Complexity of avian evolution revealed by family-level genomes.

Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method and the choice of genomic regions1-3. Here we address these issues by analysing the genomes of 363 bird species4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a marked degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous-Palaeogene boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that are a challenge to model due to either extreme DNA composition, variable substitution rates, incomplete lineage sorting or complex evolutionary events such as ancient hybridization. Assessment of the effects of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates and relative brain size following the Cretaceous-Palaeogene extinction event, supporting the hypothesis that emerging ecological opportunities catalysed the diversification of modern birds. The resulting phylogenetic estimate offers fresh insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies.

A realist evaluation of the development of extended pharmacist roles and services in community pharmacies.

BACKGROUND: Internationally, community pharmacy models of care have been moving away from a focus on dispensing to extended, clinically-focused roles for pharmacists. OBJECTIVES: To identify how community pharmacy strategies were being implemented in Aotearoa New Zealand; how changes were expected to influence health and health system outcomes; what extended services were being delivered; the responses of pharmacists, other health professionals and consumers to these developments; and the contexts and mechanisms supporting the successful implementation of new community pharmacy services. METHODS: A realist evaluation methodology was employed, to explore a complex policy intervention. Realist evaluation explores the contexts (C) within which initiatives are introduced and identifies the mechanisms (M) triggered by different contexts to produce outcomes (O). Realist evaluation processes iteratively develop, test, and refine CMO configurations. In this study, initial programme theories were developed through key government and professional policy documents, then refined through key informant interviews, a survey and interviews with pharmacists and intern (pre-registration) pharmacists, and finally, 10 case studies of diverse community pharmacies. RESULTS: Four intermediate health service outcomes were identified: development of extended community pharmacist services; consumers using extended community pharmacist services; more integrated, collaborative primary health care services; and a fit-for-purpose community pharmacy workforce. Enabling and constraining contexts are detailed for each outcome, along with the mechanisms that they trigger (or inhibit). CONCLUSIONS: There are wide-ranging and disparate levers to support the further development of extended community pharmacy services. These include aligning funding with desired services, undergraduate educators and professional leaders setting expectations for the pharmacists' role in practice, and the availability of sufficient funding and time for both specific extended service accreditation and broader postgraduate training. However, no simple "fix" can be universally applied internationally, nor even in pharmacies within a single jurisdiction, to facilitate service development.

The formation of the Indo-Pacific montane avifauna.

The processes generating the earth's montane biodiversity remain a matter of debate. Two contrasting hypotheses have been advanced to explain how montane populations form: via direct colonization from other mountains, or, alternatively, via upslope range shifts from adjacent lowland areas. We seek to reconcile these apparently conflicting hypotheses by asking whether a species' ancestral geographic origin determines its mode of mountain colonization. Island-dwelling passerine birds at the faunal crossroads between Eurasia and Australo-Papua provide an ideal study system. We recover the phylogenetic relationships of the region's montane species and reconstruct their ancestral geographic ranges, elevational ranges, and migratory behavior. We also perform genomic population studies of three super-dispersive montane species/clades with broad island distributions. Eurasian-origin species populated archipelagos via direct colonization between mountains. This mode of colonization appears related to ancestral adaptations to cold and seasonal climates, specifically short-distance migration. Australo-Papuan-origin mountain populations, by contrast, evolved from lowland ancestors, and highland distribution mostly precludes their further colonization of island mountains. Our study explains much of the distributional variation within a complex biological system, and provides a synthesis of two seemingly discordant hypotheses for montane community formation.

Diversification of flowering plants in space and time.

The rapid diversification and high species richness of flowering plants is regarded as 'Darwin's second abominable mystery'. Today the global spatiotemporal pattern of plant diversification remains elusive. Using a newly generated genus-level phylogeny and global distribution data for 14,244 flowering plant genera, we describe the diversification dynamics of angiosperms through space and time. Our analyses show that diversification rates increased throughout the early Cretaceous and then slightly decreased or remained mostly stable until the end of the Cretaceous-Paleogene mass extinction event 66 million years ago. After that, diversification rates increased again towards the present. Younger genera with high diversification rates dominate temperate and dryland regions, whereas old genera with low diversification dominate the tropics. This leads to a negative correlation between spatial patterns of diversification and genus diversity. Our findings suggest that global changes since the Cenozoic shaped the patterns of flowering plant diversity and support an emerging consensus that diversification rates are higher outside the tropics.

Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.

INTRODUCTION: Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy. METHODS AND ANALYSIS: Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.

Global health security and the health-security nexus: principles, politics and praxis.

The past four decades have seen a steady rise of references to 'security' by health academics, policy-makers and practitioners, particularly in relation to threats posed by infectious disease pandemics. Yet, despite an increasingly dominant health security discourse, the many different ways in which health and security issues and actors intersect have remained largely unassessed and unpacked in current critical global health scholarship. This paper discusses the emerging and growing health-security nexus in the wake of COVID-19 and the international focus on global health security. In recognising the contested and fluid concept of health security, this paper presents two contrasting approaches to health security: neocolonial health security and universal health security. Building from this analysis, we present a novel heuristic that delineates the multiple intersections and entanglements between health and security actors and agendas to broaden our conceptualisation of global health security configurations and practices and to highlight the potential for harmful unintended consequences, the erosion of global health norms and values, and the risk of health actors being co-opted by the security sector.

COVID-19 vaccination in pregnancy: the impact of multimorbidity and smoking status on vaccine hesitancy, a cohort study of 25,111 women in Wales, UK.

BACKGROUND: Multimorbidity, smoking status, and pregnancy are identified as three risk factors associated with more severe outcomes following a SARS-CoV-2 infection, thus vaccination uptake is crucial for pregnant women living with multimorbidity and a history of smoking. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage. METHODS: This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was employed to examine and compare the length of time to vaccination uptake in pregnancy by considering multimorbidity, smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. The study also assessed the variation in uptake by multimorbidity, smoking status, and demographics, both jointly and separately for the independent conditions, using hazard ratios (HR) derived from the Cox regression model. RESULTS: Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.002). Women living with multimorbidity were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). CONCLUSION: Younger women, living without multimorbidity, current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Pregnant individuals living with multimorbidity exhibit a slight but statistically significant reduction in vaccine hesitancy towards COVID-19 during pregnancy.

Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification.

BACKGROUND: Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters. METHODS: This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims' health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome. FINDINGS: After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71·8%) were female. Within a year of a domestic abuse incident, 3650 (41·9%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1·183 [95% CI 1·053-1·329], p=0·0048), further PPN submissions after the initial referral (1·383 [1·295-1·476]; p<0·0001), injury at the scene (1·484 [1·368-1·609]; p<0·0001), assessed high risk (1·600 [1·444-1·773]; p<0·0001), referral to other agencies (1·518 [1·358-1·697]; p<0·0001), history of violence (1·229 [1·134-1·333]; p<0·0001), attempted strangulation (1·311 [1·148-1·497]; p<0·0001), and pregnancy (1·372 [1·142-1·648]; p=0·0007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident. INTERPRETATION: The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals. FUNDING: National Institute for Health Research.

Health service utilisation by quota, family-sponsored and convention refugees in their first five years in New Zealand.

OBJECTIVE: This study examines and compares health service utilisation patterns between New Zealand's (NZ) three main refugee groups and the general NZ population. METHODS: We used Statistics NZ's Integrated Data Infrastructure to identify quota, family-sponsored and convention refugees arriving in NZ (2007-2013). We analysed contact with primary care, emergency department (ED), and specialist mental health services for the first five years in NZ. Logistic regression models, adjusted for age, sex and deprivation, compared health service use between refugee groups and the general NZ population in years 1 and 5. RESULTS: Quota refugees were more likely to be enrolled and in contact with primary care and specialist mental health services in year 1 than family-sponsored and convention refugees, but differences reduced over time. All refugee groups were more likely than the general NZ population to have presented to ED in year 1. CONCLUSIONS: Quota refugees were better connected with health services in year 1 than the other two refugee groups. The types of frontline health services accessed by refugee groups differed from the general NZ population. IMPLICATIONS FOR PUBLIC HEALTH: There should be systematic and equal support across all NZ regions to help refugees (regardless of visa type) navigate the NZ health system.

The colonial legacy of herbaria.

Herbarium collections shape our understanding of Earth's flora and are crucial for addressing global change issues. Their formation, however, is not free from sociopolitical issues of immediate relevance. Despite increasing efforts addressing issues of representation and colonialism in natural history collections, herbaria have received comparatively less attention. While it has been noted that the majority of plant specimens are housed in the Global North, the extent and magnitude of this disparity have not been quantified. Here we examine the colonial legacy of botanical collections, analysing 85,621,930 specimen records and assessing survey responses from 92 herbarium collections across 39 countries. We find an inverse relationship between where plant diversity exists in nature and where it is housed in herbaria. Such disparities persist across physical and digital realms despite overt colonialism ending over half a century ago. We emphasize the need for acknowledging the colonial history of herbarium collections and implementing a more equitable global paradigm for their collection, curation and use.

Flexibly funding WHO? An analysis of its donors' voluntary contributions.

INTRODUCTION: Since the 1970s, voluntary contributions have become an increasingly important component of WHO's budget. As voluntary contributions tend to be earmarked for donor-specified programmes and projects, there are concerns that this trend has diverted focus away from WHO's strategic priorities, made coordination and attaining coherence more difficult, undermined WHO's democratic structures and given undue power to a handful of wealthy donors. In the past few years, the WHO Secretariat has pushed for donors to increase the amount of flexible funding they provide. METHODS: This paper aims to add to the literature on WHO financing by constructing and analysing a dataset based on figures extracted from WHO documents for the period 2010-21. It aims to answer two questions: who funds WHO and how flexible is that funding? RESULTS: Our analysis demonstrates that in the last decade voluntary contributions have steadily increased as a proportion of WHO's budget, from 75% at the start of the period to 88% at the end. High-income countries and donors based in high-income countries provided 90% of voluntary contributions in 2020. Surprisingly, the share of voluntary contributions provided by upper middle-income countries was consistently less than the share by lower middle-income countries. Furthermore, in terms of their share of voluntary contributions, we found that upper middle-income countries contributed the least proportion of their gross national income to WHO. CONCLUSION: We conclude that WHO remains constrained by the conditions attached to the vast majority of funding that it receives from its donors. Further work on how to flexibly fund WHO is required. We recommend that the Agile Member States Task Group on Strengthening WHO's Budgetary, Programmatic and Financing Governance continues the work of the Working Group on Sustainable Financing by focusing on the incentives that determine donor support for specified and flexible voluntary contributions.

Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.

Ankylosing spondylitis is the second most common cause of inflammatory arthritis. However, a successful diagnosis can take a decade to confirm from symptom onset (via x-rays). The aim of this study was to use machine learning methods to develop a profile of the characteristics of people who are likely to be given a diagnosis of AS in future. The Secure Anonymised Information Linkage databank was used. Patients with ankylosing spondylitis were identified using their routine data and matched with controls who had no record of a diagnosis of ankylosing spondylitis or axial spondyloarthritis. Data was analysed separately for men and women. The model was developed using feature/variable selection and principal component analysis to develop decision trees. The decision tree with the highest average F value was selected and validated with a test dataset. The model for men indicated that lower back pain, uveitis, and NSAID use under age 20 is associated with AS development. The model for women showed an older age of symptom presentation compared to men with back pain and multiple pain relief medications. The models showed good prediction (positive predictive value 70%-80%) in test data but in the general population where prevalence is very low (0.09% of the population in this dataset) the positive predictive value would be very low (0.33%-0.25%). Machine learning can be used to help profile and understand the characteristics of people who will develop AS, and in test datasets with artificially high prevalence, will perform well. However, when applied to a general population with low prevalence rates, such as that in primary care, the positive predictive value for even the best model would be 1.4%. Multiple models may be needed to narrow down the population over time to improve the predictive value and therefore reduce the time to diagnosis of ankylosing spondylitis.

Maternal and child outcomes for pregnant women with pre-existing multiple long-term conditions: protocol for an observational study in the UK.

INTRODUCTION: One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions). METHODS AND ANALYSIS: Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses. ETHICS AND DISSEMINATION: Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.

Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.

BACKGROUND: The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy. METHODS: A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy. RESULTS: During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy. CONCLUSIONS: The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.

Machine Learning in Colorectal Cancer Risk Prediction from Routinely Collected Data: A Review.

The inclusion of machine-learning-derived models in systematic reviews of risk prediction models for colorectal cancer is rare. Whilst such reviews have highlighted methodological issues and limited performance of the models included, it is unclear why machine-learning-derived models are absent and whether such models suffer similar methodological problems. This scoping review aims to identify machine-learning models, assess their methodology, and compare their performance with that found in previous reviews. A literature search of four databases was performed for colorectal cancer prediction and prognosis model publications that included at least one machine-learning model. A total of 14 publications were identified for inclusion in the scoping review. Data was extracted using an adapted CHARM checklist against which the models were benchmarked. The review found similar methodological problems with machine-learning models to that observed in systematic reviews for non-machine-learning models, although model performance was better. The inclusion of machine-learning models in systematic reviews is required, as they offer improved performance despite similar methodological omissions; however, to achieve this the methodological issues that affect many prediction models need to be addressed.

COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from SAIL and the Born-In-Wales Birth Cohort.

BACKGROUND: Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. This study aimed to (1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health record (EHR) data linkage, and (2) explore pregnant women's views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born-In-Wales Cohort). METHODS: This was a mixed-methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) Databank (Objective 1) and the Born-In-Wales Birth Cohort participants (Objective 2). Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnic group, and deprivation area was examined using hazard ratios (HR) from Cox regression. Survey respondents were women who had a baby during the COVID-19 pandemic or were pregnant between 1st November 2021 and 24th March 2022 and participating in Born-In-Wales. Codebook thematic analysis was used to generate themes from an open-ended question on the survey. RESULTS: Population-level data linkage (objective 1): Within the population cohort, 8203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, 8572 (34.1%) remained unvaccinated throughout the follow-up period, and 8336 (33.2%) received the vaccine postpartum. Younger women (< 30 years) were less likely to have the vaccine, and those living in areas of high deprivation were also less likely to have the vaccine (HR = 0.88, 95% CI 0.82 to 0.95). Asian and Other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared with White women (HR = 1.12, 95% CI 1.00 to 1.25) and (HR = 1.18, 95% CI 1.03 to 1.37) respectively. Survey responses (objective 2): 207 (69%) of participants stated that they would be happy to have the vaccine during pregnancy. The remaining 94 (31%) indicated they would not have the vaccine during pregnancy. Reasons for having the vaccine included protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy. CONCLUSION: Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation areas.

Experiences of New Zealand public health messaging while in lockdown.

OBJECTIVE: The COVID-19 pandemic has led to greater societal divides based on alignment with vaccine mandates and social distancing requirements. This paper briefly lays out the experiences of individuals in Aotearoa New Zealand related to public health messaging. METHODS: Adults in Aotearoa New Zealand participated in a mixed-methods study involving a survey (n=1,010 analysed results) and then semi-structured interviews with a subset of surveyed participants (38 participants). Results were thematically analysed. RESULTS: Participants highlighted two key areas related to public health messaging, these related to message consistency and the impact of messaging on wellbeing. Conclusions and public health implications: As the COVID-19 pandemic continues and further disrupts health service delivery and normal societal functioning, forward planning is needed to deliver more targeted messaging.

Health and household environment factors linked with early alcohol use in adolescence: a record-linked, data-driven, longitudinal cohort study.

Introduction: Early alcohol use has significant association with poor health outcomes. Individual risk factors around early alcohol use have been identified, but a holistic, data-driven investigation into health and household environmental factors on early alcohol use is yet to be undertaken. Objectives: This study aims to investigate the relationship between preceding health events, household exposures and early alcohol use during adolescence using a two-stage data-driven approach. Methods: In stage one, a study population (N = 1,072) were derived from the Millennium Cohort Study (MCS) Wales (born between 2000-2002). MCS data were first linked with electronic-health records. Factors associated with early (<=eleven years old) alcohol use were identified using feature selection and stepwise logistic regression. In stage two, analogous risk factors from MCS were recreated for whole population (N = 59,231) of children (born between 1998-2002 in the Welsh Demographic Service Dataset) using routine data to predict the alcohol-related health events in hospital or GP records. Results: Significant risk factors from stage two included poor maternal mental (adjusted odds ratio [aOR] = 1.31) and physical health (aOR = 1.25), living with someone with alcohol-related problem (aOR = 2.16), single-adult household (aOR = 1.45), ever in deprivation (aOR = 1.66), child's high hyperactivity (aOR = 3.57), and conduct disorder (aOR = 3.26). Children with health events, whose health needs are supported (e.g., are taken to the doctor), are at lower risk of early alcohol use. Conclusion: Health events of the family members and the child can act as modifiable exposures and may therefore inform the development of prevention initiatives. Families with known alcohol problems, living in deprivation, experiencing child behavioural problems and those who are not taken to the doctor are at higher risk of early drinking behaviour and should be prioritised for early years support and interventions to target problem drinking in young people.

Real-world use of an etanercept biosimilar including selective versus automatic substitution in inflammatory arthritis patients: a UK-based electronic health records study.

Objective: Biosimilars are approved as an alternative treatment to their originators. We compared the clinical outcomes of etanercept (ETN) biosimilar compared with ETN originator in real-world practice, from two local health boards in Wales with different policies on switching: automatic vs selective. Methods: Data from the Secure Anonymised Information Linkage (SAIL) databank in Wales were used to create a retrospective cohort study using linked primary and secondary care data. Patients aged ≥18 years with diagnosis codes for RA, PsA or AS were included. Outcomes included treatment failure and DAS-28 score (for RA). The local health board with a policy of automatic switching (i.e. clinician/nurse involvement not mandated) is labelled as automatic switch area, and the other, which required clinician/nurse supervision, as selective switch. Results: Of 8925 individuals with inflammatory arthritis, 13.3% (365) received ETN biosimilar and 31.5% (863) ETN originator. The treatment discontinuation rate was similar for ETN biosimilar and originator by Kaplan-Meier analysis. More biosimilar failure patients were treated in the automatic switch area (15 vs 4.8%). In the automatic switch area, 28.8% (75 of 260) of patients switched automatically from ETN originator to biosimilar compared with 10.5% (11 of 105) in the selective switch area. ETN biosimilar reduced DAS-28 by 1.6 ± 1.8 in the selective switch area vs 0.4 ± 0.6 in the automatic switch area. Conclusion: The ETN biosimilar was well tolerated. Fewer people were switched using selective policy, but this was associated with lower failure rates. Automatic switch policy led to more patients being switched and did not lead to significant worsening of disease.