| 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. |
- Naeser, Ylva, et al.
(författare)
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Survival in patients diagnosed with melanoma in situ compared to the general population. A Swedish population-based matched cohort study
- 2023
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Background: The incidence of melanoma in situ (MIS) is increasing even more rapidly than the incidence of cutaneous malignant melanoma (CMM). No previous studies have in detail investigated the survival in individuals diagnosed with MIS compared to the general population.Methods: This population-based study included individuals with MIS diagnosed in Sweden between 2001 and 2010 and randomly selected MIS-free comparators matched on age, sex and county of residence. Exclusion criterion was a previous CMM. Data on socioeconomic status (SES) including educational level, income and marital status, comorbidity and cause of death were obtained from population-based registers. Overall survival (OS) was estimated by the Kaplan-Meier method. The mortality risk adjusted for SES and comorbidity was assessed by multivariable Cox regression analyses.Findings: The survival analyses included 7963 cases and 39,662 comparators. Median age at MIS diagnosis were 63 (IQR 50-75) and 67 (IQR 57-76) years in women and men respectively. Median follow-up time was 120 months (IQR 102-152 months). In individuals with MIS, the ten-year OS was 77% (95% CI 0.76-0.78) compared to 72% (95% CI 0.72-0.73) in comparators. The MIS patients had a higher SES and lower comorbidity burden than the comparators. In a fully adjusted multivariable analysis, including 7772 cases and 38,103 comparators, the mortality was significantly lower in women with MIS (HR 0.88, 95% CI 0.82-0.94) compared to the background population. The corresponding estimate in men was HR 0.94 (95% CI 0.88-1.0). The risk of melanoma-related deaths during the study period was ten-fold higher in MIS patients.Interpretation: Despite being at increased risk of developing CMM, MIS patients had a better OS compared to their matched comparators from the background population, findings which could not fully be explained by differences in SES and comorbidity. Our results are reassuring and should be communicated to patients who have been diagnosed with MIS.
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| 3. |
- Arabpour, Mohammad, et al.
(författare)
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ADP-ribosylating adjuvant reveals plasticity in cDC1 cells that drive mucosal Th17 cell development and protection against influenza virus infection
- 2022
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 15:4, s. 745-761
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Tidskriftsartikel (refereegranskat)abstract
- Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103(+) cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3-/- mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt(+) T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.
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| 4. |
- Alesi, Simon, et al.
(författare)
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Efficacy and safety of anti-androgens in the management of polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.
- 2023
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Ingår i: EClinicalMedicine. - 2589-5370. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS.We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640.From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n=961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens+lifestyle were superior to metformin+lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]:-1.59 [-3.06,-0.12], p=0.03; I2=74%), SHBG (7.70nmol/l [0.75, 14.66], p=0.03; I2=0%), fasting insulin and fasting insulin: glucose ratio (-2.11 μU/ml [-3.97,-0.26], p=0.03; I2=0% and-1.12 [-1.44,-0.79], p<0.0001, I2=0%, respectively), but were not superior to placebo+lifestyle for hirsutism (-0.93, [-3.37, 1.51], p=0.45; I2=76%) or SHBG (9.72nmol/l [-0.71, 20.14], p=0.07; I2=31%). Daily use was more effective for hirsutism than use every three days (-3.48 [-4.58,-2.39], p<0.0001, I2=1%), and resulted in lower androstenedione levels (-0.30ng/ml [-0.50,-0.10], p=0.004; I2=0%). Combination treatment with anti-androgens+metformin+lifestyle resulted in lower testosterone compared with metformin+lifestyle (-0.29nmol/l [-0.52,-0.06], p=0.01; I2=61%), but there were no differences in hirsutism when anti-androgens+metformin+lifestyle were compared with either anti-androgens+lifestyle or metformin+lifestyle. In limited meta-analyses (n=2 trials), combining anti-androgens with COCP resulted in poorer lipid profiles compared with COCP±placebo, with no differences in other outcomes.Current evidence does not support the use of anti-androgens preferentially to COCPs to treat hyperandrogenism in PCOS. Anti-androgens could be considered to treat hirsutism in PCOS, where COCPs are contraindicated, poorly tolerated, or present a sub-optimal response after a minimum 6-month period, with consideration of clinical context and individual risk factors and characteristics.National Health and Medical Research Council (NHMRC) of Australia Monash University.
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| 5. |
- Barman, Malin, 1983, et al.
(författare)
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Proportions of Polyunsaturated Fatty Acids in Umbilical Cord Blood at Birth Are Related to Atopic Eczema Development in the First Year of Life
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Atopic eczema, the most common atopic disease in infants, may pave the way for sensitization and allergy later in childhood. Fatty acids have immune-regulating properties and may regulate skin permeability. Here we examine whether the proportions of fatty acids among the infant and maternal plasma phospholipids at birth were associated with maternal dietary intake during pregnancy and development of atopic eczema during the first year of age in the Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) birth cohort. Dietary data were collected with a semi-quantitative food frequency questionnaire, fatty acids were measured with GC-MS and atopic eczema was diagnosed by a pediatric allergologist at 12 months of age. We found that higher proportions of n-6 PUFAs (including arachidonic acid) but lower proportions of n-3 PUFAs (including DPA) in the infant's phospholipids at birth were associated with an increased risk of atopic eczema at 12 months of age. The n-6 and n-3 PUFAs were related to maternal intake of meat and fish, respectively. Our results suggest that prenatal exposure to unsaturated fatty acids is associated with eczema development in the infant. Maternal diet during pregnancy may partly explain the fatty acid profiles in utero.
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| 6. |
- Olsson, Jan, et al.
(författare)
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Time trends in herpesvirus seroepidemiology among Swedish adults
- 2024
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Ingår i: BMC Infectious Diseases. - : Springer Nature. - 1471-2334. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human herpesviruses are widespread among the human population. The infections often occurunnoticed, but severe disease as well as long-term sequelae are part of the symptom spectrum. The prevalence variesamong subpopulations and with time. The aim of this study was to describe the seroprevalence of ImmunoglobulinG against Herpes simplex 1, Herpes simplex 2, Epstein-Barr virus and Cytomegalovirus in the adult Swedish populationover a time period of several decades.Methods: Serum samples (n = 892) from biobanks, originating from 30-year-old women, 50-year-old menand 50-year-old women sampled between 1975 and 2018, were analyzed for presence of anti-herpesvirus antibod-ies. Linear regression analysis was used to test for a correlation between birth year and seroprevalence. Multiple linearregression analysis was used to differentiate between other factors such as age and gender.Results: Birth year correlated negatively with the prevalence of immunoglobulin G against Herpes simplex 1and Epstein-Barr virus (p = 0.004 and 0.033), and positively with Immunoglobulin G against Cytomegalovirus(p = 0.039). When participant categories were analyzed separately, birth year correlated negatively with the preva-lence of Immunoglobulin G against Herpes simplex 1 and Herpes simplex 2 (p = 0.032 and 0.028) in 30-year-old women,and with the prevalence of Immunoglobulin G against Cytomegalovirus in 50-year-old men (p = 0.011).Conclusions: The prevalence of Immunoglobulin G against Herpes simplex 1, Herpes simplex 2 and Epstein-Barr virusdecreases in later birth cohorts. This indicates a trend of declining risk of getting infected with these viruses as a childand adolescen (9) (PDF) Time trends in herpesvirus seroepidemiology among Swedish adults.
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| 7. |
- Möllerberg, Marie-Louise, et al.
(författare)
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Evaluation of skin reactions during proton beam radiotherapy : patient-reported versus clinician-reporte
- 2021
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Ingår i: Technical innovations & patient support in radiation oncology. - : Elsevier. - 2405-6324. ; 19, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Skin reaction is a common side-effect of radiotherapy and often only assessed as clinician-reported outcome (CRO). The aim was to examine and compare patient-reported outcome (PRO) of skin reactions with CRO for signs of acute skin reactions for patients with primary brain tumour receiving proton beam radiotherapy (PBT). A further aim was to explore patients' experiences of the skin reactions.Methods: Acute skin reactions were assessed one week after start of treatment, mid-treatment and end of treatment among 253 patients with primary brain tumour who underwent PBT. PRO skin reactions were assessed with the RSAS and CRO according to the RTOG scale. Fleiss' kappa was performed to measure the inter-rater agreement of the assessments of skin reactions.Results: The results showed a discrepancy between PRO and CRO acute skin reactions. Radiation dose was associated with increased skin reactions, but no correlations were seen for age, gender, education, occupation, other treatment or smoking. There was a poor agreement between patients and clinicians (κ = -0.016) one week after the start of PBT, poor (κ = -0.045) to (κ = 0.396) moderate agreement at mid treatment and poor (κ = -0.010) to (κ = 0.296) moderate agreement at end of treatment. Generally, patients' symptom distress toward skin reactions was low at all time points.Conclusion: The poor agreement between PRO and CRO shows that the patient needs to be involved in assessments of skin reactions for a more complete understanding of skin reactions due to PBT. This may also improve patient experience regarding involvement in their own care.
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| 8. |
- af Klinteberg, Maja, 1980-, et al.
(författare)
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Decreasing prevalence of atopic dermatitis in Swedish schoolchildren : three repeated population-based surveys
- 2024
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Ingår i: British Journal of Dermatology. - : Oxford University Press. - 0007-0963 .- 1365-2133. ; 190:2, s. 191-198
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of atopic dermatitis (AD) has increased over several decades and now affects about one-fifth of all children in high-income countries (HICs). While the increase continues in lower-income countries, the prevalence of AD might have reached a plateau in HICs.Objectives: To investigate trends in the prevalence of AD and atopic comorbidity in schoolchildren in Sweden.Methods: The study population consisted of three cohorts of children (median age 8 years) in Norrbotten, Sweden, for 1996 (n = 3430), 2006 (n = 2585) and 2017 (n = 2785). An identical questionnaire that included questions from the International Study of Asthma and Allergies in Childhood (ISAAC) protocol was used in all three cohorts. Trends in AD prevalence were estimated, as well as trends in atopic comorbidity. AD prevalence was estimated both according to the ISAAC definition of AD and by adding the reported diagnosis by a physician (D-AD).Results: The prevalence of AD decreased in the last decade, from 22.8% (1996) and 21.3% (2006) to 16.3% (2017; P < 0.001). The prevalence of D-AD was lower, but the same pattern of decrease was seen, from 9.3% (1996) and 9.4% (2006) to 5.7% (2017; P < 0.001). In all three cohorts, AD was more common among girls than boys (18.9% vs. 13.8% in 2017; P < 0.001). Children from the mountain inlands had a higher prevalence of AD than children from coastal cities (22.0% vs. 15.1% in 2017; P < 0.001). In comparing D-AD, there were no significant differences between the sexes or between inland or coastal living. Concomitant asthma increased over the years from 12.2% (1996) to 15.8% (2006) to 23.0% (2017; P < 0.001). Concomitant allergic rhinitis and allergic sensitization increased from 1996 (15.0% and 27.5%) to 2006 (24.7% and 49.5%) but then levelled off until 2017 (21.0% and 46.7%).Conclusions: The prevalence of AD among schoolchildren in Sweden decreased over the study period, whereas atopic comorbidity among children with AD increased. Although a decrease was seen, AD is still common and the increase in atopic comorbidity among children with AD, especially the increase in asthma, is concerning.
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| 9. |
- Gio-Batta, Monica, et al.
(författare)
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Fecal short chain fatty acids in children living on farms and a link between valeric acid and protection from eczema.
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Children growing up on farms have low rates of allergy, but the mechanism for this protective effect has not been fully elucidated. Short chain fatty acids (SCFAs) produced by the gut microbiota may play a role in protection from allergy. We measured fecal SCFA levels in samples collected from 28 farming and 37 control children over the first 3years of life using gas chromatography. Data on diet and other host factors were recorded and allergy was diagnosed at 8years of age. Among all children, median propionic and butyric acid concentration increased over the first 3years, and longer SCFAs typically appeared by 1year of age. Farm children had higher levels of iso-butyric, iso-valeric and valeric acid at 3years of age than rural controls. In addition, children with elder siblings had higher levels of valeric acid at 3years of age, and dietary factors also affected SCFA pattern. High levels of valeric acid at 3years of age were associated with low rate of eczema at 8years of age. The fecal SCFA pattern in farm children suggests a more rapid maturation of the gut microbiota. Valeric acid or associated microbes may have protective potential against eczema.
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| 10. |
- Gio-Batta, Monica, et al.
(författare)
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Low Concentration of Fecal Valeric Acid at 1 Year of Age Is Linked with Eczema and Food Allergy at 13 Years of Age : Findings from a Swedish Birth Cohort
- 2022
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger. - 1018-2438 .- 1423-0097. ; , s. 398-408
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short-chain fatty acids (SCFAs) are abundant bacterial metabolites in the gut, with immunomodulatory properties. Hence, they may influence allergy development. Previous studies have linked fecal SCFA pattern during infancy with allergy. However, the association of SCFAs to allergic outcomes in adolescence is not well established. Here, we examined how the fecal SCFA pattern at 1 year of age related to allergy at 13 years of age.Methods: Levels of 8 SCFAs in fecal samples collected at 1 year of age from 110 children were quantified using gas chromatography. The same individuals were evaluated at 13 years of age for allergic symptoms, allergy diagnosis and allergy medication by questionnaire, and for sensitization using skin prick test against egg, milk, fish, wheat and soy, cat, dog, horse, birch, and timothy grass.Results: The concentration of fecal valeric acid at 1 year of age was inversely associated with eczema at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.049) and showed a trend for inverse association with food allergy at 13 years of age (OR 0.6, 95% CI: 0.4-1.0, p = 0.057). In a sub-group analysis of children with eczema at 1 year of age, a higher concentration of fecal valeric acid was linked with reduced risk of their eczema remaining at 13 years of age (OR 0.2, 95% CI: 0.0-1.5), although this latter analysis did not reach statistical significance (p = 0.12).Conclusions: Our findings lend further support to the notion of early childhood as a critical period when allergy may be programmed via the gut microbiota. Higher levels of fecal valeric acid may be characteristic of a protective gut microbiota and/or actively contribute to protection from eczema and food allergy.
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