Enabling participation of Black and Minority Ethnic (BME) and seldom-heard communities in health research: A case study from the SCAMP adolescent cohort study

Our inquiry investigated the barriers to, and facilitators for, the involvement of Black and Minority Ethnic (BME) and ‘seldom-heard’ communities, in a study researching the impact of mobile phone and wireless device usage on adolescents’ cognition, behaviour and mental health. The aim was to co-produce solutions to increase participation, and we used focus groups, telephone interviews, a community event and a public and patient involvement (PPI) café to conduct the inquiry. Five themes emerged from the data: two enablers – the value and benefits of research; and three barriers – concerns about research and about communication, and practical constraints. A central cross-cutting theme, the concept of trust, was evident from the data, and extended across all themes, including across the solutions to nonparticipation. When the data collection and analysis were completed, we ran a symposium for researchers and members of the public to share our findings and to co-produce solutions. The symposium generated ideas about improving participation, including tailoring participant information, engaging with local advocates and involving people in research design and delivery

Cohort Profile: The Study of Cognition, Adolescents and Mobile Phones (SCAMP)

The Study of Cognition, Adolescents and Mobile Phones (SCAMP) is a prospective secondary school-based cohort study established to investigate whether use of mobile phones and other wireless devices that emit radio-frequency electromagnetic fields (RF-EMF) is associated with cognitive, behavioural, educational, physical and mental health outcomes during adolescence. Specifically, the principal aim is to discern whether any observed associations may be due to: (i) RF-EMF exposure from mobile phones; (ii) a combination of various RF-EMF sources (e.g. digital enhanced cordless technology phones or wireless internet); or (iii) other behavioural reasons associated with technology use for communication and entertainment, irrespective of exposure to RF-EMF

Night-time screen-based media device use and adolescents’ sleep and health-related quality of life.

Objective: The present study investigates the relationship between night-time screen-based media devices (SBMD) use, which refers to use within one hour before sleep, in both light and dark rooms, and sleep outcomes and health-related quality of life (HRQoL) among 11 to 12-year-olds. Methods: We analysed baselined data from a large cohort of 6,616 adolescents from schools in and around London, United Kingdom, participating in the Study of Cognition Adolescents and Mobile Phone (SCAMP). Adolescents self-reported their use of any SBMD (mobile phone, tablet, laptop, television etc.). Sleep variables were derived from self-reported weekday and/or weekend bedtime, sleep onset latency (SOL) and wake time. Sleep quality was assessed using four standardised dimensions from the Swiss Health Survey. HRQoL was estimated using the KIDSCREEN-10 questionnaire. Results Over two-thirds (71.5%) of adolescents reported using at least one SBMD at night-time, and about a third (32.2%) reported using mobile phones at night-time in darkness. Night-time mobile phone and television use was associated with higher odds of insufficient sleep duration on weekdays (Odds Ratio, OR= 1.82, 95% Confidence Interval, CI [1.59, 2.07] and OR=1.40, 95% CI [1.23, 1.60], respectively). Adolescents who used mobile phones in a room with light were more likely to have insufficient sleep (OR=1.32, 95% CI [1.10, 1.60]) and later sleep midpoint (OR=1.64, 95% CI [1.37, 1.95]) on weekends compared to non-users. The magnitude of these associations was even stronger for those who used mobile phones in darkness for insufficient sleep duration on weekdays (OR=2.13, 95% CI [1.79, 2.54]) and for later sleep midpoint on weekdays (OR=3.88, 95% CI [3.25, 4.62]) compared to non-users. Night-time use of mobile phones in light was not associated with HRQoL but use in darkness was associated with a lower KIDSCREEN-10 score (β= -1.19, 95% CI [-1.83, -0.56]) compared to no use. Conclusions: We found consistent associations between night-time SBMD use and poor sleep outcomes and worse HRQoL in adolescents. The magnitude of these associations was stronger when SBMD use occurred in a dark room versus a lit room

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

Social networking site use in young adolescents: association with health-related quality of life and behavioural difficulties

Despite Social Networking Sites (SNS) having a minimum age of 13, younger adolescents are using them. In this study, we examine self-reported overall SNS use and SNS use if awake at night in relation to Health-Related Quality of Life (HRQOL, measured by KIDSCREEN-10) and behaviour (measured by Strengths and Difficulties Questionnaire, SDQ) in 5,229 adolescents aged 11-12 in the Study of Cognition, Adolescents and Mobile Phones (SCAMP) cohort. Two-thirds of the study population used SNS. Weekday and weekend SNS use on mobile phones and other devices was significantly associated with lower HRQOL in females (all p-values for linear trend < 0.01) but not males. Using SNS if awake at night was also significantly associated with lower HRQOL in females (adjusted β-coefficient - 2.20 (95% CI - 3.18, - 1.22)). Higher SNS use on mobile phones and other devices was associated with increased behavioural difficulties in both genders (p-value for trend < 0.001). Similarly, SNS use if awake at night was associated with greater behavioural difficulties (adjusted β-coefficient 2.54 (95% CI 2.09, 2.98)). We recommend further longitudinal research in this area in order have a better understanding of the direction of relationships between SNS and wellbeing and behaviour in adolescents

Exposure to disinfection by-products, fetal growth, and prematurity:A systematic review and meta-analysis

We aimed to provide quantitative estimates of exposure-response relationships between total trihalomethanes in drinking water and several adverse birth outcomes relating to fetal growth and prematurity, suitable for use in assessments of attributable burden of disease. We carried out a systematic review and meta-analysis of epidemiological studies featuring original peer-reviewed data on the association of total trihalomethane (TTHM) exposure and health outcomes related to fetal growth and prematurity. A comprehensive literature search yielded 37 studies for consideration, 15 of which were selected for the extraction of relative risks relating adverse birth outcomes to TTHM exposure. Sufficient data were available for meta-analyses to be carried out for four adverse birth outcomes: low birth weight (LBW), term low birth weight (TLBW), preterm delivery (PTD) and small for gestational age (SGA) (including intra uterine growth retardation (IUGR)). We found little or no evidence for associations between third trimester TTHM exposure and LBW (OR per 10µg TTHM/L = 0.9999 95% CI 0.9735, 1.0270), TLBW (OR per 10µg TTHM/L = 1.0337 95% CI 0.9272, 1.1525) or PTD (OR per 10µg TTHM/L = 0.9896 95% CI 0.9781, 1.0013). We found evidence for an association with SGA (OR per 10µg TTHM/L = 1.0100 95% CI 1.0006, 1.0194). We found little or no evidence for associations between TTHM concentration and most adverse birth outcomes relating to fetal growth and prematurity. We did find evidence for an association between TTHM concentration and SGA. We discuss these findings and the uncertainties—relating particularly to exposure which may have affected them

Chlorination disinfection by-products and adverse birth outcomes: a retrospective cohort study in three regions in England: ISEE-183

Recent epidemiological studies of the relationship between disinfection by-products (DBPs), from chlorination, in public drinking water supply and adverse birth outcomes, have reported inconsistent and inconclusive findings. We report here on the largest study to date to examine the relationship of total trihalomethanes (TTHMs) and the individual trihalomethanes (THMs) to birth weight and still birth prevalence, between 1993 and 1998, for regions covered by three water companies in England. Initial results from this ongoing study using modelled annual TTHM estimates were found to differ between each of the three water supply areas. There was some evidence of confounding by social deprivation and ethnicity, which was further explored by analysis of information on the lifestyle characteristics of all women of reproductive age in the study regions from National survey data. Here, we report on the next stage of the study using modelled quarterly (3 monthly) estimates of the individual THMs in water zones. We modelled THM measurements using a Bayesian hierarchical mixture model, taking into account heterogeneity in THM levels between water originating from different source types (e.g. ground, lowland surface or upland surface), quarterly variation in THM levels and uncertainty in the true value of undetected and rounded measurements. These modelled estimates were linked using Geographical Information Systems to routine birth and stillbirth records based on location of maternal residence at the time of birth to obtain a weighted third trimester exposure estimate for each birth. Exposure categories were constructed as follows: for chloroform (low (&lt; 20 mg/l). medium (20-40 mg/l) and high (&gt;40 mg/l), bromodichloromethane (low (&lt; 6 mg/l), medium (6-12 mg/l) and high (&gt;12 mg/l), dibromoehloromethane (low (&lt; 5 mg/l) and high (&gt;5 mg/l) and total brominated compounds low (&lt; 6 mg/l), medium (6-12 mg/l) and high (&gt;12 mg/l) respectively. After exclusion of multiple births and births from water zones without valid THM data, we studied a total of 934,843 live and stillbirths. Exposure-response relationships were explored using multiple logistic regression analysis with weighted third trimester individual THM estimates and adjustment for e.g. gender, maternal age and deprivation. Analysis of the individual THMs, as opposed to TTHMs. is essential to characterise more precisely the effects of complex mixtures of DBPs on the developing foctus, and refine our understanding of this important area of research

In vivo parameters influencing 2-Cys Prx oligomerization: The role of enzyme sulfinylation

Abstract2-Cys Prxs are H2O2-specific antioxidants that become inactivated by enzyme hyperoxidation at elevated H2O2 levels. Although hyperoxidation restricts the antioxidant physiological role of these enzymes, it also allows the enzyme to become an efficient chaperone holdase. The critical molecular event allowing the peroxidase to chaperone switch is thought to be the enzyme assembly into high molecular weight (HMW) structures brought about by enzyme hyperoxidation. How hyperoxidation promotes HMW assembly is not well understood and Prx mutants allowing disentangling its peroxidase and chaperone functions are lacking. To begin addressing the link between enzyme hyperoxidation and HMW structures formation, we have evaluated the in vivo 2-Cys Prxs quaternary structure changes induced by H2O2 by size exclusion chromatography (SEC) on crude lysates, using wild type (Wt) untagged and Myc-tagged S. cerevisiae 2-Cys Prx Tsa1 and derivative Tsa1 mutants or genetic conditions known to inactivate peroxidase or chaperone activity or altering the enzyme sensitivity to hyperoxidation. Our data confirm the strict causative link between H2O2-induced hyperoxidation and HMW formation/stabilization, also raising the question of whether CP hyperoxidation triggers the assembly of HMW structures by the stacking of decamers, which is the prevalent view of the literature, or rather, the stabilization of preassembled stacked decamers

Bidirectional associations between sleep problems and behavioural difficulties and health‐related quality of life in adolescents: evidence from the SCAMP longitudinal cohort study

Background: Sleep problems show associations with negative outcomes in both physical and mental health in adolescents, but the associations may be reciprocal. We aimed to assess bidirectional associations between sleep problems and mental health symptoms including behavioural difficulties (internalising and externalising difficulties) and low health‐related quality of life (HRQoL). Methods: A total of 6616 adolescents (52.4% females) across Greater London completed baseline assessments when they were aged 11–12 years, and 3803 of them (57.2% females) completed follow‐up assessments at aged 13–15 years. Weekday and weekend sleep duration were derived from self‐reported bedtime, sleep onset latency and wake time. Sleep disturbance was assessed using a standardized sleep disturbance scale. Internalising and externalising difficulties were assessed using subscales of the Strength and Difficulties Questionnaire. HRQoL was assessed using the KIDSCREEN‐10 questionnaire. Cross‐lagged structural equation modelling was used with multiple imputation to examine bidirectional associations between sleep problems and mental health symptoms. Results: Females had greater internalising difficulties, worse HRQoL and more sleep disturbance than males. Persistent insufficient weekday and weekend sleep, and sleep disturbance (i.e., at both baseline and follow‐up) were associated with internalising and externalising difficulties and low HRQoL at follow‐up (ORs ranged from 1.53 to 3.63). Persistent externalising difficulties and low HRQoL were also associated with insufficient weekend sleep and sleep disturbance at follow‐up (ORs ranged from 1.68 to 4.25). Using continuous variables, we found bidirectional associations between weekday sleep duration and HRQoL, weekend sleep duration and externalising score, sleep quality and internalising score, and sleep quality and HRQoL. The association magnitudes were mostly similar in the two directions. Conclusions: Our study showed bidirectional associations between sleep problems and mental health symptoms during adolescence, indicating that early intervention and treatment on the first‐occurring symptom may prevent the development of subsequent problems