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Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation.Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions. Keywords: Sertoli cells; basal membrane; germ cells; infertility; late effects; seminiferous tubules; spermatogonia; stem cell niche.
Prevention and management of idiosyncratic drug-induced liver injury: Systematic review and meta-analysis of randomised clinical trials.Conducting randomised clinical trials (RCTs) in idiosyncratic drug-induced liver injury (DILI) is challenging. This systematic review aims to summarise the design and findings of RCTs in the prevention and management of idiosyncratic DILI. A systematic literature search up to January 31st, 2020 was performed. Recognised scales were used to assess methodological bias and quality of the studies. Quantitative and qualitative analyses were performed. Heterogeneity was assessed with I2 statistic. Overall, 22 RCTs were included: 12 on prevention (n = 2,471 patients) and 10 in management (n = 797) of DILI/non-acetaminophen DILI-related acute liver failure (ALF). Silymarin (eight studies), bicyclol (four), magnesium isoglycyrrhizinate (three), N-acetylcysteine (three), tiopronin (one), L-carnitine (one), and traditional Chinese medicines (two) were tested in the intervention arm, while control arm mostly received standard supportive care or placebo. Main efficacy criteria in the prevention RCTs was DILI incidence or peak of liver enzymes value. In management RCTs, the efficacy parameter was usually 50 % decrease or normalisation of liver enzymes, or survival rate in DILI-related ALF patients. Overall, 15 trials described the randomisation method, eight were double-blind (n = 672) and nine had sample size estimation (n = 880). Four RCTs involving 377 patients used an intention-to-treat analysis. Based on the scarce number of trials available, tested agents showed limited efficacy in DILI prevention and management and a favourable safety profile. In conclusion, heterogeneity among studies in DILI case qualification and methodologic quality was evident, and the RCTs performed demonstrated limited efficacy of specific interventions. International research networks are needed to establish a framework on RCTs design and therapeutic endpoints.
Patients in need of comprehensive geriatric assessment: The utility of the InterRAI emergency department screener.Introduction: The interRAI Emergency Department-Screener (ED-screener) is a risk stratification instrument incorporating functional and social aspects to identify older adults in EDs. The aim was to assess the construct validity and utility of the ED-screener in comparison with more established instruments. Methods: The ED-screener, Triage Risk Screening Tool (TRST) and Identification of Seniors at Risk (ISAR) were administered to older ED-patients. Construct validity was assessed by correlation with TRST and ISAR. The ED-screener scores that corresponded to the established cut-offs for ISAR and TRST were assessed with linear regression. The sensitivity and specificity of the ED-screener for mortality at 4-months were calculated. Results: Two hundred patients were included (mean age 78.5 years, 44% male). Majority (85%) lived at home, 43% lived alone and 53% received home care. The scores of 3.02 and 3.01 on ED-screener corresponded to the cut-off score of 2 on the other instruments. The correlation of the ED-screener with ISAR and TRST was 0.56 and 0.41 respectively. A score of 3 on the ED-screener was 100% sensitive and 28% specific for 4-month mortality. Conclusion: These findings provide support for the construct validity of the ED-screener and its ability to predict outcomes in its intended setting. Keywords: Comprehensive geriatric assessment; Emergency department; InterRAI ED-screener; Screening.
Is the Thoughts and Health programme feasible in the context of Swedish schools? A quasi-experimental controlled trial study protocol.Introduction: Clinical depression is a substantial problem among adolescents, increasing significantly at about age 15 years. It causes impairment in social, academic and familial relationships, as well as ongoing cognitive and emotional difficulties for the individual. A study in Iceland demonstrated that a cognitive-behavioural, developmentally based intervention programme, 'Thoughts and Health', prevented initial episodes of depression and/or dysthymia (DYS) (major depressive disorder/DYS) in adolescents for up to 12 months following completion of the programme. We would like to test the feasibility of implementing the Icelandic method in a Swedish context and to evaluate the long-term effects of such a programme. Methods and analysis: A quasi-experimental controlled design, combined with qualitative and quantitative methods, will be used to address the research questions.In this study, 617 children aged ~14 years will be screened for depression, and those "at risk" for development of clinical depression will be offered a 12 week course, 'Thoughts and Health'. This course aims to prevent first depression in adolescents. A comparable group of children will function as controls.Depending on the type of variable, baseline comparisons between the two groups of relevant initial measures will be evaluated with t-tests or χ2 analyses. The effects of the programme on the development of clinical levels of depression will be evaluated using the follow-up data of 6, 12 and 18 months. Index parental depression at baseline will be tested as a moderator in the evaluation of the effects of the prevention programme. Ethics and dissemination: This study is approved by the Swedish Ethical Review Board (reference number 2019-03347) in Gothenburg.We plan to disseminate the knowledge gained from this study by publishing our results in peer-reviewed scientific journals and other scholarly outlets. Trial registration number: NCT04128644; Pre-results. Keywords: child & adolescent psychiatry; depression & mood disorders; public health.