| 51. |
- Berg, Marie, 1955, et al.
(författare)
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Web-Based Intervention for Women With Type 1 Diabetes inPregnancy and Early Motherhood : Critical Analysis of Adherenceto Technological Elements and Study Design
- 2018
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 20:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Numerous Web-based interventions have been implemented to promote health and health-related behaviors inpersons with chronic conditions. Using randomized controlled trials to evaluate such interventions creates a range of challenges, which in turn can influence the study outcome. Applying a critical perspective when evaluating Web-based health interventions is important.Objective: The objective of this study was to critically analyze and discuss the challenges of conducting a Web-based health intervention as a randomized controlled trial.Method: The MODIAB-Web study was critically examined using an exploratory case study methodology and the framework for analysis offered through the Persuasive Systems Design model. Focus was on technology, study design, and Web-based support usage, with special focus on the forum for peer support. Descriptive statistics and qualitative content analysis were used.Results: The persuasive content and technological elements in the design of the randomized controlled trial included all four categories of the Persuasive Systems Design model, but not all design principles were implemented. The study duration was extended to a period of four and a half years. Of 81 active participants in the intervention group, a maximum of 36 women were simultaneously active. User adherence varied greatly with a median of 91 individual log-ins. The forum for peer support was used by 63 participants. Although only about one-third of the participants interacted in the forum, there was a fairly rich exchange of experiences and advice between them. Thus, adherence in terms of social interactions was negatively affected by limited active participation due to prolonged recruitment process and randomization effects. Lessons learned from this critical analysis are that technology and study design matter and might mutually influence each other. In Web-based interventions, the use of design theories enables utilization of the full potential of technology and promotes adherence. The randomization element in a randomized controlled trial design can become a barrier to achieving a critical mass of user interactions in Web-based interventions, especially when social support is included. For extended study periods, the technology used may need to be adapted in line with newly available technical options to avoid the risk of becoming outdated in the user realm, which in turn might jeopardize study validity in terms of randomized controlled trial designs.Conclusions: On the basis of lessons learned in this randomized controlled trial, we give recommendations to consider when designing and evaluating Web-based health interventions.
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| 52. |
- Heshmati, Amy Frances, et al.
(författare)
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Childhood and adulthood socio-economic position and hypertensive disorders in pregnancy: the Uppsala Birth Cohort Multigenerational Study
- 2013
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 67:11, s. 939-946
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Tidskriftsartikel (refereegranskat)abstract
- Background Childhood and adulthood socio-economic position (SEP) is associated with cardiovascular disease in later life, but associations with hypertensive disorders in pregnancy are not well established. Objective The aim of this study was to investigate the association of childhood and adulthood SEP with hypertensive disorders in pregnancy (chronic hypertension, gestational hypertension and pre-eclampsia/eclampsia). Method Study participants were Swedish women (n=9507) from generation 3 of the Uppsala Birth Cohort Multigenerational Study (UBCoS Multigen) who delivered a live singleton offspring between 1982 and 2008. Social and health data were obtained from routine Swedish registers. Associations of own education (adulthood SEP), and parental education and social class (childhood SEP) with hypertensive disorders were studied using logistic regression with adjustments for age, calendar period, parity, smoking and body mass index. Results Low own education was associated with chronic hypertension, but not with gestational hypertension or pre-eclampsia/eclampsia. Increased risk of chronic hypertension was seen in women whose mothers had medium education compared with women whose mothers had high education (OR 2.18, 95% CI 1.03 to 4.62). Women from a manual social class during childhood had twice the risk of chronic hypertension compared with those from non-manual backgrounds (OR 2.19, 95% CI 1.28 to 3.75). Childhood SEP was not associated with gestational hypertension or pre-eclampsia/eclampsia. Conclusions Childhood and adulthood SEP was associated with chronic hypertension in pregnancy. In contrast, no association with childhood or adulthood SEP was seen for gestational hypertension or pre-eclampsia/eclampsia.
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| 53. |
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| 54. |
- Carlhäll, Sara, et al.
(författare)
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Maternal obesity (Class I-III), gestational weight gain and maternal leptin levels during and after pregnancy : a prospective cohort study
- 2016
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Ingår i: BMC Obesity. - : BioMed Central. - 2052-9538. ; 3:28
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMaternal obesity is accompanied by maternal and fetal complications during and after pregnancy. The risks seem to increase with degree of obesity. Leptin has been suggested to play a role in the development of obesity related complications. Whether maternal leptin levels differ between obese and morbidly obese women, during and after pregnancy, have to our knowledge not been previously described. Neither has the association between maternal leptin levels and gestational weight gain in obese women. The aim was to evaluate if maternal plasma leptin levels were associated with different degrees of maternal obesity and gestational weight gain.MethodsProspective cohort study including women categorized as obesity class I-III (n = 343) and divided into three gestational weight gain groups (n = 304). Maternal plasma leptin was measured at gestational week 15, 29 and 10 weeks postpartum. Maternal Body Mass Index (BMI) was calculated from early pregnancy weight. Gestational weight gain was calculated using maternal weight in delivery week minus early pregnancy weight. The mean value and confidence interval of plasma-leptin were analysed with a two-way ANOVA model. Interaction effect between BMI and gestational weight gain group was tested with a two-way ANOVA model.ResultsThe mean maternal leptin concentrations were significantly higher in women with obesity class III compared to women in obesity class I, at all times when plasma leptin were measured. The mean leptin concentrations were also significantly higher in women with obesity class II compared to women in obesity class I, except in gestational week 29. There was no difference in mean levels of plasma leptin between the gestational weight gain groups. No significant interaction between BMI and gestational weight gain group was found.ConclusionsPlasma leptin levels during and after pregnancy were associated with obesity class but not with degree of gestational weight gain. These results are in concordance with epidemiological findings where the risk of obstetric complications increases with increased maternal obesity class. The effect on obstetric outcome by degree of gestational weight gain is less pronounced than the adverse effects associated with maternal obesity.
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| 55. |
- Espes, Daniel, 1985-, et al.
(författare)
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Pregnancy induces pancreatic insulin secretion in women with long-standing type 1 diabetes
- 2022
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Ingår i: BMJ Open Diabetes Research & Care. - : BMJ Publishing Group Ltd. - 2052-4897. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Pregnancy entails both pancreatic adaptations with increasing beta-cell mass and immunological alterations in healthy women. In this study, we have examined the effects of pregnancy on beta-cell function and immunological processes in long-standing type 1 diabetes (L-T1D).Research design and methods: Fasting and stimulated C-peptide were measured after an oral glucose tolerance test in pregnant women with L-T1D (n=17) during the first trimester, third trimester, and 5-8 weeks post partum. Two 92-plex Olink panels were used to measure proteins in plasma. Non-pregnant women with L-T1D (n=30) were included for comparison.Results: Fasting C-peptide was detected to a higher degree in women with L-T1D during gestation and after parturition (first trimester: 64.7%, third trimester: 76.5%, and post partum: 64.7% vs 26.7% in non-pregnant women). Also, total insulin secretion and peak C-peptide increased during pregnancy. The plasma protein levels in pregnant women with L-T1D was dynamic, but few analytes were functionally related. Specifically, peripheral levels of prolactin (PRL), prokineticin (PROK)-1, and glucagon (GCG) were elevated during gestation whereas levels of proteins related to leukocyte migration (CCL11), T cell activation (CD28), and antigen presentation (such as CD83) were reduced.Conclusions: In summary, we have found that some C-peptide secretion, that is, an indirect measurement of endogenous insulin production, is regained in women with L-T1D during pregnancy, which might be attributed to elevated peripheral levels of PRL, PROK-1, or GCG.
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| 56. |
- Magnusson, Louise, 1992-
(författare)
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Peripheral immunity in patients with autoimmune endocrine diseases and the influence of physiological adaptions during pregnancy
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes (T1D), Hashimoto’s thyroiditis (HT), Graves’ disease (GD), and autoimmune Addison’s disease (AD) appear to share immunogenetic mechanisms. This idea is not novel, as “autoimmune tautology” is an established concept. An issue with previous studies is that no or few simultaneous comparisons between these autoimmune endocrine diseases have been made. Due to methodological limitations, immune deviations associated with these diseases have also been examined for a limited number of immune cell lineages and analytes. High-dimensional single-cell mass cytometry was thus employed to phenotypically characterise all peripheral CD45+ cell lineages, whilst immune-related proteins in plasma and cell supernatants were analysed by proximity extension assay. Patients with new-onset T1D, HT, and AD had altered frequencies of distinct clusters within antigen-presenting and cytotoxic cell lineages. Importantly, previously unreported alterations of rare cell subsets from patients with HT and AD were identified. The systemic immunoprofile of patients with autoimmune endocrine diseases was in general similar. However, an increased abundance of CDCP1 and SLAMF1 in plasma from patients with T1D, HT, and GD might reflect a higher degree of inflammation and lymphocyte activation.Pregnancy in healthy women entails two important features: 1) an increase in fractional β-cell area and 2) peripheral immunomodulation. The effects of pregnancy on T1D remain nevertheless equivocal, as there are conflicting results on β-cell function and longitudinal analyses on peripheral immunity are lacking. β-cell function and the plasma proteome in pregnant women with long-standing T1D (L-T1D) were therefore examined during three occasions: 1) first trimester, 2) third trimester, and 3) two months postpartum. An oral glucose tolerance test was performed to measure both fasting and stimulated C-peptide concentrations in plasma. Plasma proteins related to cell regulatory and immunological processes were analysed by proximity extension assay. Glucose-induced insulin secretion was regained in pregnant women with L-T1D, which decreased slowly after parturition. The plasma proteome was dynamic during gestation, although few analytes were functionally linked. A recovered β-cell function might be related to elevated plasma levels of prolactin, prokineticin-1, or glucagon. Moreover, reduced plasma levels of proteins related to leukocyte migration, T cell activation, and antigen-presentation might have further protected an improved β-cell function.
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| 57. |
- Högberg, Thomas, et al.
(författare)
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Gynekologisk onkologi
- 2008. - 2
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Ingår i: Onkologi. - Stockholm : Liber. - 9789147084012 ; , s. 488-533
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 58. |
- Marcisauskas, Simonas, 1988, et al.
(författare)
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Univariate and classification analysis reveals potential diagnostic biomarkers for early stage ovarian cancer Type 1 and Type 2
- 2019
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 196, s. 57-68
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers for early detection of ovarian tumors are urgently needed. Tumors of the ovary grow within cysts and most are benign. Surgical sampling is the only way to ensure accurate diagnosis, but often leads to morbidity and loss of female hormones. The present study explored the deep proteome in well-defined sets of ovarian tumors, FIGO stage I, Type 1 (low-grade serous, mucinous, endometrioid; n = 9), Type 2 (high-grade serous; n = 9), and benign serous (n = 9) using TMT–LC–MS/MS. Data are available via ProteomeXchange with identifier PXD010939. We evaluated new bioinformatics tools in the discovery phase. This innovative selection process involved different normalizations, a combination of univariate statistics, and logistic model tree and naive Bayes tree classifiers. We identified 142 proteins by this combined approach. One biomarker panel and nine individual proteins were verified in cyst fluid and serum: transaldolase-1, fructose-bisphosphate aldolase A (ALDOA), transketolase, ceruloplasmin, mesothelin, clusterin, tenascin-XB, laminin subunit gamma-1, and mucin-16. Six of the proteins were found significant (p <.05) in cyst fluid while ALDOA was the only protein significant in serum. The biomarker panel achieved ROC AUC 0.96 and 0.57 respectively. We conclude that classification algorithms complement traditional statistical methods by selecting combinations that may be missed by standard univariate tests. Significance: In the discovery phase, we performed deep proteome analyses of well-defined histology subgroups of ovarian tumor cyst fluids, highly specified for stage and type (histology and grade). We present an original approach to selecting candidate biomarkers combining several normalization strategies, univariate statistics, and machine learning algorithms. The results from validation of selected proteins strengthen our prior proteomic and genomic data suggesting that cyst fluids are better than sera in early stage ovarian cancer diagnostics.
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| 59. |
- Sorbe, Bengt, et al.
(författare)
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Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up
- 2008
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Ingår i: International Journal of Gynecological Cancer. - : Blackwell Publishing Ltd. - 1048-891X .- 1525-1438. ; 18:4, s. 803-808
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Tidskriftsartikel (refereegranskat)abstract
- There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma. Cisplatin and doxorubicin with or without cyclophosphamide are widely used. Response rates have improved with combination chemotherapy compared with single-agent therapy. A platinum analog seems to be an important part of the chemotherapy regimen. Since few patients are cured from their disease and since the duration of response is short, further improvement of this therapy is warranted. During the past years, the taxanes (paclitaxel) are being added to prior evaluated regimens and not only improved response rates are reported but also increased toxicity is observed. In a prospective, phase II, multicenter study, carboplatin (area under the curve = 5) and paclitaxel (175 mg/m(2)) were evaluated in treatment of primary advanced and recurrent endometrial carcinoma. In total, 66 patients were recruited during the years 2000-2004. Eighteen primary advanced tumors and 48 recurrences were treated. All histologic types and tumor grades were allowed. The median follow-up was 57 months (range 37-69 months). The overall response rate was 67% (95% CI 55-78). The complete response rate was 29% and the partial response rate 38%. Primary advanced and recurrent tumors as well as endometrioid and nonendometrioid tumors showed similar response rates. The median response duration was 14 months. The 1- and 3-year survival rates were 82% and 33%, respectively. The main toxicities were hematologic and neurologic (sensory neuropathy). The response rates were encouraging, superior to prior platinum-containing regimens, but response duration and the long-term survival rate were still short. The neurologic toxicity was frequent and was a substantial problem in this series of patients. Further research is highly needed to improve the treatment of advanced and recurrent endometrial cancer.
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| 60. |
- 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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