Fall-related attendance and associated hospitalisation of children and adolescents in Hong Kong: a 12-year retrospective study

Objectives: The present study aimed to examine the trends and characteristics of fall-related attendance in accident and emergency department (AED) by injury type and the trend in associated average length of stay (LOS) among children and adolescents in Hong Kong. Design: A retrospective approach was adopted. Setting: AED, involving all local public emergency departments from 2001 to 2012. Participants: 63 557 subjects aged 0–19 years with fall injury record were included in the analysis. Primary outcome measures: Fall-related injury number and rates were calculated and reported. Poisson and negative binomial regression models were used to study the trends of injury incidence rate at different body regions. Results: AED fall-related attendance rate increased significantly with an annual percentage change of 4.45 (95% CI 3.43 to 5.47%, p<0.0001). The attendance number of male subjects was persistently higher than female subjects. The standardised rate of fracture injury increased by 1.31% (95% CI 0.56 to 2.05%, p<0.0001) and that of non-fracture injury increased by 9.23% (95% CI 7.07 to 11.43%, p<0.0001) annually. Upper limb was the most frequently fractured location. It included forearm/elbow, shoulder/upper arm and wrist/hand with descending order of frequency. On the contrary, head was the most frequent non-fracture location, followed by forearm/elbow. Conclusions: The rates of fall-related attendance have been increasing and still remain high. There were significant increases in non-fracture injuries. Fractures were most frequently found in the upper extremity of a child while the most common non-fracture location was head. It appears that more efforts should be made and preventive measures should be implemented for children and adolescents in Hong Kong

Effectiveness of a technology-based injury prevention program for enhancing mothers’ knowledge of child safety: protocol for a randomized controlled trial

Background: Provision of anticipatory guidance for parents is recommended as an effective strategy to prevent injuries among young children. Technology-based anticipatory guidance has been suggested to reinforce the effectiveness of injury prevention and improve parents’ knowledge of child safety. Objective: This study aims to examine the effectiveness of a technology-based injury prevention program with parental anticipatory guidance for enhancing mothers’ knowledge of child safety. Methods: In this randomized controlled trial, 308 mothers will be recruited from the antenatal clinics and postnatal wards of two major public hospitals in Hong Kong. Participating mothers will be randomly assigned into intervention and control groups. Mothers in the intervention group will be given free access to a technology-based injury prevention program with anticipatory guidance, whereas mothers in the control group will be given a relevant booklet on parenting. The injury prevention program, available as a website or on a mobile app, includes behavioral components based on the Theory of Planned Behavior. The primary outcome measure will be the change in the mother’s knowledge of child safety. The secondary outcome measures will be age-appropriate domestic safety knowledge, attitudes, intentions, perceived behavioral control, and self-reported behavior related to home safety practice. We will also determine dose-response relationships between the outcome measures and the website and mobile app usage. Results: Enrolment of participants will begin in October 2016. Results are expected by June 2018. Conclusions: Parents will be able to easily access the domestic injury prevention website to find information regarding child injury prevention. It is anticipated that the technology-based intervention will help parents improve their knowledge of child safety and raise their awareness about the consequences of domestic injuries and the importance of prevention. Trial Registration: Clinicaltrials.gov Clinicaltrials.gov NCT02835768; http://clinicaltrials.gov/ct2/show/NCT02835768 (Archived by WebCite at http://www.webcitation/6lbXYM6b9)

The Polygenic and Monogenic Basis of Blood Traits and Diseases

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Associations of paternal postpartum depressive symptoms and infant development in a Chinese longitudinal study

Although fathers actively provide infant care and support to their partners in modern societies, data on fathers’ difficulties and mental health problems is still limited. This study examined paternal postpartum depression and its adverse impact on infants, and the possible mediating role of father-infant attachment in the link between fathers’ depressive symptoms and infants’ outcomes. Pregnant women and their partners were recruited from the antenatal clinics of two public hospitals in Hong Kong. Information about paternal and maternal depression, paternal-infant attachment, and infant development were collected at antenatal period, 6 weeks and 6 months postpartum. Linear regression was employed to examine risk factors for paternal depression symptoms, and mediation analysis was conducted to examine the mediating mechanisms. 121 couples joined the longitudinal study and completed all the assessments. Paternal postpartum depression symptoms were associated with fathers’ prenatal depression symptoms, and mothers’ postpartum depression symptoms. Fathers with postpartum depression symptoms experienced reduced paternal-infant attachment, which also acted as mediators between postpartum depression in fathers and adverse infants’ social development. Effective assessment and interventions targeted at preventing or identifying and reducing paternal postpartum depression and improving father-infant relationship would help to lower the risk of infant disorders and poor development. Strategies improving the fathers’ mental health during antenatal period and their partner’s psychosocial well-being may also reduce paternal postpartum depression

Effectiveness of a Technology-Based Injury Prevention Program for Enhancing Mothers’ Knowledge of Child Safety: Protocol for a Randomized Controlled Trial

Background: Provision of anticipatory guidance for parents is recommended as an effective strategy to prevent injuries among young children. Technology-based anticipatory guidance has been suggested to reinforce the effectiveness of injury prevention and improve parents’ knowledge of child safety. Objective: This study aims to examine the effectiveness of a technology-based injury prevention program with parental anticipatory guidance for enhancing mothers’ knowledge of child safety. Methods: In this randomized controlled trial, 308 mothers will be recruited from the antenatal clinics and postnatal wards of two major public hospitals in Hong Kong. Participating mothers will be randomly assigned into intervention and control groups. Mothers in the intervention group will be given free access to a technology-based injury prevention program with anticipatory guidance, whereas mothers in the control group will be given a relevant booklet on parenting. The injury prevention program, available as a website or on a mobile app, includes behavioral components based on the Theory of Planned Behavior. The primary outcome measure will be the change in the mother’s knowledge of child safety. The secondary outcome measures will be age-appropriate domestic safety knowledge, attitudes, intentions, perceived behavioral control, and self-reported behavior related to home safety practice. We will also determine dose-response relationships between the outcome measures and the website and mobile app usage. Results: Enrolment of participants will begin in October 2016. Results are expected by June 2018. Conclusions: Parents will be able to easily access the domestic injury prevention website to find information regarding child injury prevention. It is anticipated that the technology-based intervention will help parents improve their knowledge of child safety and raise their awareness about the consequences of domestic injuries and the importance of prevention. Trial Registration: Clinicaltrials.gov Clinicaltrials.gov NCT02835768; http://clinicaltrials.gov/ct2/show/NCT02835768 (Archived by WebCite at http://www.webcitation/6lbXYM6b9)

Effectiveness of a culturally attuned internet-based depression prevention program for Chinese adolescents: a randomized controlled trial

Background: Depression prevention among adolescents is crucial for reducing the global disease burden. Internet‐based depression prevention approaches are found to be effective but they were mostly evaluated in a Western context. Grasping the Opportunity is a Chinese Internet intervention, which was translated and modified from CATCH‐IT developed in the West. We aimed to evaluate the effectiveness of Grasp the Opportunity in reducing depressive symptoms in Chinese adolescents. Methods: In this randomized controlled trial, Chinese adolescents aged 13 to 17 years with mild‐to‐moderate depressive symptoms were recruited from three secondary schools in Hong Kong. The participants (n = 257) were randomly assigned to receive either intervention or attention control. The primary outcome was the improvement in depressive symptoms according to the revised Center for Epidemiologic Studies Depression Scale (CESD‐R) at the 12‐month follow‐up. Analyses were performed using intention to treat (ITT). Results: The participants were randomly assigned to receive the intervention (n = 130) or attention control (n = 127). Follow‐up data were obtained from 250 (97%) participants. Only 26 (10%) participants completed the intervention. Compared to the attention control, Grasp the Opportunity led to reductions in depressive symptoms at the 12‐month follow‐up with a medium effect size using ITT analysis (mean difference 2.6, 95% CI 0.59–5.55, effect size d = 0.36). Conclusions: Grasp the Opportunity is effective in reducing depressive symptoms in Chinese adolescents over a long follow‐up period. Poor completion rate is the major challenge in the study