The treatment of latent tuberculosis infection in migrants in primary care versus secondary care.

BACKGROUND: Control of latent tuberculosis infection (LTBI) is a priority in the World Health Organization strategy to eliminate tuberculosis (TB). Many high-income low TB incidence countries have prioritised LTBI screening and treatment in recent migrants. We tested whether a novel model of care, based entirely within primary care, was effective and safe as compared to secondary care. METHODS: This was a pragmatic cluster-randomised, parallel group, superiority trial conducted in 34 general practices in London, UK, comparing LTBI treatment in recent migrants in primary care to secondary care. The primary outcome was treatment completion, defined as taking at least 90% of antibiotic doses. Secondary outcomes included treatment acceptance, adherence, adverse effects, patient satisfaction, TB-incidence and a cost-effectiveness analysis. The trial is registered at ClinicalTrials.gov (NCT03069807). Analyses were performed on an intention-to-treat basis. RESULTS: Between September 2016 and May 2019, 362 recent migrants with LTBI were offered treatment and 276 accepted. Treatment completion was similar in primary and secondary care (82·6% versus 86·0%, aOR:0·64, 95%CI:0·31-1·29). There was no difference in drug induced liver injury (DILI) between primary and secondary care (0·7% versus 2·3%, aOR:0·29, 95%CI:0·03-2·84). Treatment acceptance was lower in primary care (65·2% (146/224) versus 94.2% (130/138), aOR:0·10, 95%CI:0·03-0·31). The estimated cost per patient completing treatment was lower in primary care, with an incremental saving of £315. 27(£313.47-£317.07). CONCLUSIONS: The treatment of LTBI in recent migrants within primary care does not result in higher rates of treatment completion but is safe and costs less when compared to secondary care.

Prevalence of non-communicable diseases among household contacts of people with tuberculosis: A systematic review and individual participant data meta-analysis.

OBJECTIVE: To investigate the prevalence of non-communicable diseases among household contacts of people with tuberculosis. METHODS: We conducted a systematic review and individual participant data meta-analysis. We searched Medline, Embase and the Global Index Medicus from inception to 16 May 2023. We included studies that assessed for at least one non-communicable disease among household contacts of people with clinical tuberculosis. We estimated the non-communicable disease prevalence through mixed effects logistic regression for studies providing individual participant data, and compared it with estimates from aggregated data meta-analyses. Furthermore, we compared age and sex-standardised non-communicable disease prevalence with national-level estimates standardised for age and sex. RESULTS: We identified 39 eligible studies, of which 14 provided individual participant data (29,194 contacts). Of the remaining 25 studies, 18 studies reported aggregated data suitable for aggregated data meta-analysis. In individual participant data analysis, the pooled prevalence of diabetes in studies that undertook biochemical testing was 8.8% (95% confidence interval [CI], 5.1%-14.9%, four studies). Age-and sex-standardised prevalence was higher in two studies (10.4% vs. 6.9% and 11.5% vs. 8.4%) than the corresponding national estimates and similar in two studies. Prevalence of diabetes mellitus based on self-report or medical records was 3.4% (95% CI 2.6%-4.6%, 14 studies). Prevalence did not significantly differ compared to estimates from aggregated data meta-analysis. There were limited data for other non-communicable diseases. CONCLUSION: The prevalence of diabetes mellitus among household contacts was high while that of known diabetes was substantially lower, suggesting the underdiagnosis. tuberculosis household contact investigation offers opportunities to deliver multifaceted interventions to identify tuberculosis infection and disease, screen for non-communicable diseases and address shared risk factors.

Differences in Factors Associated With Preterm and Term Stillbirth: A Secondary Cohort Analysis of the DESiGN Trial.

OBJECTIVE: To identify whether maternal and pregnancy characteristics associated with stillbirth differ between preterm and term stillbirth. DESIGN: Secondary cohort analysis of the DESiGN RCT. SETTING: Thirteen UK maternity units. POPULATION: Singleton pregnant women and their babies. METHODS: Multiple logistic regression was used to assess whether the 12 factors explored were associated with stillbirth. Interaction tests assessed for a difference in these associations between the preterm and term periods. MAIN OUTCOME MEASURE: Stillbirth stratified by preterm (<37+0 weeks') and term (37+0-42+6 weeks') births. RESULTS: A total of 195 344 pregnancies were included. Six hundred and sixty-seven were stillborn (3.4 per 1000 births), of which 431 (65%) were preterm. Significant interactions were observed for maternal age, ethnicity, IMD, BMI, parity, smoking, PAPP-A, gestational hypertension, pre-eclampsia and gestational diabetes but not for chronic hypertension and pre-existing diabetes. Stronger associations with term stillbirth were observed in women with obesity compared to BMI 18.5-24.9 kg/m2 (BMI 30.0-34.9 kg/m2 term adjusted OR 2.1 [95% CI 1.4-3.0] vs. preterm aOR 1.1 [0.8-1.7]; BMI ≥ 35.0 kg/m2 term aOR 2.2 [1.4-3.4] vs. preterm aOR 1.5 [1.2-1.8]; p-interaction < 0.01), nulliparity compared to parity 1 (term aOR 1.7 [1.1-2.7] vs. preterm aOR 1.2 [0.9-1.6]; p-interaction < 0.01) and Asian ethnicity compared with White (p-interaction < 0.01). A weaker or lack of association with term, compared to preterm, stillbirth was observed for older maternal age, smoking and pre-eclampsia. CONCLUSION: Differences in association exist between mothers experiencing preterm and term stillbirth. These differences could contribute to design of timely surveillance and interventions to further mitigate the risk of stillbirth.

Exploring the association between unintended pregnancies and unmet contraceptive needs among Ugandan women of reproductive age: an analysis of the 2016 Uganda demographic and health survey.

BACKGROUND: Unintended pregnancy and unmet contraceptive needs pose significant public health challenges, particularly in developing nations, where they contribute to maternal health risks. While previous research has explored determinants of unintended pregnancies, there remains a gap in understanding the association between unplanned pregnancies and unmet contraceptive needs among Ugandan women of reproductive age. This study aimed to assess unmet contraceptive needs and their correlation with unintended pregnancies and other factors in Uganda, utilizing a nationally representative sample. METHODS: Data was extracted from the 2016 Uganda Demographic Health Survey (UDHS), a cross-sectional survey conducted in the latter half of 2016. The study encompassed 18,506 women aged 15-49 with a history of at least one prior pregnancy. The primary outcome variable was the planning status of the most recent pregnancy, while the principal independent variable was unmet contraceptive need. Additional variables were controlled in the analysis. Data analysis was performed using STATA version 17, involving descriptive analysis, cross-tabulation, chi-square testing, and logistic regression. Statistical significance was set at p < 0.05. RESULTS: A substantial proportion of women reported unintended pregnancies (44.5%), with approximately 21.09% experiencing an unmet need for contraception. In the adjusted model, women with unmet contraceptive needs had 3.97 times higher odds of unintended pregnancy (95% CI = 3.61-4.37) compared to those with met contraceptive needs. Significant factors linked to unintended pregnancies included women's age, place of residence, household wealth status, decision-making authority regarding contraceptive use, educational attainment, husband's occupation, and educational level. CONCLUSION: This study revealed that both the rate of unintended pregnancies and unmet contraceptive needs in Uganda exceeded the global average, warranting urgent policy attention. Addressing unmet contraceptive needs emerges as a potential strategy to curtail unintended pregnancies. Further qualitative research may be necessary to elucidate the sociocultural and behavioral determinants of unwanted pregnancies, facilitating context-specific interventions.

Evaluation of conditional cash transfers and mHealth audio messaging in reduction of risk factors for childhood malnutrition in internally displaced persons camps in Somalia: A 2 × 2 factorial cluster-randomised controlled trial.

BACKGROUND: Cash transfer programmes are increasingly used in humanitarian contexts to help address people's needs across multiple sectors. However, their impact on the key objectives of reducing malnutrition and excess mortality remains unclear. mHealth interventions show great promise in many areas of public health, but evidence for their impact on reducing the risk factors for malnutrition is uncertain. We therefore implemented a trial to determine the impacts of 2 interventions in a protracted humanitarian context, a cash transfer conditionality and mHealth audio messages. METHODS AND FINDINGS: A 2 × 2 factorial cluster-randomised trial was implemented in camps for internally displaced people (IDP) near Mogadishu, Somalia, starting in January 2019. The main study outcomes were assessed at midline and endline and included coverage of measles vaccination and the pentavalent immunisation series, timely vaccination, caregiver's health knowledge, and child diet diversity. Twenty-three clusters (camps) were randomised to receive or not receive conditional cash transfers (CCTs) and an mHealth intervention, and 1,430 households were followed up over 9 months. All camps received cash transfers made at emergency humanitarian level (US$70/household/month) for 3 months followed by a further 6 months at a safety net level (US$35). To be eligible to receive cash, households in camps receiving CCT were required to take their children <5 years age to attend a single health screening at a local clinic and were issued with a home-based child health record card. Participants in camps receiving the mHealth intervention were asked (but not required) to listen to a series of audio messages about health and nutrition that were broadcast to their mobile phone twice a week for 9 months. Participants and investigators were not blinded. Adherence to both interventions was monitored monthly and found to be high (>85%). We conducted intention-to-treat analysis. During the humanitarian intervention phase, the CCT improved coverage of measles vaccination (MCV1) from 39.2% to 77.5% (aOR 11.7, 95% CI [5.2, 26.1]; p < 0.001) and completion of the pentavalent series from 44.2% to 77.5% (aOR 8.9, 95% CI [2.6, 29.8]; p = < 0.001). By the end of the safety net phase, coverage remained elevated from baseline at 82.2% and 86.8%, respectively (aOR 28.2, 95% CI [13.9, 57.0]; p < 0.001 and aOR 33.8, 95% CI [11.0, 103.4]; p < 0.001). However, adherence to timely vaccination did not improve. There was no change in the incidence of mortality, acute malnutrition, diarrhoea, or measles infection over the 9 months of follow-up. Although there was no evidence that mHealth increased Mother's knowledge score (aOR 1.32, 95% CI [0.25, 7.11]; p = 0.746) household dietary diversity increased from a mean of 7.0 to 9.4 (aOR 3.75, 95% CI [2.04, 6.88]; p < 0.001). However, this was not reflected by a significant increase in child diet diversity score, which changed from 3.19 to 3.63 (aOR 2.1, 95% CI [1.0, 4.6]; p = 0.05). The intervention did not improve measles vaccination, pentavalent series completion, or timely vaccination, and there was no change in the incidence of acute malnutrition, diarrhoea, measles infection, exclusive breastfeeding, or child mortality. No significant interactions between the interventions were found. Study limitations included the limited time available to develop and test the mHealth audio messages and the necessity to conduct multiple statistical tests due to the complexity of the study design. CONCLUSIONS: A carefully designed conditionality can help achieve important public health benefits in humanitarian cash transfer programmes by substantially increasing the uptake of child vaccination services and, potentially, other life-saving interventions. While mHealth audio messages increased household diet diversity, they failed to achieve any reductions in child morbidity, malnutrition, or mortality. TRIAL REGISTRATION: ISRCTN ISRCTN24757827. Registered November 5, 2018.

Sexual and reproductive health in Britain during the first year of the COVID-19 pandemic: cross-sectional population survey (Natsal-COVID-Wave 2) and national surveillance data.

OBJECTIVES: To assess sexual behaviour, and sexual and reproductive health (SRH) outcomes, after 1 year of the COVID-19 pandemic in Britain. METHODS: 6658 participants aged 18-59 and resident in Britain completed a cross-sectional web-panel survey (Natsal-COVID-Wave 2, March-April 2021), 1 year after the first lockdown. Natsal-COVID-2 follows the Natsal-COVID-Wave 1 survey (July-August 2020) which captured impacts in the initial months. Quota-based sampling and weighting resulted in a quasi-representative population sample. Data were contextualised with reference to the most recent probability sample population data (Natsal-3; collected 2010-12; 15 162 participants aged 16-74) and national surveillance data on recorded sexually transmitted infection (STI) testing, conceptions, and abortions in England/Wales (2010-2020). The main outcomes were: sexual behaviour; SRH service use; pregnancy, abortion and fertility management; sexual dissatisfaction, distress and difficulties. RESULTS: In the year from the first lockdown, over two-thirds of participants reported one or more sexual partners (women 71.8%; men 69.9%), while fewer than 20.0% reported a new partner (women 10.4%; men 16.8%). Median occasions of sex per month was two. Compared with 2010-12 (Natsal-3), we found less sexual risk behaviour (lower reporting of multiple partners, new partners, and new condomless partners), including among younger participants and those reporting same-sex behaviour. One in 10 women reported a pregnancy; pregnancies were fewer than in 2010-12 and less likely to be scored as unplanned. 19.3% of women and 22.8% of men were distressed or worried about their sex life, significantly more than in 2010-12. Compared with surveillance trends from 2010 to 2019, we found lower than expected use of STI-related services and HIV testing, lower levels of chlamydia testing, and fewer conceptions and abortions. CONCLUSIONS: Our findings are consistent with significant changes in sexual behaviour, SRH, and service uptake in the year following the first lockdown in Britain. These data are foundational to SRH recovery and policy planning.

How did the COVID-19 pandemic affect access to condoms, chlamydia and HIV testing, and cervical cancer screening at a population level in Britain? (Natsal-COVID).

OBJECTIVES: To investigate how differential access to key interventions to reduce STIs, HIV and their sequelae changed during the COVID-19 pandemic. METHODS: British participants (18-59 years) completed a cross-sectional web survey 1 year (March-April 2021) after the initial lockdown in Britain. Quota-based sampling and weighting resulted in a quasi-representative population sample. We compared Natsal-COVID data with Natsal-3, a household-based probability sample cross-sectional survey (16-74 years) conducted in 2010-2012. Reported unmet need for condoms because of the pandemic and uptake of chlamydia testing/HIV testing/cervical cancer screening were analysed among sexually experienced participants (18-44 years) (n=3869, Natsal-COVID; n=8551, Natsal-3). ORs adjusted for age and other potential confounders describe associations with demographic and behavioural factors. RESULTS: In 2021, 6.9% of women and 16.2% of men reported unmet need for condoms because of the pandemic. This was more likely among participants: aged 18-24 years, of black or black British ethnicity, and reporting same-sex sex (past 5 years) or one or more new relationships (past year). Chlamydia and HIV testing were more commonly reported by younger participants, those reporting condomless sex with new sexual partners and men reporting same-sex partners; a very similar distribution to 10 years previously (Natsal-3). However, there were differences during the pandemic, including stronger associations with chlamydia testing for men reporting same-sex partners; with HIV testing for women reporting new sexual partners and with cervical screening among smokers. CONCLUSIONS: Our study suggests differential access to key primary and secondary STI/HIV prevention interventions continued during the first year of the COVID-19 pandemic. However, there was not strong evidence that differential access has changed during the pandemic when compared with 2010-2012. While the pandemic might not have exacerbated inequalities in access to primary and secondary prevention, it is clear that large inequalities persisted, typically among those at greatest STI/HIV risk.

Prevalence of Curable Sexually Transmitted Infections in a Population-Representative Sample of Young Adults in a High HIV Incidence Area in South Africa.

BACKGROUND: Recent population-representative estimates of sexually transmitted infection (STI) prevalence in high HIV burden areas in southern Africa are limited. We estimated the prevalence and associated factors of 3 STIs among adolescents and young adults (AYA) in rural South Africa. METHODS: Between March 2020 and May 2021, a population-representative sample of AYA aged 16 to 29 years were randomly selected from a Health and Demographic Surveillance Site in rural KwaZulu-Natal, South Africa, for a 2 × 2 factorial randomized controlled trial. Participants in 2 intervention arms were offered baseline testing for gonorrhea, chlamydia, and trichomoniasis using GeneXpert. Prevalence estimates were weighted for participation bias, and logistic regression models were used to assess factors associated with STIs. RESULTS: Of 2323 eligible AYA, 1743 (75%) enrolled in the trial. Among 863 eligible for STI testing, 814 (94%) provided specimens (median age of 21.8 years, 52% female, and 71% residing in rural areas). Population-weighted prevalence estimates were 5.0% (95% confidence interval [CI], 4.2%-5.8%) for gonorrhea, 17.9% (16.5%-19.3%) for chlamydia, 5.4% (4.6%-6.3%) for trichomoniasis, and 23.7% (22.2%-25.3%) for any STI. In multivariable models, female sex (adjusted odds ratio [aOR], 2.24; 95% CI, 1.48-3.09) and urban/periurban (vs. rural) residence (aOR, 1.48; 95% CI, 1.02-2.15) were associated with STIs; recent migration was associated with lower odds of STI (aOR, 0.37; 95% CI, 0.15-0.89). Among those with an STI, 53 (31.0%) were treated within 7 days; median time to treatment was 11 days (interquartile range, 6-77 days). CONCLUSIONS: We identified a high prevalence of curable STIs among AYA in rural South Africa. Improved access to STI testing to enable etiologic diagnosis and rapid treatment is needed.

Antenatal detection of large-for-gestational-age fetuses following implementation of the Growth Assessment Protocol: secondary analysis of a randomised control trial.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP) affects the antenatal detection of large for gestational age (LGA) or maternal and perinatal outcomes amongst LGA babies. DESIGN: Secondary analysis of a pragmatic open randomised cluster control trial comparing the GAP with standard care. SETTING: Eleven UK maternity units. POPULATION: Pregnant women and their LGA babies born at ≥36+0  weeks of gestation. METHODS: Clusters were randomly allocated to GAP implementation or standard care. Data were collected from electronic patient records. Trial arms were compared using summary statistics, with unadjusted and adjusted (two-stage cluster summary approach) differences. MAIN OUTCOME MEASURES: Rate of detection of LGA (estimated fetal weight on ultrasound scan above the 90th centile after 34+0  weeks of gestation, defined by either population or customised growth charts), maternal and perinatal outcomes (e.g. mode of birth, postpartum haemorrhage, severe perineal tears, birthweight and gestational age, neonatal unit admission, perinatal mortality, and neonatal morbidity and mortality). RESULTS: A total of 506 LGA babies were exposed to GAP and 618 babies received standard care. There were no significant differences in the rate of LGA detection (GAP 38.0% vs standard care 48.0%; adjusted effect size -4.9%; 95% CI -20.5, 10.7; p = 0.54), nor in any of the maternal or perinatal outcomes. CONCLUSIONS: The use of GAP did not change the rate of antenatal ultrasound detection of LGA when compared with standard care.

Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of long-term care facilities in the VIVALDI study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused severe disease in unvaccinated long-term care facility (LTCF) residents. Initial booster vaccination following primary vaccination is known to provide strong short-term protection, but data are limited on duration of protection and the protective effect of further booster vaccinations. OBJECTIVE: To evaluate the effectiveness of third, fourth and fifth dose booster vaccination against SARS-CoV-2 related mortality amongst older residents of LTCFs. DESIGN: Prospective cohort study. SETTING: LTCFs for older people in England participating in the VIVALDI study. METHODS: Residents aged >65 years at participating LTCFs were eligible for inclusion if they had at least one polymerase chain reaction or lateral flow device result within the analysis period 1 January 2022 to 31 December 2022. We excluded individuals who had not received at least two vaccine doses before the analysis period. Cox regression was used to estimate relative hazards of SARS-CoV-2 related mortality following 1-3 booster vaccinations compared with primary vaccination, stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF size (total beds). RESULTS: A total of 13,407 residents were included. Our results indicate that third, fourth and fifth dose booster vaccination provide additional short-term protection against SARS-CoV-2 related mortality relative to primary vaccination, with consistent stabilisation beyond 112 days to 45-75% reduction in risk relative to primary vaccination. CONCLUSIONS: Successive booster vaccination doses provide additional short-term protection against SARS-CoV-2 related mortality amongst older LTCF residents. However, we did not find evidence of a longer-term reduction in risk beyond that provided by initial booster vaccination.

Informative cluster size in cluster-randomised trials: A case study from the TRIGGER trial.

BACKGROUND: Recent work has shown that cluster-randomised trials can estimate two distinct estimands: the participant-average and cluster-average treatment effects. These can differ when participant outcomes or the treatment effect depends on the cluster size (termed informative cluster size). In this case, estimators that target one estimand (such as the analysis of unweighted cluster-level summaries, which targets the cluster-average effect) may be biased for the other. Furthermore, commonly used estimators such as mixed-effects models or generalised estimating equations with an exchangeable correlation structure can be biased for both estimands. However, there has been little empirical research into whether informative cluster size is likely to occur in practice. METHOD: We re-analysed a cluster-randomised trial comparing two different thresholds for red blood cell transfusion in patients with acute upper gastrointestinal bleeding to explore whether estimates for the participant- and cluster-average effects differed, to provide empirical evidence for whether informative cluster size may be present. For each outcome, we first estimated a participant-average effect using independence estimating equations, which are unbiased under informative cluster size. We then compared this to two further methods: (1) a cluster-average effect estimated using either weighted independence estimating equations or unweighted cluster-level summaries, and (2) estimates from a mixed-effects model or generalised estimating equations with an exchangeable correlation structure. We then performed a small simulation study to evaluate whether observed differences between cluster- and participant-average estimates were likely to occur even if no informative cluster size was present. RESULTS: For most outcomes, treatment effect estimates from different methods were similar. However, differences of >10% occurred between participant- and cluster-average estimates for 5 of 17 outcomes (29%). We also observed several notable differences between estimates from mixed-effects models or generalised estimating equations with an exchangeable correlation structure and those based on independence estimating equations. For example, for the EQ-5D VAS score, the independence estimating equation estimate of the participant-average difference was 4.15 (95% confidence interval: -3.37 to 11.66), compared with 2.84 (95% confidence interval: -7.37 to 13.04) for the cluster-average independence estimating equation estimate, and 3.23 (95% confidence interval: -6.70 to 13.16) from a mixed-effects model. Similarly, for thromboembolic/ischaemic events, the independence estimating equation estimate for the participant-average odds ratio was 0.43 (95% confidence interval: 0.07 to 2.48), compared with 0.33 (95% confidence interval: 0.06 to 1.77) from the cluster-average estimator. CONCLUSION: In this re-analysis, we found that estimates from the various approaches could differ, which may be due to the presence of informative cluster size. Careful consideration of the estimand and the plausibility of assumptions underpinning each estimator can help ensure an appropriate analysis methods are used. Independence estimating equations and the analysis of cluster-level summaries (with appropriate weighting for each to correspond to either the participant-average or cluster-average treatment effect) are a desirable choice when informative cluster size is deemed possible, due to their unbiasedness in this setting.

Site staff perspectives on communicating trial results to participants: Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial.

BACKGROUND/AIMS: Sharing trial results with participants is an ethical imperative but often does not happen. Show RESPECT (ISRCTN96189403) tested ways of sharing results with participants in an ovarian cancer trial (ISRCTN10356387). Sharing results via a printed summary improved patient satisfaction. Little is known about staff experience and the costs of communicating results with participants. We report the costs of communication approaches used in Show RESPECT and the views of site staff on these approaches. METHODS: We allocated 43 hospitals (sites) to share results with trial participants through one of eight intervention combinations (2 × 2 × 2 factorial; enhanced versus basic webpage, printed summary versus no printed summary, email list invitation versus no invitation). Questionnaires elicited data from staff involved in sharing results. Open- and closed-ended questions covered resources used to share results and site staff perspectives on the approaches used. Semi-structured interviews were conducted. Interview and free-text data were analysed thematically. The mean additional site costs per participant from each intervention were estimated jointly as main effects by linear regression. RESULTS: We received questionnaires from 68 staff from 41 sites and interviewed 11 site staff. Sites allocated to the printed summary had mean total site costs of sharing results £13.71/patient higher (95% confidence interval (CI): -3.19, 30.60; p = 0.108) than sites allocated no printed summary. Sites allocated to the enhanced webpage had mean total site costs £1.91/patient higher (95% CI: -14, 18.74; p = 0.819) than sites allocated to the basic webpage. Sites allocated to the email list had costs £2.87/patient lower (95% CI: -19.70, 13.95; p = 0.731) than sites allocated to no email list. Most of these costs were staff time for mailing information and handling patients' queries. Most site staff reported no concerns about how they had shared results (88%) and no challenges (76%). Most (83%) found it easy to answer queries from patients about the results and thought the way they were allocated to share results with participants would be an acceptable standard approach (76%), with 79% saying they would follow the same approach for future trials. There were no significant effects of the randomised interventions on these outcomes. Site staff emphasised the importance of preparing patients to receive the results, including giving opt-in/opt-out options, and the need to offer further support, particularly if the results could confuse or distress some patients. CONCLUSIONS: Adding a printed summary to a webpage (which significantly improved participant satisfaction) may increase costs to sites by ~£14/patient, which is modest in relation to the cost of trials. The Show RESPECT communication interventions were feasible to implement. This information could help future trials ensure they have sufficient resources to share results with participants.

Contextual factors affecting the implementation of an anemia focused virtual counseling intervention for pregnant women in plains Nepal: a mixed methods process evaluation.

BACKGROUND: Anemia is estimated to cause 115,000 maternal deaths each year. In Nepal, 46% of pregnant women have anemia. As part of an integrated anemia-prevention strategy, family engagement and counseling of pregnant women can increase compliance to iron folic acid tablets, but marginalized women often have lower access to these interventions. We implemented the VALID (Virtual antenatal intervention for improved diet and iron intake) randomized controlled trial to test a family-focused virtual counseling mHealth intervention designed to inclusively increase iron folic acid compliance in rural Nepal; here we report findings from our process evaluation research. METHODS: We conducted semi structured interviews with 20 pregnant women who had received the intervention, eight husbands, seven mothers-in-laws and four health workers. We did four focus groups discussions with intervention implementers, 39 observations of counseling, and used routine monitoring data in our evaluation. We used inductive and deductive analysis of qualitative data, and descriptive statistics of monitoring data. RESULTS: We were able to implement the intervention largely as planned and all participants liked the dialogical counseling approach and use of story-telling to trigger conversation. However, an unreliable and inaccessible mobile network impeded training families about how to use the mobile device, arrange the counseling time, and conduct the counseling. Women were not equally confident using mobile devices, and the need to frequently visit households to troubleshoot negated the virtual nature of the intervention for some. Women's lack of agency restricted both their ability to speak freely and their mobility, which meant that some women were unable to move to areas with better mobile reception. It was difficult for some women to schedule the counseling, as there were competing demands on their time. Family members were difficult to engage because they were often working outside the home; the small screen made it difficult to interact, and some women were uncomfortable speaking in front of family members. CONCLUSIONS: It is important to understand gender norms, mobile access, and mobile literacy before implementing an mHealth intervention. The contextual barriers to implementation meant that we were not able to engage family members as much as we had hoped, and we were not able to minimize in-person contact with families. We recommend a flexible approach to mHealth interventions which can be responsive to local context and the situation of participants. Home visits may be more effective for those women who are most marginalized, lack confidence in using a mobile device, and where internet access is poor.

Thetha Nami ngithethe nawe (Let's Talk): a stepped-wedge cluster randomised trial of social mobilisation by peer navigators into community-based sexual health and HIV care, including pre-exposure prophylaxis (PrEP), to reduce sexually transmissible HIV amongst young people in rural KwaZulu-Natal, South Africa.

BACKGROUND: Antiretroviral therapy (ART) through universal test and treat (UTT) and HIV pre-exposure prophylaxis (PrEP) substantially reduces HIV-related mortality and incidence. Effective ART based prevention has not translated into population-level impact in southern Africa due to sub-optimal coverage among youth. We aim to investigate the effectiveness, implementation and cost effectiveness of peer-led social mobilisation into decentralised integrated HIV and sexual reproductive health (SRH) services amongst adolescents and young adults in KwaZulu-Natal (KZN). METHODS: We are conducting a type 1a hybrid effectiveness/implementation study, with a cluster randomized stepped-wedge trial (SWT) to assess effectiveness and a realist process evaluation to assess implementation outcomes. The SWT will be conducted in 40 clusters in rural KZN over 45 months. Clusters will be randomly allocated to receive the intervention in period 1 (early) or period 2 (delayed). 1) Intervention arm: Resident peer navigators in each cluster will approach young men and women aged 15-30 years living in their cluster to conduct health, social and educational needs assessment and tailor psychosocial support and health promotion, peer mentorship, and facilitate referrals into nurse led mobile clinics that visit each cluster regularly to deliver integrated SRH and differentiated HIV prevention (HIV testing, UTT for those positive, and PrEP for those eligible and negative). Standard of Care is UTT and PrEP delivered to 15-30 year olds from control clusters through primary health clinics. There are 3 co-primary outcomes measured amongst cross sectional surveys of 15-30 year olds: 1) effectiveness of the intervention in reducing the prevalence of sexually transmissible HIV; 2) uptake of universal risk informed HIV prevention intervention; 3) cost of transmissible HIV infection averted. We will use a realist process evaluation to interrogate the extent to which the intervention components support demand, uptake, and retention in risk-differentiated biomedical HIV prevention. DISCUSSION: The findings of this trial will be used by policy makers to optimize delivery of universal differentiated HIV prevention, including HIV pre-exposure prophylaxis through peer-led mobilisation into community-based integrated adolescent and youth friendly HIV and sexual and reproductive health care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier-NCT05405582. Registered: 6th June 2022.

Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Antibody Levels Following Second Dose of ChAdOx1 nCov-19 or BNT162b2 Vaccine in Residents of Long-term Care Facilities in England (VIVALDI).

General population studies have shown strong humoral response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations, but published data are scarce. We measured SARS-CoV-2 anti-spike antibody levels in long-term care facility residents and staff following a second vaccination dose with Oxford-AstraZeneca or Pfizer-BioNTech. Vaccination elicited robust antibody responses in older residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial.

BACKGROUND: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care. METHODS AND FINDINGS: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes. CONCLUSIONS: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings. TRIAL REGISTRATION: This trial is registered with the ISRCTN registry, ISRCTN67698474.

Impacts of COVID-19 on sexual behaviour in Britain: findings from a large, quasi-representative survey (Natsal-COVID).

OBJECTIVES: Physical restrictions imposed to combat COVID-19 dramatically altered sexual lifestyles but the specific impacts on sexual behaviour are still emerging. We investigated physical and virtual sexual activities, sexual frequency and satisfaction in the 4 months following lockdown in Britain in March 2020 and compared with pre-lockdown. METHODS: Weighted analyses of web panel survey data collected July/August 2020 from a quota-based sample of 6654 people aged 18-59 years in Britain. Multivariable regression took account of participants' opportunity for partnered sex, gender and age, to examine their independent associations with perceived changes in sexual frequency and satisfaction. RESULTS: Most participants (86.7%) reported some form of sex following lockdown with physical activities more commonly reported than virtual activities (83.7% vs 52.6%). Altogether, 63.2% reported sex with someone ('partnered sex') since lockdown, three-quarters of whom were in steady cohabiting relationships. With decreasing relationship formality, partnered sex was less frequently reported, while masturbation, sex toy use and virtual activities were more frequently reported. Around half of all participants perceived no change in partnered sex frequency compared with the 3 months pre-lockdown, but this was only one-third among those not cohabiting, who were more likely to report increases in non-partnered activities than those cohabiting. Two-thirds of participants perceived no change in sexual satisfaction; declines were more common among those not cohabiting. Relationship informality and younger age were independently associated with perceiving change, often declines, in sexual frequency and satisfaction. CONCLUSIONS: Our quasi-representative study of the British population found a substantial minority reported significant shifts in sexual repertoires, frequency and satisfaction following the introduction of COVID-19 restrictions. However, these negative changes were perceived by some more than others; predominantly those not cohabiting and the young. As these groups are most likely to experience adverse sexual health, it is important to monitor behaviour as restrictions ease to understand the longer term consequences, including for health services.

Effectiveness of BNT162b2 and ChAdOx-1 vaccines in residents of long-term care facilities in England using a time-varying proportional hazards model.

INTRODUCTION: residents of long-term care facilities (LTCFs) are at high risk of adverse outcomes from SARS-CoV-2. We aimed to estimate the vaccine effectiveness (VE) of one and two doses of BNT162b2 and ChAdOx-1 against SARS CoV-2 infection and COVID-19-related death in residents of LTCFs. METHODS: this observational study used testing, vaccination and mortality data for LTCF residents aged ≥ 65 years who were regularly tested regardless of symptoms from 8 December 2020 to 30 September 2021 in England. Adjusted VE, calculated as one minus adjusted hazard ratio, was estimated using time-varying Cox proportional hazards models for infection and death within 28 days of positive test result. Vaccine status was defined by receipt of one or two doses of vaccine and assessed over a range of intervals. RESULTS: of 197,885 LTCF residents, 47,087 (23.8%) had a positive test and 11,329 (5.8%) died within 28 days of a positive test during the study period. Relative to unvaccinated individuals, VE for infection was highest for ChAdOx-1 at 61% (40-74%) at 1-4 weeks and for BNT162b2 at 69% (52-80%) at 11-15 weeks following the second dose. Against death, VE was highest for ChAdOx-1 at 83% (58-94%) at 1-4 weeks and for BNT162b2 at 91% (75-97%) at 11-15 weeks following second dose. CONCLUSIONS: compared with unvaccinated residents, vaccination with one dose of BNT162b2 or ChAdOx-1 provided moderate protection against infection and death in residents of LTCFs. Protection against death improved after two doses. However, some waning of protection over time was noted.

Isisekelo Sempilo study protocol for the effectiveness of HIV prevention embedded in sexual health with or without peer navigator support (Thetha Nami) to reduce prevalence of transmissible HIV amongst adolescents and young adults in rural KwaZulu-Natal: a 2 × 2 factorial randomised controlled trial.

BACKGROUND: Antiretroviral therapy (ART) through universal test and treat (UTT) and HIV pre-exposure prophylaxis (PrEP) substantially reduces HIV-related mortality, morbidity and incidence. Effective individual-level prevention modalities have not translated into population-level impact in southern Africa due to sub-optimal coverage among adolescents and youth who are hard to engage. We aim to investigate the feasibility, acceptability, and preliminary population level effectiveness of HIV prevention services with or without peer support to reduce prevalence of transmissible HIV amongst adolescents and young adults in KwaZulu-Natal. METHODS: We are conducting a 2 × 2 factorial trial among young men and women aged 16-29 years, randomly selected from the Africa Health Research Institute demographic surveillance area. Participants are randomly allocated to one of four intervention combinations: 1) Standard of Care (SOC): nurse-led services for HIV testing plus ART if positive or PrEP for those eligible and negative; 2) Sexual and Reproductive Health (SRH): Baseline self-collected vaginal and urine samples with study-organized clinic appointments for results, treatment and delivery of HIV testing, ART and PrEP integrated with SRH services; 3) Peer-support: Study referral of participants to a peer navigator to assess their health, social and educational needs and provide risk-informed HIV prevention, including facilitating clinic attendance; or 4) SRH + peer-support. The primary outcomes for effectiveness are: (1) the proportion of individuals with infectious HIV at 12 months and (2) uptake of risk-informed comprehensive HIV prevention services within 60 days of enrolment. At 12 months, all participants will be contacted at home and the study team will collect a dried blood spot for HIV ELISA and HIV viral load testing. DISCUSSION: This trial will enable us to understand the relative importance of SRH and peer support in creating demand for effective and risk informed biomedical HIV prevention and preliminary data on their effectiveness on reducing the prevalence of transmissible HIV amongst all adolescents and youth. TRIAL REGISTRATION: Trial Registry: clincialtrials.gov. CLINICALTRIALS: gov Identifier NCT04532307 . Registered: March 2020.

Testing approaches to sharing trial results with participants: The Show RESPECT cluster randomised, factorial, mixed methods trial.

BACKGROUND: Sharing trial results with participants is an ethical imperative but often does not happen. We tested an Enhanced Webpage versus a Basic Webpage, Mailed Printed Summary versus no Mailed Printed Summary, and Email List Invitation versus no Email List Invitation to see which approach resulted in the highest patient satisfaction with how the results were communicated. METHODS AND FINDINGS: We carried out a cluster randomised, 2 by 2 by 2 factorial, nonblinded study within a trial, with semistructured qualitative interviews with some patients (ISRCTN96189403). Each cluster was a UK hospital participating in the ICON8 ovarian cancer trial. Interventions were shared with 384 ICON8 participants who were alive and considered well enough to be contacted, at 43 hospitals. Hospitals were allocated to share results with participants through one of the 8 intervention combinations based on random permutation within blocks of 8, stratified by number of participants. All interventions contained a written plain English summary of the results. The Enhanced Webpage also contained a short video. Both the Enhanced Webpage and Email contained links to further information and support. The Mailed Printed Summary was opt-out. Follow-up questionnaires were sent 1 month after patients had been offered the interventions. Patients' reported satisfaction was measured using a 5-point scale, analysed by ordinal logistic regression estimating main effects for all 3 interventions, with random effects for site, restricted to those who reported receiving the results and assuming no interaction. Data collection took place in 2018 to 2019. Questionnaires were sent to 275/384 randomly selected participants and returned by 180: 90/142 allocated Basic Webpage, 90/133 Enhanced Webpage; 91/141 no Mailed Printed Summary, 89/134 Mailed Printed Summary; 82/129 no Email List Invitation, 98/146 Email List Invitation. Only 3 patients opted out of receiving the Mailed Printed Summary; no patients signed up to the email list. Patients' satisfaction was greater at sites allocated the Mailed Printed Summary, where 65/81 (80%) were quite or very satisfied compared to sites with no Mailed Printed Summary 39/64 (61%), ordinal odds ratio (OR) = 3.15 (1.66 to 5.98, p < 0.001). We found no effect on patient satisfaction from the Enhanced Webpage, OR = 1.47 (0.78 to 2.76, p = 0.235) or Email List Invitation, OR = 1.38 (0.72 to 2.63, p = 0.327). Interviewees described the results as interesting, important, and disappointing (the ICON8 trial found no benefit). Finding out the results made some feel their trial participation had been more worthwhile. Regardless of allocated group, patients who received results generally reported that the information was easy to understand and find, were glad and did not regret finding out the results. The main limitation of our study is the 65% response rate. CONCLUSIONS: Nearly all respondents wanted to know the results and were glad to receive them. Adding an opt-out Mailed Printed Summary alongside a webpage yielded the highest reported satisfaction. This study provides evidence on how to share results with other similar trial populations. Further research is needed to look at different results scenarios and patient populations. TRIAL REGISTRATION: ISRCTN: ISRCTN96189403.