Cardiovascular outcomes associated with use of clarithromycin: population based study

Study question What is the association between clarithromycin use and cardiovascular outcomes? Methods In this population based study the authors compared cardiovascular outcomes in adults aged 18 or more receiving oral clarithromycin or amoxicillin during 2005-09 in Hong Kong. Based on age within five years, sex, and calendar year at use, each clarithromycin user was matched to one or two amoxicillin users. The cohort analysis included patients who received clarithromycin (n=108 988) or amoxicillin (n=217 793). The self controlled case series and case crossover analysis included those who received Helicobacter pylori eradication treatment containing clarithromycin. The primary outcome was myocardial infarction. Secondary outcomes were all cause, cardiac, or non-cardiac mortality, arrhythmia, and stroke. Study answer and limitations The propensity score adjusted rate ratio of myocardial infarction 14 days after the start of antibiotic treatment was 3.66 (95% confidence interval 2.82 to 4.76) comparing clarithromycin use (132 events, rate 44.4 per 1000 person years) with amoxicillin use (149 events, 19.2 per 1000 person years), but no long term increased risk was observed. Similarly, rate ratios of secondary outcomes increased significantly only with current use of clarithromycin versus amoxicillin, except for stroke. In the self controlled case analysis, there was an association between current use of H pylori eradication treatment containing clarithromycin and cardiovascular events. The risk returned to baseline after treatment had ended. The case crossover analysis also showed an increased risk of cardiovascular events during current use of H pylori eradication treatment containing clarithromycin. The adjusted absolute risk difference for current use of clarithromycin versus amoxicillin was 1.90 excess myocardial infarction events (95% confidence interval 1.30 to 2.68) per 1000 patients. What this study adds Current use of clarithromycin was associated with an increased risk of myocardial infarction, arrhythmia, and cardiac mortality short term but no association with long term cardiovascular risks among the Hong Kong population

Predicting dementia diagnosis from cognitive footprints in electronic health records: a case-control study protocol

INTRODUCTION: Dementia is a group of disabling disorders that can be devastating for persons living with it and for their families. Data-informed decision-making strategies to identify individuals at high risk of dementia are essential to facilitate large-scale prevention and early intervention. This population-based case-control study aims to develop and validate a clinical algorithm for predicting dementia diagnosis, based on the cognitive footprint in personal and medical history. METHODS AND ANALYSIS: We will use territory-wide electronic health records from the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong between 1 January 2001 and 31 December 2018. All individuals who were at least 65 years old by the end of 2018 will be identified from CDARS. A random sample of control individuals who did not receive any diagnosis of dementia will be matched with those who did receive such a diagnosis by age, gender and index date with 1:1 ratio. Exposure to potential protective/risk factors will be included in both conventional logistic regression and machine-learning models. Established risk factors of interest will include diabetes mellitus, midlife hypertension, midlife obesity, depression, head injuries and low education. Exploratory risk factors will include vascular disease, infectious disease and medication. The prediction accuracy of several state-of-the-art machine-learning algorithms will be compared. ETHICS AND DISSEMINATION: This study was approved by Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 18-225). Patients' records are anonymised to protect privacy. Study results will be disseminated through peer-reviewed publications. Codes of the resulted dementia risk prediction algorithm will be made publicly available at the website of the Tools to Inform Policy: Chinese Communities' Action in Response to Dementia project (https://www.tip-card.hku.hk/)

Identifying dementia from cognitive footprints in hospital records among Chinese older adults: a machine-learning study

Background: By combining theory-driven and data-driven methods, this study aimed to develop dementia predictive algorithms among Chinese older adults guided by the cognitive footprint theory. Methods: Electronic medical records from the Clinical Data Analysis and Reporting System in Hong Kong were employed. We included patients with dementia diagnosed at 65+ between 2010 and 2018, and 1:1 matched dementia-free controls. We identified 51 features, comprising exposures to established modifiable factors and other factors before and after 65 years old. The performances of four machine learning models, including LASSO, Multilayer perceptron (MLP), XGBoost, and LightGBM, were compared with logistic regression models, for all patients and subgroups by age. Findings: A total of 159,920 individuals (40.5% male; mean age [SD]: 83.97 [7.38]) were included. Compared with the model included established modifiable factors only (area under the curve [AUC] 0.689, 95% CI [0.684, 0.694]), the predictive accuracy substantially improved for models with all factors (0.774, [0.770, 0.778]). Machine learning and logistic regression models performed similarly, with AUC ranged between 0.773 (0.768, 0.777) for LASSO and 0.780 (0.776, 0.784) for MLP. Antipsychotics, education, antidepressants, head injury, and stroke were identified as the most important predictors in the total sample. Age-specific models identified different important features, with cardiovascular and infectious diseases becoming prominent in older ages. Interpretation: The models showed satisfactory performances in identifying dementia. These algorithms can be used in clinical practice to assist decision making and allow timely interventions cost-effectively. Funding: The Research Grants Council of Hong Kong under the Early Career Scheme 27110519

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.</p

Association between statins and the risk of suicide attempt, depression, anxiety, and seizure: A population-based, self-controlled case series study

Background: Risk of suicide attempt, depression, anxiety and seizure and the association with statins is an ongoing debate. We aim to investigate the association between statins and the above neuropsychological outcomes, in specific pre- and post-exposure time windows./ Methods: We identified patients aged 40–75 years old who were dispensed a statin between January 1, 2003 and December 31, 2012 from the Hong Kong Clinical Data Analysis & Reporting System (CDARS), an electronic medical records database. Patients with new onset of suicide attempt, depression, anxiety and seizure were derived from the original dataset separately, in a self-controlled case series study design. A non-parametric spline-based self-controlled case series model was built to measure continuous changes of risk./ Results: We identified 396,614 statin users. The risk of each outcome was elevated prior to statin initiation with incidence rate ratios of 1.38 (95 % CI, 1.09–1.74) for suicide attempt, 1.29 (95 % CI, 1.15–1.45) for depression, 1.35 (95 % CI, 1.19–1.53) for anxiety, and 1.45 (95 % CI, 1.21–1.73) for seizure. The incidence rate ratios remained elevated after the initiation of statins during the first 90 and 91–365 days after statin prescription and decreased to the baseline level after 1 year of continuous prescription./ Limitations: CDARS includes prescription data but not adherence data, which could lead to misclassification of exposure periods./ Conclusions: Our study does not support a direct association between statin use and suicide attempt, depression, anxiety and seizure, whose risks could be explained by cardiovascular events, for which statins were prescribed

Association between prenatal antipsychotic exposure and the risk of attention-deficit/hyperactivity disorder and autism spectrum disorder: a systematic review and meta-analysis

The paucity of evidence regarding the safety of gestational antipsychotic exposure has led to treatment discontinuation in pregnant women with severe mental health conditions. This systematic review and meta-analysis aimed to summarise the current evidence on the association between gestational antipsychotic exposure and attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children (Study protocol registered in PROSPERO:CRD42022311354). Five studies included in our meta-analysis with around 8.6 million pregnancy episodes in nine different countries/regions. Results from our meta-analysis indicate that the heightened risks of ASD and ADHD in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relationship with the antipsychotic exposure during pregnancy. The results underscore the importance of meticulously monitoring the neurodevelopment of children born to mothers with mental illnesses, which can facilitate early interventions and provide requisite support

Thromboembolic risk in hospitalised and non-hospitalised Covid-19 patients: a self-controlled case series analysis of a nation-wide cohort

Objective: An unexpectedly large number of people infected with Covid-19 had experienced a thrombotic event. This study aims to assess the associations between Covid-19 infection and thromboembolism including myocardial infarction (MI), ischaemic stroke, deep-vein thrombosis (DVT), and pulmonary embolism (PE). Patients and Methods: A self-controlled case-series study was conducted covering the whole of Scotland’s general population. The study population comprised individuals with confirmed (positive test) Covid-19 and at least one thromboembolic event between March 2018 and October 2020. Their incidence rates during the risk interval (5 days before to 56 days after the positive test) and the control interval (the remaining periods) were compared intra-personally. Results: Across Scotland, 1,449 individuals tested positive for Covid-19 and experienced a thromboembolic event. The risk of thromboembolism was significantly elevated over the whole risk period but highest in the 7 days following the positive test (IRR 12.01, 95% CI 9.91-14.56) in all included individuals. The association was also present in individuals not originally hospitalised for Covid-19 (IRR 4.07, 95% CI 2.83-5.85). Risk of MI, stroke, PE and DVT were all significantly higher in the week following a positive test. The risk of PE and DVT was particularly high and remained significantly elevated even 56 days following the test. Conclusion: Confirmed Covid-19 infection was associated with early elevations in risk with MI, ischaemic stroke, and substantially stronger and prolonged elevations with DVT and PE both in hospital and community settings. Clinicians should consider thromboembolism, especially PE, among people with Covid-19 in the community

Association of early nutritional status With child development in the Asia Pacific region

Importance: Stunting was used as a proxy for underdevelopment in early childhood in previous studies, but the associations between child development and other growth and body composition parameters were rarely studied. Objective: To estimate the association between malnutrition and early child development (ECD) at an individual level. Design, Setting, and Participants: This population-based, cross-sectional study used data from the East Asia Pacific Early Child Development Scales, a population-representative survey of children aged 3 to 5 years old, conducted in 2012 to 2014 in communities in Cambodia, China, Mongolia, Papua New Guinea, and Vanuatu. Data analysis was performed from November 2019 to April 2021. Exposures: Stunting (height-for-age [HFA] z score less than −2), wasting (weight-for-height z score less than −2), overweight (weight-for-height z score greater than 2), body mass index (BMI)–for-age z score, and body fat proportion based on existing growth standard and formula. Main Outcomes and Measures: ECD directly assessed using the validated East Asia–Pacific ECD Scales. Results: A total of 7108 children (3547 girls; mean [SD], age 4.48 [0.84] years) were included in this study. The prevalence of stunting was 27.1% (range across countries, 1.2%-55.0%), that of wasting was 13.7% (range, 5.4%-35.9%), and that of overweight was 15.9% (range, 2.2%-53.7%). Adjusted for country variations, age, sex, urbanicity, family socioeconomic status, and body fat proportion, ECD was linearly associated with HFA (β, 1.57; 95% CI, 1.35-1.80) and BMI-for-age (β, 0.64; 95% CI, 0.45-0.82). After adjustment for BMI and height, better ECD was associated with low body fat proportion (β, 0.93; 95% CI, 0.45-1.42). The association of HFA was more pronounced in Southeast Asia and the Pacific region than in East Asia, and the association of fat proportion was specific to children living in urban environments. Conclusions and Relevance: HFA, BMI-for-age, and body fat proportion were independently associated with ECD, and these findings suggest that future studies should consider using these parameters to estimate the prevalence of child underdevelopment; nutritional trials should examine to what extent the associations are causal

SABINA + Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting β2 agonists in the Chinese population

Background: Excessive use of short-acting β2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses significant health risk to patients with asthma and imposes burden on healthcare systems. This study, as part of global SABINA progamme, aimed to describe the prescribing patterns and clinical outcomes associated with SABA use in the Chinese population. Methods: Retrospective cohort study was conducted using anonymized electronic healthcare records of Clinical Data Analysis and Reporting System (CDARS) from Hong Kong Hospital Authority (HA). Patients newly diagnosed with asthma between 2011 and 2018 and aged ≥12 years were included, stratified by SABA use (≤2, 3–6, 7–10, or ≥11 canisters/year) during one-year baseline period since asthma diagnosis date. Patients were followed up from one-year post-index until earliest censoring of events: outcome occurrence and end of study period (31 December 2020). Cox proportional regression and negative binomial regression were used to estimate the mortality risk and frequency of hospital admissions associated with SABA use respectively, after adjusting for age, sex, Charlson Comorbidity Index (CCI), and inhaled corticosteroid (ICS) dose. Outcomes include all-cause, asthma-related, and respiratory-related mortality, frequency of hospital admissions for any cause, and frequency of hospital admissions due to asthma. Results: 17,782 patients with asthma (mean age 46.7 years, 40.8% male) were included and 59.1% of patients were overusing SABA (≥ 3 canisters per year). Each patient was prescribed a median of 5.61 SABA canisters/year. SABA overuse during baseline period was associated with higher all-cause mortality risk compared to patients with ≤2 canisters/year. Association was dose-dependent, highest risk in those used ≥11 canisters/year (adjusted hazard ratio: 1.42, 95% CI: 1.13, 1.79) and 3–6 canisters/year (adjusted hazard ratio: 1.22, 95% CI: 1.00, 1.50). Higher SABA prescription volume associated with increased frequency of hospital admissions with greatest risk observed in 7–10 canisters/year subgroup (adjusted rate ratio: 4.81, 95% CI: 3.66, 6.37). Conclusions: SABA overuse is prevalent and is associated with increased all-cause mortality risk and frequency of hospital admissions among the patients with asthma in Hong Kong