1. |
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- 2019
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Journal article (peer-reviewed)
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2. |
- Kjölhede, Karin, et al.
(author)
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Glycemic, maternal and neonatal outcomes in women with type 1 diabetes using continuous glucose monitoring during pregnancy – Pump vs multiple daily injections, a secondary analysis of an observational cohort study
- 2021
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:5, s. 927-933
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Journal article (peer-reviewed)abstract
- Introduction: Continuous glucose monitoring (CGM) provides detailed information about glucose level fluctuations over time. The method is increasingly being used in pregnant women with type 1 diabetes. However, only one previous study compared CGM results related to pregnancy outcomes in women using insulin pumps with those administering multiple daily injections (MDI). We performed a secondary analysis of CGM metrics from an observational cohort of pregnant women with type 1 diabetes and compared insulin pump and MDI therapies in relation to maternal and neonatal outcomes. Material and methods: The study included 185 pregnant Swedish women with type 1 diabetes undergoing CGM throughout pregnancy. Women were divided according to insulin administration mode, ie MDI (n = 131) or pump (n = 54). A total of 91 women used real-time CGM and 94 women used intermittently viewed CGM. Maternal demographics and maternal and neonatal outcome data were collected from medical records. CGM data were analyzed according to predefined glycemic indices: mean glucose; standard deviation; percentage of time within, below and above glucose target range; mean amplitude of glycemic excursion; high and low glucose indices; and coefficient variation in percent. Associations between insulin administration mode and CGM data, on the one hand, and maternal and neonatal outcomes, on the other, were analyzed with analysis of covariance and logistic regression, respectively, adjusted for confounders. Results: There were no differences in maternal characteristics or glycemic indices between the MDI and pump groups, except for a longer duration of type 1 diabetes and higher frequencies of microangiopathy and real-time CGM among pump users. Despite improvement with each trimester, glucose levels remained suboptimal throughout pregnancy in both groups. There were no differences between the MDI and pump groups concerning the respective associations with any of the outcomes. The frequency of large for gestational age was high in both groups (MDI 49% vs pump 63%) and did not differ significantly. Conclusions: Pregnant women with type 1 diabetes did not differ in glycemic control or pregnancy outcome, related to MDI or pump administration of insulin. Glycemic control remained suboptimal throughout pregnancy, regardless of insulin administration mode.
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3. |
- Kristensen, Karl, et al.
(author)
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Continuous glucose monitoring in pregnant women with type 1 diabetes : an observational cohort study of 186 pregnancies
- 2019
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 62:7, s. 1143-1153
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: The aim of this study was to analyse patterns of continuous glucose monitoring (CGM) data for associations with large for gestational age (LGA) infants and an adverse neonatal composite outcome (NCO) in pregnancies in women with type 1 diabetes. Methods: This was an observational cohort study of 186 pregnant women with type 1 diabetes in Sweden. The interstitial glucose readings from 92 real-time (rt) CGM and 94 intermittently viewed (i) CGM devices were used to calculate mean glucose, SD, CV%, time spent in target range (3.5–7.8 mmol/l), mean amplitude of glucose excursions and also high and low blood glucose indices (HBGI and LBGI, respectively). Electronic records provided information on maternal demographics and neonatal outcomes. Associations between CGM indices and neonatal outcomes were analysed by stepwise logistic regression analysis adjusted for confounders. Results: The number of infants born LGA was similar in rtCGM and iCGM users (52% vs 53%). In the combined group, elevated mean glucose levels in the second and the third trimester were significantly associated with LGA (OR 1.53, 95% CI 1.12, 2.08, and OR 1.57, 95% CI 1.12, 2.19, respectively). Furthermore, a high percentage of time in target in the second and the third trimester was associated with lower risk of LGA (OR 0.96, 95% CI 0.94, 0.99 and OR 0.97, 95% CI 0.95, 1.00, respectively). The same associations were found for mean glucose and for time in target and the risk of NCO in all trimesters. SD was significantly associated with LGA in the second trimester and with NCO in the third trimester. Glucose patterns did not differ between rtCGM and iCGM users except that rtCGM users had lower LBGI and spent less time below target. Conclusions/interpretation: Higher mean glucose levels, higher SD and less time in target range were associated with increased risk of LGA and NCO. Despite the use of CGM throughout pregnancy, the day-to-day glucose control was not optimal and the incidence of LGA remained high.
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4. |
- Nüssler, Emil Karl, et al.
(author)
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Operation for recurrent cystocele with anterior colporrhaphy or non-absorbable mesh : patient reported outcomes
- 2013
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In: International Urogynecology Journal. - : Springer London. - 0937-3462 .- 1433-3023. ; 24:11, s. 1925-1931
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Journal article (peer-reviewed)abstract
- Introduction and hypothesis: The aim of this study was to compare patient reported outcomes and complications after repair of recurrent anterior vaginal wall prolapse in routine health care settings using standard anterior colporrhaphy or non-absorbable mesh.Methods: The study is based on prospective data from the Swedish National Register for Gynaecological Surgery. 286 women were operated on for recurrent anterior vaginal wall prolapse in 2008–2010; 157 women had an anterior colporrhaphy and 129 were operated on with a non-absorbable mesh. Pre-, and perioperative data were collected from doctors and patients. Patient reported outcomes were evaluated 2 months and 12 months after the operation.Results: After 12 months, the odds ratio (OR) of patient reported cure was 2.90 (1.34–6.31) after mesh implants compared with anterior colporrhaphy. Both patient- and doctor-reported complications were found more often in the mesh group. However, no differences in serious complications were found. Thus, an organ lesion was found in 2.3 % after mesh implant compared with 2.5 % after anterior colporrhaphy (p = 0.58). Two patients in the mesh group (1.2 %) were re-operated compared with 1 patient (0.6 %) in the anterior colporrhaphy group (p = 0.58). The infection rate was higher after mesh (8.5 %) than after anterior colporrhaphy (2.5 %; OR 3.19 ; 1.07–14.25).Conclusion: Implantation of synthetic mesh during operation for recurrent cystocele more than doubled the cure rate, whereas no differences in serious complications were found between the groups. However, mesh increased the risk of infection.
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5. |
- Backe, Marie Balslev, et al.
(author)
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Lysine demethylase inhibition protects pancreatic β cells from apoptosis and improves β-cell function
- 2018
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In: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207. ; 460, s. 47-56
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Journal article (peer-reviewed)abstract
- Transcriptional changes control β-cell survival in response to inflammatory stress. Posttranslational modifications of histone and non-histone transcriptional regulators activate or repress gene transcription, but the link to cell-fate signaling is unclear. Inhibition of lysine deacetylases (KDACs) protects β cells from cytokine-induced apoptosis and reduces type 1 diabetes incidence in animals. We hypothesized that also lysine demethylases (KDMs) regulate β-cell fate in response to inflammatory stress.Expression of the demethylase Kdm6B was upregulated by proinflammatory cytokines suggesting a possible role in inflammation-induced β-cell destruction. Inhibition of KDM6 demethylases using the selective inhibitor GSK-J4 protected insulin-producing cells and human and mouse islets from cytokine-induced apoptosis by blunting nuclear factor (NF)-κB signaling and endoplasmic reticulum (ER) stress response gene expression. GSK-J4 furthermore increased expression of insulin gene and glucose-stimulated insulin secretion. Expression of genes regulating purinergic and cytokine ligand-receptor interactions was downregulated following GSK-J4 exposure, while expression of genes involved in cell maintenance and survival was upregulated. These data suggest that KDMs are important regulators of inflammation-induced β-cell dysfunction and death.
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6. |
- Cannon, J. A., et al.
(author)
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Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction
- 2017
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In: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 19:1, s. 129-137
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Journal article (peer-reviewed)abstract
- AIMS: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid-beta peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context of other recently conducted HFrEF trials. METHODS AND RESULTS: In PARADIGM-HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA Queries (SMQs) with 'broad' and 'narrow' preferred terms related to dementia. In PARADIGM-HF, 8399 patients aged 18-96 years were randomized and followed for a median of 2.25 years (up to 4.3 years). The narrow SMQ search identified 27 dementia-related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on sacubitril/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33-1.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95% CI 0.75-1.37), respectively. The rates of dementia-related AEs in both treatment groups in PARADIGM-HF were similar to those in three other recent trials in HFrEF. CONCLUSION: We found no evidence that sacubitril/valsartan, compared with enalapril, increased dementia-related AEs, although longer follow-up may be necessary to detect such a signal and more sensitive tools are needed to detect lesser degrees of cognitive impairment. Further studies to address this question are warranted.
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7. |
- Dolberg Anderson, Ulrik, et al.
(author)
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Fetal hemoglobin and alpha(1)-microglobulin as first- and early second-trimester predictive biomarkers for preeclampsia
- 2011
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In: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 204:6
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of this study was to evaluate fetal hemoglobin (HbF) and alpha(1)-microglobulin (A1M) in maternal serum as first-trimester biomarkers for preeclampsia (PE). STUDY DESIGN: The design was a case-control study. We included 96 patients in the first trimester of pregnancy (60 with PE and 36 controls). Venous serum samples were analyzed for HbF and total hemoglobin (Hb) by enzyme-linked immunosorbent assay and for A1M by radioimmunoassay. Sensitivity and specificity was calculated by logistic regression and receiver operating characteristic curve analysis. RESULTS: The HbF/Hb ratio and A1M concentration were significantly elevated in serum from women with subsequent development of PE (P < .0001). The optimal sensitivity and specificity was obtained using the biomarkers in combination; 69% sensitivity for a 5% screen positive rate and 90% sensitivity for a 23% screen positive rate. CONCLUSION: The study suggests that HbF/Hb ratio in combination with A1M is predictive biomarkers for PE.
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8. |
- Dolberg Anderson, Ulrik, et al.
(author)
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Review: Biochemical markers to predict preeclampsia.
- 2012
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In: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 33, s. 42-47
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Journal article (peer-reviewed)abstract
- Worldwide the prevalence of preeclampsia (PE) ranges from 3 to 8% of pregnancies. 8.5 million cases are reported yearly, but this is probably an underestimate due to the lack of proper diagnosis. PE is the most common cause of fetal and maternal death and yet no specific treatment is available. Reliable biochemical markers for prediction and diagnosis of PE would have a great impact on maternal health and several have been suggested. This review describes PE biochemical markers in general and first trimester PE biochemical markers specifically. The main categories described are angiogenic/anti-angiogenic factors, placental proteins, free fetal hemoglobin (HbF), kidney markers, ultrasound and maternal risk factors. The specific biochemical markers discussed are: PAPP-A, s-Flt-1/PlGF, s-Endoglin, PP13, cystatin-C, HbF, and α(1)-microglobulin (A1M). PAPP-A and HbF both show potential as predictive biochemical markers in the first trimester with 70% sensitivity at 95% specificity. However, PAPP-A is not PE-specific and needs to be combined with Doppler ultrasound to obtain the same sensitivity as HbF/A1M. Soluble Flt -1 and PlGF are promising biochemical markers that together show high sensitivity from the mid-second trimester. PlGF is somewhat useful from the end of the first trimester. Screening pregnant women with biochemical markers for PE can reduce unnecessary suffering and health care costs by early detection of mothers at increased risk for PE, thus avoiding unnecessary hospitalization of pregnant women with suspect or mild PE and enabling monitoring of the progression of the disease thereby optimizing time for delivery and hopefully reducing the number of premature births.
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9. |
- Eckdahl, Johan A., et al.
(author)
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Mineral soils are an important intermediate storage pool of black carbon in fennoscandian boreal forests
- 2022
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In: Global Biogeochemical Cycles. - : John Wiley & Sons. - 0886-6236 .- 1944-9224. ; 36:11
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Journal article (peer-reviewed)abstract
- Approximately 40% of earth's carbon (C) stored in land vegetation and soil is within the boreal region. This large C pool is subjected to substantial removals and transformations during periodic wildfire. Fire-altered C, commonly known as pyrogenic carbon (PyC), plays a significant role in forest ecosystem functioning and composes a considerable fraction of C transport to limnic and oceanic sediments. While PyC stores are beginning to be quantified globally, knowledge is lacking regarding the drivers of their production and transport across ecosystems. This study used the chemo-thermal oxidation at 375°C (CTO-375) method to isolate a particularly refractory subset of PyC compounds, here called black carbon (BC), finding an average increase of 11.6 g BC m−2 at 1 year postfire in 50 separate wildfires occurring in Sweden during 2018. These increases could not be linked to proposed drivers, however BC storage in 50 additional nearby unburnt soils related strongly to soil mass while its proportion of the larger C pool related negatively to soil C:N. Fire approximately doubled BC stocks in the mineral layer but had no significant effect on BC in the organic layer where it was likely produced. Suppressed decomposition rates and low heating during fire in mineral subsoil relative to upper layers suggests potential removals of the doubled mineral layer BC are more likely transported out of the soil system than degraded in situ. Therefore, mineral soils are suggested to be an important storage pool for BC that can buffer short-term (production in fire) and long-term (cross-ecosystem transport) BC cycling.
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10. |
- Egan, Allyson C, et al.
(author)
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The Sound of Interconnectivity; The European Vasculitis Society 2022 Report
- 2022
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In: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 7:8, s. 1745-1757
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Journal article (peer-reviewed)abstract
- The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.
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11. |
- Fahlström, Karl
(author)
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Laser welding of boron steels for light-weight vehicle applications
- 2015
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Licentiate thesis (other academic/artistic)abstract
- Laser beam welding has gained a significant interest during the last two decades. The suitability of the process for high volume production has the possibility to give a strong advantage compared to several other welding methods. However, it is important to have the process in full control since various quality issues may otherwise occur. During laser welding of boron steels quality issues such as imperfections, changes in local and global geometry as well as strength reduction can occur. The aspects that need to be considered are strongly depending on alloy content, process parameters etc. These problems that can occur could be fatal for the construction and the lowest level of occurrence is wanted, independent of industry.The focus of this study has been to investigate the properties of laser welded boron steel. The study includes laser welding of boron alloyed steels with strengths of 1500 MPa and a recently introduced 1900 MPa grade. Focus has been to investigate weldability and the occurrence of cracks, porosity and strength reducing microstructure that can occur during laser welding, as well as distortion studies for tolerances in geometry. The results show that both conventional and 1900 MPa boron alloyed steel are suitable for laser welding.Due to the martensitic structure of welds the material tends to behave brittle. Cracking and porosity do not seem to be an issue limiting the use of these steels. For tolerances in geometry for larger structures tests has been done simulating laser welding of A-pillars and B-pillars. Measurements have been done with Vernier caliper as well as a more advanced optical method capturing the movements during the welding sequence. Results from the tests done on Ushaped beams indicates that depending on the geometry of the structure and heat input distortions can be controlled to give distortions from 1 to 8 mm, at a welding length of 700 mm. This means that important geometry points can be distorted several millimeters if the laser welding process not is controlled.
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12. |
- Frändberg, Julia, et al.
(author)
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Antenatal corticosteroids : a retrospective cohort study on timing, indications and neonatal outcome
- 2018
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 97:5, s. 591-597
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Journal article (peer-reviewed)abstract
- Introduction: An antenatal corticosteroid (ACS) delivery interval of 24 h to seven days is commonly referred to as optimal timing. We aimed to investigate whether the ACS delivery interval was associated with the obstetric indication for treatment and with neonatal complications. Material and methods: The study was a retrospective chart review of clinical data from preterm neonates delivered at the Skåne University Hospital, Lund University, Sweden, from 1 January 2013 to 31 December 2016. The ACS delivery intervals were compared between groups of women with various clinical scenarios and related to neonatal outcomes. Results: The study included 498 preterm neonates from 431 women. One to seven days before delivery, 41% of the women received ACS. Women with preterm prelabor rupture of membranes or vaginal bleeding had a median ACS delivery interval of 7.5 and eight days, respectively, compared with women with maternal/fetal indications or preterm labor (three and two days, respectively) (p < 0.001). Neonates with an ACS delivery interval of more than seven days were at a higher risk of respiratory distress syndrome [odds ratio (OR) 2.00, 95% confidence interval (CI) 1.05–3.79] and moderate or severe bronchopulmonary dysplasia (OR 2.78, 95% CI 1.45–5.33) than were neonates with an ACS delivery interval of one to seven days. Conclusion: Optimal timing of ACS treatment varied significantly based on the clinical indication. Women with preterm prelabor rupture of membranes or vaginal bleeding were more likely to have an ACS delivery interval of more than seven days. A prolonged ACS delivery interval was associated with an increased risk of neonatal respiratory morbidity and a prolonged stay in the neonatal care unit, but not with neonatal mortality.
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13. |
- Gilbert, F., et al.
(author)
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Sediment reworking by the burrowing polychaete Hediste diversicolor modulated by environmental and biological factors across the temperate North Atlantic. A tribute to Gaston Desrosiers
- 2021
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In: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 541
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Journal article (peer-reviewed)abstract
- Particle mixing and irrigation of the seabed by benthic fauna (bioturbation) have major impacts on ecosystem functions such as remineralization of organic matter and sediment-water exchange. As a tribute to Prof. Gaston Desrosiers by the Nereis Park association, eighteen laboratories carried out a collaborative experiment to acquire a global snapshot of particle reworking by the polychaete Hediste diversicolor at 16 sites surrounding the Northern Atlantic. Organisms and soft sediments were collected during May - July at different geographical locations and, using a common laboratory protocol, particulate fluorescent tracers (`luminophores') were used to quantify particle transport over a 10-day period. Particle mixing was quantified using the maximum penetration depth of tracers (MPD), particle diffusive coefficients (D-b), and non-local transport coefficients (r). Non-local coefficients (reflecting centimeter scale transport steps) ranged from 0.4 to 15 yr(-1), and were not correlated across sites with any measured biological (biomass, biovolume) or environmental parameters (temperature, grain size, organic matter). Maximum penetration depths (MPD) averaged similar to 10.7 cm (6.5-14.5 cm), and were similar to the global average bioturbation depth inferred from short-lived radiochemical tracers. MPD was also not correlated with measures of size (individual biomass), but increased with grain size and decreased with temperature. Bio-diffusion (D-b) correlated inversely with individual biomass (size) and directly with temperature over the environmental range (Q(10) similar to 1.7; 5-21 degrees C). The transport data were comparable in magnitude to rates reported for localized H. diversicolor populations of similar size, and confirmed some but not all correlations between sediment reworking and biological and environmental variables found in previous studies. The results imply that measures of particle reworking activities of a species from a single location can be generally extrapolated to different populations at similar conditions.
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14. |
- Hartmann, Karin, et al.
(author)
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Cutaneous manifestations in patients with mastocytosis : Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology
- 2016
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 137:1, s. 35-45
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Journal article (peer-reviewed)abstract
- Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.
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15. |
- Iorizzo, Linda, et al.
(author)
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Reliability of the point-of care analyzer “StatStrip® Xpress™” for measurement of fetal blood lactate
- 2019
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In: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981. ; 495, s. 88-93
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Journal article (peer-reviewed)abstract
- Objectives: Measurement of lactate in fetal blood is used to assess the degree of anaerobic metabolism. The technical difficulties in obtaining enough scalp blood for analysis by a bloodgas-analyzer advocates for the use of a point-of-care device. StatStrip®Xpress™ (SSX) has shown promising properties but needs further evaluation before implementation into fetal surveillance. Methods: Arterial/venous umbilical cord blood from 112 newborns were analyzed simultaneously with SSX and the reference method ABL800™. From 321 fetuses with abnormal heart rate scalp blood was sampled and analyzed repeatedly with SSX. Results: ABL800™ -lactate ranged from 1.9–13.3 mmol/L in arterial to 1.5–10.2 mmol/L in venous cord blood with excellent correlation to SSX (R 2 = 0.95). SSX-values were lower compared to the reference method ranging from −0.79 mmol/L for low values to −1.68 mmol/L for high values. The mean CV for SSX-values in cord respectively scalp blood was: lactate ≤3 mmol/L 7.1% respectively 8.4%; lactate >3 mmol/L 3.8% respectively 6.8%. Repeated measurements of the same sample with SSX where without significant difference in cord/scalp blood (p = 0.11). Conclusion: SSX-lactate values were constantly lower but correlated excellent to the reference method. The reproducibility was good for cord and scalp blood. We suggest SSX as an attractive device for measurement of fetal lactate.
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16. |
- Khan, M. S., et al.
(author)
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Natriuretic peptide plasma concentrations and risk of cardiovascular versus non-cardiovascular events in heart failure with reduced ejection fraction: Insights from the PARADIGM-HF and ATMOSPHERE trials
- 2021
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In: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 237, s. 45-53
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Journal article (peer-reviewed)abstract
- Background : N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations are independent prognostic markers in patients with heart failure and reduced ejection fraction (HFrEF). Whether a differential risk association between NT-proBNP plasma concentrations and risk of cardiovascular (CV) vs non-CV adverse events exists is not well known. Objective : To assess if there is a differential proportional risk of CV vs non-CV adverse events by NT-proBNP plasma concentrations. Methods : In this post hoc combined analysis of PARADIGM-HF and ATMOSPHERE trials, proportion of CV vs non-CV mortality and hospitalizations were assessed by NT-proBNP levels ( <400, 400-999, 1000-1999, 2000-2999, and >3000 pg/mL) at baseline using Cox regression adjusting for traditional risk factors. Results : A total of 14,737 patients with mean age of 62 +/- 8 years (24% history of atrial fibrillation [AF]) were studied. For CV deaths, the event rates per 1000 patient-years steeply increased from 33.8 in the <= 400 pg/mL group to 142.3 in the >= 3000 pg/mL group, while the non-CV death event rates modestly increased from 9.0 to 22.7, respectively. Proportion of non-CV deaths decreased across the 5 NT-proBNP groups (21.1%, 18.4%, 17.9%, 17.4%, and 13.7% respectively). Similar trend was observed for non-CV hospitalizations (46.4%, 42.6%, 42.9%, 42.0%, and 36.9% respectively). These results remained similar when stratified according to the presence of AF at baseline and prior HF hospitalization within last 12 months. Conclusions : The absolute CV event rates per patient years of follow-up were greater and had higher stepwise increases than non-CV event rates across a broad range of NT-proBNP plasma concentrations indicating a differential risk of CV events at varying baseline NT-proBNP values. These results have implications for future design of clinical trials.
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17. |
- Kristensen, Karl, et al.
(author)
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Cystatin C, beta-2-microglobulin and beta-trace protein in pre-eclampsia
- 2007
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 86:8, s. 921-926
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Journal article (peer-reviewed)abstract
- Background. An altered renal function is an essential component of the patho-physiology of pre-eclampsia. The plasma levels of low molecular mass proteins, e. g. beta-trace protein, beta-2-microglobulin and cystatin C, are increased in the third trimester of normal pregnancy. The plasma levels of cystatin C and beta-2-microglobulin are further increased in preeclampsia, and the cystatin C level has been reported to be a reliable marker for the disease. The aim of this investigation was to study the plasma levels of beta-trace protein, beta-2-microglobulin and cystatin C in pre-eclampsia, and to determine the diagnostic performance of these proteins compared to that of urate and creatinine. Methods. A case-control study of 57 women diagnosed with pre-eclampsia, and 218 healthy women with uncomplicated singleton pregnancies in the third trimester. Women in the catchment area of Lund, Sweden, were included during an 18-month period from October 2003 to April 2005. Venous blood samples were drawn upon inclusion when diagnosis was made. The maternal plasma concentrations of the 3 proteins were analysed by automated particle-enhanced immunoturbidimetric assays. Results. The plasma levels of the 3 proteins were significantly higher in the third trimester of pre-eclamptic patients compared to healthy pregnant women in the third trimester. The upper reference limits ( parametric 97.5 percentile) were 2.57 mg/l for beta-2-microglobulin, 0.72 mg/l for beta-trace protein and 1.37 mg/l for cystatin C. ROC analysis showed similar diagnostic performance for the 3 proteins, with b-trace protein displaying the best diagnostic performance of all the analytes. Conclusions. In this study, the maternal plasma levels of beta 2-microglobulin, beta-trace protein and cystatin C were all significantly elevated in pre-eclampsia compared to those of healthy pregnant women, and displayed similar diagnostic performance for diagnosing pre-eclampsia. The results indicate that low molecular mass proteins are useful as markers of renal impairment in pre-eclampsia.
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18. |
- Kristensen, Karl, et al.
(author)
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Diagnosis of Gestational Diabetes Mellitus with Point-of-Care Methods for Glucose versus Hospital Laboratory Method Using Isotope Dilution Gas Chromatography-Mass Spectrometry as Reference
- 2020
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In: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6745 .- 2314-6753. ; 2020
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Journal article (peer-reviewed)abstract
- Background. In Sweden, both glucose analyzers in accredited laboratories and point-of-care glucose devices are used for gestational diabetes mellitus (GDM) diagnosis. The aim of this study was to compare the diagnostic performance of the HemoCue Glucose 201+ (HC201+) and RT (HC201RT) systems with that of the hospital central laboratory hexokinase method (CL) based on lyophilized citrate tubes, using the isotope dilution gas chromatography-mass spectrometry (ID GC-MS) as reference. Methods. A 75 g oral glucose tolerance test was performed on 135 women screened positive for GDM. Diagnosis was based on the World Health Organization 2013 diagnostic thresholds for fasting (n=135), 1 h (n=52), and 2 h (n=135) glucose measurements. Bland-Altman analysis and surveillance error grids were used to evaluate analytical and clinical accuracy. Results. Significantly more women were diagnosed with GDM by HC201+ (80%) and CL (80%) than with the reference (65%, P<0.001) based on fasting and/or 2 h thresholds, whereas the percentage diagnosed by HC201RT (60%) did not differ significantly from the reference. In Bland-Altman analysis, a positive bias was observed for HC201+ (4.2%) and CL (6.1%) and a negative bias for HC201RT (-1.8%). In the surveillance error grid, 95.9% of the HC201+ values were in the no-risk zone as compared to 98.1% for HC201RT and 97.5% for CL. Conclusions. A substantial positive bias was found for CL measurements resulting in overdiagnosis of GDM. Our findings suggest better performance of HC201RT than HC201+ in GDM diagnosis. The results may have possible implications for GDM diagnosis in Sweden and require further elucidation.
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19. |
- Kristensen, Karl, et al.
(author)
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Increased cystatin C expression in the pre-eclamptic placenta.
- 2007
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In: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407. ; 13, s. 189-195
-
Journal article (peer-reviewed)abstract
- Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C inhibits cysteine proteinases. The serum concentration of cystatin C is increased in late pregnancy and pre-eclampsia. We aimed to investigate whether the expression of cystatin C is increased in the pre-eclamptic placenta and to investigate the expression pattern of cystatin C mRNA and protein in placental tissue. Tissue samples from the central part of the placenta from 13 normal and 22 pre-eclamptic pregnancies were included. We used real-time polymerase chain reaction (RT-PCR) and in situ hybridization for mRNA expression analysis and immunohistochemistry and Western blotting for protein expression analysis. RT-PCR showed a significantly higher expression of cystatin C mRNA in pre-eclampsia than in normal pregnancy, with the highest expression in cases with severe pre-eclampsia. In situ hybridization revealed a distinct pattern of high expression in the extravillous trophoblast cells of the basal plate and low expression in the syncytiotrophoblast covering villi. The cystatin C protein distribution matched the mRNA expression pattern. Western blot analysis revealed an increased protein expression in cases with severe pre-eclampsia and confirmed the presence of cystatin C in amniotic fluid samples. The high expression of cystatin C mRNA in the extravillous trophoblast cells of the basal plate suggests a role for cystatin C in the regulation of proteases in placentation. Placental expression and secretion of cystatin C could contribute to the elevated maternal plasma levels seen in pre-eclampsia.
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20. |
- Kristensen, Karl, et al.
(author)
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Increased plasma levels of ss(2)-microglobulin, cystatin C and ss-trace protein in term pregnancy are not due to utero-placental production.
- 2008
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 649-653
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Journal article (peer-reviewed)abstract
- Objective . To study concentration gradients of the low molecular mass proteins, ss(2)-microglobulin, cystatin C and ss-trace protein, between the uterine and ante-cubital veins, the umbilical artery and vein and in the amniotic fluid compartment. Material and methods. The study comprised 27 healthy women with uncomplicated pregnancies undergoing caesarean section at term. Samples were collected simultaneously and paired t-tests were used to compare mean plasma concentrations. Results . There was no significant concentration gradient in the plasma levels of ss(2)-microglobulin, cystatin C or ss-trace protein between the uterine and antecubital veins. There were no correlations between the protein levels in the compartments. Conclusion . The utero-placental unit does not contribute significantly to the maternal levels of ss(2)-microglobulin, cystatin C and ss-trace protein in normal pregnancy, and the proteins are not likely to be transferred across the placental barrier.
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21. |
- Kristensen, Karl
(author)
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PLASMA PROTEINS IN NORMAL AND PREECLAMPTIC PREGNANCY
- 2007
-
Doctoral thesis (other academic/artistic)abstract
- The aim of the research presented in this thesis was to provide extended background knowledge concerning several biochemical markers, used for the medical evaluation of pregnant women with suspected or confirmed preeclampsia, in order to improve the reliability of monitoring. Plasma levels of beta-2 microglobulin, cystatin C and beta trace protein are known to reflect renal filtration in non-pregnant settings, and the plasma proteins, C-reactive protein and serum amyloid A protein, are known to be sensitive markers of inflammation. Despite pregnancy-related renal hyperfiltration, the plasma levels of beta-2 microglobulin, cystatin C and beta trace protein remained virtually unchanged in the first and second trimesters, with an elevation (20-40%) in the third trimester in a cross-sectional study including 398 women with uncomplicated pregnancies. In a case-control study including 57 women diagnosed with preeclampsia and 218 women with uncomplicated pregnancies, the protein levels were elevated further in women with preeclampsia, and the three plasma proteins had similar diagnostic capacities for the diagnosis of preeclampsia. The placental expression of cystatin C, a strong extracellular protease inhibitor, was up-regulated in the preeclamptic placenta at the mRNA and protein level in a study including placental tissue samples from 13 normal and 22 preeclamptic pregnancies. Real-time polymerase chain reaction (RT-PCR) and in situ hybridization were used for the mRNA expression analysis and immuno-histochemistry and Western blotting were used for the protein expression analysis. In a cross-sectional study including 27 healthy women undergoing planned Caesarean section at term, the concentrations of beta-2 microglobulin, cystatin C and beta trace protein in the uterine vein and the antecubital vein were analysed. No significant concentration gradients were detected, indicating that utero-placental synthesis is not a major source of these proteins in the maternal circulation. The acute-phase proteins, C-reactive protein and serum amyloid A protein were not increased in women with preeclampsia compared with women with normal pregnancy in a study of 299 healthy normotensive women with uncomplicated pregnancies and 57 women with preeclampsia. The acute-phase proteins therefore did not reflect the suggested inflammatory response to preeclampsia. The plasma levels of beta-2 microglobulin, cystatin C and beta trace protein are potential markers of preeclampsia and for the monitoring of renal deterioration as the condition progresses. The proteins could be useful in optimizing the monitoring and timing of delivery of women with preeclampsia.
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22. |
- Kristensen, Karl, et al.
(author)
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Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia.
- 2009
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In: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 67:4, s. 275-280
-
Journal article (peer-reviewed)abstract
- Aims: To study plasma levels of serum amyloid A protein and C-reactive protein in pregnant women with and without preeclampsia and non-pregnant women. Plasma levels of haptoglobin, orosomucoid and ceruloplasmin were also analyzed. Methods: The study included 295 women with uncomplicated pregnancies, 57 women diagnosed with preeclampsia, and 58 healthy non-pregnant women. Plasma concentrations of acute phase proteins were analyzed by particle-enhanced immunoassays. Non-parametric Kruskal-Wallis and Mann-Whitney U tests were used to test differences between the groups. Results: Plasma levels of C-reactive protein and ceruloplasmin were increased in pregnant women with and without preeclampsia compared to non-pregnant women. Plasma levels of serum amyloid A protein and C-reactive protein were not elevated in women with preeclampsia compared to women with normal pregnancy. Conclusion: The description of preeclampsia as a systemic inflammatory state was not reflected in the plasma levels of serum amyloid A protein and C-reactive protein.
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23. |
- Kristensen, Karl, et al.
(author)
-
Temporal changes of the plasma levels of cystatin C, beta-trace protein, beta(2)-microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process
- 2007
-
In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 67:6, s. 612-618
-
Journal article (peer-reviewed)abstract
- Objective. To determine the plasma levels of the renal functional markers creatinine, urate, cystatin C, beta(2)-microglobulin and beta-trace protein in samples from the first, second, early third and late third trimesters of 398 healthy women with uncomplicated singleton pregnancies. Material and methods. Plasma samples from 58 healthy non-pregnant women served as controls. The creatinine levels were significantly lower at all time-points in pregnancy, whereas the urate levels were lower during the first and second trimesters but increased in the late third trimester. The cystatin C, beta(2)-microglobulin and beta-trace protein levels displayed similar changes with increased levels in the third trimester but unaltered levels during the first and second trimesters. Results. The results indicate an increased filtration of low-molecular weight molecules during pregnancy, particularly during the first and second trimesters, whereas filtration of 10-30 kDa molecules is decreased in the third but unaltered in the first and second trimesters. The levels of albumin and alpha(2)-macroglobulin were measured in the same samples. Conclusions. The albumin levels decreased in the second and third trimesters, whereas the levels of alpha(2)-macroglobulin were unchanged, which is compatible with a virtually unaltered transfer of alpha(2)-macroglobulin between the intra-and extravascular space during pregnancy and a significantly increased extravascular fraction of albumin.
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24. |
- Kristensen, S. L., et al.
(author)
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Geographic variations in the PARADIGM-HF heart failure trial
- 2016
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In: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 37:41, s. 3167-3174
-
Journal article (peer-reviewed)abstract
- AIMS: The globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest and most globally representative trial in heart failure (HF) to date. METHODS AND RESULTS: We looked at five regions: North America (NA) 622 (8%), Western Europe (WE) 1680 (20%), Central/Eastern Europe/Russia (CEER) 2762 (33%), Latin America (LA) 1413 (17%), and Asia-Pacific (AP) 1487 (18%). Notable differences included: WE patients (mean age 68 years) and NA (65 years) were older than AP (58 years) and LA (63 years) and had more coronary disease; NA and CEER patients had the worst signs, symptoms, and functional status. North American patients were the most likely to have a defibrillating-device (53 vs. 2% AP) and least likely prescribed a mineralocorticoid receptor antagonist (36 vs. 61% LA). Other evidence-based therapies were used most frequently in NA and WE. Rates of the primary composite outcome of cardiovascular (CV) death or HF hospitalization (per 100 patient-years) varied among regions: NA 13.5 (95% CI 11.7-15.6), WE 9.6 (8.6-10.6), CEER 12.3 (11.4-13.2), LA 11.2 (10.0-12.5), and AP 12.5 (11.3-13.8). After adjustment for prognostic variables, relative to NA, the risk of CV death was higher in LA and AP and the risk of HF hospitalization lower in WE. The benefit of sacubitril/valsartan was consistent across regions. CONCLUSION: There were many regional differences in PARADIGM-HF, including in age, symptoms, comorbidity, background therapy, and event-rates, although these did not modify the benefit of sacubitril/valsartan. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
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25. |
- Kristensen, S. L., et al.
(author)
-
International Geographic Variation in Event Rates in Trials of Heart Failure With Preserved and Reduced Ejection Fraction
- 2015
-
In: Circulation. - 1524-4539. ; 131, s. 43-53
-
Journal article (peer-reviewed)abstract
- BACKGROUND: -International geographic differences in outcomes may exist for clinical trials of heart failure and reduced ejection fraction (HF-REF), but there are few data for those with preserved ejection fraction (HF-PEF). METHODS AND RESULTS: -We analyzed outcomes by international geographic region in the Irbesartan in Heart Failure with Preserved systolic function trial (I-Preserve), the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved trial, the CHARM-Alternative and CHARM-Added HF-REF trials, and the Controlled Rosuvastatin Multinational Trial in HF-REF (CORONA). Crude rates of heart failure hospitalization varied by geographic region, and more so for HF-PEF than for HF-REF. Rates in patients with HF-PEF were highest in the United States/Canada (HF hospitalization rate 7.6 per 100 patient-years in I-Preserve; 8.8 in CHARM-Preserved), intermediate in Western Europe (4.8/100 and 4.7/100), and lowest in Eastern Europe/Russia (3.3/100 and 2.8/100). The difference between the United States/Canada versus Eastern Europe/Russia persisted after adjustment for key prognostic variables: adjusted hazard ratios 1.34 (95% confidence interval, 1.01-1.74; P=0.04) in I-Preserve and 1.85 (95% confidence interval, 1.17-2.91; P=0.01) in CHARM-Preserved. In HF-REF, rates of HF hospitalization were slightly lower in Western Europe compared with other regions. For both HF-REF and HF-PEF, there were few regional differences in rates of all-cause or cardiovascular mortality. CONCLUSIONS: -The differences in event rates observed suggest there is international geographic variation in 1 or more of the definition and diagnosis of HF-PEF, the risk profile of patients enrolled, and the threshold for hospitalization, which has implications for the conduct of future global trials.
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26. |
- Kristensen, S. L., et al.
(author)
-
Prevalence and incidence of intraventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: Insights from PARADIGM-HF and ATMOSPHERE
- 2020
-
In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:12, s. 2370-9
-
Journal article (peer-reviewed)abstract
- AIMS: The importance of intraventricular conduction delay (IVCD), incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) is not well studied. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials. METHODS AND RESULTS: Risk of the primary composite outcome of cardiovascular death or HF hospitalization and all-cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11,861 patients without an intracardiac device. At baseline, 1,789 (15.1%) patients had left bundle branch block (LBBB), 524 (4.4%) RBBB, 454 (3.8%) non-specific IVCD, 2588 (21.8%) "mildly abnormal" QRS (110-129 milliseconds [ms]) and 6506 (54.9%) QRS <110 ms. During a median follow-up of 2.5 years, the risk of the primary composite endpoint was higher among those with a wide QRS, irrespective of morphology: hazard ratios (95% CI) LBBB 1.36 (1.23, 1.50), RBBB 1.54 (1.31, 1.79), nonspecific IVCD 1.65 (1.40, 1.94) and QRS 110-129 ms 1.35 (95% CI 1.23, 1.47), compared with QRS duration <110 ms. A total of 1,234 (15.6%) patients developed new-onset QRS-widening >/=130 ms (6.1 per 100 py). Incident LBBB occurred in 495 (6.3%) patients (2.4 per 100 py) and was associated with a higher risk of the primary composite outcome; HR 1.42 (1.12, 1.82). CONCLUSION: In patients with HFrEF, a wide QRS was associated with worse clinical outcomes irrespective of morphology. The annual incidence of new-onset LBBB was around 2.5%, and associated with a higher risk of adverse outcomes, highlighting the importance of repeat ECG review.
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27. |
- Kristensen, Søren L., et al.
(author)
-
Prevalence of Prediabetes and Undiagnosed Diabetes in Patients with HFpEF and HFrEF and Associated Clinical Outcomes
- 2017
-
In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 31:5/6, s. 545-549
-
Journal article (peer-reviewed)abstract
- © 2017 The Author(s) Purpose: The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). Methods: We examined the prevalence and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity programme (CHARM). We studied the primary outcome of HF hospitalization or cardiovascular (CV) death, and all-cause death, and estimated hazard ratios (HR) by use of multivariable Cox regression models. Results: HbA1c was measured at baseline in CHARM patients enrolled in the USA and Canada and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c < 6.0), 20 and 22% had prediabetes (HbA1c 6.0–6.4), respectively. Finally among patients with HFpEF 22% had undiagnosed diabetes (HbA1c > 6.4), and 40% had known diabetes (any HbA1c), with corresponding prevalence among HFrEF patients being 26 and 35%. The rates of both clinical outcomes of interest were higher in patients with undiagnosed diabetes and prediabetes, compared to normoglycemic patients, irrespective of HF subtype, and in general higher among HFrEF patients. For the primary composite outcome among HFpEF patients, the HRs were 1.02 (95% CI 0.63–1.65) for prediabetes, HR 1.18 (0.75–1.86) for undiagnosed diabetes and 2.75 (1.83–4.11) for known diabetes, respectively, p value for trend across groups < 0.001. Dysglycemia was also associated with worse outcomes in HFrEF. Conclusions: These findings confirm the remarkably high prevalence of dysglycemia in heart failure irrespective of ejection fraction phenotype, and demonstrate that dysglycemia is associated with a higher risk of adverse clinical outcomes, even before the diagnosis of diabetes and institution of glucose lowering therapy in patients with HFpEF as well as HFrEF.
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28. |
- Kristensen, S. L., et al.
(author)
-
Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation
- 2017
-
In: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 10:10
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. METHODS AND RESULTS: We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without (P<0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all P<0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and >/=3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400-999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; >/=3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found similar results for the components of the composite outcome and all-cause mortality. CONCLUSIONS: HF and reduced ejection fraction patients with AF had higher NT-proBNP than those without AF. However, above a concentration of 400 pg/mL (representing most patients in each group), NT-proBNP had similar predictive value for adverse cardiovascular outcomes, irrespective of AF status. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier NCT00853658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).
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29. |
- Kristensen, S. L., et al.
(author)
-
Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial
- 2016
-
In: Circulation-Heart Failure. - 1941-3289. ; 9:1
-
Journal article (peer-reviewed)abstract
- Background The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: <6.0% [<42 mmol/mol], 6.0%-6.4% [42-47 mmol/mol; pre-diabetes mellitus], and 6.5% [48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n=2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P<0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre-diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, >6.5%) and known diabetes mellitus compared with those with HbA1c<6.0% was 1.39 (1.17-1.64); P<0.001 and 1.64 (1.43-1.87); P<0.001, respectively. Patients with pre-diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10-1.47]; P<0.001) compared with those with HbA1c<6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. Conclusions In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre-diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c <6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
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30. |
- Ladfors, Linnea, et al.
(author)
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Fetal overgrowth in women with type 1 and type 2 diabetes mellitus
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:11
-
Journal article (peer-reviewed)abstract
- Objectives: Despite improved glycemic control, the rate of large-for-gestational-age (LGA) infants remains high in pregnancies complicated by diabetes mellitus type 1 (T1DM) and type 2 (T2DM). Poor glycemic control, obesity, and excessive gestational weight gain are the main risk factors. The aim of this study was to determine the relative contribution of these risk factors for LGA in women with T1DM and T2DM, after controlling for important confounders such as age, smoking, and parity. Methods: In this retrospective chart review study, we analyzed the medical files of pregnant women with T1DM and T2DM who attended the antenatal care program at Skåne University Hospital during the years 2006 to 2016. HbA1c was used as a measure of glycemic control. Maternal weight in early pregnancy and at term was registered. LGA was defined as birth weight > 2 standard deviations of the mean. Univariable and multivariable logistic regression analysis was used to calculate odds ratios (OR’s) and 95% confidence intervals (CIs) for LGA. Results: Over the 11-year period, we identified 308 singleton pregnancies in 221 women with T1DM and in 87 women with T2DM. The rate of LGA was 50% in women with T1DM and 23% in women with T2DM. The multivariable regression model identified gestational weight gain and second-trimester HbA1c as risk factors for LGA in T1DM pregnancies (OR = 1.107, 95% CI: 1.044–1.17, and OR = 1.047, 95% CI: 1.015–1.080, respectively) and gestational weight gain as a risk factor in T2DM pregnancies (OR = 1.175, 95% CI: 1.048–1.318), independent of body mass index. Conclusions: Gestational weight gain was associated with LGA in women with T1DM and T2DM, independent of maternal body mass index. The findings suggest that monitoring and regulation of gestational weight gain is important in the clinical care of these women, to minimize the risk of fetal overgrowth.
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31. |
- Madsen, Lene Duch, et al.
(author)
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Native-tissue repair of isolated primary rectocele compared with nonabsorbable mesh : patient-reported outcomes
- 2017
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In: International Urogynecology Journal. - : Springer Science and Business Media LLC. - 0937-3462 .- 1433-3023. ; 28:1, s. 49-57
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Journal article (peer-reviewed)abstract
- We evaluated patient-reported outcomes and complications after treatment of isolated primary rectocele in routine health-care settings using native-tissue repair or nonabsorbable mesh. We used prospective data from the Swedish National Register for Gynaecological Surgery and included 3988 women with a primary operation for rectocele between 2006 and 2014: 3908 women had native-tissue repair, 80 were operated with nonabsorbable mesh. No concurrent operations were performed. Pre- and perioperative data were collected from doctors and patients. Patient-reported outcomes were evaluated 2 and 12 months after the operation. Only validated questionnaires were used. One year after native-tissue repair, 77.8 % (76.4-79.6) felt they were cured, which was defined as never or hardly ever feeling genital protrusion; 74.0 % (72.2-75.7) were very satisfied or satisfied, and 84 % (82.8-85.9) reported improvement of symptoms. After mesh repair, 89.8 % (77.8-96.6) felt cured, 69.2 % (54.9-81.3) were very satisfied or satisfied, and 86.0 % (72.1-94.7) felt improvement. No significant differences were found between groups. Organ damage was found in 16 (0.4 %) patients in the native-tissue repair group compared with one (1.3 %) patient in the mesh group [odds ratio (OR) 3.08; 95 % confidence interval (CI) 0.07-20.30]. The rate of de novo dyspareunia after native-tissue repair was 33.1 % (30.4-35.8), comparable with that after mesh repair. The reoperation rate was 1.1 % (0.8-1.5) in both groups. Most patients were cured and satisfied after native-tissue repair of the posterior vaginal wall, and the patient-reported outcomes were comparable with results after mesh repair. The risk of serious complications and reoperation were comparable between groups.
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32. |
- Mogensen, U. M., et al.
(author)
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Sacubitril/valsartan reduces serum uric acid concentration, an independent predictor of adverse outcomes in PARADIGM-HF
- 2018
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In: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 20:3, s. 514-522
-
Journal article (peer-reviewed)abstract
- AIMS: Elevated serum uric acid concentration (SUA) has been associated with an increased risk of cardiovascular disease, but this may be due to unmeasured confounders. We examined the association between SUA and outcomes as well as the effect of sacubitril/valsartan on SUA in patients with heart failure with reduced ejection fraction (HFrEF) in PARADIGM-HF. METHODS AND RESULTS: The association between SUA and the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 8213 patients using quintiles (Q1-Q5) of SUA adjusted for baseline prognostic variables including estimated glomerular filtration rate (eGFR), diuretic dose, and log N-terminal pro-brain natriuretic peptide. Change in SUA from baseline over 12 months was also evaluated in each treatment group. Patients in Q5 (SUA >/=8.6 mg/dL) compared with Q1 (<5.4 mg/dL) were younger (62.8 vs. 64.2 years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123 mmHg), lower eGFR (57.4 vs. 76.6 mL/min/1.73 m(2) ), and greater diuretic use. Higher SUA was associated with a higher risk of the primary outcome (adjusted hazard ratios) Q5 vs. Q1 = 1.28 [95% confidence intervals (1.09-1.50), P = 0.003], cardiovascular death [1.44 (1.11-1.77), P = 0.001], HF hospitalization [1.37 (1.11-1.70), P = 0.004], and all-cause mortality [1.36 (1.13-1.64), P = 0.001]. Compared with enalapril, sacubitril/valsartan reduced SUA by 0.24 (0.17-0.32) mg/dL over 12 months (P < 0.0001). Sacubitril/valsartan improved outcomes, irrespective of SUA concentration. CONCLUSION: Serum uric acid concentration was an independent predictor of worse outcomes after multivariable adjustment in patients with HFrEF. Compared with enalapril, sacubitril/valsartan reduced SUA and improved outcomes irrespective of SUA.
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33. |
- Mogensen, U. M., et al.
(author)
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The effects of sacubitril/valsartan on coronary outcomes in PARADIGM-HF
- 2017
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In: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 188, s. 35-41
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Journal article (peer-reviewed)abstract
- Background Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. Methods and results We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization. At baseline, of 8399 patients, 3634 (43.3%) had a prior MI and 4796 (57.1%) had a history of any coronary artery disease. Among all patients, compared with enalapril, sacubitril/valsartan reduced the risk of the primary outcome (HR 0.80 [0.73-0.87], P <.001), the broader composite (HR 0.83 [0.76-0.90], P <.001) and the coronary composite (HR 0.83 [0.75-0.92], P <.001). Although each of the components of the coronary composite occurred less frequently in the sacubitril/valsartan group, compared with the enalapril group, only CV death was reduced significantly. Conclusions Compared with enalapril, sacubitril/valsartan reduced the risk of both the primary endpoint and a coronary composite outcome in PARADIGM-HF. Additional studies on the effect of sacubitril/valsartan on atherothrombotic outcomes in high-risk patients are merited.
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34. |
- Pearce, Neil E, et al.
(author)
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IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
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35. |
- Prasad, Rashmi B., et al.
(author)
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Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus
- 2021
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In: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 14:1
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Journal article (peer-reviewed)abstract
- Background: This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM). Methods: Seventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1–2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively. Results: The risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = − 0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = − 0.31, SE = 0.29, p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48, p = 9.72874e−11). All analyses were adjusted for age, body mass index, and ethnicity. Conclusions: This study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.
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36. |
- Rorth, R., et al.
(author)
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The prognostic value of troponin T and N-terminal pro B-type natriuretic peptide, alone and in combination, in heart failure patients with and without diabetes
- 2019
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 21:1, s. 40-49
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Journal article (peer-reviewed)abstract
- Aims We examined the prognostic importance of N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponin T (TnT) in heart failure patients with and without diabetes. Methods and results We measured NT-proBNP and TnT in the biomarker substudy of the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Of 1907 patients, 759 (40%) had diabetes. Median TnT in patients with diabetes was 18 (interquartile range 11-27) ng/L and 13 (9-21) ng/L in those without (P < 0.001). The TnT frequency-distribution curve was shifted to the right in patients with diabetes, compared to those without diabetes. By contrast, NT-proBNP did not differ between patients with and without diabetes. Diabetes and each biomarker were predictive of worse outcomes. Thus, patients with diabetes, an elevated TnT and a NT-proBNP level in the highest tertile (9% of all patients) had an absolute risk of cardiovascular death or heart failure hospitalization of 265 per 1000 person-years, compared to a rate of 42 per 1000 person-years in those without diabetes, a TnT < 18 ng/L and a NT-proBNP in the lowest tertile (16% of all patients). TnT remained an independent predictor of adverse outcomes in multivariable analyses including NT-proBNP. Conclusion TnT is elevated to a greater extent in heart failure patients with diabetes compared to those without (whereas NT-proBNP is not). TnT and NT-proBNP are additive in predicting risk and when combined help identify diabetes patients at extremely high absolute risk.
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37. |
- Rørth, R., et al.
(author)
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Comparison of BNP and NT-proBNP in Patients With Heart Failure and Reduced Ejection Fraction
- 2020
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In: Circulation. Heart failure. - 1941-3297. ; 13:2
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Journal article (peer-reviewed)abstract
- BACKGROUND: Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide) are widely used to aid diagnosis, assess the effect of therapy, and predict outcomes in heart failure and reduced ejection fraction. However, little is known about how these 2 peptides compare in heart failure and reduced ejection fraction, especially with contemporary assays. Both peptides were measured at screening in the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). METHODS: Eligibility criteria in PARADIGM-HF included New York Heart Association functional class II to IV, left ventricular ejection fraction ≤40%, and elevated natriuretic peptides: BNP ≥150 pg/mL or NT-proBNP ≥600 pg/mL (for patients with HF hospitalization within 12 months, BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL). BNP and NT-proBNP were measured simultaneously at screening and only patients who fulfilled entry criteria for both natriuretic peptides were included in the present analysis. The BNP/NT-proBNP criteria were not different for patients in atrial fibrillation. Estimated glomerular filtration rate <30 mL/min per 1.73 m2 was a key exclusion criterion. RESULTS: The median baseline concentration of NT-proBNP was 2067 (Q1, Q3: 1217-4003) and BNP 318 (Q1, Q3: 207-559), and the ratio, calculated from the raw data, was ≈6.25:1. This ratio varied considerably according to rhythm (atrial fibrillation 8.03:1; no atrial fibrillation 5.75:1) and with age, renal function, and body mass index but not with left ventricular ejection fraction. Each peptide was similarly predictive of death (all-cause, cardiovascular, sudden and pump failure) and heart failure hospitalization, for example, cardiovascular death: BNP hazard ratio, 1.41 (95% CI, 1.33-1.49) per 1 SD increase, P<0.0001; NT-proBNP, 1.45 (1.36-1.54); P<0.0001. CONCLUSIONS: The ratio of NT-proBNP to BNP in heart failure and reduced ejection fraction appears to be greater than generally appreciated, differs between patients with and without atrial fibrillation, and increases substantially with increasing age and decreasing renal function. These findings are important for comparison of natriuretic peptide concentrations in heart failure and reduced ejection fraction.
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38. |
- Scott, Eleanor M., et al.
(author)
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Continuous Glucose Monitoring Metrics and Birth Weight : Informing Management of Type 1 Diabetes Throughout Pregnancy
- 2022
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992. ; 45:8, s. 1724-1734
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Journal article (peer-reviewed)abstract
- OBJECTIVE To determine gestational weekly changes in continuous glucose monitoring (CGM) metrics and 24-h glucose profiles and their relationship to infant birth weight in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS An analysis of >10.5 million CGM glucose measures from 386 pregnant women with type 1 diabetes from two international multicenter studies was performed. CGM glucose metrics and 24-h glucose profiles were calculated for each gestational week, and the relationship to normal (10–90th percentile) and large (>90th percentile) for gestational age (LGA) birth weight infants was determined. RESULTS Mean CGM glucose concentration fell and percentage of time spent in the pregnancy target range of 3.5–7.8 mmol/L (63–140 mg/dL) increased in the first 10 weeks of pregnancy and plateaued until 28 weeks of gestation, before further improvement in mean glucose and percentage of time in range until delivery. Maternal CGM glucose metrics diverged at 10 weeks of gestation, with significantly lower mean CGM glucose concentration (7.1 mmol/L; 95% CI 7.05–7.15 [127.8 mg/dL; 95% CI 126.9–128.7] vs. 7.5 mmol/L; 95% CI 7.45–7.55 [135 mg/dL; 95% CI 134.1–135.9]) and higher percentage of time in range (55%; 95% CI 54–56 vs. 50%; 95% CI 49–51) in women who had normal versus LGA. The 24-h glucose profiles were significantly higher across the day from 10 weeks of gestation in LGA. CONCLUSIONS Normalbirthweightisassociatedwithachievingsignificantly lower mean CGM glucose concentration across the 24-h day and higher CGM time in range from before the end of the first trimester, emphasizing the need for a shift in clinical management, with increased focus on using weekly CGM glucose targets for optimizing maternal glycemia from early pregnancy.
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39. |
- Shaat, Nael, et al.
(author)
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Association between the rs1544410 polymorphism in the vitamin D receptor (VDR) gene and insulin secretion after gestational diabetes mellitus
- 2020
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Genetic variants involved in vitamin D metabolism have been associated with diabetes and related syndromes/diseases. We wanted to investigate possible associations of polymorphisms in genes involved in vitamin D metabolism with indices of insulin resistance and insulin secretion, and also with development of diabetes after gestational diabetes mellitus (GDM).MATERIALS AND METHODS: We have studied 376 women with previous GDM. Eight single nucleotide polymorphisms (SNPs) in the genes for vitamin D receptor (VDR) [rs731236, rs7975232, rs10735810, and rs1544410], vitamin D binding protein (DBP) [rs7041 and rs4588], and cytochrome P450 family 27 subfamily B member 1 (CYP27B1) [rs10877012 and rs4646536] were genotyped by TaqMan Allelic Discrimination Assay using the Quantstudio 7 Flex system. A 75-g oral glucose tolerance test (OGTT) was performed 1-2 years postpartum. The homeostasis model assessment of insulin resistance (HOMA-IR) and the disposition index [(insulinogenic index: I30/G30)/HOMA-IR] were used to calculate insulin resistance and insulin secretion, respectively. Serum samples for determination of 25(OH)D3 were collected at the time of the OGTT. Manifestation of diabetes was followed up to five years postpartum.RESULTS: After adjustment for BMI, age, and ethnicity, the A-allele of the VDR rs1544410 polymorphism was found to be associated with increased disposition index (difference per allele = 3.56, 95% CI: 0.4567-6.674; p = 0.03). The A-allele of the DBP rs7041 polymorphism was found to be associated with 25(OH)D3 levels (difference [in nmol/L] per allele = -5.478, 95% CI: -8.315 to -2.641; p = 0.0002), as was the T-allele of the DBP rs4588 polymorphism (OR = -6.319, 95% CI: -9.466 to -3.171; p = 0.0001). None of the SNPs were significantly associated with HOMA-IR or postpartum diabetes.CONCLUSIONS: This study provides evidence that the rs1544410 polymorphism of the VDR gene may be associated with increased insulin secretion in women after pregnancy complicated by GDM. Further studies in other populations are needed to confirm the results.
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40. |
- Shakouri, Farzaneh, et al.
(author)
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Effectiveness of fetal scalp stimulation test in assessing fetal wellbeing during labor, a retrospective cohort study
- 2020
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In: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 20:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: It is discussed whether fetal scalp stimulation (FSS) test is a reliable complimentary tool to cardiotocography (CTG) to assess fetal wellbeing during labor. The test is based on the assumption that a well-oxygenated fetus, in contrast to the depressed fetus, will respond to a certain stimulus. The aim of this study was to investigate the effectiveness of the FSS-test.METHODS: A retrospective observational study carried out Copenhagen University Hospital, Herlev, Denmark. Laboring women with singleton pregnancies in cephalic presentation after gestation week 33 and indication for fetal blood sampling (FBS) were eligible for inclusion. The FSS-test was classified as positive when an acceleration was absent at the time of FBS and negative when an acceleration was present. Lactate in scalp blood was measured by the point-of-care device LactatePro™ and pH in artery umbilical cord blood by the stationary blood gas analyzer ABL800. Lactate level < 4.2 mmol/L in scalp blood and arterial cord pH > 7.1 were cut-offs for normality.RESULTS: Three hundred eighty-five women were included. The cohort was divided by the FBS-to-delivery time: Group 1 (n = 128) ≤ 20 min, Group 2 (n = 117) 21-59 min and Group 3 (n = 140) ≥ 60 min. The proportion of FSS-positive tests differed significantly between the groups (p < 0.000). In Group 1 the sensitivity, specificity and likelihoods for scalp lactate ≥4.2 mmol/L were 81.5 (95% CI 67-90.1), 13.3 18.5 (95% CI 5.9-24.6), LHR+ 0.94 (95% CI 0.8-1.1) and LHR - 1.4 (95% CI 0.6-3.2) and for umbilical artery pH ≤ 7.10 the values were 82.6% (95% CI 61.2-95.1), 16% (95% CI 9.4-24.7), 1.0 (95% CI 0.8-1.2) and 1.1 (95% CI 0.4-3) respectively. Regardless of the FBS-to-delivery time the LHR+ for lactate ≥4.2 mmol/L increased to 1.38 (95% CI 1.2-1.6).CONCLUSION: The effectiveness of scalp stimulation test was poor for both ruling in and out fetal hypoxia during labor. Absence of a provoked acceleration seems to be a normal phenomenon in the second stage of labor.
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41. |
- Shen, L., et al.
(author)
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Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction
- 2019
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 21:8, s. 974-984
-
Journal article (peer-reviewed)abstract
- Aims Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). Methods and results We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM-Preserved (left ventricular ejection fraction >= 45%), I-Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N-terminal pro-B-type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end-diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient-years in patients without diabetes, and 10.2 and 17.1 per 100 patient-years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin-treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23-1.63, P < 0.001]. The adjusted HR is 1.67 (95% CI 1.20-2.32, p = 0.002) for sudden death (insulin-treated diabetes vs. other diabetes). Conclusions Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose-lowering treatments in HF needs to be evaluated in clinical trials.
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42. |
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43. |
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44. |
- Van der Veeken, Lennart, et al.
(author)
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Neurodevelopmental outcomes in children with isolated congenital diaphragmatic hernia : A systematic review and meta-analysis
- 2022
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In: Prenatal Diagnosis. - : Wiley. - 0197-3851 .- 1097-0223. ; 42:3, s. 318-329
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Research review (peer-reviewed)abstract
- Background: Congenital diaphragmatic hernia (CDH) reportedly has neurologic consequences in childhood however little is known about the impact in isolated CDH. Aims: Herein we aimed to describe the risk of neurodevelopmental complications in children born with isolated CDH. Materials & Methods: We systematically reviewed literature for reports on the neurological outcome of infants born with isolated CDH. The primary outcome was neurodevelopmental delay. Secondary outcomes included, motor skills, intelligence, vision, hearing, language and behavior abnormalities. Results: Thirteen out of 87 (15%) studies reported on isolated CDH, including 2624 out of 24,146 children. Neurodevelopmental delay was investigated in four studies and found to be present in 16% (3-34%) of children. This was mainly attributed to motor problems in 13% (2-30%), whereas cognitive dysfunction only in 5% (0-20%) and hearing in 3% (1-7%). One study assessed the effect of fetal surgery. When both isolated and non-isolated children were included, these numbers were higher. Discussion: This systematic review demonstrates that only a minority of studies focused on isolated CDH, with neurodevelopmental delay present in 16% of children born with CDH. Conclusion: To accurately counsel patients, more research should focus on isolated CDH cases and examine children that underwent fetal surgery.
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45. |
- Vikhareva, Olga, et al.
(author)
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Strategies to increase the rate of vaginal deliveries after cesarean without negative impact on outcomes
- 2022
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In: Midwifery. - : Elsevier BV. - 0266-6138. ; 106
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Journal article (peer-reviewed)abstract
- Objective: To compare the rate of vaginal birth after cesarean section (VBAC), including the maternal and perinatal outcomes, in two historical cohorts before and after the implementation of specific changes in the clinical practice. Design: A retrospective cohort study. Setting: Skåne University Hospital in Malmö, Sweden. Participants: including all women with one previous cesarean section (CS), who delivered during two 4-year periods: 2005–2008 (Group I) and 2013–2016 (Group II). Methods: Medical records were retrieved from the hospital's computerized medical system. The surgical reports of all women delivered by repeat CS were reviewed and the appearance of the lower uterine segment at CS was assessed. The primary outcome was VBAC. Secondary maternal outcomes were uterine rupture/dehiscence, hysterectomy and blood loss. The secondary perinatal outcomes were cord blood pH < 7.05 and perinatal mortality rate. Differences for categorical data were studied using the chi-square test and Fisher's exact test. To assess differences for continuous data t-tests were used. To determine which factors predicted VBAC both univariate and multivariate logistic regression analysis with the likelihood ratio test were performed. A two-tailed P-value < 0.05 was considered statistically significant Findings: 2017 patients were included to the study: 792 patients in Group I and 1225 in Group II. The rate of trial of labor after cesarean (TOLAC) was 65.0% and 76.9% and the VBAC rate was 49.8% and 62.0% in Group I and II respectively (p < 0.0001). Maternal and perinatal adverse outcomes were not statistically different between the two groups. Key conclusions and implications for practice: Appropriate management of women with one previous CS might increase the VBAC rate without a negative impact on maternal or perinatal outcomes. The antenatal teamwork has the greatest contribution to VBAC rate by increasing the number of women undergoing TOLAC.
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46. |
- Zaigham, Mehreen, et al.
(author)
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Maternal Arterial Blood Gas Values During Delivery: Effect of Mode of Delivery, Maternal Characteristics, Obstetric Interventions and Correlation to Fetal Umbilical Cord Blood
- 2020
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 99:12, s. 1674-1681
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Journal article (peer-reviewed)abstract
- Abstract Introduction: Obstetricians routinely use biochemical parameters from non-pregnant women to assess the condition of the laboring mother. However, it is well known that pregnancy leads to significant physiological changes in most organ systems. The aim of this study was to determine normal values for maternal arterial blood gases during vaginal deliveries as compared to control values from planned cesarean sections. We also wanted to elucidate the effect of various maternal characteristics, mode of delivery and obstetric interventions on blood gas values. Material and methods: We carried out a randomly selected, prospective-observational cohort study of 250 women undergoing vaginal delivery and 58 women undergoing planned cesarean section at Department of Obstetrics and Gynecology, Skåne University Hospital, Malmö, Sweden. Results: We found significant differences for gestational age, parity, umbilical venous blood pH, pCO2 and lactate values between the two study groups (P < 0.005). Significantly lower pH, pCO2 , pO2 , and sO2 were found in mothers delivering vaginally. Higher base deficit, hemoglobin, bilirubin, potassium, glucose and lactate were found in vaginal deliveries as compared to planned cesarean sections (P < 0.02). Maternal BMI, smoking and hypertension were not significantly correlated to acid base parameters in women with vaginal deliveries. On the other hand, multiple regression showed significant associations for the use of epidural anesthesia on maternal pH (P < 0.05) and pO2 (P < 0.01); and synthetic oxytocin on pCO2 (P = 0.08), glucose (P < 0.00) and lactate (P < 0.02) levels in maternal arterial blood. Maternal arterial pH, pCO2 and lactate values correlated significantly to values in venous umbilical cord blood (P < 0.000). Conclusions: Maternal arterial blood gas parameters varied significantly according to mode of delivery, the use of epidural anesthesia and synthetic oxytocin.
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