Self-controlled Case Series Study Research Articles

Abstract TP237: Acute Risk Factors Associated With Health Service Use Within 90 Days Before Stroke: A Systematic Review and Meta-Analysis

Background: While traditional risk factors are chronic in nature, it is difficult to predict the risk of stroke with respect to time. Identifying certain acute risk factors, particularly associated with a health service contact, may help to prevent stroke. We performed a systematic review to understand the acute risk factors having health service contact within 90 days before incident strokes. Methods: PubMed, Embase and Scopus were searched for studies within last 10 years (2013- September 2022). Studies selected using PRISMA guidelines underwent quality assessment with Newcastle Ottawa scale. Three reviewers independently reviewed and included case control, case-crossover, self-controlled case series and cohort studies that reported raw data or estimates of association between acute events having healthcare contact within 90 days and stroke. Results: 106 studies across 14 countries were included from 12,628 records. Most studies reported all types of strokes as the outcome, with the most evaluated risk-periods being 30 and 90 days before stroke. Groups of acute risk factors were identified based on the reason for healthcare contact. Surgeries(n=43) and medical conditions(n=37) were the commonest groups identified for contacting health services in the acute period before stroke, followed by medications(n=14) and other reasons(n=12) including vaccinations and pathology tests. Subgroups were identified based on the type of acute risk factor (Figure 1). The most commonly examined acute risk factors included infections, myocardial infarction, cardiac surgeries, use of antipsychotics and influenza vaccines. Detailed meta-analyses summarizing the magnitude of effect under each sub-group will be presented. Conclusion: Potential acute risk factors having healthcare contact within 90 days preceding stroke have been identified. Further research to assess the role of interventions in health services addressing the risk of stroke from these events is warranted.

Post-marketing active surveillance of Guillain Barré Syndrome following COVID-19 vaccination in persons aged ≥12 years in Italy: A multi-database self-controlled case series study.

Recently published studies have reported association of COVID-19 vaccine ChAdOx1-S (Vaxzevria) with Guillain Barré Syndrome (GBS). Less is known about the safety of other COVID-19 vaccines with respect to GBS outcome. This study investigated the association of COVID-19 vaccines with GBS in more than 15 million persons aged ≥12 years in Italy. Study population was all individuals aged ≥12 years who received at least one dose of COVID-19 vaccines, admitted to emergency care/hospital for GBS from 27 December 2020-30 September 2021 in Italy. Identification of GBS cases and receipt of at least one dose of mRNA-1273 (Elasomeran), BNT162b2 (Tozinameran), ChAdOx1-S (Vaxzevria) and Ad26.COV2.S (Janssen) through record linkage between regional health care and vaccination registries. Relative Incidence (RI) was estimated Self-controlled case series method adapted to event-dependent exposure using in the 42-day exposure risk period after each dose compared with other observation periods. Increased risk of GBS was found after first (RI = 6.83; 95% CI 2.14-21.85) and second dose (RI = 7.41; 2.35-23.38) of mRNA-1273 and first dose of ChAdOx1-S (RI = 6.52; 2.88-14.77). Analysis by age found an increased risk among those aged≥60 years after first (RI = 8.03; 2.08-31.03) and second dose (RI = 7.71; 2.38-24.97) of mRNA-1273. The first dose of ChAdOx1-S was associated with GBS in those aged 40-59 (RI = 4.50; 1.37-14.79) and in those aged ≥ 60 years (RI = 6.84; 2.56-18.28). mRNA-1273 and ChAdOx1-S vaccines were associated with an increased risk of GBS however this risk resulted in a small number of excess cases. Limitations were loss of GBS outpatient cases and imprecision of the estimates in the subgroup analysis due to a low number of events.

Cardiovascular Safety of COVID-19 Vaccination in Patients With Cancer: A Self-Controlled Case Series Study in Korea.

Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the cardiovascular safety of COVID-19 vaccination for cancer patients in South Korea. We conducted a self-controlled case series study using the K-COV-N cohort (2018-2021). Patients with cancer aged 12 years or older who experienced cardiovascular outcomes were identified. Cardiovascular outcomes were defined as myocardial infarction, stroke, venous thromboembolism (VTE), myocarditis, or pericarditis, and the risk period was 0-28 days after receiving each dose of COVID-19 vaccines. A conditional Poisson regression model was used to calculate the incidence rate ratio (IRR) with 95% confidence interval (CI). Among 318,105 patients with cancer, 4,754 patients with cardiovascular outcomes were included. The overall cardiovascular risk was not increased (adjusted IRR, 0.99 [95% CI, 0.90-1.08]) during the whole risk period. The adjusted IRRs of total cardiovascular outcomes during the whole risk period according to the vaccine type were 1.07 (95% CI, 0.95-1.21) in the mRNA vaccine subgroup, 0.99 (95% CI, 0.83-1.19) in the ChAdOx1 nCoV-19 vaccine subgroup, and 0.86 (95% CI, 0.68-1.10) in the mix-matched vaccination subgroup. However, in the analysis of individual outcome, the adjusted IRR of myocarditis was increased to 11.71 (95% CI, 5.88-23.35) during the whole risk period. In contrast, no increased risk was observed for other outcomes, such as myocardial infarction, stroke, VTE, and pericarditis. For cancer patients, COVID-19 vaccination demonstrated an overall safe profile in terms of cardiovascular outcomes. However, caution is required as an increased risk of myocarditis following COVID-19 vaccination was observed in this study.

Limaprost and the Risk of Bleeding: A Self-Controlled Case Series Study.

To investigate the association between the use of limaprost and the risk of bleeding. A self-controlled case series analysis was conducted using the National Health Insurance Service-National Sample Cohort database in South Korea. We identified patients aged 18 years or older who had at least one prescription of limaprost and were diagnosed with at least one case of bleeding between 2003 and 2019. The incidence rate ratio (IRR) of bleeding was calculated by dividing the incidence rate in the exposed period to limaprost by that in the unexposed period and adjusted for age using conditional Poisson regression model. Among 72,860 patients with limaprost prescriptions and bleeding diagnoses, there were 184,732 events of bleeding. After adjusting for age, the IRR was 1.47 (95% confidence interval [CI], 1.43-1.50), wherein the IRR was the highest during the 0-7 days after limaprost initiation (IRR, 2.11; 95% CI, 2.03-2.18). Risk of bleeding was higher when limaprost was concomitantly used with antithrombotics or other drugs for spinal stenosis treatment, and when higher daily doses of limaprost were administered. Our findings suggest that the risk of bleeding increased by 1.5-fold in periods of limaprost exposure compared to unexposed periods, with particularly higher risks observed during the first week after limaprost initiation, with concomitant drugs related to bleeding, and with a higher daily dose. A careful risk-benefit assessment is warranted when initiating limaprost, especially when administered with other medications or in higher daily doses.

Cardiovascular Safety of Atomoxetine and Methylphenidate in Patients With Attention-Deficit/Hyperactivity Disorder in Japan: A Self-Controlled Case Series Study

Objective: To investigate the association between atomoxetine or methylphenidate use and arrhythmia, heart failure (HF), stroke, and myocardial infarction (MI) in attention-deficit/hyperactivity disorder (ADHD) patients mainly focused on the people of working age. Methods: In a self-controlled case series study using a Japanese claims database, we identified events of arrhythmia, HF, stroke, and MI among 15,472 atomoxetine new users and 12,059 methylphenidate new users. Adjusted incidence rate ratios (aIRRs) of outcome events were estimated using multivariable conditional Poisson regression. Results: An increased risk of arrhythmia was observed during the first 7 days after the initial atomoxetine exposure (aIRR 6.22, 95% CI [1.90, 20.35]) and in the subsequent exposure (3.23, [1.58, 6.64]). No association was found between methylphenidate exposure and arrhythmia, nor between atomoxetine or methylphenidate exposure and HF. The limited number of stroke and MI cases prevented thorough analysis. Conclusions: Clinicians should consider monitoring for arrhythmia after patients initiating or re-initiating atomoxetine.

Ocular Adverse Events After Influenza Vaccination in Older Adults: Self-Controlled Case Series Using a Large Database in Japan

ABSTRACT Background To clarify the risk of adverse ocular events following influenza vaccination. Methods This self-controlled case series study used a claims database linked to vaccination records of a large city in Japan between April 2014 and September 2021. Individuals aged ≥ 65 years who developed adverse ocular events during the follow-up period were included. The exposure was influenza vaccination. The primary outcome was defined as the occurrence of at least one of the following five eye diseases: uveitis, scleritis, retinal vein occlusion, retinal artery occlusion, or optic neuritis. Conditional Poisson regression was used to estimate the within-subject incidence rate ratio of ocular adverse events during the risk period (0–56 days after vaccination) compared to the control period. Results A total of 4,527 cases were eligible for the study (median age, 74 years; male, 42%). The incidence rate ratio for the outcome during the risk period was 0.99 (95% confidence interval, 0.87 to 1.14). No increased risk was observed for individual components of the outcome either; the incidence rate ratio was 0.94 (0.78 to 1.13) for uveitis, 1.17 (0.86 to 1.59) for scleritis, 0.98 (0.76 to 1.27) for retinal vein occlusion, 0.89 (0.42 to 1.87) for retinal artery occlusion, and 0.87 (0.44 to 1.70) for optic neuritis. Conclusions This self-controlled case series showed no apparent increase in the risk of adverse ocular events after influenza vaccination among older adults. These results mitigate the concerns of older adults who may hesitate to receive influenza vaccination for fear of adverse ocular events. Abbreviation HR = hazard ratio; CI = confidence interval; RVO = retinal vein occlusion; SCCS = self-controlled case series

Errors and issues in risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies

Errors and issues in risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies

Thrombocytopenia and venous thromboembolic events after BNT162b2, CoronaVac, ChAdOx1 vaccines and SARS-CoV-2 infection: a self-controlled case series study

This study assessed the association between COVID-19 vaccines, SARS-CoV-2 infection and the risk of thrombocytopenia and venous thromboembolism (VTE). This self-controlled case series study used hospital records between 1st February 2021 and 28th February 2022 linked to the national immunisation registry and COVID-19 surveillance data in Malaysia. Conditional Poisson regression was used to estimate incidence rate ratios (IRR) of events in the risk period (day 1–21 post-exposure) relative to control period with the corresponding 95% confidence interval (CI) adjusted for calendar period. We found no significant increased risk of thrombocytopenia in 1–21 days following BNT162b2, CoronaVac and ChAdOx1 vaccines while the risk was increased following SARS-CoV-2 infection (IRR 15.52, 95% CI 13.38–18.00). Similarly, vaccination with BNT162b2, CoronaVac, or ChAdOx1 was not associated with an increased risk of VTE during the 1–21 days risk period. SARS-CoV-2 infection was associated with increased risk of VTE (IRR 39.84, 95% CI 27.45–32.44). Our findings showed low event rates of thrombocytopenia and VTE following booster vaccination with comparable safety profiles between those who received homologous and heterologous booster combinations. Our findings showed the risk of thrombocytopenia and VTE was not increased after COVID-19 vaccination while the risks were substantially higher after SARS-CoV-2 infection.

Risk of atrial tachycardias after covid-19: nationwide self-controlled cases series and matched cohort study

Abstract Background COVID-19 is a multiorgan disease. We previously identified COVID-19 as a risk factor for myocardial infarction, stroke (1), venous thromboembolism and bleeding (2). Less evidence exists on the risk of arrhythmias after COVID-19. Previous studies included mainly hospitalized patients with severe COVID-19, and there are no nationwide studies published. Purpose The aim of this study was to estimate the risk of atrial tachycardias (atrial fibrillation and atrial flutter) following COVID-19, including all individuals tested positive for SARS-CoV-2 in Sweden, regardless of disease severity. Method COVID-19 has been a notifiable disease in Sweden. All individuals in Sweden who were tested positive for SARS-CoV-2 between February 1, 2020 and May 25, 2021 were included in the study. We identified four control individuals for each COVID-19 individual matched on age, sex, and county of residence. Using Personal Identification Numbers, we cross-linked data from national registries: COVID-19 registry; Inpatient and Outpatient Registry; Cause of Death Registry; Prescribed Pharmaceutical Registry and Intensive Care Registry. Outcomes are cardiovascular events, defined using ICD-10 diagnosis codes for atrial fibrillation and atrial flutter in the registries. We performed a ‘’first-ever event’’ analysis, i.e., we excluded individuals with events before the study period. The self-controlled case series (SCCS) method was used to determine the incidence rate ratio (IRR) of a first atrial tachycardia during the risk periods 1-7, 8-14, 15-30, 31-60, 61-90, and 91-180 days after COVID-19. In the matched cohort study (MCS), Poisson regression was performed to calculate the risk ratio (RR) of a first arrhythmia event in the risk period 1-30 days following COVID-19, after adjusting for the effect of confounders, such as cardiac disease, treatment with antiarrhythmics, comorbidities and vaccination status. Results 1 057 174 cases and 4 074 844 controls were included in the study. In the SCCS, the risk of first atrial tachycardia was significantly increased up to 60 days following COVID-19. Specifically, during days 1-7 and 8-14 post-COVID-19 the IRRs were approximately 12 and 10 respectively. Similarly, in the MCS the RR for the first atrial tachycardia during day 1-30 post-COVID-19 was approximately 11. The risks were higher in patients with more severe COVID-19; and during the first pandemic wave compared to the second and third wave. Conclusions This study suggests that COVID-19 is a risk factor for atrial tachycardias, based on information obtained on all people who tested positive for SARS-CoV-2 in Sweden, regardless of disease severity. These results could impact recommendations on diagnostic and prophylactic strategies against atrial tachycardias after COVID-19. The importance of preventive strategies, such as risk factor control; vaccination to prevent severe COVID-19; and early review of high-risk individuals after COVID-19, is indicated.Overview of the SCCS study design.Results of the SCCS- and MCS-studies.

Risk of arrhythmias following COVID-19: nationwide self-controlled case series and matched cohort study

Abstract Aims COVID-19 increases the risk of cardiovascular disease, especially thrombotic complications. There is less knowledge on the risk of arrhythmias after COVID-19. In this study, we aimed to quantify the risk of arrhythmias following COVID-19. Methods and results This study was based on national register data on all individuals in Sweden who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021. The outcome was incident cardiac arrhythmias, defined as international classification of diseases (10th revision) codes in the registers as follows: atrial arrhythmias; paroxysmal supraventricular tachycardias; bradyarrhythmias; and ventricular arrhythmias. A self-controlled case series study and a matched cohort study, using conditional Poisson regression, were performed to determine the incidence rate ratio and risk ratio, respectively, for an arrhythmia event following COVID-19.A total of 1 057 174 exposed (COVID-19) individuals were included in the study as well as 4 074 844 matched unexposed individuals. The incidence rate ratio of atrial tachycardias, paroxysmal supraventricular tachycardias, and bradyarrhythmias was significantly increased up to 60, 180, and 14 days after COVID-19, respectively. In the matched cohort study, the risk ratio during Days 1–30 following COVID-19/index date was 12.28 (10.79–13.96), 5.26 (3.74–7.42), and 3.36 (2.42–4.68), respectively, for the three outcomes. The risks were generally higher in older individuals, in unvaccinated individuals, and in individuals with more severe COVID-19. The risk of ventricular arrhythmias was not increased. Conclusion There is an increased risk of cardiac arrhythmias following COVID-19, and particularly increased in elderly vulnerable individuals, as well as in individuals with severe COVID-19.

Adverse events after first and second doses of COVID-19 vaccination in England: a national vaccine surveillance platform self-controlled case series study.

To estimate the incidence of adverse events of interest (AEIs) after receiving their first and second doses of coronavirus disease 2019 (COVID-19) vaccinations, and to report the safety profile differences between the different COVID-19 vaccines. We used a self-controlled case series design to estimate the relative incidence (RI) of AEIs reported to the Oxford-Royal College of General Practitioners national sentinel network. We compared the AEIs that occurred seven days before and after receiving the COVID-19 vaccinations to background levels between 1 October 2020 and 12 September 2021. England, UK. Individuals experiencing AEIs after receiving first and second doses of COVID-19 vaccines. AEIs determined based on events reported in clinical trials and in primary care during post-license surveillance. A total of 7,952,861 individuals were vaccinated with COVID-19 vaccines within the study period. Among them, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs. Within the first seven days post-vaccination, 4.85% of all the AEIs were reported. There was a 3-7% decrease in the overall RI of AEIs in the seven days after receiving both doses of Pfizer-BioNTech BNT162b2 (RI = 0.93; 95% CI: 0.91-0.94) and 0.96; 95% CI: 0.94-0.98), respectively) and Oxford-AstraZeneca ChAdOx1 (RI = 0.97; 95% CI: 0.95-0.98) for both doses), but a 20% increase after receiving the first dose of Moderna mRNA-1273 (RI = 1.20; 95% CI: 1.00-1.44)). COVID-19 vaccines are associated with a small decrease in the incidence of medically attended AEIs. Sentinel networks could routinely report common AEI rates, which could contribute to reporting vaccine safety.

Association between antenatal corticosteroid treatment and severe adverse events in pregnant women

BackgroundAntenatal corticosteroids are considered the standard of care for pregnant women at risk for preterm birth, but studies examining their potential risks are scarce. We aimed to estimate the associations of antenatal corticosteroids with three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding, in pregnant women.MethodsOf 2,157,321 pregnant women, 52,119 at 24 weeks 0/7 days to 36 weeks 6/7 days of gestation were included in this self-controlled case series study during the study period of 2009–2018. We estimated incidence rates of three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding. Conditional Poisson regression was used to calculate incidence rate ratios (IRRs) for comparing incidence rates of the adverse events in each post-treatment period compared to those during the baseline period among pregnant women exposed to a single course of antenatal corticosteroid treatment.ResultsAmong 52,119 eligible participants who received antenatal corticosteroid treatment, the estimated incidence rates per 1000 person-years were 0.76 (95% confidence interval (CI): 0.69–0.83) for sepsis, 0.31 (95% CI: 0.27–0.36) for heart failure, and 11.57 (95% CI: 11.27–11.87) for gastrointestinal bleeding. The IRRs at 5 ~ 60 days after administration of antenatal corticosteroids were 5.91 (95% CI: 3.10–11.30) for sepsis and 4.45 (95% CI: 2.63–7.55) for heart failure, and 1.26 (95% CI: 1.02–1.55) for gastrointestinal bleeding; and the IRRs for days 61 ~ 180 were 2.00 (95% CI: 1.01–3.96) for sepsis, 3.65 (95% CI: 2.14–6.22) for heart failure, and 1.81 (95% CI: 1.56–2.10) for gastrointestinal bleeding.ConclusionsThis nationwide population-based study suggests that a single course of antenatal corticosteroids is significantly associated with a 1.3- to 5.9-fold increased risk of sepsis, heart failure, and gastrointestinal bleeding in pregnant women. Maternal health considerations, including recommendations for adverse event monitoring, should be included in future guidelines for antenatal corticosteroid treatment.

Cholinesterase inhibitors and non-steroidal anti-inflammatory drugs and the risk of peptic ulcers: A self-controlled study.

Non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution in adults aged 65 years and older. Their gastrointestinal adverse event risk might be further reinforced when using concomitant cholinesterase inhibitors (ChEIs). We aimed to investigate the association between NSAIDs and ChEI use and the risk of peptic ulcers in adults aged 65 years and older. Register-based self-controlled case series study including adults ≥65 years with a new prescription of ChEIs and NSAIDs, diagnosed with incident peptic ulcer in Sweden, 2007-2020. We identified persons from the Total Population Register individually linked to several nationwide registers. We estimated the incidence rate ratio (IRR) of peptic ulcer with a conditional Poisson regression model for four mutually exclusive risk periods: use of ChEIs, NSAIDs, and the combination of ChEIs and NSAIDs, compared with the non-treatment in the same individual. Risk periods were identified based on the prescribed daily dose, extracted via a text-parsing algorithm, and a 30-day grace period. Of 70,060 individuals initiating both ChEIs and NSAIDs, we identified 1500 persons with peptic ulcer (median age at peptic ulcer 80 years), of whom 58% were females. Compared with the non-treatment periods, the risk of peptic ulcer substantially increased for the combination of ChEIs and NSAIDs (IRR: 9.0, [6.8-11.8]), more than for NSAIDs alone (5.2, [4.4-6.0]). No increased risks were found for the use of ChEIs alone (1.0, [0.9-1.2]). We found that the risk of peptic ulcer associated with the concomitant use of NSAIDs and ChEIs was over and beyond the risk associated with NSAIDs alone. Our results underscore the importance of carefully considering the risk of peptic ulcers when co-prescribing NSAIDs and ChEIs to adults aged 65 years and older.

Pfizer COVID19 vaccine is not associated with acute cardiovascular events

Abstract Background Previous reports on acute cardiovascular events and sudden death following administration of COVID19 vaccines usually reported no association, but this issue still stirs much ado. We aimed to assess the risk for acute cardiovascular events that require hospitalization in the short-term following administration of the second Pfizer COVID19 vaccine dose in Israel. Methods We have used a self-controlled case series (SCCS) study design, and included second-dose vaccinees in the period from Jan 11th, 2021 to Oct 31st 2021, who had not been diagnosed with COVID19 and who had an acute cardiovascular event (acute myocardial infarction or acute stroke or acute thromboembolic event; myocarditis events excluded) that required hospitalization in the 60 days following vaccine administration. National databases (COVID19 vaccines; COVID19 infection; Hospitalizations) were used to assemble the study population. The first 30 days were defined ‘high risk period’ while the next 31-60 days were defined ‘control period’, and the risk for an acute cardiovascular event was compared between these periods using a conditional logistic regression model. Possible moderators such as: sex, age group and seasonality were included. Results Out of 5,700,112 second-dose vaccinees in the defined time period, 4,163 had an acute cardiovascular event in the 60 days following vaccine administration: 1,979 in the ‘risk period’ and 2,078 in the ‘control period’ (Odds ratio, OR = 0.95, 95% confidence interval, CI 0.90-1.01, p = 0.12). Moderation of sex, age group and recent (less than 60d prior to vaccination) acute cardiovascular event were not significant. A sensitivity analyses looking at 100 days of follow-up post-vaccination did not change these results. Conclusions We found no indication for an increased risk for an acute cardiovascular event in the 30 days (compared to 31-60 days) following administration of the second vaccine dose of Pfizer COVID19 vaccine. Key messages • We found no indication for an increased risk for an acute cardiovascular event in the 30 days (compared to 31-60 days) following administration of the second vaccine dose of Pfizer COVID19 vaccine. • These findings did not change when sensitivity analyses were used.

Risk of Guillain-Barré Syndrome Following COVID-19 Vaccines: A Nationwide Self-Controlled Case Series Study.

Guillain-Barré syndrome (GBS) has been inconsistently associated with some coronavirus disease 2019 (COVID-19) vaccines. We aimed to quantify the risk of GBS according to the type of COVID-19 vaccine in a large population. Using the French National Health Data System linked to the COVID-19 vaccine database, we analyzed all individuals aged 12 years or older admitted for GBS from December 27, 2020, to May 20, 2022. We estimated the relative incidence (RI) of GBS within 1-42 days after vaccination up to the first booster dose compared with baseline periods using a self-controlled case series design. We then derived the number of cases attributable to the vaccination. Analyses were adjusted for the period and stratified by age group, sex, and for the presence of severe acute respiratory syndrome coronavirus 2 or common acute infections. Of 58,530,770 people aged 12 years or older, 88.8% received at least 1 COVID-19 vaccine dose and 2,229 were hospitalized for GBS during the study period. Patients had a median age of 57 years, and 60% were male patients. The RI of GBS between 1-42 days was 2.5 (95% CI 1.8-3.6) for the first dose of ChAdOx1-S and 2.4 (95% CI 1.2-5.0) for the unique dose of Ad26.COV2.S vaccine. We estimated 6.5 attributable GBS cases per million persons having received a first dose of ChAdOx1-S and 5.7 cases per million for the Ad26.COV2.S vaccine. Except for the age group of 12-49 years after the second dose of the messenger RNA (mRNA)-1273 vaccine (RI 2.6, 95% CI 1.2-5.5), none of the RI estimates were found significantly increased for the mRNA vaccines. In summary, we found increased risks of GBS after the first administration of ChAdOx1-S and Ad26.COV2.S vaccines. In this comprehensive assessment at the French population level, there was no statistically significant increase in the risk of GBS after the administration of mRNA vaccines. This is reassuring in the context of the ongoing and future use of mRNA-based booster vaccination.

A transient positive association between direct-acting antiviral therapy for hepatitis C infection and drug-related hospitalization among people who inject drugs: Self-controlled case-series analysis of national data.

Direct-acting antiviral (DAA) treatment has an established positive effect on liver outcomes in people with hepatitis C infection; however, there is insufficient evidence regarding its effects on the 'extra-hepatic' outcomes of drug-related hospitalization and mortality (DRM) among people who inject drugs (PWID). We investigated associations between these outcomes and DAA treatment by comparing post-treatment to baseline periods using a within-subjects design to minimize selection bias concerns with cohort or case-control designs. This was a self-controlled case-series study. Scotland, 1 January 2015-30 November 2020. The study population of non-cirrhotic, DAA-treated PWID was identified using a data set linking Scotland's hepatitis C diagnosis, HCV clinical databases, national inpatient/day-case hospital records and the national deaths register. Three principal outcomes (drug overdose admission, non-viral injecting related admission and drug-related mortality) were defined using ICD codes. Self-controlled case-series methodology was used to estimate the relative incidence (RI) of each outcome associated with time on treatment and up to six 90-day exposure risk periods thereafter. A total of 6050 PWID were treated with DAAs in the sampling time-frame. Compared with the baseline period, there was a significantly lowered risk of a drug overdose hospital admission in the second to fifth exposure risk periods only [relative incidence (RI) = 0.86, 95% confidence interval (CI) = 0.80-0.99; 0.89, 95% CI = 0.80-0.99; 0.86, 95% CI = 0.77-0.96; 0.88, 95% CI = 0.78-0.99, respectively]. For non-viral injecting-related admission, there was a reduced risk in the first, third and fourth exposure risk periods (RI = 0.76, 95% CI = 0.64-0.90; 0.75, 95% CI = 0.62-0.90; 0.79, 95% CI = 0.66-0.96, respectively). There was no evidence for reduced DRM risk in any period following treatment end. Among people who inject drugs in Scotland, direct-acting antiviral treatment appears to be associated with a small, non-durable reduction in the risk of drug-related hospital admission, but not drug-related mortality. Direct-acting antiviral therapy, despite high effectiveness against liver disease, does not appear to offer a panacea for reducing other drug-related health harms.

Use of hypnotic-sedative medication and risk of falls and fractures in adults: A self-controlled case series study.

To evaluate the risk of falls and fractures in users of benzodiazepines, Z-drugs, or melatonin. We followed 699,335 adults with a purchase of benzodiazepines, Z-drugs, or melatonin in the Danish National Prescription Registry between 2003 and 2016 for falls and fractures in the Danish National Patient Registry between 2000 and 2018. A self-controlled case-series analysis and conditional Poisson regression were used to derive incidence rate ratios (IRR) of falls and fractures during six predefined periods. In total 62,105 and 36,808 adults, respectively, experienced a fall or fracture. For older adults, the risk of falls was highest during the 3-month pre-treatment period (IRRmen+70 , 4.22 (95% confidence interval, 3.53-5.05), IRRwomen + 70 , 3.03 (2.59-3.55)) compared to the baseline (>1 year before initiation). The risk continued to be higher in the later treatment periods. Contrarily, in men and women aged 40-69 years, the risk was only higher in the 3-month pre-treatment period. The incidence of falls among young men and women was slightly lower after initiation of sedating medication (treatment period, IRRmen15-39 , 0.66 (0.50-0.86), IRRwomen15-39 , 0.65 (0.51-0.83)). Analyses with fractures as outcome yielded similar results. Although falls and fractures occur more often in persons using sedative-hypnotic medication, the higher risk of falls and fractures in the pre-treatment period relative to the period directly after treatment, suggests that this association is better explained by other factors that elicited the prescription of this medication rather than the adverse effects of the sedative-hypnotic medication.

Risk of Thrombosis Following the First Dose of ChAdOx1 nCoV-19 Vaccine in Patients Undergoing Maintenance Hemodialysis: A Self-Controlled Case Series Study.

The ChAdOx1 nCoV-19 vaccine is associated with vaccine-induced thrombosis and thrombocytopenia (VITT). Patients with end-stage renal disease (ESRD) under hemodialysis are at elevated risk of heparin-induced thrombocytopenia, which shares similar mechanisms with VITT. We aimed to examine the risk of VITT after the first dose of ChAdOx1 nCoV-19 vaccine using a self-controlled case series analysis (SCCS) in the hemodialyzed ESRD population. Drawing from the largest multi-center electronic medical records database in Taiwan, we identified adult patients, with or without hemodialysis, between 1st December, 2020, and 31st December, 2021, who received a first dose of ChAdOx1 nCoV-19 vaccine and had an outcome of thrombocytopenia, venous thrombosis, or arterial thrombosis. We calculated the incident rate ratios (IRRs) of outcomes in different periods at risk, compared to periods not at risk. We identified 59 hemodialysis patients and 41 non-dialysis patients with an outcome. The SCCS analyses showed, for the hemodialysis group, a significantly increased risk of outcomes during the period 31 to 60 days post-exposure to ChAdOx1 nCoV-19 vaccine (IRR: 2.823; 95% CI: 1.423-5.600). However, in non-dialysis patients there was no increase in risks during any of the post-exposure risk periods. For ESRD patients under hemodialysis, the first dose of ChAdOx1 nCoV-19 vaccine was associated with a 2.8-fold increase in risk of thrombosis.

Acute Cardiovascular Events After COVID-19 in England in 2020: A Self-Controlled Case Series Study.

To assess the risk of incident cardiovascular outcomes after COVID-19 by level of cardiovascular risk in waves one and two of the pandemic in England in 2020. We conducted a self-controlled case-series study among adults aged 40-84 years with no pre-existing cardiovascular disease using linked data from the Clinical Practice Research Datalink. We generated season-adjusted incidence ratios (IRs) for first acute cardiovascular event after SARS-CoV-2 infection compared with baseline time before and >91 days after infection. We used composite and individual acute cardiovascular event outcomes including myocardial infarction, major ventricular arrhythmia, left ventricular heart failure, and ischemic stroke. We stratified by cardiovascular risk, using diagnosed hypertension and QRISK3 predicted risk, and by wave one and two of the pandemic. We included 1762 individuals, 76.6% had a QRISK3 score ≥10% and 59.4% had hypertension. The risk of any cardiovascular event was elevated in the 1-7 days after infection (IR 7.14 [95% CI 6.06-8.41]) and, while the effect size tapered, the risk remained for 15-28 days after infection (1.74 [1.33-2.26]). Risks were similar for individual event type, differing by level of cardiovascular risk, and in wave one and two of the pandemic. . SARS-CoV-2 infection is associated with early elevations in the risk of first acute cardiovascular event, across cardiovascular risk levels and in both wave one and two of the pandemic. Prevention of COVID-19 is important to avert cardiovascular complications.

Increased Risk of Thyroid Eye Disease Following Covid-19 Vaccination.

SARS-CoV-2 infection and Covid-19 vaccines have been associated with thyroid disorders. We analyzed the risk of thyroid eye disease (TED) following Covid-19 vaccination. This was a self-controlled case series study at a tertiary referral center for TED. A total of 98 consecutive patients with newly developed (n = 92) or reactivated (n = 6) TED occurring between January 1, 2021, and August 31, 2022, were included. TED was assessed in patients undergoing Covid-19 vaccination. Person-days were defined as exposed if TED occurred 1 to 28 days after vaccination, and unexposed if occurring outside this time window. Conditional Poisson regression models were fitted to calculate incidence rate ratio (IRR) and 95% CI of exposed vs unexposed. Sensitivity analyses were conducted considering different exposed periods, and effect modification by potential TED risk factors. Covid-19 vaccines were administered in 81 people, 25 (31%) of whom developed TED in exposed and 56 (69%) in unexposed periods. The IRR for TED was 3.24 (95% CI 2.01-5.20) and 4.70 (95% CI 2.39-9.23) in patients below 50 years of age. Sex, smoking, and radioiodine treatment did not modify the association between TED and vaccination. TED risk was unrelated to the number of vaccine doses, and progressively decreased over time following vaccination (P trend = .03). The risk of TED was significantly increased after Covid-19 vaccination, especially in people below 50 years of age. Possible mechanisms include spike protein interaction with the angiotensin-converting enzyme II receptor, cross-reactivity with thyroid self-proteins, and immune reactions induced by adjuvants. We suggest monitoring of individuals undergoing Covid-19 vaccination, especially if young and at risk for autoimmunity.