and dissemination This study has been approved by the Centre Hospitalier de l’Université de Montréal Research Ethics Board. The findings from this study will help identify key factors affecting substitute decision-making in deceased organ donation, reasons for non-consent and barriers to achieve congruency between SDM and patient wishes. Ultimately, these data will contribute to the development and evaluation of tools and training for healthcare providers to support SDMs in making decisions about organ donation.Trial registration number NCT03850847.