| 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. |
- 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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| 3. |
- Papachristou, Panagiotis, et al.
(författare)
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Evaluation of an artificial intelligence-based decision support for the detection of cutaneous melanoma in primary care: a prospective real-life clinical trial
- 2024
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Ingår i: BRITISH JOURNAL OF DERMATOLOGY. - : OXFORD UNIV PRESS. - 0007-0963 .- 1365-2133.
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Tidskriftsartikel (refereegranskat)abstract
- Background Use of artificial intelligence (AI), or machine learning, to assess dermoscopic images of skin lesions to detect melanoma has, in several retrospective studies, shown high levels of diagnostic accuracy on par with - or even outperforming - experienced dermatologists. However, the enthusiasm around these algorithms has not yet been matched by prospective clinical trials performed in authentic clinical settings. In several European countries, including Sweden, the initial clinical assessment of suspected skin cancer is principally conducted in the primary healthcare setting by primary care physicians, with or without access to teledermoscopic support from dermatology clinics.Objectives To determine the diagnostic performance of an AI-based clinical decision support tool for cutaneous melanoma detection, operated by a smartphone application (app), when used prospectively by primary care physicians to assess skin lesions of concern due to some degree of melanoma suspicion.Methods This prospective multicentre clinical trial was conducted at 36 primary care centres in Sweden. Physicians used the smartphone app on skin lesions of concern by photographing them dermoscopically, which resulted in a dichotomous decision support text regarding evidence for melanoma. Regardless of the app outcome, all lesions underwent standard diagnostic procedures (surgical excision or referral to a dermatologist). After investigations were complete, lesion diagnoses were collected from the patients' medical records and compared with the app's outcome and other lesion data.Results In total, 253 lesions of concern in 228 patients were included, of which 21 proved to be melanomas, with 11 thin invasive melanomas and 10 melanomas in situ. The app's accuracy in identifying melanomas was reflected in an area under the receiver operating characteristic (AUROC) curve of 0.960 [95% confidence interval (CI) 0.928-0.980], corresponding to a maximum sensitivity and specificity of 95.2% and 84.5%, respectively. For invasive melanomas alone, the AUROC was 0.988 (95% CI 0.965-0.997), corresponding to a maximum sensitivity and specificity of 100% and 92.6%, respectively.Conclusions The clinical decision support tool evaluated in this investigation showed high diagnostic accuracy when used prospectively in primary care patients, which could add significant clinical value for primary care physicians assessing skin lesions for melanoma. We investigated the diagnostic performance of an AI-based decision support in the form of a mobile app to detect melanoma when used by primary care physicians. The app proved to have high levels of diagnostic accuracy in distinguishing melanomas from other skin lesions. We conclude that it appears to be a potentially valuable diagnostic aid for the primary care physician in the assessment of skin lesions of concern.
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| 4. |
- 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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| 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. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- Löfvendahl, Sofia, et al.
(författare)
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Prevalence and incidence of generalized pustular psoriasis in Sweden : a population-based register study
- 2022
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Ingår i: British Journal of Dermatology. - : John Wiley & Sons. - 0007-0963 .- 1365-2133. ; 186:6, s. 970-976
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Generalized pustular psoriasis (GPP) is a severe form of pustular psoriasis with generalized eruption of sterile pustules, often along with systemic symptoms. There is a scarcity of population-based estimates of GPP prevalence and incidence.OBJECTIVES: To estimate (i) the prevalence and incidence of GPP in the Swedish general population and (ii) the prevalence of psoriasis vulgaris within the GPP population.METHODS: We identified cases (2004-2015) with one ICD-10 diagnostic code (base case) for GPP within the Swedish National Patient Register, which covers inpatient and outpatient secondary care. Cases were linked to the Swedish Total Population Register, and point prevalence was estimated as on 31 December 2015. In two alternative analyses we changed case definitions to: (i) requiring two visits (strict case 1) and (ii) requiring two visits of which one was within dermatology/internal medicine (strict case 2).RESULTS: The base case point prevalence of GPP was estimated at 9.1 per 100 000 (women, 11.2; men, 7.0) and the annual prevalence in 2015 was estimated at 1.53 per 100 000. Among the GPP population, 43% also had a psoriasis vulgaris code. The incidence of GPP in 2015 was estimated at 0.82 per 100 000 (women, 0.93; men, 0.74). The criteria used had an impact on prevalence and incidence estimates: prevalence strict case 1 gave 3.8 per 100 000 and incidence strict case 1 gave 0.42 per 100 000.CONCLUSIONS: Results indicate that the estimated GPP population in Sweden is within the range of previous published estimates. However, estimates were sensitive to the GPP case criteria used. The findings enhance demands for studies using validated diagnostic algorithms.
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