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Evaluation of waning of IgG antibody responses after rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modelling study from the PREVAC randomized trial.
Get PDFrVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo are WHO-prequalified vaccination regimens against Ebola virus disease (EVD). Challenges associated with measuring long-term clinical protection warrant the evaluation of immune response kinetics after vaccination. Data from a large phase 2 randomized double-blind clinical trial (PREVAC) were used to evaluate waning of anti-Ebola virus (EBOV) glycoprotein (GP1,2) antibody concentrations after rVSVΔG-ZEBOV-GP or Ad26.ZEBOV, MVA-BN-Filo vaccination with linear mixed-effect regression models. After a post-vaccination peak, each vaccination strategy was associated with a decrease of anti-EBOV GP1,2 antibody concentrations with distinct kinetics, highlighting a less-rapid decline in antibody levels after vaccination by rVSVΔG-ZEBOV-GP. One year after administration of the vaccine, antibody concentrations were higher in children compared to adults for both vaccines, although with different effect sizes: 1.74-fold higher concentrations (95% confidence interval [CI] [1.48; 2.02]) for children 12-17 years old to 3.10-fold higher concentrations (95% CI [2.58; 3.69]) for those 1-4 years old compared to adults for Ad26.ZEBOV, MVA-BN-Filo versus 1.36-fold (95% CI [1.12; 1.61]) to 1.41-fold (95% CI [1.21; 1.62]) higher than these values for adults, with relatively small changes from one age category of children to another, for rVSVΔG-ZEBOV-GP. Antibody concentrations also differed according to geographical location, pre-vaccination antibody concentration, and sex. In combination with knowledge on memory response, characterization of the major determinants of immune response durability of both vaccinations may guide future EVD control protocols.Trial registration: ClinicalTrials.gov identifier: NCT02876328
Using Quantitative Bias Analysis to Adjust for Misclassification of COVID-19 Outcomes: An Applied Example of Inhaled Corticosteroids and COVID-19 Outcomes.
Get PDFBACKGROUND: During the pandemic, there was concern that underascertainment of COVID-19 outcomes may impact treatment effect estimation in pharmacoepidemiologic studies. We assessed the impact of outcome misclassification on the association between inhaled corticosteroids (ICS) and COVID-19 hospitalisation and death in the United Kingdom during the first pandemic wave using probabilistic bias analysis (PBA). METHODS: Using data from the Clinical Practice Research Datalink Aurum, we defined a cohort with chronic obstructive pulmonary disease (COPD) on 1 March 2020. We compared the risk of COVID-19 hospitalisation and death among users of ICS/long-acting β-agonist (LABA) and users of LABA/LAMA using inverse probability of treatment weighted (IPTW) logistic regression. We used PBA to assess the impact of non-differential outcome misclassification. We assigned beta distributions to sensitivity and specificity and sampled from these 100 000 times for summary-level and 10 000 times for record-level PBA. Using these values, we simulated outcomes and applied IPTW logistic regression to adjust for confounding and misclassification. Sensitivity analyses excluded ICS + LABA + LAMA (triple therapy) users. RESULTS: Among 161 411 patients with COPD, ICS users had increased odds of COVID-19 hospitalisations and death compared with LABA/LAMA users (OR for COVID-19 hospitalisation 1.59 (95% CI 1.31-1.92); OR for COVID-19 death 1.63 (95% CI 1.26-2.11)). After IPTW and exclusion of people using triple therapy, ORs moved towards the null. All implementations of QBA, both record- and summary-level PBA, modestly shifted the ORs away from the null and increased uncertainty. CONCLUSIONS: We observed increased risks of COVID-19 hospitalisation and death among ICS users compared to LABA/LAMA users. Outcome misclassification was unlikely to change the conclusions of the study, but confounding by indication remains a concern
Serological insights from SARS-CoV-2 heterologous prime and boost responses in Thailand.
Get PDFDuring the COVID-19 pandemic, heterologous vaccination strategies were employed to alleviate the strain on vaccine supplies. The Thailand Ministry of Health adopted these strategies using vector, inactivated, and mRNA vaccines. However, this approach has introduced challenges for SARS-CoV-2 sero-epidemiology studies. Our study analysed 647 samples from healthcare workers who received CoronaVac, ChAdOx1 nCoV-19, and BNT162b2 vaccines. The serological profile encompassed responses to various SARS-CoV-2 variants and vectors, measuring IgG, IgM, and IgA isotypes, alongside IgG avidity assays. The results demonstrated that heterologous CoronaVac/ChAdOx1 nCoV-19 schedules elicited significantly stronger antibody responses compared to homologous schedules (IgG: 1.2-fold, IgM: 10.9-fold, IgA: 3.1-fold increase). Additionally, a heterologous BNT162b2 boost at 4-weeks post-initial vaccination showed greater antibody levels than a ChAdOx1 nCoV-19 boost (IgG: 1.1-fold, IgM: slight decrease, IgA: 1.5-fold increase). Using a combination of three analytes, IgG against wild-type Spike trimer, nucleoprotein and Omicron receptor binding domains, enabled the clustering of responses within a statistical Gaussian mixture model that successfully discriminates between breakthrough infections and vaccination types (F-score = 0.82). The development of statistical models to predict breakthrough infections can improve serological surveillance. Overall, our study underscores the necessity for vaccine (re-)development and the creation of serological tools to monitor vaccine performance
A Scoping Review of Sexual and Reproductive Health Interventions With Youth in U.S. Juvenile Facilities.
Get PDFYouth placed in U.S. juvenile detention facilities face multilevel barriers that contribute to disparate sexual and reproductive health (SRH) outcomes when compared to their peers in the general adolescent population. Minimal information is available about evidence-based interventions that have been effective in changing these outcomes. The aim of this scoping review was to focus on the current state of SRH and identify recommendations for SRH care. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews guidelines, we searched electronic databases for publications published through March 2024. The search terms were designed to find intervention studies focusing on SRH in U.S. juvenile detention facilities. Eighteen articles were identified, all of which found some combination of positive results. While some intervention content focused on SRH knowledge and attitudes, the majority of studies had sexual risk behaviors in combination with sexually transmitted infections, substance use, or partner violence as their focus. The minimal number of research interventions focused on the structurally vulnerable population of youth in detention facilities across the United States underscores a significant gap in the existing literature, with negative health outcomes for juveniles in detention facilities
How Do Early Weight Trajectories Explain Social Inequalities in Lung Function in Children With Cystic Fibrosis?: A Longitudinal Interventional Disparity Effects Analysis With Time-varying Mediators and Intermediate Confounders.
Get PDFBACKGROUND: Children with cystic fibrosis (CF) from socioeconomically deprived areas have poorer growth, worse lung function, and shorter life expectancy than their less-deprived peers. While early growth is associated with lung function around age 6, it is unclear whether improving early growth in the most deprived children reduces inequalities in lung function. METHODS: We used data from the UK CF Registry, tracking children born 2000-2010 up to 2016. We extended the interventional disparity effects approach to the setting of a longitudinally measured mediator. Applying this approach, we estimated the association between socioeconomic deprivation (children in the least vs. most deprived population quintile; exposure) and lung function at first measurement (ages 6-8, outcome), and the role of early weight trajectories (ages 0-6) as mediators of this relationship. We adjusted for baseline confounding by sex, birthyear, and genotype and time-varying intermediate confounding by lung infection. RESULTS: The study included 853 children, with 165 children from the least and 172 from the most deprived quintiles. The average lung function difference between the least and most deprived quintiles was 4.5% of predicted forced expiratory volume in 1 second (95% confidence interval: 1.1-7.9). If the distribution of early weight trajectories in the most deprived children matched that in the least deprived children, this difference would reduce to 4% (95% confidence interval: 0.57- 7.4). CONCLUSION: Socioeconomic deprivation has a strong negative association with lung function for children with CF. We estimate that improving early weight trajectories in the most deprived children would only marginally reduce these inequalities
Strengthening teamwork and respect (STAR) in maternity units: developing a health system intervention in South Africa.
Get PDFDisrespect and abuse in maternity services in South Africa has been described over several decades and are rooted in the country's complex socio-political landscape and unequal health system which places strain on public sector health professionals. Strategies to improve the quality of health care typically involve once-off didactic teaching or outside technical consultants focused on improving specific health programmes. These approaches fail to encourage self-reflection or to establish learning cultures. Participatory learning processes, embedded in routine service delivery, are a potentially powerful way to improve ownership and accountability for health system performance. We describe the process followed to develop the Strengthening Teamwork and Respect (STAR) intervention which is being implemented in nine district hospitals in two rural districts of KwaZulu-Natal. The intervention approach draws on a conceptual framework for learning health systems, with intervention strategies informed by participatory learning and action theory. The intervention design was an iterative process informed by literature reviews, formative data collection, consultation with provincial, district and hospital management stakeholders, expert reviewer inputs and piloting of proposed activities. This process produced the STAR intervention approach and toolkit, consisting of: identification and training of champions, creation of STAR teams, convening of learning sessions to work through STAR toolkit activities, identification, implementation and monitoring of change projects, and onsite and virtual mentorship from the STAR development team. Endline cross-sectional surveys and a parallel process evaluation will advance the evidence base for interventions to improve respectful care and cultures of teamwork and learning within maternity units in rural low- and middle-income settings
What is the relationship between hospital management practices and quality of care? A systematic review of the global evidence.
Get PDFThere is a widely held view that good management improves organizational performance. However, hospitals are complex organizations, and the relationship between management practices and health service delivery is not straightforward. We conducted a global, systematic literature review of the quantitative evidence on the link between the adoption of management practices and quality of care in hospitals. We searched in PubMed, EMBASE, EconLit, Global Health, and Web of Science on 16 October 2024, without language or country restrictions. We included empirical studies from 1 January 2000 onwards, examining the quantitative association between hospital management practices and quality of care. Outcomes included structural quality (availability of resources such as drugs and equipment), clinical quality (adherence to guidelines), health outcomes, and patient satisfaction or experience with care. In every study, each tested association was categorized as significantly positive (at the 5% level), null, or significantly negative. The study was registered with PROSPERO (CRD42022301462). Of 11 731 articles, 25 studies met the inclusion criteria and had an acceptable risk of bias. Studies were equally distributed between high-income and low- and middle-income countries, with 22 cross-sectional and three intervention studies. Of 111 associations, 55 (49.5%) were significantly positive, one (1%) was significantly negative, and 55 (49.5%) were null. Among the associations tested, the majority were significantly positive for structural quality (79%), clinical quality (60%), and health outcomes (57%), while most associations between hospital management and patient satisfaction (80%) were null. The findings are mixed, with a similar proportion of positive and null associations between management practices and quality of care across studies. The evidence is limited by the risk of bias introduced by nonrandomized study designs. Evidence of positive associations in some settings warrants further investigation of the association through intervention studies or natural experiments. This could leverage methodological developments in quantitatively measuring management, highlighted by this review
Visual preferences for communicating modelling: a global analysis of COVID-19 policy and decision makers.
Get PDFEffective communication of modelling results to policy and decision makers has been a longstanding challenge in times of crises. This communication takes many forms - visualisations, reports, presentations - and requires careful consideration to ensure accurate maintenance of the key scientific messages. Science-to-policy communication is further exacerbated when presenting fundamentally uncertain forms of science such as infectious disease modelling and other types of modelled evidence, something which has been understudied. Here we assess the communication and visualisation of infectious disease modelling results to national COVID-19 policy and decision makers in 13 different countries. We present a synthesis of recommendations on what aspects of visuals, graphs, and plots policymakers found to be most helpful in their COVID-19 response work. This work serves as a first evidence base for developing guidelines on the communication and translation of infectious disease modelling into policy
The effect of COVID-19 vaccination on change in contact and implications for transmission.
Get PDFBACKGROUND: Monitoring human behavior as epidemic intelligence can critically complement traditional surveillance systems during epidemics. Retrospective analysis of novel behavioral data streams initiated during the COVID-19 pandemic help illustrate their utility. During the pandemic, behavior changed rapidly and was increasingly influenced by individual choice in response to changes such as newly available vaccines. Vaccines provided substantial protection against severe disease and deaths; however, their effect on behavior is understudied and it is unclear if vaccine effects against infection fully offset relaxation of social distancing behaviors. METHODS & RESULTS: We analyzed data from a longitudinal cohort sampled from U.S. households that measured contact rates, risk mitigation and COVID-19 vaccination status between August 2020-April 2022. Contact rates universally increased across survey rounds among all sociodemographic groups, but unvaccinated individuals had persistently higher contact rates. Using a multilevel generalized linear mixed effects model, we found that individuals who newly completed a primary vaccine series had an additional increase of 1.93 (95 % CI: 0.27-3.59) contacts compared to individuals who remained unvaccinated. Using observed contact rates to estimate transmission, we found that observed increases in contact rates were not fully offset by vaccine protection against infection, but transmission was still maintained below levels without distancing and vaccination despite clusters of individuals with high contact and no vaccination. CONCLUSION: We estimated changes in contact rates following vaccination and inferred the joint effect of changes in vaccination and contacts on population-level transmission, finding that observed increases in contact rates were not fully offset by vaccine effects. Our work highlights the potential utility of ongoing longitudinal monitoring of contact patterns during epidemics
