Self-controlled Case Series Study Research Articles

Antidepressants and risk of postural hypotension: a self-controlled case series study.

Background Antidepressants are associated with postural hypotension (PH), but it is not typically recognised as a common adverse effect. PH is linked with serious complications in older adults (e.g. falls, stroke, cognitive decline). Randomised Controlled Trials (RCTs) examining antidepressants often exclude older people and do not focus on adverse effects. Aim To examine risk of PH associated with antidepressants in adults aged ≥60 in UK primary care. Design & setting Self-controlled case series using routinely collected primary care data from the IQVIA Medical Research Database (IMRD). Method We obtained data from >41,000 adults aged ≥60 in IMRD between 1 Jan 2000 to 31 Dec 2018. Antidepressant prescriptions were determined using code lists based on British National Formulary classification. Risk of PH was examined during four risk-periods (90-days pre-prescription; day 1-28, 29-56, 57+) compared with periods outside these risk windows. Results Amongst 41,005 people with incident PH in the study period, 8,313 were prescribed a selective-serotonin reuptake inhibitor (SSRI); 8,899 were prescribed a tricyclic antidepressant (TCA); and 4,656 were prescribed an "Other antidepressant". We observed a consistent increased risk of PH in day 1-28 in all antidepressants, that reduced thereafter. Risk of PH was highest with SSRIs (IRR 4.22, 95% CI: 3.76-4.74), followed by "Other antidepressants" (IRR 2.17 (95% CI: 1.76- 2.68), TCAs (IRR 2.12, 95% CI: 1.79-2.50). Conclusion A striking increased risk of PH was observed with all antidepressants in the first month, particularly SSRIs. Prescribers should be aware of this risk and may consider PH monitoring when initiating antidepressants.

Uptake and safety of Sotrovimab for prevention of severe COVID-19 in a cohort and self-controlled case series study

BackgroundSotrovimab is a neutralising monoclonal antibody (nMAB) currently available to treat extremely clinically vulnerable COVID-19 patients in England. Trials have shown it to have mild to moderate side effects, however, evidence regarding its safety in real-world settings remains insufficient.MethodsDescriptive and multivariable logistic regression analyses were conducted to evaluate uptake, and a self-controlled case series analysis performed to measure the risk of hospital admission (hospitalisation) associated with 49 pre-specified suspected adverse outcomes in the period 2–28 days post-Sotrovimab treatment among eligible patients treated between December 11, 2021 and May 24, 2022.ResultsHere we show that among treated and untreated eligible individuals, the mean ages (54.6 years, SD: 16.1 vs 54.1, SD: 18.3) and sex distribution (women: 60.9% vs 58.1%; men: 38.9% vs 41.1%) are similar. There are marked variations in uptake between ethnic groups, which is higher amongst individuals categorised ethnically as Indian (15.0%; 95%CI 13.8, 16.3), Other Asian (13.7%; 95%CI 11.9, 15.8), white (13.4%; 95%CI 13.3, 13.6), and Bangladeshi (11.4%; 95%CI 8.8, 14.6); and lower amongst Black Caribbean individuals (6.4%; 95%CI 5.4, 7.5) and Black Africans (4.7%; 95%CI 4.1, 5.4). We find no increased risk of any of the suspected adverse outcomes in the period 2–28 days post-treatment.ConclusionsWe find no safety signals of concern for possible adverse outcomes in the period 2-28 days post treatment with Sotrovimab. However, there is evidence of unequal uptake of Sotrovimab treatment across ethnic groups.

Safety Assessment of Influenza Vaccination for Neurological Outcomes Among Older Adults in Japan: A Self-Controlled Case Series Study.

To assess adverse neurological risks following influenza vaccination in older adults. Using a linked database of healthcare administrative claims data and vaccination records from an urban city in Japan (April 1, 2014, to March 31, 2020), we conducted an observational study utilizing a self-controlled case series design. We identified individuals aged ≥ 65 years who experienced adverse neurological outcomes, defined as hospitalizations related to epilepsy, paralysis, facial paralysis, neuralgia, neuritis, optic neuritis, migraine, extrapyramidal disorders, Guillain-Barre syndrome, or narcolepsy. We used conditional Poisson regression to analyze within-subject incidence rate ratios, comparing the risk of these outcomes during risk periods following influenza vaccination (0-6 days and 7-29 days after each vaccination) with nonvaccination periods. Our analysis was adjusted for age and season groups as time-varying covariates. We enrolled 3283 eligible individuals (men: 1643; mean [standard deviation] age: 76 [7.3] years). The incidence rate ratio for the outcome during the risk periods was 0.93 (95% confidence interval, 0.66-1.30) in risk period 1 (0-6 days after vaccination) and 1.14 (0.96-1.35) in risk period 2 (7-29 days after vaccination), respectively. We found no evidence that the risk of adverse neurological events was increased after influenza vaccination in older adults. These results may help reassure older adults who are hesitant to receive influenza vaccination because of concerns regarding adverse neurological outcomes.

Risk of Kawasaki Disease/Multisystem Inflammatory Syndrome Following COVID-19 Vaccination in Korean Children: A Self-Controlled Case Series Study.

Rare cases of Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) have been reported following the coronavirus disease 2019 (COVID-19) vaccination; however, the association between COVID-19 vaccination and the risk of developing KD/MIS-C has not yet been established. We conducted a self-controlled case series analysis using a large-linked database that connects the COVID-19 immunization registry with nationwide claims data. We identified individuals aged < 18 years who received their initial COVID-19 vaccination and had a KD/MIS-C diagnosis with a prescription for intravenous immunoglobulin or corticosteroids between October 18, 2021, and April 15, 2023. The observation period was set as 240 days from the date of the COVID-19 vaccination. The risk window was 60 days after vaccination, with the remaining observation period serving as the control window. The incidence rate ratios (IRRs) and 95% confidence intervals (CIs) in the risk versus control windows were estimated using the conditional Poisson regression model. We further analyzed the vaccine doses and types for secondary analysis. We also performed subgroup analyses stratified by sex, age, comorbidities, and other conditions and sensitivity analyses by varying the length of the risk window and outcome definition. Among 2,369,490 individuals who received the COVID-19 vaccination, 12 cases of KD/MIS-C were identified, which included five and seven patients in the risk and control windows, respectively. There was no increased risk of KD/MIS-C within the 60-day period of vaccination (IRR, 0.53; 95% CI, 0.17-1.60). Secondary subgroup and sensitivity analyses showed no significant increase in the risk of KD/MIS-C after COVID-19 vaccination, which is consistent with the results of the main analysis. The results of this nationwide study suggest that the risk of developing KD/MIS-C did not increase after COVID-19 vaccination. However, owing to the lack of a sufficient number of cases, future studies utilizing multinational long-term follow-up databases should be conducted. Considering the increasing incidence of KD/MIS-C and the limited understanding of its precise biological mechanisms, additional research on KD/MIS-C is warranted.

Assessing the Risk of Gastrointestinal Perforation Associated with COVID-19: A Self-Controlled Case Series Study.

Although some case reports have reported gastrointestinal perforation after COVID-19, epidemiological studies investigating this association are scarce. We aimed to assess the risk of gastrointestinal perforation associated with COVID-19. We conducted a self-controlled case series (SCCS) study using a Japanese nationwide, large-scale claims database. We identified patients diagnosed with COVID-19 between March 2020 and October 2022 who had undergone surgery for gastrointestinal perforation. Conditional Poisson regression was used to estimate the incidence rate ratio (IRR) and 95% confidence intervals (CIs) of gastrointestinal perforation during the 4-week risk period compared with the control period. Our SCCS study included 276 patients. The IRR for gastrointestinal perforation was 6.62 (95% CI 3.52 to 12.47) for the first week, 3.27 (95% CI 1.51 to 7.09) for the second week, and 1.45 (95% CI 0.63 to 3.33) for the third and fourth weeks following COVID-19. The risk was lower in female patients than in male patients. In a subgroup analysis, the results were consistent regardless of age. This study suggests a significant association between COVID-19 and gastrointestinal perforation, particularly during the first 2 weeks. These findings highlight the need to recognize COVID-19 as a risk factor for gastrointestinal perforation.

Myasthenia gravis following statin therapy: evidence from target trial emulation and self-controlled case series study

Several international pharmacovigilance agencies have issued warnings regarding the potential risk of myasthenia gravis (MG) following statin therapy. Our study investigated this association using population-based electronic health records in Hong Kong. We conducted a sequence of target trial emulation (TTE) for interpersonal comparison and a self-controlled case series (SCCS) study for intrapersonal comparison. In the TTE for MG onset, the incidence rates (per 100,000 person-years) and adjusted HRs were 51.91(31.80, 84.74)[HR:6.11 (3.73, 10.01)] in month 1, 16.27(9.81, 26.99)[HR:1.92(1.15, 3.19) in months 2-4, and 15.27(9.05, 25.79)[HR:1.80(1.06, 3.04)] in months 5–7. For risk of exacerbation, the adjusted HRs were 10.69(5.48, 20.84) in month 1, 1.50(0.55, 4.06) in months 2–4, and 2.79(1.33, 5.84) in months 5–7. No increased risks were found during the subsequent 18 months. A similar pattern was observed in SCCS analysis. Our findings recommend a minimum monitoring period of approximately six months for MG symptoms for patients starting using statin.

Risk of self-harm and suicide on reaching the age at which a parent died by suicide or other causes: A Danish, population-based self-controlled case series study.

Risk factors for suicide after parental suicide may include points in the lifecourse when reminders of the deceased trigger grief resurgence. We hypothesized that risk of suicide attempt and suicide is elevated among suicide-bereaved offspring on reaching the age at which a parent died by suicide. We conducted a self-controlled case series (SCCS) study using national register data on all individuals bereaved by parental suicide living in Denmark from 1980 to 2016. We compared relative incidence of our combined outcome (any secondary-care episode of self-harm or suicide) during the exposure period (2 years centred on the birthday representing age correspondence) and the 15-year unexposed periods either side. We repeated these models for offspring bereaved by parental non-suicide death as an indirect comparison. Risk of self-harm or suicide was elevated on reaching the age at parental suicide (n = 188; IRRadj: 2.02, 95% CI: 1.21-3.38) relative to flanking periods, but not at parental non-suicide death (n = 734; IRRadj: 0.76; 95% CI: 0.39-1.50). Reaching the age at which a parent died by suicide appears to represent a vulnerable period for suicidality, countering public perceptions that time heals linearly. This indicates a need for support in the lead up to age correspondence.

Risk of cardiovascular events following hemodialysis initiation: a self-controlled case series study.

Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease (CVD). We aimed to evaluate whether hemodialysis (HD) initiation is associated with CVD risk in patients with CKD. This self-controlled case series, using data from a nationwide Korean health claims database, included patients with CKD who initiated HD between 2007 and 2019 and experienced CVD, including acute stroke or myocardial infarction (MI), between 2008 and 2020. The risk periods were categorized relative to HD initiation (-60 to -31, -30 to -11, -10 to -1, +1 to +10, +11 to +30, +31 to +60, and +61 to +150 days); the remaining period was set as baseline. The age-adjusted incidence rate ratio (IRR) of CVD in each risk period relative to the baseline was calculated. Of the 74,584 patients with CKD on incident HD, 12,875 patients with CVD (6,367 with ischemic stroke, 2,396 with hemorrhagic stroke, and 4,112 with MI) were included. Compared with the baseline period, the risk of CVD increased in the post-dialysis periods, decreasing with time since HD initiation; the adjusted IRR during the first 10 days after HD initiation was 2.95 (95% confidence interval, 2.44-3.56). Although the risks of ischemic stroke and MI decreased at 1 to 2 months after HD initiation, the hemorrhagic stroke risk was higher for 5 months. After HD initiation, the CVD risk increases in patients with CKD. For CVD prevention, the CVD risk should be carefully evaluated in patients with CKD who require HD.

Risk for Facial Palsy after COVID-19 Vaccination, South Korea, 2021-2022.

We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1-28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination.

Ocular Adverse Events Following Coronavirus Disease 2019 Infection: A Self-controlled Case Series Study from the Entire Korean Population

This study aimed to assess the risk of ocular adverse events, including retinal artery occlusion (RAO), retinal vein occlusion (RVO), noninfectious uveitis (NIU), noninfectious scleritis (NIS), optic neuritis (ON), ischemic optic neuropathy (ION), and ocular motor cranial nerve palsy (OMCNP), after coronavirus disease 2019 (COVID-19) infection. Population-based self-controlled case series (SCCS). The study included patients from the entire Korean population of 52 million who experienced incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP between January 1, 2021, and October 29,2022. This nationwide SCCS utilized data from the Korea National Health Insurance Service and the Korea Disease Control and Prevention Agency. The risk period after infection was defined as up to 24 weeks after COVID-19 infection. Conditional Poisson regression was used to calculate the relative incidence rate ratios (IRRs) for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the designated risk periods. The IRRs for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the risk periods. The study included 9336, 103362, 201010, 25428, 23744, 3026, 69933, and 16335 cases of incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP, respectively. The IRRs (95% confidence interval) during the early risk period (1-8 weeks) were 0.94 (0.83-1.07), 1.01 (0.97-1.04), 1.00 (0.98-1.03), 0.96 (0.90-1.03), 1.00 (0.94-1.07), 0.97 (0.81-1.17), 0.97 (0.93-1.01), and 1.02 (0.94-1.11), respectively. In the late risk period (9-24 weeks), the IRRs were 1.02 (0.92-1.12), 1.01 (0.98-1.04), 1.01 (0.99-1.03), 1.02 (0.97-1.08), 1.02 (0.97-1.08), 0.99 (0.85-1.15), 1.02 (0.99-1.06), and 0.97 (0.90-1.03), respectively. Stratified analyses showed that in patients with a history of cerebro-cardiovascular disease, the risk of RAO increased during the late risk period, with an IRR (95% confidence interval) of 1.19 (1.02-1.40). The risk of incident RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP did not increase after COVID-19 infection. The risk of incident RAO increased only in individuals with preexisting cardio-cerebrovascular disease. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk of major adverse cerebro-cardiovascular events following BNT162b2, CoronaVac, and ChAdOx1 vaccination and SARS-CoV-2 infection: A self-controlled case-series study

ObjectiveTo assess the potential risk of major adverse cerebro-cardiovascular events (MACCE) associated with COVID-19 vaccination and SARS-CoV-2 infection. MethodsThis self-controlled case series study used nationwide health database from Malaysia. The study included individuals aged ≥18 years who were hospitalised between 24 February 2021 and 30 June 2022. Outcomes were composite of MACCE: stroke, acute ischaemic heart disease, and cardiovascular death. Exposures were COVID-19 vaccination and SARS-CoV-2 infection. The risk period was day 1 to day 21 following exposure. Conditional Poisson regression model was used to estimate the incidence rate ratios (IRRs) and 95 % confidence interval (CI) comparing the outcomes in the risk and control periods. ResultsThe risk of MACCE within 21 days after vaccination per 100,000 doses administered were 12.0 (95% CI 11.9–12.1) (BNT162b2), 9.2 (95% CI 9.1–9.3) (CoronaVac), and 6.8 (95% CI 6.6–7.0) (ChAdOx1). The incidence rate ratios showed no increased risk of MACCE associated with the first, second, or third doses of BNT162b2, CoronaVac, and ChAdOx1 vaccines for individuals without prior cardiovascular disease (CVD). This finding was consistent for individuals with CVD. Vaccine booster dose, whether in a homologous or heterologous schedule, did not show increased risk of MACCE. Analysis by ethnic groups detected a slightly elevated risk of MACCE in Indian after the first dose of ChAdOx1 (IRR 1.64; 95% CI 1.08–2.48) in those without CVD. No significant association were observed in other subgroup analyses. SARS-CoV-2 infection was associated with significantly increased risk of MACCE in individuals without CVD (IRR 3.54; 95% CI 3.32–3.76) and with CVD (IRR 1.98; 95% CI 1.61–2.34). ConclusionsOur findings support the favourable safety profile of these COVID-19 vaccines and indicate that the overall benefit-risk ratio of the COVID-19 vaccines remains positive.

Relationship between proton pump inhibitor prescription and asthma exacerbation among adult patients: a self-controlled case series study.

Proton-pump inhibitors (PPI) are empirically used to treat asthma symptoms such as cough; however, the effectiveness of PPI on asthma exacerbation has not been well studied. We aimed to evaluate the relationship between PPI use and asthma exacerbation using a large administrative claims database in Japan. We conducted a self-controlled case series using the JMDC Claims Database (JMDC, Inc., Tokyo, Japan). The cases included adult patients with asthma who were prescribed PPI and experienced at least one outcome event between January 2015 and December 2019. The primary outcome was the composite outcome of hospital admissions and unscheduled outpatient clinic visits due to asthma exacerbation. We also conducted stratified analyses based on PPI generation, the presence of gastroesophageal reflux disease (GERD), asthma severity, and the number of allergic comorbidities. A total of 7379 eligible patients were included in the study. PPI prescription was associated with a decrease in the composite outcomes (incidence rate ratio, 0.90; 95% confidence interval, 0.87-0.93). However, PPI prescriptions did not affect the outcomes of hospital admissions (incidence rate ratio, 1.34; 95% confidence interval, 0.86-2.10). Stratified analyses based on PPI generation, the presence of GERD, asthma severity (except for severe asthma), and the number of allergic comorbidities yielded consistent results. PPI use was associated with a moderate decrease in asthma exacerbation, regardless of the patient profile. However, this effect was not as strong as the prevention of hospital admissions, and outcome events were not prevented in patients with severe asthma.

Human papillomavirus nonavalent (HPV9) vaccination and risk of immune mediated diseases, myocarditis, pericarditis, and thromboembolic outcomes in Denmark: self-controlled case series study

ObjectiveTo assess the associations between vaccination with the nonavalent human papillomavirus (HPV9) vaccine and immune mediated diseases, myocarditis, pericarditis, arterial thromboembolism, and venous thromboembolism with or without thrombocytopenia, in adolescent...

Risk benefit analysis to evaluate risk of thromboembolic events after mRNA COVID-19 vaccination and COVID-19

We compared the risks and benefits of COVID-19 vaccines using a causal pathway analysis to weigh up possible risk factors of thromboembolic events post-vaccination. The self-controlled case series (SCCS) method examined the association between thromboembolic events and vaccination while a case-control study assessed the association between thromboembolic events and COVID-19, addressing under-reported infection data issues. The net vaccine effect was estimated using results from SCCS and case-control studies. We used electronic health record data from Corewell Health (16,640 subjects in SCCS and 106,143 in case-control). We found increased risks of thromboembolic events post-vaccination (incidence rate ratio: 1.19, 95% CI: [1.08, 1.31] after the first dose; 1.22, 95% CI: [1.11, 1.34] after the second dose). Vaccination attenuated infection-associated thromboembolic risks (odds ratio: 4.65, 95% CI: [4.18, 5.17] in unvaccinated vs 2.77, 95% CI: [2.40, 3.24] in vaccinated). After accounting for vaccine efficacy and protection against infection-associated thromboembolic events, vaccination decreases thromboembolic event risk, especially during high infection rate periods.

Drug-drug interaction between diltiazem and tacrolimus in relation to CYP3A5 genotype status in Chinese pediatric patients with nephrotic range proteinuria: a retrospective study.

Tacrolimus is widely used to treat pediatric nephrotic range proteinuria (NRP). Diltiazem, a CYP3A4/5 inhibitor, is often administered with tacrolimus, affecting its pharmacokinetic profile. The impact of this combination on tacrolimus exposure, particularly in CYP3A5*3 genetic polymorphism, remains unclear in pediatric NRP patients. This study aimed to evaluate the effects of diltiazem on tacrolimus pharmacokinetics, focusing on the CYP3A5*3 polymorphism. We conducted a retrospective clinical study involving pediatric NRP patients, divided into two groups: those receiving tacrolimus with diltiazem and those receiving tacrolimus alone. Propensity score matching (PSM) was used to balance the baseline characteristics between the groups. We compared daily dose-adjusted trough concentrations (C0/D) of tacrolimus in both the original and PSM cohorts. The influence of diltiazem on tacrolimus C0/D, stratified by CYP3A5*3 genetic polymorphism, was assessed in a self-controlled case series study. Before PSM, the tacrolimus C0/D in patients taking diltiazem was significantly higher compared to those with tacrolimus alone (75.84 vs. 56.86ng/mL per mg/kg, P = 0.034). This finding persisted after PSM (75.84 vs. 46.93ng/mL per mg/kg, P= 0.028). In the self-controlled case study, tacrolimus C0/D elevated about twofold (75.84 vs. 34.76ng/mL per mg/kg, P < 0.001) after diltiazem administration. CYP3A5 expressers (CYP3A5*1/*1 and *1/*3) and CYP3A5 non-expressers (CYP3A5*3/*3) experienced a 1.8-fold and 1.3-fold increase in tacrolimus C0/D when combined with diltiazem, respectively. Diltiazem significantly increased tacrolimus C0/D, with CYP3A5*3 expressers showing higher elevations than non-expressers among pediatric NRP patients. These findings highlight the importance of personalized tacrolimus therapy based on CYP3A5*3 genotypes in pediatric patients taking diltiazem.

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

Cholinesterase Inhibitor Initiation Does Not Increase the Risk of Fall-Related Injury in Older Adults Treated With Beta-Blockers: A Self-Controlled Case Series Design.

Prescribing cholinesterase inhibitors (ChEIs) concurrently with beta-blockers might cause syncope that increases the risk of fall-related injuries (FRIs). This self-controlled case series study assesses the risk of FRIs associated with initiating ChEIs while receiving beta-blockers among Medicare fee-for-service-insured nursing home (NH) residents in the United States. We identified individuals at their first dispensing of a beta-blocker between 2016 and 2019 after at least 45 days of long-stay NH residency. Individuals were followed from the first day of beta-blocker use until beta-blocker discontinuation, Medicare disenrollment, death, or study end. ChEI initiation was classified as the first 60 days of new ChEI dispensing after 45 days of no ChEI exposure. FRIs were assessed during beta-blocker use periods, and age-adjusted incidence rate ratios (IRR) for ChEI-initiation days versus other days were calculated using conditional Poisson regression models. Analyses were weighted for event-dependent observation periods due to the high risk of mortality after an FRI in this population. Subgroup analyses were conducted for several key time-fixed variables, including sex, age, ChEI type, ChEI dose, beta-blocker selectivity, and beta-blocker dose. The FRI risk after ChEI initiation was not elevated among 837 residents who experienced an FRI while using beta-blockers (IRR=0.90 [95%CLs 0.71, 1.15]). Analyses of ChEI initiation in several subgroups yielded similar results. There was no substantial difference in FRI risk when initiating ChEIs among older NH residents receiving beta-blocker therapy versus periods without ChEI initiation, suggesting that there is no clinically significant pharmacodynamic drug-drug interaction between beta-blockers and ChEIs.

Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.

The self-controlled case series (SCCS) is often used to monitor vaccine safety. The evaluation of intussusception after the rotavirus vaccine is complicated because the baseline rate varies with age. Time-varying baseline risk adjustments with data from unexposed cohorts are utilised. Self-controlled risk interval (SCRI), with a shorter observation period, can also mitigate the problem by studying a control period close to the risk period. An Indian rotavirus vaccine has previously been studied using SCCS. The risk of intussusception in the high-risk windows (21 days after vaccination) was comparable to the background risk. The aim was to re-analyse data of an existing SCCS study using alternate statistical methods to examine vaccine safety. We examined the mean age of intussusception in the vaccinated and the unvaccinated. We performed an SCRI analysis of the surveillance data from the SCCS study, limiting the observation period to 180 days. We analysed the time-to-intussusception from the last vaccination. Finally, we performed an SCCS analysis, excluding unvaccinated cases from the analysis. We found that the mean age of intussusception was significantly lower in the vaccinated (205 days) compared to the unvaccinated (223 days) (p-value 0.0026). The Incident Risk Ratio (IRR) on SCRI analysis was 1.62 (95% CI 1.07-2.44). There were significantly more intussusceptions in the first 30 days after vaccination compared to the next 30-day window. (92 vs 63 p-value = 0.009). We found that excluding unvaccinated infants from the SCCS analysis demonstrated significantly increased risk for the risk period 1-21 days after the 3rd dose (IRR 2.47, 95% CI 1.70-3.59). The risks of intussusception were missed in traditional SCCS analysis using unvaccinated infants as controls. Traditional risk adjustments using data from unexposed cohorts in SCCS may not be appropriate for investigating the risk of intussusception where vaccination lowers the mean age of intussusception.

Risk of falls or fall-related injuries associated with potentially inappropriate medication use among older adults with dementia.

Potentially inappropriate medications (PIMs) are prevalent in older adults with dementia and subsequent falls or fall-related injuries. The present study determined the risk of falls or fall-related injuries associated with PIM use in older adults with dementia. The National Health Insurance Service-Elderly Cohort Database 2.0 (NHIS-ECDB2.0) was used for this self-controlled case series (SCCS) study. This study included 1430 participants who went through exposure and non-exposure periods of PIM application among patients with dementia and experienced outcome events of falls or fall-related injuries between January 2016 and December 2019. The incidence of falls or fall-related injuries during the exposure and post-exposure periods was compared with that during the non-exposure period. Beers Criteria were used to define PIMs in patients with dementia. Negative binomial regression was conducted. The incidence rate ratio (IRR) was used to determine the risk of falls or fall-related injuries. During the exposure periods in which falls or fall-related injuries occurred, the mean number of PIMs among patients with dementia was 3.76 (SD = 2.99), and the most commonly used PIMs among patients with dementia were first-generation antihistamines (n = 283; 59.1%). Compared to the non-exposure period, the adjusted IRR during the exposure period was 1.57 (95% CI = 1.39-1.76). The risk of falls or fall-related injuries was increased when PIM use in patients with dementia was initiated (1-14days: IRR = 2.76, 95% CI = 2.31-3.28; 15-28days: IRR = 1.95, 95% CI = 1.48-2.56; ≥ 29days: IRR = 1.17, 95% CI = 1.01-1.35). Especially, an increased risk of falls or fall-related injuries was associated with greater PIM use among patients with dementia. Among older adults with dementia, PIMs significantly increase the risk of falls and fall-related injuries. Therefore, strategies should be developed to manage PIM prescriptions in patients with dementia to prevent falls.

COVID-19 Vaccination and Ocular Adverse Events: A Self-Controlled Case Series Study From the Entire South Korean Population

This study aimed to assess the risk of ocular adverse events, including retinal artery occlusion (RAO), retinal vein occlusion (RVO), noninfectious uveitis (NIU), noninfectious scleritis (NIS), optic neuritis (ON), ischemic optic neuropathy (ION), and ocular motor cranial nerve palsy (OMCNP), following Coronavirus Disease 2019 (COVID-19) vaccination. Population-based self-controlled case series METHODS: This study utilized nationwide claims and vaccination data provided by the Korea National Health Insurance Service and Korea Disease Control and Prevention Agency. From the entire South Korean population of 52 million individuals, patients with incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP between January 2021 and March 2022 were included. The postvaccination risk period was defined as up to 56 days after COVID-19 vaccination. The relative incidence rate ratios (IRRs) for RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP during the risk periods were measured using conditional Poisson regression. The study included 6,590, 70,120, 137,958, 17,921, 15,492, 2,039, 49,089, and 11,312 cases of incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, and OMCNP, respectively. The IRRs (95% confidence interval) during the early risk period (0-28 days) were 0.95 (0.88-1.01), 0.96 (0.94-0.98), 0.93 (0.91-0.94), 0.93 (0.89-0.96), 0.96 (0.92-1.01), 1.04 (0.92-1.18), 0.98 (0.95-1.00), and 0.91 (0.86-0.96), respectively. In the late risk period (29-56 days), the IRRs were 0.96 (0.89-1.03), 0.93 (0.91-0.96), 0.96 (0.95-0.98), 1.00 (0.95-1.04), 0.96 (0.91-1.01), 1.00 (0.87-1.15), 1.01 (0.98-1.04), and 0.95 (0.90-1.01), respectively. COVID-19 vaccination did not increase the risk of incident RAO, RVO, anterior NIU, nonanterior NIU, NIS, ON, ION, or OMCNP during the postvaccination period.