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Background Health literacy concerns the ability of citizens to meet the complex demands of health in modern society. Data on the distribution of health literacy in general populations and how health literacy impacts health behavior and general health remains scarce. The present study aims to investigate the prevalence of health literacy levels and associations of health literacy with socioeconomic position, health risk behavior, and health status at a population level. Methods A nationwide cross-sectional survey linked to administrative registry data was applied to a randomly selected sample of 15,728 Danish individuals aged ≥25 years. By the short form HLS-EU-Q16 health literacy was measured for the domains of healthcare, disease prevention, and health promotion. Adjusted multinomial logistic regression analyses were used to estimate associations of health literacy with demographic and socioeconomic characteristics, health risk behavior (physical activity, smoking, alcohol consumption, body weight), and health status (sickness benefits, self-assessed health). Results Overall, 9007 (57.3%) individuals responded to the survey. Nearly 4 in 10 respondents faced difficulties in accessing, understanding, appraising, and applying health information. Notably, 8.18% presented with inadequate health literacy and 30.94% with problematic health literacy. Adjusted for potential confounders, regression analyses showed that males, younger individuals, immigrants, individuals with basic education or income below the national average, and individuals receiving social benefits had substantially higher odds of inadequate health literacy. Among health behavior factors (smoking, high alcohol consumption, and inactivity), only physical behavior [sedentary: OR: 2.31 (95% CI: 1.81; 2.95)] was associated with inadequate health literacy in the adjusted models. The long-term health risk indicator body-weight showed that individuals with obesity [OR: 1.78 (95% CI: 1.39; 2.28)] had significantly higher odds of lower health literacy scores. Poor self-assessed health [OR: 4.03 (95% CI: 3.26; 5.00)] and payments of sickness absence compensation benefits [OR: 1.74 (95% CI: 1.35; 2.23)] were associated with lower health literacy scores. Conclusions Despite a relatively highly educated population, the prevalence of inadequate health literacy is high. Inadequate health literacy is strongly associated with a low socioeconomic position, poor health status, inactivity, and overweight, but to a lesser extent with health behavior factors such as smoking and high alcohol consumption.

Among older men in Denmark, the incidence of death from any cause at a median follow-up of 5.6 years was not significantly lower among those randomly invited to undergo screening for subclinical cardiovascular disease.

Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice. National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.

Background Older patients with colorectal cancer (CRC) experience chemotherapy dose reductions or discontinuation. Comprehensive geriatric assessment (CGA) predicts survival and chemotherapy completion in patients with cancer, but the benefit of geriatric interventions remains unexplored. Methods The GERICO study is a randomised Phase 3 trial including patients ≥70 years receiving adjuvant or first-line palliative chemotherapy for CRC. Vulnerable patients (G8 questionnaire ≤14 points) were randomised 1:1 to CGA-based interventions or standard care, along with guideline-based chemotherapy. The primary outcome was chemotherapy completion without dose reductions or delays. Secondary outcomes were toxicity, survival and quality of life (QoL). Results Of 142 patients, 58% received adjuvant and 42% received first-line palliative chemotherapy. Interventions included medication changes (62%), nutritional therapy (51%) and physiotherapy (39%). More interventional patients completed scheduled chemotherapy compared with controls (45% vs. 28%, P  = 0.0366). Severe toxicity occurred in 39% of controls and 28% of interventional patients ( P  = 0.156). QoL improved in interventional patients compared with controls with the decreased burden of illness ( P  = 0.048) and improved mobility ( P  = 0.008). Conclusion Geriatric interventions compared with standard care increased the number of older, vulnerable patients with CRC completing adjuvant chemotherapy, and may improve the burden of illness and mobility. Trial registration ClinicalTrials.gov ID: NCT 02748811.

AbstractObjectiveTo determine the association between levels of low density lipoprotein cholesterol (LDL-C) and all cause mortality, and the concentration of LDL-C associated with the lowest risk of all cause mortality in the general population.DesignProspective cohort study.SettingDenmark; the Copenhagen General Population Study recruited in 2003-15 with a median follow-up of 9.4 years.ParticipantsIndividuals randomly selected from the national Danish Civil Registration System.Main outcome measuresBaseline levels of LDL-C associated with risk of mortality were evaluated on a continuous scale (restricted cubic splines) and by a priori defined centile categories with Cox proportional hazards regression models. Main outcome was all cause mortality. Secondary outcomes were cause specific mortality (cardiovascular, cancer, and other mortality).ResultsAmong 108 243 individuals aged 20-100, 11 376 (10.5%) died during the study, at a median age of 81. The association between levels of LDL-C and the risk of all cause mortality was U shaped, with low and high levels associated with an increased risk of all cause mortality. Compared with individuals with concentrations of LDL-C of 3.4-3.9 mmol/L (132-154 mg/dL; 61st-80th centiles), the multivariable adjusted hazard ratio for all cause mortality was 1.25 (95% confidence interval 1.15 to 1.36) for individuals with LDL-C concentrations of less than 1.8 mmol/L (<70 mg/dL; 1st-5th centiles) and 1.15 (1.05 to 1.27) for LDL-C concentrations of more than 4.8 mmol/L (>189 mg/dL; 96th-100th centiles). The concentration of LDL-C associated with the lowest risk of all cause mortality was 3.6 mmol/L (140 mg/dL) in the overall population and in individuals not receiving lipid lowering treatment, compared with 2.3 mmol/L (89 mg/dL) in individuals receiving lipid lowering treatment. Similar results were seen in men and women, across age groups, and for cancer and other mortality, but not for cardiovascular mortality. Any increase in LDL-C levels was associated with an increased risk of myocardial infarction.ConclusionsIn the general population, low and high levels of LDL-C were associated with an increased risk of all cause mortality, and the lowest risk of all cause mortality was found at an LDL-C concentration of 3.6 mmol/L (140 mg/dL).

As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P < 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P < 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P < 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).

We tested whether high remnant cholesterol is associated with high myocardial infarction risk, independent of whether an individual is normal weight, overweight, or obese. A total of 106216 individuals from the Copenhagen General Population Study were followed for up to 11 years, during which 1565 experienced a myocardial infarction. Individuals were grouped by clinically meaningful remnant cholesterol concentrations of <0.5 mmol/L (19 mg/dL), 0.5 to 0.99 mmol/L (19-38 mg/dL), 1.0 to 1.49 mmol/L (39-58 mg/dL), and ≥1.5 mmol/L (58 mg/dL), and by body mass index (BMI) of <18.5 kg/m (underweight), 18.5 to 24.9 kg/m (normal weight), 25 to 29.9 kg/m (overweight), and ≥30 kg/m (obese). Median calculated remnant cholesterol was 0.40 mmol/L [interquartile range (IQR), 0.30-0.55 mmol/L] [15 mg/dL (12-21 mg/dL)] for underweight, 0.50 mmol/L (IQR, 0.37-0.71 mmol/L) [19 mg/dL (14-27 mg/dL)] for normal weight, 0.70 mmol/L (IQR, 0.49-1.00 mmol/L) [27 mg/dL (19-39 mg/dL)] for overweight, and 0.85 mmol/L (IQR, 0.61-1.20 mmol/L) [(33 mg/dL (24-46 mg/dL)] for obese individuals. On continuous scales, remnant cholesterol was positively correlated with BMI until reaching a plateau of approximately 1 mmol/L (39 mg/dL) at BMI >35 kg/m . from an unadjusted linear regression for the correlation between calculated remnant cholesterol and BMI was 12%. Stepwise higher remnant cholesterol was associated with stepwise higher myocardial infarction risk in a similar pattern for normal weight, overweight, and obese individuals. When compared with individuals with remnant cholesterol <0.5 mmol/L (19 mg/dL), individuals with remnant cholesterol ≥1.5 mmol/L (58 mg/dL) had hazard ratios for myocardial infarction of 2.0 (95% CI, 1.3-3.2) for normal weight, 1.9 (95% CI, 1.4-2.6) for overweight, and 2.3 (95% CI, 1.4-3.5) for obese individuals. Directly measured remnant cholesterol increased 0.91 mmol/L (95% CI, 0.89-0.94 mmol/L) [35 mg/dL (34-36 mg/dL)] per 1 mmol/L (39 mg/dL) increase in calculated remnant cholesterol. Remnant cholesterol and BMI were positively correlated; however, high remnant cholesterol was associated with higher myocardial infarction risk across the examined BMI subcategories, indicating that remnant cholesterol is a risk factor for myocardial infarction independent of overweight and obesity.

BackgroundThe effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial.Methods4104 men and women, healthy heavy smokers/former smokers were randomised to five annual low-dose CT screenings or no screening. Two experienced chest radiologists read all CT scans and registered the location, size and morphology of nodules. Nodules between 5 and 15 mm without benign characteristics were rescanned after 3 months. Growing nodules (>25% volume increase and/or volume doubling time<400 days) and nodules >15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice.ResultsParticipation rates were high in both groups (screening: 95.5%; control: 93.0%; p<0.001). Lung cancer detection rate was 0.83% at baseline and mean annual detection rate was 0.67% at incidence rounds (p=0.535). More lung cancers were diagnosed in the screening group (69 vs 24, p<0.001), and more were low stage (48 vs 21 stage I–IIB non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC), p=0.002), whereas frequencies of high-stage lung cancer were the same (21 vs 16 stage IIIA–IV NSCLC and extensive stage SCLC, p=0.509). At the end of screening, 61 patients died in the screening group and 42 in the control group (p=0.059). 15 and 11 died of lung cancer, respectively (p=0.428).ConclusionCT screening for lung cancer brings forward early disease, and at this point no stage shift or reduction in mortality was observed. More lung cancers were diagnosed in the screening group, indicating some degree of overdiagnosis and need for longer follow-up.

SummaryThe Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated the effectiveness of a two-step screening program for osteoporosis in women. We found no overall reduction in fractures from systematic screening compared to the current case-finding strategy. The group of moderate- to high-risk women, who accepted the invitation to DXA, seemed to benefit from the program.IntroductionThe purpose of the ROSE study was to investigate the effectiveness of a two-step population-based osteoporosis screening program using the Fracture Risk Assessment Tool (FRAX) derived from a self-administered questionnaire to select women for DXA scan. After the scanning, standard osteoporosis management according to Danish national guidelines was followed.MethodsParticipants were randomized to either screening or control group, and randomization was stratified according to age and area of residence. Inclusion took place from February 2010 to November 2011. Participants received a self-administered questionnaire, and women in the screening group with a FRAX score ≥ 15% (major osteoporotic fractures) were invited to a DXA scan. Primary outcome was incident clinical fractures. Intention-to-treat analysis and two per-protocol analyses were performed.ResultsA total of 3416 fractures were observed during a median follow-up of 5 years. No significant differences were found in the intention-to-treat analyses with 34,229 women included aged 65–80 years. The per-protocol analyses showed a risk reduction in the group that underwent DXA scanning compared to women in the control group with a FRAX ≥ 15%, in regard to major osteoporotic fractures, hip fractures, and all fractures. The risk reduction was most pronounced for hip fractures (adjusted SHR 0.741, p = 0.007).ConclusionsCompared to an office-based case-finding strategy, the two-step systematic screening strategy had no overall effect on fracture incidence. The two-step strategy seemed, however, to be beneficial in the group of women who were identified by FRAX as moderate- or high-risk patients and complied with DXA.

Intensive treatment of multiple cardiovascular risk factors can halve mortality among people with established type 2 diabetes. We investigated the effect of early multifactorial treatment after diagnosis by screening. In a pragmatic, cluster-randomised, parallel-group trial done in Denmark, the Netherlands, and the UK, 343 general practices were randomly assigned screening of registered patients aged 40–69 years without known diabetes followed by routine care of diabetes or screening followed by intensive treatment of multiple risk factors. The primary endpoint was first cardiovascular event, including cardiovascular mortality and morbidity, revascularisation, and non-traumatic amputation within 5 years. Patients and staff assessing outcomes were unaware of the practice's study group assignment. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00237549. Primary endpoint data were available for 3055 (99·9%) of 3057 screen-detected patients. The mean age was 60·3 (SD 6·9) years and the mean duration of follow-up was 5·3 (SD 1·6) years. Improvements in cardiovascular risk factors (HbA 1c and cholesterol concentrations and blood pressure) were slightly but significantly better in the intensive treatment group. The incidence of first cardiovascular event was 7·2% (13·5 per 1000 person-years) in the intensive treatment group and 8·5% (15·9 per 1000 person-years) in the routine care group (hazard ratio 0·83, 95% CI 0·65–1·05), and of all-cause mortality 6·2% (11·6 per 1000 person-years) and 6·7% (12·5 per 1000 person-years; 0·91, 0·69–1·21), respectively. An intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death. National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Wellcome Trust, UK Medical Research Council, UK NIHR Health Technology Assessment Programme, UK National Health Service R&D, UK National Institute for Health Research, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Novo Nordisk, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Merck.