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Background: Quantitative flow ratio (QFR) is a tool for physiological lesion assessment based on invasive coronary angiography.Aims: We aimed to assess the reproducibility of QFR computed from the same angiograms as assessed by multiple observers from different, international sites.Methods: We included 50 patients previously enrolled in dedicated QFR studies. QFR was computed twice, one month apart by five blinded observers. The main analysis was the coefficient of variation (CV) as a measure of infra- and inter-observer reproducibility. Key secondary analysis was the identification of clinical and procedural characteristics predicting reproducibility.Results: The intra-observer CV ranged from 2.3% (1.5-2.8) to 10.2% (6.6-12.0) among the observers. The inter-observer CV was 9.4% (8.0-10.5). The QFR observer, low angiographic quality, and low fractional flow reserve (FFR) were independent predictors of a large absolute difference between repeated QFR measurements defined as a difference larger than the median difference (>0.03).Conclusions: The inter- and intra-observer reproducibility for QFR computed from the same angiograms ranged from high to poor among multiple observers from different sites with an average agreement of 0.01 +/--0.08 for repeated measurements. The reproducibility was dependent on the observer, angiographic quality and the coronary artery stenosis severity as assessed by FFR.

QUESTION: What are the relative effects of group-based exercise, individual exercise and home-based exercise on clinical outcomes and costs in patients with subacromial pain?DESIGN: Multicentre, three-arm, randomised controlled trial with concealed allocation and intention-to-treat analysis.PARTICIPANTS: A total of 208 patients referred to municipal rehabilitation for management of subacromial pain in six municipalities in the Central Denmark Region.INTERVENTIONS: Patients were randomly allocated to group-based exercise rehabilitation (GE), individual exercise rehabilitation (IE) or home exercise rehabilitation (HE) for a period of 8 weeks.OUTCOME MEASURES: The primary outcome measure was the shortened version of the Disabilities of the Arm, Shoulder and Hand questionnaire (Quick-DASH). The secondary outcome measures included the EQ-5D-5L index, pain intensity, fear avoidance, psychological wellbeing, and the participant's perception of improvement and satisfaction. Healthcare and productivity costs were extracted from national health and social registers.RESULTS: There was no important between-group difference in Quick-DASH scores at 6 months: adjusted mean differences GE minus IE -2 (95% CI -9 to 5), GE minus HE -2 (95% CI -9 to 5) and HE minus IE 1 (95% CI -6 to 7). The estimates of the between-group differences were able to exclude any clinically important differences in the three regimens' effects on health benefits according to the EQ-5D-5L index and other secondary outcomes. The total average costs were highest for the IE group and lowest for the HE, but not statistically different across groups.CONCLUSION: In people with subacromial pain, group-based exercise, individually supervised exercise and home-based supervised exercise regimens have similar benefits. The home exercise intervention was associated with lowest costs.TRIAL REGISTRATION: ClinicalTrials.gov: NCT03055117.

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

Timely reperfusion in ST-elevation myocardial infarction (STEMI) is essential. This study aimed to evaluate the reduction in system delay (time from emergency medical service [EMS] call to primary percutaneous coronary intervention [PPCI]) in patients with STEMI when using helicopter EMS (HEMS) rather than ground-based EMS (GEMS). This was a retrospective, nationwide cohort study of consecutive patients with STEMI treated with PPCI at 5 PPCI centers in Denmark. Polynomial spline curves were constructed to describe the association between system delay and distance to the PPCI center stratified by transportation mode. A total of 26,433 patients with STEMI were treated with PPCI between January 1, 1999, and December 31, 2016. In 16,436 patients field triaged directly to the PPCI center, the proportion treated within 120 minutes of the EMS call was 75% for those living 0 to 25 km from the PPCI center compared with 65% for all patients transported by GEMS (median transport distance 50 km [interquartile range 23 to 90]) and 64% for all patients transported by HEMS (median transport distance 119 km [interquartile range 99 to 142]). The estimated reduction in system delay owed to using HEMS rather than GEMS was 14, 16, 20, and 29 minutes for patients living 75, 100, 125, and 170 km from a PPCI center. In conclusion, this study confirmed that using HEMS ensures that most patients with STEMI, living up to 170 km from a PPCI center, can be treated within 120 minutes of their EMS call provided they are field triaged directly to the PPCI center.

INTRODUCTION: The seafood industry is the largest industry in Greenland. Work-related diseases and accidents appear to constitute health risks in this sector. The aim was to describe the prevalence of work-related diseases and accidents among workers in the seafood industry in Greenland.METHODS: Data from 311 workers included a questionnaire, lung function measurements, skin prick tests, blood samples, clinical examinations, personal inhalable dust samples and stationary dust measurements. Accident risk was evaluated by work site observations and safety walks. Statistical analyses included mean values and percentage distribution.RESULTS: Exposure levels were highest in shrimp production; 16.1% were sensitised to snow crab, 10.1% to shrimp and 0.3% to fish; 5.2% had probable occupational asthma. Regarding accidents, the annual incidence rate per 100 workers was 10.3%.CONCLUSIONS: Workers in the seafood industry in Greenland have a high prevalence of sensitisation to work-related allergens and occupational asthma closely related to high exposures to shrimp and snow crab allergens. The rate of severe workplace injuries was high. Preventive measures are required.FUNDING: The Health Science Research Council; The Work Environment Council of Greenland; The Greenlandic Workers' Union; Greenland Business Association; Royal Greenland; Polar Seafood; The BANK of Greenland; The Danish Working Environment Research Fund.TRIAL REGISTRATION: The Scientific Ethical Committee for Greenland (2015-11317); The Danish Data Protection Agency, the Central Denmark Region (2012-58-006).

Objectives: Due to the long lag-time for health outcomes, historical asbestos exposure measurements are valuable to support assessments of associated occupational health effects, and also to assess time trends and effects of preventive measures. Methods: Different sources of stored data were collated, assessed and refined to create a harmonized database on historical asbestos fibre concentrations measured in specific work tasks and different industries. The final database contains 9236 asbestos measurements from Danish workplaces collected from 1971 to 1997. Results: The geometric mean of asbestos concentrations in different occupations and tasks ranged from 0.003 to 35 fibres cm−3. Highest concentrations were registered during handling of asbestos products in the construction services during the period 1981–1997. Although all the measured asbestos exposures without the use of respiratory equipment by the worker in the period of 1971–1997 exceeded the current 8-h time-weighted average exposure limit of 0.1 fibres cm−3, the majority of samples collected in the earlier period of 1971 to 1980 did not exceed the exposure limit of 2 fibres cm−3, which was in place at the time. All exposure data obtained from 1980 and onwards were found to be one seventh of the mean fibre concentrations in the previous measurement period. The impact of time shows a clear exponentially decreasing trend-line. Conclusions: Despite limitations in coverage of different occupations and tasks associated with the inventoried historical asbestos measurements, the data are helpful to identify specific work scenarios within an industry, where relatively high asbestos exposure levels may still occur or have occurred from 1971 to 1997.

Background: The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed. Objective: The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA). Methods and analysis: Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up. Conclusions: The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.

Additional file 1: Table S1. Results of the non-response analysis between respondents and non-respondents presented as frequencies and percentages N (%).

Introduction: The fishing- and the seafood processing industries are the largest industrial sectors in Greenland. Despite this, only a few cases of occupational diseases in this industry have been reported to the Danish Labor Market Insurance. Occupational asthma and allergy are well-known occupational diseases in the seafood processing industry worldwide and underreporting of occupational diseases in Greenland is suspected.Objective: The aim of the current study was to examine the associations between job exposures and occupational asthma and rhino conjunctivitis in workers in the Greenlandic seafood processing industry and to compare the prevalence of sensitization by type and degree of exposure to snow crab, shrimp, fish, and the fish parasite, Anisakis simplex.Methods: Data from 382 Greenlandic seafood processing workers were collected during 2016–2018. Data included questionnaire answers, lung function measurements, skin prick tests, and blood samples with ImmunoCAP. For all analyses, p < 0.05 was considered the level of significance.Results: 5.5% of the workers had occupational asthma and 4.6% had occupational rhino conjunctivitis. A large proportion of the workers were sensitized to allergens specific to the workplace; 18.1% to snow crab, 13.6% to shrimp, 1.4% to fish, and 32.6% to the fish parasite, A. simplex. We found a dose-response relationship between the risk of being sensitized to snow crab and A. simplex and years of exposure to the allergens in the seafood processing industry.Conclusion: This study showed that a considerable proportion of workers in the Greenlandic seafood processing industry had occupational asthma and rhino conjunctivitis. Additionally, the study showed high sensitization levels toward snow crab, shrimp, and the fish parasite, A. simplex. This supports the hypothesis of a considerable degree of underreporting of occupational allergic airway disease in the Greenlandic seafood processing industry. Prospectively, it is important to inform workers, leaders, and health care professionals of the health problems and the law on worker's compensation, and to initiate preventive actions at factory and trawler level. The fishing- and the seafood processing industries are the largest industrial sectors in Greenland. In 2018, these sectors occupied approximately 16% of the Greenlandic workforce of approximately 26.800 people. High sensitization rates toward snow crab and shrimp have been found in Canadian studies as well as a high prevalence of both occupational asthma and occupational allergy (symptoms at work from the upper airways in combination with sensitization to seafood) in the seafood processing industry). Overall, the studies have shown an occupational asthma prevalence of 2–36% and an occupational allergy prevalence of 5–24% in the seafood processing industry. A dose–response relationship between the prevalence of occupational asthma and the level of exposure to seafood aeroallergens has been established, showing a higher prevalence of asthma with higher exposure levels.

Selenium levels in the Inuit population of Greenland have been declining during the last decades. The association between Selenium and asthma has been investigated previously, but with conflicting results. The objective was to measure human serum Se (s-Se) in Greenlandic seafood processing workers, to compare with levels recorded in previous decades and to establish if s-Se is associated with asthma or lung function. Data, including questionnaire answers, spirometry, skin-prick test and s-Se from 324 seafood processing workers in Greenland were collected during 2016–2017. Mean s-Se values were compared by t-test and one-way ANOVA. Associations between s-Se and asthma, symptoms from the lower airways at work and lung function were assessed using linear regression. The mean s-Se was 96.2 µg/L. S-Se was higher among non-smokers and workers living in settlements. Workers with asthma did not have s-Se levels significantly different from those of non-asthmatics. We found a positive association between s-Se levels and FEV1 values. Selenium levels appear to continue declining in Greenland, presumably because of a more Westernised lifestyle. The health effects of declining Selenium levels remain unclear. We did not establish an association between s-Se and asthma, but we did record a positive association between s-Se and FEV1.

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.

Combustion produces complex mixtures of ambient air pollutants, depending on the fuel, oxidant availability, temperature, turbulence, engine, among others. This complexity combined with the complexity of exposure to the pollutant, with variable duration, frequency, spatial position, multiple-sources and co-pollutants, activity level, and interindividual variation in susceptibility, makes it challenging to assess human health effects from exposure to ultrafine combustion particles. Controlled human exposure studies refer to those where selected study participants are exposed under controlled conditions of exposure and activity for the investigation of selected health outcomes and biomarkers. This is usually done in an exposure chamber although some studies have also attempted to control conditions in real-life settings. This design has been particularly used to investigate acute health effects from short-term exposures to combustion particles, providing mechanistic support of observations from epidemiological and animal studies. This chapter reviews and compares controlled human exposure studies in chambers, on healthy subjects, involving combustion-generated particles, which are dominated by the ultrafine size mode. In total, 64 studies including 12 chamber studies on wood smoke, 33 on diesel exhaust, 15 on concentrated ambient particles and 4 other carbonaceous particles (candles and others) were identified. The studies differ by designs (crossover or sequential), protocol definitions (with or without physical activity), particulate matter source (diesel exhaust, wood smoke or others), exposure metrics (with or without ultrafine size mode description), combustion generation conditions (for the same source), administrated doses and duration of exposure, as well as biomarkers and functional markers under study. The biological effects assessed have been mainly focused on lung function, cardiovascular function, heart rate variability, and inflammatory, oxidative stress and genotoxicity markers. The strengths and limitations of the controlled human exposure studies are revisited. The importance of the ultrafine particles is discussed and the results are compared with studies using real-life air concentrations of pollutants to generate a gradient of exposure.

Background The frailty phenotype is predictive of mortality and has been identified in the working population. This cross-sectional study aimed to investigate the prevalence of frailty and individual frailty symptoms among active and retired Danish manual workers and to delineate the relationship between frailty and lifestyle factors. Methods Manual workers aged 50–70 years answered questions relating to the Fried criteria for frailty (weight loss, exhaustion, slowness, weakness and inactivity). Only men were included in the analyses and respondents were stratified according to work status: active workers (n = 1555), early retirees (n = 289) and workers retired at or after normal pension age (n = 291). Associations between pre-frailty/frailty, work status and various lifestyle factors were estimated using binomial logistic regression. Results Overall, the prevalence of pre-frailty (one or two symptoms) and frailty (three or more symptoms) was 33.3% and 1.5%, respectively. Those who had retired early were more likely to be pre-frail/frail compared with active workers (odds ratio 2.20, 95% CI 1.61–3.01). Exhaustion was the most prominent symptom reported by 22.2% of active workers, 34.6% of early retirees and 16.5% of workers retired at normal retirement age. Lifestyle factors including obesity, physical inactivity and smoking but not alcohol intake were associated with pre-frailty/frailty. Conclusion Symptoms of frailty are identifiable and present among both active and retired manual workers. Data suggest discrepancies among Danish manual workers, with some having unhealthy lifestyles and being more prone to develop pre-frailty and frailty already in their sixth decade of life.

Background: E-cigarette use has been shown to have short-term acute effects among active users but less is known of the acute passive effects, particularly among individuals with existing respiratory diseases. Objective: To investigate local and systemic effects of short-term passive vape exposure among patients with mild or moderate chronic obstructive pulmonary disease (COPD). Methods: In a double-blinded crossover study 16 non-smoking COPD-patients (mean age 68) were randomly exposed for 4 h to passive vape (median PM2.5: 18 µg/m3 (range: 8-333)) and clean air (PM2.5 < 6 µg/m3) separated by 14 days. Particles were measured using an ultrafine particle counter (P-TRAK) and a scanning mobility particle sizer (SMPS). Health effects including Surfactant Protein-A (SP-A) and albumin in exhaled air, spirometry, FeNO, and plasma proteins were evaluated before, right after, and 24 hours after exposure. Participants reported symptoms throughout exposure sessions. Data were analyzed using mixed models. Results: SP-A in exhaled air was negatively affected by exposure to vape and several plasma proteins increased significantly. Throat irritation was more pronounced during passive vape exposure, while FVC and FEV1 decreased, however, not significantly. Conclusions: SP-A in exhaled air and some plasma proteins were affected by passive vape in patients with COPD indicating inflammation, showing that passive vape exposure is potentially harmful.

Background: E-cigarette use has been shown to have short-term acute effects among active users but less is known of the acute passive effects, particularly among individuals with existing respiratory diseases. Objective: To investigate local and systemic effects of short-term passive vape exposure among patients with mild or moderate chronic obstructive pulmonary disease (COPD). Methods: In a double-blinded crossover study 16 non-smoking COPD-patients (mean age 68) were randomly exposed for 4 h to passive vape (median PM 2.5: 18 µg/m 3 (range: 8–333)) and clean air (PM 2.5 3) separated by 14 days. Particles were measured using an ultrafine particle counter (P-TRAK) and a scanning mobility particle sizer (SMPS). Health effects including Surfactant Protein-A (SP-A) and albumin in exhaled air, spirometry, FeNO, and plasma proteins were evaluated before, right after, and 24 hours after exposure. Participants reported symptoms throughout exposure sessions. Data were analyzed using mixed models. Results: SP-A in exhaled air was negatively affected by exposure to vape and several plasma proteins increased significantly. Throat irritation was more pronounced during passive vape exposure, while FVC and FEV 1 decreased, however, not significantly. Conclusions: SP-A in exhaled air and some plasma proteins were affected by passive vape in patients with COPD indicating inflammation, showing that passive vape exposure is potentially harmful.

BackgroundMeasles is a highly contagious and serious infection. Before the introduction of vaccination, measles caused yearly epidemics putting vulnerable children at risk of brain damage and death. Despite safe and cost-effective vaccines, measles remains a leading cause of death in children globally. Due to insufficient vaccine coverage and low levels of in utero transferred antibodies from vaccinated mothers, outbreaks of measles in Denmark and other high-income countries are observed at increasing frequency.The current vaccine was introduced in Denmark in 1987 as a one-shot measles-mumps-rubella vaccine at 15 months, a timing chosen to avoid inhibition of the infant’s immune response by maternal antibodies. One generation later, the MMR vaccinated mothers have lower antibody levels compared to the naturally infected, and their infants are already susceptible at 6 months of age or earlier, thus increasing the risk of epidemics.MethodsThe Danish MMR trial is a double-blind randomized clinical trial recruiting between March 2019 and December 2021 with last patient last visit in February 2022. AltogetherN = 6500 infants aged 6 months will be randomly assigned to intramuscular vaccination with routine MMR (M-M-R VaxPro) or placebo (solvent only). According to the Danish Childhood vaccination program, all infants will receive a routine MMR vaccination at 15 months of age. At randomization, 1 month later, and 1 month after routine MMR vaccination at 15 months of age, a blood sample is drawn from app. 10% (N = 600) of the population. Additionally, hair, saliva, and urine are sampled at randomization. The co-primary study outcomes are immunogenicity 1 month after MMR vaccination at 6 months of age assessed as plaque-reduction neutralization test, and incidence of infectious disease hospitalizations from randomization to 12 months of age. Six weeks post randomization, all participants are interviewed regarding adverse events.Trial registrationThe trial is registered in the EU Clinical Trials Registry. EudraCT registration number:2016-001901-18. Registered on 14 February 2017.