| 31. |
- 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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| 32. |
- Gyllensten, Ulf B., et al.
(författare)
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Preoperative Fasting and General Anaesthesia Alter the Plasma Proteome
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Blood plasma collected at time of surgery is an excellent source of patient material for investigations into disease aetiology and for the discovery of novel biomarkers. Previous studies on limited sets of proteins and patients have indicated that pre-operative fasting and anaesthesia can affect protein levels, but this has not been investigated on a larger scale. These effects could produce erroneous results in case-control studies if samples are not carefully matched. Methods: The proximity extension assay (PEA) was used to characterize 983 unique proteins in a total of 327 patients diagnosed with ovarian cancer and 50 age-matched healthy women. The samples were collected either at time of initial diagnosis or before surgery under general anaesthesia. Results: 421 of the investigated proteins (42.8%) showed statistically significant differences in plasma abundance levels comparing samples collected at time of diagnosis or just before surgery under anaesthesia. Conclusions: The abundance levels of the plasma proteome in samples collected before incision, i.e., after short-time fasting and under general anaesthesia differs greatly from levels in samples from awake patients. This emphasizes the need for careful matching of the pre-analytical conditions of samples collected from controls to cases at time of surgery in the discovery as well as clinical use of protein biomarkers.
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| 33. |
- Linge, Helena, et al.
(författare)
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The Antibacterial Chemokine MIG/CXCL9 Is Constitutively Expressed in Epithelial Cells of the Male Urogenital Tract and Is Present in Seminal Plasma.
- 2008
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Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 28:3, s. 190-196
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT The integrity of the urogenital tract against potentially invasive pathogens is important for the health of the individual, fertilization, and continuance of species. Antibiotic peptides with broad antimicrobial activity, among them chemokines, are part of the innate immune system. We investigated the presence of the antibacterial interferon (IFN)-dependent CXC chemokines, MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11, in the human male reproductive system. MIG/CXCL9 was detected at 25.0 nM (range 8.1-40.6 nM; n = 14), whereas IP-10/CXCL10 and I-TAC/CXCL11 were detected at lower levels (mean 1.8 nM, range 0.3-5.8 nM and mean 0.6, 0.2-1.6 nM, respectively) in seminal plasma of fertile donors. The levels of MIG/CXCL9 are more than 300-fold higher than those previously reported in blood plasma. In vasectomized donors, significantly lower levels of MIG/CXCL9 (mean 14.7 nM, range 6.6-21.8) were found, suggesting that the testis and epididymis, in addition to the prostate, significantly contribute to the MIG/CXCL9 content of seminal plasma. Strong expression of MIG/CXCL9 was found in the epithelium of testis, epididymis, and prostate, as detected by immunohistochemistry. MIG/CXCL9 at concentrations in the order of those found in seminal plasma possessed antibacterial activity against the urogenital pathogen Neisseria gonorrhoeae. The relatively high levels of MIG/CXCL9 in seminal plasma point to roles for this chemokine in both host defense of the male urogenital tract and during fertilization.
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| 34. |
- Meijnikman, A. S., et al.
(författare)
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A systems biology approach to study non-alcoholic fatty liver (NAFL) in women with obesity
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:8
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) is now the most frequent global chronic liver disease. Individuals with NAFLD exhibited an increased risk of all-cause mortality driven by extrahepatic cancers and liver and cardiovascular disease. Once the disease is established, women have a higher risk of disease progression and worse outcome. It is therefore critical to deepen the current knowledge on the pathophysiology of NAFLD in women. Here, we used a systems biology approach to investigate the contribution of different organs to this disease. We analyzed transcriptomics profiles of liver and adipose tissues, fecal metagenomes, and plasma metabolomes of 55 women with and without NAFLD. We observed differences in metabolites, expression of human genes, and gut microbial features between the groups and revealed that there is substantial crosstalk between these different omics sets. Multi-omics analysis of individuals with NAFLD may provide novel strategies to study the pathophysiology of NAFLD in humans.
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| 35. |
- Barman, Malin, 1983, et al.
(författare)
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Exposure to a farm environment during pregnancy increases the proportion of arachidonic acid in the cord sera of offspring
- 2019
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Growing up in a farm environment is protective against allergy development. Various explanations have been put forward to explain this association. Fatty acids are regulators of immune function and the composition of fatty acids in the circulation system may affect immune development. Here, we investigate whether the fatty acid composition of cord serum differs for infants born to Farm (n = 26) or non-Farm mothers (n =29) in the FARMFLORA birth-cohort. For comparison, the levels of fatty acids in the maternal diet, serum and breast milk around 1 month post-partum were recorded. The fatty acids in the cord sera from infants born to Farm mothers had higher proportions of arachidonic acid (20:4 n-6) and adrenic acid (22:4 n-6) than those from infants born to non-Farm mothers. No differences were found for either arachidonic acid or adrenic acid in the diet, samples of the serum, or breast milk from Farm and non-Farm mothers obtained around 1 month post-partum. The arachidonic and adrenic acid levels in the cord blood were unrelated to allergy outcome for the infants. The results suggest that a farm environment may be associated with the fatty acid composition to which the fetus is exposed during pregnancy. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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| 36. |
- Bornehag, Carl-Gustaf, 1957-, et al.
(författare)
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The SELMA study : a birth cohort study in Sweden following more than 2000 mother-child pairs
- 2012
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Ingår i: Paediatric and Perinatal Epidemiology. - Hoboken, USA : Wiley-Blackwell. - 0269-5022 .- 1365-3016. ; 26:5, s. 456-467
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Tidskriftsartikel (refereegranskat)abstract
- Background: This paper describes the background, aim and study design for the Swedish SELMA study that aimed to investigate the importance of early life exposure during pregnancy and infancy to environmental factors with a major focus on endocrine disrupting chemicals for multiple chronic diseases/disorders in offspring.Methods: The cohort was established by recruiting women in the 10th week of pregnancy. Blood and urine from the pregnant women and the child and air and dust from home environment from pregnancy and infancy period have been collected. Questionnaires were used to collect information on life styles, socio-economic status, living conditions, diet and medical history.Results: Of the 8394 reported pregnant women, 6658 were invited to participate in the study. Among the invited women, 2582 (39%) agreed to participate. Of the 4076 (61%) non-participants, 2091 women were invited to a non-respondent questionnaire in order to examine possible selection bias. We found a self-selection bias in the established cohort when compared with the non-participant group, e.g. participating families did smoke less (14% vs. 19%), had more frequent asthma and allergy symptoms in the family (58% vs. 38%), as well as higher education among the mothers (51% vs. 36%) and more often lived in single-family houses (67% vs. 60%).Conclusions: These findings indicate that the participating families do not fully represent the study population and thus, the exposure in this population. However, there is no obvious reason that this selection bias will have an impact on identification of environmental risk factors.
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| 37. |
- Collins, Elin, et al.
(författare)
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Physicians' assessment of complications after gynecological surgery in Sweden : The GYNCOM survey
- 2023
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 102:11, s. 1479-1487
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Complications after gynecological surgery in Sweden are registered in the well-established Swedish National Quality Register of Gynecological Surgery, GynOp. The aim of this study was to analyze interrater reliability in assessing complications according to the methods in GynOp, and to explore physicians' perceptions of registering complications.Material and methods: A digital survey was sent to gynecologists and residents in gynecology in Sweden. Participating clinics were recruited through the Swedish network for national clinical studies in Obstetrics and Gynecology, SNAKS. Twenty fictional cases, intended to represent normal postoperative course, failure to cure, and varying degrees of complications, were developed by the research group. The clinical scenarios included abdominal and laparoscopic surgery of the uterus and adnexa, vaginal hysterectomies, as well as hysteroscopy. The respondents graded each case on the presence of a complication (yes/no). Type of complication, severity, and what action the complication required according to Clavien-Dindo was registered if a complication was acknowledged, according to the method in GynOp. Interrater reliability and the opinions of the respondents were presented descriptively. More than 80% of respondents making the same assessment was considered as agreement.Results: The response rate was 41%, with 104 responding physicians from 16 gynecological clinics. Type and severity of complication was considered relevant to register by 88% and 89% of respondents, respectively. Agreement on whether the case described a complication was >80% in 85% (17/20) of cases and agreement using the Clavien-Dindo classification was >90% in 80% (16/20) of cases. There was high agreement in assessments of classically severe complications, such as pulmonary embolism and ureteral damage, in both presence of complication and severity, as well as Clavien-Dindo (>90% for all methods). Cases with agreement <80% on whether the case described a complication were bordering between normal postoperative course and minor complication.Conclusions: This study provides validation for the methods used to register complications after gynecological surgery according to the GynOp register, including the use of Clavien-Dindo in gynecology. However, the results indicate a need to define what should be considered symptoms inherent to each type of surgery.
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| 38. |
- Fritz, Tomas, et al.
(författare)
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Outcome of extremely preterm infants after iatrogenic or spontaneous birth
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:11, s. 1388-1395
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The risks of preterm birth are known. We investigated the perinatal and infant mortality and morbidity after iatrogenic or spontaneous onset of extremely preterm birth. Material and methods: The present study used data from the population-based EXPRESS study comprising all infants delivered before 27+0 gestational weeks in Sweden between 2004 and 2007. All fetuses alive at admission and with known mode of onset of delivery were included (682 live-born infants; 65 intrapartum deaths). Four multivariate regression models were applied with adjustments for gestational age, fetal gender, multiple pregnancy, and birthweight. Results: After adjustment for gestational age, no significant differences were found between iatrogenic and spontaneous onsets of birth regarding intrapartum death, early neonatal death (0-6 d), or death within 364 days. In the group with iatrogenic onset of delivery, there was an increased risk for severe morbidity (odds ratio [OR] 1.86, 95% confidence interval [95% CI] 1.15-3.02), severe bronchopulmonary dysplasia (OR 1.90, 95% CI 1.10-3.26), and retinopathy of prematurity (OR 1.99, 95% CI 1.21-3.27) after adjustment for gestational age, fetal gender, and multiple pregnancy. After additional adjustment for weight z-scores at 36 gestational weeks, the associations were not significant. Within the group with spontaneous onset of delivery, fetuses with preterm prelabor rupture of membranes had increased mortality risk. Conclusion: No evidence was found for mode of onset of delivery (iatrogenic vs spontaneous) having an impact on neonatal or infant mortality or morbidity in extremely preterm infants. Instead, gestational age and growth deviation at birth seem to be associated with the outcome.
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| 39. |
- Herbst, Andreas, et al.
(författare)
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Infections and antibiotic prophylaxis in reconstructive vascular surgery
- 1989
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Ingår i: European Journal of Vascular Surgery. - 0950-821X. ; 3:4, s. 303-307
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Tidskriftsartikel (refereegranskat)abstract
- In 98 patients undergoing elective vascular surgery, specimens for bacterial cultures were obtained from urine, ischaemic ulcers, incisional wounds and the implanted grafts. Wound and graft infections were registered and compared with the results of these cultures and suspected risk factors in an attempt to find the source of infections. Antibiotic prophylaxis with cefuroxime was given for 24 h beginning at the start of surgery. Patients with ischaemic ulcers also received "spread prophylaxis", directed against isolated bacteria, for ten days. Three cases of graft infection and twelve cases of wound infection occurred. Positive postoperative cultures from wounds did not correlate with pre- or peroperative cultures. Peroperative cultures revealed small numbers of staphylococcus epidermidis in eleven patients, and none of them developed graft infection. Ischaemic ulcers, diabetes or re-do procedures were not accompanied by a significantly increased frequency of wound or graft infection, although each of three patients with graft infection had one of these risk factors. Bacteria, sensitive to cefuroxime, were found in one graft infection, six wound infections, and in two patients with urosepsis, whereas cefuroxime resistant organisms were isolated from one graft infection and three infected wounds. One of the three graft infections was probably caused by bacteria originating from the patient's ischaemic ulcer. In the other two patients the source of bacteria could not be determined. Cefuroxime seems to be an adequate alternative for prophylaxis of vascular graft infection, but in some patients with bacteriuria or indwelling catheters, a one day regimen may be too short.
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| 40. |
- Karlsson, C, et al.
(författare)
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Endothelium-derived prostanoids reduce 5-hydroxytryptamine-induced contraction in the human uterine artery
- 1998
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Ingår i: Human Reproduction. - 0268-1161. ; 13:7, s. 1947-1951
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of endothelium-linked mechanisms to the contraction induced by 5-hydroxytryptamine (5-HT) was investigated in the isolated human uterine artery. 5-HT contracted the uterine artery concentration-dependently. Removal of the endothelium or treatment with the cyclooxygenase inhibitor indomethacin potentiated the contractile response to 5-HT. The nitric oxide synthase inhibitor L-N(G)-monomethyl-arginine (L-NMMA) did not influence the contraction induced by 5-HT. Indomethacin did not affect the response to 5-HT in endothelium-denuded vessels. The 5-HT1 receptor agonist 5-carboxyamidotryptamine (5-CT) did not relax precontracted arteries. Removal of the endothelium did not change the response to 5-HT in the presence of the 5-HT(1B/D) receptor antagonist GR127935 and the 5-HT1A and 5-HT1B receptor antagonist -pindolol. The 5-HT1B receptor antagonist SB224289 did not affect the contraction induced by 5-HT. The results indicate that the 5-HT-induced contraction in the human uterine artery is accompanied by the release of an endothelium-derived relaxing factor (EDRF). This EDRF seems to be a prostanoid, probably prostacyclin (PGI2). The endothelium-linked mechanism seems to be mediated via a 5-HT1 receptor, but it is not possible to further classify the receptor subtype by the information obtained in this study.
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