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Background Childhood vision impairment (VI) can adversely impact health and social outcomes and limit life chances. We investigated whether its adverse impacts into adult life changed during a period in which legislation, policy and services to address inequalities relating to disability were implemented. Methods Cross-cohort study comprising 14 247 participants from the 1946, 1958 and 1970 British birth cohorts (BC). Participants dichotomized as VI at age 15/16 (distance visual acuity was 6/12 or worse in the better-seeing eye) or normally sighted. Associations of childhood VI with health, well-being, socioeconomic and social participation outcomes in mid-adult life were investigated using regression models adjusted for participants' early life socioeconomic markers and sex. Change in adjusted odds ratios of >10% in the same direction in successive cohorts, or a > 20% difference between 1970BC and one older cohort were considered meaningful. Results Trends over time in impacts of childhood onset VI into mid-adult life were complex. This included worsening of odds of poorer physical health (odds ratio 1.47; 95% confidence interval 1.02–2.14), living in unsatisfactory (1.54; 1.03–2.29) or overcrowded (2.34; 1.26–4.06) households, being unemployed (2.19; 1.19–3.97) and not gaining additional educational qualifications during mid-adult life (1.61; 1.08–2.47). By contrast the odds of not participating in some social activities (e.g. seeing friends) improved over time. Associations with other outcomes were unchanged. Conclusions Many adverse impacts of childhood VI do not appear ameliorated over time by legislation, policies and provision that would have been expected to reduce inequalities. Moreover, some were increased. Childhood VI continues to cast a life-long shadow. [ABSTRACT FROM AUTHOR]

Background To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. Methods Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). Results In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1 , VPS37C , TGFB1 , MX2 , and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%–98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%–97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. Conclusions MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C. [ABSTRACT FROM AUTHOR]

Objectives Clinicians concerned about long-term safety of biologics in JIA may consider tapering or stopping treatment once remission is achieved despite uncertainty in maintaining drug-free remission. This analysis aims to (i) calculate how many patients with JIA stop biologics for remission, (ii) calculate how many later re-start therapy and after how long, and (iii) identify factors associated with re-starting biologics. Methods Patients starting biologics between 1 January 2010 and 7 September 2021 in the UK JIA Biologics Register were included. Patients stopping biologics for physician-reported remission, those re-starting biologics and factors associated with re-starting, were identified. Multiple imputation accounted for missing data. Results Of 1451 patients with median follow-up of 2.7 years (IQR 1.4, 4.0), 269 (19%) stopped biologics for remission after a median of 2.2 years (IQR 1.7, 3.0). Of those with follow-up data (N = 220), 118 (54%) later re-started therapy after a median of 4.7 months, with 84% re-starting the same biologic. Patients on any-line tocilizumab (prior to stopping) were less likely to re-start biologics (vs etanercept; odds ratio [OR] 0.3; 95% CI: 0.2, 0.7), while those with a longer disease duration prior to biologics (OR 1.1 per year increase; 95% CI: 1.0, 1.2) or prior uveitis were more likely to re-start biologics (OR 2.5; 95% CI: 1.3, 4.9). Conclusions This analysis identified factors associated with successful cessation of biologics for remission in JIA as absence of uveitis, prior treatment with tocilizumab and starting biologics earlier in the disease course. Further research is needed to guide clinical recommendations. [ABSTRACT FROM AUTHOR]

Background Microscopy is the gold standard for malaria diagnosis but is dependent on trained personnel. Rapid diagnostic tests (RDTs) form the mainstay of diagnosis in endemic areas without access to high-quality microscopy. We aimed to evaluate whether RDT alone could rule out imported malaria in children presenting to UK emergency departments (EDs). Methods UK-based, multi-center, retrospective, diagnostic accuracy study. Included : any child <16 years presenting to ED with history of fever and travel to a malaria-endemic country, between 01/01/2016 and 31/12/2017. Diagnosis: microscopy for malarial parasites (clinical reference standard) and RDT (index test). UK Health Research Authority approval: 20/HRA/1341. Results There were 47 cases of malaria out of 1,414 eligible cases (prevalence 3.3%) in a cohort of children whose median age was 4 years (IQR 2–9), of whom 43% were female. Cases of Plasmodium falciparum totaled 36 (77%, prevalence 2.5%). The sensitivity of RDT alone to detect malaria infection due to any Plasmodium species was 93.6% (95% CI 82.5–98.7%), specificity 99.4% (95% CI 98.9–99.7%), positive predictive value 84.6% (95% CI 71.9–93.1%) and negative predictive value 99.8% (95% CI 99.4–100.0%). Sensitivity of RDT to detect P. falciparum infection was 100% (90.3–100%), specificity 98.8% (98.1–99.3%), positive predictive value 69.2% (54.9–81.2%, n = 46/52) and negative predictive value 100% (99.7–100%, n = 1,362/1,362). Conclusions RDTs were 100% sensitive in detecting P. falciparum malaria. However, lower sensitivity for other malaria species and the rise of pfhrp2 and pfhrp3 (pfhrp2/3) gene deletions in the P. falciparum parasite mandate the continued use of microscopy for diagnosing malaria. [ABSTRACT FROM AUTHOR]

Background In developing evidence-based physical activity (PA) guidelines for youth, a knowledge gap exists regarding the health effects of sedentary time (SED). The aim of this study was to determine the joint associations of moderate- and vigorous-intensity PA (MVPA) and SED with adiposity during adolescence. Methods The study sample was 2619 non-obese participants (56.7% female) from the UK Avon Longitudinal Study of Parents and Children. Accelerometer-measured MVPA and SED at age 11, 13, 15 years and self-reported TV viewing at age 13 and 16 years were used to create two exposure variables: six MVPA&SED combinations based on two MVPA patterns [≥60 (active) and <60 min/day (inactive)] and three SED patterns [≈25 (low), ≈30 (middle) and ≈35 min/h (high)] and six MVPA&TV combinations based on two MVPA patterns and three TV viewing patterns [<1–2 (low), 1–2 (middle) and >1–2 h/day (high)]. Adiposity was evaluated using fat mass index (FMI) at age 17 years. Results SED was not significantly associated with FMI in either active or inactive adolescents. However, higher TV viewing was associated with higher FMI in both active [adjusted FMI = 4.53 vs. 5.09 (95% CI = 4.87, 5.33) for low TV vs. high TV] and inactive adolescents [adjusted FMI = 4.91 vs. 5.21 (95% CI = 5.02, 5.39) for low TV vs. high TV]. Conclusions Higher TV viewing time, but not total SED, was prospectively associated with higher adiposity among both active and inactive adolescents, suggesting a specific sedentary behavior target for public health. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE. Methods Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n  = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n  = 129) was used to calculate positive/negative predictive values of the criteria. Results At both first and last visits, the number of patients fulfilling the different classification criteria varied significantly (P < 0.001). The sensitivity of the SLICC-2012 criteria was higher when compared with that of the ACR/EULAR-2019 criteria at first and last visits (98% vs 94% for first visit, and 98% vs 96% for last visit; P < 0.001), when all available CYP were considered. The ACR/EULAR-2019 criteria were more specific when compared with the SLICC-2012 criteria (77% vs 67% for first visit, and 81% vs 71% for last visit; P < 0.001). Significant differences between the classification criteria were mainly caused by the variation in ANA positivity across ages. In the unselected cohort of ANA-positive CYP, the ACR/EULAR-2019 criteria produced the highest false-positive classification (6/129, 5%). Conclusion In CYP, the ACR/EULAR-2019 criteria are not superior to those of the SLICC-2012 or ACR-1997 criteria. If classification criteria are designed to include CYP and adult populations, paediatric rheumatologists should be included in the consensus and evaluation process, as seemingly minor changes can significantly affect outcomes. [ABSTRACT FROM AUTHOR]

Objectives To define the incidence and prevalence of Behçet's syndrome (BS) in children and young people (CYP) up to the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). Methods A prospective epidemiological study was undertaken with the support of the British Paediatric Surveillance Unit (BPSU) and the British Society of Paediatric Dermatologists (BSPD). Consultants reported anonymised cases of BS seen. A follow-up study at one year examined progression of disease and treatment. Results Over a two-year period, 56 cases met the International Criteria for Behçet's Disease. For children under 16 years of age, the two-year period prevalence estimate was 4.2 per million (95% CI: 3.2, 5.4) and the incidence was 0.96 per million person years (95% CI: 0.66, 1.41). Mucocutaneous disease was the most common phenotype (56/100%), with ocular (10/56; 17.9%), neurological (2/56; 3.6%) and vascular involvement (3/56; 5.4%) being less common. Median age at onset was 6.34 years and at diagnosis was 11.72 years. There were slightly more female than male children reported (32/56; 55.6%). The majority of cases (85.7%) were white Caucasian. Apart from genital ulcers, which were more common in females, there were no significant differences in frequency of manifestations between male or females, nor between ethnicities. Over 83% of cases had three or more non-primary care healthcare professionals involved in their care. Conclusion BS is extremely rare in CYP in the UK and ROI and most have mucocutaneous disease. Healthcare needs are complex, and coordinated care is key. [ABSTRACT FROM AUTHOR]

Background: Although physical activity has many known health benefits, its association with lung function in childhood/adolescence remains unclear. We examined the association of physical-activity trajectories between 11 and 15 years with lung function at 15 years in 2266 adolescents.Methods: A population-based cohort of 14 305 singleton births alive at 1 year was recruited in the UK population-based Avon Longitudinal Study of Parents and Children cohort. Physical activity (counts/minute and moderate-to-vigorous physical activity) was assessed for 7 days using an accelerometer at 11, 13 and 15 years. We identified sex-specific physical-activity trajectories applying K-means for longitudinal data in children with at least two accelerometer measurements (n = 3584). We then estimated the sex-specific associations of these trajectories with post-bronchodilation lung-function parameters using multivariable linear-regression models (n = 2266, 45% boys).Results: Fewer than 7% of participants met the WHO physical-activity recommendations (i.e. daily average of at least 60 minutes of moderate-to-vigorous physical activity). Boys were substantially more active than girls. In both sexes, we identified three distinct physical-activity trajectories ('low': 39.8% boys, 45.8% girls; 'moderate': 42.9% boys, 41.4% girls; and 'high' physical activity: 17.3% boys, 12.8% girls). Girls in the moderate and high physical-activity trajectories had 0.11 L [95% confidence interval (CI): 0.04-0.19] and 0.15 L (95% CI: 0.03-0.26) higher forced vital capacity than their less-active peers. No association was observed in boys.Conclusions: Higher childhood physical activity relates to higher lung-function levels in adolescent girls. A better understanding of the mechanisms underlying this association should be pursued. [ABSTRACT FROM AUTHOR]

The article discusses the 1970 British cohort study on the relationship between public care during childhood and the biomedical risk factors in Middle Age. Topics include the association between socioeconomic disadvantages in childhood with cardiovascular disease and adult mortality, the association of care with biomarkers of mortality like glucose metabolism, and the history of early-life public care in Great Britain.

Longitudinal data sources offer new opportunities for the evaluation of sequential interventions. To adjust for time-dependent confounding in these settings, longitudinal targeted maximum likelihood based estimation (TMLE), a doubly robust method that can be coupled with machine learning, has been proposed. This paper provides a tutorial in applying longitudinal TMLE, in contrast to inverse probability of treatment weighting and g-computation based on iterative conditional expectations. We apply these methods to estimate the causal effect of nutritional interventions on clinical outcomes among critically ill children in a United Kingdom study (Control of Hyperglycemia in Paediatric Intensive Care, 2008-2011). We estimate the probability of a child's being discharged alive from the pediatric intensive care unit by a given day, under a range of static and dynamic feeding regimes. We find that before adjustment, patients who follow the static regime "never feed" are discharged by the end of the fifth day with a probability of 0.88 (95% confidence interval: 0.87, 0.90), while for the patients who follow the regime "feed from day 3," the probability of discharge is 0.64 (95% confidence interval: 0.62, 0.66). After adjustment for time-dependent confounding, most of this difference disappears, and the statistical methods produce similar results. TMLE offers a flexible estimation approach; hence, we provide practical guidance on implementation to encourage its wider use. [ABSTRACT FROM AUTHOR]

Background: Development of verbal skills during early childhood and school age years is consequential for children's educational achievement and adult outcomes. We examine ethnic differences in longitudinal latent verbal profiles and assess the contribution of family process and family resource factors to observed differences. Methods: Using data from the UK Millennium Cohort Study and the latent profile analysis, we estimate longitudinal latent verbal profiles using verbal skills measured 4 times from age 3-11 years. We investigate the odds of verbal profiles by ethnicity (reported in infancy), and the extent observed differences are mediated by the home learning environment, family routines, and psychosocial environment (measured at age 3). Results: Indian children were twice as likely (OR = 2.14, CI: 1.37-3.33) to be in the high achieving profile, compared to White children. Socioeconomic markers attenuated this advantage to nonsignificance. Pakistani and Bangladeshi children were significantly more likely to be in the low performing group (OR = 2.23, CI: 1.61- 3.11; OR = 3.37, CI: 2.20-5.17, respectively). Socioeconomic and psychosocial factors had the strongest mediating influence on the association between lower achieving profiles and Pakistani children, whereas for Bangladeshi children, there was mediation by the home learning environment, family routines, and psychosocial factors. Conclusion: Family process and resource factors explain ethnic differences in longitudinal latent verbal profiles. Family resources explain verbal advantages for Indian children, whereas a range of home environment and socioeconomic factors explain disparities for Pakistani and Bangladeshi children. Future policy initiatives focused on reducing ethnic disparities in children's development should consider supporting and enhancing family resources and processes. [ABSTRACT FROM AUTHOR]

Much adult physical inactivity research ignores early-life factors from which later influences may originate. In the 1958 British birth cohort (followed from 1958 to 2008), leisure-time inactivity, defined as activity frequency of less than once a week, was assessed at ages 33, 42, and 50 years (n = 12,776). Early-life factors (at ages 0–16 years) were categorized into 3 domains (i.e., physical, social, and behavioral). We assessed associations of adult inactivity 1) with factors within domains, 2) with the 3 domains combined, and 3) allowing for adult factors. At each age, approximately 32% of subjects were inactive. When domains were combined, factors associated with inactivity (e.g., at age 50 years) were prepubertal stature (5% lower odds per 1–standard deviation higher height), hand control/coordination problems (14% higher odds per 1-point increase on a 4-point scale), cognition (10% lower odds per 1–standard deviation greater ability), parental divorce (21% higher odds), institutional care (29% higher odds), parental social class at child's birth (9% higher odds per 1-point reduction on a 4-point scale), minimal parental education (13% higher odds), household amenities (2% higher odds per increase (representing poorer amenities) on a 19-point scale), inactivity (8% higher odds per 1-point reduction in activity on a 4-point scale), low sports aptitude (13% higher odds), and externalizing behaviors (i.e., conduct problems) (5% higher odds per 1–standard deviation higher score). Adjustment for adult covariates weakened associations slightly. Factors from early life were associated with adult leisure-time inactivity, allowing for early identification of groups vulnerable to inactivity. [ABSTRACT FROM PUBLISHER]

Although there is increasing evidence that immune dysregulation in children who develop acute lymphoblastic leukemia (ALL) is detectable from birth, debate about the role of infectious exposures in infancy continues. With the aim of quantifying children's infectious exposures, investigators have used a number of infection exposure proxies, but there is a lack of consistency in findings, with some markers indicating increased ALL risks and others decreased risks, the disparity being evident both within and between studies. Accordingly, the authors conducted an in-depth analysis of key infection exposure proxies used in the United Kingdom Childhood Cancer Study, a national population-based case-control study conducted over the period 1991–1996, which combined data from medical records, parental interview, and population census. This longitudinal approach revealed the marked deterioration in immune response that emerged around 5 months prior to ALL diagnosis and confirmed that infectious diagnoses in the first year of life were significantly increased (P < 0.05) in children who developed leukemia between 2 and 14 years of age, as well as in those who had birth orders >1, were not breastfed, lived in deprived areas, or were diagnosed with eczema. By contrast, no association between infectious illness and preschool activity was detected, the lower infection levels among controls whose mothers reported attendance contributing to a significantly reduced ALL odds ratio. [ABSTRACT FROM PUBLISHER]

Background: Since 2006, banning smoking in cars with children has become a rapidly growing tobacco control policy. However, to date, there have been few studies examining support and correlates of support for car smoking bans, and none of the existing studies have been international in nature. We conducted such a study among smokers in four countries. Methods: 6716 adult current smokers from the 2007 Wave of the International Tobacco Control Four Country Survey, a nationally representative, longitudinal cohort telephone survey of smokers in the USA, Canada, UK and Australia. Controlling for demographics, heaviness of smoking, smoking health knowledge/beliefs and quit intentions, we compared support and correlates of support for banning smoking in cars with children across the four countries. Results: The majority of smokers supported banning smoking in cars with children. Support was highest in Australia (83%), followed by the UK (75%) and Canada (74%); support was lower—but still high—in the USA (60%). Support was highest among smokers who: had stronger quit intentions, were lighter smokers, had lower education, had no children in the home, believed that cigarette smoke is dangerous to non-smokers and could cause asthma in children, and were concerned about modelling smoking to children. Conclusions: These findings indicate that a majority of smokers in the four countries support banning smoking in cars with children, and lend support to banning smoking in cars with children. Additionally, they suggest that support may be increased by educating smokers about the dangers of cigarette smoke exposure. [ABSTRACT FROM AUTHOR]