Physical Fitness and Body Mass Index Status of Hong Kong Primary Schoolchildren across the COVID-19 Pandemic, before and after School Closure.

OBJECTIVE: To determine whether health-related physical fitness and body mass index (BMI) status differed before and after school closure from the COVID-19 pandemic in a population-based cohort of Hong Kong primary schoolchildren. STUDY DESIGN: We examined the BMI z score, BMI status, and physical fitness z scores including (i) upper limb muscle strength, (ii) 1-minute sit-up test, (iii) sit-and-reach test, and (iv) endurance run tests, among 3 epochs: prepandemic (September 2018-August 2019), before school closure (September 2019-January 2020), and partial school reopening (September 2021-August 2022), using a repeated cross-sectional approach. RESULTS: A total of 137 752 primary schoolchildren aged 6-12 years were recruited over 3 academic years. Obesity increased significantly from 25.9% in 2018/19 to 31.0% in 2021/22, while underweight increased slightly from 6.1% to 6.5%. All tested parameters were adversely affected by the pandemic. The negative trend over time was far more pronounced in all 4 physical fitness scores in the underweight group, although performance in handgrip strength had no significance between 2018/19 and 2021/22. CONCLUSIONS: Schoolchildren who are both underweight and overweight/obese are vulnerable to adverse changes in physical fitness during the COVID-19 pandemic. To eliminate the negative health and fitness outcomes, it is urgent to develop strategies for assisting schoolchildren in achieving a healthy weight, especially in the postpandemic era.

Low-dose aspirin does not lower the risk of colorectal cancer in patients with type 2 diabetes taking metformin.

BACKGROUND: Low-dose aspirin and metformin have been individually associated with a reduced risk of cancer. Whether their concurrent use in adults with type 2 diabetes mellitus (T2DM) is associated with a reduced risk of colorectal cancer (CRC) is unclear. OBJECTIVE: Among individuals with T2DM taking metformin, we sought to evaluate the association between low-dose aspirin versus no aspirin and the risk of CRC. METHODS: A multiple-database new-user cohort study of patients with T2DM taking metformin was conducted between 2007 and 2010 (Clinical Data Analysis and Reporting System [CDARS], Hong Kong) and 2007-2016 (The Health Improvement Network [THIN], UK). The primary outcome was incident CRC. Patients were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any cancer, death, or until 31 December 2019. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Estimates were pooled using an inverse variance random effects model, and heterogeneity was assessed using I2 . RESULTS: After one-to-one propensity-score matching, 57,534 patients were included (CDARS = 16,276; THIN = 41,258). The median (IQR) follow-up was 9.3 (6.5-10.7) years in CDARS and 3.2 (1.1-5.8) years in THIN. The concurrent use of low-dose aspirin and metformin was not associated with a lower risk of CRC compared to metformin only (HR = 0.89, 95% CI 0.75-1.05, I2  = 0%). CONCLUSION: Low-dose aspirin was not associated with a lower risk of CRC in patients with T2DM taking metformin. Our study does not support the routine use of low-dose aspirin in this population.

Association between polypharmacy and depression relapse in individuals with comorbid depression and type 2 diabetes: a UK electronic health record study.

BACKGROUND: Individuals with physical comorbidities and polypharmacy may be at higher risk of depression relapse, however, they are not included in the 'high risk of relapse' group for whom longer antidepressant treatment durations are recommended. AIMS: In individuals with comorbid depression and type 2 diabetes (T2DM), we aimed to investigate the association and interaction between depression relapse and (a) polypharmacy, (b) previous duration of antidepressant treatment. METHOD: This was a cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) from years 2000 to 2018. We used Cox regression models with penalised B-splines to describe the association between restarting antidepressants and our two exposures. RESULTS: We identified 48 001 individuals with comorbid depression and T2DM, who started and discontinued antidepressant treatment during follow-up. Within 1 year of antidepressant discontinuation, 35% of participants restarted treatment indicating depression relapse. As polypharmacy increased, the rate of restarting antidepressants increased until a maximum of 18 concurrent medications, where individuals were more than twice as likely to restart antidepressants (hazard ratio (HR) = 2.15, 95% CI 1.32-3.51). As the duration of previous antidepressant treatment increased, the rate of restarting antidepressants increased - individuals with a previous duration of ≥25 months were more than twice as likely to restart antidepressants than those who previously discontinued in <7 months (HR = 2.36, 95% CI 2.25-2.48). We found no interaction between polypharmacy and previous antidepressant duration. CONCLUSIONS: Polypharmacy and longer durations of previous antidepressant treatment may be associated with depression relapse following the discontinuation of antidepressant treatment.

Association between the pharmacological treatment of bipolar disorder and risk of traumatic injuries: a self-controlled case series study.

BACKGROUND: Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries. METHODS: Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001-2019). A self-controlled case series design was applied to control for time-invariant confounders. RESULTS: A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71-5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88-1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09-1.66), p = 0.006]. CONCLUSIONS: This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.

Treatment with methylphenidate and the risk of fractures among children and young people: A systematic review and self-controlled case series study.

AIMS: Animal studies suggest that methylphenidate treatment for around 3 months may lead to less mineralized and weaker appendicular bones. A systematic review was conducted to summarize the evidence from observational studies, and a self-controlled case series study was used to compare the risk before and after treatment initiation. METHODS: Literature search was conducted using PubMed, Embase and the Cochrane Library to identify observational studies on methylphenidate and fractures. We also conducted a self-controlled case series study with individuals aged 5-24 years who received methylphenidate treatment and experienced fractures from 2001 to 2020 in Hong Kong. Incidence rate ratios and 95% confidence intervals were calculated by comparing the incidence rate in the methylphenidate-exposed period compared with nonexposed period. RESULTS: Six cohort studies and 2 case-control studies were included in the systematic review. For all-cause fractures, studies found a 39-74% lower risk in treated-attention deficit hyperactivity disorder (ADHD) group compared with untreated ADHD but no difference between stimulants and nonstimulants. Differences between sexes and treatment duration were also found-significant results were shown in males and those with longer treatment duration. Among 43 841 individuals with ADHD medication before the year 2020, 2023 were included in the self-controlled case series analysis. The risks of fractures were lower by 32-41% in different treatment periods when compared with 6 months before treatment initiation. CONCLUSION: Methylphenidate treatment may lower the risk of all-cause fractures from both study designs; however, further evidence is needed about the treatment duration and sex effect. Conclusions on stress fractures are not yet established, and further research is required.

Maternal Benzodiazepines and Z-Drugs Use during Pregnancy and Adverse Birth and Neurodevelopmental Outcomes in Offspring: A Population-Based Cohort Study.

INTRODUCTION: The use of benzodiazepines and/or z-drugs in women of childbearing age has increased. OBJECTIVE: The aim of the study was to evaluate whether gestational benzodiazepine and/or z-drug exposure is associated with adverse birth and neurodevelopmental outcomes. METHODS: A population-based cohort including mother-child pairs from 2001 to 2018 in Hong Kong was analysed to compare gestationally exposed and nonexposed children on the risk of preterm birth, small for gestational age, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) through logistic/Cox proportional hazards regression with a 95% confidence interval (CI). Sibling-matched analyses and negative control analyses were applied. RESULTS: When comparing gestationally exposed with gestationally nonexposed children, the weighted odds ratio (wOR) was 1.10 (95% CI = 0.97-1.25) for preterm birth and 1.03 (95% CI = 0.76-1.39) for small for gestational age, while the weighted hazard ratio (wHR) was 1.40 (95% CI = 1.13-1.73) for ASD and 1.15 (95% CI = 0.94-1.40) for ADHD. Sibling-matched analyses showed no association between gestationally exposed children and their gestationally nonexposed siblings for all outcomes (preterm birth: wOR = 0.84, 95% CI = 0.66-1.06; small for gestational age: wOR = 1.02, 95% CI = 0.50-2.09; ASD: wHR = 1.10, 95% CI = 0.70-1.72; ADHD: wHR = 1.04, 95% CI = 0.57-1.90). Similarly, no significant differences were observed when comparing children whose mothers took benzodiazepines and/or z-drugs during pregnancy to children whose mothers took benzodiazepines and/or z-drugs before but not during pregnancy for all outcomes. CONCLUSIONS: The findings do not support a causal relationship between gestational benzodiazepines and/or z-drugs exposure and preterm birth, small for gestational age, ASD, or ADHD. Clinicians and pregnant women should carefully balance the known risks of benzodiazepines and/or z-drugs use against those of untreated anxiety and sleep problems.

Trends of polypharmacy among older people in Asia, Australia and the United Kingdom: a multinational population-based study.

BACKGROUND: Polypharmacy among older people represents a global challenge due to its association with adverse drug events. The reported prevalence of polypharmacy varies widely across countries, and is particularly high in Asian countries. However, there is no multinational study using standardised measurements exploring variations in prescribing trends. OBJECTIVE: To compare polypharmacy trends in older people in Asia, Australia and the United Kingdom. DESIGN: Multinational, retrospective, time-trend, observational study using a common study protocol. SETTING: Outpatient and community settings. SUBJECTS: All individuals aged ≥ 65 years between 2013 and 2016. METHODS: We defined polypharmacy as the concomitant use of ≥5 medications for ≥45 days per year. We estimated the annual prevalence of polypharmacy and calculated average annual percentage change (AAPC) to assess the time trends. RESULTS: A total of 1.62 million individuals were included in this study. The highest prevalence of polypharmacy was observed in Hong Kong (46.4%), followed by Taiwan (38.8%), South Korea (32.0%), the United Kingdom (23.5%) and Australia (20.1%) in 2016. For the time trend, the Asian region showed a steady increase, particularly in Hong Kong and South Korea (AAPC: Hong Kong, 2.7%; South Korea, 1.8%; Taiwan, 1.0%). However, Australia and the United Kingdom showed a decreasing trend (Australia, -4.9%; the United Kingdom, -1.1%). CONCLUSIONS: Polypharmacy prevalence in older people was higher in Hong Kong, Taiwan and South Korea, with an increasing trend over time, compared with Australia and the United Kingdom. Our findings underline the necessity to monitor polypharmacy among older people in Asia by conducting government-level interventions and introducing medicine-optimisation strategies.

Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation : A Multinational Population-Based Cohort Study.

BACKGROUND: Current guidelines recommend using direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), but head-to-head trial data do not exist to guide the choice of DOAC. OBJECTIVE: To do a large-scale comparison between all DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in routine clinical practice. DESIGN: Multinational population-based cohort study. SETTING: Five standardized electronic health care databases, which covered 221 million people in France, Germany, the United Kingdom, and the United States. PARTICIPANTS: Patients who were newly diagnosed with AF from 2010 through 2019 and received a new DOAC prescription. MEASUREMENTS: Database-specific hazard ratios (HRs) of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model. RESULTS: A total of 527 226 new DOAC users met the inclusion criteria (apixaban, n = 281 320; dabigatran, n = 61 008; edoxaban, n = 12 722; and rivaroxaban, n = 172 176). Apixaban use was associated with lower risk for GIB than use of dabigatran (HR, 0.81 [95% CI, 0.70 to 0.94]), edoxaban (HR, 0.77 [CI, 0.66 to 0.91]), or rivaroxaban (HR, 0.72 [CI, 0.66 to 0.79]). No substantial differences were observed for other outcomes or DOAC-DOAC comparisons. The results were consistent for patients aged 80 years or older. Consistent associations between lower GIB risk and apixaban versus rivaroxaban were observed among patients receiving the standard dose (HR, 0.72 [CI, 0.64 to 0.82]), those receiving a reduced dose (HR, 0.68 [CI, 0.61 to 0.77]), and those with chronic kidney disease (HR, 0.68 [CI, 0.59 to 0.77]). LIMITATION: Residual confounding is possible. CONCLUSION: Among patients with AF, apixaban use was associated with lower risk for GIB and similar rates of ischemic stroke or systemic embolism, ICH, and all-cause mortality compared with dabigatran, edoxaban, and rivaroxaban. This finding was consistent for patients aged 80 years or older and those with chronic kidney disease, who are often underrepresented in clinical trials. PRIMARY FUNDING SOURCE: None.

The management of ADHD in children and adolescents: bringing evidence to the clinic: perspective from the European ADHD Guidelines Group (EAGG).

ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems.

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study.

BACKGROUND: The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. METHODS: This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. RESULTS: Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. CONCLUSIONS: There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy.

Autoimmune conditions following mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccination: A descriptive cohort study among 1.1 million vaccinated people in Hong Kong.

BACKGROUND: Concerns regarding the autoimmune safety of COVID-19 vaccines may negatively impact vaccine uptake. We aimed to describe the incidence of autoimmune conditions following BNT162b2 and CoronaVac vaccination and compare these with age-standardized incidence rates in non-vaccinated individuals. METHODS: This is a descriptive cohort study conducted in public healthcare service settings. Territory-wide longitudinal electronic medical records of Hong Kong Hospital Authority users (≥16 years) were linked with COVID-19 vaccination records between February 23, 2021 and June 30, 2021. We classified participants into first/second dose BNT162b2 groups, first/second dose CoronaVac groups and non-vaccinated individuals for incidence comparison. The study outcomes include hospitalized autoimmune diseases (16 types of immune-mediated diseases across six body systems) within 28 days after first and second dose of vaccination. Age-standardized incidence rate ratios (IRRs) with exact 95% confidence intervals (CIs) were estimated using Poisson distribution. RESULTS: This study included around 3.9 million Hong Kong residents, of which 1,122,793 received at least one dose of vaccine (BNT162b2: 579,998; CoronaVac: 542,795), and 721,588 completed two doses (BNT162b2: 388,881; CoronaVac: 332,707). Within 28 days following vaccination, cumulative incidences for all autoimmune conditions were below 9 per 100,000 persons, for both vaccines and both doses. None of the age-standardized incidence rates were significantly higher than the non-vaccinated individuals, except for an observed increased incidence of hypersomnia following the first dose of BNT162b2 (standardized IRR: 1.47; 95% CI: 1.10-1.94). CONCLUSIONS: Autoimmune conditions requiring hospital care are rare following mRNA and inactivated COVID-19 vaccination with similar incidence to non-vaccinated individuals. The association between first dose BNT162b2 vaccination and immune-related sleeping disorders requires further research. Population-based robust safety surveillance is essential to detect rare and unexpected vaccine safety events.

c4c: Paediatric pharmacovigilance: Methodological considerations in research and development of medicines for children - A c4c expert group white paper.

Children frequently respond differently to therapies compared to adults. Differences also exist between paediatric age groups for pharmacokinetics and pharmacodynamics in both efficacy and safety. Paediatric pharmacovigilance requires an understanding of the unique aspects of children with regard to, for example, drug response, growth and development, clinical presentation of adverse drug reactions (ADRs), how they can be detected and population-specific factors (e.g., more frequent use of off-label/unlicensed drugs). In recognition of these challenges, a group of experts has been formed in the context of the conect4children (c4c) project to support paediatric drug development. This expert group collaborated to develop methodological considerations for paediatric drug safety and pharmacovigilance throughout the life-cycle of medicinal products which are described in this article. These considerations include practical points to consider for the development of the paediatric section of the risk management plan (RMP), safety in paediatric protocol development, safety data collection and analysis. Furthermore, they describe the specific details of post-marketing pharmacovigilance in children using, for example, spontaneous reports, electronic health care records, registries and record-linkage, as well as the use of paediatric pharmacoepidemiology studies for risk characterisation. Next the details of the assessment of benefit-risk and challenges related to medicinal product formulation in the context of a Paediatric Investigation Plan (PIP) are presented. Finally, practical issues in paediatric signal detection and evaluation are included. This paper provides practical points to consider for paediatric pharmacovigilance throughout the life-cycle of medicinal products for RMPs, protocol development, safety data collection and analysis and PIPs.

Pharmacokinetic modeling and simulation to understand diamorphine dose-response in neonates, children, and adolescents.

Pharmacokinetic-pharmacodynamic modeling and simulation can facilitate understanding and prediction of exposure-response relationships in children with acute or chronic pain. The pharmacokinetics of diamorphine (diacetylmorphine, heroin), a strong opioid, remain poorly quantified in children and dose is often guided by clinical acumen. This tutorial demonstrates how a model to describe intranasal and intravenous diamorphine pharmacokinetics can be fashioned from a model for diamorphine disposition in adults and a model describing morphine disposition in children. Allometric scaling and maturation models were applied to clearances and volumes to account for differences in size and age between children and adults. The utility of modeling and simulation to gain insight into the analgesic exposure-response relationship is demonstrated. The model explains reported observations, can be used for interrogation, interpolated to determine equianalgesia and inform future clinical studies. Simulation was used to illustrate how diamorphine is rapidly metabolized to morphine via its active metabolite 6-monoacetylmorphine, which mediates an early dopaminergic response accountable for early euphoria. Morphine formation is then responsible for the slower, prolonged analgesic response. Time-concentration profiles of diamorphine and its metabolites reflected disposition changes with age and were used to describe intravenous and intranasal dosing regimens. These indicated that morphine exposure in children after intranasal diamorphine 0.1 mg.kg-1 was similar to that after intranasal diamorphine 5 mg in adults. A target concentration of morphine 30 µg.L-1 can be achieved by a diamorphine intravenous infusion in neonates 14 µg.kg-1 .h-1 , in a 5-year-old child 42 µg.kg-1 .h-1 and in an 15 year-old-adolescent 33 µg.kg-1 .h-1 .

Carer preferences of route of administration of transmucosal diamorphine and willingness to take part in a randomised controlled trial: an interview study (DIPPER).

BACKGROUND: Children and young people are usually given liquid morphine by mouth for breakthrough pain, which can take thirty minutes to work. A faster-acting, quickly absorbed, needle-free pain medicine, that is easy to administer is needed such as transmucosal (sublingual, buccal, intranasal) diamorphine. Research evidence relating to the administration of medication for breakthrough pain in children and young people is limited. This study aims to describe the experiences and preferences of parents and/or children and young people regarding the route of administration of diamorphine, barriers and facilitators comparative to oral morphine, and participation in a randomised controlled trial. METHODS: In-depth, semi-structured interviews with parents and/or children and young people at home or hospital/hospice. RESULTS: Thirteen interviews with: nine mothers, one father, and three sets of parents jointly. No interviews took place with a child/young person. Most families had experience of the buccal route which was effective in ease of administration and time to control pain. The intranasal route was preferred by parents irrespective of experience. Parents' willingness for their child to take part in a trial depended on the time commitment, their child's pain trajectory and the stability of analgesic requirements. CONCLUSION: A randomised controlled trial of oral morphine versus transmucosal diamorphine would need to consider trial logistics, especially time commitment. Parents felt that the trial should be introduced initially by the clinical team, with written information from the research team, and sufficient time to ask questions. Patients who had discontinued oral morphine because of side effects, or those with gastrointestinal failure, should be excluded. Maintaining stability in pain management was essential to families, so the timing of the trial is a potential issue.

Metabolic events associated with the use of antipsychotics in children, adolescents and young adults: a multinational sequence symmetry study.

It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6-30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00-1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88-1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04-1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85-1.12) and 1.24 (95% CI 0.97-1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns.

Vulnerability and resilience in children during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is having a profound impact on the health and development of children worldwide. There is limited evidence on the impact of COVID-19 and its related school closures and disease-containment measures on the psychosocial wellbeing of children; little research has been done on the characteristics of vulnerable groups and factors that promote resilience. METHODS: We conducted a large-scale cross-sectional population study of Hong Kong families with children aged 2-12 years. Parents completed an online survey on family demographics, child psychosocial wellbeing, functioning and lifestyle habits, parent-child interactions, and parental stress during school closures due to COVID-19. We used simple and multiple linear regression analyses to explore factors associated with child psychosocial problems and parental stress during the pandemic. RESULTS: The study included 29,202 individual families; of which 12,163 had children aged 2-5 years and 17,029 had children aged 6-12 years. The risk of child psychosocial problems was higher in children with special educational needs, and/or acute or chronic disease, mothers with mental illness, single-parent families, and low-income families. Delayed bedtime and/or inadequate sleep or exercise duration, extended use of electronic devices were associated with significantly higher parental stress and more psychosocial problems among pre-schoolers. CONCLUSIONS: This study identifies vulnerable groups of children and highlights the importance of strengthening family coherence, adequate sleep and exercise, and responsible use of electronic devices in promoting psychosocial wellbeing during the COVID-19 pandemic.

Examining family pre-pandemic influences on adolescent psychosocial wellbeing during the COVID-19 pandemic.

During the COVID-19 lockdown, with social distancing measures in place and a decrease in social activities, emotional states are more likely to be transferred between family members via increased interactions and communication. However, longitudinal evidence, particularly for early adolescents, is lacking. This study investigated family pre-pandemic influences on parental stress and adolescent psychosocial wellbeing during the COVID-19 pandemic. Data were collected from 233 adolescents and their parents before and during the initial phase of the pandemic. Parents reported their own stress level and perception of adolescent adjustment problems, whereas adolescents reported their own psychological distress level. In addition, adolescents also reported their satisfaction with family life in the pre-pandemic survey. Cross-lagged path models indicated reciprocal associations between parental stress and perception of adolescent adjustment problems. Compared to adolescents low in pre-pandemic family life satisfaction, those adolescents with higher levels of family life satisfaction before the pandemic reported lower levels of anxiety and stress only when parental stress showed no increase during the pandemic. Findings provide support for the mutual influences between parental stress and perceived adolescent adjustment problems during the pandemic. Special attention should be paid to those adolescents who undergo significant family life changes during the pandemic.

Comorbidity of ADHD and allergic diseases in early adolescence: The role of parental smoking at home.

A growing body of research suggests an association between attention deficit hyperactivity disorder (ADHD) and allergic disorders, but little work has been done to explore the role of external factors such as parental smoking at home in the development of comorbid ADHD and allergic disorders. This study aimed to examine the association between allergic diseases and ADHD adjusted for exposure to parental smoking at home in early adolescents. We recruited 250 male (41.7%) and 350 female (58.3%) adolescents (mean [SD] age, 13.29 [0.52] years) via chain-referral sampling. Their ADHD symptoms were assessed by the parent proxy-report version of the Chinese Strengths and Weaknesses of Attention-Deficit/Hyperactivity-symptoms and Normal-behaviours (SWAN) rating scale. Data on the participants' history of clinician-diagnosed allergic diseases, family socio-demographics, and parental smoking habit were collected using a parent-completed questionnaire. Regression analyses were performed to examine the associations of interest. The levels of ADHD symptoms were comparable between allergic and non-allergic participants after controlling for child and family demographics and parental smoking at home. Notably, the risk of probable ADHD was particularly high in participants with food allergies (odd ratio = 4.51, p = 0.011) but not in those with allergic rhinitis after adjusting for parental smoking at home. Our findings suggest that second-hand smoke exposure at home is a potential risk factor underlying the link between ADHD and allergic diseases. Current management guidelines should emphasize the importance of early identification and cessation of tobacco smoke exposure for prevention of comorbidity of ADHD and allergic disorders. Clinical Trial Registration (if any): NA.

Long-term Outcome of Short-course High-dose Glucocorticoids for Severe Acute Respiratory Syndrome (SARS): A 17-Year Follow-up in SARS Survivors.

Use of high-dose glucocorticoids for COVID-19 (caused by SARS-CoV-2) is controversial because of safety concerns. We examined the long-term consequences of glucocorticoid use in severe acute respiratory syndrome (caused by SARS-CoV-1) survivors. Results showed that high-dose glucocorticoids greatly increased the long-term risk of avascular necrosis but not other major diseases.

Delay in Retreatment of Helicobacter pylori Infection Increases Risk of Upper Gastrointestinal Bleeding.

BACKGROUND & AIMS: Little is known about risk of upper gastrointestinal bleeding (UGIB) in patients failed by Helicobacter pylori eradication therapy. We investigated the effects of different time until retreatment, after failure of initial H pylori eradication therapy, on subsequent risk of UGIB. METHODS: We performed a territory-wide retrospective cohort study of 70,518 patients with H pylori infection who had received their first course of clarithromycin-based triple therapy from January 2003 through December 2012 in Hong Kong. Patients who required retreatment after failed initial therapy (n = 8330, 11.8%) were categorized based on time between initial and final H pylori eradication (3 months or less, 3-12 months, and more than 12 months). We collected clinical data from 30 days after prescription of the last course of H pylori therapy until hospitalization for non-variceal UGIB, death, or the end of the study (30 Jun 2016; median follow-up time, 7.65 years). The primary outcome was difference in development UGIB (determined from ICD-9 codes) between patients who required retreatment and those who did not (reference group). RESULTS: Compared with the reference group, patients who required retreatment had an overall higher risk of UGIB, even after last eradication therapy (adjusted hazard ratio (HR), 1.50, 95% CI, 1.34-1.69). There was a progressive increase in risk of UGIB with longer time from initial until final eradication therapy: hazard ratio for time less than 3 months, 1.16; 95% CI, 0.88-1.54, hazard ratio for time 3-12 months, 1.35; 95% CI, 1.07-1.69, and hazard ratio for time more than 12 months, 1.68; 95% CI, 1.46-1.94 (P for trend = .038). CONCLUSION: In a retrospective study of patients in Hong Kong, we found that those failed by initial H pylori eradication have an increased risk of UGIB, compared to patients who responded to the initial therapy. Risk increased progressively with longer time until retreatment. Early retreatment within 3 months should be considered to minimize subsequent UGIB risk.