Long-Term Exposure to AIR Pollution and COVID-19 Mortality and Morbidity in DENmark: Who Is Most Susceptible? (AIRCODEN).

INTRODUCTION: Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective cohort studies is still sparse. Here, we have examined, in a general population, whether long-term exposure to air pollution is associated with the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19, resulting in hospitalization or death and who is most susceptible. We also examined whether long-term exposure to air pollution is associated with hospitalization or death due to COVID-19 in those who have tested positive for SARS-CoV-2. METHODS: We included all Danish residents 30 years or older who resided in Denmark on March 1, 2020. and followed them in the National COVID-19 Surveillance System until first positive test (incidence), COVID-19 hospitalization, or death until April 26, 2021. We estimated mean levels of nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <2.5 µm (PM2.5), black carbon (BC), and ozone (O3) at cohort participants' residence in 2019 by the Danish Eulerian Hemispheric Model/Urban Background Model. We used Cox proportional hazard models to estimate the associations of air pollutants with COVID-19 incidence, hospitalization, and mortality adjusting for age, sex, and socioeconomic status (SES) at the individual and area levels. We examined effect modification by age, sex, SES (education, income, wealth, employment), and comorbidities with cardiovascular disease, respiratory disease, acute lower respiratory infections, diabetes, lung cancer, and dementia. We used logistic regression to examine association of air pollutants with COVID-19-related hospitalization or death among SARS-CoV-2 positive patients, adjusting for age, sex, individual- and area-level SES. RESULTS: Of 3,721,810 people, 138,742 were infected, 11,270 hospitalized, and 2,557 died from COVID-19 during 14 months of follow-up. We detected strong positive associations with COVID-19 incidence, with hazard ratio (HR) and 95% confidence interval (CI) of 1.10 (CI: 1.05-1.14) per 0.5-µg/m3 increase in PM2.5 and 1.18 (CI: 1.14-1.23) per 3.6-µg/m3 increase in NO2. For COVID-19 hospitalizations and for COVID-19 deaths, corresponding HRs and 95% CIs were 1.09 (CI: 1.01-1.17) and 1.19 (CI: 1.12-1.27), respectively for PM2.5, and 1.23 (CI: 1.04-1.44) and 1.18 (CI: 1.03-1.34), respectively for NO2. We also found strong positive and statistically significant associations with BC and negative associations with O3. Associations were strongest in those aged 65 years old or older, participants with the lowest SES, and patients with chronic cardiovascular, respiratory, metabolic, lung cancer, and neurodegenerative disease. Among 138,742 individuals who have tested positive for SARS-Cov-2, we detected positive association with COVID-19 hospitalizations (N = 11,270) with odds ratio and 95% CI of 1.04 (CI: 1.01- 1.08) per 0.5-µg/m3 increase in PM2.5 and 1.06 (CI: 1.01-1.12) per 3.6-µg/m3 increase in NO2, but no association with PM with an aerodynamic diameter <10 µm (PM10), BC, or O3, and no association between any of the pollutants and COVID-19 mortality (N = 2,557). CONCLUSIONS: This large nationwide study provides strong new evidence in support of association between long-term exposure to air pollution and COVID-19.

Core Imaging Library - Part I: a versatile Python framework for tomographic imaging.

We present the Core Imaging Library (CIL), an open-source Python framework for tomographic imaging with particular emphasis on reconstruction of challenging datasets. Conventional filtered back-projection reconstruction tends to be insufficient for highly noisy, incomplete, non-standard or multi-channel data arising for example in dynamic, spectral and in situ tomography. CIL provides an extensive modular optimization framework for prototyping reconstruction methods including sparsity and total variation regularization, as well as tools for loading, preprocessing and visualizing tomographic data. The capabilities of CIL are demonstrated on a synchrotron example dataset and three challenging cases spanning golden-ratio neutron tomography, cone-beam X-ray laminography and positron emission tomography. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

Pelvic insufficiency fractures frequently occur following preoperative chemo-radiotherapy for rectal cancer - a nationwide MRI study.

AIM: The aim of this prospective case-control study was to evaluate the rate of pelvic insufficiency fractures (PIFs) in Denmark using MRI at the 3-year follow-up. All patients had rectal cancer and had undergone surgery with or without preoperative chemo-radiotherapy (CRT). METHOD: Patients registered with primary rectal cancer in the Danish Colorectal Cancer Group database, who underwent rectal cancer resection from April 2011 through August 2012, were invited to participate in a national MRI study aiming to detect local recurrence and evaluate quality of the surgical treatment. Pelvic MRI including bone-specific sequences 3 years after treatment was obtained. The primary outcome was the rate of PIFs; secondary outcome was risk factors of PIFs evaluated in multivariate analysis. RESULTS: During the study period, 890 patients underwent rectal cancer surgery. Of these, 403 patients were included in the MRI study and had a 3-year follow-up MRI. PIFs were detected in 49 (12.2%; 95% CI 9.0-15.4) patients by MRI. PIFs were detected in 39 patients (33.6%; 95% CI 24.9-42.3) treated with preoperative CRT compared to 10 (3.5%; 95% CI 1.3-5.6) non-irradiated patients (P < 0.001). In a multivariate analysis female gender (OR = 3.52; 95% CI 1.7-7.5), age above 65 years (OR = 3.20; 95% CI 1.5-6.9) and preoperative CRT (OR = 14.20; 95% CI 6.1-33.1) were significant risk factors for PIFs. CONCLUSION: Preoperative CRT in the treatment of rectal cancer was associated with a 14-fold higher risk of PIFs after 3 years, whereas female gender and age above 65 years each tripled the risk of PIFs.

Periapical infection may affect birth outcomes via systemic inflammation.

OBJECTIVES: Maternal dental periapical infections are associated with preterm birth and intrauterine growth restriction. This study investigates whether the association is mediated through bacterial spread from periapical lesions to placenta (direct pathway) or systemic inflammatory reaction (indirect pathway). MATERIALS AND METHODS: We compared birth outcomes in Malawian mothers with and without periapical infection. As markers of a direct pathway, we identified placental bacteria using a 16S rDNA approach and assessed histological evidence of inflammation in the placenta and amniotic membranes. We measured C-reactive protein, alpha-1-acid glycoprotein, and salivary cortisol as markers of an indirect pathway. We used regression models to associate the predictor variables with duration of pregnancy and newborn size. RESULTS: Of 1,024 women, 23.5% had periapical infection. There was no association of periapical infection with either bacterial DNA or histological inflammation in placenta or membranes. Periapical infection was associated with C-reactive protein, alpha-1-acid glycoprotein, and cortisol concentrations in a dose-dependent manner at 36 weeks. Addition of alpha-1-acid glycoprotein or cortisol concentration into regression models attenuated the association between periapical infection and pregnancy outcomes. CONCLUSION: There was no evidence of direct spread of periapical bacteria to the placenta. Periapical infections and adverse pregnancy outcomes are in part mediated through systemic inflammation.

Echinococcus multilocularis in Denmark 2012-2015: high local prevalence in red foxes.

In Western Europe, the Echinococcus multilocularis lifecycle is predominantly sylvatic, typically involving red foxes (Vulpes vulpes) as the main definitive hosts with Microtus spp. and Arvicola spp. as intermediate hosts. During a 4-year surveillance study (2012-2015), Danish red foxes and raccoon dogs (n = 1345) were examined for E. multilocularis. Moreover, 134 insectivores and rodents collected in South Jutland during spring and summer 2016 were examined for the presence of metacestodes. The sedimentation and counting technique and molecular typing were used to identify E. multilocularis infections in the carnivores, while the rodent livers were examined macro- and microscopically for parasite lesions. Following morphological identification of E. multilocularis adult worms, the identity was verified by sequence analysis of the 12S rRNA gene in most cases (n = 13). Echinococcus multilocularis infection was demonstrated in 19 red foxes (Vulpes vulpes) originating from only two specific areas of South Jutland, namely Højer and Grindsted, and in two raccoon dogs (Nyctereutes procyonoides), originating from Højer. In Højer, 28.5% (CI 95% 11.7-45.3) of the examined red foxes were E. multilocularis positive per year. Moreover, positive red foxes were identified each year from 2012 to 2015, while E. multilocularis positive red foxes were only identified in Grindsted in 2013 (4.0%) and 2014 (6.4%). In contrast, all collected rodents were negative for E. multilocularis. We conclude that E. multilocularis is locally endemic in South Jutland with a high local prevalence in Højer.

Timeline of changes in appetite during weight loss with a ketogenic diet.

BACKGROUND/OBJECTIVE: Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low-energy diet (VLED). SUBJECTS/METHODS: Thirty-one sedentary adults (18 men), with obesity (body mass index: 37±4.5 kg m-2) underwent 8 weeks (wks) of a VLED followed by 4 wks of weight maintenance. Body weight and composition, subjective feelings of appetite and appetite-related hormones (insulin, active ghrelin (AG), active GLP-1, total PYY and CCK) were measured in fasting and postprandially, at baseline, on day 3 of the diet, 5 and 10% WL, and at wks 9 and 13. Data are shown as mean±s.d. RESULTS: A significant increase in fasting hunger was observed by day 3 (2±1% WL), (P<0.01), 5% WL (12±8 days) (P<0.05) and wk 13 (17±2% WL) (P<0.05). Increased desire to eat was observed by day 3 (P<0.01) and 5% WL (P<0.05). Postprandial prospective food consumption was significantly reduced at wk 9 (16±2% WL) (P<0.01). Basal total PYY was significantly reduced at 10% WL (32±8 days) (P<0.05). Postprandial active GLP-1 was increased at 5% WL (P<0.01) and CCK reduced at 5 and 10% WL (P<0.01, for both) and wk 9 (P<0.001). Basal and postprandial AG were significantly increased at wk 13 (P<0.001, both). CONCLUSIONS: WL with a ketogenic VLED transiently increases the drive to eat up to 3 weeks (5% WL). After that, and while participants are ketotic, a 10-17% WL is not associated with increased appetite. However, hunger feelings and AG concentrations increase significantly from baseline, once refeeding occurs.

Editor's Choice - The National Norwegian Carotid Study: Time from Symptom Onset to Surgery is too Long, Resulting in Additional Neurological Events.

OBJECTIVE/BACKGROUND: The objective was to observe for 1 year all patients in Norway operated on for symptomatic carotid stenosis with respect to (i) the time from the index event to surgery and neurological events during this time; (ii) the level in the healthcare system causing delay of surgical treatment; and (iii) the possible relationship between peri-operative use of platelet inhibitors and neurological events while awaiting surgery. METHODS: This was a prospective national multicentre study of a consecutive series of symptomatic patients. Patients were eligible for inclusion when referred for surgery. An index event was defined as the neurological event prompting contact with the healthcare system. All 15 departments in Norway performing carotid endarterectomy (CEA) participated. RESULTS: Three hundred and seventy one patients were eligible for inclusion between 1 April 2014 and 31 March 2015, and 368 patients (99.2%) were included. Fifty-four percent of the patients contacted their general practitioner on the day of the index event. Primary healthcare referred 84.2% of the patients to hospital on the same day as examined. In hospital median time from admission to referral for vascular surgery was 3 days. Median time between referral to the operating unit and actual CEA was 5 days. Overall, 61.7% of the patients were operated on within 2 weeks of the index event. Twelve patients (3.3%) suffered a new neurological event while awaiting surgery. The percentage of patients on dual antiplatelet therapy was lower (25.0%) in this group than among the other patients (62.6%) (p = .008). The combined 30 day mortality and stroke rate was 3.8%. CONCLUSION: This national study with almost complete inclusion and follow-up shows that the delays occur mainly at patient level and in hospital. The delay is associated with new neurological events. Dual antiplatelet therapy is associated with reduced risk of having a new neurological event before surgery.

Automated angular and translational tomographic alignment and application to phase-contrast imaging.

X-ray computerized tomography (CT) is a 3D imaging technique that makes use of x-ray illumination and image reconstruction techniques to reproduce the internal cross-sections of a sample. Tomographic projection data usually require an initial relative alignment or knowledge of the exact object position and orientation with respect to the detector. As tomographic imaging reaches increasingly better resolution, thermal drifts, mechanical instabilities, and equipment limitations are becoming the main dominant factors contributing to sample positioning uncertainties that will further introduce reconstruction artifacts and limit the attained resolution in the final tomographic reconstruction. Alignment algorithms that require manual interaction impede data analysis with ever-increasing data acquisition rates, supplied by more brilliant sources. We present in this paper an iterative reconstruction algorithm for wrapped phase projection data and an alignment algorithm that automatically takes 5 degrees of freedom, including the possible linear and angular motion errors, into consideration. The presented concepts are applied to simulated and real measured phase-contrast data, exhibiting a possible improvement in the reconstruction resolution. A MATLAB implementation is made publicly available and will allow robust analysis of large volumes of phase-contrast tomography data.

The International Haemovigilance Network Database for the Surveillance of Adverse Reactions and Events in Donors and Recipients of Blood Components: technical issues and results.

BACKGROUND AND OBJECTIVES: The International Haemovigilance Network's ISTARE is an online database for surveillance of all adverse reactions (ARs) and adverse events (AEs) associated with donation of blood and transfusion of blood components, irrespective of severity or the harm caused. ISTARE aims to unify the collection and sharing of information with a view to harmonizing best practices for haemovigilance systems around the world. MATERIALS AND METHODS: Adverse reactionss and adverse events are recorded by blood component, type of reaction, severity and imputability to transfusion, using internationally agreed standard definitions. RESULTS: From 2006 to 2012, 125 national sets of annual aggregated data were received from 25 countries, covering 132.8 million blood components issued. The incidence of all ARs was 77.5 per 100 000 components issued, of which 25% were severe (19.1 per 100 000). Of 349 deaths (0.26 per 100 000), 58% were due to the three ARs related to the respiratory system: transfusion-associated circulatory overload (TACO, 27%), transfusion-associated acute lung injury (TRALI, 19%) and transfusion-associated dyspnoea (TAD, 12%). Cumulatively, 594 477 donor complications were reported (rate 660 per 100 000), of which 2.9% were severe. CONCLUSIONS: ISTARE is a well-established surveillance tool offering important contributions to international efforts to maximize transfusion safety.

Danish translation and validation of the Oslo Sports Trauma Research Centre questionnaires on overuse injuries and health problems.

The Oslo Sports Trauma Research Centre Overuse Injury Questionnaire (OSTRC-O) and the Oslo Sports Trauma Research Centre questionnaire on Health Problems (The OSTRC-H) make it possible to monitor illness and injury at regular intervals capturing prevalence and incidence of acute injury, overuse injury, and illnesses. The aim of this study was to translate, culturally adapt, and establish the face validity of the OSTRC-O and the OSTRC-H into a Danish context (DK) through cognitive interviews and the assessment of test-retest reliability. The OSTRC-O.DK was distributed to 57 heterogenous respondents; response rate was 89%. The OSTRC-H was distributed to 58 heterogenous respondents; response rate was 86%. No major disagreements were observed between the original and translated versions of the questionnaires. The OSTRC-O had high internal consistency (Cronbach's alpha 0.80-0.93). The primary reliability analyses including all participants, showed reliability ICC: 0.62 (95% CI: 0.42-0.77. The secondary reliability analyses that only included subjects who did not change injury region from the test to the retest showed an ICC of 0.86 (95% CI: 0.77-0.92).The questionnaires were found to be valid, reliable, and acceptable for use in a Danish population.

Danish VISA-A questionnaire with validation and reliability testing for Danish-speaking Achilles tendinopathy patients.

The VISA-A questionnaire has proven to be a valid and reliable tool for assessing severity of Achilles tendinopathy (AT). The aim was to translate and cross-culturally adapt the VISA-A questionnaire for a Danish-speaking AT population, and subsequently perform validity and reliability tests. Translation and following cross-cultural adaptation was performed as translation, synthesis, reverse translation, expert review, and pretesting. The final Danish version (VISA-A-DK) was tested for reliability on healthy controls (n = 75) and patients (n = 36). Tests for internal consistency, validity, and structure were performed on 71 patients. VISA-A-DK showed good reliability for patients (r = 0.80 ICC = 0.79) and healthy individuals (r = 0.98 ICC = 0.97). Internal consistency was 0.73 (Cronbach's alpha). The mean VISA-A-DK score in AT patients was 51 [47-55]. This was significantly lower than healthy controls with a score of 93 (90-95). Criterion validity was considered good when comparing the scores of the Danish version with the original version in both healthy individuals and patients. VISA-A-DK is a valid and reliable instrument and has shown compatible to the original version in assessment of AT patients. VISA-A-DK is a useful tool in the assessment of AT, both in research and in a clinical setting.

Pain following blood donation: a questionnaire study of long-term morbidity (LTM) in blood donors.

BACKGROUND: Nerve injury is a main cause of long-term morbidity following blood donation, but little is known about symptoms, impact, prognosis and underlying cause. MATERIALS AND METHODS: A questionnaire, designed to characterize pain and estimate the prevalence of neuropathic pain, was sent to all blood donors registered with a complication related to 3 297 674 blood donations in Denmark from 2000-2009, with a local complication mainly characterized by pain, with severity grade 'long-term morbidity' and imputability grade 'definite' or 'probably'. RESULTS: The questionnaire was sent to 152 donors (4·6 per 100 000 donations). Response rate was 88/152 (57·9%). At the time of the questionnaire, which was between 12 months and 10 years after the blood donation, 69/88, who responded (78·4%) still experienced symptoms. Of the 69 donors with persistent symptom, pain occurred in 51 donors (74%) was moderate to severe in 24/69 donors (35%) and had an impact on daily activity in 17/69 (25%). Neuropathic pain was estimated to be the underlying cause of symptom in 30-52% of the 69 donors with persistent symptoms, using three different systems for estimation, corresponding to 0·6-1·1/100 000 donations. DISCUSSION: Although a rare complication, nerve injury after blood donation may lead to long-term morbidity and may become chronic in a small proportion of donors. The most common symptoms are pain, and we estimate that neuropathic pain can be the underlying cause.

Translation and validation of the Danish Foot Function Index (FFI-DK).

The objective of this study was to translate the Foot Function Index (FFI) for use in Danish-speaking patients with foot complaints. The FFI consists of 23 items scored on a numeric rating scale from 0 to 10. The 23 items are grouped into three subscales: pain (nine items), activity limitation (five items), and disability (nine items). The Danish FFI was developed according to the recommended forward/backward translation protocol. The data analysis included reliability [intraclass correlation coefficient (ICC) 2.1] and internal consistency (Cronbach's alpha). Excellent internal consistency was shown for the three subscales: pain (0.99), disability (0.98), and activity limitation (0.98), as for the total score (0.97). The test-retest reliability was excellent: pain subscale: ICC 0.98 [95% confidence interval (CI): 0.97-0.99]; activity limitation subscale: ICC: 0.95 (95% CI: 0.91-0.98); disability subscale: ICC 0.97 (95% CI: 0.95-0.98); total score: ICC: 0.95 (95% CI: 0.91 to 0.98). The mean difference between test and retest was below 1 point and P > 0.08. Bland-Altman plots showed no significant or clinically relevant differences from test to retest in any of the subscales or in the total score. The Danish version of the FFI was found to be valid and reliable and therefore acceptable for use in the Danish population.

Persistent infections with infectious pancreatic necrosis virus (IPNV) of different virulence in Atlantic salmon, Salmo salar L.

Infectious pancreatic necrosis virus (IPNV) is a prevalent pathogen in fish worldwide. The virus causes substantial mortality in Atlantic salmon juveniles and smolts when transferred to sea water and persistent infection in surviving fish after disease outbreaks. Here, we have investigated the occurrence of the virus as well as the innate immune marker Mx in the head kidney (HK) of Atlantic salmon throughout an experimental challenge covering both a fresh and a seawater phase. The fish were challenged with a high (HV) and low virulence (LV) IPNV. Both isolates caused mortality due to reactivation of the virus after transfer to sea water. In the freshwater phase, higher levels of virus transcripts were detected in the HK of fish infected with LV IPNV compared to HV, suggesting that the HV isolate is able to limit its own replication to a level where the innate immune system is not alerted. Further, ex vivoHK leucocytes derived from fish infected with the two isolates were stimulated with CpG DNA. Significantly, higher IFN levels were found in the LV compared to the HV group in the freshwater phase. This suggests that the viruses attenuate the antiviral host immune response at different levels which may contribute to the observed differences in disease outcome.

Overexpression of PLIN5 in skeletal muscle promotes oxidative gene expression and intramyocellular lipid content without compromising insulin sensitivity.

AIMS/HYPOTHESIS: While lipid deposition in the skeletal muscle is considered to be involved in obesity-associated insulin resistance, neutral intramyocellular lipid (IMCL) accumulation per se does not necessarily induce insulin resistance. We previously demonstrated that overexpression of the lipid droplet coat protein perilipin 2 augments intramyocellular lipid content while improving insulin sensitivity. Another member of the perilipin family, perilipin 5 (PLIN5), is predominantly expressed in oxidative tissues like the skeletal muscle. Here we investigated the effects of PLIN5 overexpression - in comparison with the effects of PLIN2 - on skeletal muscle lipid levels, gene expression profiles and insulin sensitivity. METHODS: Gene electroporation was used to overexpress PLIN5 in tibialis anterior muscle of rats fed a high fat diet. Eight days after electroporation, insulin-mediated glucose uptake in the skeletal muscle was measured by means of a hyperinsulinemic euglycemic clamp. Electron microscopy, fluorescence microscopy and lipid extractions were performed to investigate IMCL accumulation. Gene expression profiles were obtained using microarrays. RESULTS: TAG storage and lipid droplet size increased upon PLIN5 overexpression. Despite the higher IMCL content, insulin sensitivity was not impaired and DAG and acylcarnitine levels were unaffected. In contrast to the effects of PLIN2 overexpression, microarray data analysis revealed a gene expression profile favoring FA oxidation and improved mitochondrial function. CONCLUSIONS/INTERPRETATION: Both PLIN2 and PLIN5 increase neutral IMCL content without impeding insulin-mediated glucose uptake. As opposed to the effects of PLIN2 overexpression, overexpression of PLIN5 in the skeletal muscle promoted expression of a cluster of genes under control of PPARα and PGC1α involved in FA catabolism and mitochondrial oxidation.

Polymorphisms in the interleukin-1 gene locus and chronic periodontitis in patients with atherosclerotic and aortic aneurysmal vascular diseases.

Chronic periodontitis (CP) and atherosclerotic and aortic aneurysmal vascular diseases (VD) are inflammatory conditions that share a number of predisposing factors. They have a complex genetic heritability and may share genetic risk factors, but a well-defined relationship is still not determined. In addition, distinct genetic patterns of predisposition have been associated with these diseases. Here, we investigated the association of polymorphisms in the IL-1 gene locus with CP in a case-case study analysing VD patients with or without CP. Seventy-four patients with VD of whom 36 had CP were genotyped for single nucleotide polymorphisms in the IL1A -889 (rs1800587), IL1B +3954 (rs1143634) and IL1B at -511 (rs16944) genes and for VNTR polymorphisms in the IL1RN gene. A significantly higher frequency (17%) for allele 1 (four repeats) of the IL1RN VNTR gene was found among the VD patients with CP compared to those without CP. In addition, the frequency of the IL1RN VNTR genotypes 1/1 (4/4 repeats) and 2/2 (2/2 repeats) were significantly higher and lower, respectively, in VD patients with CP. These findings suggest an association of genetic polymorphisms in the IL1-gene locus with risk for CP in patients with VD. The carriage of the risk genotypes, the development and the subsequent influence of CP on systemic health may constitute an additional burden in the pathogenesis of VD. This emphasizes the importance of effective periodontal treatment in patients with VD.

Metabolic effects of lifestyle intervention in obese pregnant women. Results from the randomized controlled trial 'Lifestyle in Pregnancy' (LiP).

AIMS: The Lifestyle in Pregnancy intervention in obese pregnant women resulted in significantly lower gestational weight gain compared with the control group, but without improvement in rates of clinical pregnancy complications. The impact of the lifestyle intervention on metabolic measurements in the study participants is now reported. METHODS: The Lifestyle in Pregnancy study was a randomized controlled trial among 360 obese women (BMI 30-45 kg/m²) who were allocated in early pregnancy to lifestyle interventions with diet counselling and physical activities or to the control group. Fasting blood samples, including plasma glucose, insulin, lipid profile and capillary blood glucose during a 2-h oral glucose tolerance test were carried out three times throughout pregnancy. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance. RESULTS: Three hundred and four women (84%) were followed until delivery. Women in the intervention group had a significantly lower change in insulin resistance (HOMA-IR) from randomization to 28-30 weeks' gestation compared with control subjects (mean ± SD: 0.7 ± 1.3 vs. 1.0 ± 1.3, P = 0.02). Despite a significantly lower gestational weight gain in the intervention group, there was no difference between the groups with respect to total cholesterol, HDL, LDL or triglycerides. CONCLUSIONS: Lifestyle intervention in obese pregnant women resulted in attenuation of the physiologic pregnancy-induced insulin resistance. Despite restricted gestational weight gain, there were no changes in glucose or lipid metabolism between the groups.

Including ethical considerations in models for first-trimester screening for pre-eclampsia.

Recent efforts to develop reliable and efficient early pregnancy screening programmes for pre-eclampsia have focused on combining clinical, biochemical and biophysical markers. The same model has been used for first-trimester screening for fetal aneuploidies i.e. prenatal diagnosis (PD), which is routinely offered to all pregnant women in many developed countries. Some studies suggest combining PD and pre-eclampsia screening, so women can be offered testing for a number of conditions at the same clinical visit. A combination of these tests may be practical in terms of saving time and resources; however, the combination raises ethical issues. First-trimester PD and pre-eclampsia screening entail qualitative differences which alter the requirements for disclosure, non-directedness and consent with regard to the informed consent process. This article explores the differences related to the ethical issues raised by PD and pre-eclampsia in order to elucidate which factors are relevant to deciding the type of information and consent required in each context from the perspective of the ethical principles of beneficence and autonomy. Furthermore, it argues that ensuring respect for patient autonomy is context dependent and, consequently, pre-eclampsia screening and PD should be performed independently of one another.

Increasing use of antibiotics in pregnancy during the period 2000-2010: prevalence, timing, category, and demographics.

OBJECTIVE: The aim of this study was to describe the use of antibiotics in a national population-based cohort of pregnant Danish women between 2000 and 2010. DESIGN: Register-based, population-wide, cohort study. SETTING: Denmark, from 2000 to 2010. POPULATION: All pregnancies among Danish residents during the period 2000-2010 were included for analysis. METHODS: Data were obtained from the Danish Medical Birth Registry, the Danish National Patient Registry, and the Registry of Medicinal Product Statistics. The filled prescriptions for systemic antibacterial, antimycotic, and antiviral drugs, as well as intravaginally applied antibiotics, were analysed. Associations with demographic variables were assessed using multivariate analysis. MAIN OUTCOME MEASURES: Filled prescriptions for antibiotic drugs during pregnancy. RESULTS: We included 987 973 pregnancies in Denmark from 2000 to 2010; 38.9% of women with a delivery and 14.8% of women with a miscarriage or termination of pregnancy had one or more antibiotic treatments during pregnancy. Systemic antibacterial drugs were the most frequently used drug group, with filled prescriptions for 33.4% of all deliveries and 12.6% of all abortions. This proportion increased from 28.4% in 2000 to 37.0% in 2010 among deliveries. The biggest change was seen for pivmecillinam, which increased among deliveries from 6.3% in 2000 to 19.5% in 2010. Obese (odds ratio 1.51; 95% CI 1.47-1.56), young (odds ratio 1.35; 95% CI 1.30-1.39), and low-educated women (odds ratio 1.37; 95% CI 1.35-1.1.39) tended to fill more prescriptions of antibiotics during pregnancy. CONCLUSIONS: Overall, the number of women who filled prescriptions of antibiotics increased during the 11-year study period. In 2010, at least 41.5% of all deliveries were exposed to antibiotic therapy during pregnancy.