Clinical Outcomes With Electronic Nudges to Increase Influenza Vaccination : A Prespecified Analysis of a Nationwide, Pragmatic, Registry-Based, Randomized Implementation Trial.

BACKGROUND: In the NUDGE-FLU (Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake) trial, electronic letters incorporating cardiovascular (CV) gain-framing and repeated messaging increased influenza vaccination by approximately 1 percentage point. OBJECTIVE: To evaluate the effects of the successful nudging interventions on downstream clinical outcomes. DESIGN: Prespecified exploratory analysis of a nationwide randomized implementation trial. (ClinicalTrials.gov: NCT05542004). SETTING: The 2022 to 2023 influenza season. PARTICIPANTS: 964 870 Danish citizens aged 65 years or older. INTERVENTION: Usual care or 9 different electronically delivered behavioral nudging letters. MEASUREMENTS: Cardiovascular, respiratory, and other clinical end points during follow-up from intervention delivery (16 September 2022) through 31 May 2023. RESULTS: The analysis set included 691 820 participants. Hospitalization for pneumonia or influenza occurred in 3354 of 346 327 (1.0%) participants in the usual care group, 396 of 38 586 (1.0%) in the CV gain-framing group (hazard ratio [HR], 1.06 [95% CI, 0.95 to 1.18]; versus usual care), and 403 of 38 231 (1.1%) in the repeated letter group (HR, 1.09 [CI, 0.98 to 1.21]; versus usual care). In the usual care group, 44 682 (12.9%) participants were hospitalized for any cause, compared with 5002 (13.0%) in the CV gain-framing group (HR, 1.00 [CI, 0.97 to 1.03]; versus usual care) and 4965 (13.0%) in the repeated letter group (HR, 1.01 [CI, 0.98 to 1.04]; versus usual care). A total of 6341 (1.8%) participants died in the usual care group, compared with 721 (1.9%) in the CV gain-framing group (HR, 1.02 [CI, 0.94 to 1.10]; versus usual care) and 646 (1.7%) in the repeated letter group (HR, 0.92 [CI, 0.85 to 1.00]; versus usual care). LIMITATION: Prespecified but exploratory analysis, potential misclassification of events in routinely collected registry data, and results may not be generalizable to other health systems or countries with other racial compositions and/or cultural or societal norms. CONCLUSION: In a prespecified exploratory analysis, modest increases in influenza vaccination rates seen with electronic nudges did not translate into observable improvements in clinical outcomes. Seasonal influenza vaccination should remain strongly recommended. PRIMARY FUNDING SOURCE: Sanofi.

Behavioural intervention to promote the uptake of planned care in urgent dental care attenders: a feasibility randomised controlled trial.

BACKGROUND: Urgent dental care may be the only place where many people, especially vulnerable groups, access care. This presents an opportunity for delivery of a behavioural intervention promoting planned dental visiting, which may help address one of the factors contributing to a socio-economic gradient in oral health. Although we know that cueing events such as having a cancer diagnosis may create a 'teachable moment' stimulating positive changes in health behaviour, we do not know whether delivering an opportunistic intervention in urgent dental care is feasible and acceptable to patients. METHODS: The feasibility study aimed to recruit 60 patients in a Dental Hospital and dental practices delivering urgent care within and outside working hours. Follow-up was by telephone, e mail and post over 4 months. RESULTS: Although the recruitment window was shortened because of COVID-19, of 47 patients assessed for eligibility, 28 were enrolled (70.1% of screened patients provided consent). A relatively high proportion were from disadvantaged backgrounds (46.4%, 13/28 receiving State benefits). Retention was 82.1% (23/28), which was also the rate of completion of the Oral Health Impact Profile co-primary outcome. The other primary outcome involved linking participant details at recruitment, with centrally-held data on services provided, with 84.6% (22/26) records partly or fully successfully matched. All intervention participants received at least some of the intervention, although we identified aspects of dental nurse training which would improve intervention fidelity. CONCLUSIONS: Despite recruitment being impacted by the pandemic, when the majority of clinical trials experienced reduced rates of recruitment, we found a high recruitment and consenting rate, even though patients were approached opportunistically to be enrolled in the trial and potentially receive an intervention. Retention rates were also high even though a relatively high proportion had a low socio-economic background. Therefore, even though patients may be in pain, and had not anticipated involvement before their urgent care visit, the study indicated that this was a feasible and acceptable setting in which to position an opportunistic intervention. This has the potential to harness the potential of the 'teachable moment' in people's lives, and provide support to help address health inequalities. TRIAL REGISTRATION: ISRCTN 10,853,330 07/10/2019.

Effectiveness of high-dose versus standard-dose quadrivalent influenza vaccine against recurrent hospitalizations and mortality in relation to influenza circulation: A post-hoc analysis of the DANFLU-1 randomized clinical trial.

OBJECTIVES: To evaluate the relative effectiveness of high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) against recurrent hospitalizations and its potential variation in relation to influenza circulation. METHODS: We did a post-hoc analysis of a pragmatic, open-label, randomized trial of QIV-HD versus QIV-SD performed during the 2021-2022 influenza season among adults aged 65-79 years. Participants were enrolled in October 2021-November, 2021 and followed for outcomes from 14 days postvaccination until 31 May, 2022. We investigated the following outcomes: Hospitalizations for pneumonia or influenza, respiratory hospitalizations, cardio-respiratory hospitalizations, cardiovascular hospitalizations, all-cause hospitalizations, and all-cause death. Outcomes were analysed as recurrent events. Cumulative numbers of events were assessed weekly. Cumulative relative effectiveness estimates were calculated and descriptively compared with influenza circulation. The trial is registered at Clinicaltrials.gov: NCT05048589. RESULTS: Among 12,477 randomly assigned participants, receiving QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza (10 vs. 33 events, incidence rate ratio [IRR] 0.30 [95% CI, 0.14-0.64]; p 0.002) and all-cause hospitalizations (647 vs. 742 events, IRR 0.87 [95% CI, 0.76-0.99]; p 0.032) compared with QIV-SD. Trends favouring QIV-HD were consistently observed over time including in the period before active influenza transmission; i.e. while the first week with a ≥10% influenza test positivity rate was calendar week 10, 2022, the first statistically significant reduction in hospitalizations for pneumonia or influenza was already observed by calendar week 3, 2022 (5 vs. 15 events, IRR 0.33 [95% CI, 0.11-0.94]; p 0.037). DISCUSSION: In a post-hoc analysis, QIV-HD was associated with lower incidence rates of hospitalizations for pneumonia or influenza and all-cause hospitalizations compared with QIV-SD, with trends evident independent of influenza circulation levels. Our exploratory results correspond to a number needed to treat of 65 (95% CI 35-840) persons vaccinated with QIV-HD compared with QIV-SD to prevent one additional all-cause hospitalization per season. Further research is needed to confirm these hypothesis-generating findings.

Release of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation.

Histone modifications influence the recruitment of reader proteins to chromosomes to regulate events including transcription and cell division. The idea of a histone code, where combinations of modifications specify unique downstream functions, is widely accepted and can be demonstrated in vitro. For example, on synthetic peptides, phosphorylation of Histone H3 at threonine-3 (H3T3ph) prevents the binding of reader proteins that recognize trimethylation of the adjacent lysine-4 (H3K4me3), including the TAF3 component of TFIID. To study these combinatorial effects in cells, we analyzed the genome-wide distribution of H3T3ph and H3K4me2/3 during mitosis. We find that H3T3ph anti-correlates with adjacent H3K4me2/3 in cells, and that the PHD domain of TAF3 can bind H3K4me2/3 in isolated mitotic chromatin despite the presence of H3T3ph. Unlike in vitro, H3K4 readers are still displaced from chromosomes in mitosis in Haspin-depleted cells lacking H3T3ph. H3T3ph is therefore unlikely to be responsible for transcriptional downregulation during cell division.

Does the Self-Reported Behavioural Automaticity Index provide a valid measure of toothbrushing behaviour in adults?

BACKGROUND: Studies to promote regular toothbrushing usually rely on self-reports of toothbrushing frequency (SRF). However, toothbrushing frequency measures may be open to responder bias since twice-daily toothbrushing is a commonly accepted social norm. The validity of SRF measures is unclear, meaning that their use as outcomes in interventional work may be flawed. The study's aim was to compare two different self-reported toothbrushing measures: SRF and the Self-Reported Behavioural Automaticity Index (SRBAI); with measurement of observed toothbrushing frequency tracked over 6 weeks. A secondary aim was to explore the interaction effect of various moderators (age, ethnicity, socioeconomic status (SES), sex, self-efficacy, participant personality and routine preference) upon the correlation between SRBAI and observed toothbrushing frequency. METHODS: One hundred and sixty-four adults were recruited via a number of different community groups and workplaces outside the dental setting. After consent, participants completed a questionnaire which collected demographic and participant characteristics measures (age, ethnicity, SES, sex, self-efficacy, participant personality and routine preference) and self-reported toothbrushing habits. Participants then attached a 'Brushlink' device to their toothbrush for 6 weeks to track their observed toothbrushing frequency. RESULTS: Using the Pearson correlation coefficient, a moderately strong positive linear association (r = 0.65) between SRBAI and observed toothbrushing frequency was found. By comparison, the correlation between SRF and observed toothbrushing frequency was weak (r = 0.39). There was a weak positive association between self-reported behaviour frequency and SRBAI score (r = 0.35). Using multivariable linear regression, no statistically significant interactional effect was demonstrated for any moderator variable upon the correlation coefficient of SRBAI and observed toothbrushing frequency. CONCLUSIONS: The SRBAI provided a stronger association with observed toothbrushing frequency than the SRF measure. A moderately strong relationship between SRBAI and observed toothbrushing frequency was found, compared to a weak positive relationship between self-reported behaviour frequency and SRBAI score. This suggests that the SRBAI score could be a suitable proxy to measure observed toothbrushing behaviour and preferable to SRF in interventional work.

Antimicrobial and Adjuvant Potencies of Di-n-alkyl Substituted Diazalariat Ethers.

Lariat ethers are macrocyclic polyethers-crown ethers-to which sidearms are appended. 4,13-Diaza-18-crown-6 having twin alkyl chains at the nitrogens show biological activity. They exhibit antibiotic activity, but when co-administered at with an FDA-approved antibiotic, the latter's potency is often strongly enhanced. Potency enhancements and resistance reversals have been documented in vitro for a range of Gram-negative and Gram-positive bacteria with a variety of antimicrobials. Strains of E. coli and Staphylococcus aureus having resistance to a range of drugs have been studied and the potency enhancements (checkerboards) are reported here. Drugs included in the present study are ampicillin, cefepime, chlortetracycline, ciprofloxacin, doxycycline, kanamycin, minocycline, norfloxacin, oxycycline, penicillin G, and tetracycline. Enhancements of norfloxacin potency against S. aureus 1199B of up to 128-fold were observed. The properties of these lariat ethers have been studied to determine solubility, their membrane penetration, cytotoxicity and mammalian cell survival, and their effect on bacterial efflux pumps. It is shown that in some cases, the lariat ethers have complex antimicrobials with considerable selectivity. Based on these observations, including 1:1 complexation between lariat ethers and antimicrobials and the cytotoxicity of the MeI salts showing a separation index of 32-fold, they hold significant potential for further development.

"Out of the blue": A qualitative study exploring the experiences of women and next of kin receiving unexpected results from BRA-STRAP research gene panel testing.

In the genomic era, the availability of gene panel and whole genome/exome sequencing is rapidly increasing. Opportunities for providing former patients with new genetic information are also increasing over time and recontacting former patients with new information is likely to become more common. Breast cancer Refined Analysis of Sequence Tests-Risk And Penetrance (BRA-STRAP) is an Australian study of individuals who had previously undertaken BRCA1 and BRCA2 genetic testing, with no pathogenic variants detected. Using a waiver of consent, stored DNA samples were retested using a breast/ovarian cancer gene panel and clinically significant results returned to the patient (or next of kin, if deceased). This qualitative study aimed to explore patient experiences, opinions, and expectations of recontacting in the Australian hereditary cancer setting. Participants were familial cancer clinic patients (or next of kin) who were notified of a new pathogenic variant identified via BRA-STRAP. In-depth, semi-structured interviews were conducted approximately 6 weeks post-result. Interviews were transcribed verbatim and analyzed using an inductive thematic approach. Thirty participants (all female; average age = 57; range 36-84) were interviewed. Twenty-five were probands, and five were next of kin. Most women reported initial shock upon being recontacted with unexpected news, after having obtained a sense of closure related to their initial genetic testing experiences and cancer diagnosis. For most, this initial distress was short-lived, followed by a process of readjustment, meaning-making and adaptation that was facilitated by perceived clinical and personal utility of the information. Women were overall satisfied with the waiver of consent approach and recontacting process. Results are in line with previous studies suggesting that patients have positive attitudes about recontacting. Women in this study valued new genetic information gained from retesting and were satisfied with the BRA-STRAP recontact model. Practice implications to facilitate readjustment and promote psychosocial adaptation were identified.

Developmental progression of the nasopharyngeal microbiome during childhood and association with the lower airway microbiome.

Background: The upper (URT) and lower (LRT) respiratory tract feature distinct environments and responses affecting microbial colonization but investigating the relationship between them is technically challenging. We aimed to identify relationships between taxa colonizing the URT and LRT and explore their relationship with development during childhood. Methods: We employed V4 16S rDNA sequencing to profile nasopharyngeal swabs and tracheal aspirates collected from 183 subjects between 20 weeks and 18 years of age. These samples were collected prior to elective procedures at the Children's Hospital of Philadelphia over the course of 20 weeks in 2020, from otherwise healthy subjects enrolled in a study investigating potential reservoirs of SARS-CoV-2. Findings: After extraction, sequencing, and quality control, we studied the remaining 124 nasopharyngeal swabs and 98 tracheal aspirates, including 85 subject-matched pairs of samples. V4 16S rDNA sequencing revealed that the nasopharynx is colonized by few, highly-abundant taxa, while the tracheal aspirates feature a diverse assembly of microbes. While no taxa co-occur in the URT and LRT of the same subject, clusters of microbiomes in the URT correlate with clusters of microbiomes in the LRT. The clusters identified in the URT correlate with subject age across childhood development. Interpretations: The correlation between clusters of taxa across sites may suggest a mutual influence from either a third site, such as the oropharynx, or host-extrinsic, environmental features. The identification of a pattern of upper respiratory microbiota development across the first 18 years of life suggests that the patterns observed in early childhood may extend beyond the early life window.

Introgression underlies phylogenetic uncertainty but not parallel plumage evolution in a recent songbird radiation.

Instances of parallel phenotypic evolution offer great opportunities to understand the evolutionary processes underlying phenotypic changes. However, confirming parallel phenotypic evolution and studying its causes requires a robust phylogenetic framework. One such example is the "black-and-white wagtails", a group of five species in the songbird genus Motacilla: one species, Motacilla alba, shows wide intra-specific plumage variation, while the four others form two pairs of very similar-looking species (M. aguimp + M. samveasnae and M. grandis + M. maderaspatensis, respectively). However, the two species in each of these pairs were not recovered as sisters in previous phylogenetic inferences. Their relationships varied depending on the markers used, suggesting that gene tree heterogeneity might have hampered accurate phylogenetic inference. Here, we use whole genome resequencing data to explore the phylogenetic relationships within this group, with a special emphasis on characterizing the extent of gene tree heterogeneity and its underlying causes. We first used multispecies coalescent methods to generate a "complete evidence" phylogenetic hypothesis based on genome-wide variants, while accounting for incomplete lineage sorting (ILS) and introgression. We then investigated the variation in phylogenetic signal across the genome, to quantify the extent of discordance across genomic regions, and test its underlying causes. We found that wagtail genomes are mosaics of regions supporting variable genealogies, because of ILS and inter-specific introgression. The most common topology across the genome, supporting M. alba and M. aguimp as sister species, appears to be influenced by ancient introgression. Additionally, we inferred another ancient introgression event, between M. alba and M. grandis. By combining results from multiple analyses, we propose a phylogenetic network for the black-and-white wagtails that confirms that similar phenotypes evolved in non-sister lineages, supporting parallel plumage evolution. Furthermore, the inferred reticulations do not connect species with similar plumage coloration, suggesting that introgression does not underlie parallel plumage evolution in this group. Our results demonstrate the importance of investigation of genome-wide patterns of gene tree heterogeneity to help understanding the mechanisms underlying phenotypic evolution.

The potential health and economic impacts of new tuberculosis vaccines under varying delivery strategies in Delhi and Gujarat, India: a modelling study.

Background: India has the largest tuberculosis burden globally, but this burden varies nationwide. All-age tuberculosis prevalence in 2021 ranged from 747/100,000 in Delhi to 137/100,000 in Gujarat. Previous modelling has demonstrated the benefits and costs of introducing novel tuberculosis vaccines in India overall. However, no studies have compared the potential impact of tuberculosis vaccines in regions within India with differing tuberculosis disease and infection prevalence. We used mathematical modelling to investigate how the health and economic impact of two potential tuberculosis vaccines, M72/AS01E and BCG-revaccination, could differ in Delhi and Gujarat under varying delivery strategies. Methods: We applied a compartmental tuberculosis model separately for Delhi (higher disease and infection prevalence) and Gujarat (lower disease and infection prevalence), and projected epidemiological trends to 2050 assuming no new vaccine introduction. We simulated M72/AS01E and BCG-revaccination scenarios varying target ages and vaccine characteristics. We estimated cumulative cases, deaths, and disability-adjusted life years averted between 2025-2050 compared to the no-new-vaccine scenario and compared incremental cost-effectiveness ratios to three cost-effectiveness thresholds. Results: M72/AS01E averted a higher proportion of tuberculosis cases than BCG-revaccination in both regions (Delhi: 16.0% vs 8.3%, Gujarat: 8.5% vs 5.1%) and had higher vaccination costs (Delhi: USD$118 million vs USD$27 million, Gujarat: US$366 million vs US$97 million). M72/AS01E in Delhi could be cost-effective, or even cost-saving, for all modelled vaccine characteristics. M72/AS01E could be cost-effective in Gujarat, unless efficacy was assumed only for those with current infection at vaccination. BCG-revaccination could be cost-effective, or cost-saving, in both regions for all modelled vaccine scenarios. Discussion: M72/AS01E and BCG-revaccination could be impactful and cost-effective in Delhi and Gujarat. Differences in impact, costs, and cost-effectiveness between vaccines and regions, were determined partly by differences in disease and infection prevalence, and demography. Age-specific regional estimates of infection prevalence could help to inform delivery strategies for vaccines that may only be effective in people with a particular infection status. Evidence on the mechanism of effect of M72/AS01E and its effectiveness in uninfected individuals, which were important drivers of impact and cost-effectiveness, particularly in Gujarat, are also key to improve estimates of population-level impact.

Screening of atrial fibrillation in dental practices: a qualitative feasibility study.

OBJECTIVES: To increase the detection of unknown atrial fibrillation (AF), general practitioners have started screening their patients using small hand-held devices. It is thought that dental settings could be utilized for screening as they have regular access to patients. The aim of this study was to explore the perceptions of dental staff of screening for AF using a hand-held electronic device in primary dental care. METHODS: The research took place in one large mixed NHS and private general dental practice. Views from staff including dentists, dental therapists, dental nurses, and managers were elicited via semi-structured interviews conducted face-to-face, audio recorded, and transcribed verbatim. Interviews continued until there were no new themes or patterns emerging from the data, and thematic saturation had been achieved. RESULTS: Eleven participants were interviewed. The main themes generated were methodology for screening, acceptability for screening within the practice, attitudes to screening, and implementation of screening. Overall, participants were positive about implementing AF screening in a dental practice but expressed concerns about time and remuneration. Staff also gave encouraging feedback regarding the simplicity of the portable screening device. CONCLUSIONS: Participants felt that AF screening in primary care dental practices was a good concept but may be challenging to implement in NHS Dentistry, especially due to the pandemic.

A two-arm, randomised feasibility trial using link workers to improve dental visiting in people with severe mental illness: a protocol paper.

BACKGROUND: People with severe mental illness (e.g. psychosis, bipolar disorder) experience poor oral health compared to the general population as shown by more decayed, missing and filled teeth and a higher prevalence of periodontal disease. Attending dental services allows treatment of oral health problems and support for prevention. However, people with severe mental illness face multiple barriers to attending routine dental appointments and often struggle to access care. Link work interventions use non-clinical support staff to afford vulnerable populations the capacity, opportunity, and motivation to navigate use of services. The authors have co-developed with service users a link work intervention for supporting people with severe mental illness to access routine dental appointments. The Mouth Matters in Mental Health Study aims to explore the feasibility and acceptability of this intervention within the context of a feasibility randomised controlled trial (RCT) measuring outcomes related to the recruitment of participants, completion of assessments, and adherence to the intervention. The trial will closely monitor the safety of the intervention and trial procedures. METHODS: A feasibility RCT with 1:1 allocation to two arms: treatment as usual (control) or treatment as usual plus a link work intervention (treatment). The intervention consists of six sessions with a link worker over 9 months. Participants will be adults with severe mental illness receiving clinical input from secondary care mental health service and who have not attended a planned dental appointment in the past 3 years. Assessments will take place at baseline and after 9 months. The target recruitment total is 84 participants from across three NHS Trusts. A subset of participants and key stakeholders will complete qualitative interviews to explore the acceptability of the intervention and trial procedures. DISCUSSION: The link work intervention aims to improve dental access and reduce oral health inequalities in people with severe mental illness. There is a dearth of research relating to interventions that attempt to improve oral health outcomes in people with mental illness and the collected feasibility data will offer insights into this important area. TRIAL REGISTRATION: The trial was preregistered on ISRCTN (ISRCTN13650779) and ClinicalTrials.gov (NCT05545228).

Multimodal, broadly neutralizing antibodies against SARS-CoV-2 identified by high-throughput native pairing of BCRs from bulk B cells.

TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. We adapted our previously described pairSEQ technology to pair B cell receptor heavy and light chains of SARS-CoV-2 spike protein-binding antibodies derived from enriched antigen-specific memory B cells and bulk antibody-secreting cells. We identified approximately 60,000 productive, in-frame, paired antibody sequences, from which 2,093 antibodies were selected for functional evaluation based on abundance, isotype and patterns of somatic hypermutation. The exceptionally diverse antibodies included RBD-binders with broad neutralizing activity against SARS-CoV-2 variants, and S2-binders with broad specificity against betacoronaviruses and the ability to block membrane fusion. A subset of these RBD- and S2-binding antibodies demonstrated robust protection against challenge in hamster and mouse models. This high-throughput approach can accelerate discovery of diverse, multifunctional antibodies against any target of interest.

New tuberculosis vaccines in India: modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01E and BCG-revaccination.

BACKGROUND: India had an estimated 2.9 million tuberculosis cases and 506 thousand deaths in 2021. Novel vaccines effective in adolescents and adults could reduce this burden. M72/AS01E and BCG-revaccination have recently completed phase IIb trials and estimates of their population-level impact are needed. We estimated the potential health and economic impact of M72/AS01E and BCG-revaccination in India and investigated the impact of variation in vaccine characteristics and delivery strategies. METHODS: We developed an age-stratified compartmental tuberculosis transmission model for India calibrated to country-specific epidemiology. We projected baseline epidemiology to 2050 assuming no-new-vaccine introduction, and M72/AS01E and BCG-revaccination scenarios over 2025-2050 exploring uncertainty in product characteristics (vaccine efficacy, mechanism of effect, infection status required for vaccine efficacy, duration of protection) and implementation (achieved vaccine coverage and ages targeted). We estimated reductions in tuberculosis cases and deaths by each scenario compared to the no-new-vaccine baseline, as well as costs and cost-effectiveness from health-system and societal perspectives. RESULTS: M72/AS01E scenarios were predicted to avert 40% more tuberculosis cases and deaths by 2050 compared to BCG-revaccination scenarios. Cost-effectiveness ratios for M72/AS01E vaccines were around seven times higher than BCG-revaccination, but nearly all scenarios were cost-effective. The estimated average incremental cost was US$190 million for M72/AS01E and US$23 million for BCG-revaccination per year. Sources of uncertainty included whether M72/AS01E was efficacious in uninfected individuals at vaccination, and if BCG-revaccination could prevent disease. CONCLUSIONS: M72/AS01E and BCG-revaccination could be impactful and cost-effective in India. However, there is great uncertainty in impact, especially given the unknowns surrounding the mechanism of effect and infection status required for vaccine efficacy. Greater investment in vaccine development and delivery is needed to resolve these unknowns in vaccine product characteristics.

Years of life lost to drug overdose in the Latinx community during the most recent wave of overdose deaths.

BACKGROUND AND OBJECTIVES: This study estimated years of life lost (YLL) among US Latinx individuals during the most recent wave of drug overdose deaths. METHODS: A serial cross-sectional study of YLL (life expectancy minus age at death) from death certificate records of Latinx individuals who died from drug overdoses from 2015 to mid-2022. RESULTS: Over the study period, 58,209 Latinx individuals aged 15-64 years died from drug overdoses resulting in 2,266,784 YLL. Age-group YLL differences remained stable, but gender YLL trajectories diverged. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This study extends our understanding of the immense loss to Latinx communities from preventable drug deaths.

A self-guided curriculum on endocrinology standard of care for gender diverse youth, including ethical considerations.

Objective: While the field of pediatric endocrinology, and the American Board of Pediatrics, continues expanding training to include gender-affirming care, many pediatric endocrinology fellowship programs do not have formal curriculum for this patient population. Members of the Pediatric Endocrine Society (PES) that have a special interest in transgender health designed a curriculum based on Endocrine Society practice guidelines to expand the knowledge of gender affirming care for medical trainees' and faculty. Methods: PES members designed a 5-part self-guided educational module series with embedded knowledge questions. Uniquely, medical ethical reflections were included within each module. Participants completed baseline demographic and baseline and follow-up knowledge surveys. Results: Most participants were pediatric endocrinology fellows and 44 % percent (n = 21) completed all study components, including the follow up knowledge survey. Knowledge question data analysis demonstrated knowledge gained in medical management of pubertal youth and surgical interventions. Conclusion: This is the first medical education curriculum in gender-affirming care created by pediatric endocrinologists grounded in the Endocrine Society practice guidelines. This study demonstrates medical knowledge gained in caring for gender diverse youth and is the first to incorporate ethical considerations for this patient population. While initially designed for pediatric endocrinology trainees and faculty, this curriculum may be of great utility for any provider interested in caring for gender diverse youth.

Prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) in Saudi Arabia: Systematic Review and Meta-analysis.

Liver disease is fast emerging as a global health priority. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries, with an increasing prevalence associated with the rising prevalence of diabetes mellitus and obesity. The worldwide prevalence of NAFLD may be in the order of 25%, but in the Middle East, it may be even higher. This study aimed to estimate the prevalence of NAFLD in the Kingdom of Saudi Arabia (KSA). A systematic review and meta-analysis were undertaken. Electronic searches were carried out through Medline, EMBASE, CINAHL, Web of Science, and Google Scholar, for articles from inception to April 2020. Studies conducted on adult populations in any setting reporting NAFLD prevalence were included. Pooled proportions and associated 95% confidence intervals (CIs) were presented in forest plots using a random effect model. Eight studies, including 4045 participants, were included. The pooled prevalence of NAFLD among all adult populations in KSA was 16.8% (11.1%-22.5%). Amongst those with type 2 diabetes, the prevalence was 58.0% (45.0%-70.9%). There were no true general population studies of the prevalence of NAFLD in KSA available. This review suggests that NAFLD is common in the KSA, and that type 2 diabetes is a risk factor in KSA as identified elsewhere in the world.

Dissecting the regulatory network of transcription factors in T cell phenotype/functioning during GVHD and GVT.

Transcription factors play a major role in regulation and orchestration of immune responses. The immunological context of the response can alter the regulatory networks required for proper functioning. While these networks have been well-studied in canonical immune contexts like infection, the transcription factor landscape during alloactivation remains unclear. This review addresses how transcription factors contribute to the functioning of mature alloactivated T cells. This review will also examine how these factors form a regulatory network to control alloresponses, with a focus specifically on those factors expressed by and controlling activity of T cells of the various subsets involved in graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) responses.

Trends and inequalities in realised access to NHS primary care dental services in England before, during and throughout recovery from the COVID-19 pandemic.

Introduction The COVID-19 pandemic triggered unprecedented disruption to NHS dental services in England. This work describes changes in realised access to NHS primary care dental services between 2019 and 2022, with a particular focus on geographic and deprivation-based inequalities.Methods Data from the NHS Business Services Authority and Office for National Statistics were combined to calculate the proportion of resident populations utilising NHS primary care dental services. These data were compared over multiple six-monthly time periods between 2019 and 2022, across several levels of geography and by quintiles of area-level deprivation.Results The proportion of the England population utilising services fell substantially after the start of the COVID-19 pandemic, recovering to 75-80% of pre-pandemic levels in the first half of 2022. Substantial geographic variation was observed in the pre-pandemic time points and re-emerged as the recovery period progressed. Deprivation-based inequalities in service use were persistently present, although these were consistently greater in child than adult populations. While inequalities for children increased in the initial post-pandemic period, this pattern returned almost to pre-pandemic levels by 2022.Conclusions Socioeconomic inequalities and geographic variations in the use of NHS primary care dental services, seen before the COVID-19 pandemic, have re-emerged afterwards.