| 1. |
- Teede, Helena J, et al.
(författare)
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Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.
- 2023
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Ingår i: Fertility and sterility. - 1556-5653. ; 120:4, s. 767-793
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Tidskriftsartikel (refereegranskat)abstract
- What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference?International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS.The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist.The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and diversity and inclusion were considered throughout.This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC).The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only; ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; iii) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research; iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma; and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management.Overall, recommendations are strengthened and evidence is improved, but remain generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided.The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation programme supports the Guideline with an integrated evaluation program.This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and the Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the sponsoring organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (www.monash.edu/medicine/mchri/pcos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck; consulting fees from Ferring and Titus Health Care; speaker's fees from Ferring; unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs; and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche; consulting fees from Gedeon Richter and Organon; speaker's fees from Gedeon Richter and Exeltis; travel support from Gedeon Richter and Exeltis; unpaid consultancy for Roche Diagnostics; and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck; and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd.; consulting fees from Ferring B.V; speaker's fees from Ferring Arzneimittell GmbH; travel support from Organon; and sits on an advisory board for the Office of Health Economics. RJN has received speaker's fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker's fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.
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| 2. |
- Brundin, Peik M. A., 1975-
(författare)
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Sex differences in immune response and sex hormone receptor expression in healthy individuals and during viral infection
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is sex-bias in morbidity and mortality from infectious diseases. Infections kill more men than women and several studies have pointed out differences in the immune system as a reason. The sex hormones estrogen, progesterone and testosterone all shape the effect of the immune response on multiple levels. Women at fertile age have been suggested to have higher proinflammatory responses from inflammatory stimuli compared to men and post-menopausal women, which has been ascribed to their higher estrogen levels. This could possibly lead to a more active pathogen response but may also result in a detrimental immunopathology to infections or development of autoimmune reaction.The overall aim of this thesis is to study the contribution of sex hormones and sex hormone receptors (SHR) to sex differences in immune response. We focus on peripheral blood mononuclear cells (PBMCs) to study such relationships in healthy individuals, as well as in individuals with asymptomatic Torque Teno Virus infection, and individuals with acute Puumala virus infection.In Paper I, we investigated expression of SHR and immune response genes in PBMC from healthy premenopausal (pre-MP) women during the menstrual cycle. The expression levels were estimated using a qPCR Array (Taqman low-density array, TLDA). SHR expression did not change significantly during the menstrual cycle, but several key immune regulatory genes were significantly more expressed during the ovulatory and mid luteal phase. Further, we separated PBMC into cell subsets (CD4+ T-cells, CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) and analyzed the expression through qPCR of estrogen receptors (ERs), ERα, ERβ1 (wildtype) and the isoform ERβ2. For the first time and unexpectedly, we demonstrate that the isoform ERβ2 was more abundant than wildtype ERβ1. The data from this paper provides new knowledge on the contribution of the menstrual cycle on immune response.In Paper II, we explored the use of Torque Teno Virus as a secondary functional immune marker in men and women. Expression of viral TTV DNA in PBMCs was estimated using a qPCR kit from Argene (R-gene) and analyzed in relation to serum sex hormone levels. The results showed that 50% of the men, 25% the post-MP women, and 18% of the pre-MP women were TTV+. Interestingly, all pre-MP women that were TTV+ had hormonal aberrances and were either anovulatory and/or hypothyroid. TTV+ pre-MP women also had significantly lower progesterone levels than TTV- pre-MP women. This paper indicates that the prevalence of TTV in PBMC differs between men, pre-MP and post-MP women. Furthermore, hormonal aberrances (at least in pre-MP women) will lead to increased prevalence of TTV.In Paper III we investigated the expression of ERα, ERβ1 and ERβ2 in PBMC from patients with Nephropathia epidemica, the viral zoonotic disease caused by Puumala virus, a Hanta virus known to affect more men than women. Expression of ERs in PBMCs and clinical laboratory results during the acute and convalescent phases were analyzed using a principal component analysis (PCA). The results show differences in ER expression and support previous findings that men and women have a different clinical pictureIn conclusion, the results in this thesis reveal distinct patterns of immune response related to sex hormone levels, SHR expression and the phases of the menstrual cycle supporting that there a link between sex hormone levels and immune responses. Further, we show that the ER isoform ERβ2 is more abundant in PBMCs than what was previously described. The data in this thesis adds to the knowledge to the sex differences in immune response and exemplifies the importance of taking these differences into account in the clinic.
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| 3. |
- Björkman, Kristoffer, et al.
(författare)
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Clinical course of patients with single large-scale mtDNA deletions and childhood onset anemia
- 2022
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Ingår i: 14th European Paediatric Neurology Society Congress, Glasgow, UK (ISBN 978-3-00-072065-9).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To add to our knowledge of the clinical spectrum of patients with single large-scale mitochondrial DNA (mtDNA) deletion and childhood onset anemia. Methods: Retrospective collection of clinical data from medical records for patients, both living and deceased, with a single large-scale mtDNA deletion from seven mitochondrial disease centers in five countries. Statistical analysis with descriptive methods and Kaplan-Meier survival analysis. Results: Seventeen patients matching the genetic criterium and with anemia onset before six years of age. Exocrine pancreatic insufficiency was only seen in five patients in this group. Multiple organs were involved in all patients, with the most common non-hematologic ones being skeletal muscle, central nervous system, endocrine, eyes, gastrointestinal system, kidneys, hearing, liver and heart. Psychomotor retardation was seen in ten patients, hearing impairment in nine patients, failure to thrive in eight patients. Eight later developed Kearns-Sayre syndrome. Eleven patients were deceased, with a median age at death of 7.5 years. Conclusions: The classically described phenotype of patients with large-scale mtDNA deletions and early onset anemia is Pearson marrow-pancreas syndrome, characterized by sideroblastic anemia and exocrine pancreas dysfunction. Only a minority of our patients fulfill the original criteria of Pearson syndrome though. Involvement of other organs than the pancreas is more common. The clinical course vary, but multi-system impact is the rule and life-expectancy is low. Early onset anemia in patients with large-scale mtDNA deletions is most frequently not associated with exocrine pancreas dysfunction. Better knowledge of the phenotype is helpful for diagnosis and more accurate prognosis.
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| 4. |
- Hellstrand Tang, Ulla, et al.
(författare)
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Exploring the Role of Complexity in Health Care Technology Bottom-Up Innovations : Multiple-Case Study Using the Nonadoption, Abandonment, Scale-Up, Spread, and Sustainability Complexity Assessment Tool
- 2024
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Ingår i: JMIR Human Factors. - : JMIR Publications. - 2292-9495. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: New digital technology presents new challenges to health care on multiple levels. There are calls for further research that considers the complex factors related to digital innovations in complex health care settings to bridge the gap when moving from linear, logistic research to embracing and testing the concept of complexity. The nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) framework was developed to help study complexity in digital innovations.OBJECTIVE: This study aims to investigate the role of complexity in the development and deployment of innovations by retrospectively assessing challenges to 4 digital health care innovations initiated from the bottom up.METHODS: A multicase retrospective, deductive, and explorative analysis using the NASSS complexity assessment tool LONG was conducted. In total, 4 bottom-up innovations developed in Region Västra Götaland in Sweden were explored and compared to identify unique and shared complexity-related challenges.RESULTS: The analysis resulted in joint insights and individual learning. Overall, the complexity was mostly found outside the actual innovation; more specifically, it related to the organization's readiness to integrate new innovations, how to manage and maintain innovations, and how to finance them. The NASSS framework sheds light on various perspectives that can either facilitate or hinder the adoption, scale-up, and spread of technological innovations. In the domain of condition or diagnosis, a well-informed understanding of the complexity related to the condition or illness (diabetes, cancer, bipolar disorders, and schizophrenia disorders) is of great importance for the innovation. The value proposition needs to be clearly described early to enable an understanding of costs and outcomes. The questions in the NASSS complexity assessment tool LONG were sometimes difficult to comprehend, not only from a language perspective but also due to a lack of understanding of the surrounding organization's system and its setting.CONCLUSIONS: Even when bottom-up innovations arise within the same support organization, the complexity can vary based on the developmental phase and the unique characteristics of each project. Identifying, defining, and understanding complexity may not solve the issues but substantially improves the prospects for successful deployment. Successful innovation within complex organizations necessitates an adaptive leadership and structures to surmount cultural resistance and organizational impediments. A rigid, linear, and stepwise approach risks disregarding interconnected variables and dependencies, leading to suboptimal outcomes. Success lies in embracing the complexity with its uncertainty, nurturing creativity, and adopting a nonlinear methodology that accommodates the iterative nature of innovation processes within complex organizations.
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| 5. |
- Solinas, Giovanni, et al.
(författare)
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An adipoincretin effect links adipostasis with insulin secretion.
- 2024
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Ingår i: Trends in endocrinology and metabolism: TEM. - 1879-3061. ; 35:6, s. 466-477
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Forskningsöversikt (refereegranskat)abstract
- The current paradigm for the insulin system focuses on the phenomenon of glucose-stimulated insulin secretion and insulin action on blood glucose control. This historical glucose-centric perspective may have introduced a conceptual bias in our understanding of insulin regulation. A body of evidence demonstrating that in vivo variations in blood glucose and insulin secretion can be largely dissociated motivated us to reconsider the fundamental design of the insulin system as a control system for metabolic homeostasis. Here, we propose that a minimal glucose-centric model does not accurately describe the physiological behavior of the insulin system and propose a new paradigm focusing on the effects of incretins, arguing that under fasting conditions, insulin is regulated by an adipoincretin effect.
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| 6. |
- Zhang, C., et al.
(författare)
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The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
- 2020
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
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| 7. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 8. |
- Tejedor, Sandra, et al.
(författare)
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The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice : An Ex Vivo and In Vivo Investigation
- 2024
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. Results: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. Conclusion: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.
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| 9. |
- Husdal, Rebecka, et al.
(författare)
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Organisation of primary diabetes care in people with type 2 diabetes in relation to all-cause mortality: A nationwide register-based cohort study
- 2020
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 167
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine if personnel resources and organisational features in Swedish primary health-care centres (PHCCs) are associated to all-cause mortality (ACM) in people with type 2 diabetes mellitus (T2DM). Methods: A total of 187,570 people with T2DM registered in the Swedish National Diabetes Register (NDR) during 2013 were included in this nationwide cohort study. Individual NDR data were linked to data from a questionnaire addressing personnel resources and organisational features for 787 (68%) PHCCs as well as to individual data on socio-economic status and comorbidities. Furthermore, data on ACM were obtained and followed up until 30 January 2018. Hierarchical Cox regression analyses were applied. Results: After a median follow-up of 4.2 years, 27,136 (14.5%) participants had died. An association was found between number of whole-time-equivalent (WTE) general practitioner's (GP's) devoted to diabetes care/500 people with T2DM and lower risk of early death (hazard ratio 0.919 [95% confidence interval 0.895–0.945] per additional WTE GP; p = 0.002). No other personnel resources or organisational features were significantly associated with ACM. Conclusions: This nationwide register-based cohort study suggests that the number of WTE GPs devoted to diabetes care have an impact on the risk of early death in people with T2DM. © 2020 Elsevier B.V.
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| 10. |
- Hjelm, Katarina, 1958-, et al.
(författare)
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Migrant Middle Eastern women with gestational diabetes seven years after delivery - positive long-term development of beliefs about health and illness shown in follow-up interviews
- 2021
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Ingår i: Primary Health Care Research and Development. - : Cambridge University Press. - 1463-4236 .- 1477-1128. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Aim: No previous studies have been found focusing on the long-term development of beliefs about health, illness and healthcare in migrant women with gestational diabetes mellitus (GDM). The aim of this study was to explore this and the influence on health-related behaviour (i.e. self-care and care seeking) in migrant women from the Middle East living in Sweden seven years after delivery.Background: GDM is increasing, particularly in migrant women. The risk of adverse outcomes of GDM for health can be improved by interventions reducing blood glucose and lifestyle modifications which medicalise the woman's pregnancy due to intensive follow-up and demanding self-care. The reactions might have an enduring impact on the women's long-term psychological and physical health and adoption of preventive health behaviours.Method: Qualitative exploratory study. Semi-structured follow-up interviews 7 years after delivery with women previously interviewed in gestational weeks 34-38 and 3 and 14 months after delivery. Data analysed with qualitative content analysis.Findings: Health meant freedom from illness, feeling well and living long to be able to care for the children. The present situation was described either positively, changing to a healthier lifestyle, or negatively, with worries about being affected by type 2 diabetes. Beliefs changed among the majority of women, leading to a healthier lifestyle, and they looked positively back at the time when diagnosed and their reactions to it. With few exceptions, they were confident of being aware of future health risks and felt responsible for their own and their children's health/lifestyle. None except those diagnosed with type 2 diabetes had been in contact with healthcare since the last follow-up a year after delivery. Yet, they still would like and need a healthcare model delivering more information, particularly on developing a healthy lifestyle for children, and with regular check-ups also after the first year after delivery.
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