Tracking of MVPA across childhood and adolescence.

OBJECTIVES: Tracking of physical activity from childhood onwards is an important public health issue, but evidence on tracking is limited. This study quantified the tracking of Moderate-Vigorous Physical Activity (MVPA) across childhood and adolescence in a recent cohort from England. DESIGN: Longitudinal, with a socio-economically representative sample from North-East England, over an 8-year period. METHODS: Measures of time spent in MVPA, with an Actigraph GT1M accelerometer, were made at age 7-8y (n = 622, T1), age 9-10y (n = 585, T2), age 12-13y (n = 525, T3) and age 14-16y (n = 361, T4). Tracking of MVPA was assessed using rank order correlations between time spent in MVPA T1-T2, T1-T3, and T1-T4, and by using Cohen's kappa to examine tracking of meeting the MVPA guideline (mean of 60 min/d). We examined whether tracking varied by sex, socio-economic status (SES), initial MVPA, or initial body fatness. RESULTS: Rank order correlations were all statistically significant at p < 0.01 and moderate: 0.58 between T1 and T2; 0.42 between T1 and T3; 0.41 between T1 and T4. Cohen's kappas for meeting the global MVPA guideline were all significant, weakening from moderate to low over the 8 years. Tracking was stronger in higher SES compared to lower SES groups, and there was some evidence that it was stronger in girls than boys, but the other explanatory variables had little influence on tracking. CONCLUSIONS: Tracking of MVPA from mid-childhood to mid-adolescence in this cohort was moderate. This study suggests there is a need to establish high MVPA by mid-childhood, and to mitigate the age-related reduction in MVPA which occurs from mid-childhood.

Cumulative methotrexate dose is not associated with liver fibrosis in patients with a history of moderate to severe psoriasis.

BACKGROUND: Liver fibrosis (LF) has established risk factors, but data on the impact of methotrexate on LF in psoriasis patients are lacking. This cross-sectional study aimed to determine the prevalence of LF in psoriasis patients and to evaluate the relationship between LF, cumulative methotrexate dose and other LF risk factors. METHODS: Adults with a history of moderate to severe chronic plaque psoriasis were recruited between June 2020 and March 2021. Patients underwent transient elastography to evaluate LF. Three values for liver stiffness measurement (LSM) were assessed, indicating mild or worse LF (≥7kPa), moderate or worse LF (≥7.9 kPa) and advanced LF (≥9.5kPa). Cumulative methotrexate dose and other potential risk factors for LF were assessed. RESULTS: 240 patients were recruited and 204 participants with valid LSM values were included in the analysis (median age 48 (IQR 37,57) years; 51% female; 56% Body Mass Index (BMI) ≥30 kg/m2 and median Alcohol Use Disorders Identification Test (AUDIT) score 4 (IQR 1,7, 23% score ≥ 8)). 91% had received methotrexate (median duration 36 months (IQR 14,78)). Prevalence of LF was 36%, 25% and 17 % using LSM ≥7kPa, ≥7.9 kPa and ≥9.5kPa respectively. There was no association between cumulative methotrexate dose (median 2.16 (IQR 0.93, 5.2) and continuous LSM values (unstandardised coefficient 0.16, (95% CI -0.49-0.82, p=0.626) or using the categorical LSM cut off values: ≥7kPa (unadjusted odds ratio 1.06 (95% CI 0.97-1.15), p= 0.192), ≥7.9 kPa (unadjusted odds ratio 1.03 (95% CI 0.94- 1.12), p= 0.577) and ≥9.5kPa (unadjusted odds ratio 1.01 (95% CI 0.91-1.12) p=0.843).The following risk factors were associated with higher LSM values: BMI (p=<0.001), Waist circumference (p=<0.001), metabolic syndrome (p=<0.001), AUDIT score (P=0.020), FIB-4 score (p= 0.03). BMI ≥28, diabetes and metabolic syndrome were shown to be better predictors of LF compared to Fib 4 score. CONCLUSION: This study confirms a high prevalence of significant LF in patients with psoriasis. Cumulative methotrexate dose was not associated with LF. Patients with BMI ≥28 kg/m2, metabolic syndrome and diabetes are at higher risk for LF. These risk factor may help to identify when a more detailed liver health assessment is needed.

Associations between early infections and childhood cognition in the Newcastle Thousand Families Study birth cohort.

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.

A Randomised Control Trial Investigating the Efficacy of the MapMe Intervention on Parental Ability to Correctly Categorise Overweight in Their Child and the Impact on Child BMI Z-Score Change at 1 Year.

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.

Radiation exposure and leukaemia risk among cohorts of persons exposed to low and moderate doses of external ionising radiation in childhood.

BACKGROUND: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear. METHODS: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted. RESULTS: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards. DISCUSSION: We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy.

Differences Between Self-Reported and Objectively Measured Hearing Loss at Age 61-63 Years: The Newcastle Thousand Families Birth Cohort.

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.

Knowledge, attitude and practice of infection prevention and control precautions among laboratory staff: a mixed-methods systematic review.

BACKGROUND: Clinical laboratories provide diagnostic testing services to support the effective delivery of care in today's complex healthcare systems. Processing clinical material and the use of chemicals or radiation presents potential hazard to laboratory workers, from both biological and chemical sources. Nevertheless, the laboratory should be a safe workplace if the identification of possible hazards, clear guidelines, safety rules and infection prevention and control (IPC) precautions are applied and followed. The main aim of this systematic review was to identify, critically appraise and synthesise the research evidence to gain a clear explanation of the implementation and knowledge, attitude and practice (KAP) of IPC guidelines among hospital laboratory staff. METHODS: For this systematic review we searched MEDLINE, EMBASE, Scopus and CINAHL (EBSCO), PubMed, grey literature, reference lists and citations for studies published between database inception and November, 2021. All qualitative, quantitative and mixed-methods studies whose aim was to explore risk perception and KAP of IPC guidelines among laboratory staff in any healthcare setting were included, without language or date restrictions. Evidence was narratively synthesised into group of themes. The quality of the evidence was assessed with Joanna Briggs Institutes Critical Appraisal Tools. RESULTS: After the full-text screening, a total of 34 articles remained and were included in the final review. Thirty papers were considered to be of high quality and the remaining four were considered to be of low quality. The available evidence shows that there was good knowledge, good attitudes and moderate immunisation status, but there was still poor practice of IPC precautions and an inadequate level of training among laboratory workers. CONCLUSION: There is a gap among KAP related to the implementation of IPC guidelines, which indicates that laboratory staff may be at high risk of acquiring infections in the workplace. These findings suggest that training (including IPC precautions, safety policies, safety equipment and materials, safety activities, initial biohazard handling, ongoing monitoring and potential exposure) of laboratory staff to increase their knowledge about IPC precautions could improve their use of these precautions.

Physical activity in young children across developmental and health states: the ActiveCHILD study.

Background: Evidence about physical activity of young children across developmental and health states is very limited. Using data from an inclusive UK cohort, ActiveCHILD, we investigated relationships between objectively measured physical activity, child development, social context, and health-related quality of life (HRQoL). Methods: Children (12-36 months), purposively sampled across health pathways, developmental abilities, and sociodemographic factors, were recruited through thirteen National Health Service organisations in England. Data were collected from 07/2017 to 08/2019 on: weekly physical activity (3-7 days) using waist-worn accelerometer (ActiGraph 3GTX); sociodemographics, parent actions, child HRQoL, and child development using questionnaires; and child health conditions using clinical records. A data-driven, unsupervised method, called hidden semi-Markov model (HSMM) segmented the accelerometery data and provided estimates of the total time spent active (any intensity) and very active (greater intensity) for each child. Relationships with the explanatory factors were investigated using multiple linear regression. Findings: Physical activity data were obtained for 282 children (56% females, mean age 21 months, 37.5% with a health condition) covering all index of multiple deprivation deciles. The patterns of physical activity consisted of two daily peaks, children spending 6.44 (SD = 1.39) hours active (any intensity), of which 2.78 (SD = 1.38) hours very active, 91% meeting WHO guidelines. The model for total time active (any intensity) explained 24% of variance, with mobility capacity the strongest predictor (ß = 0.41). The model for time spent very active explained 59% of variance, with mobility capacity again the strongest predictor (ß = 0.76). There was no evidence of physical activity explaining HRQoL. Interpretation: The findings provide new evidence that young children across developmental states regularly achieve mainstream recommended physical activity levels and challenges the belief that children with development problems need lower expectations for daily physical activity compared to peers. Advancing the rights of all children to participate in physical activity requires inclusive, equally ambitious, expectations for all. Funding: Niina Kolehmainen, HEE/NIHR Integrated Clinical Academic Senior Clinical Lecturer, NIHR ICA-SCL-2015-01-00, was funded by the NIHR for this research project. Christopher Thornton, Olivia Craw, Laura Kudlek, and Laura Cutler were also funded from this award. Tim Rapley is a member of the NIHR Applied Research Collaboration North East and North Cumbria, with part of his time funded through the related award (NIHR200173). The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS, or the UK Department of Health and Social Care. The work of Kianoush Nazarpour is supported by Engineering and Physical Sciences Research Council (EPSRC), under grant number EP/R004242/2.

Dental antibiotics and referrals in general medical practice: Wales 1974-2017.

OBJECTIVES: This study aimed to explore trends and predictors for antibiotic prescriptions and referrals for patients seeking dental care at General Medical Practitioners (GMPs) over a 44-year period in Wales, UK. METHODS: This retrospective observational study analysed data from the nationwide Secure Anonymised Information Linkage Databank of visits to GMPs. Read codes associated with dental diagnoses were extracted from 1974-2017. Data were analysed using descriptive statistics, univariate and multivariable logistic regression. RESULTS: Over the 44-year period, there were a total of 160,952 antibiotic prescriptions and 2,947 referrals associated with a dental attendance. Antibiotic prescriptions were associated with living in the most deprived (OR 0.91, 95% CI 0.89-0.93) or rural (OR 0.83, 95% CI 0.82-0.84) areas, whereas referrals were associated with living in an urban area (OR 2.16, 95% CI 1.99-2.35) or rural and less deprived area (OR 1.71, 95% CI 1.26-2.33). The number of antibiotic prescriptions decreased over time whereas the number of referrals increased. CONCLUSIONS: These changes coincide with dental attendance rates at GMPs over the same period and indicate that appointment outcome and repeat patient attendance are linked. Rurality and deprivation may also influence care provided. CLINICAL SIGNIFICANCE: General medical practices are not the most appropriate place for patients seeking dental care to attend, and efforts should be made to change current practice and policy to support patients to seek care from dental practices. When patients do seek dental care from GMPs they should be encouraged to refer the patient to a dentist rather than prescribe antibiotics as an important element of national antimicrobial stewardship efforts, as well as to discourage repeat attendance.

Quality of life and home parenteral nutrition: a survey of UK healthcare professionals' knowledge, practice and opinions.

BACKGROUND: There is increasing interest in the assessment of health-related quality of life (QoL) in the care of patients treated with home parenteral nutrition (HPN). However, it is not known whether healthcare professionals (HCPs) have embedded QoL assessment into routine clinical practice in line with current guidelines to favour a more holistic approach to HPN care. The aim of this study was to assess knowledge, current practice and the opinions of HCPs regarding QoL in care of patients on HPN. METHODS: An online survey was distributed via email to HCPs working with HPN patients throughout England, Scotland, Wales and Northern Ireland. Participants were identified using a mailing list for the British Intestinal Failure Alliance, a specialist group within the British Association for Parenteral and Enteral Nutrition. RESULTS: The survey was completed by 67 professionals comprising 24 dietitians, 17 nurses, 14 gastroenterologists, 6 pharmacists, 5 surgeons and 1 psychologist. Of these, 54 (80%) participants agreed that the measurement of QoL is useful. In contrast, 38 (57%) of all participants, including 27 (50%) of those participants who agreed that the measurement of QoL was useful, never measured QoL. Knowledge of QoL literature was rated as poor or very poor by 27 (40%) participants. CONCLUSIONS: Despite the perceived usefulness and importance of QoL assessment, very few HCPs embed it into clinical practice. Knowledge of QoL literature and QoL tools is variable, and there is significant variability in QoL practice. This is clear in terms of the frequency of QoL assessments and heterogeneity in methodology. In contrast, there was almost unanimous agreement that the complications associated with HPN contribute to poorer QoL. There is a need for specific, evidence-based, clinical practice guidelines detailing how to define and measure QoL in this patient population.

Muscle Function, Body Composition, Insulin Sensitivity and Physical Activity in Adolescents Born Preterm: Impact of Gestation and Vitamin D Status.

Whilst several studies have explored adolescent metabolic and cognitive function after preterm birth, few have explored muscle function and physical activity. We set out to examine the relationship between gestational age and muscle metabolism in a cohort of adolescents who were born preterm. Participants were recruited from the Newcastle preterm birth growth study cohort. They did not have severe neurological disease and were not on daily medication. Participants underwent an assessment of oxidative muscle function using phosphorus magnetic resonance spectroscopy that included the half-time for recovery of equilibrium of phosphocreatine, τ½PCr. In addition, we measured key variables that might affect muscle function including physical activity levels determined by 3-day accelerometry, body composition using air displacement plethysmography, insulin sensitivity using the homeostatic model assessment/Matsuda index and serum vitamin D concentrations. 60 adolescents (35F) median age 15.6 years (range 12.1−18.8) with a median gestation of 31 weeks (range 24 to 34 weeks) underwent a single assessment. Males were more active and spent less time in sedentary mode. Time spent in light activity was associated with insulin sensitivity (IS) (Matsuda Index; p < 0.05) but there were no strong correlations between activity levels and gestational age. Greater fat mass, waist circumference and body mass index were all associated with lower IS. Gestational age was negatively associated with adjusted measures of oxidative muscle function (τ½PCr). In a stepwise multivariate linear regression model, gestational age at birth was the most significant predictor of oxidative muscle function (p = 0.005). Higher serum vitamin D levels were also associated with faster phosphocreatine recovery time (p = 0.045). Oxidative function in the skeletal muscle of adolescents born preterm is associated with gestational age and vitamin D concentrations. Our study suggests that being born preterm may have a long-term impact on muscle metabolism.

The effects of radiofrequency exposure on male fertility and adverse reproductive outcomes: A protocol for two systematic reviews of human observational studies with meta-analysis.

BACKGROUND: The World Health Organization (WHO) is bringing together evidence on radiofrequency electromagnetic field (RF-EMF) exposure in relation to health outcomes, previously identified as priorities for evaluation by experts in the field, to inform exposure guidelines. A suite of systematic reviews are being undertaken by a network of topic experts and methodologists in order to collect, assess and synthesise data relevant to these guidelines. Here, we present the protocol for the systematic review on the effect of exposure to RF on adverse reproductive outcomes (human observational studies), also referred to as Systematic Review (SR) 3 within the series of systematic reviews currently being commissioned. OBJECTIVES: Following the WHO handbook for guideline development and the COSTER conduct guidelines, we will systematically review the effect of RF-EMF exposure on both male fertility (SR3A) and adverse pregnancy outcomes (SR3B) in human observational studies. Herein we adhere to the PRISMA-P reporting guidelines. DATA SOURCES: We will conduct a broad search for potentially relevant records relevant for both reviews within the following bibliographic databases: MEDLINE; Embase; and EMF Portal. We will also conduct searches of grey literature through relevant databases and organisational websites. RF-EMF experts will also be consulted. We will hand search citation and reference lists of included study records. STUDY ELIGIBILITY CRITERIA: We will include quantitative human observational studies on the effect of RF-EMF exposure: (in SR3A) in adult male participants on infertility, sperm morphology, concentration or total sperm count or motility; and (in SR3B) in preconception adults or pregnant women on preterm birth, small for gestational age (associated with intrauterine growth restriction), miscarriage, stillbirth and congenital anomalies. STUDY APPRAISAL AND SYNTHESIS METHODS: Titles, abstracts and then full texts will be screened in blinded duplicate against eligibility criteria with input from a third reviewer as required. Data extraction from included studies will be completed by two reviewers as will risk of bias assessment using the Office of Health Assessment and Translation (OHAT) tool. If appropriate we will undertake meta-analysis to pool effect measures and explore heterogeneity using sub-group analyses or meta-regression as feasible. We will conduct sensitivity analysis to assess the impact of any assumptions made throughout the review process. The OHAT methodology, based on the GRADE guidelines for evidence assessment, will be used to evaluate the certainty of evidence per outcome and to conclude the level of evidence of a health effect. CONCLUSION: This manuscript details the protocols for two systematic reviews. The aims of publishing details of both protocols are to: pre-specify their scope and methods; reduce the impact of reviewer bias; promote transparency and replicability; and improve the review process. PROSPERO REGISTRATION: CRD42021265401 (SR3A), CRD42021266268 (SR3B).

Failure to Launch: Predictors of Unfavourable Physical Activity and Sedentary Behaviour Trajectories from Childhood to Adolescence: The Gateshead Millennium Study.

In a previous study based on this cohort, only 15% of the participants belonged to a favourable physical activity/sedentary behaviour trajectory group (characterised by relatively high moderate-vigorous intensity physical activity and relatively low sedentary behaviour across childhood and adolescence). Since this favourable trajectory is protective against obesity, we aimed to identify factors associated with membership of this group. In this longitudinal study, 671 participants were assessed at ages 7, 9, 12 and 15 years. Participants' demographics, socio-economic status (SES) and physical activity environment such as, sports club participation and commuting school were assessed at ages 7, 9 and 12 and analysed with favourable trajectory membership as an outcome using multinomial logistic regression. Sex (male) and SES (higher) were the non-modifiable factors associated with favourable trajectory group. Of the modifiable factors, commuting to school at age 7, a safe environment to play at age 7 and sports club participation at age 12 were all associated with more than 2.0 times increased probability of being in the most favourable trajectory. Future interventions to promote a favourable trajectory could focus on girls and participants with low SES. Promoting active commuting, safe local spaces to play and sports participation should also help lead to a favourable trajectory for physical activity and sedentary behaviour across childhood and adolescence.

Moderate-To-Vigorous Intensity Physical Activity and Sedentary Behaviour across Childhood and Adolescence, and Their Combined Relationship with Obesity Risk: A Multi-Trajectory Analysis.

The combined role of objectively assessed moderate-vigorous intensity physical activity (MVPA) and sedentary behaviour (SB) is unclear in obesity prevention. This study aimed to identify latent groups for MVPA and SB trajectories from childhood to adolescence and examine their relationship with obesity risk at adolescence. From the Gateshead Millennium Study, accelerometer-based trajectories of time spent in MVPA and SB at ages 7, 9, 12, and 15 were derived as assigned as the predictor variable. Fat mass index (FMI), using bioelectrical impedance at age 15, was the outcome variable. From 672 children recruited, we identified three distinct multiple trajectory groups for time spent in MVPA and SB. The group with majority membership (54% of the cohort) had high MVPA and low SB at childhood, but MVPA declined and SB increased by age 15. One third of the cohort (31%) belonged to the trajectory with low MVPA and high time spent sedentary throughout. The third trajectory group (15% of the cohort) that had relatively high MVPA and relatively low SB throughout had lower FMI (-1.7, 95% CI (-3.4 to -1.0) kg/m2, p = 0.034) at age 15 compared to the inactive throughout group. High MVPA and low SB trajectories when combined are protective against obesity.

Osteoporosis, fracture, osteoarthritis & sarcopenia: A systematic review of circulating microRNA association.

Circulating microRNAs (c-miRs) show promise as biomarkers. This systematic review explores their potential association with age-related fracture/osteoporosis (OP), osteoarthritis (OA) and sarcopenia (SP), as well as cross-disease association. Most overlap occurred between OA and OP, suggesting potentially shared microRNA activity. There was little agreement in results across studies. Few reported receiver operating characteristic analysis (ROC) and many identified significant dysregulation in disease, but direction of effect was commonly conflicting. c-miRs with most evidence for consistency in dysregulation included miR-146a, miR-155 and miR-98 for OA (upregulated). Area under the curve (AUC) for miR-146a biomarker performance was AUC 0.92, p = 0.028. miR-125b (AUC 0.76-0.89), miR-100, miR-148a and miR-24 were consistently upregulated in OP. Insufficient evidence exists for c-miRs in SP. Study quality was typically rated intermediate/high risk of bias. Wide study heterogeneity meant meta-analysis was not possible. We provide detailed critique and recommendations for future approaches in c-miR analyses based on this review.

Early diet in preterm infants and later cognition: 10-year follow-up of a randomized controlled trial.

BACKGROUND: Achieving adequate nutrition in preterm infants is challenging. The post-discharge period may be critical for influencing growth and cognitive outcomes. We studied the effects of post-discharge nutrition on childhood cognition. METHODS: Preterm-born children were randomized at ~36 weeks corrected age (CGA) to either preterm formula (PTF) or term formula (TF) until 6 months, or PTF until 40 weeks CGA, then TF until 6 months (crossover group). Childhood cognition was assessed using the short form Wechsler Intelligence Scale for Children III, allowing computation of full-scale intelligence quotient (FSIQ) and four-factor index scores; verbal comprehension, freedom from distractibility (FDI), perceptual organization (POI), and processing speed (PSI). RESULTS: Ninety-two children were recruited (mean 10.1 years). FSIQ did not differ by group. PTF-fed children had 10-point higher PSI (p = 0.03) compared to crossover. Faster weight gain from term to 12 weeks CGA was associated with 5-point higher FSIQ (p = 0.02) and four-point higher POI (p = 0.04). Infant head growth was positively associated with FSIQ (+3.8 points, p = 0.04) and FDI (+6 points, p = 0.003). CONCLUSIONS: While there is no long-term impact of post-discharge macronutrient enrichment on childhood cognition, greater weight and head growth in specific epochs is associated with better outcomes. Further studies are needed to determine optimal early diet in preterm infants. IMPACT: Achieving adequate nutrient intakes in preterm infants before and after hospital discharge is challenging. Nutrient intakes prior to discharge affect later cognitive and metabolic outcomes. Follow-up of a randomized controlled trial shows no cognitive benefit in later childhood from a more nutrient-dense formula compared to standard formula after hospital discharge. Growth in the first year of life is strongly correlated with childhood cognition and emphasizes the importance of nutrition in early life.

Ranibizumab and aflibercept intravitreal injection for treatment naïve and refractory macular oedema in branch retinal vein occlusion.

BACKGROUND: Branch retinal vein occlusion complicated by macular oedema is a common disease treated with intravitreal injection of anti-vascular endothelial growth factor. Controversy exists surrounding anti-vascular endothelial growth factor selection for both treatment naïve and refractory cases. METHODS: A retrospective electronic medical record review at a single UK centre generated a cohort of 259 treatment naïve eyes from 258 patients receiving ranibizumab, aflibercept or a combination (n = 83, 97 and 79, respectively) from 2013 to 2018 with ⩾6 months follow-up. Number of intravitreal injections, visual acuity and macular oedema presence were noted at 3, 6, 12, 24, 36 and 48 months. A subgroup analysis examined refractory cases switched from ranibizumab to aflibercept (n = 77) or maintained on ranibizumab (n = 35). RESULTS: Eyes receiving ranibizumab or aflibercept had equivocal vision gain at 1 year, 8.0 (95% CI 5.0-11.0) and 9.6 (7.2-12.1) Early Treatment of Diabetic Retinopathy Study letters, respectively. About 35.6% had no macular oedema at 12 months with ranibizumab compared with 50.0% with aflibercept (p = 0.07) following 5.1 (4.7-5.6) and 6.0 (5.6-6.4) intravitreal injections, respectively. Visual prognosis declined significantly as treatment delay extended (p = 0.003) which was only apparent with ⩾3 months delay. Eyes with refractory macular oedema also had equivocal functional and anatomical outcomes whether they were maintained on ranibizumab or switched to aflibercept. CONCLUSION: These real world data demonstrate more modest clinical improvements from anti-vascular endothelial growth factor treatment than reported in clinical trials. The functional outcomes of ranibizumab and aflibercept in both treatment naïve and refractory cases were equivocal while the anatomical outcomes of aflibercept may be superior.

The Biological and Social Determinants of Childhood Obesity: Comparison of 2 Cohorts 50 Years Apart.

OBJECTIVE: To determine whether the same relationships between early-life risk factors and socioeconomic status (SES) with childhood body mass index (BMI) are observed in a modern cohort (2000) compared with a historic cohort (1947). STUDY DESIGN: The relationships between early-life factors and SES with childhood BMI were examined in 2 prospective birth cohorts from the same region, born 50 years apart: 711 children in the 1947 Newcastle Thousand Families Study (NTFS) and 475 from the 2000 Gateshead Millennium Study (GMS). The associations between birth weight, breastfeeding, rapid infancy growth (0-12 months), early-life adversity (0-12 months), and parental SES (birth and childhood) with childhood BMI z-scores and whether overweight/obese (BMI >91st percentile using UK 1990 reference) aged 9 years were examined using linear regression, path analyses, and logistic regression. RESULTS: In the NTFS, the most advantaged children were taller than the least (+0.91 height z-score, P = .001), whereas in GMS they had lower odds of overweight/obese than the least (0.35 [95% CI 0.14-0.86]). Rapid infancy growth was associated with increased BMI z-scores in both cohorts, and with increased likelihood of overweight/obese in GMS. CONCLUSIONS: This study suggests that children exposed to socioeconomic disadvantage or who have rapid infancy growth in modern environments are now at lower risk of growth restriction but greater risk of overweight.

The HARMONIC project: study design for the assessment of radiation doses and associated cancer risks following cardiac fluoroscopy in childhood.

The HARMONIC project (Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Paediatrics) is a European study aiming to improve our understanding of the long-term health risks from radiation exposures in childhood and early adulthood. Here, we present the study design for the cardiac fluoroscopy component of HARMONIC. A pooled cohort of approximately 100 000 patients who underwent cardiac fluoroscopy procedures in Belgium, France, Germany, Italy, Norway, Spain or the UK, while aged under 22 years, will be established from hospital records and/or insurance claims data. Doses to individual organs will be estimated from dose indicators recorded at the time of examination, using a lookup-table-based dosimetry system produced using Monte Carlo radiation transport simulations and anatomically realistic computational phantom models. Information on beam geometry and x-ray energy spectra will be obtained from a representative sample of radiation dose structured reports. Uncertainties in dose estimates will be modelled using 2D Monte Carlo methods. The cohort will be followed up using national registries and insurance records to determine vital status and cancer incidence. Information on organ transplantation (a major risk factor for cancer development in this patient group) and/or other conditions predisposing to cancer will be obtained from national or local registries and health insurance data, depending on country. The relationship between estimated radiation dose and cancer risk will be investigated using regression modelling. Results will improve information for patients and parents and aid clinicians in managing and implementing changes to reduce radiation risks without compromising medical benefits.

Communication disorders in young children with cerebral palsy.

AIM: To test the prediction of communication disorder severity at 5 years of age from characteristics at 2 years for children with cerebral palsy (CP) whose communication is giving cause for concern. METHOD: In this cohort study, 77 children (52 males; 25 females) with communication difficulties and CP were visited at home at 2 (mean 2y 4mo; SD 3mo) and 5 (mean 5y 5mo; SD 4mo) years of age. Information on the type and distribution of motor disorder, seizures, gross and fine motor function, hearing, and vision were collected from medical notes. Non-verbal cognition, language comprehension, language expression, spoken vocabulary, and methods of communication were assessed directly at age 2 years. At 5 years, communication and speech function were rated using the Communication Function Classification System (CFCS), Functional Communication Classification System (FCCS), and Viking Speech Scale (VSS). RESULTS: In multivariable regression models, CP type, Gross Motor Function Classification System level, vision, the amount of speech understood by strangers, non-verbal cognition, and number of consonants produced at age 2 years predicted the CFCS level at age 5 years (R2 =0.54). CP type, Manual Ability Classification System level, amount of speech understood, vision, and number of consonants predicted the FCCS level (R2 =0.49). CP type, amount of speech understood by strangers, and number of consonants predicted the VSS level (R2 =0.50). INTERPRETATION: Characteristics at 2 years of age predict communication and speech performance at 5 years, and should inform referral to speech and language therapy.