Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial.

Background: In a cluster randomized trial (clinicaltrials.gov: NCT02810678) a flexible but comprehensive health system intervention significantly increased the number of household contacts (HHC) identified and started on tuberculosis preventive treatment (TPT). A follow-up study was conducted one year later to test the hypotheses that these effects were sustained, and were reproducible with a simplified intervention. Methods: We conducted a follow-up study from May 1, 2018 until April 30, 2019, as part of a multinational cluster randomized trial. Eight sites in 4 countries that had received the intervention in the original trial received no further intervention; eight other sites in the same countries that had not received the intervention (control sites in the original trial) now received a simplified version of the intervention. This consisted of repeated local evaluation of the Cascade of care for TB infection, and stakeholder decision making. The number of HHC identified and starting TPT were repeatedly measured at all 16 sites and expressed as rates per 100 newly diagnosed index TB patients. The sustained effect of the original intervention was estimated by comparing these rates after the intervention in the original trial with the last 6 months of the follow-up study. The reproducibility was estimated by comparing the pre-post intervention changes in rates at sites receiving the original intervention with the pre-post changes in rates at sites receiving the later, simplified intervention. Findings: With regard to the sustained impact of the original intervention, compared to the original post-intervention period, the number of HHC identified and treated per 100 newly diagnosed TB patients was 10 more (95% confidence interval: 84 fewer to 105 more), and 1 fewer (95% CI: 22 fewer to 20 more) respectively up to 14 months after the end of the original intervention. With regard to the reproducibility of the simplified intervention, at sites that had initially served as control sites, the number of HHC identified and treated per 100 TB patients increased by 33 (95% CI: -32, 97), and 16 (-69, 100) from 3 months before, to up to 6 months after receiving a streamlined intervention, although differences were larger, and significant if the post-intervention results were compared to all pre-intervention periods. Interpretation: Up to one year after it ended, a health system intervention resulted in sustained increases in the number of HHC identified and starting TPT. A simplified version of the intervention was associated with non-significant increases in the identification and treatment of HHC. Inferences are limited by potential bias due to other temporal effects, and the small number of study sites. Funding: Funded by the Canadian Institutes of Health Research (Grant number 143350).

High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial.

BACKGROUND: Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT. METHODS: This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03988933 (active). RESULTS: Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (-0·5% [95% CI -2·4 to 1·5]; non-inferiority met). Completion was lower in the 20 mg/kg group (-7·8% [95% CI -13·6 to -2·0]) and the 30 mg/kg group (-15·4% [-21·4 to -9·4]) than in the standard-dose group. INTERPRETATION: In this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg daily (the latter, a fully blinded comparison); we do not consider 30 mg/kg to be a good option for TPT. Rifampicin at 20 mg/kg daily for 2 months was as safe as standard treatment, but with lower completion. This difference remains unexplained. FUNDING: Canadian Institutes of Health Research.

Barriers and supports for uptake of human papillomavirus vaccination in Indigenous people globally: A systematic review.

Despite the availability of effective and safe human papillomavirus (HPV) vaccines that reduce the incidence and impact of cervical cancer and other cancers, HPV vaccine coverage rates remain persistently low and the cervical cancer burden disproportionately high among Indigenous people globally. This study aimed to systematically identify, appraise, and summarize the literature on documented barriers and supports to HPV vaccination in Indigenous populations internationally. Forty-three studies were included and an inductive, qualitative, thematic synthesis was applied. We report on 10 barrier themes and 7 support themes to vaccine uptake, and provide a quantitative summary of metrics. Focusing on Indigenous perspectives reported in the literature, we propose recommendations on community-research collaboration, culturally safe intergenerational and gender-equitable community HPV vaccine education, as well as multi-level transparency to ensure informed consent is secured in the context of reciprocal relationships. Although the voices of key informant groups (e.g., HPV-vaccine eligible youth and community Elders) are underrepresented in the literature, the identification of barriers and supports to HPV vaccination in a global Indigenous context might help inform researchers and health policy makers who aim to improve HPV vaccine uptake in Indigenous populations.

Canadian tuberculosis health care workers' perspectives on education and counselling for patients and family members who are born outside of Canada.

Tuberculosis health care workers (TB HCWs) in low incidence settings have important perspectives on providing TB education and counselling to patients and family members born in other countries. The purpose of this qualitative study was to explore HCWs' perspectives on barriers and facilitators for capacity-building education and counselling with patients and family members born outside of Canada experiencing advanced infectious TB in Calgary, a city in western Canada. Data were collected through semi-structured interviews and field notes and thematically analysed. Twenty-four HCWs representing clerical staff, nurses, physicians, and allied health professionals employed in TB care were interviewed. HCWs described how multi-level barriers such as patients' fear of death, complex intra-family communication, information-laden appointments, and patients' precarious employment collided resulting in overwhelmed patients and reduced connection to family. Some HCWs were unsure how to discuss TB stigma with patients and family members. HCWs perceived that increased continuity of care and providing patients and family members with digestible amounts of information earlier were important steps towards better practice. HCWs identified that patients and families could benefit from preparation for initial appointments, increased continuity, and improved patient education materials. HCWs should also receive skills-training to facilitate individual and family counselling.

One child, one appointment: how institutional discourses organize the work of parents and nurses in the provision of childhood vaccination for First Nations children.

To effectively support childhood vaccine programs for First Nations Peoples, Canada's largest population of Indigenous Peoples, it is essential to understand the context, processes, and structures organizing vaccine access and uptake. Rather than assuming that solutions lie in compliance with current regulations, our aim was to identify opportunities for innovation by exploring the work that nurses and parents must do to have children vaccinated. In partnership with a large First Nations community, we used an institutional ethnography approach that included observing vaccination clinic appointments, interviewing individuals involved in childhood vaccinations, and reviewing documented vaccination processes and regulations (texts). We found that the 'work' nurses engage in to deliver childhood vaccines is highly regulated by standardized texts that prioritize discourses of safety and efficiency. Within the setting of nursing practice in a First Nations community, these regulations do not always support the best interests of families. Nurses and parents are caught between the desire to vaccinate multiple children and the requirement to follow institutionally authorized processes. The success of the vaccination program, when measured solely by the number of children who follow the vaccine schedule, does not take into consideration the challenges nurses encounter in the clinic or the work parents do to get their children vaccinated. Exploring new ways of approaching the processes could lead to increased vaccination uptake and satisfaction for parents and nurses.

Barriers, supports, and effective interventions for uptake of human papillomavirus- and other vaccines within global and Canadian Indigenous peoples: a systematic review protocol.

BACKGROUND: Despite the existence of human papilloma virus (HPV) vaccines with demonstrated safety and effectiveness and funded HPV vaccination programs, coverage rates are persistently lower and cervical cancer burden higher among Canadian Indigenous peoples. Barriers and supports to HPV vaccination in Indigenous peoples have not been systematically documented, nor have interventions to increase uptake in this population. This protocol aims to appraise the literature in Canadian and global Indigenous peoples, relating to documented barriers and supports to vaccination and interventions to increase acceptability/uptake or reduce hesitancy of vaccination. Although HPV vaccination is the primary focus, we anticipate only a small number of relevant studies to emerge from the search and will, therefore, employ a broad search strategy to capture literature related to both HPV vaccination and vaccination in general in global Indigenous peoples. METHODS: Eligible studies will include global Indigenous peoples and discuss barriers or supports and/or interventions to improve uptake or to reduce hesitancy, for the HPV vaccine and/or other vaccines. Primary outcomes are documented barriers or supports or interventions. All study designs meeting inclusion criteria will be considered, without restricting by language, location, or data type. We will use an a priori search strategy, comprised of key words and controlled vocabulary terms, developed in consultation with an academic librarian, and reviewed by a second academic librarian using the PRESS checklist. We will search several electronic databases from date of inception, without restrictions. A pre-defined group of global Indigenous websites will be reviewed for relevant gray literature. Bibliographic searches will be conducted for all included studies to identify relevant reviews. Data analysis will include an inductive, qualitative, thematic synthesis and a quantitative analysis of measured barriers and supports, as well as a descriptive synthesis and quantitative summary of measures for interventions. DISCUSSION: To our knowledge, this study will contribute the first systematic review of documented barriers, supports, and interventions for vaccination in general and for HPV vaccination. The results of this study are expected to inform future research, policies, programs, and community-driven initiatives to enhance acceptability and uptake of HPV vaccination among Indigenous peoples. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration Number: CRD42017048844.

Revelations of HIV-infected patients treated with highly active antiretroviral therapy (HAART) in rural Uganda.

The purpose of this qualitative study was to explore the psychosocial changes revealed by persons living with HIV/AIDS (PLWHA) in western Uganda as a result of the introduction of highly active antiretroviral therapy (HAART). Fourteen participants were interviewed on two occasions. Two focus groups discussions were also conducted. Patients experienced important personal benefits as a result of HAART and the resulting clinical improvement. These benefits included a restoration of hope, self-esteem and personal agency. Patients were also relieved of the great fear which they had about the conditions of their death. The financial and social struggles introduced by AIDS illness continued after the introduction of HAART. The conclusion is that the HAART programs should provide more holistic care to patients to address the persistent family issues identified in this study.