Incidence and familial risk of premature ovarian insufficiency in the Finnish female population

STUDY QUESTION: What is the incidence of premature ovarian insufficiency (POI), has the incidence of POI changed over time, and what is the risk of POI among relatives of POI women? SUMMARY ANSWER: The incidence of POI increased among females aged 15-19 years from 2007 onwards and decreased in older age groups, and among relatives of women with POI the risk of POI is significantly increased. WHAT IS KNOWN ALREADY: So far, there has been no good quality, nationwide studies of the incidence of POI. Early menopause has been associated with the elevated risk of early menopause among relatives, but the knowledge of the familial risk of POI is scarce. Lower socioeconomic status has been associated with lower age at natural menopause. STUDY DESIGN, SIZE, DURATION: Population-based study with 5011 women diagnosed with POI in 1988-2017. The data were collected from national registries and covers POI subjects in entire Finland. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with hormone replacement therapy reimbursement for POI were identified from Social Insurance Institution (SII). We calculated POI incidence in different age groups and studied the changes in the incidence rate over time in 5-year segments. Four population-based controls were selected from the Digital and Population Data Services Agency (DVV) for each POI woman. Family members of the POI cases and controls were identified from the DVV and linked to SII reimbursement data to identify POI diagnoses among them. The familial risk of POI was estimated with a logistical regression model. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence was highest in the 35-39 age group, ranging from 73.8/100 000 women-years in 1993-1997 to 39.9/100 000 women-years in 2013-2017. From 2007, the incidence among 15- to 19-year-olds rose from 7.0 to 10.0/100 000 women-years in 2015-2017. Cumulative incidence of POI for women under 40 years in 1988-2017 was 478/100 000 women. The relative risk of POI among relatives of women with POI was 4.6 (95% CI 3.3-6.5) compared to relatives of women without POI. POI women tended to have slightly lower socioeconomic status and level of education compared to controls. LIMITATIONS, REASONS FOR CAUTION: For some women with POI, diagnosis or reimbursement may be lacking. However, we presume that these women represent a minority due to the nature of the disease and the economic benefits of reimbursement. Some changes in the incidence of POI can reflect changes in clinical practice and changing treatments and reimbursement criteria. WIDER IMPLICATIONS OF THE FINDINGS: The risk of developing POI is significantly higher in women who have first-degree relatives diagnosed with POI. Raising awareness of the increased risk might lead to earlier diagnosis and initiation of hormonal replacement therapy, possibly preventing adverse effects of low oestrogen levels, such as osteoporosis. STUDY FUNDING/COMPETING INTEREST(S): This work was financially supported by the Oulu University Hospital. H.S. received a grant from Finnish Menopause Society. S.M.S. received a grant from the Finnish Menopause Society, the Finnish Medical Foundation and the Juho Vainio Foundation. The authors do not have any competing interests to declare.publishedVersionPeer reviewe

Mentors' self‐assessed competence in mentoring nursing students in clinical practice: A systematic review of quantitative studies

Aims and objectives: To examine registered nurses' self‐evaluation of their competence in mentoring nursing students in clinical practice. Background: Clinical mentors have significant roles and responsibility for nursing students' clinical learning. Moreover, the mentors' role is becoming increasingly important internationally, as the role of nurse teachers in mentoring students in clinical practice has declined. However, in most EU countries there are no specific educational requirements for clinical mentors, although they need targeted education to increase their competence in mentoring nursing students. Design: The systematic review of quantitative studies was designed according to guidelines of the Centre for Reviews and Dissemination and PRISMA protocol. Methods: Studies published during 2000–2019 that met inclusion criteria formulated in PiCOS format were systematically reviewed by three independent reviewers. CINAHL (Ebsco), PubMed (MEDLINE), Scopus, ERIC and Medic databases were used to retrieve the studies. Three independent reviewers conducted the systematic review process. The studies were tabulated, thematically compared and narratively reported. Results: In total, 16 peer‐reviewed studies met the inclusion criteria. The studies identified various dimensions of mentors´ competence and associated environmental factors. Generally, participating mentors rated competences related to the clinical environment, mentoring, supporting students' learning processes and relevant personal characteristics fairly high. They also rated organisational practices in their workplaces, resources in the clinical environment and their mentor–student and mentor–stakeholder pedagogical practices, as respectable or satisfactory. Conclusion: The results indicate considerable scope for improving mentors' competence, particularly through enhancing organisational mentoring practices and relevant resources in clinical environments. Relevance for clinical practice: Pedagogical practices of mentors in relations with both students and stakeholders should be enhanced to improve future nurses' learning. This systematic review addresses a gap in knowledge of mentors' self‐evaluated competence that could assist the formulation of effective educational programmes for mentors internationally and improving clinical environments.We would like to acknowledge European Commission, Erasmus+, KA2: Strategic partnership for providing funding for the project Quality mentorship for developing competent nursing students (QualMent)

Distinct Early Molecular Responses to Mutations Causing vLINCL and JNCL Presage ATP Synthase Subunit C Accumulation in Cerebellar Cells

Variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), caused by CLN6 mutation, and juvenile neuronal ceroid lipofuscinosis (JNCL), caused by CLN3 mutation, share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and CbCln6nclf/nclf cerebellar cells and compared them to wild-type and CbCln3Δex7/8/Δex7/8 cerebellar cells. CbCln6nclf/nclf cells and CbCln3Δex7/8/Δex7/8 cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6nclf/nclf cells, while fluid-phase endocytosis and LysoTracker® labeled vesicles were decreased in both CbCln6nclf/nclf and CbCln3Δex7/8/Δex7/8 cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3Δex7/8 and Cln6nclf mutations. Thus, these data support the hypothesis that CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival