Investigating the air quality surrounding new schools in England: polluted playgrounds and school buildings are a source of avoidable harm.

OBJECTIVE: To assess levels of pollutants at the sites of new schools and whether pupils are likely to be protected from associated risks. SETTING: Air pollution causes damage to children's health by increasing respiratory tract infection rates, asthma exacerbations, allergies and childhood cancers. Further effects include poorer neurocognitive outcomes and multisystemic illness in adulthood. DESIGN: We obtained a list of all 187 proposed new schools in England from 2017 to 2025 and found locations for 147 of them. We assessed air quality against WHO air quality targets and the air quality percentile of the location relative to pollution levels across the UK. We review relevant legislation and guidance. RESULTS: Our analysis found 86% of new schools (126/147) exceeded all three WHO targets, and every location exceeded at least one. Nationally, 76% (112/147) of sites were in the 60th or greater pollution percentile. Within London, the median pollution percentile was the 90th, with a minimum of 76th and maximum of 99th (IQR=83 rd to 94th). CONCLUSION: The guidance for school proposals does not include any requirement to assess air quality at the identified site. Building regulations also fail to consider how widespread poor air quality is, and significantly underestimates the levels of major air pollutants surrounding schools. Therefore it is unlikely that adequate action to reduce pupil and staff exposure is undertaken.We argue that air quality assessment should be mandatory at the proposal and planning stage of any new school building and that national guidance and legislation urgently needs to be updated.

Acute kidney injury in patients receiving immune checkpoint inhibitors: a retrospective real-world study.

BACKGROUND: Immune checkpoint inhibitors (ICPi) can cause immune-related adverse events (irAEs) including acute kidney injury (AKI). We investigated the incidence of ICPi-associated AKI (ICPi-AKI) and AKI from other causes (non-ICPi-AKI) in cancer patients treated with ICPi. METHODS: This was a single-centre retrospective cohort study of patients receiving ICPi therapy between December 2011 and August 2020. AKI was defined and staged by the Kidney Disease Improving Global Outcomes creatinine criteria. The primary outcome was the incidence of AKI and ICPi-AKI. RESULTS: A total of 1037 patients were included in the final analysis. The median age was 63 years, 60% were male, and 22% had pre-existing chronic kidney disease. Overall, 189 patients (18.2%) developed AKI of whom 37 patients (3.6%) had ICPi-AKI. In patients with progressive cancer, AKI was not associated with increased mortality. In treatment responders, non-ICPi-AKI was associated with an increased risk of mortality (adjusted hazard ratio [HR] 2.03; 95% confidence interval [CI] 1.12-3.67), whereas ICPi-AKI was not linked to an increased risk of death (adjusted HR 0.60; 95% CI 0.18-1.96). Patients with ICPi-AKI were more likely to have higher AKI stages and less likely to have complete kidney recovery compared with non-ICPi-AKI (54% versus 79%, p = 0.01). CONCLUSION: AKI was common in cancer patients treated with ICPi. Patients with ICPi-AKI had worse kidney outcomes compared to those with AKI from other causes. However, non-ICPi-AKI was associated with a higher risk of death. These findings emphasise the importance of identifying different sub-phenotypes of AKI.

Cervical cerclage technique: what do experts actually achieve?

BACKGROUND: Cervical cerclage is a recognized intervention in the management of women at risk of preterm birth and midtrimester loss. The mechanism of action of cerclage is unclear, and the technique has been poorly researched. OBJECTIVE: This study aimed to evaluate cerclage technique among experienced obstetricians, using a previously developed and evaluated cerclage simulator. STUDY DESIGN: This prospective experimental simulation and observational study used identical simulators for 28 consultant obstetricians who were asked to perform their normal cerclage. Suture type, height, knot site, and free thread length were recorded. Using computed tomography, depth of bite and tension (by reduction in area of cervix) were calculated. RESULTS: A total of 52 cervical cerclages were completed (Mersilene tape, n=20; monofilament suture, n=32). Mean suture height was 33 mm (standard deviation, 7.7 mm), greater with monofilament suture than with Mersilene tape, and associated with smaller needle size. Mean depth of bite and mean reduction of starting area did not differ by suture type. Seven procedures showed ≥1 suture bite that had entered the cervical canal once or more. CONCLUSION: This study assessed cerclage technique of experienced obstetricians using simulators and computed tomography imaging, and demonstrated wide variation in technique; this may affect the efficacy of the procedure. Further work should establish optimal technique and consensus for training and clinical practice.

Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).

BACKGROUND: The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described. METHODS: We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders. RESULTS: Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31). CONCLUSIONS: Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant. STUDY REGISTRATION NUMBER: NCT04330599.

Determinants of Antibody Responses to SARS-CoV-2 Vaccines: Population-Based Longitudinal Study (COVIDENCE UK).

Antibody responses to SARS-CoV-2 vaccines vary for reasons that remain poorly understood. A range of sociodemographic, behavioural, clinical, pharmacologic and nutritional factors could explain these differences. To investigate this hypothesis, we tested for presence of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies before and after 2 doses of ChAdOx1 nCoV-19 (ChAdOx1, AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine between December 2020 and July 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacologic and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Additionally, percentage differences in antibody titres between groups were estimated in the sub-set of participants who were seropositive post-vaccination using linear regression. Anti-spike antibodies were undetectable in 378/9101 (4.2%) participants at a median of 8.6 weeks post second vaccine dose. Increased risk of post-vaccination seronegativity associated with administration of ChAdOx1 vs. BNT162b2 (adjusted odds ratio (aOR) 6.6, 95% CI 4.2−10.4), shorter interval between vaccine doses (aOR 1.6, 1.2−2.1, 6−10 vs. >10 weeks), poor vs. excellent general health (aOR 3.1, 1.4−7.0), immunodeficiency (aOR 6.5, 2.5−16.6) and immunosuppressant use (aOR 3.7, 2.4−5.7). Odds of seronegativity were lower for participants who were SARS-CoV-2 seropositive pre-vaccination (aOR 0.2, 0.0−0.6) and for those taking vitamin D supplements (aOR 0.7, 0.5−0.9). Serologic responses to vaccination did not associate with time of day of vaccine administration, lifestyle factors including tobacco smoking, alcohol intake and sleep, or use of anti-pyretics for management of reactive symptoms after vaccination. In a sub-set of 8727 individuals who were seropositive post-vaccination, lower antibody titres associated with administration of ChAdOx1 vs. BNT162b2 (43.4% lower, 41.8−44.8), longer duration between second vaccine dose and sampling (12.7% lower, 8.2−16.9, for 9−16 weeks vs. 2−4 weeks), shorter interval between vaccine doses (10.4% lower, 3.7−16.7, for <6 weeks vs. >10 weeks), receiving a second vaccine dose in October−December vs. April−June (47.7% lower, 11.4−69.1), older age (3.3% lower per 10-year increase in age, 2.1−4.6), and hypertension (4.1% lower, 1.1−6.9). Higher antibody titres associated with South Asian ethnicity (16.2% higher, 3.0−31.1, vs. White ethnicity) or Mixed/Multiple/Other ethnicity (11.8% higher, 2.9−21.6, vs. White ethnicity), higher body mass index (BMI; 2.9% higher, 0.2−5.7, for BMI 25−30 vs. <25 kg/m2) and pre-vaccination seropositivity for SARS-CoV-2 (105.1% higher, 94.1−116.6, for those seropositive and experienced COVID-19 symptoms vs. those who were seronegative pre-vaccination). In conclusion, we identify multiple determinants of antibody responses to SARS-CoV-2 vaccines, many of which are modifiable.

Termination of wanted pregnancy and suicidal ideation in hyperemesis gravidarum: A mixed methods study.

Background: Difficulty accessing medication and poor patient experience have been implicated as risk factors for termination of pregnancy and suicidal ideation in women with hyperemesis gravidarum. We aimed to gain further insight into these factors in order to further inform and improve patient care. Methods: We performed a sub-analysis on quantitative data generated through a UK-wide survey of 5071 participants. A qualitative analysis of free text comments was performed using an inductive thematic approach. Results: 41.2% % of women taking prescribed medications had to actively request them. 'Extremely poor' or 'poor' experiences were described in 39.4% and 30.0% of participants in primary and secondary care respectively. Protective factors for termination of pregnancy and suicidal ideation include holistic support from family, friends and healthcare providers. Conclusion: Optimal care in hyperemesis gravidarum should incorporate timely access to pharmacotherapy, assessment of mental health, consideration of referral to specialist services and care being delivered in a compassionate manner.

Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT162b2 and after booster vaccination with BNT162b2 or mRNA-1273: A population-based cohort study (COVIDENCE UK).

Background: Little is known about how demographic, behavioural, and vaccine-related factors affect risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations. Methods: This prospective, population-based, UK study in adults (≥16 years) vaccinated against SARS-CoV-2 assessed risk of breakthrough SARS-CoV-2 infection up to February, 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT162b2) and those who received a booster dose (BNT162b2 or mRNA-1273). Cox regression models explored associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and test-positive breakthrough infection, adjusted for local weekly SARS-CoV-2 incidence. Findings: 1051 (7·1%) of 14 713 post-primary participants and 1009 (9·5%) of 10 665 post-booster participants reported breakthrough infection, over a median follow-up of 203 days (IQR 195-216) and 85 days (66-103), respectively. Primary vaccination with ChAdOx1 (vs BNT162b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1·63, 95% CI 1·41-1·88) and after an mRNA-1273 booster (1·26 [1·00-1·57] vs BNT162b2 primary and booster). Lower risk of infection was associated with older age (post-primary: 0·97 [0·96-0·97] per year; post-booster: 0·97 [0·97-0·98]), whereas higher risk of infection was associated with lower educational attainment (post-primary: 1·78 [1·44-2·20] for primary/secondary vs postgraduate; post-booster: 1·46 [1·16-1·83]) and at least three weekly visits to indoor public places (post-primary: 1·36 [1·13-1·63] vs none; post-booster: 1·29 [1·07-1·56]). Interpretation: Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough infection after primary and booster vaccinations. Funding: Barts Charity, UK Research and Innovation Industrial Strategy Challenge Fund.

Short-term and long-term impacts of COVID-19 on economic vulnerability: a population-based longitudinal study (COVIDENCE UK).

OBJECTIVE: To determine whether COVID-19 has a significant impact on adequacy of household income to meet basic needs (primary outcome) and work absence due to sickness (secondary outcome), both at the onset of illness (short term) and subsequently (long term). DESIGN: Multilevel mixed regression analysis of self-reported data from monthly online questionnaires, completed 1 May 2020 to 28 October 2021, adjusting for baseline characteristics including age, sex, socioeconomic status and self-rated health. SETTING AND PARTICIPANTS: Participants (n=16 910) were UK residents aged 16 years or over participating in a national longitudinal study of COVID-19 (COVIDENCE UK). RESULTS: Incident COVID-19 was independently associated with increased odds of participants reporting household income as being inadequate to meet their basic needs in the short term (adjusted OR (aOR) 1.39, 95% CI 1.12 to 1.73) though this did not persist in the long term (aOR 1.00, 95% CI 0.86 to 1.16). Exploratory analysis revealed a stronger short-term association among those who reported long COVID, defined as the presence of symptoms lasting more than 4 weeks after disease onset, than those reporting COVID-19 without long COVID (p for trend 0.002). Incident COVID-19 associated with increased odds of reporting sickness absence from work in the long term (aOR 4.73, 95% CI 2.47 to 9.06) but not in the short term (aOR 1.34, 95% CI 0.52 to 3.49). CONCLUSIONS: We demonstrate an independent association between COVID-19 and increased risk of economic vulnerability among COVIDENCE participants, measured by both household income sufficiency and sickness absence from work. Taking these findings together with pre-existing research showing that socioeconomic disadvantage increases the risk of developing COVID-19, this may suggest a 'vicious cycle' of impaired health and poor economic outcomes. TRIAL REGISTRATION NUMBER: NCT04330599.

Correlation Between Postvaccination Anti-Spike Antibody Titers and Protection Against Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Population-Based Longitudinal Study.

In this population-based cohort of 7538 adults, combined immunoglobulin (Ig) G, IgA, and IgM (IgG/A/M) anti-spike titers measured after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination were predictive of protection against breakthrough SARS-CoV-2 infection. Discrimination was significantly improved by adjustment for factors influencing risk of SARS-CoV-2 exposure, including household overcrowding, public transport use, and visits to indoor public places. Anti-spike IgG/A/M titers showed positive correlation with neutralizing antibody titers (rs = 0.80 [95% confidence interval, .72-.86]; P < .001) and S peptide-stimulated interferon-γ concentrations (rs = 0.31 [.13-.47]; P < .001).

Incidence of Clostridioides difficile infection (CDI) related to antibiotic prescribing by GP surgeries in Wales.

BACKGROUND: Clostridioides difficile infection (CDI) is a healthcare-acquired infection (HAI) causing significant morbidity and mortality. Welsh CDI rates are high in comparison with those in England and Scotland. OBJECTIVES: This retrospective ecological study used aggregated disease surveillance data to understand the impact of total and high-risk Welsh GP antibiotic prescribing on total and stratified inpatient/non-inpatient CDI incidence. METHODS: All cases of confirmed CDI, during the financial years 2014-15 to 2017-18, were linked to aggregated rates of antibiotic prescribing in their GP surgery and classified as 'inpatient', 'non-inpatient' or 'unknown' by Public Health Wales. Multivariable negative-binomial regression models, comparing CDI incidence with antibiotic prescribing rates, were adjusted for potential confounders: location; age; social deprivation; comorbidities (estimated from prevalence of key health indicators) and proton pump inhibitor (PPI) prescription rates. RESULTS: There were 4613 confirmed CDI cases, with an incidence (95% CI) of 1.44 (1.40-1.48) per 1000 registered patients. Unadjusted analysis showed that an increased risk of total CDI incidence was associated with higher total antibiotic prescribing [relative risk (RR) (95% CI) = 1.338 (1.170-1.529) per 1000 items per 1000 specific therapeutic group age-sex related GP prescribing units (STAR-PU)] and that high-risk antibiotic classes were positively associated with total CDI incidence. Location, age ≥65 years and diabetes were associated with increased risk of CDI. After adjusting for confounders, prescribing of clindamycin showed a positive association with total CDI incidence [RR (95% CI) = 1.079 (1.001-1.162) log items per 1000 registered patients]. CONCLUSIONS: An increased risk of CDI is demonstrated at a primary care practice population level, reflecting their antibiotic prescribing rates, particularly clindamycin, and population demographics.

Adiposity and cardiovascular outcomes in three-year-old children of participants in UPBEAT, an RCT of a complex intervention in pregnant women with obesity.

BACKGROUND: Maternal obesity is associated with offspring cardiometabolic risk. UPBEAT was a randomised controlled trial of an antenatal diet and physical activity intervention in 1555 women with obesity. The intervention was associated with lower gestational weight gain, healthier diet and metabolic profile in pregnancy, and reduced infant adiposity at six months. OBJECTIVE: We have investigated whether the UPBEAT intervention influenced childhood cardiometabolic outcomes or was associated with sustained improvements in maternal lifestyle 3-years after delivery. METHODS: In UPBEAT mother-child dyads at the 3-year follow-up, we assessed childhood blood pressure, resting pulse rate, and adiposity (body mass index, skinfold thicknesses, body fat, waist and arm circumferences) and maternal diet, physical activity, and anthropometry. RESULTS: 514 three-year-old children attended the appointment (49% intervention, 51% standard care). There was no difference in the main outcome of interest, subscapular skinfold thickness, between the trial arms (-0.30 mm, 95% confidence interval: -0.92, 0.31). However, the intervention was associated with a lower resting pulse rate (-5 bpm [-8.41, -1.07]). There was also a non-significant lower odds of overweight/obesity (OR 0.73; 0.50, 1.08). Maternal dietary improvements observed in the UPBEAT trial, including glycaemic load and saturated fat were maintained 3-years postpartum. CONCLUSION: This study has demonstrated that an antenatal dietary and physical activity intervention in women with obesity is associated with lower offspring pulse rate and sustained improvement in maternal diet. Whilst larger than previous cohorts, there remains potential for bias from attrition and these findings require validation in future cohorts.