Self-controlled Case Series Method Research Articles

Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database

PurposeTo investigate the risk of ocular adverse events after COVID-19 mRNA vaccination.DesignMatched cohort and self-controlled case series (SCCS) studies.Subjects/ControlsWe used a population-based database of medical claims and vaccination records in a large city of Japan. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from non-vaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events from February 2021 to the end of follow-up.MethodsIn the matched cohort study, we applied the Kaplan–Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio of ocular adverse events during the risk periods (0–21 days after the first dose and 0–84 days after the second dose) compared to the remaining periods.Main Outcome MeasuresComposite outcome of uveitis, scleritis, retinal vein occlusion, and optic neuritis.ResultsThere were 99,718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100,000 persons and 51.3 (16.2 to 84.3) events/100,000 persons, respectively, for the first and second dose. The SCCS study showed the incidence rate ratios of 0.89 (0.62 to 1.28) and 0.89 (0.71 to 1.11) for the first and second doses, respectively.ConclusionsThe matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events.

Safety of routine childhood vaccine coadministration versus separate vaccination

IntroductionAs new vaccines are developed more vaccine coadministrations vaccines are being offered to make delivery more practical for health systems and patients. We compared the safety of coadministered vaccines with...

The effectiveness and safety of mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines among individuals with chronic kidney diseases

The effectiveness and safety of mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines among individuals with chronic kidney diseases

COVID-19 Vaccination May Not Increase Rates of Corneal Graft Rejection.

The aim of the study was to present the rates of rejection from 2018 to 2021 and evaluate the purported association between COVID-19 vaccination and corneal graft rejection. Cases of corneal graft rejection diagnosed between January 2018 and December 2021 were reviewed. The conditional Poisson regression model of the self-controlled case series method was used to estimate the incidence risk ratio of graft rejection after COVID-19 vaccination risk period compared with the control period. Based on outcomes of eyes that underwent keratoplasty from January 2018 to December 2020, Cox proportional hazard models were fitted with previous COVID-19 vaccination as a time-varying covariate. Over the past 4 years, the annual tally of diagnosed cases of graft rejection (19 cases in year 2018, 19 cases in year 2019, 21 cases in year 2020, and 18 cases in year 2021) has remained relatively stable. Using the conditional Poisson regression analysis, no significant increase in the incidence rate of rejection in the risk period after COVID-19 vaccination was found (incidence risk ratio = 0.56, 95% confidence interval [CI] = 0.13-2.28, P = 0.70). Fitted as a time-varying covariate, previous COVID-19 vaccination was not associated with graft rejection in both unadjusted (hazard ratio =0.77, 95% CI = 0.29-5.46, P = 0.77) and adjusted Cox models (hazard ratio = 0.75, 95% CI = 0.10-5.52, P = 0.78). No notable increase in rates of corneal graft rejection was noted in year 2021 when COVID-19 vaccination was broadly implemented. The apparent temporal relationship between COVID vaccination and corneal graft rejection may not represent a causative association.

Association between BNT162b2 or CoronaVac COVID-19 vaccines and major adverse cardiovascular events among individuals with cardiovascular disease.

AimsConcern about the cardiovascular safety of coronavirus disease 2019 (COVID-19) vaccines among individuals with cardiovascular disease (CVD) may lead to vaccine hesitancy. We sought to assess the association between two COVID-19 vaccines, BNT162b2 and CoronaVac, and the risk of major adverse cardiovascular events (MACE) in individuals with established CVD.Methods and resultsWe identified individuals with a history of CVD before 23 February 2021 and a diagnosis of MACE between 23 February 2021 and 31 January 2022 in Hong Kong. MACE was defined as a composite of myocardial infarction, stroke, revascularization, and cardiovascular death. Electronic health records from the Hong Kong Hospital Authority were linked to vaccination records from the Department of Health. A self-controlled case-series method was used to evaluate the risk of MACE for 0–13 and 14–27 days after two doses of COVID-19 vaccine. We estimated incidence rate ratios (IRRs) to compare the risk of MACE between each risk period and the baseline period. A total of 229 235 individuals with CVD were identified, of which 1764 were vaccinated and had a diagnosis of MACE during the observation period (BNT162b2 = 662; CoronaVac = 1102). For BNT162b2, IRRs were 0.48 [95% confidence interval (CI) 0.23–1.02] for the first dose and 0.87 (95% CI 0.50–1.52) for the second dose during the 0–13 days risk period, 0.40 (95% CI 0.18–0.93) for the first dose and 1.13 (95% CI 0.70–1.84) for the second dose during the 14–27 days risk period. For CoronaVac, the IRRs were 0.43 (95% CI 0.24–0.75) for the first dose and, 0.73 (95% CI 0.46–1.16) for the second dose during the 0–13 days risk period, 0.54 (95% CI 0.33–0.90) for the first dose and 0.83 (95% CI 0.54–1.29) for the second dose during the 14–27 days risk period. Consistent results were found in subgroup analyses for different sexes, age groups and different underlying cardiovascular conditions.ConclusionOur findings showed no evidence of an increased risk of MACE after vaccination with BNT162b2 or CoronaVac in patients with CVD. Future research is required to monitor the risk after the third dose of each vaccine.

Proton Pump Inhibitors and Risk of Cardiovascular Disease: A Self-Controlled Case Series Study.

We investigated cardiovascular risk due to proton pump inhibitor (PPI) treatment using a self-controlled case series (SCCS) study design, a type of case-only design and an approach to overcome between-person confounding in which individuals act as their own control. We conducted an SCCS study using the National Health Insurance Service-Health Screening cohort in Korea (2002-2015). The cohort included 303,404 adult participants without prior cardiovascular events, who were followed up until December 2015. The primary outcome was a composite of stroke or myocardial infarction. The SCCS method estimated the age-adjusted incidence rate ratio between periods with and without exposure to PPI among patients with primary outcomes. As sensitivity analysis, conventional multivariable Cox proportional regression analyses were performed, which treated the exposure to PPI and H2 blocker during follow-up as time-dependent variables. In the SCCS design, 10,952 (3.6%) patients with primary outcomes were included. There was no association between PPI exposure and primary outcome (incidence rate ratio 0.98, 95% confidence interval [CI] 0.89-1.09). In the time-dependent Cox regression analyses, both PPI (adjusted hazard ratio 1.36, 95% CI 1.24-1.49) and H2 blocker (adjusted hazard ratio 1.46, 95% CI 1.38-1.55) were associated with an increased risk of the primary outcome. Negative findings in the SCCS design suggest that association between increased cardiovascular risk and PPI, frequently reported in prior observational studies, is likely due to residual confounding related to conditions with PPI treatment, rather than a true relationship.

The self-controlled case series method and covid-19

The self-controlled case series method is one of two approaches used to estimate the association between covid-19 and venous thromboembolism or bleeding. This article briefly describes the method, its assumptions,...

A modified self-controlled case series method for event-dependent exposures and high event-related mortality, with application to COVID-19 vaccine safety.

We propose a modified self‐controlled case series (SCCS) method to handle both event‐dependent exposures and high event‐related mortality. This development is motivated by an epidemiological study undertaken in France to quantify potential risks of cardiovascular events associated with COVID‐19 vaccines. Event‐dependence of vaccinations, and high event‐related mortality, are likely to arise in other SCCS studies of COVID‐19 vaccine safety. Using this case study and simulations to broaden its scope, we explore these features and the biases they may generate, implement the modified SCCS model, illustrate some of the properties of this model, and develop a new test for presence of a dose effect. The model we propose has wider application, notably when the event of interest is death.

Inclusion of unexposed subjects improves the precision and power of self-controlled case series method

ABSTRACT The self-controlled case series is an important method in the studies of the safety of biopharmaceutical products. It uses the conditional Poisson model to make comparison within persons. In models without adjustment for age (or other time-varying covariates), cases who are never exposed to the product do not contribute any information to the estimation. We provide analytic proof and simulation results that the inclusion of unexposed cases in the conditional Poisson model with age adjustment reduces the asymptotic variance of the estimator of the exposure effect and increases power. We re-analysed a vaccine safety dataset to illustrate.

Association between dipeptidyl peptidase-4 inhibitors and increased risk for bullous pemphigoid within 3 months from first use: A 5-year population-based cohort study using the Japanese National Database.

Aims/IntroductionWe assessed the association between dipeptidyl peptidase‐4 inhibitors (DPP‐4is) and bullous pemphigoid (BP) and time‐dependent changes in the risk for developing BP after DPP‐4i initiation.Materials and MethodsThe present population‐based, real‐world study was carried out using the Japanese National Database dataset collected between 2013 and 2018. To assess independent correlations between DPP‐4is and the development of BP, the self‐controlled case series method was used.ResultsAmong the cohort followed up for a median of 1,540 days, 53,027 patients were likely to develop BP. The possible incidence rate of BP in all 150,328,339 patients was 10.4/100,000 person‐years. Among the 9,705,814 patients with type 2 diabetes, 15,634 were likely to develop BP. The possible incidence rate of BP in patients with type 2 diabetes was 38.1/100,000 person‐years, whereas that in patients with type 2 diabetes who did and did not use DPP‐4is was 40.7 and 30.0/100,000 person‐years, respectively. Analysis of the 28,705 patients with type 2 diabetes likely to develop BP after initial DPP‐4i use showed a risk ratio of 2.15 (95% confidence interval [CI] 1.75–2.63), 1.70 (95% CI 1.37–2.11), 1.44 (95% CI 1.15–1.82), 1.25 (95% CI 0.98–1.59), 0.84 (95% CI 0.63–1.10), 0.84 (95% CI 0.64–1.11) and 1.05 (95% CI 0.92–1.20), for the risk period of ≤30, 31–60, 61–90, 91–120, 121–150, 151–180 and 181–365 days, respectively.ConclusionsAlthough DPP‐4is were associated with increased risk for BP, the risk was particularly significant within 3 months from first use.

200Pneumonia hospitalization and the subsequent risk of incident ischemic cardiovascular disease in Chinese adults

Abstract Background Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond one month, and the potential modifying effect of cardiovascular risk factors on such an association is less well established. Methods The China Kadoorie Biobank study enrolled 512,726 participants from 10 areas across China during 2004-08. By the end of 2017, a total of 5,444 participants with ischemic heart disease (IHD) and 4,846 with ischemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischemic cardiovascular disease (CVD) after pneumonia. Results The risk of ischemic CVD increased during days 1-3 after pneumonia hospitalization, with a RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35), and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischemic CVD risks. Besides, the risk of ischemic CVD was also higher among the participants aged ≥70 years (Pinteraction<0.001 for IHD and =0.033 for IS). Conclusions Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischemic CVD risk for up to one year. Key messages Pneumonia hospitalizations were associated with increased subsequent risk of ischemic CVD.

Hospital-Initiated Care Bundle, Posthospitalization Care, and Outcomes in Adults with Asthma Exacerbation

Hospitalization for asthma exacerbation is an opportune setting for initiating preventive efforts. However, hospital-initiated preventive asthma care remains underdeveloped and its effectiveness is uncertain. To examine the effectiveness of a hospital-initiated asthma care bundle on posthospitalization asthma care and clinical outcomes. Prospective multicenter study of adults (18-54 years) hospitalized for asthma exacerbation in 2017 to 2019. During the hospitalization, we implemented an asthma-care bundle (inpatient laboratory testing, asthma education, and discharge care), and prospectively measured chronic asthma care (eg, immunoglobulin E testing, specialist care) and asthma exacerbation (ie, systemic corticosteroid use, emergency department [ED] visit, hospitalizations) outcomes. By applying a self-controlled case series method, we examined within-person changes in these outcomes before (2-year period) and after (1-year period) the bundle implementation. Of 103 adults hospitalized for asthma exacerbation, the median age was 40 years and 72% were female. Compared with the preimplementation period, the postimplementation period had improved posthospitalized asthma care, including serum specific immunoglobulin E testing (rate ratio [RR] 2.18; 95% confidence interval [95% CI] 0.99-4.84; P= .051) and evaluation by asthma specialist (RR 2.66; 95% CI 1.77-4.04; P<.001). Likewise, after care bundle implementation, patients had significantly lower annual rates of systemic corticosteroid use (4.2 vs 2.9 per person-year; RR 0.70; 95% CI 0.61-0.80; P<.001), ED visits (3.2 vs 2.7 per person-year; RR 0.83; 95% CI 0.72-0.95; P= .008), and hospitalizations (2.1 vs 1.8 per person-year; RR 0.82; 95% CI 0.69-0.97; P= .02). Stratified analyses by sex, race and ethnicity, and health insurance yielded consistent results. After hospital-initiated care bundle implementation, patients had improved posthospitalization care and reduced rates of asthma exacerbation.

Pneumonia hospitalizations and the subsequent risk of incident ischaemic cardiovascular disease in Chinese adults.

Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established. The China Kadoorie Biobank enrolled 512 726 participants aged 30-79 years from 10 areas across China during 2004-2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia. The risk of ischaemic CVD increased during days 1-3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35) and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction < 0.05). Besides, the risk of ischaemic CVD was also higher among the participants aged ≥70 years (Pinteraction < 0.001 for IHD and 0.033 for IS). Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year.

Sirolimus Can Increase the Disappearance Rate of Cardiac Rhabdomyomas Associated with Tuberous Sclerosis: A Prospective Cohort and Self-Controlled Case Series Study

To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P=.027) and female patients (hazard ratio=2.08, P=.015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.

Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa: A population-level self-controlled case series study.

The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified. We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance. In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention.

Risk of intussusception after monovalent rotavirus vaccine (Rotavac) in Indian infants: A self-controlled case series analysis

BackgroundAn association between rotavirus vaccination and intussusception has been documented in post-licensure studies in some countries. We evaluated the risk of intussusception associated with monovalent rotavirus vaccine (Rotavac) administered at 6, 10 and 14 weeks of age in India. MethodsActive prospective surveillance for intussusception was conducted at 22 hospitals across 16 states from April 2016 through September 2017. Data on demography, clinical features and vaccination were documented. Age-adjusted relative incidence for 1–7, 8–21, and 1–21 days after rotavirus vaccination in children aged 28–364 days at intussusception onset was estimated using the self-controlled case-series (SCCS) method. Only Brighton Collaboration level 1 cases were included. ResultsOut of 670 children aged 2–23 months with intussusception, 311 (46.4%) children were aged 28–364 days with confirmed vaccination status. Out of these, 52 intussusception cases with confirmed receipt of RVV were included in the SCCS analysis. No intussusception case was observed within 21 days of dose 1. Only one case occurred during 8–21 days after the dose 2. Post-dose 3, two cases in 1–7 days and 7 cases during 8–21 days period were observed. There was no increased risk of intussusception during 1–7 days after the doses 1 and 2 (zero cases observed) or dose 3 (relative incidence [RI], 1.71 [95% confidence interval {CI} 0.0–5.11]). Similarly, no increased risk during 8–21 days after the dose 1 (zero cases observed), dose 2 (RI, 0.71 [95% CI, 0.0–3.28]) or dose 3 (RI, 2.52 [95% CI, 0.78–5.61]). The results were similar for 1–21 day periods after the doses separately or pooled. ConclusionsThe risk of intussusception during the first 21 days after any dose of rotavirus vaccine (Rotavac) was not higher among the Indian infants than the background risk, based on limited SCCS analysis of 52 children.

Incidence and seasonality of type 1 diabetes: a population-based 3-year cohort study using the National Database in Japan.

IntroductionTo investigate the incidence of type 1 diabetes by age group (0–19, 20–39, 40–59, ≥60 years) in Japan and whether there is seasonality in this incidence.Research design and methodsThe incidence of type 1 diabetes from September 2014 to August 2017 was estimated using 2013–2018 data from the National Database of Health Insurance Claims and Specific Health Check-ups of Japan. The incidence rate was analyzed using Tango’s Index and the self-controlled case series method.ResultsOverall, 10 400 of the 79 175 553 included individuals were diagnosed with type 1 diabetes. The incidence of type 1 diabetes from September 2014 to August 2017 was 4.42/100 000 person-years. The incidence rates for men aged 0–19, 20–39, 40–59, and ≥60 years were 3.94, 5.57, 5.70, and 3.48, respectively. Among women, the incidence rates for the same age ranges were 5.22, 4.83, 4.99, and 3.31, respectively. Tango’s index showed that the incidence rate of type 1 diabetes was significantly associated with seasons among those aged 0–19 years. Further, the self-controlled case series method showed a significant interaction between age and season, with the incidence of type 1 diabetes being higher in spring for patients younger than 20 years of age.ConclusionsIn Japan, men aged 40–59 years and women aged 0–19 years are the groups with the highest incidence of type 1 diabetes. Further, the incidence of younger-onset diabetes in Japan was higher in spring (from March to May).

Assessment of risk of intussusception after pilot rollout of rotavirus vaccine in the Indian public health system

BackgroundPre-licensure trials of ROTAVAC® were not adequately powered to assess risk of intussusception, a rare adverse event associated with other rotavirus vaccines in some settings. We examined the risk of intussusception after ROTAVAC® vaccination among Indian infants during pilot rollout of the vaccine in the public health system in three states - Himachal Pradesh, Maharashtra and Tamil Nadu. MethodsPassive surveillance for intussusception was set up in 35 sentinel health facilities covering 26.3 million population in the three states under monitoring of an Interministerial-Interagency Steering Committee. Clinical and immunization data were collected by independent teams. An expert committee blinded to vaccination status, classified intussusception cases using Brighton criteria. The self-controlled case-series method was used to estimate risk of intussusception (Brighton Level 1) after ROTAVAC® vaccination. Results151 intussusception cases were included in the analysis. The relative incidence (incidence during the risk period compared to the control period) 1–21 days after doses 1 and 2 combined was 1.56 (95% CI, 0.0–5.28) and that for three doses combined was 1.88 (95% CI, 0.76–4.30). Attributable risk 1–21 days after doses 1 and 2 combined was 0.11 (95% CI, 0.0–0.25) and that for 3 doses combined was 0.42 (95% CI, 0.0–0.70) per 100,000 doses. ConclusionsNo increased risk of intussusception within 21 days of receipt of the first two doses combined or all 3 doses combined of ROTAVAC® was detected.

The risk of Kawasaki disease after pneumococcal conjugate & meningococcal B vaccine in England: A self-controlled case-series analysis

Kawasaki disease (KD) is an uncommon condition occasionally reported after childhood vaccination. Admissions with a KD-compatible diagnosis identified from a national database in England were linked to immunisation records to investigate the risk after pneumococcal conjugate (PCV) or meningococcal B (MenB) vaccines. Both are given at 2/4/12 months of age but were introduced sequentially, allowing their effects to be separately assessed. A total of 553 linked admissions in 512 individuals were validated as KD. The relative incidence (RI) within 28 days of PCV doses 1 or 2 measured by the self-controlled case-series method was 0.62 (95% confidence interval (CI) 0.38–1.00) with a significantly decreased risk after dose 3 (RI 0.30 (95% CI 0.11–0.77)). For MenB vaccine, the RI after doses 1 or 2 was 1.03 (95% CI 0.51–2.05) and 0.64 (95% CI 0.08–5.26) after dose 3. This study shows no evidence of an increased risk of KD after either vaccine.

Safety of live attenuated herpes zoster vaccine in adults 70–79 years: A self-controlled case series analysis using primary care data from Australia’s MedicineInsight program

BackgroundAustralia introduced a funded shingles vaccination program for older adults in November 2016, administered predominantly in primary care clinics. MedicineInsight, a nationally representative primary care database, was used to investigate the risk of pre-specified outcomes following live attenuated herpes zoster vaccine (ZVL) in Australia. MethodsIndividuals aged 70–79 years who received ZVL between 1 November 2016 and 31 July 2018 were identified from MedicineInsight. The self-controlled case series (SCCS) method was used to estimate the seasonally-adjusted relative incidence (RI) of seven pre-specified outcome events (injection site reaction (ISR) [positive control], burn [negative control], myocardial infarction (MI), stroke, rash, rash with an antiviral prescription, and clinical attendance) during a plausible post-vaccination at-risk window compared with times distant from vaccination. Sensitivity analyses examined the effect of common concomitant vaccinations and restriction to first outcome events. ResultsA total of 332,988 vaccination encounters among 150,054 individuals were identified during the study period; over 2 million clinical attendances were observed. There was an increased RI of ISR in the seven days following ZVL (RI = 77.4, 95% CI 48.1–124.6); the RI of clinical attendance (RI = 0.94, 95% CI 0.94–0.95) and stroke (RI = 0.58, 95% CI 0.44–0.78) were lower in the 42 days following administration of ZVL compared to control periods. There was no evidence of a change in the RI of MI (RI = 0.74, 95% CI 0.41–1.33), rash (RI = 0.97, 95% CI 0.88–1.08), or rash with antiviral prescription (RI = 0.83, 95% CI 0.62–1.10) in the 42 days following ZVL compared to control periods. ConclusionNo new safety concerns were identified for ZVL in this study based on a novel, Australian primary care data source. An expected increased risk of ISR was identified; findings in relation to cardiovascular disease were reassuring but require confirmation using additional data, including hospital records.