PaCO2 trajectories in mechanically ventilated patients with COVID-19: A population-based cohort study.

OBJECTIVE: To identify PaCO2 trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) during the first and second waves of the pandemic in Denmark. DESIGN: A population-based cohort study with retrospective data collection. PATIENTS: All COVID-19 patients were treated in eight intensive care units (ICUs) in the Capital Region of Copenhagen, Denmark, between March 1, 2020 and March 31, 2021. MEASUREMENTS: Data from the electronic health records were extracted, and latent class analyses were computed based on up to the first 3 weeks of mechanical ventilation to depict trajectories of PaCO2 levels. Multivariable Cox regression analyses were used to calculate adjusted hazard ratios (aHRs) for Simplified Acute Physiology Score 3, sex and age with 95% confidence intervals (CIs) for death according to PaCO2 trajectories. MAIN RESULTS: In latent class trajectory models, including 25,318 PaCO2 measurements from 244 patients, three PaCO2 latent class trajectories were identified: a low isocapnic (Class I; n = 130), a high isocapnic (Class II; n = 80), as well as a progressively hypercapnic (Class III; n = 34) trajectory. Mortality was higher in Class II [aHR: 2.16 {1.26-3.68}] and Class III [aHR: 2.97 {1.63-5.40}]) compared to Class I (reference). CONCLUSION: Latent class analysis of arterial blood gases in mechanically ventilated COVID-19 patients identified distinct PaCO2 trajectories, which were independently associated with mortality.

The Danish National Health Survey: Study design, response rate and respondent characteristics in 2010, 2013 and 2017.

Aim: This article aims to describe the study design, including descriptive statistics on changes in response rates, characteristics associated with response and response mode distribution, in the Danish National Health Survey (DNHS) in 2010, 2013 and 2017. Methods: Each survey was based on five regional stratified random samples and one national random sample drawn from the Danish Civil Registration System. The subsamples were mutually exclusive. Around 300,000 individuals (aged ⩾16 years) were invited to participate in each survey using a mixed-mode approach (paper/web). A questionnaire with a minimum of 52 questions was used in all subsamples. In 2010 and 2013, invitations were sent via the regular postal service, whereas a secure electronical mail service was used to invite the majority (around 90%) in 2017. Weights accounted for survey design and non-response. Results: Participation decreased from 59.5% in 2010 to 54.0% in 2013 after which it increased to 58.7% in 2017. The proportion answering the web questionnaire increased from 31.0% to 77.4% between 2013 and 2017 and varied from 73.8% to 79.7% between the subsamples in 2017. Overall, the response rate was low among young men and old women and among individuals who were unmarried, had low sociodemographic status, were from ethnic minority backgrounds or were living in the eastern part of Denmark. Conclusions: The survey mode, response mode distribution as well as response rate have changed over time. Weights to handle non-response can be applied to accommodate possible problems in generalising the results. However, efforts should continuously be made to ensure that response is missing at random.

Poor social support and loneliness in chronic headache: Prevalence and effect modifiers.

OBJECTIVE: To explore the prevalence of poor social support and loneliness among people with chronic headache, and how these might be effect modifiers in the relationships between chronic headache and stress, medication overuse, and self-rated health. BACKGROUND: Poor social support and loneliness are consistently linked to worse health outcomes. There are few epidemiologic studies on their effect on headache. METHODS: The Danish Capital Region Health Survey, a cross-sectional survey, was conducted in 2017. Participants were asked about headache, pain medication use, social support, loneliness, perceived stress, and self-rated health. Data were accessed from sociodemographic registers. Logistic regression analyses were performed to test for effect modification. RESULTS: The response rate was 52.6% (55,185 respondents) and was representative of the target population. People with chronic headache were more likely to report poor social support and loneliness compared to those without chronic headache (p < 0.0001 for both). Odds ratios for the combination of chronic headache and poor social support were very high for stress (odds ratio 8.1), medication overuse (odds ratio 21.9), and poor self-rated health (odds ratio 10.2) compared to those without chronic headache and with good social support. Those who reported both chronic headache and loneliness had a very high odds ratio for stress (odds ratio 14.4), medication overuse (odds ratio 20.1), and poor self-rated health (odds ratio 15.9) compared to those without chronic headache and low loneliness score. When adjusted for sociodemographic factors, poor social support and loneliness were not significant effect modifiers in almost all these associations. Loneliness was a significant effect modifier in the association between chronic headache and medication overuse, but exerted greater effect among those who did not report they were lonely. CONCLUSION: Poor social support and loneliness were prevalent among people with chronic headache. The combination of chronic headache and poor social support or loneliness showed higher odds ratios for stress, medication overuse, and poor self-rated health compared to those with good social support and low loneliness scores. The effect of loneliness in the relationship between chronic headache and medication overuse warrants further study.

Chronic Diseases in High-Cost Users of Hospital, Primary Care, and Prescription Medication in the Capital Region of Denmark.

BACKGROUND: A small proportion of patients account for the majority of health care costs. This group is often referred to as high-cost users (HCU). A frequently described characteristic of HCU is chronic disease. Yet, there is a gap in understanding the economic burden of chronic diseases associated with HCU to different types of health care services. OBJECTIVE: To analyze which frequent chronic diseases have the strongest association with HCU overall, and HCU in hospital, primary care, and prescription medication. DESIGN: This is a register-based observational study on Danish health service costs for various diseases in different medical settings. PARTICIPANTS: A total of 1,350,677 individuals aged ≥ 18 years living in the Capital Region of Denmark by 1 January 2012 were included. MAIN MEASURES: Chronic diseases, costs, and sociodemographic data were extracted from the nationwide registers, including data from hospitals, primary care, and medicine consumption. These information were merged on an individual level. KEY RESULTS: Cancer, mental disorders except depression, and heart diseases have the strongest association with HCU overall. Mental disorders except depression were in the three diseases most prevalent in HCU in all the three health care services. CONCLUSIONS: Our results show that the chronic diseases that have the strongest association with HCU differ between different types of health care services. Our findings may be helpful in informing future policies about health care organization and may guide to different prevention, treatment, and rehabilitation strategies that could lessen the burden in the hospital.

Recent temporal trends in sleep duration, domain-specific sedentary behaviour and physical activity. A survey among 25-79-year-old Danish adults.

BACKGROUND: Prevalence of sedentary behaviour is high in many countries, but little is known about temporal trends in sitting time. OBJECTIVE: To examine temporal changes in sleep and domain-specific sedentary behaviour and moderate to vigorous leisure time physical activity (MVPA). METHODS: Two cross-sectional population-based surveys of 25-79-year-old inhabitants were conducted in The Capital Region of Denmark in 2007 (N = 69.800, response rate 52.3%) and 2010 (N = 77.517, response rate 54.8%). Information on sedentary behaviour and physical activity was obtained from self-report questionnaire and sociodemographic information from central registers. Data were weighted for survey design and for non-response and were analysed by multiple regression analyses. RESULTS: In 2007, the entire survey population reported a mean daily sleeping duration of 7.4 hours, leisure time sitting of 3.4 hours per day, occupational sitting of 4.4 hours per day, MVPA of 0.87 hours per day and a total 24-hour energy expenditure of 40.12 METs per day. In 2010, duration of sleep was unaltered (p = 0.1), sedentary leisure time and sedentary work time had increased by 12.6 minutes (p < 0.0001) and 13.2 minutes (p < 0.0001) per day, respectively. Time spent on MVPA had increased by 2.9 minutes per day (p < 0.0001). The 24-hour energy expenditure had decreased by 0.41 METs (p < 0.0001). CONCLUSIONS: Adult Danish men and women spend an increased amount of time sitting down at work and during leisure time, but also on leisure time MVPA. As duration of sleep is unaltered findings suggest that low intensity physical activity may be displaced in everyday life.

Hormone therapy and different ovarian cancers: a national cohort study.

Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women taking unopposed oral estrogen therapy had increased risks of both serous tumors (incidence rate ratio (IRR) = 1.7, 95% confidence interval: 1.4, 2.2) and endometrioid tumors (IRR = 1.5, 95% confidence interval: 1.0, 2.4) but decreased risk of mucinous tumors (IRR = 0.3, 95% confidence interval: 0.1, 0.8). Similar increased risks of serous and endometrioid tumors were found with estrogen/progestin therapy, whereas no association was found with mucinous tumors. Consistent with results from recent cohort studies, the authors found that ovarian cancer risk varied according to tumor histology. The types of ovarian tumors should be given attention in future studies.

Hormone therapy and ovarian borderline tumors: a national cohort study.

PURPOSE: Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk. METHODS: A total of 909,875 Danish women 50-79 years old without previous hormone-sensitive cancers or bilateral oophorectomy were followed in this nationwide cohort study 1995-2005. The National Register of Medicinal Product Statistics provided exposure information on all women who redeemed prescriptions on hormone therapy. The National Cancer and Pathology Register provided data on borderline ovarian tumors. Information on confounding factors was available from other national registers. Poisson regression analyses provided risk estimates with hormone exposures as time-dependent covariates. RESULTS: In an average of 8.0 years of follow-up, 703 incident ovarian borderline tumors were detected. Compared with never users, hormone use for more than 4 years increased the risk of borderline tumors: relative risk (RR) 1.40; 95% confidence interval (CI), 1.09-1.81. Combined estrogen and progestin therapy for more than 4 years increased the risk: RR 1.49 (1.10-2.01), with no difference between cyclic and continuous combined therapy (p = 0.83); RR 1.56 (1.08-2.25) and 1.45 (0.87-2.43), respectively. The RR with estrogen therapy did not differ significantly from RR with combined therapy (p = 0.58): RR 1.27 (0.82-1.98). Disregarding the type of hormone therapy, hormone use for 4 years or less did not increase the risk of borderline tumors. CONCLUSIONS: Combined hormone therapy for more than 4 years increases the risk of ovarian borderline tumors.

Social disparities in children's exposure to second hand smoke at home: a repeated cross-sectional survey.

BACKGROUND: Exposure to second hand smoke (SHS) is an important preventable cause of morbidity and mortality in children. We hypothesised that there has been a growth in social inequality in children's exposure to SHS at home over time. The purpose of this study was to investigate temporal change in smoking in homes including children, focusing on the socioeconomic differences. METHODS: Data is from a repeated cross-sectional survey, 'Health Profiles of the Capital Region of Denmark' conducted in 2007 and 2010, in 29 municipalities. The response rate was 52.3%, in both surveys. Our study included persons aged 25 to 64, living with children ≤15 years of age; N=9,289 in 2007 and 12,696 in 2010. Analyses were weighted for size of municipality and for non-response, which was higher among men and among persons who were younger, had a lower income, were living alone, were unemployed, and/or were of an ethnicity other than Danish. Regression analyses were used to investigate smoking in homes including children across parent/adult education levels, focusing on temporal changes. RESULTS: There were significant large socioeconomic differences in both 2007 and 2010. In 2010 it was more than 11 times more likely for a child to be exposed to SHS at home if the parent had very low education than if they were highly educated (p<0.001). Smoking in a home with children decreased from 16.2% in 2007 to 10.9% in 2010. The odds of a temporal decrease in domestic smoking did not differ significantly across parent education levels (p=0.40). CONCLUSIONS: Marked social inequalities in children's exposure to SHS and a significant temporal decrease in exposure, independent of the education level of the parent/adult, were found in repeated large cross-sectional population-based studies. Social disparities have persisted over time, but not increased. Both clinical and population policy interventions will be needed in order to control child SHS exposure. We call for legislative protection of children from tobacco smoke inside their home as a supplement to parental education and support for smoking cessation.

The Danish National Health Survey 2010. Study design and respondent characteristics.

AIMS: In 2010 the five Danish regions and the National Institute of Public Health at the University of Southern Denmark conducted a national representative health survey among the adult population in Denmark. This paper describes the study design and the sample and study population as well as the content of the questionnaire. METHODS: The survey was based on five regional stratified random samples and one national random sample. The samples were mutually exclusive. A total of 298,550 individuals (16 years or older) were invited to participate. Information was collected using a mixed mode approach (paper and web questionnaires). A questionnaire with a minimum of 52 core questions was used in all six subsamples. Calibrated weights were computed in order to take account of the complex survey design and reduce non-response bias. RESULTS: In all, 177,639 individuals completed the questionnaire (59.5%). The response rate varied from 52.3% in the Capital Region of Denmark sample to 65.5% in the North Denmark Region sample. The response rate was particularly low among young men, unmarried people and among individuals with a different ethnic background than Danish. CONCLUSIONS: The survey was a result of extensive national cooperation across sectors, which makes it unique in its field of application, e.g. health surveillance, planning and prioritizing public health initiatives and research. However, the low response rate in some subgroups of the study population can pose problems in generalizing data, and efforts to increase the response rate will be important in the forthcoming surveys.

Prophylactic anticoagulation with low molecular weight heparin in COVID-19: cohort studies in Denmark and Sweden.

OBJECTIVES: To evaluate safety and effectiveness of prophylactic anticoagulation with low molecular weight heparin (LMWH) in individuals hospitalised for COVID-19. METHODS: Using healthcare records from the Capital Region of Denmark (March 2020-February 2021) and Karolinska University Hospital in Sweden (February 2020-September 2021), we conducted an observational cohort study comparing clinical outcomes 30 days after admission among individuals hospitalised for COVID-19 starting prophylactic LMWH during the first 48 hours of hospitalisation with outcomes among those not receiving prophylactic anticoagulation. We used inverse probability weighting to adjust for confounders and bias due to missing information. Risk ratios, risk differences and robust 95% confidence intervals (CI) were estimated using binomial regression. Country-specific risk ratios were pooled using random-effects meta-analysis. RESULTS: We included 1692 and 1868 individuals in the Danish and Swedish cohorts. Of these, 771 (46%) and 1167 (62%) received prophylactic LMWH up to 48 hours after admission. The combined mortality in Denmark and Sweden was 12% (N = 432) and the pooled risk ratio was 0.91 (CI 0.60-1.38) comparing individuals who received LMWH to those who did not. The relative risk of ICU admission was 1.12 (0.76-1.66), while we observed no increased risk of bleeding 0.63 (0.13-2.94). The relative risk of venous thromboembolism was 0.80 (0.43-1.47). CONCLUSION: We found no benefit on mortality with prophylactic LMWH and no increased risk of bleeding among COVID-19 patients receiving prophylactic LMWH.

Comprehensive discharge follow-up in patients' homes by GPs and district nurses of elderly patients. A randomized controlled trial.

OBJECTIVES: Many hospital admissions are due to inappropriate medical treatment, and discharge of fragile elderly patients involves a high risk of readmission. The present study aimed to assess whether a follow-up programme undertaken by GPs and district nurses could improve the quality of the medical treatment and reduce the risk of readmission of elderly newly discharged patients. DESIGN AND SETTING: The patients were randomized to either an intervention group receiving a structured home visit by the GP and the district nurse one week after discharge followed by two contacts after three and eight weeks, or to a control group receiving the usual care. PATIENTS: A total of 331 patients aged 78+ years discharged from Glostrup Hospital, Denmark, were included. MAIN OUTCOME MEASURES: Readmission rate within 26 weeks after discharge among all randomized patients. Control of medication, evaluated 12 weeks after discharge on 293 (89%) of the patients by an interview at home and by a questionnaire to the GP. RESULTS: Control-group patients were more likely to be readmitted than intervention-group patients (52% v 40%; p = 0.03). In the intervention group, the proportions of patients who used prescribed medication of which the GP was unaware (48% vs. 34%; p = 0.02) and who did not take the medication prescribed by the GP (39% vs. 28%; p = 0.05) were smaller than in the control group. CONCLUSION: The intervention shows a possible framework securing the follow-up on elderly patients after discharge by reducing the readmission risk and improving medication control.

Impact of a sodium-reduced bread intervention with and without dietary counseling on sodium intake-a cluster randomized controlled trial among Danish families.

BACKGROUND/OBJECTIVES: Excessive intake of sodium is a dietary risk factor for morbidity and mortality. Currently, intake of sodium is much higher than the recommended level in most western countries, and effective strategies to reduce population sodium intake are lacking. The objective of the present study was to investigate the effect of two different sodium reduction strategies on the intake of sodium, potassium, and the sodium to potassium ratio among Danish families SUBJECTS/METHODS: The study was a 4-month, single-blinded, cluster randomized controlled trial with a parallel design. Eighty-nine healthy Danish families, with a minimum of one child and one parent (n = 309), were randomly assigned to receive sodium-reduced bread (Intervention A), sodium-reduced bread and dietary counseling (Intervention B) or regular sodium bread (Control). The primary outcome was change in daily sodium intake, measured by 24-h urinary sodium excretion. Secondary outcomes included changes in dietary potassium and the sodium to potassium ratio. RESULTS: No significant differences in daily sodium intake were observed in the two intervention groups compared with the control. When analyzing the results separately for children and adults, a reduction in dietary sodium of 0.6 g/day (-1.0, -0.2), p = 0.005 occurred among adults in intervention B compared with control. CONCLUSIONS: This study demonstrates that providing sodium-reduced bread in combination with dietary counseling is an effective strategy to reduce dietary sodium among adults, but the effect is lacking in children. The study was not able to show significant effects when providing sodium-reduced bread alone in neither adults nor children.

The Effects of Two Intervention Strategies to Reduce the Intake of Salt and the Sodium-To-Potassium Ratio on Cardiovascular Risk Factors. A 4-Month Randomised Controlled Study among Healthy Families.

The aim was to examine the effects of two different salt reduction strategies on selected cardiovascular risk factors. The study was a four-month cluster randomised controlled study. Eighty-nine healthy Danish families (309 individuals) were randomly assigned to either (A) gradually salt-reduced bread, (B) gradually salt-reduced bread and dietary counselling to further reduce salt intake and increase potassium intake or (C) standard bread (control). The effect was assessed using linear mixed models. Intention to treat analyses comparing changes in the three groups showed a significant reduction in body fat percent (-1.31% (-2.40; -0.23)) and a borderline significant reduction in total plasma cholesterol (-0.25 mmol/L (-0.51; 0.01) and plasma renin (-0.19 pmol/L (-0.39; 0.00) in group A compared to the control group. Adjusted complete case analyses showed a significant reduction in total plasma cholesterol (-0.29 mmol/L (-0.50; -0.08), plasma LDL cholesterol (-0.08 mmol/L (-0.15; -0.00)), plasma renin (-0.23 pmol/L (-0.41; -0.05)), plasma adrenaline (-0.03 nmol/L (-0.06; -0.01)) and body fat percent (-1.53% (-2.51; -0.54)) in group A compared to the control group. No significant changes were found in group B compared to the control group. In conclusion, receiving sodium reduce bread was associated with beneficial changes in cardiovascular risk factors. No adverse effects were observed.

Estimating the effect of current, previous and never use of drugs in studies based on prescription registries.

PURPOSE: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do not carry any information on the time of discontinuation of treatment.In this study, we investigated the amount of misclassification of exposure (never, current, previous use) to hormone therapy (HT) when the exposure variable was based on prescription data. Furthermore, we evaluated the significance of this misclassification for analysing the risk of breast cancer. MATERIALS AND METHODS: Prescription data were obtained from Danish Registry of Medicinal Products Statistics and we applied various methods to approximate treatment episodes. We analysed the duration of HT episodes to study the ability to identify discontinuation of therapy from prescription data. Furthermore, we compared to results based on self-reported duration of HT from the Danish Nurse Cohort.Finally, we analysed the effect of HT exposure on time to breast cancer for the different prescription based exposure variables as well as for self-reported HT use. RESULTS: The results of time to discontinuation varied strongly across the different HT assessments. However, misclassification of HT exposure at baseline was limited and hence analysis of the effect of HT on time to breast cancer showed stability across the different exposure assessments with Hazard Ratios ranging from 1.68 to 1.78 for current use compared to never use. CONCLUSIONS: The findings suggest that it is possible to estimate the effect of never, current and previous use of HT on breast cancer using prescription data.

Hormone therapy and risk of myocardial infarction: a national register study.

AIM: To assess the risk of myocardial infarction (MI) as a result of hormone therapy (HT), with focus on the influence of age, duration of HT, various regimens and routes, progestagen type, and oestrogen dose. METHODS AND RESULTS: All healthy Danish women (n = 698,098, aged 51-69) were followed during 1995-2001. On the basis of a central prescription registry, daily updated national capture on HT was determined. National Registers identified 4947 MI incidents. Poisson regression analyses estimated rate ratios (RRs). Overall, we found no increased risk [RR 1.03 (95% CI: 0.95-1.11)] of MI with the current HT compared with women who never used HT; age-stratified RR among women aged 51-54, 55-59, 60-64, and 65-69 years were 1.24 (1.02-1.51), 0.96 (0.82-1.12), 1.11 (0.97-1.27), and 0.92 (0.80-1.06), respectively. An increasing risk with longer duration was found for younger women, which was not observed with older age groups. In all age groups, the highest risk of MI was found with continuous HT regimen. No increased risk was found with unopposed oestrogen, cyclic combined therapy, or tibolone. Significantly lower risk was found with dermal route than oral unopposed oestrogen therapy (P = 0.04). No associations were found with progestagen type or oestrogen dose. CONCLUSION: In a National cohort study, we found that HT regimen and route of application could modify the influence of HT on the risk of MI.

Hormone therapy and ovarian cancer.

CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian cancers, of which 2681 were epithelial cancers, were detected. Compared with women who never took hormone therapy, current users of hormones had incidence rate ratios for all ovarian cancers of 1.38 (95% confidence interval [CI], 1.26-1.51) and 1.44 (95% CI, 1.30-1.58) for epithelial ovarian cancer. The risk declined with years since last use: 0 to 2 years, 1.22 (95% CI, 1.02-1.46); more than 2 to 4 years, 0.98 (95% CI, 0.75-1.28); more than 4 to 6 years, 0.72 (95% CI, 0.50-1.05), and more than 6 years, 0.63 (95% CI, 0.41-0.96). For current users the risk of ovarian cancer did not differ significantly with different hormone therapies or duration of use. The incidence rates in current and never users of hormones were 0.52 and 0.40 per 1000 years, respectively, ie, an absolute risk increase of 0.12 (95% CI, 0.01-0.17) per 1000 years. This approximates 1 extra ovarian cancer for roughly 8300 women taking hormone therapy each year. CONCLUSION: Regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk of ovarian cancer.

Salt Reduction Intervention in Families Investigating Metabolic, Behavioral and Health Effects of Targeted Intake Reductions: Study Protocol for a Four Months Three-Armed, Randomized, Controlled "Real-Life" Trial.

Reductions in salt intake have the potential to markedly improve population health at low cost. Real life interventions that explore the feasibility and health effects of a gradual salt reduction lasting at least four weeks are required. The randomized controlled SalT Reduction InterVEntion (STRIVE) trial was developed to investigate the metabolic, behavioral and health effects of four months of consuming gradually salt reduced bread alone or in combination with dietary counselling. This paper describes the rationale and methods of STRIVE. Aiming at 120 healthy families, participants were recruited in February 2018 from the Danish Capital Region and randomly allocated into: (A) Salt reduced bread; (B) Salt reduced bread and dietary counseling; (C) Standard bread. Participants were examined before the intervention and at four months follow-up. Primary outcome is change in salt intake measured by 24 h urine. Secondary outcomes are change in urine measures of potassium and sodium/ potassium ratio, blood pressure, plasma lipids, the renin-angiotensin system, the sympathetic nervous response, dietary intake as well as salt taste sensitivity and preferences. The results will qualify mechanisms affected during a gradual reduction in salt intake in compliance with the current public health recommendations.

Using prescription registries to define continuous drug use: how to fill gaps between prescriptions.

Pharmacoepidemiological studies often use prescription registries to assess patients' drug episodes. The databases usually provide information on the date of the redemption of the prescription as well as on the dispensed amount, and this allows us to define episodes of drug use. However, when patients take less medication than prescribed, apparent gaps between prescriptions occur, and most studies handle this issue by allowing for small gaps when defining continuous drug use. This paper argues that it becomes crucial whether gaps are 'filled' prospectively or retrospectively. In the latter case the inferred exposure status depends on the patient's future dispensing behaviour and this can lead to severe bias in the findings of the study. In this paper we investigate this potential bias in a study of the risk of acute myocardial infarction (AMI) for women using hormone therapy (HT), and we show that the retrospective exposure definition introduces an artificially protective effect of HT.

National incidence and survival of patients with non-invasive papillary urothelial carcinoma: a Danish population study.

OBJECTIVE: To estimate national relative survival of low and high grade non-invasive papillary urothelial carcinoma (Ta LG and Ta HG) and urothelial carcinoma in situ (CIS). MATERIALS AND METHODS: All Danish citizens (17,941 patients) with a primary urothelial bladder tumour diagnosis in the period 2000- 2010 were followed until 1 January 2016 and recorded in the Danish Bladder Cancer Cohort database. Survival was compared to the background population matched on age and gender and adjusted by civil status, income, education, and comorbidity. RESULTS: Patients treated in daily practice with Ta LG have 46% (HR = 1.46 (1.42-1.51) p < 0.001) higher risk of death compared to a background population matched for age and gender. This risk of death ceases to 28% (HR = 1.28 (1.24-1.32) p < 0.001) after adjustment for civil status, income, education, and comorbidity. Relative survival of Ta LG patients is 0.94 (0.93-0.95). These estimates are constant throughout the observation period. Significantly higher mortality is found for patients with Ta HG and CIS, but, in contrast to Ta LG, the relative risk of death of Ta HG (HR = 1.79 (1.69-1.90) p < 0.001) and CIS (HR = 2.02 (1.79-2.26) p < 0.001) decreases considerably after 5 years survival (HR = 1.43 (1.30-1.57) p < 0.001 and HR = 1.64 (1.36-1.98) p < 0.001, respectively). CONCLUSION: Patients with Ta LG have a continuous lower survival and a 28% higher risk of death at any time compared to a matched background population when treated in daily practice.