| 161. |
- Molin, Johanna, 1970-
(författare)
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Metformin treatment during pregnancy : metabolic and immunological aspects
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Randomized controlled trials have shown that metformin treatment during pregnancy slows down gestational weight gain (GWG) and reduces the risk of preterm birth in women with polycystic ovary syndrome (PCOS), but these trials have not investigated why metformin treatment produces these effects. Studies of metformin's mechanisms of action have mostly been in-vitro studies of cell lines or animal models, or clinical studies of non-pregnant human populations, and it is unknown whether the results of these studies are applicable to human pregnancy. Neonatal outcomes following metformin treatment have been extensively evaluated against insulin treatment for gestational diabetes mellitus (GDM). However, previous assessments have generally combined results from participants treated with metformin alone and results from those who also required supplemental insulin, which makes it difficult to assess effects of metformin per se, and evaluations against diet and lifestyle treatment are lacking.Aim: The objectives of this thesis were to explore the potential mechanisms by which metformin treatment during pregnancy slows down GWG, affects fetal growth, and reduces the risk of preterm birth in women with PCOS, and to assess the risk of neonatal hypoglycemia following metformin-treated, insulin-treated, and diet-and-lifestyle-treated GDM.Method: In Studies I-III, we investigated appetite-regulating hormones and immunological factors in serum and placental tissue obtained from women with PCOS treated with either metformin or placebo. In addition, a group of healthy women with normal pregnancies were included as a reference group. In Study IV, we evaluated associations between metformin treatment and neonatal hypoglycemia, and other neonatal outcomes associated with fetal hyperinsulinemia. We used a register-based approach, and a population-based cohort that consisted of more than 16 000 women with GDM, and their singleton offspring. Metformin as a single adjunctive treatment was assessed separately from metformin combined with insulin treatment.Results: Women with excessive GWG were more leptin resistant throughout pregnancy, and displayed a lower physiological serum allopregnanolone increase in late pregnancy than women who maintained a healthy GWG (Paper I). Metformin treatment improved leptin sensitivity and counteracted excessive GWG in women with PCOS (Paper I). This treatment effect was uncorrelated with placental leptin and leptin-receptor mRNA expression in women with PCOS (Paper II). Placental leptin mRNA expression correlated positively with the birthweight/placental weight ratio in placebo-treated women with PCOS (Paper II). PCOS status was associated with enhanced decidual immune-cell mobilization, particularly greater abundance of CD4+ T cells, and with altered placental IL-18 and IL-5 cytokine mRNA expression (Paper III). Metformin treatment altered the immunological landscape at the maternal-fetal interface in women with PCOS. This was shown by greater abundance of decidual CD56+ cells, downregulation of placental IL-4 and IL-18 mRNA expression, fewer placental pro-inflammatory intra-class cytokine mRNA correlations, and different cytokine mRNA expression profiles compared with placebo (Paper III). Offspring exposed in utero to only metformin as a pharmacological treatment for GDM appeared to be at similar risk of neonatal hypoglycemia to infants exposed to diet and lifestyle treatment alone, and at lower risk compared to offspring exposed to insulin, regardless of whether the insulin was administered as monotherapy or in combination with metformin (Paper IV).Conclusions and implications: Metformin treatment effectively reduces the risk of excessive GWG and appears to counteract physiological leptin resistance during pregnancy in women with PCOS. However, a positive correlation between placental leptin mRNA expression and the placental-efficiency measure ‘birthweight/placental weight ratio’, was erased by metformin treatment. The clinical implication of this finding is unclear, and future research should aim for deeper insight into this mechanism for clarification. Metformin treatment induced complex immunomodulatory effects at the maternal-fetal interface in women with PCOS, but further research is required to determine if these findings can explain why metformin reduces the risk of preterm birth in PCOS. The similar risk of neonatal hypoglycemia to diet and lifestyle treatment is reassuring for all metformin-treated women with GDM that achieve glycemic targets without requiring supplemental insulin. In summary, this thesis contributes to increasing knowledge of how metformin treatment during pregnancy affects metabolic adaptations of importance for maternal weight gain and fetal growth in women with PCOS. Further, it provides some insights into how PCOS status and metformin treatment affect the immunological landscape at the maternal fetal interface; expands previous knowledge of how metformin treatment for GDM associates with neonatal hypoglycemia; and demonstrates the importance of differentiating between metformin with and without supplemental insulin when assessing treatment-associated risk of adverse outcomes.
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| 162. |
- Myrberg, Tomi, et al.
(författare)
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Restrictive spirometry versus restrictive lung function using the GLI reference values
- 2022
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 42:3, s. 181-189
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Tidskriftsartikel (refereegranskat)abstract
- Background: Restrictive lung function may indicate various underlying diseases. The aim of this study was to evaluate the accuracy of different restrictive spirometry patterns (RSPs) to identify restrictive lung function (total lung capacity [TLC] < lower limit of normal [LLN]) according to reference values by the Global Lung Function Initiative (GLI) in a wide age-ranged, general population sample. Methods: A general population sample (n = 607, age 23–72 years, smokers 18.8%) with proper dynamic spirometry and TLC measurements, was included. Accuracy of two main categories of RSP to identify TLC < LLN were evaluated: traditional RSPs (definition 1: FVC < 80% of predicted and FEV1/FVC ≥ 0.7 and definition 2: FVC < LLN and FEV1/FVC ≥ LLN) and RSPs defined by Youden's method (definition 3: FVC < 85.5% of predicted and FEV1/FVC ≥ LLN and definition 4: FVC Z-score < −1.0 and FEV1/FVC ≥ LLN). Results: The prevalence of restrictive lung function (TLC < LLN) was 5.3%. The most accurate cut-offs for FVC to identify TLC < LLN were 85.5% for FVC% of predicted, and −1.0 for FVC Z-score. The traditional RSP definitions 1 and 2 had higher specificity (95.0% and 96.9%) but substantially lower sensitivity compared to RSP definitions 3 and 4. Conclusion: Based on the GLI reference values, the RSP definition FVC < LLN and FEV1/FVC ≥ LLN yielded the highest specificity and may appropriately be used to rule out restrictive lung function. The RSP definition with the most favourable trade-off between sensitivity and specificity, FVC < 85.5% of predicted and FEV1/FVC ≥ LLN, may serve as an alternative with higher sensitivity for screening. © 2022 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.
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| 163. |
- Nilsson, Helena, et al.
(författare)
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An empirical application of herding behavior and compliance in the COVID-19 crisis
- 2024
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Ingår i: Kyklos (Basel). - : John Wiley & Sons. - 0023-5962 .- 1467-6435. ; 77:2, s. 428-457
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence that individuals engage in herding behavior in diverse settings, ranging from fashion choices to financial markets. By examining the exogenous shock caused by the outbreak of COVID-19 and unique data measuring the footfalls in downtown Jonkoping, Sweden, we empirically assess how individuals respond to the restrictions imposed by the government and to the behavior of others, that is, herding. To this end, a regression discontinuity analysis with time as the running variable is applied. We find a negative effect of the restriction on footfalls, indicating that individuals follow the imposed governmental restrictions. However, we also find indications that individuals imitate the actions of others and engage in herd behavior even when the cost of doing so is very high; that is, it could result in severe illness or even death. With the use the unique setting of Sweden, where there have been no enforced lockdowns, we contribute with knowledge related to how effective voluntary restrictions are and the influence of others on one's decision making. Although the nature of the studied sample limits the external generalizability of the results, it may offer guidance for future interventions in clearly delineated settings.
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| 164. |
- Nilsson, Helena, et al.
(författare)
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Retail employee turnover and turnover destinations–the role of human capital
- 2024
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Ingår i: International Review of Retail Distribution & Consumer Research. - : Taylor & Francis. - 0959-3969 .- 1466-4402.
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Tidskriftsartikel (refereegranskat)abstract
- This paper assesses the role of human capital in labor turnover and turnover destinations of full-time retail employees. We use register data that encompasses the full population of Swedes above the age of 16 and follow the career paths of those that have, at one point in time between 2002 and 2018, worked full-time in retail. We use logit- and multinomial logit-estimations to assess the role of firm-specific (proxied by establishment tenure) and worker-specific human capital (proxied by industry tenure, formal education, retail education, and occupational complexity) in the propensity to quit a retail establishment and the retail sector. Results indicate that establishment tenure, industry tenure, retail education, and occupational complexity decrease the probability of quitting, while formal education has the opposite effect. Moreover, we find that industry tenure, retail education, and occupational complexity increase the probability of staying in the retail sector.
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| 165. |
- Nilsson, Ulf, et al.
(författare)
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Cardiac biomarkers of prognostic importance in chronic obstructive pulmonary disease
- 2020
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIschemic heart disease is common in COPD and associated with worse prognosis. This study aimed to investigate the presence and prognostic impact of biomarkers of myocardial injury and ischemia among individuals with COPD and normal lung function, respectively.MethodsIn 2002–04, all individuals with airway obstruction (FEV1/VC < 0.70, n = 993) were identified from population-based cohorts, together with age and sex-matched non-obstructive referents. At re-examination in 2005, spirometry, Minnesota-coded ECG and analyses of high-sensitivity cardiac troponin I (hs-cTnI) were performed in individuals with COPD (n = 601) and those with normal lung function (n = 755). Deaths were recorded until December 31st, 2010.ResultsHs-cTnI concentrations were above the risk stratification threshold of ≥5 ng/L in 31.1 and 24.9% of those with COPD and normal lung function, respectively. Ischemic ECG abnormalities were present in 14.8 and 13.4%, while 7.7 and 6.6% had both elevated hs-cTnI concentrations and ischemic ECG abnormalities. The 5-year cumulative mortality was higher in those with COPD than those with normal lung function (13.6% vs. 7.7%, p < 0.001). Among individuals with COPD, elevated hs-cTnI both independently and in combination with ischemic ECG abnormalities were associated with an increased risk for death (adjusted hazard ratio [HR]; 95% confidence interval [CI] 2.72; 1.46–5.07 and 4.54; 2.25–9.13, respectively). Similar associations were observed also among individuals with COPD without reported ischemic heart disease.ConclusionsIn this study, elevated hs-cTnI concentrations in combination with myocardial ischemia on the electrocardiogram were associated with a more than four-fold increased risk for death in a population-based COPD-cohort, independent of disease severity.
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| 166. |
- Nilsson, Ulf, et al.
(författare)
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Elevated cardiac troponin predicts 11-year mortality in COPD
- 2020
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:Suppl 64
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Ischemic heart disease (IHD) is a common multimorbidity in individuals with COPD. High sensitive cardiac troponin I (hs-cTnI) has been shown to predict short-term mortality, but longer follow-ups has rarely been performed in population-cohorts.Aim: To evaluate the predictive value of elevated hs-cTnI on mortality among individuals with COPD compared with normal lung function (NLF).Methods: In 2002-04, subjects with FEV1/VC <0.70 (COPD, n=993) and age and sex-matched referents withoutCOPD were identified from OLIN’s population-based cohorts. In 2005, structured interviews, post-bronchodilator spirometry, blood sampling and ECG were performed in individuals with COPD (n=599) and NLF (n=756). Hs-cTnI was analysed in serum and concentrations ≥5 ng/L were defined as elevated. Mortality data were collected until 2016.Results: In 2005, the prevalence of reported IHD and elevated hs-cTnI was higher in COPD than NLF (16.2% vs 11.9% p=.02 and 31.1% vs 25.0% p=.01). The cumulative mortality was higher in COPD than NLF, both overall (36.5% vs 19.2% p<.001), and when restricting comparison to individuals with hs-cTnI≥5 (59.1% vs 34.9% p<.001). In a Cox-regression model adjusting for common confounders including reported IHD and ischemic ECG changes, hs-cTnI≥5 was associated with an increased risk for death in COPD (HR 1.41, 95%CI 1.03-1.93), but not in NLF (HR 0.84 95%CI 0.58-1.22). The increased risk remained after adjusting for FEV1% predicted.Conclusion: Elevated hs-cTnI was associated with increased mortality over a 11 -year follow-up among individuals with COPD, but not among those with NLF in this population-based study. The use of troponin could identify individuals with stable COPD at the highest risk of death.
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| 167. |
- Nilsson, Ulf, et al.
(författare)
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Ischemic ECG abnormalities are associated with an increased risk for death among subjects with COPD, also among those without known heart disease
- 2017
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : Dove Medical Press. - 1176-9106 .- 1178-2005. ; 12, s. 2507-2514
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiovascular comorbidity contributes to increased mortality among subjects with COPD. However, the prognostic value of ECG abnormalities in COPD has rarely been studied in population-based surveys.Aim: To assess the impact of ischemic ECG abnormalities (I-ECG) on mortality among individuals with COPD, compared to subjects with normal lung function (NLF), in a population-based study.Methods: During 2002–2004, all subjects with FEV1/VC <0.70 (COPD, n=993) were identified from population-based cohorts, together with age- and sex-matched referents without COPD. Re-examination in 2005 included interview, spirometry, and 12-lead ECG in COPD (n=635) and referents [n=991, whereof 786 had NLF]. All ECGs were Minnesota-coded. Mortality data were collected until December 31, 2010.Results: I-ECG was equally common in COPD and NLF. The 5-year cumulative mortality was higher among subjects with I-ECG in both groups (29.6% vs 10.6%, P<0.001 and 17.1% vs 6.6%, P<0.001). COPD, but not NLF, with I-ECG had increased risk for death assessed as the mortality risk ratio [95% confidence interval (CI)] when compared with NLF without I-ECG, 2.36 (1.45–3.85) and 1.65 (0.94–2.90) when adjusted for common confounders. When analyzed separately among the COPD cohort, the increased risk for death associated with I-ECG persisted after adjustment for FEV1% predicted, 1.89 (1.20–2.99). A majority of those with I-ECG had no previously reported heart disease (74.2% in NLF and 67.3% in COPD) and the pattern was similar among them.Conclusion: I-ECG was associated with an increased risk for death in COPD, independent of common confounders and disease severity. I-ECG was of prognostic value also among those without previously known heart disease.
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| 168. |
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| 169. |
- Nurmi, Elias, et al.
(författare)
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Agreement between self-reported and registered age at asthma diagnosis in Finland
- 2024
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Ingår i: BMC PULMONARY MEDICINE. - 1471-2466. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionIn epidemiological studies, the age at asthma onset is often defined by patients' self-reported age at diagnosis. The reliability of this report might be questioned. Our objective was to evaluate the agreement between self-reported and registered age at asthma diagnosis and assess features contributing to the agreement.MethodsAs part of the FinEsS respiratory survey in 2016, randomly selected population samples of 13,435 from Helsinki and 8000 from Western Finland were studied. Self-reported age at asthma diagnosis was compared to age at asthma diagnosis registered in the Finnish register on special reimbursement for asthma medication. The reimbursement right is based on lung function criteria according to GINA and Finnish guidelines. If the difference was less than 5 years, self-reported diagnosis was considered reliable. Features associated with the difference between self-reported and registered age at asthma diagnosis were evaluated.ResultsAltogether 197 subjects from Helsinki and 144 from Western Finland were included. Of these, 61.9% and 77.8%, respectively, reported age at diagnosis reliably. Median difference between self-reported and registered age at diagnoses was - 2.0 years (IQR - 9.0 to 0) in Helsinki and - 1.0 (IQR - 4.3 to 0) in Western Finland indicating earlier self-reported age at diagnosis. More reliable self-report was associated with non-allergic subjects and subjects who reported having asthma diagnosis more recently.ConclusionsAgreement between self-reported and registered age at asthma diagnosis was good especially with adult-onset asthma patients. Poor agreement in early-onset asthma could be related to delay in registration due to reimbursement criteria. Self-reported age at asthma diagnosis was compared with health register data.Agreement between self-report and register was good in adult-onset asthma.If the diagnosis was reported far in the past, agreement with register was poorer.
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| 170. |
- Pakkasela, Johanna, et al.
(författare)
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Age at asthma diagnosis in subjects with and without allergic rhinitis
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Onset of allergic asthma has a strong association with childhood. Much less is known about adult onset asthma and its association with allergy.Objectives: To assess the proportion of allergic and non-allergic asthma in adulthood in relation to the age at asthma diagnosis.Methods: Postal questionnaires were sent to 8000 randomly selected recipients aged 20-69 years in Finland in 2016. The participation rate was 52% (n=4173). Asthma was classified allergic when a physician-diagnosed asthma and a physician-diagnosed allergic rhinitis were both reported.Results: The prevalence of physician-diagnosed asthma and allergic rhinitis were 11% (n=445) and 18%, respectively. Mean ages at diagnosis of allergic asthma and non-allergic asthma were 19 and 35 years, respectively. Among subjects with asthma diagnosis at ages 0-19, 20-39 and 50-69 years, 67%, 55% and 23%, respectively, were allergic. For non-allergic asthma, the incidence rate of asthma was lowest in children and young adults (0.7/1000/year). It increased after middle age and was highest in older age groups (2.4/1000/year in 50-59 years old).Conclusions: The study results support the well-recognized fact that childhood asthma is mostly allergic. To our knowledge, this is the first study to show that the proportion of allergic asthma steadily declines with advancing age at asthma diagnosis and non-allergic asthma becomes the dominant phenotype with asthma diagnosed in middle age.
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