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

BNT162b2 or CoronaVac Vaccinations Are Associated With a Lower Risk of Myocardial Infarction and Stroke After SARS‐CoV‐2 Infection Among Patients With Cardiovascular Disease

Background: COVID‐19 vaccines have demonstrated effectiveness against SARS‐CoV‐2 infection, hospitalization, and mortality. The association between vaccination and risk of cardiovascular complications shortly after SARS‐CoV‐2 infection among patients with cardiovascular disease remains unknown. Methods and Results: A case–control study was conducted with cases defined as patients who had myocardial infarction or stroke within 28 days after SARS‐CoV‐2 infection between January 1, 2022 and August 15, 2022. Controls were defined as all other patients who attended any health services and were not cases. Individuals without history of cardiovascular disease were excluded. Each case was randomly matched with 10 controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Adjusted odds ratio with 95% CI was estimated using conditional logistic regression. We identified 808 cases matched with 7771 controls among all patients with cardiovascular disease. Results showed that vaccination with BNT162b2 or CoronaVac was associated with a lower risk of myocardial infarction or stroke after SARS‐CoV‐2 infection with a dose–response relationship. For BNT162b2, risk decreased from 0.49 (95% CI, 0.29–0.84) to 0.30 (95% CI, 0.20–0.44) and 0.17 (95% CI, 0.08–0.34) from 1 to 3 doses, respectively. Similar trends were observed for CoronaVac, with risk decreased from 0.69 (95% CI, 0.57–0.85) to 0.42 (95% CI, 0.34–0.52) and 0.32 (95% CI, 0.21–0.49) from 1 to 3 doses, respectively. Conclusions: Vaccination with BNT162b2 or CoronaVac is associated with a lower risk of myocardial infarction or stroke after SARS‐CoV‐2 infection among patients with cardiovascular disease

Safety of BNT162b2 or CoronaVac COVID-19 vaccines in patients with heart failure: A self-controlled case series study

BACKGROUND: COVID-19 vaccines are important for patients with heart failure (HF) to prevent severe outcomes but the safety concerns could lead to vaccine hesitancy. This study aimed to investigate the safety of two COVID-19 vaccines, BNT162b2 and CoronaVac, in patients with HF. METHODS: We conducted a self-controlled case series analysis using the data from the Hong Kong Hospital Authority and the Department of Health. The primary outcome was hospitalization for HF and the secondary outcomes were major adverse cardiovascular events (MACE) and all hospitalization. We identified patients with a history of HF before February 23, 2021 and developed the outcome event between February 23, 2021 and March 31, 2022 in Hong Kong. Incidence rate ratios (IRR) were estimated using conditional Poisson regression to evaluate the risks following the first three doses of BNT162b2 or CoronaVac. FINDINGS: We identified 32,490 patients with HF, of which 3035 were vaccinated and had a hospitalization for HF during the observation period (BNT162b2 = 755; CoronaVac = 2280). There were no increased risks during the 0–13 days (IRR 0.64 [95% confidence interval 0.33–1.26]; 0.94 [0.50–1.78]; 0.82 [0.17–3.98]) and 14–27 days (0.73 [0.35–1.52]; 0.95 [0.49–1.84]; 0.60 [0.06–5.76]) after the first, second and third doses of BNT162b2. No increased risks were observed for CoronaVac during the 0–13 days (IRR 0.60 [0.41–0.88]; 0.71 [0.45–1.12]; 1.64 [0.40–6.77]) and 14–27 days (0.91 [0.63–1.32]; 0.79 [0.46–1.35]; 1.71 [0.44–6.62]) after the first, second and third doses. We also found no increased risk of MACE or all hospitalization after vaccination. INTERPRETATION: Our results showed no increased risk of hospitalization for HF, MACE or all hospitalization after receiving BNT162b2 or CoronaVac vaccines in patients with HF. FUNDING: The project was funded by a Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01). F.T.T.L. (Francisco T.T. Lai) and I.C.K.W. (Ian C.K. Wong)'s posts were partly funded by the D24H; hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission

Waning effectiveness against COVID-19-related hospitalisation, severe complications, and mortality with two to three doses of CoronaVac and BNT162b2: a case-control study

BACKGROUND: This study aims to evaluate waning effectiveness against severe and fatal COVID-19 with 2-3 doses of CoronaVac/BNT162b2, where data is limited. METHODS: A case-control study included individuals aged ≥18 years, unvaccinated or received 2-3 doses of CoronaVac/BNT162b2, using electronic healthcare databases in Hong Kong. Those with first COVID-19-related hospitalisation, severe complications, or mortality between 1 January and 15 August 2022 were defined as cases and matched with up-to-10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness (VE) against COVID-19-related outcomes was estimated at different time intervals from second and third dose vaccination (0-13 up-to 210-240 days) using conditional logistic regression adjusted for comorbidities and medications. RESULTS: By 211-240 days after second dose, VE against COVID-19-related hospitalisation reduced to 46.6% (40.7%-51.8%) for BNT162b2 and 36.2% (28.0%-43.4%) for CoronaVac, and VE against COVID-19-related mortality were 73.8% (55.9%-84.4%) and 76.6% (60.8%-86.0%). After third dose, VE against COVID-19-related hospitalisation decreased from 91.2% (89.5%-92.6%) for BNT162b2 and 76.7% (73.7%-79.4%) for CoronaVac at 0-13 days, to 67.1% (60.4%-72.6%) and 51.3% (44.2%-57.5%) at 91-120 days. VE against COVID-19-related mortality for BNT162b2 remained high from 0-13 days [98.2% (95.0%-99.3%)] to 91-120 days [94.6% (77.7%-98.7%)], and for CoronaVac reduced from 0-13 days [96.7% (93.2%-98.4%)] to 91-120 days [86.4% (73.3%-93.1%)]. CONCLUSIONS: Significant risk reduction against COVID-19-related hospitalisation and mortality after CoronaVac or BNT162b2 vaccination was observed for >240 and >120 days after second and third dose compared to unvaccinated, despite significant waning over time. Timely administration of booster doses could provide higher levels of protection

Effectiveness of BNT162b2 and CoronaVac vaccinations against mortality and severe complications after SARS-CoV-2 Omicron BA.2 infection: a case–control study

Data regarding protection against mortality and severe complications after Omicron BA.2 infection with CoronaVac and BNT162b2 vaccines remains limited. We conducted a case–control study to evaluate the risk of severe complications and mortality following 1–3 doses of CoronaVac and BNT162b2 using electronic health records database. Cases were adults with their first COVID-19-related mortality or severe complications between 1 January and 31 March 2022, matched with up-to 10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness against COVID-19-related mortality and severe complications by type and number of doses was estimated using conditional logistic regression adjusted for comorbidities and medications. Vaccine effectiveness (95% CI) against COVID-19-related mortality after two doses of BNT162b2 and CoronaVac were 90.7% (88.6–92.3) and 74.8% (72.5–76.9) in those aged ≥65, 87.6% (81.4–91.8) and 80.7% (72.8–86.3) in those aged 50–64, 86.6% (71.0–93.8) and 82.7% (56.5–93.1) in those aged 18–50. Vaccine effectiveness against severe complications after two doses of BNT162b2 and CoronaVac were 82.1% (74.6–87.3) and 58.9% (50.3–66.1) in those aged ≥65, 83.0% (69.6–90.5) and 67.1% (47.1–79.6) in those aged 50–64, 78.3% (60.8–88.0) and 77.8% (49.6–90.2) in those aged 18–50. Further risk reduction with the third dose was observed especially in those aged ≥65 years, with vaccine effectiveness of 98.0% (96.5–98.9) for BNT162b2 and 95.5% (93.7–96.8) for CoronaVac against mortality, 90.8% (83.4–94.9) and 88.0% (80.8–92.5) against severe complications. Both CoronaVac and BNT162b2 vaccination were effective against COVID-19-related mortality and severe complications amidst the Omicron BA.2 pandemic, and risks decreased further with the third dose

Sex-based differences in risk of ischaemic stroke or systemic embolism after BNT162b2 or CoronaVac COVID-19 vaccination in patients with atrial fibrillation: a self-controlled case series and nested case-control study

AIMS: Patients with atrial fibrillation (AF) have a higher risk of ischemic stroke or systemic embolism with a greater risk for female patients. This study aims to evaluate the risk of ischemic stroke or systemic embolism and bleeding following COVID-19 vaccination in patients with AF and the sex differences. METHODS AND RESULTS: Self-controlled case series (SCCS) analysis was conducted to evaluate the risk of ischemic stroke or systemic embolism and bleeding following BNT162b2 or CoronaVac in patients with AF, using the territory-wide electronic medical records from the Hospital Authority and vaccination records from the Department of Health in Hong Kong. Patients with a primary diagnosis of ischemic stroke or systemic embolism or bleeding in the inpatient setting between February 23, 2021 and March 31, 2022 were included. A nested case-control analysis was also conducted with each case randomly matched with ten controls according to sex, age, Charlson comorbidity index and date of hospital admission. Conditional Poisson regression was used in the SCCS analysis and conditional logistic regression was used in nested case-control analysis to assess the risks and all analyses were stratified by sex and type of vaccines. Among 51 158 patients with AF, we identified an increased risk of ischemic stroke or systemic embolism after the first dose of BNT162b2 in SCCS analysis during 0-13 days (incidence rate ratio 6.60[95% CI 1.51-28.77]) and 14-27 days (6.53[95% CI 1.31-32.51]), and nested case-control analysis during 0-13 days (adjusted odds ratio 6.21 [95% CI 1.14-33.91]) and 14-27 days (5.52 [95% CI 1.12-27.26]) only in female patients. The increased risk in female patients following the first dose of CoronaVac was only detected during 0-13 days (3.88 [95% CI 1.67-9.03]) in the nested case-control analysis. No increased risk of ischemic stroke or systemic embolism was identified in male patients and no increased risk of bleeding was detected in all patients with AF for both vaccines. An increased risk of ischemic stroke or systemic embolism after COVID-19 was also observed in both females (17.42 [95% CI 5.08-59.73]) and males (6.63 [95% CI 2.02-21.79]). CONCLUSIONS: The risk of ischemic stroke or systemic embolism after COVID-19 vaccination was only increased in female patients with AF. However, as the risk after COVID-19 was even higher, proactive uptake of COVID-19 vaccines is recommended to prevent the potential severe outcomes after infection

Sex-based differences in risk of ischaemic stroke or systemic embolism after BNT162b2 or CoronaVac COVID-19 vaccination in patients with atrial fibrillation: a self-controlled case series and nested case-control study

AimsPatients with atrial fibrillation (AF) have a higher risk of ischaemic stroke or systemic embolism, with a greater risk for female patients. This study aims to evaluate the risk of ischaemic stroke or systemic embolism and bleeding following COVID-19 vaccination in patients with AF and the sex differences.Methods and resultsSelf-controlled case series (SCCS) analysis was conducted to evaluate the risk of ischaemic stroke or systemic embolism and bleeding following BNT162b2 or CoronaVac in patients with AF, using the territory-wide electronic medical records from the Hospital Authority and vaccination records from the Department of Health in Hong Kong. Patients with a primary diagnosis of ischaemic stroke, systemic embolism, or bleeding in the inpatient setting between 23 February 2021 and 31 March 2022 were included. A nested case-control analysis was also conducted with each case randomly matched with 10 controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Conditional Poisson regression was used in the SCCS analysis, and conditional logistic regression was used in the nested case-control analysis to assess the risks, and all analyses were stratified by sex and type of vaccines. Among 51 158 patients with AF, we identified an increased risk of ischaemic stroke or systemic embolism after the first dose of BNT162b2 in SCCS analysis during 0-13 days [incidence rate ratio 6.60, 95% confidence interval (CI) 1.51-28.77] and 14-27 days (6.53, 95% CI 1.31-32.51), and nested case-control analysis during 0-13 days (adjusted odds ratio 6.21, 95% CI 1.14-33.91) and 14-27 days (5.52, 95% CI 1.12-27.26) only in female patients. The increased risk in female patients following the first dose of CoronaVac was only detected during 0-13 days (3.88, 95% CI 1.67-9.03) in the nested case-control analysis. No increased risk of ischaemic stroke or systemic embolism was identified in male patients, and no increased risk of bleeding was detected in all patients with AF for both vaccines. An increased risk of ischaemic stroke or systemic embolism after COVID-19 was also observed in both females (17.42, 95% CI 5.08-59.73) and males (6.63, 95% CI 2.02-21.79).ConclusionsThe risk of ischaemic stroke or systemic embolism after COVID-19 vaccination was only increased in female patients with AF. However, as the risk after COVID-19 was even higher, proactive uptake of COVID-19 vaccines is recommended to prevent the potential severe outcomes after infection

Pancancer Analysis of Neurovascular-Related NRP Family Genes as Potential Prognostic Biomarkers of Bladder Urothelial Carcinoma

Background. Neurovascular-related genes have been implicated in the development of cancer. Studies have shown that a high expression of neuropilins (NRPs) promotes tumourigenesis and tumour malignancy. Method. A multidimensional bioinformatics analysis was performed to examine the relationship between NRP genes and prognostic and pathological features, tumour mutational burden (TMB), microsatellite instability (MSI), and immunological features based on public databases and find the potential prognostic value of NRPs in pancancer. Results. Survival analysis revealed that a low NRP1 expression in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), low-grade glioma (LGG), and stomach adenocarcinoma (STAD) was associated with poor prognosis. A high NRP2 expression in bladder urothelial carcinoma (BLCA), kidney renal papillary cell carcinoma (KIRP), and mesothelioma (MESO) was associated with poor prognosis. Moreover, NRP1 and NRP2 were associated with TMB and MSI. Subsequent analyses showed that NRP1 and NRP2 were correlated with immune infiltration and immune checkpoints. Genome-wide association analysis revealed that the NRP1 expression was strongly associated with kidney renal clear cell carcinoma (KIRC), whereas the NRP2 expression was closely associated with BLCA. Ultimately, NRP2 was found to be involved in the development of BLCA. Conclusions. Neurovascular-related NRP family genes are significantly correlated with cancer prognosis, TME, and immune infiltration, particularly in BLCA

Antibiotic Use Prior to COVID-19 Vaccine Is Associated with Higher Risk of COVID-19 and Adverse Outcomes: A Propensity-Scored Matched Territory-Wide Cohort

Background: Antibiotics may increase the risk of COVID-19 among non-vaccinated subjects via probable gut dysbiosis. We aimed to investigate whether antibiotics also affect the clinical outcomes of COVID-19 vaccine recipients. Methods: This was a territory-wide cohort study of 3,821,302 COVID-19 vaccine recipients (aged ≥ 18 years) with ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior COVID-19, prior gastrointestinal surgery, and immunocompromised status. The primary outcome was COVID-19 infection and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Exposure was pre-vaccination antibiotic use (within 180 days of first vaccine dose). Covariates included age, sex, Charlson Comorbidity Index, and concomitant medication use. Subjects were followed from the index date (first dose vaccination) until outcome occurrence, death, an additional dose of vaccination, or 15 November 2022. Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with antibiotic use. Results: Among 342,338 PS matched three-dose vaccine recipients (mean age: 57.4 years; male: 45.1%) with a median follow-up of 13.6 months (IQR: 9.2–16.3), antibiotics were associated with a higher risk of COVID-19 infection (aIRR: 1.16;95% CI: 1.14–1.19), hospitalization (aIRR: 1.75;95% CI: 1.65–1.86), and severe infection (aIRR: 1.60; 95% CI: 1.21–2.11). Notably, antibiotic use was associated with a higher risk of severe infection and death among CoronaVac recipients (aIRR: 1.62 95% CI: 1.18–2.22 and aIRR: 2.70, 95% CI: 1.54–4.73 for the two secondary outcomes, respectively), but not BNT162b2 recipients. Conclusions: Pre-vaccination use of antibiotics was associated with a higher risk of COVID-19 infection, hospitalization, and severe disease outcomes