Safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in adolescents aged 12-15 years : Interim analysis of a large community-randomized controlled trial

This community-randomized controlled trial was initiated to assess the overall and herd effects of 2 different human papillomavirus (HPV) immunization strategies in over 80,000 girls and boys aged 1215 y in 33 communities in Finland (ClinicalTrials.gov NCT00534638). Overall, 14,838 adolescents received HPV-16/18 vaccine (2,440 boys and 12,398 girls) and 17,338 received hepatitis-B virus (HBV) vaccine {9,221 boys and 8,117 girls). In an interim analysis, vaccine safety was assessed by active monitoring and surveillancece via health registry linkage. Active monitoring showed that the HPV-16/18 vaccine has acceptable safety and reactogenicity in boys. In all study participants, the observed incidences (per 100,000 person-years) of serious adverse events (SAEs) possibly, related to vaccination were 54.3 (95% Confidence Interval [CI]: 34.0-82.1) in the HPV-16/18 group and 64.0 (95% CI: 43.2-91.3) in the HBV group. During the follow-up period for this interim analysis, the most common new-onset autoimmune diseases (NOADs; with incidence rate >= 15 per 100,000) in any group based on hospital discharge registry (HILMO) download were ulcerative colitis, juvenile arthritis, celiac disease insulin-dependent diabetes mellitus (IDDM) and Crohn's disease. No increased NOAD incidences were observed in HPV-16/18 vaccine recipients compared to HBV vaccine recipients. In both the SAE possibly related- and HILMO-analyses, a lower incidence of IDDM was observed in HPV-16/18 vaccinees compared to HBV vaccinees (relative risks, 0.26 [95% CI: 0.03-1.24] and 0.16 [95% CI: 0.03-0.55], respectively).Peer reviewe

Risk of spontaneous abortion and other pregnancy outcomes in 15–25 year old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom

AbstractBackgroundWe assessed the risk of spontaneous abortion (SA) after inadvertent exposure to HPV-16/18-vaccine during pregnancy using an observational cohort design.MethodsThe study population included women aged 15–25 years registered with the Clinical Practice Research Datalink General Practice OnLine Database in the United Kingdom (UK), who received at least one HPV-16/18-vaccine dose between 1st September 2008 and 30th June 2011. Exposed women had the first day of gestation between 30 days before and 45 days (90 days for the extended exposure period) after any HPV-16/18-vaccine dose. Non-exposed women had the first day of gestation 120 days–18 months after the last dose. SA defined as foetal loss between weeks 1 and 23 of gestation (UK definition).ResultsThe frequency of SA was 11.6% (among 207 exposed) and 9.0% (632 non-exposed), women: hazard ratio (HR) adjusted for age at first day of gestation 1.30 (95% confidence interval: 0.79–2.12). Sensitivity analysis per number of doses administered (−30 to +45-day risk period) showed a HR for SA of 1.11 (0.64–1.91) for 18/178 women with one dose during the risk period versus 2.55 (1.09–5.93) in 6/29 women with two doses within a 4–5 weeks period. The proportion of pre-term/full-term/postterm deliveries, small/large for gestational age infants, and birth defects was not significantly different between exposed and non-exposed women. Results were consistent using a (United States) SA definition of foetal loss between weeks 1–19 and/or the extended risk period.ConclusionThere was no evidence of an increased risk of SA and other adverse pregnancy outcomes in young women inadvertently HPV-16/18-vaccinated around gestation. Nevertheless, women who are pregnant or trying to become pregnant are advised to postpone vaccination until completion of pregnancy

Safety of the AS04-adjuvanted human papillomavirus (HPV)-16/18 vaccine in adolescents aged 12–15 years: end-of-study results from a community-randomized study up to 6.5 years

This manuscript discloses end-of-study safety data of a community-randomized controlled trial in Finland (NCT00534638), assessing the effectiveness of two vaccination strategies (gender-neutral versus females only) using the AS04-adjuvanted human papillomavirus (HPV)-16/18 (AS04-HPV-16/18) vaccine. The total vaccination cohort included 32,175 adolescents aged 12–15 y at vaccination of whom 14,837 received the AS04-HPV-16/18 vaccine and 17,338 received the hepatitis-B virus vaccine (control). Spontaneous reporting of serious adverse events (SAEs) combined with surveillance using nation-wide health registries showed an acceptable safety profile of the AS04-HPV-16/18 vaccine. During the study period (up to 6.5 y), the incidences (per 100,000 person-years) of reported SAEs considered as possibly related to vaccination were 39.1 (95% confidence interval [CI]: 25.3–57.7) and 39.8 (95%CI: 26.8–56.8) in the HPV and control groups, respectively. The most frequently reported new-onset autoimmune diseases (NOADs) were ulcerative colitis (incidence rates of 28.2 and 33.1 per 100,000 person-years in the HPV and control groups, respectively), insulin-dependent diabetes mellitus (21.9 and 37.1), Crohn’s disease (15.6 and 22.5), celiac disease (15.6 and 21.2), and juvenile idiopathic arthritis (14.1 and 15.9). Of 1,344 pregnancies reported (777 and 567 in the HPV and control groups, respectively), most resulted in elective termination (58.4% and 58.6%), birth of a live infant (32.7% and 32.3%), or in spontaneous abortion (8.0% and 7.9%). No major, registered congenital anomalies were identified. The incidence rates of NOADs and pregnancy outcomes were generally balanced between groups. No specific safety signals were identified in the population-based health registry surveillance

Risk of new onset autoimmune disease in 9- to 25-year-old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom

To assess the risk of autoimmune disease (AD) in 9-25 year-old women within 1 year after the first AS04-HPV-16/18vaccine dose, a retrospective, observational database cohort study was conducted using CPRD GOLD. From CPRD GOLD 4 cohorts (65,000 subjects each) were retrieved: 1 exposed female cohort (received ≥1 AS04-HPV-16/18 vaccine dose between Sep2008-Aug2010) and 3 unexposed cohorts: historical female (Sep2005-Aug2007), concurrent male, and historical male. Co-primary endpoints were confirmed neuroinflammatory/ophthalmic AD and other AD, secondary endpoints were confirmed individual AD. Risk of new onset of AD was compared between cohorts (reference: historical cohort) using Poisson regression. The main analysis using confirmed cases showed no neuroinflammatory/ophthalmic AD cases in the female exposed cohort. Incidence rate ratio (IRR) (95% CI) of other AD was 1.41 (0.86 to 2.31) in female and 1.77 (0.94 to 3.35) in male cohorts when compared to the female and male historical cohort, respectively. Secondary endpoints were evaluated for diseases with \u3e10 cases, which were Crohn\u27s disease (IRR: 1.21 [0.37 to 3.95] for female and 4.22 [0.47 to 38.02] for male cohorts), autoimmune thyroiditis (IRR: 3.75 [1.25 to 11.31] for female and no confirmed cases for male cohorts) and type 1 diabetes (IRR: 0.30 [0.11 to 0.83] for female and 2.46 [1.08 to 5.60] for male cohorts). Analysis using confirmed and non-confirmed cases showed similar results, except for autoimmune thyroiditis in females, IRR: 1.45 (0.79 to 2.64). There was no evidence of an increased risk of AD in women aged 9 to 25 years after AS04-HPV-16/18 vaccination

Health Care Utilization and Spending for Children With Mental Health Conditions in Medicaid

ObjectiveTo examine how characteristics vary between children with any mental health (MH) diagnosis who have typical spending and the highest spending; to identify independent predictors of highest spending; and to examine drivers of spending groups.MethodsThis retrospective analysis utilized 2016 Medicaid claims from 11 states and included 775,945 children ages 3 to 17 years with any MH diagnosis and at least 11 months of continuous coverage. We compared demographic characteristics and Medicaid expenditures based on total health care spending: the top 1% (highest-spending) and remaining 99% (typical-spending). We used chi-squared tests to compare the 2 groups and adjusted logistic regression to identify independent predictors of being in the top 1% highest-spending group.ResultsChildren with MH conditions accounted for 55% of Medicaid spending among 3- to 17-year olds. Patients in the highest-spending group were more likely to be older, have multiple MH conditions, and have complex chronic physical health conditions (P <.001). The highest-spending group had $164,003 per-member-per-year (PMPY) in total health care spending, compared to$6097 PMPY in the typical-spending group. Ambulatory MH services contributed the largest proportion (40%) of expenditures ($2455 PMPY) in the typical-spending group; general health hospitalizations contributed the largest proportion (36$58,363 PMPY) in the highest-spending group.ConclusionsAmong children with MH conditions, mental and physical health comorbidities were common and spending for general health care outpaced spending for MH care. Future research and quality initiatives should focus on integrating MH and physical health care services and investigate whether current spending on MH services supports high-quality MH care

Antidotes in Clinical Toxicology—Critical Review

Poisoning and overdose are very important aspects in medicine and toxicology. Chemical weapons pose a threat to civilians, and emergency medicine principles must be followed when dealing with patients who have been poisoned or overdosed. Antidotes have been used for centuries and modern research has led to the development of new antidotes that can accelerate the elimination of toxins from the body. Although some antidotes have become less relevant due to modern intensive care techniques, they can still save lives or reduce the severity of toxicity. The availability of antidotes is crucial, especially in developing countries where intensive care facilities may be limited. This article aims to provide information on specific antidotes, their recommended uses, and potential risks and new uses. In the case of poisoning, supportive therapies are most often used; however, in many cases, the administration of an appropriate antidote saves the patient’s life. In this review, we reviewed the literature on selected antidotes used in the treatment of poisonings. We also characterised the antidotes (bio)chemically. We described the cases in which they are used together with the dosage recommendations. We also analysed the mechanisms of action. In addition, we described alternative methods of using a given substance as a drug, an example of which is N-acetylcysteine, which can be used in the treatment of COVID-19. This article was written as part of the implementation of the project of the Polish Ministry of Education and Science, “Toxicovigilance, poisoning prevention, and first aid in poisoning with xenobiotics of current clinical importance in Poland”, grant number SKN/SP/570184/2023