Mark Stephen Pearce

Background: We investigated the development of physical activity in children across developmental capabilities from age 1 to 5 years, assessing whether trajectories associate with sociodemographic, developmental and health characteristics. Methods: Participants were recruited through thirteen National Health Service organisations in England. Data were collected every six months over six waves, with accelerometry (up to 7 days); parent questionnaire (sociodemographics and development); and clinical data (health conditions). A data-driven method provided estimates of the total time active (any intensity) and intense activity (e.g. walking, running, playing). Physical activity trajectories were modelled using piecewise linear mixed effects models, including explanatory variables. Bayesian piecewise mixture models identified clusters within the trajectories, and multinomial logistic regression models related explanatory variables to cluster membership.Findings: 301 children (56% female, 96 with a diagnosed health condition) provided valid accelerometry data for 10.5±1.36 hours/day at a median of 4 waves (IQR: 3-5). Overall, total time active increased gradually with age (1yr: 351±85 min/day ; 4yr: 389±92 min/day), while intense activity increased rapidly from 1 (56±36 min/day) to 3 (103±43 min/day) years and then more gradually to 4 years (112±46 min/day). For total physical activity, activity increased sharply (156.6 minutes/year) until age 15 months, then more gradual (7.4 minutes/year) up to the age 5 years. We found no distinct clusters for total activity trajectories. For intense activity trajectories, we found three distinct clusters, where children with developmental problems (OR=16.14, 95% CI: [1.70, 152.66]) and children from lower socioeconomic backgrounds (OR=0.86, 95% CI: [0.75, 0.97]) were more likely to be in the slower cluster. Interpretation: The results show that children with developmental and socioeconomic challenges are at an increased risk of slower growth in their everyday physical activity from a young age, with inequities particularly prominent in intensive activity. Future work should identify interventions for enabling participation.

Due to limitations in current therapies (immunoglobulin replacement therapy), complications in X-linked agammaglobulinemia (XLA) such as bronchiectasis may continue to occur, with subsequent significant impacts on health-related quality of life (HRQoL). There were no significant differences in PedsQL 4.0 total scores against UK healthy norms (self 80.98, P = 0.277; parent 79.76, P = 0.465). There were no significant differences in the SF36v2 physical component score (PCS) against UK healthy norms (49.10, P = 0.712). However, XLA patients with bronchiectasis had significantly worse PCS than patients without (47.88 versus 55.14, P < 0.001) and significantly worse PCS than UK healthy norms (P = 0.004). In the absence of bronchiectasis, HRQoL is comparable to UK healthy norms. However, XLA patients with bronchiectasis have significantly worse HRQoL than patients without bronchiectasis and UK healthy norms. These data demonstrate that further work into novel therapies are needed to prevent bronchiectasis to enable XLA patients to have a normal quality of life.

Signal transduction and activator of transcription 3 hyperimmunoglobulin E syndrome (STAT3-HIES) is a multisystem disorder causing recurrent skin and respiratory infection with bronchiectasis, pneumatoceles, and aspergillosis; lymphoma; and extraimmune manifestations including fractures and vasculopathy. Published data on immune and extraimmune hematopoietic stem cell transplant (HSCT) outcomes focus on case reports or small cohorts. We conducted an international multicenter retrospective study of HSCT in STAT3-HIES. Primary end points were overall survival (OS) and event-free survival (EFS; events were death, graft failure, chronic graft-versus-host disease [GVHD]). We identified 41 patients over a 28-year period. HSCT indication was infection (93%) or lymphoma (7%). Median age at HSCT was 14 years (range, 4-45). Most patients had pre-HSCT respiratory disease (93%), including parenchymal lung disease (68%), and prior suspected/confirmed pulmonary fungal infection (32%). Patients received peripheral blood stem cells (51%) or marrow (49%) from HLA 10/10–matched unrelated donors (44%), matched family donors (44%), mismatched family donors (10%), or 1 9/10–mismatched unrelated donor (2%). Conditioning regimens were predominantly treosulfan-based (59%; with thiotepa, 34%); other patients received busulfan-based (24%) or melphalan-based (17%) regimens. Median follow-up for surviving patients was 5 years (0.8-28). The 5-year OS was 93%, and 5-year EFS 90%. Cumulative incidence of grade 2 to 4 acute GVHD was 22%. Median whole blood donor chimerism at latest follow-up was 100%. Eighty-seven percent of patients have reduced or no bacterial or fungal respiratory infection. After HSCT, 20% developed new skeletal fractures. This worldwide study expanded data on HSCT for STAT3-HIES to 41 patients; despite significant pre-HSCT pulmonary morbidity, OS was high, and patients have improved skin and respiratory disease though the impact on extraimmune manifestations appears limited.

Childhood infections have been shown to stunt growth, contribute to malnutrition and reduce cognition in early adulthood. This study aimed to assess relationships between early life infections and childhood cognition at age 11 years in the Newcastle Thousand Families Study (NTFS). The analysis included 741 members from the NTFS who had complete data for infections between birth and 5 years, and the 11-plus examinations. School records from the 11-plus examinations showed cognitive (IQ), English (EQ) and arithmetic (AQ) abilities. Housing conditions, overcrowding, birth order and social class were recorded at birth. Helicobacter pylori seropositivity was measured at age 49–51 years. Multivariable linear regression was used to examine relationships between infections and cognition. The total number of infections in the first 5 years of life was not significantly associated with IQ, EQ or AQ, nor were there significant relationships between cognitive outcomes and most infections. Tonsillitis did display a positive, significant association with IQ after adjustment for confounders (b = 6.43, 95% CI 0.92, 11.94, p = 0.022). Lower respiratory tract infections (LRTIs) showed significant negative relationships with all cognitive outcomes. H. pylori seropositivity at age 50 exhibited negative, significant relationships with EQ (p = 0.014) and AQ (p = 0.024) after adjustment for confounders. Although no significant relationship between overall infections and cognition were found, there were indications that LRTIs and gastrointestinal system infections may limit cognitive development. Given these infections remain prevalent, further research regarding severity and recurrence of infections and how they affect childhood cognition is needed.

Research suggests parental ability to recognise when their child has overweight is limited. It is hypothesised that recognition of child overweight/obesity is fundamental to its prevention, acting as a potential barrier to parental action to improve their child’s health-related behaviours and/or help seeking. The purpose of this study was to investigate the efficacy of an intervention (MapMe) to improve parental ability to correctly categorise their child as having overweight one-month post-intervention, and reduce child body mass index (BMI) z-score 12 months post-intervention. MapMe consists of body image scales of known child BMI and information on the consequences of childhood overweight, associated health-related behaviours and sources of support. We conducted a three-arm (paper-based MapMe, web-based MapMe and control) randomised control trial in fifteen English local authority areas with parents/guardians of 4–5- and 10–11-year-old children. Parental categorisation of child weight status was assessed using the question ‘How would you describe your child’s weight at the moment?’ Response options were: underweight, healthy weight, overweight, and very overweight. Child weight status and BMI z-scores were calculated using objectively measured height and weight data and UK90 clinical thresholds. There was no difference in the percentage of parents correctly categorising their child as having overweight/very overweight (n = 264: 41% control, 48% web-based, and 43% paper-based, p = 0.646). BMI z-scores were significantly reduced for the intervention group at 12 months post-intervention compared to controls (n = 338, mean difference in BMI z-score change −0.11 (95% CI −0.202 to −0.020, p = 0.017). MapMe was associated with a decrease in BMI z-score 12 months post-intervention, although there was no direct evidence of improved parental ability to correctly categorise child overweight status. Further work is needed to replicate these findings in a larger sample of children, investigate mechanisms of action, and determine the use of MapMe as a public health initiative.

Purpose: Hearing loss is most prevalent among older adults, yet underestimated by patients, clinicians, and research communities. This study aimed to assess the accuracy of self-reported hearing difficulties among a group of adults aged 61–63 years, against audiometric measures. Method: The analysis used a sample ( N = 346) of the Newcastle Thousand Families Study birth cohort. Data from audiological examinations and self-reported hearing difficulties were used to compare subjective and objective hearing. Hearing aid use was also assessed. Results: Over 40% of the participants had some level of hearing loss ( n = 155, 44.8%), and 31% ( n = 133) of these reported having hearing problems during subjective assessment. Only 18 (10%) of those with objectively measured hearing loss reported using hearing aids. Conclusions: There was an inconsistency between measured and self-perceived hearing loss among adults aged 61–63 years in this cohort. The small number of hearing aid users in the cohort is a concern, in that people in this age group appear not to be getting the help they need. The data also add to the research evidence that people at this age underestimate their hearing loss.