Immunogenicity of COVID-19 vaccines in patients with follicular lymphoma receiving frontline chemoimmunotherapy.

Immune responses to primary COVID-19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016-004010-10). COVID-19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4+ T cells) or cyclophosphamide-based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS-CoV-2 spike protein using the Abbott Architect and interferon-gamma ELISpot assays respectively. Compared to 149 healthy controls, patients with FL exhibited lower antibody but preserved T-cell responses. Within the FL cohort, multivariable analysis identified low pre-treatment serum IgA levels and V2 administration during induction or maintenance treatment as independent determinants of lower antibody and higher T-cell responses, and bendamustine and high/intermediate FLIPI-2 score as additional determinants of a lower antibody response. Several clinical scenarios were identified where dichotomous immune responses were estimated with >95% confidence based on combinations of predictive variables. In conclusion, the immunogenicity of COVID-19 vaccines in FL patients is influenced by multiple disease- and treatment-related factors, among which B-cell depletion showed differential effects on antibody and T-cell responses.

Overview of the Global and US Burden of Preterm Birth.

Preterm birth (PTB) is the leading cause of morbidity and mortality in children globally, yet its prevalence has been difficult to accurately estimate due to unreliable methods of gestational age dating, heterogeneity in counting, and insufficient data. The estimated global PTB rate in 2020 was 9.9% (95% confidence interval: 9.1, 11.2), which reflects no significant change from 2010, and 81% of prematurity-related deaths occurred in Africa and Asia. PTB prevalence in the United States in 2021 was 10.5%, yet with concerning racial disparities. Few effective solutions for prematurity prevention have been identified, highlighting the importance of further research.

Estimating Gestational Age and Prediction of Preterm Birth Using Metabolomics Biomarkers.

Preterm birth (PTB) is a leading cause of morbidity and mortality in children aged under 5 years globally, especially in low-resource settings. It remains a challenge in many low-income and middle-income countries to accurately measure the true burden of PTB due to limited availability of accurate measures of gestational age (GA), first trimester ultrasound dating being the gold standard. Metabolomics biomarkers are a promising area of research that could provide tools for both early identification of high-risk pregnancies and for the estimation of GA and preterm status of newborns postnatally.

Community health worker perspectives on advocacy: design-based research to develop a digital advocacy training course.

Introduction: While community health workers (CHWs) are well-positioned as health advocates, they frequently lack support and feel undervalued. Advocacy training may prepare CHWs to support communities better. Methods: This study uses a design-based research approach to (1) explore how participation in curriculum-development workshops for a digital advocacy course influenced CHWs' (n = 25) perceptions of advocacy and (2) describe how CHW involvement shaped course development. Data were collected via five discussion groups and seven surveys over six months. Results: Initially, the CHWs perceived themselves as community-advocates but not as self-advocates. They increasingly reflected on the merits of advocating for better working conditions and aspired to greater involvement in decision-making. CHWs reflected positively on their advisory role in shaping the course to improve content acceptability and validity. Discussion: Training efforts to engage CHWs in advocacy must overcome systemic barriers and norms internalized by CHWs that deter them from reaching their full potential as advocates.

Exploring the role of community health organizations in promoting public health during a health crisis: a qualitative study of COVID-19 responses in South Africa and Zambia.

While the COVID-19 pandemic amplified the need for accurate and actionable health information, uncertainty and the proliferation of misinformation have contributed to significant mistrust in public health messages, especially among marginalized communities. Community health organizations can play an important role in creating trust and providing targeted health information to vulnerable groups. This qualitative study, which is focused on community health organizations supporting vulnerable populations in South Africa and Zambia, finds that during the pandemic, community health organizations expanded their roles and leveraged their established access and trust to support the communities they serve with health education and services. However, the reliance on external support limits the organizations' ability to respond in an effective and efficient manner during health crises.

International clinical assessment of smell: An international, cross-sectional survey of current practice in the assessment of olfaction.

OBJECTIVES: Olfactory dysfunction (OD) is common and carries significant personal and societal burden. Accurate assessment is necessary for good clinical and research practice but is highly dependent on the assessment technique used. Current practice with regards to UK/international clinical assessment is unknown. We aimed to capture current clinical practice, with reference to contemporaneously available guidelines. We further aimed to compare UK to international practice. DESIGN: Anonymous online questionnaire with cross-sectional non-probability sampling. Subgroup analysis according to subspeciality training in rhinology ('rhinologists' and 'non-rhinologists') was performed, with geographical comparisons only made according to subgroup. PARTICIPANTS: ENT surgeons who assess olfaction. RESULTS: Responses were received from 465 clinicians (217 from UK and 17 countries total). Country-specific response rate varied, with the lowest rate being obtained from Japan (1.4%) and highest from Greece (72.5%). Most UK clinicians do not perform psychophysical smell testing during any of the presented clinical scenarios-though rhinologists did so more often than non-rhinologists. The most frequent barriers to testing related to service provision (e.g., time/funding limitations). Whilst there was variability in practice, in general, international respondents performed psychophysical testing more frequently than those from the UK. Approximately 3/4 of all respondents said they would like to receive training in psychophysical smell testing. Patient reported outcome measures were infrequently used in the UK/internationally. More UK respondents performed diagnostic MRI scanning than international respondents. CONCLUSIONS: To our knowledge, this is the most comprehensive UK-based, and only international survey of clinical practice in the assessment of OD. We present recommendations to improve practice, including increased education and funding for psychophysical smell testing. We hope this will promote accurate and reliable olfactory assessment, as is the accepted standard in other sensory systems.

Characterizing Sensory Phenotypes of Subgroups with a Known Genetic Etiology Pertaining to Diagnoses of Autism Spectrum Disorder and Intellectual Disability.

We aimed to identify unique constellations of sensory phenotypes for genetic etiologies associated with diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Caregivers reported on sensory behaviors via the Sensory Profile for 290 participants (younger than 25 years of age) with ASD and/or ID diagnoses, of which ~ 70% have a known pathogenic genetic etiology. Caregivers endorsed poor registration (i.e., high sensory threshold, passive behaviors) for all genetic subgroups relative to an "idiopathic" comparison group with an ASD diagnosis and without a known genetic etiology. Genetic profiles indicated prominent sensory seeking in ADNP, CHD8, and DYRK1A, prominent sensory sensitivities in SCN2A, and fewer sensation avoidance behaviors in GRIN2B (relative to the idiopathic ASD comparison group).

The Use of Open-Source Online Course Content for Training in Public Health Emergencies: Mixed Methods Case Study of a COVID-19 Course Series for Health Professionals.

BACKGROUND: The onset of the COVID-19 pandemic generated an urgent need for credible and actionable information to guide public health responses. The massive open-source online course (MOOC) format may be a valuable path for disseminating timely and widely accessible training for health professionals during public health crises; however, the reach and effectiveness of health worker-directed online courses during the pandemic remain largely unexplored. OBJECTIVE: This study investigated the use of an open-source online course series designed to provide critical COVID-19 knowledge to frontline health workers and public health professionals globally. The study investigated how open-source online educational content can be optimized to support knowledge sharing among health professionals in public health emergencies, particularly in resource-limited contexts. METHODS: The study examined global course enrollment patterns (N=2185) and performed in-depth interviews with a purposive subsample of health professionals enrolled in the course series (N=12) to investigate the sharing of online content in pandemic responses. Interviewed learners were from Ethiopia, India, Kenya, Liberia, Malawi, Rwanda, Thailand, Uganda, the United Arab Emirates, and the United States. Inductive analysis and constant comparative methods were used to systematically code data and identify key themes emerging from interview data. RESULTS: The analysis revealed that the online course content helped fill a critical gap in trustworthy COVID-19 information for pandemic responses and was shared through health worker professional and personal networks. Enrollment patterns and qualitative data illustrate how health professionals shared information within their professional networks. While learners shared the knowledge they gained from the course, they expressed a need for contextualized information to more effectively educate others in their networks and in their communities. Due to technological and logistical barriers, participants did not attempt to adapt the content to share with others. CONCLUSIONS: This study illustrates that health professional networks can facilitate the sharing of online open-source health education content; however, to fully leverage potential benefits, additional support is required to facilitate the adaptation of course content to more effectively reach communities globally.

SARS-CoV-2 antibody responses post-vaccination in UK healthcare workers with pre-existing medical conditions: a cohort study.

OBJECTIVES: To examine antibody responses after the second vaccination in healthcare workers (HCWs) with underlying health conditions. DESIGN: Cohort study. SETTING: Oxford University Hospitals in the United Kingdom. PARTICIPANTS: Healthcare workers who had SARS-CoV-2 serological data available and received two SARS-CoV- 2 vaccinations. PRIMARY OUTCOME: Peak SARS-CoV-2 anti-spike IgG responses after the second vaccination and associations with underlying health conditions and the estimated risk of severe COVID-19 using an occupational health risk assessment tool. METHODS: We used univariable and multivariable linear regression models to investigate associations between antibody levels and demographics (age, sex, ethnicity), healthcare role, body mass index, underlying health conditions, vaccination status, prior infection and the Association of Local Authority Medical Advisors COVID-age risk score. RESULTS: 1635 HCWs had anti-spike IgG measurements 14-84 days after second vaccination and data on any underlying health conditions. Only five HCWs (0.3%), all on immunosuppressive treatment, (including four organ transplant recipients), did not seroconvert after second vaccination. Antibody levels were independently lower with older age, diabetes, immunosuppression, respiratory disorders other than asthma and markedly so in organ transplant recipients. Levels were independently lower in ChAdOx1 versus BNT162b2 recipients and higher following previous infection. HCWs with 'very high' COVID-age risk scores had lower median antibody levels than those with 'low', 'medium' or 'high' risk scores; 4379 AU/mL, compared with 12 337 AU/mL, 9430 AU/mL and 10 524 AU/mL, respectively. CONCLUSIONS: Two vaccine doses are effective in generating antibody responses among HCWs, including those with a high occupational risk. However, HCWs with underlying health conditions, especially diabetes, immunosuppression and organ transplant, had lower antibody levels, and vaccine response monitoring may be needed.

Improving the precision of maternal, newborn, and child health impact through geospatial analysis of the association of contextual and programmatic factors with health trends in Bihar, India.

Background: There is a scarcity of research that comprehensively examines programme impact from a context-specific perspective. We aimed to determine the conditions under which the Bihar Technical Support Programme led to more favourable outcomes for maternal and child health in Bihar. Methods: We obtained block-level data on maternal and child health indicators during the state-wide scale-up of the pilot Ananya programme and data on health facility readiness, along with geographical and sociodemographic variables. We examined the associations of these factors with increases in the levels of indicators using multilevel logistic regression, and the associations with rates of change in the indicators using Bayesian Hierarchical modelling. Results: Frontline worker (FLW) visits between 2014-2017 were more likely to increase in blocks with better night lighting (odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.01-1.51). Birth preparedness increased in blocks with increasing FLW visits (OR = 3.43, 95% CI = 1.15-10.21), while dry cord care practice increased in blocks where satisfaction with FLW visits was increasing (OR = 1.52, 95% CI = 1.10-2.11). Age-appropriate frequency of complementary feeding increased in blocks with higher development index (OR = 1.55, 95% CI = 1.16-2.06) and a higher percentage of scheduled caste or tribe (OR = 3.21, 95% CI = 1.13-9.09). An increase in most outcomes was more likely in areas with lower baseline levels. Conclusions: Contextual factors (eg, night lighting and development) not targeted by the programme and FLW visits were associated with favourable programme outcomes. Intervention design, including intervention selection for a particular geography, should be modified to fit the local context in the short term. Expanding collaborations beyond the health sector to influence modifiable contextual factors in the long term can result in a higher magnitude and more sustainable impact. Registration: ClinicalTrials.gov: NCT02726230.

Digital Education for Health Professionals: An Evidence Map, Conceptual Framework, and Research Agenda.

BACKGROUND: Health professions education has undergone major changes with the advent and adoption of digital technologies worldwide. OBJECTIVE: This study aims to map the existing evidence and identify gaps and research priorities to enable robust and relevant research in digital health professions education. METHODS: We searched for systematic reviews on the digital education of practicing and student health care professionals. We searched MEDLINE, Embase, Cochrane Library, Educational Research Information Center, CINAHL, and gray literature sources from January 2014 to July 2020. A total of 2 authors independently screened the studies, extracted the data, and synthesized the findings. We outlined the key characteristics of the included reviews, the quality of the evidence they synthesized, and recommendations for future research. We mapped the empirical findings and research recommendations against the newly developed conceptual framework. RESULTS: We identified 77 eligible systematic reviews. All of them included experimental studies and evaluated the effectiveness of digital education interventions in different health care disciplines or different digital education modalities. Most reviews included studies on various digital education modalities (22/77, 29%), virtual reality (19/77, 25%), and online education (10/77, 13%). Most reviews focused on health professions education in general (36/77, 47%), surgery (13/77, 17%), and nursing (11/77, 14%). The reviews mainly assessed participants' skills (51/77, 66%) and knowledge (49/77, 64%) and included data from high-income countries (53/77, 69%). Our novel conceptual framework of digital health professions education comprises 6 key domains (context, infrastructure, education, learners, research, and quality improvement) and 16 subdomains. Finally, we identified 61 unique questions for future research in these reviews; these mapped to framework domains of education (29/61, 47% recommendations), context (17/61, 28% recommendations), infrastructure (9/61, 15% recommendations), learners (3/61, 5% recommendations), and research (3/61, 5% recommendations). CONCLUSIONS: We identified a large number of research questions regarding digital education, which collectively reflect a diverse and comprehensive research agenda. Our conceptual framework will help educators and researchers plan, develop, and study digital education. More evidence from low- and middle-income countries is needed.

Lactate, Base Excess, and the Pediatric Index of Mortality: Exploratory Study of an International, Multicenter Dataset.

OBJECTIVES: To investigate the relationship between ICU admission blood lactate, base excess, and ICU mortality and to explore the effect of incorporating blood lactate into the Pediatric Index of Mortality. DESIGN: Retrospective cohort study based on data prospectively collected on every PICU admission submitted to the U.K. Pediatric Intensive Care Audit Network and to the Australia and New Zealand Pediatric Intensive Care Registry. SETTING: Thirty-three PICUs in the United Kingdom/Republic of Ireland and nine PICUs and 20 general ICUs in Australia and New Zealand. PATIENTS: All ICU admissions between January 1, 2012, and December 31, 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three thousand two hundred fifty-two admissions were recorded in both datasets; 81,576 (66.2%) in the United Kingdom/Republic of Ireland and 41,676 (33.8%) in Australia and New Zealand. Of these 75,070 (61%) had a base excess recorded, 63,316 (51%) had a lactate recorded, and 60,876 (49%) had both base excess and lactate recorded. Median lactate value was 1.5 mmol/L (interquartile range, 1-2.4 mmol/L) (United Kingdom/Republic of Ireland: 1.5 [1-2.5]; Australia and New Zealand: 1.4 [1-2.3]). Children with a lactate recorded had a higher illness severity, were more likely to be invasively ventilated, admitted after cardiac surgery, and had a higher mortality rate, compared with admissions with no lactate recorded (p < 0.001). The relationship between lactate and mortality was stronger (odds ratio, 1.32; 95% CI, 1.31-1.34) than between absolute base excess and mortality (odds ratio, 1.13; 95% CI, 1.12-1.14). Addition of lactate to the Pediatric Index of Mortality score led to a small improvement in performance over addition of absolute base excess, whereas adding both lactate and absolute base excess achieved the best performance. CONCLUSIONS: At PICU admission, blood lactate is more strongly associated with ICU mortality than absolute base excess. Adding lactate into the Pediatric Index of Mortality model may result in a small improvement in performance. Any improvement in Pediatric Index of Mortality performance must be balanced against the added burden of data capture when considering potential incorporation into the Pediatric Index of Mortality model.

Dynamic cognitive inhibition in the context of frustration: Increasing racial representation of adolescent athletes using mobile community-engaged EEG methods.

Introduction: Concussive events and other brain injuries are known to reduce cognitive inhibition, a key aspect of cognition that supports ones' behaviors and impacts regulation of mood or affect. Our primary objective is to investigate how induction of negative affect (such as frustration) impacts cognitive inhibition and the dynamic process by which youth athletes modulate responses. Secondary objective is to address the lack of Black representation in the scientific literature that promotes brain health and investigates pediatric sports-related brain injury. In particular, neuroscience studies predominantly include White participants despite broad racial representation in sport, in part due to technological hurdles and other obstacles that challenge research access for Black participants. Methods: Using electroencephalography (EEG), we evaluate the dynamic brain processes associated with cognitive inhibition in the context of frustration induction in adolescent athletes during pre-season conditioning (i.e., prior to contact; N = 23) and a subset during post-season (n = 17). Results: The N2 component was sensitive to frustration induction (decreased N2 amplitude, slower N2 latency), although effects were less robust at postseason. Trial-by-trial changes indicated a steady decrease of the N2 amplitude during the frustration block during the preseason visit, suggesting that affective interference had a dynamic effect on cognitive inhibition. Lastly, exploratory analyses provide preliminary evidence that frustration induction was less effective for athletes with a previous history of concussion or migraines (trending result) yet more effective for athletes endorsing a history with mental health disorders. Discussion: We emphasize the urgent need to improve representation in cognitive neuroscience, particularly as it pertains to brain health. Importantly, we provide detailed guides to our methodological framework and practical suggestions to improve representative participation in studies utilizing high-density mobile EEG.

Real world external validation of metabolic gestational age assessment in Kenya.

Using data from Ontario Canada, we previously developed machine learning-based algorithms incorporating newborn screening metabolites to estimate gestational age (GA). The objective of this study was to evaluate the use of these algorithms in a population of infants born in Siaya county, Kenya. Cord and heel prick samples were collected from newborns in Kenya and metabolic analysis was carried out by Newborn Screening Ontario in Ottawa, Canada. Postnatal GA estimation models were developed with data from Ontario with multivariable linear regression using ELASTIC NET regularization. Model performance was evaluated by applying the models to the data collected from Kenya and comparing model-derived estimates of GA to reference estimates from early pregnancy ultrasound. Heel prick samples were collected from 1,039 newborns from Kenya. Of these, 8.9% were born preterm and 8.5% were small for GA. Cord blood samples were also collected from 1,012 newborns. In data from heel prick samples, our best-performing model estimated GA within 9.5 days overall of reference GA [mean absolute error (MAE) 1.35 (95% CI 1.27, 1.43)]. In preterm infants and those small for GA, MAE was 2.62 (2.28, 2.99) and 1.81 (1.57, 2.07) weeks, respectively. In data from cord blood, model accuracy slightly decreased overall (MAE 1.44 (95% CI 1.36, 1.53)). Accuracy was not impacted by maternal HIV status and improved when the dating ultrasound occurred between 9 and 13 weeks of gestation, in both heel prick and cord blood data (overall MAE 1.04 (95% CI 0.87, 1.22) and 1.08 (95% CI 0.90, 1.27), respectively). The accuracy of metabolic model based GA estimates in the Kenya cohort was lower compared to our previously published validation studies, however inconsistency in the timing of reference dating ultrasounds appears to have been a contributing factor to diminished model performance.

Implementing health communication tools at scale: mobile audio messaging and paper-based job aids for front-line workers providing community health education to mothers in Bihar, India.

INTRODUCTION: As part of an investment by the Bill & Melinda Gates Foundation to support the Government of Bihar to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) statewide, BBC Media Action implemented multiple communication tools to support front-line worker (FLW) outreach. We analyse the impacts of a package of mHealth audio messaging and paper-based job aids used by FLWs during government-sponsored village health, sanitation and nutrition days (VHSNDs) on knowledge and practices of childbearing women across the RMNCHN continuum of care. METHODS: Data from two surveys collected between July and September 2016 were analysed using logistic regression to compare health-related knowledge and behaviours between women who had been exposed at VHSNDs to the mHealth GupShup Potli (GSP) audio recordings or interpersonal communication (IPC) tools versus those who were unexposed. RESULTS: Exposure to GSP recordings (n=2608) was associated with improved knowledge across all continuum-of-care domains, as well as improved health-related behaviours in some domains. The odds of having taken iron-folic acid (IFA) tablets were significantly higher in exposed women (OR 1.5, 95% CI 1.1 to 2.2), as was contraceptive use (OR 2.0, 95% CI 1.2 to 3.2). There were no differences in birth preparedness or complementary feeding practices between groups. Exposure to IPC paper-based tools (n=2002) was associated with a twofold increased odds of IFA consumption (OR 2.3, 95% CI 1.7 to 3.2) and contraceptive use (OR 1.8, 95% CI 1.2 to 2.8). Women exposed to both tools were generally at least twice as likely to subsequently discuss the messages with others. CONCLUSION: BBC Media Action's mHealth audio messaging job aids and paper-based IPC tools were associated with improved knowledge and practices of women who were exposed to them across multiple domains, suggesting their important potential for improving health outcomes for beneficiaries at scale in low-resource settings. TRIAL REGISTRATION NUMBER: NCT02726230.

Design preferences for global scale: a mixed-methods study of "glocalization" of an animated, video-based health communication intervention.

BACKGROUND: Designing health communication interventions for global scaling promotes health literacy and facilitates rapid global health messaging. Limited literature explores preferences for animation prototypes and other content characteristics across participants in different global regions. Prior research underscores an urgent need for health communication interventions that are compelling and accessible across culturally and geographically diverse audiences. This study presents feedback from global learners on animation design preferences and other key considerations for the development of educational video content intended for global adaptation and scaling. METHODS: We used a mixed-methods, sequential explanatory design, with a qualitative descriptive approach to the analysis of the qualitative data. We recruited participants from an international group of learners enrolled in a massive open online course. Through an online quantitative survey (n = 330), we sought preferences from participants in 73 countries for animation design prototypes to be used in video-based health communication interventions. To learn more about these preferences, we conducted in-depth interviews (n = 20) with participants selected using maximum variation purposive sampling. RESULTS: Generally, respondents were willing to accept animation prototypes that were free of cultural and ethnic identifiers and believed these to be preferable for globally scalable health communication videos. Diverse representations of age, gender roles, and family structure were also preferred and felt to support inclusive messaging across cultures and global regions. Familiar-sounding voiceovers using local languages, dialects, and accents were preferred for enhancing local resonance. Across global regions, narratives were highlighted as a compelling approach to facilitating engagement and participants preferred short videos with no more than two or three health messages. CONCLUSIONS: Our findings suggest that global learners may be willing to accept simplified visuals, designed for broad cross-cultural acceptability, especially if the content is localized in other ways, such as through the use of locally resonating narratives and voiceovers. Diverse, inclusive portrayals of age, gender roles and family structure were preferred.

Maternal Larp6 controls oocyte development, chorion formation and elevation.

La-related protein 6 (Larp6) is a conserved RNA-binding protein found across eukaryotes that has been suggested to regulate collagen biogenesis, muscle development, ciliogenesis, and various aspects of cell proliferation and migration. Zebrafish have two Larp6 family genes: larp6a and larp6b Viable and fertile single and double homozygous larp6a and larp6b zygotic mutants revealed no defects in muscle structure, and were indistinguishable from heterozygous or wild-type siblings. However, larp6a mutant females produced eggs with chorions that failed to elevate fully and were fragile. Eggs from larp6b single mutant females showed minor chorion defects, but chorions from eggs laid by larp6a;larp6b double mutant females were more defective than those from larp6a single mutants. Electron microscopy revealed defective chorionogenesis during oocyte development. Despite this, maternal zygotic single and double mutants were viable and fertile. Mass spectrometry analysis provided a description of chorion protein composition and revealed significant reductions in a subset of zona pellucida and lectin-type proteins between wild-type and mutant chorions that paralleled the severity of the phenotype. We conclude that Larp6 proteins are required for normal oocyte development, chorion formation and egg activation.