Open-label placebos appear to have positive clinical effects compared to no treatment. Caution is warranted when interpreting these results due to the limited number of trials identified, lack of blinding, and the fact that positive messages were included alongside open-label placebos. Larger definitive trials are now warranted to explore the potential patient benefit of open-label placebos, to investigate the relative contributions of positive suggestions, and ethical implications.

Haematopoietic cells constitutively express CD31/PECAM1 a signalling, adhesion receptor associated with controlling responses to inflammatory stimuli. Although expressed on CD4+ T cells, its function on these cells is unclear. To address this we have used a model of systemic Salmonella infection that induces high levels of T cell activation and depends upon CD4+ T cells for resolution. Infection of CD31-deficient (CD31KO) mice demonstrates that these mice fail to control infection effectively. During infection, CD31KO mice have diminished numbers of total CD4+ T cells and IFN-γ-secreting Th1 cells. This is despite a higher proportion of CD31KO CD4+ T cells exhibiting an activated phenotype, and an undiminished capacity to prime normally and polarize to Th1. Reduced numbers of T cells reflected the increased propensity of naive and activated CD31KO T cells to undergo apoptosis after infection compared to wild-type (WT) T cells. Using adoptive transfer experiments we show that loss of CD31 on CD4+ T cells alone is sufficient to account for the defective CD31KO T cell accumulation. These data are consistent with CD31 helping to control T cell activation as in its absence T cells have a greater propensity to become activated, resulting in increased susceptibility to become apoptotic. The impact of CD31 loss on T cell homeostasis becomes most pronounced during severe, inflammatory and immunological stresses such as those caused by systemic Salmonella infection. This identifies a novel role for CD31 in regulating CD4 T cell homeostasis.

The study aims to identify ‘missing’ diagnoses amongst paediatric admissions during the UK’s first national lockdown, compared with the previous 5 years. A retrospective observational cohort study of all children (0–15 years) attending for urgent care across Oxfordshire, during the first UK lockdown in 2020, compared to matched dates in 2015–2019, across two paediatric hospitals providing secondary care, including one with tertiary services. Our outcome measures were changes in numbers of patients attending and inpatient diagnoses (using ICD-10 classification) during the first 2020 lockdown, compared with the previous 5 years, were used. We found that total Emergency Department (ED) attendances ( n = 4030) and hospital admissions ( n = 1416) during the first UK lockdown were reduced by 56.8% and 59.4%, respectively, compared to 2015–2019 (5-year means n = 7446.8 and n = 2491.6, respectively). Proportions of patients admitted from ED and length of stay were similar across 2015–2020. ICD-10 diagnoses in lockdown of 2020 ( n = 2843) versus matched 2015–2019 dates ( n = 19,946) demonstrated significantly greater neoplasm diagnoses ( p = 0.0123). Of diagnoses ‘missing’ in lockdown, 80% were categorised as infectious diseases or their sequelae and 20% were non-specific pains/aches/malaise and accidental injury/poisonings. Conclusions : Pandemic public health measures significantly altered paediatric presentations. Oxfordshire hospitals had a 58% reduction in ED attendances/inpatient admissions, with ‘missing’ diagnoses predominantly infection-related illnesses. These are likely driven by a combination of the following: (1) public health infection control measures successfully reducing disease transmission, (2) parents/carers keeping mild/self-limiting disease at home, and (3) pandemic-related healthcare anxieties. Prospective studies are needed to ensure referral pathways identify vulnerable children, those with social concerns, and avoid delayed presentation. What is Known: • Significant reductions of paediatric ED attendances and inpatient admissions are reported globally, throughout national and regional lockdowns for COVID-19. • Previous studies (supplemental table 5 ) examined only ED diagnoses or specific inpatient diagnoses during lockdown periods, demonstrating reductions of infectious diseases, accidents/injuries, and safeguarding referrals. What is New: • Using ICD-10 coding, robustly controlling for five historical years and adopting a hypothesis-independent analysis, demonstrating 80% of ‘missing’ inpatient diagnoses during national COVID-19 lockdown were infectious dise...