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

Safety of two-dose COVID-19 vaccination (BNT162b2 and CoronaVac) in adults with cancer: a territory-wide cohort study

BACKGROUND: The World Health Organization has defined a list of adverse events of special interest (AESI) for safety surveillance of vaccines. AESI have not been adequately assessed following COVID-19 vaccination in patients with cancer contributing to vaccine hesitancy in this population. We aimed to evaluate the association between BNT162b2 and CoronaVac vaccines and the risk of AESI in adults with active cancer or a history of cancer. PATIENTS AND METHODS: We conducted a territory-wide cohort study using electronic health records managed by the Hong Kong Hospital Authority and vaccination records provided by the Department of Health. Patients with a cancer diagnosis between January 1, 2018, and September 30, 2021, were included and stratified into two cohorts: active cancer and history of cancer. Within each cohort, patients who received two doses of BNT162b2 or CoronaVac were 1:1 matched to unvaccinated patients using the propensity score. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for AESI 28 days after the second vaccine dose. RESULTS: A total of 74,878 patients with cancer were included (vaccinated: 25,789 [34%]; unvaccinated: 49,089 [66%]). Among patients with active cancer, the incidence of AESI was 0.31 and 1.02 per 10,000 person-days with BNT162b2 versus unvaccinated patients and 0.13 and 0.88 per 10,000 person-days with CoronaVac versus unvaccinated patients. Among patients with history of cancer, the incidence was 0.55 and 0.89 per 10,000 person-days with BNT162b2 versus unvaccinated patients and 0.42 and 0.93 per 10,000 person-days with CoronaVac versus unvaccinated patients. Neither vaccine was associated with a higher risk of AESI for patients with active cancer (BNT162b2: HR 0.30, 95% CI 0.08-1.09; CoronaVac: 0.14, 95% CI 0.02-1.18) or patients with history of cancer (BNT162b2: 0.62, 95% CI 0.30-1.28; CoronaVac: 0.45, 95% CI 0.21-1.00). CONCLUSIONS: In this territory-wide cohort study of patients with cancer, the incidence of AESI following vaccination with two doses of either BNT162b2 or CoronaVac vaccines was low. The findings of this study can reassure clinicians and patients with cancer about the overall safety of BNT162b2 and CoronaVac in patients with cancer, which could increase the COVID-19 vaccination rate in this vulnerable group of patients

COVID-19 Vaccination Preferences of University Students and Staff in Hong Kong

IMPORTANCE: COVID-19 has required universities to rapidly develop vaccination policies for students and staff, yet little is known about the preferences of these individuals toward vaccination. OBJECTIVE: To quantify student and staff preferences for COVID-19 vaccination at a university in Hong Kong. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional online survey study was conducted from July 20 to September 21, 2021, before the announcement of a campus-wide vaccine mandate. A survey of 42 451 eligible university students and staff used discrete-choice experiment methods to quantify 7 attributes of COVID-19 vaccination: risk of a mild or moderate adverse event after vaccination, risk of a severe adverse event after vaccination, efficacy against COVID-19 infection, efficacy against severe manifestation of COVID-19 infection, duration of protection after vaccination, incentive for completing vaccination, and out-of-pocket costs. MAIN OUTCOMES AND MEASURES: A mixed logit regression model was used to estimate the preferences of attributes for COVID-19 vaccines and marginal willingness to pay (mWTP) adjusted for background characteristics, role, vaccination, and COVID-19 infection status of family or friends, adverse event status after vaccination among family and friends of participants, and scenario block. RESULTS: Among 42 451 eligible university students and staff invited, 3423 individuals completed the survey (mean [SD] age, 27.1 [9.9] years; 2053 [60.0%] women). Participants included 2506 students (73.2%) and 917 staff (26.8%), with a response rate of 8.1%. Quarantine-free travel was preferred (β = 0.86; 95% CI, 0.72-0.99; mWTP: $235.9; 95$190.3-$294.2), followed by efficacy against any COVID-19 infection (β = 0.30; 95$84.1; 95% CI, $71.8-$100.8), against severe manifestation of COVID-19 infection (β = 0.25; 95% CI, 0.24-0.27; mWTP: $69.7; 95$465-$653), and risk of severe adverse events following vaccination (β = −0.24; 95$66.8; 95% CI, −$81.5 to −$55.3). Participants were less concerned about protection duration (β = 0.17; 95% CI, 0.15-0.18; mWTP: $46.0; 95$38.6-$56.2) and risk of mild to moderate adverse events (β = −0.12; 95$32.7; 95% CI, −$41.2 to −$26.4). CONCLUSIONS AND RELEVANCE: Preference of all attributes were significant and were considered important by the participants for vaccine decision-making. Insights drawn could assist policy makers in future vaccination decisions, such as campus vaccine mandate and requirement of a third dose

Psychotropic medicine consumption in 65 countries and regions, 2008–19: a longitudinal study.

BACKGROUND: The WHO Comprehensive Mental Health Action Plan 2013–2030 encourages routine collection and reporting of a set of essential mental health indicators, including the availability of psychotropic medicines. The global monitoring of country-level psychotropic medicine consumption trends can provide information on the extent of the availability of psychotropic medicines. The primary objective of this study was to investigate global trends in psychotropic medicines consumption from 2008 to 2019 across 65 countries and regions according to country income level and geographical region. METHODS: In this longitudinal trends study, we used pharmaceutical sales data from the IQVIA-Multinational Integrated Data Analysis System (IQVIA-MIDAS). We analysed monthly sales data of psychotropic medicines between Jan 1, 2008, and Dec 31, 2019. Total psychotropic medicine consumption included sales of antidepressants, antipsychotics, tranquilisers, sedatives or hypnotics, and mood stabilisers. Population estimates of each country or region (eight lower-middle-income countries, 19 upper-middle-income countries, and 38 high-income countries) were based on the UN World Population Prospects 2019 report. Average annual sales trends of psychotropic medicines, expressed as defined daily dose (DDD) per 1000 inhabitants per day, were estimated using a random-effects model adjusted for income level and region. Relative changes in the annual consumption of psychotropic medicines by income, expressed as DDD per 1000 inhabitants per day, were assessed as percentage change for each medicine class. FINDINGS: Psychotropic medicine sales increased from 28·54 DDD per 1000 inhabitants per day in 2008 to 34·77 DDD per 1000 inhabitants per day in 2019, corresponding to a 4·08% (95% CI 2·96–5·21) relative average increase annually. The absolute annual increase was greater in high-income countries (3·31 DDD per 1000 inhabitants per day, 95% CI 3·01–3·61) compared with upper-middle-income countries (1·94 DDD per 1000 inhabitants per day, 1·45–2·44) and low-middle-income countries (0·88 DDD per 1000 inhabitants per day, 0·62–1·13; p<0·0001). The relative average annual increase in psychotropic medicine sales from 2008 to 2019 was greater in upper-middle-income countries (7·88%, 95% CI 6·99–8·77) than in lower-middle-income countries (2·90%, 2·40–3·39) and high-income countries (1·02%, 0·80–1·24). In 2019, the regional consumption of psychotropic medicines varied greatly, with the highest sales of all psychotropic medicine classes reported in northern America (167·54 DDD per 1000 inhabitants per day) and lowest sales reported in Asia (5·59 DDD per 1000 inhabitants per day). 17 countries had very low consumption of psychotropic medicines in 2019, including high-income countries and countries with a high prevalence of mental disorders. INTERPRETATION: The consumption of psychotropic medicines has increased over a 12-year period, and although the absolute growth rate was highest in high-income countries, the relative growth is highest in middle-income countries and especially upper-middle-income countries. Disparities in psychotropic medicine consumption of countries can only partly be explained by geographical location and income. Greater efforts are needed to increase the availability of psychotropic medicines in countries with very low consumption, which is probably due to financial or cultural reasons as well as scarcity of trained health-care professionals to prescribe psychotropic medicines

Lipid levels and major adverse cardiovascular events in patients initiated on statins for primary prevention: an international population-based cohort study protocol

Background Clinical guidelines recommend specific targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) for primary prevention of cardiovascular disease (CVD). Furthermore, individual variability in lipid response to statin therapy requires assessment of the association in diverse populations.Aim To assess whether lower concentrations of LDL-C and non-HDL-C are associated with a reduced risk of major adverse cardiovascular events (MACE) in primary prevention of CVD.Design & setting An international, new-user, cohort study will be undertaken. It will use data from three electronic health record databases from three global regions: Clinical Practice Research Datalink, UK; PREDICT-CVD, New Zealand (NZ); and the Clinical Data and Analysis Reporting System, Hong Kong (HK).Method New statin users without a history of atherosclerotic CVD, heart failure, or chronic kidney disease, with baseline and follow-up lipid levels will be eligible for inclusion. Patients will be classified according to LDL-C ([less than]1.4, 1.4–1.7, 1.8–2.5, and ≥2.6 mmol/l) and non-HDL-C ([less than] 2.2, 2.2–2.5, 2.6–3.3, and ≥3.4 mmol/l) concentrations 24 months after initiating statin therapy. The primary outcome of interest is MACE, defined as the first occurrence of coronary heart disease, stroke, or cardiovascular death. Secondary outcomes include all-cause mortality and the individual components of MACE. Sensitivity analyses will be conducted using lipid levels at 3 and 12 months after starting statin therapy.Conclusion Results will inform clinicians about the benefits of achieving guideline recommended concentrations of LDL-C for primary prevention of CVD

Bostonia: The Boston University Alumni Magazine. Volume 17

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states

Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials.

ObjectiveTo assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates.MethodsSystematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic.ResultsWe included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty).ConclusionsThe eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate