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Anja Lærke Frederiksen,1 Birgitte Hamann Laustsen,2,3 Jesper Bælum,4 Michael Lynge Pedersen,1,3 Jakob Hjort Bønløkke5 1Steno Diabetes Center Greenland, Nuuk, Greenland; 2Department of Clinical Medicine, Faculty of Medicine, Danish Ramazzini Centre, Aalborg University, Aalborg, Denmark; 3Greenland Center for Health Research, Institute of Nursing and Health Science, University of Greenland, Nuuk, Greenland; 4Research Unit for General Practice, Department of Public Health, University of Southern Denmark, Odense, Denmark; 5Department of Occupational and Environmental Medicine, Danish Ramazzini Centre, Aalborg University Hospital, Aalborg, DenmarkCorrespondence: Jakob Hjort Bønløkke, Department of Occupational and Environmental Medicine, Danish Ramazzini Centre, Aalborg University Hospital, Havrevangen 1, Aalborg, 9000, Denmark, Tel + 45 97664109, Email jahb@rn.dkIntroduction: For decades, the prevalence of smoking has been high in Greenland. Even so, the prevalence of chronic obstructive pulmonary disease (COPD), a smoking-related disease, remains largely unexplored. This cross-sectional study aimed to estimate the prevalence of COPD and chronic bronchitis (CB) among Inuit workers in the seafood industry in Greenland.Methods: A total of 355 participants, 254 males and 101 females, met the inclusion criteria. Participants had a mean age of 38 years (standard deviation 13.5; range 17– 68 years). COPD was diagnosed based on post-bronchodilator ratio between forced expiratory volume within one second and forced vital capacity (FEV1/FVC) below the lower limit of normal (LLN) according to the Global Lung Function Initiative. Participants completed a questionnaire aiming to diagnose CB.Results: The overall prevalence was 9.9% for COPD; 7.4% for CB. Participants were predominantly smokers; 73.2% active smokers, 91.8% active or former smokers. The prevalence of COPD was high, especially among those under 40 years of age. Both COPD and CB were associated with smoking status.Discussion: This study among Greenlandic seafood workers found that smoking was a risk factor for COPD and CB among Greenlanders of Inuit origin. The high prevalence of COPD and the high prevalence of smoking underlines the importance of further initiatives to reduce smoking in Greenland.Keywords: chronic obstructive pulmonary disease, chronic bronchitis, Greenland, Inuit, smoking, lung function

AIMS: To investigate the associations between both high- and low-intensity leisure-time physical activity on physical-work ability and chronic musculoskeletal complaints among manual workers aged 50-70 years.METHODS: In this cross-sectional study, 1763 manual workers (mean age 57.1, SD ± 4.7 years) replied to questions about leisure-time physical activity, physical-work ability, chronic musculoskeletal complaints as well as health and lifestyle factors. Ordinal and binomial logistic regression models were constructed to assess the influence of the duration of both low- and high-intensity physical activity on physical-work ability and chronic musculoskeletal complaints, respectively. Models were adjusted for gender, age, smoking, alcohol intake, body mass index, physical-work demand, work experience, chronic disease and, regarding physical-work ability, also for chronic musculoskeletal complaints.RESULTS: A statistically significant association between greater physical-work ability and high-intensity physical activity was found for workers engaged in 3-4 h/wk and ⩾ 5 h/wk (OR 1.59, 95% CI 1.15-2.19 and OR 1.56, 95% CI 1.10-2.22, respectively). For both high- and low-intensity physical activity, a duration of 3-4 h/wk was associated with lower odds of reporting chronic musculoskeletal complaints in the knees (OR 0.65, 95% CI 0.42-1.00 and OR 0.61, 95% CI 0.38-0.99, respectively).CONCLUSIONS: Engaging in ⩾ 3 h/wk of high-intensity leisure-time physical activity was associated with greater physical-work ability among manual workers aged 50-70 years. Both high- and low-intensity physical activity related to lower odds of having chronic musculoskeletal complaints in the knees.

The present study investigated the influence of age and musculoskeletal pain on force variability during a continuous isometric handgrip force task performed at 30% of maximal voluntary contraction carried out until failure. We recruited 96 male manual workers aged 51–72 years. The participants were stratified according to their age (50–59 and 60+ years) and by pain status (no pain, acute pain and chronic pain). The amplitude and structure of variability expressed as respectively standard deviation (SD) and coefficient of variation (CV), and sample entropy (SaEn) were calculated from the endurance task. The oldest group had an approximately 18% longer endurance time than the youngest group. No between-group differences were found in SD or CV, whereas a significant interaction between age and pain stage was found for SaEn. The youngest group showed lower SaEn than the oldest for both those with chronic pain and those without pain, indicating less force complexity, whereas a tendency for the opposite was found in the acute pain group. Within the pain stage groups, workers with acute pain had higher SaEn compared with both the no pain and chronic pain groups. These findings suggest that age and musculoskeletal pain differentially affects the structure of force variability in manual workers.

Objective To identify risk factors (air pollution and family related) for the onset of asthma and persistent wheezing in children. Design Nationwide case-control study. Setting Denmark. Participants All Danish children born from 1997 to 2014 and followed for asthma onset and persistent wheezing from age 1 year to 15 years. Main outcome measure Onset of asthma and persistent wheezing. Results A higher incidence of asthma was found in children of parents with asthma (adjusted hazard ratio 2.29 (95% confidence interval 2.22 to 2.35) and mothers who smoked during pregnancy (1.20, 1.18 to 1.22), whereas a lower incidence was found in children of parents with high educational attainment (0.72, 0.69 to 0.75) and high incomes (0.85, 0.81 to 0.89). Exposure to particulate matter ≤2.5 µm (PM 2.5 ) and ≤10 µm (PM 10 ) and nitrate was associated with an increased risk of asthma and persistent wheezing, with hazard ratios per 5 µg/m 3 increase in pollutant concentrations 1.05 (1.03 to 1.07) for PM 2.5 , 1.04 (1.02 to 1.06) for PM 10 , and 1.04 (1.03 to 1.04) for nitrogen dioxide. Only the positive association of PM 2.5 with asthma and persistent wheezing remained robust across the different models and in sensitivity analyses. Conclusions The findings of this study suggest that children exposed to higher levels of PM 2.5 are more likely to develop asthma and persistent wheezing than children who are not exposed. Other risk factors associated with these outcomes were parental asthma, parental education, and maternal smoking during pregnancy.

Background Percutaneous coronary intervention in complex bifurcation lesions is prone to suboptimal implantation results and is associated with increased risk of subsequent clinical events. Angiographic ambiguity is high during bifurcation stenting, but it is unknown if procedural guidance by intravascular optical coherence tomography (OCT) improves clinical outcome. Methods and design OCTOBER is a randomized, investigator-initiated, multicenter trial aimed to show superiority of OCT-guided stent implantation compared to standard angiographic-guided implantation in bifurcation lesions. The primary outcome measure is a 2-year composite end point of cardiac death, target lesion myocardial infarction, and ischemia-driven target lesion revascularization. The calculated sample size is 1,200 patients in total, and allocation is 1:1. Eligible patients have stable or unstable angina pectoris or stabilized non–ST elevation myocardial infarction, and a coronary bifurcation lesion with significant main vessel stenosis and more than 50 % stenosis in a side branch with a reference diameter ≥2.5mm. Treatment is performed by the provisional side branch stenting technique or 2-stent techniques, and the systematic OCT guiding protocol is aimed to evaluate (1) plaque preparation, (2) lesion length, (3) segmental reference sizes, (4) lesion coverage, (5) stent expansion, (6) malapposition, (7) wire positions, and (8) ostial results. Implications A positive outcome of the OCTOBER trial may establish OCT as a routine tool for optimization of complex percutaneous coronary intervention, whereas a negative result would indicate that OCT remains a tool for ad hoc evaluation in selected cases.

BACKGROUND AND AIMS: Common genetic risk variants may contribute to the heritability of early-onset coronary artery disease (CAD). We aimed to investigate the association of a genetic risk score (GRS) with age upon CAD-onset and to test the association between the GRS, familial clustering, and CAD severity in early-onset CAD.METHODS: 134 early-onset CAD patients (55 years/female >65 years), and 89 healthy controls were genotyped for 45 CAD-associated SNPs and a GRS was created. In early-onset CAD patients, family pedigrees with information on 1585 1st and 2nd degree relatives were used to calculate a stratified log-rank family score (SLFS) as a measure of familial clustering.RESULTS: Early-onset patients had a higher mean GRS than late-onset CAD patients (p = 0.02) and healthy controls (p < 0.0001). In the adjusted model, a GRS increase of one SD was associated with 1.2 years (95% CI 0.1-2.2) earlier onset. The GRS was not associated with the SLFS in the regression model (p = 0.41) and did not differ between SLFS tertiles (p = 0.98). The SLFS predicted the number of affected coronary vessels (OR [95% CI] per SD increase in SLFS: 2.0 [1.4-3.0]), whereas the association between the GRS and CAD severity was not statistically significant (OR [95% CI] per SD increase in GRS: 1.3 [0.9-1.9]).CONCLUSIONS: The GRS was increased in early-onset CAD patients, but not associated with the SLFS, suggesting that these common genetic variants are of minor importance in familial clustering of early-onset CAD. Furthermore, family pedigree analysis may predict CAD severity more precisely than common variants.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden. The ERIC-PPCI trial was funded by a British Heart Foundation clinical study grant (grant number CS/14/3/31002) and a University College London Hospitals/University College London Biomedical Research Centre clinical research grant. The CONDI-2 trial was funded by Danish Innovation Foundation grants (grant numbers 11-108354 and 11-115818), Novo Nordisk Foundation (grant number NNF13OC0007447), and TrygFonden (grant number 109624). DJH was supported by the British Heart Foundation (grant number FS/10/039/28270), the National Institute for Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the Duke-National University Singapore Medical School, the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (grant number NMRC/CSA-SI/0011/2017) and its Collaborative Centre Grant scheme (grant number NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (grant number MOE2016-T2-2-021). HEB was supported by the Novo Nordisk Foundation (grant numbers NNF14OC0013337, NNF15OC0016674). RKK is supported by the Oxford NIHR Biomedical Centre. The research was also supported by the NIHR infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health. This article is based on the work of COST Action EU-CARDIOPROTECTION (CA16225) and supported by COST (European Cooperation in Science and Technology). We thank all study personnel for their invaluable assistance. Sí

Exposure to low, naturally occurring, levels of ozone do not alter the bronchial response profile to pollen allergen, or lower the PD20 in atopic individuals, estimated by applying a novel non-linear model approachhttp://bit.ly/2XQjzwI

The purpose of this study was to explore the interacting effects of age and musculoskeletal pain on balance in manual workers. Ninety male manual workers aged 51–72 yr were recruited and stratified according to lower extremity musculoskeletal pain intensity (pain/no pain) and work status (working/retired). The five-repetition sit-to-stand (STS) test was used to assess lower extremity function including completion time, stand time, sit time and dynamic rate of force development both in the upwards (RFDup) and downwards moving phase (RFDdown). Dynamic balance was expressed as the range, velocity, standard deviation (SD), maximum Lyapunov Exponent and sample entropy of centre of pressure displacement in the anterior-posterior and medial-lateral direction, as well as free moment during the STS test. Except for higher age, no marked differences were seen between working and retired participants. Both age and musculoskeletal pain were negatively associated with motor function. Age × pain interactions showed that completion time, stand time, RFDup and RFDdown were negatively associated with age for participants without pain, but positively for those with pain. Similar findings were seen for dynamic balance. These findings indicate that the effects of lower extremity musculoskeletal pain on lower extremity function and dynamic balance are age dependent.

Aims: To show non-inferiority of the 67- or 87 µm thick, sirolimus-eluting Orsiro drug eluting stent (DES) to the 122 µm thick, biolimus-eluting Nobori DES regarding size of vessel lumen outside the stent at 13-month follow-up.Methods and results: This study was a substudy to the SORT-OUT VII trial, a prospective, 1:1-randomized, comparison of the two stents in patients with stable coronary artery disease or acute coronary syndrome. Optical coherence tomography was acquired after percutaneous coronary intervention and at 13-month follow-up. The substudy was powered to access non-inferiority (Δ = 0.60 mm2) of the Orsiro DES to the Nobori DES for the primary endpoint of mean extra stent lumen (ESL) i.e. vessel lumen outside the stent at 13-month follow-up. We randomized 124 patients to Orsiro (n = 60) or Nobori (n = 64). Due to a difference in the one-sided 95%-confidence interval of 0.26 mm2, but increased to 0.82 mm2 after appropriate log-transformation, it could not be rejected that Orsiro exceeded the non-inferiority limit. Testing for superiority, Orsiro had a significantly larger mean ESL at follow-up (Orsiro: 0.11 mm2 [0.02;0.30] mm2, Nobori: 0.03 mm2 [0.00;0.17] mm2, P = 0.04). Stent strut coverage was, Orsiro: 97.6 % [93.8;99.4]%, and Nobori: 96.3 % [90.5;98,6]% (P = 0.13).Conclusion: Orsiro DES had a significantly larger mean ESL at follow-up and it could not be excluded that Orsiro exceeded the limit for non-inferiority. Nobori DES had a more heterogeneous distribution of neointima but stent strut coverage did not differ significantly between the two stents.

Background: Health impact assessment (HIA) of exposure to air pollution is commonly based on city level (fine) particle concentration and may underestimate health consequences of changing local traffic. Exposure to traffic-related air pollution can be assessed at a high resolution by modelling levels of nitrogen dioxide (NO2), which together with ultrafine particles mainly originate from diesel-powered vehicles in urban areas. The purpose of this study was to estimate the health benefits of reduced exposure to vehicle emissions assessed as NO2 at the residence among the citizens of Copenhagen Municipality, Denmark. Methods: We utilized residential NO2 concentrations modelled by use of chemistry transport models to calculate contributions from emission sources to air pollution. The DYNAMO-HIA model was applied to the population of Copenhagen Municipality by using NO2 concentration estimates combined with demographic data and data from nationwide registers on incidence and prevalence of selected diseases, cause specific mortality, and total mortality of the population of Copenhagen. We used exposure-response functions linking NO2 concentration estimates at the residential address with the risk of diabetes, cardiovascular diseases, and respiratory diseases derived from a large Danish cohort study with the majority of subjects residing in Copenhagen between 1971 and 2010. Different scenarios were modelled to estimate the dynamic impact of NO2 exposure on related diseases and the potential health benefits of lowering the NO2 level in the Copenhagen Municipality. Results: The annual mean NO2 concentration was 19.6 μg/m3 and for 70% of the population the range of exposure was between 15 and 21 μg/m3. If NO2 exposure was reduced to the annual mean rural level of 6 μg/m3, life expectancy in 2040 would increase by one year. The greatest gain in disease-free life expectancy would be lifetime without ischemic heart disease (1.4 years), chronic obstructive pulmonary disease (1.5 years for men and 1.6 years for women), and asthma (1.3 years for men and 1.5 years for women). Lowering NO2 exposure by 20% would increase disease-free life expectancy for the different diseases by 0.3–0.5 years. Using gender specific relative risks affected the results. Conclusions: Reducing the NO2 exposure by controlling traffic-related air pollution reduces the occurrence of some of the most prevalent chronic diseases and increases life expectancy. Such health benefits can be quantified by DYNAMO-HIA in a high resolution exposure modelling. This paper demonstrates how traffic planners can assess health benefits from reduced levels of traffic-related air pollution.

Importance: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain.Objective: To determine whether TTM at 33°C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM.Design, Setting, and Participants: This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016.Interventions: Patients were randomized to TTM (33 ± 1°C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5°C per hour until reaching 37°C.Main Outcomes and Measures: The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use.Results: In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour group had a favorable outcome at 6 months compared with 64% (112/176) in the 24-hour group (difference, 4.9%; 95% CI, -5% to 14.8%; relative risk [RR], 1.08; 95% CI, 0.93-1.25; P = .33). Six-month mortality was 27% (48/175) in the 48-hour group and 34% (60/177) in the 24-hour group (difference, -6.5%; 95% CI, -16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour group (97%) than in the 24-hour group (91%) (difference, 5.6%; 95% CI, 0.6%-10.6%; RR, 1.06; 95% CI, 1.01-1.12; P = .04). The median length of intensive care unit stay (151 vs 117 hours; P Conclusions and Relevance: In unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33°C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33°C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted.Trial Registration: clinicaltrials.gov Identifier: NCT01689077.

AIMS: To determine the effect of the glucagon-like peptide-1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes.METHODS AND RESULTS: LIVE was an investigator-initiated, randomised, double-blinded, placebo-controlled multicentre trial. Patients (n = 241) with reduced left ventricular ejection fraction (LVEF ≤45%) were recruited (February 2012 to August 2015). Patients were clinically stable and on optimal heart failure treatment. Intervention was liraglutide 1.8 mg once daily or matching placebo for 24 weeks. The LVEF was similar at baseline in the liraglutide and the placebo group (33.7 ± 7.6% vs. 35.4 ± 9.4%). Change in LVEF did not differ between the liraglutide and the placebo group; mean difference (95% confidence interval) was -0.8% (-2.1, 0.5; P = 0.24). Heart rate increased with liraglutide [mean difference: 7 b.p.m. (5, 9), P CONCLUSION: Liraglutide did not affect left ventricular systolic function compared with placebo in stable chronic heart failure patients with and without diabetes. Treatment with liraglutide was associated with an increase in heart rate and more serious cardiac adverse events, and this raises some concern with respect to the use of liraglutide in patients with chronic heart failure and reduced left ventricular function. More data on the safety of liraglutide in different subgroups of heart failure patients are needed.

Aims: To compare in a randomised trial the safety and efficacy of the FemoSeal vascular closure device (VCD) versus manual compression (MC) after femoral access coronary angiography (CAG). Methods and results: In 13 months, 1,014 patients were included and 1,001 patients entered analysis. Median [interquartile range] closure time was 8.0 [6-10] minutes after MC versus 1.0 [1-1] minute (p

Background: The TTH48 trial aims to determine whether prolonged duration (48 hours) of targeted temperature management (TTM) at 33 (±1) °C results in better neurological outcomes compared to standard duration (24 hours) after six months in comatose out-of-hospital cardiac arrest (OHCA) patients. Methods: TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised, controlled superiority trial of 24 and 48 hours of TTM at 33 (±1) ° C performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to ten intensive care units (ICUs) in six Northern European countries. The primary outcome of the study is the Cerebral Performance Category (CPC) score observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor neurological outcomes. The secondary outcomes are as follows: mortality within six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the presence of any adverse events such as cerebral, circulatory, respiratory, gastrointestinal, renal, metabolic measures, infection or bleeding. With the planned sample size, we have 80% power to detect a 15% improvement in good neurological outcomes at a two-sided statistical significance level of 5%. Discussion: We present a detailed statistical analysis protocol (SAP) that specifies how primary and secondary outcomes should be evaluated. We also predetermine covariates for adjusted analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned SAP will reduce analysis bias and add validity to the findings of this trial on the effect of length of TTM on important clinical outcomes after cardiac arrest. Trial registration: ClinicalTrials.gov: NCT01689077, 17 September 2012, SCOPUS: ar.j, info:eu-repo/semantics/published

Background Danish patients with musculoskeletal disorders are commonly referred for primary care physiotherapy treatment but little is known about their general health status, pain diagnoses, clinical course and prognosis. The objectives of this study were to 1) describe the clinical course of patients with musculoskeletal disorders referred to physiotherapy, 2) identify predictors associated with a satisfactory outcome, and 3) determine the influence of the primary pain site diagnosis relative to those predictors. Methods This was a prospective cohort study of patients (n = 2,706) newly referred because of musculoskeletal pain to 30 physiotherapy practices from January 2012 to May 2012. Data were collected via a web-based questionnaire 1–2 days prior to the first physiotherapy consultation and at 6 weeks, 3 and 6 months, from clinical records (including primary musculoskeletal symptom diagnosis based on the ICPC-2 classification system), and from national registry data. The main outcome was the Patient Acceptable Symptom State. Potential predictors were analysed using backwards step-wise selection during longitudinal Generalised Estimating Equation regression modelling. To assess the influence of pain site on these associations, primary pain site diagnosis was added to the model. Results Of the patients included, 66% were female and the mean age was 48 (SD 15). The percentage of patients reporting their symptoms as acceptable was 32% at 6 weeks, 43% at 3 months and 52% at 6 months. A higher probability of satisfactory outcome was associated with place of residence, being retired, no compensation claim, less frequent pain, shorter duration of pain, lower levels of disability and fear avoidance, better mental health and being a non-smoker. Primary pain site diagnosis had little influence on these associations, and was not predictive of a satisfactory outcome. Conclusion Only half of the patients rated their symptoms as acceptable at 6 months. Although satisfactory outcome was difficult to predict at an individual patient level, there were a number of prognostic factors that were associated with this outcome. These factors should be considered when developing generic prediction tools to assess the probability of satisfactory outcome in musculoskeletal physiotherapy patients, because the site of pain did not affect that prognostic association. Electronic supplementary material The online version of this article (doi:10.1186/s12891-017-1487-3) contains supplementary material, which is available to authorized users.

SummaryBackground A variety of different environmental exposure chambers (EECs) have been used to evaluate treatments for allergic rhinitis. Objective To describe and test a system for a homogenous distribution of grass pollen, Phleum Pratense, in an EEC to be used for controlled pollen exposure studies in allergic participants. Methods A chamber made of stainless steel with completely rounded corners, seating four individuals at a time, was used. Room pressure, temperature, humidity and the air change rate were kept constant throughout the study period. A rotating pipette dispensed a uniform supply of pollen into a turntable's v-shaped grooves. A stainless steel capillary tube sucked the pollens into a venturi throat at which time the pollens were mixed with a high-pressure airstream of compressed high-efficiency particulate arrestance filtered air and then transported to a spreading plate inside the EEC. To achieve uniform concentrations in the EEC, the turntable's rotating speed was continuously adjusted using information from video-coupled feedback and feed forward mechanisms. Pollen levels were detected using standard volumetric air samplers and laser particle counters. The target pollen exposure level was 1000 pollens/m3. Twenty-one participants were exposed to pollens in the EEC twice for 210 min. Participants evaluated their symptoms every 30 min using a total nasal symptom score (TNSS) consisting of blocked nose, runny nose, nasal itching and sneezing. Results Across fifteen study days, the average pollen level was 982 pollens/m3 (SD, 102 pollens/m3). On average, participants experienced a 10% difference in overall pollen levels between their two visits to the EEC. The mean TNSSs rose throughout the exposure period, with a low at baseline of 0.43 (SD, 0.68) to a high of 4.71 (SD, 2.43) just before exiting the EEC. Conclusion and Clinical Relevance This EEC provides a reproducible, precise and homogenous distribution of pollens making it suitable for single-centre allergy clinical trials.

Aims To evaluate whether the distance from the site of event to an invasive heart centre, acute coronary angiography (CAG)/percutaneous coronary intervention (PCI) and hospital-level of care (invasive heart centre vs. local hospital) is associated with survival in out-of-hospital cardiac arrest (OHCA) patients. Methods and results Nationwide historical follow-up study of 41 186 unselected OHCA patients, in whom resuscitation was attempted between 2001 and 2013, identified through the Danish Cardiac Arrest Registry. We observed an increase in the proportion of patients receiving bystander CPR (18% in 2001, 60% in 2013, P Conclusion Admission to an invasive heart centre and regional performance of acute CAG/PCI were associated with improved survival in OHCA patients, whereas distance to the invasive centre was not. These results support a centralized strategy for immediate post-resuscitation care in OHCA patients.

OBJECTIVE:To compare inflammation and lung function in swine workers after periods with and without respiratory protection during work.METHODS:Twenty-three workers were examined before and after two nonprotected work shifts. One shift was preceded by a period with diminished exposure by use of respirators. The other shift was preceded by an unprotected period of work.RESULTS:Endotoxin concentrations were similarly high (24,636 and 28,775 endotoxin units/m(3)). A 3.1% cross-shift decline in forced vital capacity occurred after the period with respiratory protection (P = 0.01). Blood leukocytes increased more (P = 0.01) and bactericidal/permeability-increasing protein was reduced (P = 0.015) only after the period with respiratory protection. Plasma interleukin-6 increased (P < 0.0001) during both visits.CONCLUSION:Respiratory protection resulted in cross-shift inflammatory and respiratory reactions at return to unprotected work. OBJECTIVE:: To compare inflammation and lung function in swine workers after periods with and without respiratory protection during work. METHODS:: Twenty-three workers were examined before and after two nonprotected work shifts. One shift was preceded by a period with diminished exposure by use of respirators. The other shift was preceded by an unprotected period of work. RESULTS:: Endotoxin concentrations were similarly high (24,636 and 28,775 endotoxin units/m). A 3.1% cross-shift decline in forced vital capacity occurred after the period with respiratory protection (P = 0.01). Blood leukocytes increased more (P = 0.01) and bactericidal/permeability-increasing protein was reduced (P = 0.015) only after the period with respiratory protection. Plasma interleukin-6 increased (P

Exposure to wood smoke in the general population is increasing and concurrently, also our awareness. This article describes a wood-smoke generating system for studying human exposure to wood smoke and symptoms related to this exposure. Twenty nonsmoking atopic human participants with normal lung function and normal bronchial reactivity were randomly exposed for 3h at three different exposure conditions; clean filtered air (control exposure) and wood smoke with a characteristic particulate matter (PM) concentration of 200 µg/m3 (low) and 400 µg/m3 (high) under controlled environmental conditions. The range for PM2.5 load observed for single experiments was 165–303 µg/m3 for the low exposure and 205–662 µg/m3 for the high exposure, whereas particle loads during clean air exposure most often were below the detection limit (

Air pollution is a well-documented cause of morbidity and mortality. Cardiovascular and pulmonary effects associated with short- as well as long-term pollution exposure have been known for long1,2 and confirmed in recent studies.3 Studies have been conducted in a wide range of cities and regions of the world, confirming the adverse effect of polluted air from a variety of sources on cardiopulmonary health. The strongest associations are most often ascribed to fine particulate matter,4 but effects of gases such as ozone and SO2 have also been observed.5,6 Air pollution is a complex mixture of these and numerous other pollutants of which many stem from combustion sources. Indeed, evidence is growing that combustion-derived pollutants (ie, smoke) especially from traffic are the major drivers of adverse health effects.7 In less affluent regions of the World, smoke from the combustion of wood (and other biomass) is a very important contributor to both ambient and indoor air pollution (eg, from open fireplaces). Severe health effects have been shown in relation to such exposures, in particular on respiratory health and less so on cardiovascular health.8,9 In more affluent regions, wood smoke contributes less to the air pollution although some evidence exists for local wood smoke contributions to both ambient and indoor air pollution as well as to health effects.10 Associations between wood smoke and respiratory and cardiovascular effects have been demonstrated in both epidemiological10–12 and experimental studies.13 Because of decreases in other air pollutants and increases in the combustion of wood and other biomass in recent years, there is a need for better understanding of health effects of wood smoke. People with chronic respiratory disease and cardiovascular diseases may be particularly prone to adverse effects of wood smoke.14 A handful of short-term experimental wood smoke exposure studies have been conducted in healthy subjects so far.13,15–19 In these studies, effects on pneumoproteins—in particular, Clara cell protein (CC16), an anti-inflammatory protein secreted in large amounts in the bronchioli of healthy humans—exhaled NO, and symptoms of mucosal irritation have repeatedly been demonstrated, though no single effect was observed in all of the studies. In previous publications from the present study on atopic subjects, we have reported on short-term wood smoke-induced increase in symptoms20 without finding any effects on the airways,21 the microvascular function, or a range of markers of oxidative stress and inflammation in peripheral blood mononuclear cells.22 Yet inflammation23 and changes in heart rate variability (HRV)24,25 have been shown to occur with exposure to ambient air pollution including wood smoke.13 Both mechanisms may be relevant in the causal pathway to cardiovascular and pulmonary disease.23 Pollution-induced inflammation in the airways causes the formation of reactive oxidative species and the release of numerous cellular mediators, such as cytokines into the bloodstream, where they can affect coagulation and endothelial function. In association with deceased HRV, these mechanisms are plausibly involved in the development of cardiovascular disease such as myocardial infarction. Our aim was to investigate whether short-term systemic effects of wood smoke could be observed in a population of atopic volunteers. We hypothesized that at optimal wood burning conditions emitting fine particle concentrations above 200 μg/m3 blood coagulability and heart rate variability would be affected and that these effects would be accorded by an increase in circulating markers of epithelial damage such as pneumoproteins and cytokines. In addition, we hypothesized that controlled experimental conditions, blinding, and randomization would enable us to observe even small changes in the outcomes. Finally, we hypothesized that increased effects could be observed at higher concentrations.

Exposure to particles from combustion of wood is associated with respiratory symptoms, whereas there is limited knowledge about systemic effects. We investigated effects on systemic inflammation, oxidative stress and DNA damage in humans who lived in a reconstructed Viking Age house, with indoor combustion of wood for heating and cooking. The subjects were exposed to high indoor concentrations of PM2.5 (700-3,600 µg/m(3)), CO (10.7-15.3 ppm) and NO2 (140-154 µg/m(3)) during a 1-week stay. Nevertheless, there were unaltered levels of genotoxicity, determined as DNA strand breaks and formamidopyrimidine DNA glycosylase and oxoguanine DNA glycosylase 1 sensitive sites in peripheral blood mononuclear cells. There were also unaltered expression levels of OGG1, HMOX1, CCL2, IL8, and TNF levels in leukocytes. In serum, there were unaltered levels of C-reactive protein, IL6, IL8, TNF, lactate dehydrogenase, cholesterol, triglycerides, and high-density lipoproteins. The wood smoke exposure was associated with decreased serum levels of sICAM-1, and a tendency to decreased sVCAM-1 levels. There was a minor increase in the levels of circulating monocytes expressing CD31, whereas there were unaltered expression levels of CD11b, CD49d, and CD62L on monocytes after the stay in the house. In conclusion, even a high inhalation exposure to wood smoke was associated with limited systemic effects on markers of oxidative stress, DNA damage, inflammation, and monocyte activation.

Objective. The aim of this study was to develop a method to assess the potential effects of air pollution mitigation on healthcare costs and to apply this method to assess the potential savings related to a reduction in fine particle matter in Denmark.Methods. The effects of air pollution on health were used to identify “exposed” individuals (i.e., cases). Coronary heart disease, stroke, chronic obstructive pulmonary disease, and lung cancer were considered to be associated with air pollution. We used propensity score matching, two-part estimation, and Lin’s method to estimate healthcare costs. Subsequently, we multiplied the number of saved cases due to mitigation with the healthcare costs to arrive to an expression for healthcare cost savings.Results. The potential cost saving in the healthcare system arising from a modelled reduction in air pollution was estimated at €0.1–2.6 million per 100,000 inhabitants for the four diseases.Conclusion. We have illustrated an application of a method to assess the potential changes in healthcare costs due to a reduction in air pollution. The method relies on a large volume of administrative data and combines a number of established methods for epidemiological analysis.

Objectives: To study snow crab sensitization, occupational allergy and asthma in the snow crab industry in Greenland, as high rates have been found in Canada, but no reports have emerged from the same industry in Greenland. Study design: Pilot survey. Methods: Twenty workers (19 of Inuit and 1 of other origin) in a snow crab ( Chionoecetes opilio ) and Atlantic shrimp ( Pandalus borealis ) processing plant in Greenland were assessed with skin prick tests (SPTs) with common aeroallergens and specific allergens from snow crab and shrimp extracts, spirometry, blood sampling for total IgE and specific IgE determination. Eighteen workers contributed a questionnaire-based medical interview. Results: Positive skin prick test reactions were common to snow crab (40%) and shrimp (20%). Specific IgE to snow crab were positive in 4 workers (21%). Two workers had elevated total IgE levels. Symptoms suggestive of asthma were common (45%). Work-related symptoms of skin rash, rhinitis, and/or conjunctivitis were reported by 50%, and symptoms from the lower airways by 39%. Combining history of work-related symptoms with results from specific SPTs and/or specific IgE determination suggested that 11 and 22% of workers suffered from probable and possible occupational asthma, respectively, whereas 22% had possible occupational dermatitis or rhinitis. Conclusions: Greenlander Inuit do not appear to be protected against sensitization to snow crab or shrimp when occupationally exposed to these. This pilot study suggests that occupational allergy and asthma may be as common a problem in Greenlandic workers as in Canadian. Keywords: occupational allergy; occupational asthma; organic dusts; sensitizers; crustacea; Anisakis (Published: 7 August 2012) Citation: Int J Circumpolar Health 2012, 71 : 19126 - http://dx.doi.org/10.3402/ijch.v71i0.19126

Background There is growing evidence that particulate air pollution derived from wood stoves causes acute inflammation in the respiratory system, increases the incidence of asthma and other allergic diseases, and increases respiratory morbidity and mortality. The objective of this study was to evaluate acute respiratory effects from short-term wood smoke exposure in humans. Twenty non-smoking atopic volunteers with normal lung function and without bronchial responsiveness were monitored during three different experimental exposure sessions, aiming at particle concentrations of about 200 μg/m3, 400 μg/m3, and clean air as control exposure. A balanced cross-over design was used and participants were randomly allocated to exposure orders. Particles were generated in a wood-burning facility and added to a full-scale climate chamber where the participants were exposed for 3 hours under controlled environmental conditions. Health effects were evaluated in relation to: peak expiratory flow (PEF), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC). Furthermore, the effects were assessed in relation to changes in nasal patency and from markers of airway inflammation: fractional exhaled nitric oxide (FENO), exhaled breath condensate (EBC) and nasal lavage (NAL) samples were collected before, and at various intervals after exposure. Results No statistically significant effect of wood smoke exposure was found for lung function, for FENO, for NAL or for the nasal patency. Limited signs of airway inflammation were found in EBC. Conclusion In conclusion, short term exposure with wood smoke at a concentration normally found in a residential area with a high density of burning wood stoves causes only mild inflammatory response.

Background Exposure to wood smoke is associated with respiratory symptoms, whereas knowledge on systemic effects is limited. We investigated effects on systemic inflammation, oxidative stress and microvascular function (MVF) after controlled wood smoke exposure. Methods In a randomised, double-blinded, cross-over study 20 non-smoking atopic subjects were exposed at rest to 14, 220, or 354 μg/m3 of particles from a well-burning modern wood stove for 3 h in a climate controlled chamber with 2 week intervals. We investigated the level of oxidatively damaged DNA, inflammatory markers and adhesion molecules before and 0, 6 and 20 h after exposure. Six h after exposure we measured MVF non-invasively by digital peripheral artery tonometry following arm ischemia. Results The MVF score was unaltered after inhalation of clean air (1.58 ± 0.07; mean ± SEM), low (1.51 ± 0.07) or high (1.61 ± 0.09) concentrations of wood smoke particles in atopic subjects, whereas unexposed non-atopic subjects had higher score (1.91 ± 0.09). The level of oxidatively damaged DNA, mRNA of ITGAL, CCL2, TNF, IL6, IL8, HMOX1, and OGG1 and surface marker molecules ICAM1, ITGAL and L-selectin in peripheral blood mononuclear cells were not affected by inhalation of wood smoke particles. Conclusions Exposure to wood smoke had no effect on markers of oxidative stress, DNA damage, cell adhesion, cytokines or MVF in atopic subjects.

Swine confinement workers are exposed to various contaminants. These agents can cause airway inflammation and bronchoconstriction. This study was undertaken to evaluate if the bronchoconstrictive effects of swine barn air and settled dust are mediated by endotoxin, and if these effects are directly mediated on airway smooth muscles. Mouse tracheas where isolated and mounted isometrically in organ baths. Tracheas, with or without epithelium, were attached to a force transducer and tension was recorded. Concentrated swine building air at 68 EU/ml or settled dust extract at 0.01 g/ml were added for 20 minutes and tracheal smooth muscle contraction was measured. Direct role of LPS was assessed by removing it from air concentrates with an endotoxin affinity resin. Swine barn air and settled dust extract caused contraction of tracheal smooth muscle by 26 and 20%, respectively, of the maximal induced by methacholine. Removal of epithelium did not affect the contractile effects. LPS alone and LPS with peptidoglycans did not induce contraction. However, when endotoxin was removed from swine barn air concentrates, it lost 24% of its contractile effect. Concentrated swine barn air and settled dust have direct effects on airway smooth muscles. This effect is partially due to LPS but a synergy with other components of the environment of swine confinement buildings is required.

Short-term exposure to dust and dust added with beta-(1,3)-d-glucan or aldehydes may cause sensory reactions. In random order, we exposed 36 volunteers in a climate chamber to clean air, office dust, dust with glucan, and dust with aldehydes. Three groups of subjects were exposed, eleven were non-atopic with nasal histamine hyperreactivity, 13 were non-atopic, and 12 were atopic. Subjective ratings of symptoms and general health were registered four times during four 6-h exposure sessions. Six symptom intensity indices were constructed. The nasal hyperreactive group had a high and time-dependent increase of mucous membrane irritations, whereas the atopic group had a low and stable rate of irritations with exposure time, close to the reference group (P = 0.02 for differences between the groups with respect to time under exposure for Weak Inflammatory Responses and P = 0.05 for Irritative Body Perception, significance mainly because of the nasal hyperreactive group). Exposure to dust, with or without glucan or aldehydes, showed increased discomfort measured by the index for Constant Indoor Climate, and dust with glucan had a similar effect for the index for Lower Respiratory Effects. For Psychological and Neurological Effects these were dependent on group affiliation, thus preventing a uniform statement of exposure effects for all three investigated groups.PRACTICAL IMPLICATIONS:Opportunities for identifying persons with high or low sensitivity to low-level exposures are important in preventive medicine and will reduce intra-group variability and thus increase the power of experimental and epidemiological studies searching for correlations between exposures and health effects. The contrast between nasal hyperreactive on one side and atopic and reference subjects on the other side is particularly important. The atopic group indicated a non-homogenous reaction depending on their hyperreactive status, a finding that could be important but needs further confirmation.

AIM: Limited knowledge precludes evidence-based interventions targeting return to work among employees on sick leave. The objective of this study was to examine the vocational effect of an intervention focused on motivation, goal setting, and planning of return to work.DESIGN AND METHODS: A total of 2,795 people, across 6 municipalities, on sick leave for at least 21 days received a questionnaire; 1,256 with a self-assessed poor prognosis for fast return to work were eligible for the study. An examination by a specialist in social medicine, followed by additional counselling by a social worker, was offered to 510 residents in two municipalities and accepted by 264 (52%). The goal was to enhance motivation, goal setting, and planning of return to work. Residents in the remaining municipalities (n=746) received the standard case management offered by the municipalities; 845 (67%) persons completed a follow-up questionnaire gathering data on general health and employment status. The duration of the sick leave was analysed by Cox regression, and the chance of being gainfully employed was analysed by logistic regression analysis, both adjusted for several covariates.RESULTS: The intervention neither shortened sick leave periods nor increased the likelihood of gainful employment after one year (OR 0.76; 95% CI 0.45-1.28).CONCLUSIONS: A low-cost counselling programme addressing motivation, goal setting, and planning of return to work did not improve vocational outcomes or reduce the duration of sick leave.

Organic dust is associated with adverse effects on human airways. This study was done to investigate whether the addition of beta-(1,3)-D glucan or aldehydes to office dust causes enhanced inflammation in human airways.Thirty-six volunteers were exposed randomly to clean air, office dust, dust spiked with glucan, and dust spiked with aldehydes. The three dust exposures contained between 332 and 379 microg dust/m(3). Spiking with 1 gram of dust was done with 10 milligrams of glucan or 0.1 microliters of aldehydes. Acoustic rhinometry, rhinostereometry, nasal lavage, and lung function tests were applied.After the exposures to dust spiked with the glucan and aldehydes, the nasal volume decreased (-1.33 and -1.39 cm(3) (mean), respectively) when compared with the -0.9 cm(3) after clean air or office dust (P=0.036 for a difference in decrease between exposures). After 2-3 hours the aldehyde-spiked dust caused a 0.6-mm swelling of the inferior turbinate, and glucan-spiked dust produced a 0.7-mm swelling (P=0.039 for a difference in the swelling between the four exposures). The preexposure nasal lavage cleaned off the mucosa, and lower cytokine concentrations were found after all of the exposures. For interleukin-8, this decrease in concentration was smaller after the dust exposures spiked with glucan and aldehydes (-2.9 and -25.8 pg/ml, respectively) than after office dust or clean air (-65.9 and -74.1 pg/ml, respectively) (P=0.042). The nasal eosinophil cell concentration increased after exposure to dust spiked with glucan (P=0.045).beta-(1,3)-D glucan and aldehydes in office dust enhance the inflammatory effects of dust on the upper airways.

Objective The purpose of this study was to determine the association of an eating disorder that was diagnosed before pregnancy and a preterm delivery and/or the delivery of a low-birth-weight or small-for-gestational-age infant. Study design This was a register-based follow-up study. We included 302 women who were hospitalized with an eating disorder before pregnancy who were delivered of 504 children and 900 control subjects who were delivered of 1552 children. The association of eating disorders, birth weight, and gestational age was assessed by bivariate and multivariate analyses. Results The risk of a low-birth-weight infant was twice as high in women with a previous eating disorder compared with women with no such disorder (odds ratio, 2.2; 95% CI, 1.4-3.2). The risk of preterm delivery and a small-for-gestational-age infant was increased to 70% and 80% (odds ratio, 1.7 [95% CI, 1.1-2.6]; odds ratio, 1.8 [95% CI, 1.3-2.4]), respectively. Conclusion Women who were hospitalized for an eating disorder that was diagnosed before pregnancy were at increased risk of impaired pregnancy outcome.

Udgivelsesdato: 2004-Feb OBJECTIVE: To determine the prevalence of respiratory symptoms among workers processing herring and assess ex vivo cytokine release in response to agents at their workplace. METHODS: We applied a questionnaire, and performed skin prick testing and pulmonary investigations in 36 workers at two herring factories, using 31 municipal workers as controls. In a whole blood assay (WBA), venous blood from the subjects was incubated with lipopolysaccharide (LPS), beta(1,3)-glucan or sterile-filtered, fish constituents such as skin and rinsing water. We determined the IL-1beta and IL-8 release in the plasma by chemiluminescence ELISA. RESULTS: Among smoking fish-factory workers the forced vital capacity (FVC) was higher (per cent predicted 92.0 vs 85.0; P=0.028) than among municipal workers. Fish rinsing water induced WBA IL-8 release to higher levels than LPS and glucan. Among non-smokers the induced IL-1beta release for rinsing water ( P=0.007) and the IL-8 release for skin ( P=0.001) and meat ( P=0.003) were higher in fish-factory workers than in municipal workers. The IL-1beta release for rinsing water ( P=0.028) and skin ( P=0.041) was higher among non-smokers than among smokers, and so was the IL-8 release for rinsing water ( P=0.008). CONCLUSIONS: Assessing the cytokine release by use of the WBA we identified substances in the occupational environment with a pro-inflammatory potential comparable to that of LPS. The cytokine release for fish constituents was highest among non-smoking fish-factory workers. The results suggest a priming effect of the work exposure.

The aim of the project was to investigate whether there were diminished health effects in swine farm workers during summer compared with winter, as seasonal differences in concentrations of bioaerosols have been reported. Twenty-four workers were visited once during each season. Before and after a work shift, they underwent lung function testing and blood sampling. During work, they wore personal air sampling equipment. The mean endotoxin exposure of the workers was highest during winter (25,690 vs. 6,553 EU/m(3); p = 0.004). Although exposures to endotoxin and CO(2) varied between the seasons, no differences in lung function were found between them. White blood cell concentration increased over the work shift from 5.74-6.82 in winter (p0.0001) and from 5.80-6.38 in summer (p = 0.014). These increases differed between the two seasons (p = 0.032). Plasma tumour necrosis factor concentrations fell over the work shift only during winter (1.34-1.24 pg/ml (p = 0.03) (p = 0.014 for the difference between seasons). Plasma interleukin-6 increased over the work shift independently of season (p = 0.0006). The study supported our hypothesis of adverse effects on lung function and immune system, but less so during summer than during winter among Quebec swine farm workers.