Background incidence rates of adverse events of special interest related to COVID-19 vaccines in Ontario, Canada, 2015 to 2020, to inform COVID-19 vaccine safety surveillance

Background: Background incidence rates are critical in pharmacovigilance to facilitate identification of vaccine safety signals. We estimated background incidence rates of nine adverse events of special interest related to COVID-19 vaccines in Ontario, Canada. Methods: We conducted a population-based retrospective observational study using linked health administrative databases for hospitalizations and emergency department visits among Ontario residents. We estimated incidence rates of Bells palsy, idiopathic thrombocytopenia, febrile convulsions, acute disseminated encephalomyelitis, myocarditis, pericarditis, Kawasaki disease, Guillain-Barre syndrome, and transverse myelitis during five pre-pandemic years (2015-2019) and 2020. Results: The average annual population was 14 million across all age groups with 51% female. The pre-pandemic mean annual rates per 100,000 population during 2015-2019 were 43.9 for idiopathic thrombocytopenia, 27.8 for Bells palsy, 25.0 for febrile convulsions, 22.8 for acute disseminated encephalomyelitis, 11.3 for myocarditis/pericarditis, 8.6 for pericarditis, 2.9 for myocarditis, 1.9 for Guillain-Barre syndrome, 1.7 for transverse myelitis, and 1.6 for Kawasaki disease. Females had higher rates of acute disseminated encephalomyelitis and transverse myelitis while males had higher rates of myocarditis, pericarditis, and Guillain-Barre syndrome. Bells palsy, acute disseminated encephalomyelitis, and Guillain-Barre syndrome increased with age. The mean rates of myocarditis and/or pericarditis increased with age up to 79 years; males had higher rates than females: from 12-59 years for myocarditis and 12 years and older for pericarditis. Febrile convulsions and Kawasaki disease were predominantly childhood diseases and generally decreased with age. Conclusions: Our estimated background rates will permit estimating numbers of expected events for these conditions and facilitate detection of potential safety signals following COVID-19 vaccination.

Trends in Pancreatic Cancer Incidence and Mortality in Lithuania, 1998–2015

Background: Pancreatic cancer is one of the deadliest cancers worldwide, and its incidence is increasing. The aim of this study was to examine the time trends in the incidence and mortality rates of pancreatic cancer for the period of 1998–2015 for the first time in Lithuania by sex, age, subsite, and stage. Methods: This study was based on all cases (deaths) of pancreatic cancer diagnosed between 1998 and 2015. Age-standardized incidence (mortality) rates and group-specific rates were calculated for each sex using the direct method (European Standard). TNM classification-based information reported to the cancer registry was grouped into three categories: (1) localized cancer: T1-3/N0/M0; (2) cancer with regional metastasis: any 1-3/N+/M0; (3) advanced cancer: any T/any N/M+. Joinpoint regression was used to provide annual percentage changes (APCs) and to detect points in time where statistically significant changes in the trends occurred. Results: Overall, 8514 pancreatic cancer cases (4364 in men and 3150 in women) were diagnosed and 7684 persons died from cancer of the pancreas. Pancreatic cancer incidence rates were considerably lower for women than for men, with a female:male ratio of 1:2. Incidence rates changed during the study period from 14.2 in 1998 to 15.0/100,000 in the year 2015 in men, and from 6.7 to 9.8/100,000 in women. Incidence rates over the study period were stable for men (APC = 0.1%) and increasing for women by 1.1% per year. Similarly, mortality rates increased in women by 0.9% per year, and were stable in men. During the study period, incidence and mortality rates of pancreatic cancer were close. For the entire study period, rates increased significantly in the 50–74 years age group; only cancer of the head of pancreas showed a decline by 0.9%, while tail and not-specified pancreatic cancer incidence increased by 11.4% and 4.51%, respectively. Conclusions: The increasing pancreatic cancer incidence trend in the Lithuanian population may be related to the prevalence of its main risk factors (smoking, obesity, physical inactivity, diet, and diabetes).

Dengue Fever in Italy: The “Eternal Return” of an Emerging Arboviral Disease

Enhanced surveillance for dengue virus (DENV) infections in Italy has been implemented since 2012, with annual reports from the National Health Institute. In this study, we summarize available evidence on the epidemiology of officially notified DENV infections from 2010–2021. In total, 1043 DENV infection cases were diagnosed, and most of them occurred in travelers, with only 11 autochthonous cases. The annual incidence rates of DENV infections peaked during 2019 with 0.277 cases per 100,000 (95% confidence interval [95% CI] 0.187–0.267), (age-adjusted incidence rate: 0.328, 95% CI 0.314–0.314). Cases of DENV were clustered during the summer months of July (11.4%), August (19.3%), and September (12.7%). The areas characterized by higher notification rates were north-western (29.0%), and mostly north-eastern Italy (41.3%). The risk for DENV infection in travelers increased in the time period 2015–2019 (risk ratio [RR] 1.808, 95% CI 1.594–2.051) and even during 2020–2021 (RR 1.771, 95% CI 1.238–2.543). Higher risk for DENV was additionally reported in male subjects compared with females subjects, and aged 25 to 44 years, and in individuals from northern and central Italy compared to southern regions and islands. In a multivariable Poisson regression model, the increased number of travelers per 100 inhabitants (incidence rate ratio [IRR] 1.065, 95% CI 1.036–1.096), the incidence in other countries (IRR 1.323, 95% CI 1.165–1.481), the share of individuals aged 25 to 44 years (IRR 1.622, 95% CI 1.338–1.968), and foreign-born residents (IRR 2.717, 95% CI 1.555–3.881), were identified as effectors of annual incidence. In summary, although the circulation of DENV remains clustered among travelers, enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.

New Insights into the Epidemiology of Vulvar Cancer: Systematic Literature Review for an Update of Incidence and Risk Factors

The aim of this review was an update of vulvar cancer incidence rates and trends and of all known and putative risk factors for the disease. The most recent incidence data were sought from official sources (WHO Cancer Incidence in Five Continents). To obtain an estimate of time trends in some areas, we compared data from Cancer Incidence in Five Continents with the few available studies that measured incidence using comparable methods. With respect to risk factors, a systematic PubMed search identified 1585 relevant articles published between 1980 and 2021. Abstracts and full texts were screened. Sixty-nine eligible original cohort and case-control studies were selected. Information was extracted using a PRISMA predesigned form. Nineteen risk factors, or risk factor categories, were investigated by two or more original studies. Solitary, unreplicated studies addressed the putative role of eight more factors. Recent advances have provided further evidence supporting the carcinogenic model centred on human papillomavirus infection with different defects of the immune function. Conversely, the model centred on the role of vulvar lichen sclerosus and the often associated differentiated vulvar intraepithelial neoplasia has continued to be epidemiologically understudied. More research on the association between these two conditions and vulvar cancer is a priority.

Risk of Cardiometabolic Risk Factors in Women With and Without a History of Breast Cancer: The Pathways Heart Study

PURPOSE The incidence of cardiometabolic risk factors in breast cancer (BC) survivors has not been well described. Thus, we compared risk of hypertension, diabetes, and dyslipidemia in women with and without BC. METHODS Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California (KPNC) were identified and matched 1:5 to noncancer controls on birth year, race, and ethnicity. Cumulative incidence rates of hypertension, diabetes, and dyslipidemia were estimated with competing risk of overall death. Subdistribution hazard ratios (sHRs) were estimated by Fine and Gray regression, adjusted for cardiovascular disease–related risk factors, and stratified by treatment and body mass index (BMI). RESULTS A total of 14,942 BC cases and 74,702 matched controls were identified with mean age 61.2 years and 65% non-Hispanic White. Compared with controls, BC cases had higher cumulative incidence rates of hypertension (10.9% v 8.9%) and diabetes (2.1% v 1.7%) after 2 years, with higher diabetes incidence persisting after 10 years (9.3% v 8.8%). In multivariable models, cases had higher risk of diabetes (sHR, 1.16; 95% CI, 1.07 to 1.26) versus controls. Cases treated with chemotherapy (sHR, 1.23; 95% CI, 1.11 to 1.38), left-sided radiation (sHR, 1.29; 95% CI, 1.13 to 1.48), or endocrine therapy (sHR, 1.23; 95% CI, 1.12 to 1.34) continued to have higher diabetes risk. Hypertension risk was higher for cases receiving left-sided radiation (sHR, 1.11; 95% CI, 1.02 to 1.21) or endocrine therapy (sHR, 1.10; 95% CI, 1.03 to 1.16). Normal-weight (BMI < 24.9 kg/m2) cases had higher risks overall and within treatment subgroups versus controls. CONCLUSION BC survivors at KPNC experienced elevated risks of diabetes and hypertension compared with women without BC depending on treatments received and BMI. Future studies should examine strategies for cardiometabolic risk factor prevention in BC survivors.

Very Low Incidence of HIV-infection and Decreasing Incidence of STI Among PrEP Users in 2020 After Introduction of Health Insurance Coverage in Germany

IntroductionObjectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence and prevalence of infections with HIV, Chlamydia, Gonorrhea, Syphilis, Hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with Chlamydia/Gonorrhea and Syphilis infections were assessed.MethodsAnonymous data of PrEP users were collected at HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Logistic regression was used to analyze risk factors associated with sexually transmitted infections (STIs).Results4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), PrEP indication 98.6% men who have sex with men (MSM). Duration of PrEP use were 5132 py; median duration 451 days (IQR 357-488).Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two suboptimal adherence was reported and in the third case suboptimal adherence and resistance to emtricitabine was observed. One infection was likely acquired before PrEP start.Incidence rates were 21.6/100py for Chlamydia, 23.7/100py for Gonorrhea, 10.1/100py for Syphilis and 55.4/100py for any STI and decreased significantly. 65.5% of Syphilis, 55.6% of Chlamydia and 50.1% of Gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for Chlamydia/Gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for Chlamydia/Gonorrhea and Syphilis.ConclusionsWe found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV-infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were likely influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

Diabetic macular edema and proliferative diabetic retinopathy treated with anti-vascular endothelial growth factor under the reimbursement policy in Taiwan

The purpose of this retrospective interventional case series is to compare the functional and anatomical outcomes in eyes with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) treated intravitreally with aflibercept or ranibizumab under the Taiwan National Insurance Bureau reimbursement policy. 84 eyes were collected and all eyes were imaged with spectral-domain optical coherence tomography (SD-OCT), color fundus photographs (CFPs), and fluorescein angiography (FA). At 24 months after therapy initiation, the logMAR BCVA improved from 0.58 ± 0.33 to 0.47 ± 0.38 (p < 0.01), the CRT decreased from 423.92 ± 135.84 to 316.36 ± 90.02 (p < 0.01), and the number of microaneurysms decreased from 142.14 ± 57.23 to 75.32 ± 43.86 (p < 0.01). The mean injection count was 11.74 ± 5.44. There was no intergroup difference in logMAR BCVA (p = 0.96), CRT (p = 0.69), or injection count (p = 0.81). However, the mean number of microaneurysms was marginally reduced (p = 0.06) in eyes treated with aflibercept at the end of the follow-up, and the incidence rates of supplementary panretinal photocoagulation (PRP) (p = 0.04) and subthreshold micropulse laser (SMPL) therapy sessions (p = 0.01) were also reduced. Multivariate analysis revealed that only initial logMAR BCVA influenced the final VA improvements (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.21 ~ 0.93, p < 0.01); in contrast, age (OR − 0.38, 95% CI − 6.97 ~ − 1.85, p < 0.01) and initial CRT (OR 0.56, 95% CI 0.34 ~ 0.84, p < 0.01) both influenced the final CRT reduction at 24 months. To sum up, both aflibercept and ranibizumab are effective in managing DME with PDR in terms of VA, CRT and MA count. Eyes receiving aflibercept required less supplementary PRP and SMPL treatment than those receiving ranibizumab. The initial VA influenced the final VA improvements at 24 months, while age and initial CRT were prognostic predictors of 24-month CRT reduction.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunisation Stress-related Responses with COVID-19 mRNA Vaccine

Background: With the implementation of mass vaccination campaigns against COVID 19, the safety of vaccine needs to be evaluated. Objective: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunisation stress related responses (ISRR) with the Moderna COVID 19 vaccine. Methods: This nested case control study included recipients who received the Moderna vaccine at a mass vaccination centre, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1:4) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. Results: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2,478 recipients (cases 2) showed 318 events of IHSR and 2,558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2,129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and history of allergy; for ISRR, they were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. Conclusion: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should beware of the occurrence of ISRR. Risk factor identification may contribute to the stratification of high risk recipients for IHSR and ISRR.

Change in Abdominal Aortic Aneurysm Sac Diameter After Endovascular Repair: A Single-Center Experience From Taiwan

Purpose: The purpose of this study was to investigate the change in the diameter of infrarenal abdominal aortic aneurysm (AAA) sacs after endovascular aortic repair (EVAR) in Taiwanese patients and to depict its association with clinical outcomes. Materials and Methods: This retrospective cohort study was conducted on patients who underwent EVAR for infrarenal AAA between January 2011 and December 2016. All preoperative and follow-up computed tomography (CT) images were reviewed. Postoperative CT angiography was arranged after 1 month and annually thereafter. The maximal diameter on the axial plane and the maximal diameter perpendicular to the centerline on the coronal and sagittal planes were measured. The study examined post-EVAR sac diameter change over time and compared the differences in adverse events (AEs) among groups. Results: The survey included a total of 191 patients with a median follow-up duration of 2.5 (interquartile range: 1.1–2.9) years. Overall survival rates at 1, 2, and 5 years were 92%, 81%, and 76%, respectively. According to their last CT scans, the patients were categorized into 3 groups as follows: shrinkage, stationary, and enlargement, which comprised 58 (30.4%), 118 (61.8%), and 15 (7.9%) patients, respectively. Pre-EVAR characteristics and sac diameters were similar among the groups. Sac shrinkage was exclusively observed in the first 2 years, whereas sac enlargement developed at all follow-up periods. Patients with sac enlargement had higher incidence rates of endoleaks, complications, and reintervention than the other groups. Conclusion: Based on our observations, post-EVAR sac shrinkage only occurs in the first 2 years; however, post-EVAR sacs may enlarge at any point and even after 5 years. In our study, patients with sac enlargement had higher rates of adverse events and reintervention.