The Danish Investigation on Iodine Intake and Thyroid Disease (DanThyr): history and implications.

Due to mild to moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from WHO, the Danish Investigation on Iodine Intake and Thyroid Disease (DanThyr) was established to monitor the effect on thyroid health and diseases. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low-adequacy. The level of thyroglobulin and thyroid volume decreased following IF and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Taking no for an answer. Nurses' consultations with people with cardiac disease about rehabilitation: A qualitative study.

BACKGROUND: Research shows that many people with cardiac disease decline cardiac rehabilitation. There is little or no knowledge on how health professionals respond to these people. OBJECTIVES: To investigate how nurses respond to people who do not wish to participate in cardiac rehabilitation and what influences the nurses´ approach towards these people. DESIGN: A qualitative study involving interviews and video-recordings using an analysis inspired by ethnographic principles and categorisation theory. SETTING: A rehabilitation clinic at a large hospital in the Capital Region of Denmark. PARTICIPANTS: Five cardiac nurses and 28 people with cardiac disease. METHODS: We video-recorded the first consultation people with cardiac disease attended regarding cardiac rehabilitation, where the nurses followed up on these people's recovery, medication, lifestyle and need for rehabilitation. We conducted semi-structured interviews with the cardiac nurses. We asked the nurses about the purpose of the first rehabilitation consultation and how they handle people with cardiac disease who say no to rehabilitation. The nurses were shown video-clips with the people they had talked to in their consultation in order to facilitate a dialogue. RESULTS: When people with cardiac disease were reluctant to participate in rehabilitation, the nurses made an individual assessment of how much effort to put into motivating them, taking a complex range of factors into account. The effort among the nurses towards people with cardiac disease who decline rehabilitation was smaller in cases when the nurses believed an individual would benefit less from rehabilitation or have difficulty participating. It was important for the nurses to balance their motivational efforts with showing respect for people's autonomy. CONCLUSION: Even when nurses endorse rehabilitation, some people with cardiac disease decline rehabilitation. The nurses' recommendation of the rehabilitation programme is influenced by the knowledge they obtain about the people with cardiac disease during consultations.

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

Trends in the risk of early and late-onset heart failure as an adverse outcome of acute myocardial infarction: A Cardiovascular Disease in Norway project.

Aims Heart failure is a serious complication of acute myocardial infarction, leading to a poor prognosis. We explored trends in the risk of heart failure among patients hospitalised with an incident acute myocardial infarction in Norway during 2001-2009. Methods and results A total of 69,372 patients were followed for an episode of heart failure occurring either during (early-onset heart failure) or within one year of discharge from the incident acute myocardial infarction hospitalisation (late-onset heart failure). Logistic regression and competing risk regression models were used to explore trends in early and late-onset heart failure respectively. Overall, 17.1% of patients had early-onset heart failure. The odds of heart failure increased by 2.3% per year (odds ratio = 1.023; 95% confidence interval: 1.015-1.031), influenced by an increase of 5.9% per year among younger (25-69 years) patients while no statistically significant changes occurred among older (70-84 years) patients. Among 47,673 patients discharged alive, without early-onset heart failure, 5.4% experienced late-onset heart failure. The risk of heart failure declined by 6.3% per year (subhazard ratio = 0.937; 95% confidence interval: 0.921-0.954). The decline was statistically significant in both age groups (6.8% per year and 5.9% per year respectively). Overall, the risk of heart failure occurring at any time during the follow up did not change significantly. However, it increased by 3.3% per year in younger patients and declined by 1.5% per year in older patients. Conclusions Heart failure occurring during acute myocardial infarction hospitalisation accounts for the majority of heart failure cases and is characterised by unfavourable trends, while heart failure rates following acute myocardial infarction discharge declined over the study period.

Prognostic Impact of In-Hospital and Postdischarge Heart Failure in Patients With Acute Myocardial Infarction: A Nationwide Analysis Using Data From the Cardiovascular Disease in Norway (CVDNOR) Project.

BACKGROUND: Heart failure (HF) is a serious complication of acute myocardial infarction (AMI). We explored the excess mortality associated with HF as an early or late complication of AMI and describe changes over time in such excess mortality. METHODS AND RESULTS: All patients hospitalized with an incident AMI and without history of prior HF hospitalization were followed up to 1 year after AMI discharge for episodes of HF. New HF episodes were classified as in-hospital HF if diagnosed during the AMI hospitalization or postdischarge HF if diagnosed within 1 year after discharge from the incident AMI. Logistic and Cox regression models were used to explore the excess mortality associated with HF categories. Changes over time in the excess mortality were assessed by testing the interaction between HF status and study year. In-hospital HF increased in-hospital mortality 1.79 times (odds ratio [OR], 1.79; 95% CI: 1.68-1.91). The excess mortality associated with HF increased by 4.3 times from 2001 to 2009 (P interaction<0.001) as a consequence of a greater decline of in-hospital mortality among AMI patients without (9% per year) compared to those with in-hospital HF (3% per year). Postdischarge HF increased all-cause and CVD mortality 5.98 times (hazard ratio, 5.98; 95% CI: 5.39-6.64) and 7.93 times (subhazard ratio, 7.93; 95% CI: 6.84 -9.19), respectively. The relative excess 1-year mortality associated with HF did not change significantly over time. CONCLUSIONS: Development of HF-either as an early or late complication of AMI-has a negative impact on patients' survival. Changes in the excess mortality associated with HF are driven by modest improvements in survival among AMI patients with HF as compared to those without HF.

Carriers of a VEGFA enhancer polymorphism selectively binding CHOP/DDIT3 are predisposed to increased circulating levels of thyroid-stimulating hormone.

BACKGROUND: Levels of serum thyroid-stimulating hormone (TSH) indicate thyroid function, because thyroid hormone negatively controls TSH release. Genetic variants in the vascular endothelial growth factor A (VEGFA) gene are associated with TSH levels. The aim of this study was to characterise the association of VEGFA variants with TSH in a Danish cohort and to identify and characterise functional variants. METHODS: We performed an association study of the VEGFA locus for circulating TSH levels in 8445 Danish individuals. Lead variants were tested for allele-specific effects in vitro using luciferase reporter and gel-shift assays. RESULTS: Four SNPs in VEGFA were associated with circulating TSH (rs9472138, rs881858, rs943080 and rs4711751). For rs881858, the presence of each G-allele was associated with a corresponding decrease in TSH levels of 2.3% (p=8.4×10-9) and an increase in circulating free T4 levels (p=0.0014). The SNP rs881858 is located in a binding site for CHOP (C/EBP homology protein) and c/EBPß (ccaat enhancer binding protein ß). Reporter-gene analysis showed increased basal enhancer activity of the rs881858 A-allele versus the G-allele (34.5±9.9% (average±SEM), p=0.0012), while co-expression of CHOP effectively suppressed the rs881858 A-allele activity. The A-allele showed stronger binding to CHOP in gel-shift assays. CONCLUSIONS: VEGF is an important angiogenic signal required for tissue expansion. We show that VEGFA variation giving allele-specific response to transcription factors with overlapping binding sites associate closely with circulating TSH levels. Because CHOP is induced by several types of intracellular stress, this indicates that cellular stress could be involved in the normal or pathophysiological response of the thyroid to TSH. TRIAL REGISTRATION NUMBER: NCT00289237, NCT00316667; Results.

The Danish Adult Diabetes Registry.

AIM OF THE DATABASE: The aim of the Danish Adult Diabetes Registry (DADR) is to provide data from both the primary health care sector (general practice [GP]) and the secondary sector (specialized outpatient clinics) to assess the quality of treatment given to patients with diabetes. The indicators represent process and outcome indicators selected from the literature. STUDY POPULATION: The total diabetes population in Denmark is estimated to be ~300,000 adult diabetes patients. Approximately 10% have type 1 diabetes, which is managed mainly in the secondary sector, and 90% have type 2 diabetes with the majority (80%) being treated in primary health care. In 2014, DADR included data from a total of 70,826 patients. MAIN VARIABLES: The following variables are assessed: date of analysis as well as the outcome for hemoglobin A1c, blood pressure, lipids, urinary albumin-creatinine ratio, smoking status, glucose-, blood pressure-, and lipid-lowering treatment (yes/no), insulin pump treatment (yes/no), and date of last eye and foot examination. DESCRIPTIVE DATA: In 2014, the annual report included data regarding over 38,000 patients from outpatient clinics, which is assumed to have included almost all patients in this setting, and >32,000 from GPs, reflecting improved but still limited coverage from this setting. The annual results are published in a compiled report of Danish Diabetes Care, which included DADR, data from the pediatric diabetes database, and the national ophthalmological diabetes database. The annual report is published, which included data on national, regional, and local level (individual outpatient clinics and corresponding GPs). This allows a comprehensive overview of diabetes care in Denmark. CONCLUSION: The database covers an increasing fraction of patients with diabetes in Denmark, and the structure for full coverage is in place. Annual reporting has helped to ensure focus on the quality of diabetes treatment in the primary and secondary health care. Furthermore, it is an important resource for Danish register-based diabetes research.

The Danish National Database for Obstructive Sleep Apnea.

AIM: The aim of the Danish National Database for Obstructive Sleep Apnea (NDOSA) was to evaluate the clinical quality (diagnostic, treatment, and management) for obstructive sleep apnea and obesity hypoventilation syndrome in Denmark using a real-time national database reporting to the Danish National Patient Registry. STUDY POPULATION: All patients diagnosed with obstructive sleep apnea or obesity hypoventilation syndrome at public and private in- and out-hospital departments in Denmark were included. MAIN VARIABLES: The NDOSA contains information about baseline characteristics, comorbidity, diagnostic procedures conducted, treatment (continuous positive airway pressure and similar treatments, surgery, mandibular advancement devices, etc) complications, and treatment status. DESCRIPTIVE DATA: Yearly report with indicators for diagnostic procedures, treatment, and follow-up comparing different departments was involved in the management of sleep apnea in Denmark for the purpose of quality improvement. CONCLUSION: The NDOSA has proven to be a real-time national database using diagnostic and treatment procedures reported to the Danish National Patient Registry.

The Danish Schizophrenia Registry.

AIM OF DATABASE: To systematically monitor and improve the quality of treatment and care of patients with schizophrenia in Denmark. In addition, the database is accessible as a resource for research. STUDY POPULATION: Patients diagnosed with schizophrenia and receiving mental health care in psychiatric hospitals or outpatient clinics. During the first year after the diagnosis, patients are classified as incident patients, and after this period as prevalent patients. MAIN VARIABLES: The registry currently contains 21 clinical quality measures in relation to the following domains: diagnostic evaluation, antipsychotic treatment including adverse reactions, cardiovascular risk factors including laboratory values, family intervention, psychoeducation, postdischarge mental health care, assessment of suicide risk in relation to discharge, and assessment of global functioning. DESCRIPTIVE DATA: The recorded data are available electronically for the reporting clinicians and responsible administrative personnel, and they are updated monthly. The registry publishes the national and regional results of all included quality measures in the annual audit reports. External researchers may obtain access to the data for use in specific research projects by applying to the steering committee. CONCLUSION: The Danish Schizophrenia Registry represents a valuable source of informative data to monitor and improve the quality of care of patients with schizophrenia in Denmark. However, continuous resources and time devoted is necessary to maintain the integrity of the registry and the validity of the data.

The Danish Cardiac Rehabilitation Database.

AIM OF DATABASE: The Danish Cardiac Rehabilitation Database (DHRD) aims to improve the quality of cardiac rehabilitation (CR) to the benefit of patients with coronary heart disease (CHD). STUDY POPULATION: Hospitalized patients with CHD with stenosis on coronary angiography treated with percutaneous coronary intervention, coronary artery bypass grafting, or medication alone. Reporting is mandatory for all hospitals in Denmark delivering CR. The database was initially implemented in 2013 and was fully running from August 14, 2015, thus comprising data at a patient level from the latter date onward. MAIN VARIABLES: Patient-level data are registered by clinicians at the time of entry to CR directly into an online system with simultaneous linkage to other central patient registers. Follow-up data are entered after 6 months. The main variables collected are related to key outcome and performance indicators of CR: referral and adherence, lifestyle, patient-related outcome measures, risk factor control, and medication. Program-level online data are collected every third year. DESCRIPTIVE DATA: Based on administrative data, approximately 14,000 patients with CHD are hospitalized at 35 hospitals annually, with 75% receiving one or more outpatient rehabilitation services by 2015. The database has not yet been running for a full year, which explains the use of approximations. CONCLUSION: The DHRD is an online, national quality improvement database on CR, aimed at patients with CHD. Mandatory registration of data at both patient level as well as program level is done on the database. DHRD aims to systematically monitor the quality of CR over time, in order to improve the quality of CR throughout Denmark to benefit patients.

The Danish Heart Failure Registry.

AIM OF DATABASE: The aim of the Danish Heart Failure Registry (DHFR) is to monitor and improve the care of patients with incident heart failure (HF) in Denmark. STUDY POPULATION: The DHFR includes inpatients and outpatients (≥18 years) with incident HF. Reporting to the DHFR is mandatory for the Danish hospital departments treating patients with incident HF. Final decision to register a patient in the DHFR is made by a cardiologist to ensure the validity of the diagnosis. Approximately 42,400 patients with incident HF were registered in the DHFR in July 2015. MAIN VARIABLES AND DESCRIPTIVE DATA: The main variables recorded in the DHFR are related to the indicators for quality of care in patients with incident HF: performance of echocardiography, functional capacity (New York Heart Association functional classification), pharmacological therapy (angiotensin converting enzyme/angiotensin II antagonist inhibitors, beta-blockers, and mineralocorticoid receptor antagonist), nonpharmacological therapy (physical training, patient education), 4-week readmission rate, and 1-year mortality. Furthermore, basic patient characteristics and prognostic factors (eg, smoking and alcohol) are recorded. At the annual national audit in the DHFR, the indicators and standards for good clinical quality of care for patients with HF are discussed, and recommendations are reported back to clinicians to promote quality improvement initiatives. Furthermore, results and recommendations are communicated to the public in an annual report. All standards for the quality indicators have been met at a national level since 2014. Indicators for treatment status 1 year after diagnosis are under consideration (now prevalent HF). CONCLUSION: The DHFR is a valuable tool for continuous improvement of quality of care in patients with incident HF in Denmark. Furthermore, it is an important resource for the Danish registry-based HF research.

The Danish Registry of Diabetic Retinopathy.

AIM OF DATABASE: To monitor the development of diabetic eye disease in Denmark and to evaluate the accessibility and effectiveness of diabetic eye screening programs with focus on interregional variations. TARGET POPULATION: The target population includes all patients diagnosed with diabetes. Denmark (5.5 million inhabitants) has ~320,000 diabetes patients with an annual increase of 27,000 newly diagnosed patients. The Danish Registry of Diabetic Retinopathy (DiaBase) collects data on all diabetes patients aged ≥18 years who attend screening for diabetic eye disease in hospital eye departments and in private ophthalmological practice. In 2014-2015, DiaBase included data collected from 77,968 diabetes patients. MAIN VARIABLES: The main variables provide data for calculation of performance indicators to monitor the quality of diabetic eye screening and development of diabetic retinopathy. Data with respect to age, sex, best corrected visual acuity, screening frequency, grading of diabetic retinopathy and maculopathy at each visit, progression/regression of diabetic eye disease, and prevalence of blindness were obtained. Data analysis from DiaBase's latest annual report (2014-2015) indicates that the prevalence of no diabetic retinopathy, nonproliferative diabetic retinopathy, and proliferative diabetic retinopathy is 78%, 18%, and 4%, respectively. The percentage of patients without diabetic maculopathy is 97%. The proportion of patients with regression of diabetic retinopathy (20%) is greater than the proportion of patients with progression of diabetic retinopathy (10%). CONCLUSION: The collection of data from diabetic eye screening is still expanding in Denmark. Analysis of the data collected during the period 2014-2015 reveals an overall decrease of diabetic retinopathy compared to the previous year, although the number of patients newly diagnosed with diabetes has been increasing in Denmark. DiaBase is a useful tool to observe the quality of screening, prevalence, and progression/regression of diabetic eye disease.

Danish Registry of Childhood and Adolescent Diabetes.

AIM: The aims of the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) are to monitor and improve the quality of care for children and adolescents with diabetes in Denmark and to follow the incidence and prevalence of diabetes. STUDY POPULATION: The study population consists of all children diagnosed with diabetes before the age of 15 years since 1996. Since 2015, every child followed up at a pediatric center (<18 years of age) will be included. MAIN VARIABLES: The variables in the registry are the quality indicators, demographic variables, associated conditions, diabetes classification, family history of diabetes, growth parameters, self-care, and treatment variables. The quality indicators are selected based on international consensus of measures of good clinical practice. The indicators are metabolic control as assessed by HbA1c, blood pressure, albuminuria, retinopathy, neuropathy, number of severe hypoglycemic events, and hospitalization with ketoacidosis. DESCRIPTIVE DATA: The number of children diagnosed with diabetes is increasing with ∼3% per year mainly for type 1 diabetes (ie, 296 new patients <15 years of age were diagnosed in 2014). The disease management has changed dramatically with more children treated intensively with multiple daily injections, insulin pumps, and increased number of self-monitored blood glucose values per day. These initiatives have resulted in a significant improvement in HbA1c over the years and a decrease in the number of children experiencing severe hypoglycemia, diabetic nephropathy, and retinopathy. CONCLUSION: The systematic collection of data in DanDiabKids documents improved quality of care over the last 12 years, despite a substantial increase in the number of patients cared for by pediatric departments in Denmark, fulfilling the purpose of the registry.

The Danish Vascular Registry, Karbase.

AIM: The Danish Vascular Registry (DVR), Karbase, is monitoring arterial and advanced vein interventions conducted at all vascular departments in Denmark. The main aim of the DVR is to improve the quality of treatment for patients undergoing vascular surgery in Denmark by using the registry for quality assessment and research. STUDY POPULATION: All patients undergoing vascular interventions (surgical and endovascular) at any vascular department in Denmark are registered in the DVR. The DVR was initiated in 1989, and each year, ∼9,000 procedures are added. By January 2016, >180,000 procedures have been recorded. Since 2001, data completeness has been >90% (compared to the Danish National Patient Register). MAIN VARIABLES: Variables include information on descriptive patient data (ie, age, sex, height, and weight) and comorbidity (ie, previous cardiovascular disease and diabetes). Process variable includes waiting time (time from event to medical contact and treatment) and the type of procedures conducted. Outcome variables for in-hospital complications (ie, wound complications, myocardial infarction, stroke, amputation, respiratory complications, and renal insufficiency) and 30-day patency are submitted. Variables for medical treatment (antithrombotic and statin treatment), amputation, and survival are extracted from nationwide, administrative registers. CONCLUSION: The DVR reports outcome on key indicators for monitoring the quality at all vascular departments in Denmark for the purpose of quality improvement. Furthermore, data are available for research and are being used in international collaborations on changes in clinical practices.

Estimating salt intake in a Caucasian population: can spot urine substitute 24-hour urine samples?

BACKGROUND: A simple and valid alternative for 24-hour urine collection to estimate populational 24-hour urinary sodium excretion would be desirable for monitoring sodium intake in populations. AIM: To assess the validity of the predicted 24-hour urinary sodium excretion using spot urine and two different prediction methods in a Danish population. METHODS: Overall, 473 Danish individuals provided a para-aminobenzoic acid-validated complete 24-hour urine collection and a spot urine sample. Data were collected in the DanThyr study (248 women aged 25-30 years and 60-65 years) and the Inter99 study (102 men and 113 women aged 30-60 years), respectively. The measured 24-hour urine sodium excretion was compared with the predicted 24-hour sodium excretion from a causal urine specimen, using both the Tanaka prediction method and a prediction model developed in a Danish population. RESULTS: The measured 24-hour sodium excretion (median, 5th to 95th percentile) was men 195 (110 to 360) and women 139 (61 to 258), whereas the predicted 24-hour sodium excretion for the Tanaka model was men 171 (117 to 222) and women 153 (92 to 228) and for the Danish model was men 207 (146 to 258); women 134 (103 to 163). The Spearman correlation between predicted and measured 24-hour sodium excretion was 0.39 and 0.49 for the Tanaka and the Danish model, respectively. For both prediction models, the proportion of individuals classified in the same or adjacent quintile was 74% for men and 64% for women. CONCLUSIONS: Both prediction models gave a reasonable classification of individuals according to their sodium excretion. However, the median daily sodium intake was estimated more precisely by the Danish model, especially among men.