Thrombocytopenia is a clinically relevant outcome in HIV. However, the epidemiology of this condition, including frequency, severity, and duration, has not been well-characterized in the era of highly active antiretroviral therapy (HAART). In this study, we describe the epidemiology of thrombocytopenia using two methods. We conducted a systematic review of the literature published between 1997 and 2009 to characterize the frequency of thrombocytopenia in different populations in the HAART era. Secondly, we examined the frequency, severity, and duration of thrombocytopenia among HIV patients in the Collaborations in HIV Outcomes Research/US (CHORUS) Cohort from 1997 to 2006 and among HIV patients participating in GlaxoSmithKline HIV Clinical Trials between 1996 and 2004. Prevalence estimates of thrombocytopenia (<150 000 platelets/µl) in the literature varied greatly but were generally above 10%. The thrombocytopenia prevalence estimates in the CHORUS Cohort and the HIV Clinical Trials were both 14%. In the CHORUS Cohort, the platelet count was ≤50 000/µl among 3.1% and ≤30 000/µl among 1.7%; in the HIV clinical trials database, the platelet count was ≤50 000/µl among 1.3% and ≤30 000/µl among 0.67%. Duration of severe thrombocytopenia varied greatly, with the medium duration to ≥75 000 platelets/µl taking 147 days in the CHORUS Cohort and 33 days in the HIV clinical trials database. Among 111 patients with severe thrombocytopenia in the CHORUS Cohort, 23% never achieved a higher platelet count over follow-up. In conclusion, while the prevalence of severe thrombocytopenia was low, it occurred at levels associated with bleeding and was persistent among a small proportion of patients despite receipt of HAART.

Liver toxicity is a recognized adverse event associated with small molecule tyrosine kinase inhibitors (TKIs). Electronic Medical Record (EMR) databases offer the most precise data to investigate the rate of liver function test (LFT) elevations; however, they can be limited in sample size and costly to access and analyze. Health insurance claims databases often contain larger samples sizes but may lack key health information. We evaluated the feasibility of utilizing a large claims database to calculate incidence rates (IRs) of LFT elevations among a general cohort of cancer patients and a cohort of patients treated with TKIs by comparing the results to a “gold standard” oncology-specific EMR database. IRs for the TKI cohorts were very similar between the two databases; however, IRs were higher in the EMR database for the cancer cohorts. Possible explanations for these differences include lack of specificity when defining a cancer case, poor capture of laboratory data, or inaccurate assessment of person-time in the insurance claims database. This study suggests that insurance claims data may provide reliable results when investigating liver toxicities associated with oncology drug exposure; however, there are limitations when assessing laboratory outcomes for cohorts defined solely by disease status.

Background: Myocarditis and pericarditis are recognised risks following COVID-19 vaccination, including the mRNA-1273 vaccine. Most cases occur shortly following the second dose of this vaccine, and incidence is highest among young males. However, little is known about risk factors beyond age and sex and about the longer-term clinical course. This study aims to identify possible risk factors for myocarditis and pericarditis following mRNA-1273 vaccination, to characterise the clinical course of myocarditis and pericarditis, both associated with mRNA-1273 vaccination and not associated with vaccination, and to identify risk factors for severe outcomes (i.e., cardiac or thromboembolic complications, severe hospital outcomes, all-cause hospital readmission, and death). Methods: This study is being conducted within the Vaccine Monitoring Collaboration for Europe (VAC4EU) association using routinely collected healthcare data from five data sources from four European countries (Denmark, Norway, Spain, and the United Kingdom). The study is being performed using a common data model, and all analyses are performed separately in each data source in a federated manner following a common protocol. A case–cohort analysis set is identified within each data source for identifying potential risk factors for myocarditis and pericarditis following mRNA-1273 vaccination using logistic regression analysis. The clinical course of myocarditis and pericarditis is being assessed using a cohort study design and describes all cases (i.e., cases associated with mRNA-1273 and unexposed cases). Cox regression analysis is applied to assess the associations between risk factors and several follow-up outcomes. Conclusions: This protocol describes the study methodology of an international collaborative initiative with the aim of assessing the risk factors and clinical course of myocarditis and pericarditis following mRNA-1273 vaccination using a federated network of five European data sources.