Background More than ten years have elapsed since human papillomavirus (HPV) vaccination was implemented. We performed a systematic review and meta-analysis of the population-level impact of female-only HPV vaccination on HPV infections, anogenital wart diagnoses (AGW) and cervical intraepithelial neoplasia grade 2+ (CIN2+) to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination. Methods We updated our prior review (01/01/2007-28/02/2014), by searching Medline and Embase (01/02/2014-11/10/2018) for studies that examined changes, between pre-and post-vaccination periods, in HPV infections, AGW, or CIN2+. We stratified all analyses by sex, age, and years since HPV vaccination introduction. We used random-effects models to estimate pooled relative risks and performed subgroup analysis to identify the main sources of heterogeneity. Findings We identified 65 eligible articles conducted in 14 high-income countries. After 5-8 years of vaccination, HPV-16/18, AGW, and CIN2+ decreased significantly by about 80%, 70%, and 50% among girls aged 15-19 years and by 65%, 55%, and 30% among women aged 20-24 years. Significant cross-protection and herd effects were also observed. HPV-31/33/45 decreased significantly by 50% among girls aged 15-19 years and AGW decreased significantly by 30-50% among boys/men aged 15-24 years. After 5-8 years of vaccination, countries with multi-cohort vaccination and high coverage (≥50%) had greater reductions in AGW, 44 and 85 percentage points among girls and boys aged 15-19 years, respectively, than countries with single-cohort vaccination and/or low vaccination coverage. Interpretation Our meta-analysis, including data from >60 million individuals from 14 high-income countries, shows a substantial impact of female-only HPV vaccination programs on AGW among girls/women and boys/men, and HPV infections and CIN2+ among girls/women. In addition, programs with multi-cohort vaccination and high vaccination coverage lead to greater and faster direct impact and herd effects. CONTRIBUTIONS MD, MB, and MCB conceived the study. MD, EB and NP did the literature search and performed the analysis. MB and MCB participated in the analysis. MD and MB co-drafted the first version of the article.

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Background and Purpose-Stroke patients with hemorrhagic (HS) and ischemic strokes were compared with regard to stroke severity, mortality, and cardiovascular risk factors. Methods-A registry started in 2001, with the aim of registering all hospitalized stroke patients in Denmark, now holds information for 39 484 patients. The patients underwent an evaluation including stroke severity (Scandinavian Stroke Scale), CT, and cardiovascular risk factors. They were followed-up from admission until death or censoring in 2007. Independent predictors of death were identified by means of a survival model based on 25 123 individuals with a complete data set. Results-Of the patients 3993 (10.1%) had HS. Stroke severity was almost linearly related to the probability of having HS (2% in patients with the mildest stroke and 30% in those with the most severe strokes). Factors favoring ischemic strokes vs HS were diabetes, atrial fibrillation, previous myocardial infarction, previous stroke, and intermittent arterial claudication. Smoking and alcohol consumption favored HS, whereas age, sex, and hypertension did not herald stroke type. Compared with ischemic strokes, HS was associated with an overall higher mortality risk (HR, 1.564; 95% CI, 1.441-1.696). The increased risk was, however, time-dependent; initially, risk was 4-fold, after 1 week it was 2.5-fold, and after 3 weeks it was 1.5-fold. After 3 months stroke type did not correlate to mortality. Conclusion-Strokes are generally more severe in patients with HS. Within the first 3 months after stroke, HS is associated with a considerable increase of mortality, which is specifically associated with the hemorrhagic nature of the lesion.

We confirmed that tubal ligation reduces the risk of epithelial ovarian cancer and particularly endometrioid cancer. To our knowledge, this is the first observational publication to report on salpingectomy and ovarian cancer risk and our promising findings warrant further investigation.