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.

The association between seasonal influenza-like illness cases and foetal death: a time series analysis.

It has been reported that foetal death follows a seasonal pattern. Influenza virus infection has been postulated as one possible contributor to this seasonal variation. This ecological study explored the temporal association between the influenza activity and the frequency of foetal death. Time series analysis was conducted using weekly influenza-like illness consultation proportions from the Danish sentinel surveillance system and weekly proportions of spontaneous abortions and stillbirths from hospital registers from 1994 to 2009. The association was examined in an autoregressive (AR) integrated (I) moving average (MA) model and subsequently analysed with cross-correlation functions. Our findings confirmed the well-known seasonality in influenza, but also seasonality in spontaneous abortion. No clear pattern of seasonality was found for stillbirths, although the analysis exposed dependency between observations. One final AR integrated MA model was identified for the influenza-like illness (ILI) series. We found no statistically significant relationship between weekly influenza-like illness consultation proportions and weekly spontaneous abortion proportions (five lags: P = 0.52; 11 lags: P = 0.91) or weekly stillbirths (five lags: P = 0.93; 11 lags: P = 0.40). Exposure to circulating influenza during pregnancy was not associated with rates of spontaneous abortions or stillbirths. Seasonal variations in spontaneous abortion were confirmed and this phenomenon needs further investigation.

Criterion validity of the Physical Activity Scale (PAS2) in Danish adults.

BACKGROUND: The Physical Activity Scale (PAS2) was developed to measure physical activity (PA) during work, transportation and leisure time, in the Danish adult population. The objective of this study was to assess the criterion validity of PAS2 against a combined accelerometer and heart rate monitor in Danish adults and to investigate if the criterion validity differed by socio-demographic factors and body mass index. METHOD: A total of 330 Danish adults (mean age = 46.7 years, 38.5% men) participating in the Health2008 study completed the PAS2 questionnaire and wore a combined accelerometer and heart rate sensor for seven days. Average daily estimates from PAS2 were categorised into time spent in sedentary behaviour, light PA, moderate PA and vigorous PA and were compared to the objective measures. RESULTS: PAS2 accounted for 19.5 hours/day on average. Time spent in sedentary behaviour, light and moderate-intensity PA was weakly correlated with objective data (polychoric correlation coefficients (PCC): 0.18-0.20), whereas vigorous intensity PA was moderately correlated (PCC: 0.54, p = 0.04). Mean bias was -2.3 hours/day (95% limits of agreement (LoA): -9.04 to 4.34) for sedentary behaviour, 1.68 hours/day (LoA: 8.02 to -4.62) for light activity, 0.55 hours/day (LoA: 3.37 to -2.26) for moderate activity and 0.12 hours/day (LoA: 0.57 to 0.33) for vigorous activity. Criterion validity was lower in women, in participants who were above 40 years, overweight, had short education and were unemployed. CONCLUSIONS: PAS2 overestimated time spent on light, moderate and vigorous intensity PA and underestimated time spent on sedentary behaviour. Validity differed by key socio-demographic characteristics.

Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors.

AIMS: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). METHODS: Data from national and regional health surveys in Norway (1974-2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. RESULTS: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98-3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77-2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48-2.24). CONCLUSIONS: Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial.

AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS: During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION: Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

Advanced paternal age and mortality of offspring under 5 years of age: a register-based cohort study.

STUDY QUESTION: Do children born to fathers of advanced age have an increased risk of dying before the age of 5 years? SUMMARY ANSWER: Children born to fathers aged 40 years or more have an increased risk of dying in early childhood due to an excess risk of fatal congenital anomalies, malignancies and external causes. WHAT IS KNOWN ALREADY: Advanced paternal age has previously been associated with adverse reproductive outcomes and some long-term health problems in the offspring. This is possibly due to specific point mutations, a condition known to increase in the sperm with increasing paternal age. STUDY DESIGN, SIZE, DURATION: A Danish population-based register study, designed as a prospective cohort study, of 1 575 521 live born children born from 1978 to 2004. The age of the child (in days) was used as the underlying time and the children entered the cohort the day they were born and were followed until 31 December 2009. The children were censored on date of turning 5 years, date of death or date of emigration, whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from population-covering registers from Statistics Denmark including the Integrated Database for Labour Market Research, the Medical Birth Registry and the Registry of Causes of Death was linked using the unique civil registry number. Hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the risk of under-five mortality. The effect of paternal age was examined using restricted cubic splines and paternal age groups. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with children born to fathers aged 30-34 years, a statistically significant excess risk was found for children born to fathers aged 40-44 years [HR: 1.10 (95% CI: 1.00-1.21)] and children born to fathers aged 45+ years [HR: 1.16 (95% CI: 1.02-1.32)]. When only looking at 1-5 year olds, the relative risk (HR) among children born to fathers aged 40-44 years increased to 1.24 (95% CI: 1.00-1.53) and the risk in the oldest paternal age group (45+ years) rose to 1.65 (95% CI: 1.24-2.18). The results suggest that the elevated risk for children of fathers aged 40 years or more was primarily attributed to an elevated risk of dying from congenital malformations, malignancies and external causes. LIMITATIONS, REASONS FOR CAUTION: Specific causes of death might be misclassified; however, this is not likely to be dependent on paternal age. In some cases, the biological father may differ from the father registered. This misclassification is most likely non-differential. WIDER IMPLICATIONS OF THE FINDINGS: The excess risk of mortality among children born to older fathers is in accordance with the literature. The association needs further attention as it can provide valuable knowledge of the etiology of genetic diseases. Also, the association could become of greater importance in the future if the proportion of fathers aged 40+ years keeps growing. STUDY FUNDING/COMPETING INTEREST (S): None.

Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries.

OBJECTIVE: To assess disparities in pre-eclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries. DESIGN: Cross-country comparative study of linked population-based databases. SETTING: Provincial or regional obstetric delivery data from Australia, Canada, Spain and the USA and national data from Denmark and Sweden. POPULATION: All immigrant and non-immigrant women delivering in the six industrialised countries within the most recent 10-year period available to each participating centre (1995-2010). METHODS: Data was collected using standardised definitions of the outcomes and maternal regions of birth. Pooled data were analysed with multilevel models. Within-country analyses used stratified logistic regression to obtain odds ratios (OR) with 95% confidence intervals (95% CI). MAIN OUTCOME MEASURES: Pre-eclampsia, eclampsia and pre-eclampsia with prolonged hospitalisation (cases per 1000 deliveries). RESULTS: There were 9,028,802 deliveries (3,031,399 to immigrant women). Compared with immigrants from Western Europe, immigrants from Sub-Saharan Africa and Latin America & the Caribbean were at higher risk of pre-eclampsia (OR: 1.72; 95% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native-born women, European and East Asian immigrants were at lower risk in most industrialised countries. Spain exhibited the largest disparities and Australia the smallest. CONCLUSION: Immigrant women from Sub-Saharan Africa and Latin America & the Caribbean require increased surveillance due to a consistently high risk of pre-eclampsia and eclampsia.

Suppression of Cucumber Powdery Mildew by Supplemental UV-B Radiation in Greenhouses Can be Augmented or Reduced by Background Radiation Quality.

This study demonstrates that the spectral quality of radiation sources applied with ultraviolet-B (UV-B; background radiation) affects the suppression of cucumber powdery mildew (Podosphaera xanthii) by UV-B. Suppression provided by daily UV-B exposure of 1 W/m2 for 10 min was greatest in the presence of red light or by a complete lack of background light, and powdery mildew suppression was least in the presence of ultraviolet-A (UV-A) or blue radiation compared with plants exposed only to 16 h of daily natural light supplemented with high-pressure sodium lamps that supply broad-spectrum radiation with peaks in the yellow-orange region. Exposure of powdery mildew-inoculated plants to supplemental red light without UV-B, beginning at the end of the daylight period, also reduced disease severity; however, supplemental blue light applied in the same fashion had no effect. Daily application of UV-B at 1 W/m2 beginning on the day of inoculation significantly reduced the severity of powdery mildew to 15% compared with 100% severity on control plants. Maximum suppression of powdery mildew was observed following 15 min of exposure to UV-B (1.1% severity compared with 100% severity on control plants) but exposure time had to be limited to 5 to 10 min to reduce phytotoxicity. There was no additional disease suppression when plants were exposed to UV-B beginning 2 days prior to inoculation compared with plants exposed to UV-B beginning on the day of inoculation. UV-B inhibited germination, infection, colony expansion, and sporulation of P. xanthii. The results suggest that efficacy of UV-B treatments, alone or in combination with red light, against P. xanthii can be enhanced by exposure of inoculated plants to these wavelengths of radiation during the night, thereby circumventing the counteracting effects of blue light and UV-A radiation. The effect of UV-B on powdery mildew seemed to be directly upon the pathogen, rather than induced resistance of the host. Night exposure of plants to 5 to 10 min of UV-B at 1 W/m2 and inexpensive, spectral-specific, light-emitting diodes may provide additional tools to suppress powdery mildews of diverse greenhouse crops.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome -- a randomized study (SYSDIET).

BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. METHODS: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra. CONCLUSIONS: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

VEGFA variants are associated with pre-school lung function, but not neonatal lung function.

BACKGROUND: Vascular endothelial growth factor (VEGF) is implicated in airway remodelling and asthma development. We studied VEGFA gene variants and plasma levels and the development of lung function, bronchial hyperresponsiveness and asthma in childhood. METHODS: We analysed 13 SNPs in the VEGFA gene in 411 children from the COPSAC2000 high-risk birth cohort. Asthma was diagnosed prospectively, and lung function measurements were obtained at birth and 6 years of age. Plasma VEGF levels were measured at 18 months of age. We used a Bonferroni adjusted significance level. Findings were replicated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort at age 8. RESULTS: At age six, three SNPs from the same linkage block were associated with FEV1 (rs699947, P = 1.31E-05), independent of asthma, and there were suggestive associations between FEV1/FVC ratio and rs833052 and maximal mid-expiratory flow and rs6900017. Replication in the PIAMA cohort showed borderline association between FEV1 and rs699947 and significant meta-analysis result. SNPs upstream and nearby rs699947 were nominally associated with VEGF plasma levels. VEGF levels were not associated with asthmatic symptoms or lung function measures. CONCLUSIONS AND CLINICAL RELEVANCE: VEGF gene variants are associated with lung function at school age, but not at birth, suggesting a role of VEGF in post-natal lung function development.

Deep phenotyping of the unselected COPSAC2010 birth cohort study.

BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.

PET hypoxia imaging with FAZA: reproducibility at baseline and during fractionated radiotherapy in tumour-bearing mice.

PURPOSE: Tumour hypoxia is linked to treatment resistance. Positron emission tomography (PET) using hypoxia tracers such as fluoroazomycin arabinoside (FAZA) may allow identification of patients with hypoxic tumours and the monitoring of the efficacy of hypoxia-targeting treatment. Since hypoxia PET is characterized by poor image contrast, and tumour hypoxia undergoes spontaneous changes and is affected by therapy, it remains unclear to what extent PET scans are reproducible. Tumour-bearing mice are valuable in the validation of hypoxia PET, but identification of a reliable reference tissue value (blood sample or image-derived muscle value) for repeated scans may be difficult due to the small size of the animal or absence of anatomical information (pure PET). Here tumour hypoxia was monitored over time using repeated PET scans in individual tumour-bearing mice before and during fractionated radiotherapy. METHODS: Mice bearing human SiHa cervix tumour xenografts underwent a PET scan 3 h following injection of FAZA on two consecutive days before initiation of treatment (baseline) and again following irradiation with four and ten fractions of 2.5 Gy. On the last scan day, mice were given an intraperitoneal injection of pimonidazole (hypoxia marker), tumours were collected and the intratumoral distribution of FAZA (autoradiography) and hypoxia (pimonidazole immunohistology) were determined in cryosections. RESULTS: Tissue section analysis revealed that the intratumoral distribution of FAZA was strongly correlated with the regional density of hypoxic (pimonidazole-positive) cells, even when necrosis was present, suggesting that FAZA PET provides a reliable measure of tumour hypoxia at the time of the scan. PET-based quantification of tumour tracer uptake relative to injected dose showed excellent reproducibility at baseline, whereas normalization using an image-derived nonhypoxic reference tissue (muscle) proved highly unreliable since a valid and reliable reference value could not be determined. The intratumoral distribution of tracer was stable at baseline as shown by a voxel-by-voxel comparison of the two scans (R = 0.82, range 0.72-0.90). During treatment, overall tracer retention changed in individual mice, but there was no evidence of general reoxygenation. CONCLUSION: Hypoxia PET scans are quantitatively correct and highly reproducible in tumour-bearing mice. Preclinical hypoxia PET is therefore a valuable and reliable tool for the development of strategies that target or modify hypoxia.

Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial.

AIMS: Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady-state liraglutide 1.8 mg versus placebo on postprandial plasma lipid concentrations after 3 weeks of treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: In a cross-over trial, patients with T2DM (n = 20, 18-75 years, BMI 18.5-40 kg/m²) were randomized to once-daily subcutaneous liraglutide (weekly dose escalation from 0.6 to 1.8 mg) and placebo. After each 3-week period, a standardized fat-rich meal was provided, and the effects of liraglutide on triglyceride (primary endpoint AUC(0-8h)), apolipoprotein B48, non-esterified fatty acids, glycaemic responses and gastric emptying were assessed. ClinicalTrials.gov ID: NCT00993304. FUNDING: Novo Nordisk A/S. RESULTS: After 3 weeks, mean postprandial triglyceride (AUC(0-8h) liraglutide/placebo treatment-ratio 0.72, 95% CI [0.62-0.83], p = 0.0004) and apolipoprotein B48 (AUC(0-8h) ratio 0.65 [0.58-0.73], p < 0.0001) significantly decreased with liraglutide 1.8 mg versus placebo, as did iAUC(0-8h) and C(max) (p < 0.001). No significant treatment differences were observed for non-esterified fatty acids. Mean postprandial glucose and glucagon AUC(0-8h) and C(max) were significantly reduced with liraglutide versus placebo. Postprandial gastric emptying rate [assessed by paracetamol absorption (liquid phase) and the ¹³C-octanoate breath test (solid phase)] displayed no treatment differences. Mean low-density lipoprotein and total cholesterol decreased significantly with liraglutide versus placebo. CONCLUSIONS: Liraglutide treatment in patients with T2DM significantly reduced postprandial excursions of triglyceride and apolipoprotein B48 after a fat-rich meal, independently of gastric emptying. Results indicate liraglutide's potential to reduce CVD risk via improvement of postprandial lipaemia.

Restorative proctocolectomy for ulcerative colitis: development and validation of a new scoring system for pouch dysfunction and quality of life.

AIM: The purpose of this study was to develop and validate a pouch dysfunction score that could identify the aspects of function which have the greatest impact on quality of life as perceived by the patient. METHOD: All (n = 1757) patients having restorative proctocolectomy in Denmark between 1980 and 2010 were identified. Of these, 1229 were available for study and were sent a questionnaire on bowel function and quality of life (QoL) designed specifically for this study. Function was correlated with QoL in a multivariate model using ordinal logistic regression with QoL as a dependent variable. The pouch dysfunction score was developed from a randomly selected half of the study population and the validity was tested on the other half. RESULTS: 1047 (85%) patients returned the questionnaire. On multivariate analysis, the symptom domains of 'incomplete emptying', 'severity of urgency', 'number of bowel movements/24 h', 'major incontinence' and 'use of anti-diarrhoeal medication' were associated with reduced QoL. The score was divided into three categories including 'none', 'minor' and 'some/major' pouch dysfunction. The corresponding coefficients gave the score a range from 0 to 7.5. There was a highly significant difference (P < 0.001) in score between the categories. The area under the receiver operating curve was 0.81. CONCLUSION: Urgency, incomplete emptying, number of bowel movements/24 h, major incontinence and use of anti-diarrhoeal medication have a major impact on QoL. There was a high accuracy for the score, demonstrating its potential clinical usefulness in relating symptoms to QoL.

R-CHOEP-14 improves overall survival in young high-risk patients with diffuse large B-cell lymphoma compared with R-CHOP-14. A population-based investigation from the Danish Lymphoma Group.

BACKGROUND: Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has in other patient groups been shown to be effective. Further improvement has been accomplished with the use of rituximab in combination with the regimens every 2 weeks (R-CHOP-14, R-CHOEP-14). The aim of the present retrospective population-based study was to compare R-CHOP-14 with R-CHOEP-14 in a cohort of high-risk patients aged 18-60 years with two or more risk factors (stage III-IV, elevated lactate dehydrogenase levels, performance status 2-4). To our knowledge, this is the first study comparing these two regimens in this patient group. METHODS: We obtained data for the period 2004-2009 from the Danish Lymphoma Database. One hundred and fifty-nine patients were eligible to enter the study. Primary end point was overall survival (OS) and secondary end points were response to treatment, progression-free survival (PFS) and safety. RESULTS: Four-year OS was superior in the R-CHOEP-14 group: 75% compared with 62% for R-CHOP-14 (P=0.04). This superiority was also seen for PFS: 4-year PFS was 70% for the R-CHOEP-14 group compared with 58% for the R-CHOP-14 group (P=0.02). CONCLUSION: R-CHOEP-14 is a promising regimen for young patients with high-risk DLBCL with improved OS and PFS compared with R-CHOP-14.

Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project.

BACKGROUND: In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. METHODS: In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII(®)). RESULTS: By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). CONCLUSIONS: Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.

Early-life environment influencing susceptibility to cytomegalovirus infection: evidence from the Leiden Longevity Study and the Longitudinal Study of Aging Danish Twins.

Human cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins aged 73-94 years were included (n=302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42% vs. partners: 51%, P=0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding number for partners was 71% (P<0·001). In the LSADT, MZ and DZ twins had high and similar CMV-positive concordance rates (MZ: 90% vs. DZ: 88%, P=0·51) suggesting that shared family environment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection--even under continuous within-partnership exposure--appears to be more strongly influenced by early-life environment than by genetic factors and adult environment.

Suppression of Powdery Mildew (Podosphaera pannosa) in Greenhouse Roses by Brief Exposure to Supplemental UV-B radiation.

Ultraviolet (UV)-B (280 to 315 nm) irradiance from 0.1 to 1.2 W m-2 and exposure times from 2 min to 2 h significantly suppressed powdery mildew (Podosphaera pannosa) in pot rose (Rosa × hybrida 'Toril') via reduced spore germination, infection efficiency, disease severity, and sporulation of surviving colonies. Brief daily exposure to UV-B suppressed disease severity by more than 90% compared with unexposed controls, and severity was held at low levels as long as daily brief exposures continued. Selective removal of wavelengths below 290 nm from the UV lamp sources by cellulose diacetate filters resulted in significant reduction of treatment efficacy. Exposure of plants to 2 h of UV-B during night for 1 week followed by inoculation with P. pannosa did not affect subsequent pathogen development, indicating that the treatment effect was directly upon the exposed pathogen and not operated through the host. Following 20 to 30 days of exposure, chlorophyll and flavonoid content was slightly higher in plants exposed to the highest UV-B levels. Brief daily exposure to UV-B for 5 min at 1.2 W m-2 or 1 h at 0.1 W m-2 substantially reduced mildew severity without significant phytotoxicity, and may represent a useful nonchemical option for suppression of powdery mildew in greenhouse roses and, possibly, other crops.

Litter on the seafloor along the African coast and in the Bay of Bengal based on trawl bycatches from 2011 to 2020.

We present the occurrence of seafloor litter on the coast of Africa and in the Bay of Bengal based on records from the EAF-NANSEN Programme in 2011 to 2020. Litter bycatch records from 534 bottom trawls were standardized to km2 before analysis. Three percent of the records indicated areas of high littering and the highest densities occurred from 100 to 300 m in depth and 50 to 100 km from the coast. Littering was lower in the Indian Ocean compared to Atlantic Africa. Plastic objects and fishing gear dominated the recorded items (47 % and 22 % respectively) but, regional differences were pronounced. Plastic dominated North Atlantic and East African records (58 % and 80 % respectively) and fishing gear dominated (69 %) in South Atlantic Africa while records from the Bay of Bengal were a mix of categories. The relation between littering and population density, marine industry, major cities, and rivers is discussed.

Total and cause-specific mortality rates in a prospective study of community-acquired hepatitis C virus infection in northern Norway.

Knowledge of the natural course and especially the total and cause-specific mortality of community-acquired chronic HCV infection is limited. The aims of our study were to determine the total and cause-specific mortality in patients infected with chronic hepatitis C in a community-based setting in northern Norway. This prospective cohort study included 1010 HCV-positive patients diagnosed with recombinant immunoblot assay between 1 January 1990 and 1 January 2000, with a median observation time from diagnosis to follow-up of 7 years. Data were collected from medical records in the period between 1 January 2004 and 30 June 2006. Time and cause of death were ascertained from the Norwegian Causes of Death Register. Age-adjusted death rates and standardised mortality ratios (SMRs) were compared with those of the general Norwegian population. In total, 122 deaths were recorded. The Kaplan-Meier estimate of survival was 88% at 14 years. The SMR in the cohort relative to the general population was 6.66. Most of the excess deaths in both genders were because of liver-related causes, those associated with a drug-using lifestyle and suicide. The statistically significant increase in SMRs ranged from 4.2 for death by cancer in women to 64.6 for liver disease in women. There was no statistically significant increase in SMRs from cardiovascular disease in either gender or from cancer in men. In conclusion, our study shows that the death rate in patients infected with hepatitis C is 6.66 times higher than in the general Norwegian population.