COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Background rates of adverse events of special interest for COVID-19 vaccines: A multinational Global Vaccine Data Network (GVDN) analysis.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) project was established in 2021 under the multinational Global Vaccine Data Network (GVDN) consortium to facilitate the rapid assessment of the safety of newly introduced vaccines. This study analyzed data from GVDN member sites on the background incidence rates of conditions designated as adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring. METHODS: Eleven GVDN global sites obtained data from national or regional healthcare databases using standardized methods. Incident events of 13 pre-defined AESI were included for a pre-pandemic period (2015-19) and the first pandemic year (2020). Background incidence rates (IR) and 95% confidence intervals (CI) were calculated for inpatient and emergency department encounters, stratified by age and sex, and compared between pre-pandemic and pandemic periods using incidence rate ratios. RESULTS: An estimated 197 million people contributed 1,189,652,926 person-years of follow-up time. Among inpatients in the pre-pandemic period (2015-19), generalized seizures were the most common neurological AESI (IR ranged from 22.15 [95% CI 19.01-25.65] to 278.82 [278.20-279.44] per 100,000 person-years); acute disseminated encephalomyelitis was the least common (<0.5 per 100,000 person-years at most sites). Pulmonary embolism was the most common thrombotic event (IR 45.34 [95% CI 44.85-45.84] to 93.77 [95% CI 93.46-94.08] per 100,000 person-years). The IR of myocarditis ranged from 1.60 [(95% CI 1.45-1.76) to 7.76 (95% CI 7.46-8.08) per 100,000 person-years. The IR of several AESI varied by site, healthcare setting, age and sex. The IR of some AESI were notably different in 2020 compared to 2015-19. CONCLUSION: Background incidence of AESIs exhibited some variability across study sites and between pre-pandemic and pandemic periods. These findings will contribute to global vaccine safety surveillance and research.

Induced Abortions Among Women Having Undergone Total Hip Replacement: A Nationwide Register Study in Finland.

BACKGROUND AND AIMS: No previous studies have analyzed the connection between total hip replacement and induced abortion. We evaluated the nationwide induced abortion rates among women with and without total hip replacement. MATERIALS AND METHODS: Data for this cohort study were gathered from national registers from 1987 to 2007. All fertile-aged (15-44 years old) females who had undergone primary total hip replacement in Finland were selected. The total hip replacement patient group comprised 1713 women and the reference group 5148 women. Information on all pregnancies for both groups before and after total hip replacement/index date was gathered from the medical birth register and the register of induced abortion. Logistic regression model was used to analyze the adjusted odds ratio for induced abortion. Adjustment was made for age at induced abortion, parity, previous induced abortions, previous deliveries, and marital status. RESULTS: Women had higher induced abortion proportions after total hip replacement (17.9%) compared with women before total hip replacement (14.1%) and the referents (13.9%), but the differences were not statistically significant. Women in the total hip replacement patient group had significantly more induced abortions after total hip replacement due to maternal health issues (14.7%) compared with the referents (2.7%), p = 0.003. Patients in the total hip replacement group were not more likely to have their pregnancy ending in induced abortion than the women in the reference group (odds ratio 1.32, 95% confidence interval 0.89-1.96, p = 0.17). However, in the adjusted analysis, there was a trend for higher risk for pregnancy to end in induced abortion in the total hip replacement group in relation to the reference group (adjusted odds ratio 1.50 (confidence interval 0.99-2.28, p = 0.05). CONCLUSION: The total hip replacement patient group had higher, but statistically insignificant, induced abortion proportions compared with the reference group before and after the operation. After total hip replacement, the patients were not more likely to have a pregnancy ending in induced abortion. This finding remained statistically insignificant after adjusting with possible confounders.

Breast cancer extent and survival among diabetic women in a Finnish nationwide cohort study.

Breast cancer (BC) and diabetes mellitus (DM) are major health problems. We examined the association between DM and BC stage at diagnosis and subsequent survival in a Finnish cohort of female BC patients. All BC cases (N = 73,170) diagnosed in 1995-2013 with dates and causes of death were identified from the Finnish Cancer Registry. Participation in organized mammography screening was obtained from Mass Inspection Registry. Information on DM diagnoses and background conditions recorded during 1995-2013 were obtained from national Care Register for Health Care and merged to data on medication use from the national Prescription Register. Logistic regression with adjustment for mammography screening and age at BC diagnosis was used to evaluate the risk of advanced stage BC at diagnosis. Cox regression was used to evaluate overall and BC survival. Analyses were adjusted for age, background conditions and mammography screening. Survival analyses were further adjusted for tumor extent, histology and primary treatment. Of the cohort 11,676 (16.0%) had DM. Screening participation did not differ by diabetes. Compared to non-diabetic women, diabetics had more often locally advanced (odds ratio, OR 1.26; 95% CI 1.18-1.35) or metastatic BC (OR 1.59; 95% CI 1.44-1.75) at diagnosis. During a median follow-up of 5.8 years after BC diagnosis 10,900 (14.9%) women died of BC. Risk of BC death was higher among diabetic compared to non-diabetic women (HR 1.36; 95% CI 1.27-1.46). Risk of BC death increased with duration of DM. This supports DM as a risk factor for fatal BC.

Determinants of non-participation in a mass screening program for colorectal cancer in Finland.

BACKGROUND: For an effective colorectal cancer (CRC) screening program, high participation rate is essential. However, non-participation in CRC screening program has increased in Finland. MATERIAL AND METHODS: The study was based on a population-based nationwide cohort of persons invited for CRC screening in 2004-2011. Information on the first round of the CRC screening participation and related background factors was obtained from the Finnish Cancer Registry, and information about health behavior factors from the Health Behavior Survey (HBS) in 1978-1999. Non-participation in CRC screening was analyzed with Poisson regression as incidence rate ratios (IRR) with 95% confidence intervals (95% CI). RESULTS: Of all persons invited for CRC screening (79 871 men and 80 891 women) 35% of men and 21% of women refused. Of those invited for screening, 2456 men (3.1%) and 2507 women (3.1%) were also invited to the HBS. Persons, who declined HBS, were also more likely to refuse CRC screening (men IRR 1.40, 95% CI 1.26-1.56, women 1.75, 1.52-2.02) compared to HBS participants. Never married persons had about a 75% higher risk for refusing than married ones. The youngest age group (60 years) was more likely to refuse screening than the older age groups (62 or >64 years). Smoking was associated with non-participation in screening (current smokers, men: IRR 1.32, 95% CI 1.05-1.67, women: 2.10, 1.61-2.73). CONCLUSIONS: Participation in CRC screening was affected by gender, age, and marital status. Persons, who refused the HBS, were also more likely to refuse CRC screening. Smoking was a risk factor for non-participation in CRC screening.

Use of antidepressants and association with elective termination of pregnancy: population based case-control study.

OBJECTIVE: To assess whether the use of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, mirtazapine, venlafaxine or other antidepressants is associated with late elective termination of pregnancy. DESIGN: Case-control study using data from national registers. SETTING: Denmark, Finland, and Norway during the period 1996-2007. POPULATION: A total of 14,902 women were included as cases and 148,929 women were included as controls. METHODS: Cases were women with elective termination of pregnancy at 12-23 weeks of gestation. Controls continued their pregnancy and were matched with cases on key factors. MAIN OUTCOME MEASURES: Association between antidepressant use during pregnancy and elective termination of pregnancy at 12-23 weeks of gestation for fetal anomalies, or for maternal ill health or socio-economic disadvantage. RESULTS: At least one prescription of antidepressants was filled by 3.7% of the cases and 2.2% of the controls. Use of any type of antidepressant was associated with elective termination of pregnancy for maternal ill health or socio-economic disadvantage (odds ratio, OR 2.3; 95% confidence interval, 95% CI 2.0-2.5). Elective termination of pregnancy for fetal anomalies was associated with the use of mirtazapine (OR 2.2, 95% CI 1.1-4.5). There was no association between the use of any of the other antidepressants and elective termination of pregnancy for fetal anomalies. CONCLUSION: The use of any type of antidepressants was associated with elective termination of pregnancy at 12-23 weeks for maternal ill health or socio-economic disadvantage, but not with terminations for fetal anomalies. Further studies need to confirm the findings concerning mirtazapine and termination of pregnancy for fetal anomalies.

Antiepileptic drug use of women with epilepsy and congenital malformations in offspring.

OBJECTIVE: To compare the risk for congenital malformations in offspring between women with epilepsy being treated with antiepileptic drugs (AEDs) during pregnancy and those who discontinued their antiepileptic medication before pregnancy in a population-based cohort of female patients with epilepsy. METHODS: All patients with epilepsy (n = 20,101) eligible for AED reimbursement for the first time during 1985 to 1994 were identified from the Social Insurance Institution of Finland. Information on births during 1991 to 2000 was obtained from the National Medical Birth Registry. Information on AED use during pregnancy and on pregnancy outcomes was abstracted from medical records. RESULTS: Congenital malformations were more common among offspring of women on antiepileptic medication (65/1,411; 4.6%) than among offspring of untreated patients (26/939; 2.8%) (p = 0.02). The risk of malformations was substantially higher in the offspring of patients using valproate as monotherapy (OR = 4.18; 95% CI: 2.31, 7.57) or valproate as polytherapy (OR = 3.54; 95% CI: 1.42, 8.11) than of untreated patients. Polytherapy without valproate was not associated with increased risk of malformations. CONCLUSION: Excess risk was confined to patients using valproate during pregnancy. The risk for malformations was not elevated in offspring of mothers using carbamazepine, oxcarbazepine, or phenytoin (as monotherapy or polytherapy without valproate).

Birth rate among patients with epilepsy: a nationwide population-based cohort study in Finland.

Few reports on population-based studies of birth rate among epilepsy patients have been published. In most previous studies, fertility has been lower among epilepsy patients than in the rest of the population. However, conflicting results have also been reported. Because of small samples and selective material, the generalizability of these results is also limited. The authors conducted a population-based cohort study of birth rate (1985-2001) in a nationwide Finnish cohort of patients with newly diagnosed epilepsy and a population-based reference cohort. All patients (n = 14,077) approved as eligible for reimbursement for antiepileptic medication from the Social Insurance Institution of Finland (KELA) for the first time between 1985 and 1994 were identified from the KELA database. A reference cohort (n = 29,828) was identified from the Finnish Population Register Center, with frequency-matching on age. Information on follow-up status and livebirths were also obtained from the Finnish Population Register Center. The birth rate was lower in patients with epilepsy than in the reference cohort among both men (hazard ratio = 0.58, 95% confidence interval: 0.54, 0.62) and women (hazard ratio = 0.88, 95% confidence interval: 0.83, 0.93). There were a clear decreasing trend by age at observation in men with epilepsy and a moderate decreasing trend by age at start of follow-up in women with epilepsy.