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1.
  • Olafsson, S, et al. (author)
  • Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations
  • 2017
  • In: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 2, s. 24-
  • Journal article (peer-reviewed)abstract
    • A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10−7, 4.3 × 10−9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.
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  • Frisch, M, et al. (author)
  • Cultural bias in the AAP's 2012 Technical Report and Policy Statement on male circumcision
  • 2013
  • In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 131:4, s. 796-800
  • Journal article (peer-reviewed)abstract
    • The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report’s conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non–US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.
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  • Thorgeirsson, T, et al. (author)
  • Randomized Trial for Weight Loss Using a Digital Therapeutic Application
  • 2022
  • In: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 16:5, s. 1150-1158
  • Journal article (peer-reviewed)abstract
    • Smartphones present a near-ubiquitous channel through which structured lifestyle change can reduce risk or progression of the most common noncommunicable diseases. We explored whether a digital structured lifestyle program enhances weight loss. Methods: We randomized overweight and obese participants attending a four-month lifestyle change program to either standard weekly coaching sessions (controls), or standard treatment supplemented with a digital therapeutic mobile application (intervention). Changes in body mass index after four months were the main outcome measure. Odds ratios of achieving 5% weight loss were estimated with unconditional logistic regression. Results: Of 234 eligible persons, 146 (62%) agreed to participate, were block-randomized, showed up for the baseline measures, and constituted the intention-to-treat (ITT) sample ( n = 95 intervention group, n = 51 control group). In the intervention group, 70 (74%) downloaded the mobile application and completed the program (intervention per-protocol). Significant weight loss and BMI reduction were observed for both the intention-to-treat intervention group ( P < 0.05, P = 0.01) and the per-protocol intervention group ( P < 0.0001, P < 0.0001). For the intervention per-protocol group, the odds ratio of achieving 5% weight loss, compared to not treated per-protocol, was 3.3 (95% CI 1.3-8.2), adjusting for age and weight at baseline.Attendance to weekly coaching sessions decreased by 18% during the program in the control group while it increased by 3% amongst the per-protocol group ( P = 0.004). Conclusions: These preliminary findings support the benefit of a digital therapeutic to enhance weight reduction and attendance in a structured lifestyle change program. Larger trials of longer duration are needed to confirm these findings.
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  • Gunnarsdottir, Anna, et al. (author)
  • Skurðaðgerðir við launeista á Barnaspítala Hringsins 1970-1993
  • 2003
  • In: Laeknabladid. - 0023-7213. ; 89:2, s. 119-123
  • Journal article (peer-reviewed)abstract
    • Objective: Cryptorchidism is a common congenital genito-urological anomali in males with increased risk of infertility and testicular cancer. In this retrospective study the results of operations for undescended testis at Landspitalinn University Hospital were reviewed with special emphasis on patients diagnosed with testicular cancer later in life. Material and methods: The study includes 593 males with undescended testis who were operated on between 1970 and 1993. Information was gathered from hospital records, including birth-weight, age at diagnosis and operation, localization of the testes and complications to surgery. Information on patients diagnosed with testicular cancer was aquired from the Icelandic Cancer Registry. Results: The average birth-weight was 3461 g, including 58 boys (10%) with low birth-weight (
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  • Middelboe, T, et al. (author)
  • The Nordic Study on schizophrenic patients living in the community. Subjective needs and perceived help.
  • 2001
  • In: European psychiatry. - 0924-9338 .- 1778-3585. ; 16:4, s. 207-14
  • Journal article (peer-reviewed)abstract
    • In a community sample of 418 persons diagnosed with schizophrenia, subjective needs and perceived help was measured by the Camberwell Assessment of Need (CAN). The mean number of reported needs was 6.2 and the mean number of unmet needs 2.6. The prevalence of needs varied substantially between the need areas from 3.6% ('telephone') to 84.0% ('psychotic symptoms'). The rate of satisfaction estimated as the percentage of persons satisfied with the help provided within an area varied between 20.0% ('telephone') and 80.6% ('food'). The need areas concerning social and interpersonal functioning demonstrated the highest proportion of unmet to total needs. In a majority of need areas the patients received more help from services than from relatives, but in the areas of social relations the informal network provided substantial help. In general the patients reported a need for help from services clearly exceeding the actual amount of help received. In a linear regression model symptom load (BPRS) and impaired functioning (GAF) were significant predictors of the need status, explaining 30% of the variance in total needs and 20% of the variance in unmet needs. It is concluded that the mental health system fails to detect and alleviate needs in several areas of major importance to schizophrenic patients. Enhanced collaboration between the care system and the informal network to systematically map the need profile of the patients seems necessary to minimise the gap between perceived needs and received help.
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  • Bengtsson-Tops, A, et al. (author)
  • Subjective versus interviewer assessment of global quality of life among persons with schizophrenia living in the community: A Nordic multicentre study
  • 2005
  • In: Quality of Life Research. - : Springer Science and Business Media LLC. - 1573-2649 .- 0962-9343. ; 14:1, s. 221-229
  • Journal article (peer-reviewed)abstract
    • Background: Few studies have investigated differences between subjective and externally assessed quality of life in individuals with a severe mental illness. In a sample of 387 patients with schizophrenia living in the community the present study investigated the association between subjective and interviewer-rated quality of life, clinical and sociodemographic factors related to the two assessments, and if discrepancies in the assessments were related to any clinical or social features of the patients. Method: The study was a Nordic multicentre study with a cross-sectional design. Instruments used were the Lancashire Quality of Life Profile, the Brief Psychiatric Rating Scale, the Interview Schedule for Social Interaction, Camberwell Assessment of Needs and General Assessment of Functioning. Results: The correlation between subjective and interviewer-rated quality of life was moderate (ICC=0.33). More severe affective symptoms, fewer emotional relations and a lower monthly income were related to poorer subjectively rated quality of life but in a stepwise multiple regression analysis accounted for only 14.1 of the variance. Poorer interviewer-rated quality of life was mainly related to a more severe psychopathology but also to a lower monthly income, fewer emotional relations and not being employed. Together these factors accounted for 45.5 of the variance. A greater discrepancy between the subjective and the interviewer rating was found in patients with less affective symptoms, unemployment, and a better social network. Conclusion: Only a moderate correlation between subjective and interviewer-assessed global quality of life was found, implying that the sources of assessment differed, as was also shown in subsequent regression models. It is concluded that both perspectives on the patient's quality of life may be valuable for treatment planning, especially in cases where differences in quality of life assessment related to the patient's psychopathology may be expected.
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  • Birkebaek, N. H., et al. (author)
  • Body mass index standard deviation score and obesity in children with type 1 diabetes in the Nordic countries. HbA(1c) and other predictors of increasing BMISDS
  • 2018
  • In: Pediatric Diabetes. - : WILEY. - 1399-543X .- 1399-5448. ; 19:7, s. 1198-1205
  • Journal article (peer-reviewed)abstract
    • Background: Intensified insulin therapy may increase body weight and cause obesity. This study compared body mass index standard deviation score (BMISDS) and obesity rate in children with type 1 diabetes (T1D) in Denmark, Iceland, Norway and Sweden, and uncovered predictors for increasing BMISDS. Methods: Data registered in the Nordic national childhood diabetes databases during the period 2008-2012 on children below 15 years with T1D for more than 3 months were compiled, including information on gender, age, diabetes duration, hemoglobin A(1c) (HbA(1c)), insulin dose, severe hypoglycemia (SH), treatment modality, height and weight. The Swedish reference chart for BMI was used for calculating BMISDS. Results: Totally, 11025 children (48% females) (30994 registrations) were included. Medians by the last recorded examination were: age, 13.5 years; diabetes duration, 4.3 years; HbA(1c), 7.9% (63 mmol/mol); insulin dose, 0.8 IU/kg/d and BMISDS, 0.70. Obesity rate was 18.5%. Adjusted mean BMISDS (BMISDS adj) was inversely related to HbA(1c) and directly to diabetes duration. Higher BMISDS adj was found in those with an insulin dose above 0.6 IU/kg/d, and in girls above 10 years. Pump users had higher BMISDS adj than pen users, and patients with registered SH had higher BMISDS adj than patients without SH (both P amp;lt; .001). Conclusion: Obesity rate in children with T1D in the Nordic countries is high, however, with country differences. Low HbA(1c), long diabetes duration, higher insulin dose, pump treatment and experiencing a SH predicted higher BMISDS. Diabetes caregivers should balance the risk of obesity and the benefit of a very low HbA(1c).
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  • Bjarnason, B, et al. (author)
  • Assessment of budesonide patch tests
  • 1999
  • In: Contact dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 41:4, s. 211-217
  • Journal article (peer-reviewed)
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  • Bjarnason, B, et al. (author)
  • Reactivity at edges of corticosteroid patch tests may be an indicator of a strong positive test response
  • 1999
  • In: Dermatology (Basel, Switzerland). - : S. Karger AG. - 1018-8665 .- 1421-9832. ; 199:2, s. 130-134
  • Journal article (peer-reviewed)abstract
    • <b>Background:</b> The importance of the reactivity at the edges of corticosteroid patch tests is unknown. <b>Objective:</b> To study the clinical importance of edge reactivity in budesonide patch tests. <b>Methods:</b> Ten subjects previously positive for budesonide patch tests were retested with 0.1% budesonide in Finn Chambers<sup>®</sup> and with budesonide-printed polyester squares in serial doses (150–0.074 μg/cm<sup>2</sup>). Six exposure periods were used for each polyester square dose (3 h to 4 days). Tests were followed up to 11 days. Doubtful or weakly visible reactivity at the test edges was assessed additionally by test perfusion assessments. <b>Results:</b> Nine of 10 subjects reacted with some edge reactivity and later exhibited positive reactions. Perfusion assessments helped to confirm early edge reactivity. Some allergic subjects showed edge reactivity only at high doses, while longer applications were required for weaker doses. <b>Conclusion:</b> Edge reactivity may be an indicator of a strong suppressed test response.
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  • Cui, Yanhua, et al. (author)
  • Prior exposure to alkylating agents negatively impacts testicular organoid formation in cells obtained from childhood cancer patients
  • 2024
  • In: HUMAN REPRODUCTION OPEN. - : OXFORD UNIV PRESS. - 2399-3529. ; 2024:3
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION Can human pre- and peri-pubertal testicular cells obtained from childhood cancer patients, previously treated with chemotherapy, form testicular organoids (TOs)?SUMMARY ANSWER Organoid formation from testicular tissue collected from childhood cancer patients positively correlates with SRY-Box transcription factor 9 (SOX9) expression in Sertoli cells, which in turn negatively correlates with previous exposure to alkylating chemotherapy.WHAT IS KNOWN ALREADY Pre- and peri-pubertal boys exposed to highly gonadotoxic therapies can only safeguard their fertility potential through testicular tissue cryopreservation. Today, there is no established clinical tool to restore fertility using these testicular samples. Organoids hold promise in providing fundamental early insights in creating such platforms. However, the generation of TOs that closely resemble the innate testis, to enable a thorough monitoring of the necessary steps for germ cell differentiation and somatic functionalities, remains a challenge.STUDY DESIGN, SIZE, DURATION We used a Matrigel-based three-layer gradient culture system to generate human TOs and to reveal whether chemotherapy exposure affects TO formation capacity and the functionality of pre- and peri-pubertal testicular somatic cells. Testicular cells of 11 boys (aged 7.7 +/- 4.1 (mean +/- SD) years) were assessed for TO formation in relation to previous chemotherapy exposure and SOX9 expression in histological sections of paraffin-embedded testicular tissue samples collected on the day of biopsy and compared with testicular tissue samples obtained from 28 consecutive patients (aged 6.9 +/- 3.8 (mean +/- SD) years). All 39 patients were part of the fertility preservation project NORDFERTIL; an additional 10 samples (from boys aged 5.5 +/- 3.5 (mean +/- SD) years, without an underlying pathology) in an internal biobank collection were used as controls.PARTICIPANTS/MATERIALS, SETTING, METHODS We obtained 49 testicular tissue samples from boys aged 0.8-13.4 years. Fresh samples (n = 11) were dissociated into single-cell suspensions and applied to a three-layer gradient culture system for organoid formation. Histological sections of another 28 samples obtained as part of the fertility preservation project NORDFERTIL, and 10 samples from a sample collection of a pathology biobank were used to evaluate the effects of prior exposure to alkylating agents on testicular samples. Testicular organoid formation was defined based on morphological features, such as compartmentalized structures showing cord formation, and protein expression of testicular cell-specific markers for germ and somatic cells was evaluated via immunohistochemical staining. Hormone secretion was analysed by specific enzyme-linked immunosorbent assays for testosterone and anti-M & uuml;llerian hormone (AMH) production.MAIN RESULTS AND THE ROLE OF CHANCE Our results revealed that 4 out of 11 prepubertal testicular samples formed TOs that showed compartmentalized cord-like structures surrounded by interstitial-like areas and increasing levels of both testosterone as well as AMH over a 7-day culture period. We observed that SOX9 expression was correlated positively with TO formation. Moreover, exposure to alkylating agents before biopsy was inversely correlated with SOX9 expression (P = 0.006).LARGE SCALE DATA N/A.LIMITATIONS, REASONS FOR CAUTION Due to the limited amount of material available, only 11 out of the 39 pre- and peri-pubertal testicular tissue samples could be used for the organoid formation experiments. The testicular tissue samples obtained from a sample collection of the internal biobank of Department of Pathology, Karolinska University Hospital were considered normal and included in the study if no testicular pathology was reported. However, detailed information regarding previous medical treatments and/or testicular volumes of the patients included in this biobank was not available.WIDER IMPLICATIONS OF THE FINDINGS Our observations suggest that SOX9 expression may serve as a putative indicator of TO formation, indicating a critical role of Sertoli cells in promoting organoid formation, seminiferous tubule integrity, and testicular function in pre- and peri-pubertal testicular tissue.STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115; TJ2020-0023) (J.-B.S.), Finnish Cancer Society (K.J.), Finnish Foundation for Paediatric Research (K.J.), Swedish Research Council (2018-03094; 2021-02107) (J.-B.S.), and Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2020-00335; 2021-00073; 2022-00317) (J.-B.S. and K.J.). Y.C. and Y.Y. received a scholarship from the Chinese Scholarship Council. J.P.A-L. was supported by a Starting Grant in Medicine and Health (2022-01467) from the Swedish Research Council. R.T.M. was supported by a UKRI Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health was supported by an MRC Centre Grant (MR/N022556/1). The authors declare no competing interests.
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  • Cui, Yanhua, et al. (author)
  • Prior exposure to alkylating agents negatively impacts testicular organoid formation in cells obtained from childhood cancer patients
  • 2024
  • In: Human Reproduction Open. - : Oxford University Press. - 2399-3529. ; 2024:3
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION: Can human pre- and peri-pubertal testicular cells obtained from childhood cancer patients, previously treated with chemotherapy, form testicular organoids (TOs)?SUMMARY ANSWER: Organoid formation from testicular tissue collected from childhood cancer patients positively correlates with SRY-Box transcription factor 9 (SOX9) expression in Sertoli cells, which in turn negatively correlates with previous exposure to alkylating chemotherapy.WHAT IS KNOWN ALREADY: Pre- and peri-pubertal boys exposed to highly gonadotoxic therapies can only safeguard their fertility potential through testicular tissue cryopreservation. Today, there is no established clinical tool to restore fertility using these testicular samples. Organoids hold promise in providing fundamental early insights in creating such platforms. However, the generation of TOs that closely resemble the innate testis, to enable a thorough monitoring of the necessary steps for germ cell differentiation and somatic functionalities, remains a challenge.STUDY DESIGN, SIZE, DURATION: We used a Matrigel-based three-layer gradient culture system to generate human TOs and to reveal whether chemotherapy exposure affects TO formation capacity and the functionality of pre- and peri-pubertal testicular somatic cells. Testicular cells of 11 boys (aged 7.7 ± 4.1 (mean ± SD) years) were assessed for TO formation in relation to previous chemotherapy exposure and SOX9 expression in histological sections of paraffin-embedded testicular tissue samples collected on the day of biopsy and compared with testicular tissue samples obtained from 28 consecutive patients (aged 6.9 ± 3.8 (mean ± SD) years). All 39 patients were part of the fertility preservation project NORDFERTIL; an additional 10 samples (from boys aged 5.5 ± 3.5 (mean ± SD) years, without an underlying pathology) in an internal biobank collection were used as controls.PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained 49 testicular tissue samples from boys aged 0.8-13.4 years. Fresh samples (n = 11) were dissociated into single-cell suspensions and applied to a three-layer gradient culture system for organoid formation. Histological sections of another 28 samples obtained as part of the fertility preservation project NORDFERTIL, and 10 samples from a sample collection of a pathology biobank were used to evaluate the effects of prior exposure to alkylating agents on testicular samples. Testicular organoid formation was defined based on morphological features, such as compartmentalized structures showing cord formation, and protein expression of testicular cell-specific markers for germ and somatic cells was evaluated via immunohistochemical staining. Hormone secretion was analysed by specific enzyme-linked immunosorbent assays for testosterone and anti-Müllerian hormone (AMH) production.MAIN RESULTS AND THE ROLE OF CHANCE: Our results revealed that 4 out of 11 prepubertal testicular samples formed TOs that showed compartmentalized cord-like structures surrounded by interstitial-like areas and increasing levels of both testosterone as well as AMH over a 7-day culture period. We observed that SOX9 expression was correlated positively with TO formation. Moreover, exposure to alkylating agents before biopsy was inversely correlated with SOX9 expression (P = 0.006).LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Due to the limited amount of material available, only 11 out of the 39 pre- and peri-pubertal testicular tissue samples could be used for the organoid formation experiments. The testicular tissue samples obtained from a sample collection of the internal biobank of Department of Pathology, Karolinska University Hospital were considered normal and included in the study if no testicular pathology was reported. However, detailed information regarding previous medical treatments and/or testicular volumes of the patients included in this biobank was not available.WIDER IMPLICATIONS OF THE FINDINGS: Our observations suggest that SOX9 expression may serve as a putative indicator of TO formation, indicating a critical role of Sertoli cells in promoting organoid formation, seminiferous tubule integrity, and testicular function in pre- and peri-pubertal testicular tissue.STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115; TJ2020-0023) (J.-B.S.), Finnish Cancer Society (K.J.), Finnish Foundation for Paediatric Research (K.J.), Swedish Research Council (2018-03094; 2021-02107) (J.-B.S.), and Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2020-00335; 2021-00073; 2022-00317) (J.-B.S. and K.J.). Y.C. and Y.Y. received a scholarship from the Chinese Scholarship Council. J.P.A-L. was supported by a Starting Grant in Medicine and Health (2022-01467) from the Swedish Research Council. R.T.M. was supported by a UKRI Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health was supported by an MRC Centre Grant (MR/N022556/1). The authors declare no competing interests.
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  • Hansson, Lars, et al. (author)
  • Living situation, subjective quality of life and social network among individuals with schizophrenia living in community settings.
  • 2002
  • In: Acta Psychiatrica Scandinavica. - : Wiley. - 1600-0447 .- 0001-690X. ; 106:5, s. 343-350
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To investigate the relationships between characteristics of the living situation in the community and subjective quality of life and social network among community-based individuals with schizophrenia. METHOD: A total of 418 individuals with schizophrenia from 10 sites were interviewed with regard to quality of life, psychopathology, social network and needs for care. Characteristics of the living situation investigated were: living alone or not, living with family or not, and having an independent or a sheltered housing situation. RESULTS: An independent housing situation was related to a better quality of life concerning living situation and living with the family to a better quality of life concerning family relations. An independent housing situation was associated with a better social network regarding availability and adequacy of emotional relations. CONCLUSION: People with schizophrenia with an independent housing situation have a better quality of life associated with more favorable perceptions of independence, influence, and privacy. Their social network is better irrespective of whether they live alone or not, or with family or not.
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  • Hansson, L, et al. (author)
  • Predictors of subjective quality of life in schizophrenic patients living in the community. A Nordic multicentre study.
  • 1999
  • In: International Journal of Social Psychiatry. - 0020-7640 .- 1741-2854. ; 45:4, s. 247-58
  • Journal article (peer-reviewed)abstract
    • As part of a Nordic multi-centre study investigating the life and care situation of community samples of schizophrenic patients the aim of the present part of the study was to examine the relationship between global subjective quality of life and objective life conditions, clinical characteristics including psychopathology and number of needs for care, subjective factors such as satisfaction with different life domains, social network, and self-esteem. A sample of 418 persons with schizophrenia from 10 sites was used. The results of a final multiple regression analysis, explaining 52.3% of the variance, showed that five subjective factors were significantly associated with global subjective quality of life, together with one objective indicator, to have a close friend. No clinical characteristics were associated with global subjective quality of life. The largest part of the variance was explained by satisfaction with health, 36.3% of the variance, and self-esteem, 7.3% of the variance. It is concluded that the actual relationship between objective life conditions and subjectively experienced quality of life still remains unclear. Furthermore, it seems obvious that personality related factors such as self-esteem, mastery and sense of autonomy also play a role in the appraisal of subjective quality of life, which implies that factors like these are important to consider in clinical and social interventions for patients with schizophrenia in order to improve quality of life for these persons.
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  • Hansson, L, et al. (author)
  • The relationship of needs and quality of life in persons with schizophrenia living in the community. A Nordic multi-center study
  • 2003
  • In: Nordic Journal of Psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 57:1, s. 5-11
  • Journal article (peer-reviewed)abstract
    • The relationship between needs for care and support and subjective quality of life was investigated in a cross-sectional multi-center study including 418 individuals with schizophrenia from 10 centers in Nordic countries. Needs in 22 domains were investigated by interviews with key workers and their patients using the Camberwell Assessment of Need scale, and quality of life by the Lancashire Quality of Life Profile. The results showed that key workers rated slightly more needs than patients. To have more unmet needs, as rated by both key workers and patients, were correlated to a worse overall subjective quality of life, while met needs showed no such association. A regression analysis, controlling for clinical and social characteristics of the patients, showed more unmet needs to be associated with a worse quality of life, accounting for 6% out of a total of 41% explained variance in subjective quality of life. Regression analyses of the relationship of unmet needs in specific life domains and overall quality of life showed that unmet needs in five domains as perceived by patients accounted for 17% of the explained variance in overall quality of life. More than half of this variance was related to an unmet need in the domain of social relationships. It is concluded that unmet needs are of specific importance in needs assessment and that attention must be paid to separate met needs for care and services from unmet needs, since the latter seem more important to consider in order to improve outcome of interventions with regard to quality of life. Specific attention should in this context also be paid to unmet needs concerning social relationships and problems with accommodation.
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  • Kiemeney, Lambertus A, et al. (author)
  • A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
  • 2010
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
  • Journal article (peer-reviewed)abstract
    • Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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  • Kurek, Magdalena, et al. (author)
  • Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation
  • 2021
  • In: Cells. - : MDPI AG. - 2073-4409. ; 10:2
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Petersson, U., et al. (author)
  • Quality of life and hernia development 5 years after open abdomen treatment with vacuum-assisted wound closure and mesh-mediated fascial traction
  • 2016
  • In: Hernia. - : Springer Science and Business Media LLC. - 1265-4906 .- 1248-9204. ; 20:5, s. 755-764
  • Journal article (peer-reviewed)abstract
    • To report incisional hernia (IH) incidence, abdominal wall (AW) discomfort and quality of life (QoL) 5 years after open abdomen treatment with vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM). Five-year follow-up of patients included in a prospective study 2006-2009. The protocol included physical examination, patient interview, chart review, questionnaires on abdominal wall and stoma complaints and the SF-36 questionnaire. Fifty-five (12 women, 43 men; median age 70 years) of 111 included patients were alive. Follow-up rate was 91 %. Cumulative IH incidence during the whole study was 62 %. One-third of the IHs was repaired. At 5-year follow-up 59 % of IHs were clinically detectable. AW symptoms were equivalent in patients with (15/23) and without (11/21) IH (p = 0.541). SF-36 scores were lower than population mean for component scores and all subscales except bodily pain. Patients with major co-morbidity had lower physical component score [31.6 (95 %, CI 25.6-37.4)] compared to those without [48.9 (95 %, CI 46.2-51.4)]. Major co-morbidity was not associated with IH (p = 0.56), AW symptoms (p = 0.54) or stoma (p = 0.10). Patients with IH or other AW symptoms had similar SF-36 results compared to those without, whereas patients with a stoma had > 5 point lower mean scores for general health, social function and physical component score compared to those without. VAWCM treatment results in high incidence of IH. However, at five years, there was no detectable difference in abdominal wall complaints and QoL in patients with IH compared to those without. Lower QoL appeared mainly to be associated with the presence of major co-morbidity.
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34.
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35.
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36.
  • Sorgaard, KW, et al. (author)
  • Schizophrenia and contact with health and social services: A Nordic multi-centre study
  • 2003
  • In: Nordic Journal of Psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 57:4, s. 253-261
  • Journal article (peer-reviewed)abstract
    • Background: In a Nordic multi-centre study investigating the life and care situation of persons with schizophrenia living in the community, factors explaining use of health and social services were examined. Method: Four hundred and eighteen individuals with schizophrenia from 10 sites were interviewed about their contact with different services (support functions within and outside the mental health services, general practitioners (GPs), physicians in the mental health, psychotherapy, day-care and inpatient treatment), psychopathology, social network and needs for care. Results: Physicians and support contacts within the mental health system were most used and GPs and psychotherapy least. Three groups of variables were stabile predictors of contact: rural-urban differences, diagnoses (hebephrenic schizophrenia associated with less contact with physicians in the mental services and more with GPs) and health needs as experienced by the patients. No differences between the centres with regard to total service use were found, but the patterns of contact reflected urban-rural variance. A low number of health needs predicted contact with physicians within the mental health services, whereas a high number of such needs was related to contact with GPs and support functions within the mental health services. Social relations exhibited the highest number of unmet needs. Conclusions: Contact with physicians working in the mental health services was much more common than contact with GPs. Based on a broad spectre of demographic, clinical and network variables, it was not possible to find models that explained substantial parts of the variance of service use. Patterns of contact were different in rural, town and city-surroundings, and with the exception of psychotherapy, the rural pattern was characterized by use of less specialized services. The importance of health needs and diagnosis as predictors of contact illustrate the profound and lasting effects on health of having a diagnosis of schizophrenia.
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37.
  • Stukenborg, J. -B., et al. (author)
  • Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy
  • 2018
  • In: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 33:9, s. 1677-1683
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION: Does chemotherapy exposure (with or without alkylating agents) or primary diagnosis affect spermatogonial quantity in human prepubertal testicular tissue? SUMMARY ANSWER: Spermatogonial quantity is significantly reduced in testes of prepubertal boys treated with alkylating agent therapies or with hydroxyurea for sickle cell disease. WHAT IS KNOWN ALREADY: Cryopreservation of spermatogonial stem cells, followed by transplantation into the testis after treatment, is a proposed clinical option for fertility restoration in children. The key clinical consideration behind this approach is a sufficient quantity of healthy cryopreserved spermatogonia. However, since most boys with malignancies start therapy with agents that are not potentially sterilizing, they will have already received some chemotherapy before testicular tissue cryopreservation is considered. STUDY DESIGN, SIZE, DURATION: We examined histological sections of prepubertal testicular tissue to elucidate whether chemotherapy exposure or primary diagnosis affects spermatogonial quantity. Quantity of spermatogonia per transverse tubular cross-section (S/T) was assessed in relation to treatment characteristics and normative reference values in histological sections of paraffin embedded testicular tissue samples collected from 32 consecutive boy patients (aged 6.3 +/- 3.8 [mean +/- SD] years) between 2014 and 2017, as part of the NORDFERTIL study, and in 14 control samples (from boys aged 5.6 +/- 5.0 [mean +/- SD] years) from an internal biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: Prepubertal boys in Sweden, Finland and Iceland who were facing treatments associated with a very high risk of infertility, were offered the experimental procedure of testicular cryopreservation. Exclusion criteria were testicular volumes > 10 ml and high bleeding or infection risk. There were 18 patients with a diagnosis of malignancy and 14 patients a nonmalignant diagnosis. While 20 patients had the testicular biopsy performed 1-45 days after chemotherapy, 12 patients had not received any chemotherapy. In addition, 14 testicular tissue samples of patients with no reported testicular pathology, obtained from the internal biobank of the Department of Pathology at Karolinska University Hospital, were included as control samples in addition to reference values obtained from a recently published meta-analysis. The quantity of spermatogonia was assessed by both morphological and immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The main finding was a significant reduction in spermatogonial cell counts in boys treated with alkylating agents or with hydroxyurea for sickle cell disease. The mean S/T values in boys exposed to alkylating agents (0.2 +/- 0.3, n = 6) or in boys with sickle cell disease and exposed to hydroxyurea (0.3 +/- 0.6, n = 6) were significantly lower (P = 0.003 and P = 0.008, respectively) than in a group exposed to non-alkylating agents or in biobank control samples (1.7 +/- 1.0, n = 8 and 4.1 +/- 4.6, n = 14, respectively). The mean S/T values of the testicular tissue samples included in the biobank control group and the patient group exposed to nonalkylating agents were within recently published normative reference values. LIMITATIONS, REASONS FOR CAUTION: Normal testicular tissue samples included in this study were obtained from the internal biobank of Karolinska University Hospital. Samples were considered normal and included in the study if no testicular pathology was reported in the analysed samples. However, detailed information regarding previous medical treatments and testicular volumes of patients included in this biobank were not available. WIDER IMPLICATIONS OF THE FINDINGS: This study summarizes, for the first time, spermatogonial quantity in a prepubertal patient cohort just before and after potentially sterilizing treatments. Boys facing cancer and cytotoxic therapies are regarded as the major group who will benefit from novel fertility preservation techniques. There are no previous reports correlating spermatogonial quantity to cumulative exposure to alkylating agents and anthracyclines (non-alkylating agents) and no information about the timing of cytotoxic exposures among this particular patient cohort. For prepubertal boys in whom fertility preservation is indicated, testicular tissue should be obtained before initiation of chemotherapy with alkylating agents, whilst for those with sickle cell disease and treated with hydroxyurea, this approach to fertility preservation may not be feasible. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from The Swedish Childhood Cancer Foundation (PR2016-0124; TJ2016-0093; PR2015-0073, TJ2015-0046) (J.-B.S. and K.J.), the Jane and Dan Olssons Foundation (2016-33) (J.-B.S.), the Finnish Cancer Society (K.J.), the Foundation for Paediatric Research (J.-B.S.), Kronprinsessan Lovisas Forening For Barnasjukvard/Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation (J.-B.S.), the Vare Foundation for Paediatric Cancer Research (K.J.) and the Swedish Research Council (2012-6352) (O.S.). R.T.M. was supported by a Wellcome Trust Fellowship (09822). J.P.A.-L. and M.K. were supported by the ITN Marie Curie program 'Growsperm' (EU-FP7-PEOPLE-2013-ITN 603568). The authors declare no conflicts of interest.
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38.
  • Sørgaard, KW, et al. (author)
  • Self-esteem in persons with schizophrenia. A Nordic multicentre study
  • 2002
  • In: Journal of Mental Health. - : Informa UK Limited. - 1360-0567 .- 0963-8237. ; 11:4, s. 405-415
  • Journal article (peer-reviewed)abstract
    • Background: Deinstitutionalisation has led to many people with serious mental illness spending most of their time outside psychiatric institutions. Not much is known about their subjective life. The paper presents the results of analysis of self-esteem in a group of non-institutionalised people with schizophrenia. Methods: Interviews were conducted with random samples of people with schizophrenia receiving out-patient services in ten psychiatric centres in the five Nordic countries. The following instruments were used: The Interview Schedule for Social Interaction (ISSI), Camberwell Assessment of Needs, Lancashire Quality of Life Profile and the Rosenberg self-esteem scale, GAF and BPRS. The Rosenberg scale provided the main data for this paper and three different measures of self-esteem were used (positive self-esteem, negative self-esteem and overall self-esteem). Results: A total of 418 people took part in the study. Total participation rate was 55%. Multiple regression analysis showed the three self-esteem measurements to be mainly related to mental health and other subjective variables, and to lesser extent to social network. Demography played a negligible role, only (female) sex being associated with positive and gross self-esteem. Anxiety/depression and affect balance were the strongest predictors of positive, negative and gross self-esteem, and having at least one close friend was associated with positive and gross self-esteem. Conclusion: variations in self-esteem were mainly explained by differences in anxiety/depression and affect balance, and to extent also with satisfaction with the relations to one's family. Having at least one friend was the strongest social network predictor and sex the only significant demographic variable.
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39.
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40.
  • Vanhees, L, et al. (author)
  • Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III).
  • 2012
  • In: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 19:6, s. 1333-1356
  • Journal article (peer-reviewed)abstract
    • The beneficial effect of exercise training and exercise-based cardiac rehabilitation on symptom-free exercise capacity, cardiovascular and skeletal muscle function, quality of life, general healthy lifestyle, and reduction of depressive symptoms and psychosocial stress is nowadays well recognized. However, it remains largely obscure, which characteristics of physical activity (PA) and exercise training - frequency, intensity, time (duration), type (mode), and volume (dose: intensity × duration) of exercise - are the most effective. The present paper, therefore, will deal with these exercise characteristics in the management of individuals with cardiovascular disease, i.e. coronary artery disease and chronic heart failure patients, but also in patients with congenital or valvular heart disease. Based on the current literature, and if sufficient evidence is available, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding frequency, intensity, time and type of PA, and safety aspects during exercise in patients with cardiovascular disease. This paper is the third in a series of three papers, all devoted to the same theme: the importance of the exercise characteristics in the management of cardiovascular health. Part I is directed to the general population and Part II to individuals with cardiovascular risk factors. In general, PA recommendations and exercise training programmes for patients with coronary artery disease or chronic heart failure need to be tailored to the individual's exercise capacity and risk profile, with the aim to reach and maintain the individually highest fitness level possible and to perform endurance exercise training 30-60 min daily (3-5 days per week) in combination with resistance training 2-3 times a week. Because of the frequently reported dose-response relationship between training effect and exercise intensity, one should seek sufficiently high training intensities, although more scientific evidence on effect sizes and safety is warranted. At present, there is insufficient data to give more specific recommendations on type, dosage, and intensity of exercise in some other cardiovascular diseases, such as congenital heart disease, valve disease, cardiomyopathies, channelopathies, and patients with implanted devices.
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41.
  • Vanhees, L, et al. (author)
  • Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors : recommendations from the EACPR. Part II.
  • 2012
  • In: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 19:5, s. 1005-33
  • Journal article (peer-reviewed)abstract
    • In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose–response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.
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