Behçet's disease in Wales: an epidemiological description of national surveillance data.

OBJECTIVES: Behçet's disease is a rare, chronic, incurable, multisystemic disease. It causes significant morbidity, with patients experiencing symptoms including mucous membrane ulcers, and joint pain and swelling. It is an important cause of avoidable blindness due to ocular involvement. The aetiology is unknown. The aims were to identify population prevalence of Behçet's disease in Wales in comparison to other endemic and non-endemic regions, and provide an epidemiological profile of a case series of adult patients. This is the first analysis of data from the Adult Rare Diseases Surveillance Registry for Wales, established in 2020 as part of the COVID-19 pandemic response. RESULTS: Between 1995 and 2020, 347 adults and 5 children were recorded in Wales with a diagnosis of Behçet's disease. Population prevalence was calculated as 11.1 per 100,000 population. Of the adult cases, 76.9% were female, and 6.6% died before the end of the study period. When comparing genders, there were no statistically significant differences in age at diagnosis, mortality or socioeconomic status. There was no evidence that the age at which cases were diagnosed had changed over time. Survival analyses showed no significant differences in durations of survival between genders or individuals residing in different WIMD 2019 quintiles. Age at diagnosis was the only factor significantly and independently associated with poorer durations of survival (p < 0.001).

Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial.

BACKGROUND: Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine. METHODS: In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248. FINDINGS: Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebos -1·29%, 95% CI -14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, -6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (-12·9%, -34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%, -13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, -5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, -11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected. INTERPRETATION: Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need. FUNDING: National Institute for Health Research Policy Research Programme.

Macrolide and lincosamide antibiotic exposure in the first trimester of pregnancy and risk of congenital anomaly: A European case-control study.

This study investigated the risk of congenital heart defects (CHD) and other congenital anomalies (CA) associated with first trimester use of macrolide antibiotics (mainly erythromycin, spiramycin, clarithromycin and azithromycin) and lincosamides (clindamycin) using a case-malformed control design. Data included 145,936 babies with a CA diagnosis (livebirths, stillbirths and terminations of pregnancy for CA) from 15 population-based EUROCAT registries in 13 European countries, covering 9 million births 1995-2012. Cases were babies with CHD, anencephaly, orofacial clefts, genital and limb reduction anomalies associated with antibiotic exposure in the literature. Controls were babies with other CA or genetic conditions. Main outcomes were odds ratios adjusted (AOR) for maternal age and registry, with 95 % Confidence Intervals (95 %CI). Macrolide and lincosamide exposure was recorded for 307 and 28 cases, 72 and 4 non-genetic controls, 57 and 7 genetic controls, respectively. AOR for CHD was not significantly raised (AOR 0.94, 95 %CI: 0.70-1.26 vs non-genetic controls; AOR 1.01, 95 %CI: 0.73-1.41 vs genetic controls), nor significantly raised for any specific macrolide. The risk of atrioventricular septal defect was significantly raised with exposure to any macrolide (AOR 2.98; 95 %CI: 1.48-6.01), erythromycin (AOR 3.68, 95 %CI: 1.28-10.61), and azithromycin (AOR 4.50, 95 %CI: 1.30-15.58). Erythromycin, clarithromycin, azithromycin, and clindamycin were associated with an increased risk of at least one other CA. Further research is needed on the risk of specific CA associated with macrolide and lincosamide use in the first trimester, particularly relevant for the potential use of azithromycin in the treatment of COVID-19.