Characteristics of 5-year-olds who catch-up with MMR: findings from the UK Millennium Cohort Study

Objectives To examine predictors of partial and full measles, mumps and rubella (MMR) vaccination catch-up between 3 and 5 years. Design Secondary data analysis of the nationally representative Millennium Cohort Study (MCS). Setting Children born in the UK, 2000–2002. Participants 751 MCS children who were unimmunised against MMR at age 3, with immunisation information at age 5. Main outcome measures Catch-up status: unimmunised (received no MMR), partial catch-up (received one MMR) or full catch-up (received two MMRs). Results At age 5, 60.3% (n=440) children remained unvaccinated, 16.1% (n=127) had partially and 23.6% (n=184) had fully caught-up. Children from families who did not speak English at home were five times as likely to partially catch-up than children living in homes where only English was spoken (risk ratio 4.68 (95% CI 3.63 to 6.03)). Full catch-up was also significantly more likely in those did not speak English at home (adjusted risk ratio 1.90 (1.08 to 3.32)). In addition, those from Pakistan/Bangladesh (2.40 (1.38 to 4.18)) or ‘other’ ethnicities (such as Chinese) (1.88 (1.08 to 3.29)) were more likely to fully catch-up than White British. Those living in socially rented (1.86 (1.34 to 2.56)) or ‘Other’ (2.52 (1.23 to 5.18)) accommodations were more likely to fully catch-up than home owners, and families were more likely to catch-up if they lived outside London (1.95 (1.32 to 2.89)). Full catch-up was less likely if parents reported medical reasons (0.43 (0.25 to 0.74)), a conscious decision (0.33 (0.23 to 0.48)), or ‘other’ reasons (0.46 (0.29 to 0.73)) for not immunising at age 3 (compared with ‘practical’ reasons). Conclusions Parents who partially or fully catch-up with MMR experience practical barriers and tend to come from disadvantaged or ethnic minority groups. Families who continue to reject MMR tend to have more advantaged backgrounds and make a conscious decision to not immunise early on. Health professionals should consider these findings in light of the characteristics of their local populations

Distribution-free hyperrectangular tolerance regions for setting multivariate reference regions in laboratory medicine

Reference regions are important in laboratory medicine to interpret the test results of patients, and usually given by tolerance regions. Tolerance regions of dimensions are highly desirable when the test results contains outcome measures. Nonparametric hyperrectangular tolerance regions are attractive in real problems due to their robustness with respect to the underlying distribution of the measurements and ease of intepretation, and methods to construct them have been recently provided by Young and Mathew [Stat Methods Med Res. 2020;29:3569-3585]. However, their validity is supported by a simulation study only. In this paper, nonparametric hyperrectangular tolerance regions are constructed by using Tukey's [Ann Math Stat. 1947;18:529-539; Ann Math Stat. 1948;19:30-39] elegant results of equivalence blocks. The validity of these new tolerance regions is proven mathematically in [Ann Math Stat. 1947;18:529-539; Ann Math Stat. 1948;19:30-39] under the only assumption that the underlying distribution of the measurements is continuous. The methodology is applied to analyze the kidney function problem considered in Young and Mathew [Stat Methods Med Res. 2020;29:3569-3585]

New tools for network time series with an application to COVID-19 hospitalisations

Network time series are becoming increasingly important across many areas in science and medicine and are often characterised by a known or inferred underlying network structure, which can be exploited to make sense of dynamic phenomena that are often high-dimensional. For example, the Generalised Network Autoregressive (GNAR) models exploit such structure parsimoniously. We use the GNAR framework to introduce two association measures: the network and partial network autocorrelation functions, and introduce Corbit (correlation-orbit) plots for visualisation. As with regular autocorrelation plots, Corbit plots permit interpretation of underlying correlation structures and, crucially, aid model selection more rapidly than using other tools such as AIC or BIC. We additionally interpret GNAR processes as generalised graphical models, which constrain the processes' autoregressive structure and exhibit interesting theoretical connections to graphical models via utilization of higher-order interactions. We demonstrate how incorporation of prior information is related to performing variable selection and shrinkage in the GNAR context. We illustrate the usefulness of the GNAR formulation, network autocorrelations and Corbit plots by modelling a COVID-19 network time series of the number of admissions to mechanical ventilation beds at 140 NHS Trusts in England & Wales. We introduce the Wagner plot that can analyse correlations over different time periods or with respect to external covariates. In addition, we introduce plots that quantify the relevance and influence of individual nodes. Our modelling provides insight on the underlying dynamics of the COVID-19 series, highlights two groups of geographically co-located `influential' NHS Trusts and demonstrates superior prediction abilities when compared to existing techniques

Age-related gait standards for healthy children and young people: the GOS-ICH paediatric gait centiles

Objective To develop paediatric gait standards in healthy children and young people. Methods This observational study builds on earlier work to address the lack of population standards for gait measurements in children. Analysing gait in children affected by neurological or musculoskeletal conditions is an important component of paediatric assessment but is often confounded by developmental changes. The standards presented here do not require clinician expertise to interpret and offer an alternative to developmental tables of normalised gait data. Healthy children aged 1-19 years were recruited from community settings in London and Hertfordshire, U.K. The GAITRite ® walkway was used to record measurements for each child for velocity, cadence, step length, base of support, and stance, single and double support (as percentage of gait cycle). We fitted generalized linear additive models for location, scale and shape (gamlss). Results We constructed percentile charts for seven gait variables measured on 624 (321 males) contemporary healthy children using gamlss package in R. A clinical application of gait standards was explored. Conclusion Age-related, gender-specific standards for seven gait variables were developed and are presented here. They have a familiar format and can be used clinically to aid diagnoses, and to monitor change over time for both medical therapy and natural history of the condition. The clinical example demonstrates the potential of the GOS-ICH Paediatric Gait Centiles (GOS-ICH PGC) to enable meaningful interpretation of change in an individual’s performance, and describes characteristic features of gait from a specific population throughout childhood.Peer reviewedFinal Accepted Versio

Effect of impaired vision on physical activity from childhood to adolescence

International physical activity (PA) guidelines are set irrespective of disabilities. Yet the levels of and changes in PA across transition from childhood into adolescence among those with impaired vision are not well understood due to the challenges of longitudinal population-based studies of rare conditions. Our study investigated whether children and adolescents with impaired vision can achieve PA levels equivalent to those without impaired vision

Do adolescents with impaired vision have different intentions and ambitions for their education, career and social outcomes compared to their peers? Findings from the Millennium Cohort Study

BACKGROUND/AIMS: To investigate if impaired vision adversely impacts the intentions/ambitions of adolescents concerning their future education, careers and social outcomes. METHODS: Population-based birth cohort study in the UK comprising 9273 participants from the Millennium Cohort Study who were followed up to age 17 years. Children were classified as having normal vision or unilateral or bilateral impaired vision caused by significant eye conditions based on detailed parental-structured questionnaire data on sight problems and treatment coded by clinicians. Ten domains covering education, career and social outcomes by age 30 were investigated. RESULTS: Adjusted regression models showed few differences by vision status. Bilateral impaired vision was associated with increased odds of intending to remain in full-time education after statutory school age (adjusted OR (aOR) 2.00, 95% CI 1.08 to 3.68) and of home ownership at age 30 (aOR 1.83, 95% CI 1.01 to 3.32). Impaired vision was not associated with intending to attend university. A significantly higher proportion of parents of children with bilateral or unilateral impaired vision thought that their child would not get the exam grades required to go to university than parents of those with normal vision (29% or 26% vs 16%, p=0.026). CONCLUSION: Adolescents with impaired vision have broadly the same intentions/ambitions regarding future education, careers and social outcomes as their peers with normal vision. The known significant gaps in attainment in these domains among young adults with vision impairment are therefore likely to be due to barriers that they face in achieving their ambitions. Improved implementation of existing interventions is necessary to ensure equality of opportunities

Fright but not fight‐or‐flight: Violent video games elevated stress markers, but did not impact muscle function, memory recall or food intake, in a randomized trial in healthy young men

Objectives: Regular video game playing has been linked with obesity, but the underlying mechanisms remain unclear. Drawing on evolutionary life history theory, we hypothesized that playing violent video games, through activating the stress response, might increase the immediate demand for fuel by muscle and brain tissue, resulting in elevated appetite and food consumption. // Methods: We randomized 71 young adult men to play video games, involving either violent content or nonviolent puzzle-solving, for 1 h. Over this period, we measured stress markers (blood pressure [BP], heart rate, visual-analogue scale [VAS] self-ratings), muscle function (handgrip strength) and cognitive function (memory recall test). Appetite was assessed by VAS, and by food intake using a test-meal after the intervention. Linear mixed-effects models were fitted to assess group effects and group:time effects. // Results: During the intervention, the violent video game group showed elevated systolic BP (∆ = 4.7 mm Hg, 95% CI 1.0, 8.4) and reported feeling more alert but less calm or happy. They showed no difference in grip strength or memory recall. They reported lower feelings of “fullness” but consumed similar food-energy during the test-meal. // Conclusions: Although playing a video game with violent content elevated physiological and perceived stress markers compared with a nonviolent game, this was not associated with markers of altered fuel distribution toward two tissues (muscle and brain) that contribute to the “fight-or-flight” response. Rather than more energy being allocated to the brain overall, energy may have been reallocated within the brain. This may explain why there was no compensatory increase in energy intake in the violent video game group

Performance on the iSTEP and 10 m-ISWT in boys with haemophilia

INTRODUCTION: Boys with haemophilia (BwH) have improved health outcomes. Measures of physical function in haemophilia are not challenging or sensitive enough to reflect physical limitations or guide rehabilitation. To identify meaningful tests, we aimed to: evaluate the performance of BwH on two physical performance measures: iSTEP and 10 m-ISWT; identify factors which predict performance and compare BwH to their unaffected peers. METHODS: BwH completed both iSTEP and 10 m-ISWT. Disease severity, age, BMI, HJHS, lower limb muscle torque, time spent in moderate to vigorous physical activity, sedentary time, were included as factors to predict performance. Results were compared to unaffected peers. RESULTS: 43 boys median age 10 (10 mild/moderate, 26 severe, 7 inhibitors) were recruited. BwH were less likely to complete the iSTEP and performed less well on the 10 m-ISWT than age matched peers. Ceiling effects were apparent for iSTEP, but not the 10 m-ISWT test. Age was the only significant predictor for performance in the iSTEP, with older boys being more likely to achieve a higher level or complete the test. Greater age, lower BMI, milder disease severity and more time spent in MVPA all predicted better performance on the 10 m-ISWT, with BMI and habitual physical activity a potential rehabilitation focus for underperforming individuals. HJHS and muscle strength did not predict performance on either test. CONCLUSION: Despite the space need to conduct the 10 m-ISWT, it appears to be a superior performance measure than the iSTEP in BwH and provides clinically meaningful information, which can be interpreted using age-specific normative reference equations

The synergy factor: a statistic to measure interactions in complex diseases

<p>Abstract</p> <p>Background</p> <p>One challenge in understanding complex diseases lies in revealing the interactions between susceptibility factors, such as genetic polymorphisms and environmental exposures. There is thus a need to examine such interactions explicitly. A corollary is the need for an accessible method of measuring both the size and the significance of interactions, which can be used by non-statisticians and with summarised, e.g. published data. The lack of such a readily available method has contributed to confusion in the field.</p> <p>Findings</p> <p>The synergy factor (<it>SF</it>) allows assessment of binary interactions in case-control studies. In this paper we describe its properties and its novel characteristics, e.g. in calculating the power to detect a synergistic effect and in its application to meta-analyses. We illustrate these functions with real examples in Alzheimer's disease, e.g. a meta-analysis of the potential interaction between a <it>BACE1 </it>polymorphism and <it>APOE</it>4: <it>SF </it>= 2.5, 95% confidence interval: 1.5–4.2; <it>p </it>= 0.0001.</p> <p>Conclusion</p> <p>Synergy factors are easy to use and clear to interpret. Calculations may be performed through the Excel programmes provided within this article. Unlike logistic regression analysis, the method can be applied to datasets of any size, however small. It can be applied to primary or summarised data, e.g. published data. It can be used with any type of susceptibility factor, provided the data are dichotomised. Novel features include power estimation and meta-analysis.</p