The aim of this study was to evaluate the total burden and health care provider costs of prevention, management and treatment of HP-related genital disease outcomes including all organized and opportunistic screening tests. Information about HPV-related disease outcomes in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. We estimated the incidence, health care resource use, health provider costs and life years lost due to cervical, vaginal and vulvar cancer and intraepithelial neoplasia (CIN, VaIN, VIN), cervical adenocarcinoma in situ, and external genital warts. The average annual disease burden of HPV-related genital disease in the female population of Finland comprises altogether 241 cases of cervical, vaginal and vulvar cancer, 2,898 new cases of CIN, 34,432 cases of minor cytological abnormalities, and almost 4,000 cases of external genital warts. The total annual costs of screening, further diagnostics and treatment of HPV-related genital disease were €44.7 million of which the annual costs due to cervical cancer screening were €22.4 million and due to diagnostics, management and treatment of HPV-related genital disease outcomes were €22.3 million. The latter included €8.4 million due to minor cervical abnormalities detected by the current cervical screening practice. The extensive opportunistic Pap testing fails to keep the incidence of cervical cancer from increasing among women aged 30–34. In addition opportunistic screening among this and younger age group detects a significant number of cytological abnormalities, most of which are probably treated unnecessarily.
The c.1102C>T, p.(Gln368Ter) variant in the myocilin (MYOC) gene is a known risk allele for glaucoma. It is the most common MYOC risk variant for glaucoma among individuals of European ancestry, and its prevalence is highest in Finland. Furthermore, exfoliation syndrome has high prevalence in Scandinavia, making the Finnish population ideal to study the association of the variant with different types of glaucoma.To examine the association and penetrance of MYOC p.(Gln368Ter) (rs74315329) variant with different types of glaucoma in a Finnish population.This genetic association study included individuals of Finnish ancestry in the FinnGen project. The participants were collected from Finnish biobanks, and the disease end points were defined using nationwide registries. The MYOC c.1102C>T variant was either directly genotyped or imputed with microarrays. Recruitment of samples to FinnGen was initiated in 2017, and data analysis was performed between December 2019 and May 2020.The main outcomes were odds ratios (ORs) and penetrance with different types of glaucoma and in different age groups.A total of 218 792 individuals were included in this study (mean [SD] age 52.4 [17.5] years; 123 579 women [56.5%]), including 8591 (3.9%) with glaucoma, 3412 (1.6%) with primary open-angle glaucoma, 1515 (0.7%) with exfoliation glaucoma, 892 (0.4%) with normal-tension glaucoma, and 4766 (2.2%) with suspected glaucoma. The minor allele frequency of MYOC p.(Gln368Ter) was 0.28%. Individuals with the heterozygous variant had higher odds of primary open-angle glaucoma (OR, 3.36; 95% CI, 2.55-4.37), overall glaucoma (OR, 2.58; 95% CI, 2.12-3.13), suspected glaucoma (OR, 2.53; 95% CI, 1.93-3.26), exfoliation glaucoma (OR, 2.61; 95% CI, 1.60-4.02), and undergoing glaucoma-related operations (OR, 5.45; 95% CI, 2.95-9.28). The penetrance of heterozygous MYOC p.(Gln368Ter) was 5.2% in individuals with primary open-angle glaucoma, 9.6% in individuals with glaucoma, 5.4% in individuals with suspected glaucoma, and 1.9% in individuals with exfoliation glaucoma. There was no significant association with normal-tension glaucoma (OR, 1.69; 95% CI, 0.72-3.35).This genetic association study found that the MYOC p.(Gln368Ter) variant was associated with exfoliation glaucoma. The association with normal-tension glaucoma could not be replicated. These findings suggest that MYOC p.(Gln368Ter) was associated with open-angle glaucoma and exfoliation glaucoma in a Finnish population.
Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10 −72 ), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls ( P = 1.7 × 10 −4 ), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls ( P = 1.4 × 10 −5 ). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.
The relationship between length of prediagnostic history and course and sequelae of childhood bacterial meningitis was prospectively examined by collecting data from 286 children with bacteriologically confirmed bacterial meningitis. The cases were divided into three groups: short (≤24 hours, N = 141); intermediate (>24 to 48 hours, N = 75); and long (>48 hours, N = 70) history. The level of consciousness and serum C-reactive protein normalized sooner during hospitalization in patients with a longer history. They also showed neck stiffness more often and longer and had thrombocytosis earlier and more prominently than patients with a shorter history. The differences were not influenced by etiology, sex or age. The occurrence of neurologic abnormalities in the hospital or during the first 6 months after discharge was not affected by duration of illness before hospitalization. We conclude that our results support the view that bacterial meningitis presents in two forms. At presentation the more acute form often has a history of less than 24 hours and poses a great danger to the patient. In contrast the other form develops insidiously and is more difficult to detect but does not have a worse prognosis than the acute form.
Abstract Successful development of novel therapies requires that clinical trials are conducted in patient cohorts with the highest benefit-to-risk ratio. Population-based biobanks with comprehensive health and genetic data from large numbers of individuals hold promise to facilitate identification of trial participants, particularly when interventions need to start while symptoms are still mild, such as for Alzheimer’s disease (AD). This study describes a process for clinical recall studies from FinnGen. We demonstrate the feasibility to systematically ascertain customized clinical data from FinnGen participants with ICD10 diagnosis of AD or mild cognitive disorder (MCD) in a single-center cross-sectional study testing blood-based biomarkers and cognitive functioning in-person, computer-based and remote. As a result, 19% (27/140) of a pre-specified FinnGen subcohort were successfully recalled and completed the study. Hospital records largely validated registry entries. For 8/12 MCD patients, other reasons than AD were identified as underlying diagnosis. Cognitive measures correlated across platforms, with highest consistencies for dementia screening (r = 0.818) and semantic fluency (r = 0.764), respectively, for in-person versus telephone-administered tests. Glial fibrillary acidic protein (GFAP) (p < 0.002) and phosphorylated-tau 181 (pTau-181) (p < 0.020) most reliably differentiated AD from MCD participants. We conclude that informative, customized clinical recall studies from FinnGen are feasible.
Pneumococcal conjugate vaccines have potential to prevent significant proportion of childhood pneumonia. Finnish Invasive Pneumococcal disease vaccine trial was designed to assess the vaccine effectiveness (VE) of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against several outcomes. We now report results for pneumonia.In this nationwide, cluster-randomised, double-blind trial, children younger than 19 months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants younger than 7 months at the first vaccination received either 3+1 or 2+1 vaccination schedule, children aged 7-11 months received 2+1, and those 12-18 months of age two-dose schedule. All hospitalizations and outpatient visits to hospital associated with ICD-10 codes compatible with pneumonia were identified through the National Care Register and 1-3 frontal chest X-ray images per event were collected. External readers who were unaware of the patients' vaccination status retrospectively interpreted the images. The evaluated outcomes were hospital-diagnosed, hospital-treated pneumonia as primary diagnosis, and radiologically confirmed pneumonia during the blinded, intention-to-treat follow-up period from the first vaccination to the end of 2011. Total VE was calculated as 1 minus rate ratio of all pneumonia episodes.47 366 children were enrolled from February 2009, to October 2010. VE against all episodes of hospital-diagnosed pneumonia was 27% (95% confidence interval [CI]: 14%, 38%), 32% (95% CI: 3%, 52%), and 23% (95% CI: -5%, 44%) in subjects enrolled at age <7, 7-11, and 12-18 months, respectively. Corresponding rate reductions were 3.4, 4.7, and 2.5 per 1000 person-years. VE estimates against pneumonia with alveolar consolidation or pleural effusion (WHO criteria) in the three cohorts were 45% (95% CI: 26%, 60%), 56% (95% CI: 14%, 77%), and 48% (95% CI: 2%, 73%), respectively.PHiD-CV10 vaccination remarkably reduced disease burden due to pneumonia in infants and young children.Main trial NCT00861380, nested carriage and otitis media trial NCT00839254 (ClinicalTrials.gov).
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