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PURPOSE: This study estimated epilepsy prevalence, psychiatric co-morbidity and annual costs associated with epilepsy.METHODS: We used Danish national health registers to identify persons diagnosed with epilepsy and psychiatric disorders, and persons using antiseizure medication and persons using drugs for psychiatric disorders. We calculated the prevalence of epilepsy and co-morbid psychiatric disorders in Denmark on December 31, 2016, using information on epilepsy and psychiatric disorders based on combinations of hospital contacts and use of antiseizure and psychoactive medication. Further, direct and indirect annual costs associated with epilepsy were calculated using individual-level data from a range of socioeconomic registers.RESULTS: There were 5,044,367 persons alive and living in Denmark on December 31, 2016, including 33,628 persons with at least one hospital contact with epilepsy in the previous five years (epilepsy prevalence 0.67% (0.69% males; 0.65% females)). Among these persons with epilepsy, we identified 12,562 (37.4%) persons with a psychiatric disorder or use of drugs used for psychiatric disorders as compared with 801,052 (15.9%) persons in the general population. The estimated total annual individual net costs associated with epilepsy was €30,683. Compared with prevalence estimates on December 31, 2006, the prevalence of epilepsy on December 31, 2016, was slightly higher in the older population and slightly lower in children CONCLUSIONS: Population estimates from national registers provide epilepsy prevalence estimates of approximately 0.6-0.7% - similar to previous reviews of epilepsy prevalence. In addition, the national sample allowed idenitfication of high prevalence of psychiatric disorders and high societal costs associated with epielspy.

Objective: Patients with chronic obstructive pulmonary disease (COPD) commonly present with cardiovascular disease (CVD). We investigated the association between COPD exacerbations and major cardiovascular (CV) events in a COPD population with a history of CVD.Methods: This population-based and register-based cohort study identified all Danish COPD patients aged ≥ 40 years who visited a hospital-based, pulmonary outpatient clinic for COPD between 1st January, 2010, and 31st December, 2016, from a nationwide COPD registry. Patients with a history of a major CV event 36‒6 months prior to their COPD measurement date and no CV event 6 months before this date were included. During a 6-month assessment period, the risks of a new CV event (hospitalization with fatal/non-fatal stroke, myocardial infarction, or heart failure) and moderate and severe COPD exacerbations were evaluated. Odds ratios with 95% confidence intervals for CV events and death were estimated using adjusted logistic regression models.Results: Of the 1501 COPD patients included, 55% experienced a COPD exacerbation and 13% experienced both an exacerbation and a CV event during follow-up (6 months). The odds of a CV event were 1.5 times higher in patients with a moderate exacerbation and more than 6-times higher in those with a severe exacerbation vs patients with no exacerbation(s). The majority of CV events occurred within 30 days post exacerbation in patients who experienced both an exacerbation and a CV event. In total, 113 patients died during the study period: 28% of deaths were caused by CVD and 72% by reasons other than CVD, mostly COPD.Conclusion: In patients with known CVD, severe COPD exacerbations are associated with increased odds of major CV events that occur within 30 days post exacerbation, highlighting the need to prevent exacerbations in COPD patients with concomitant CVD to potentially improve both respiratory and CV health.Keywords: concomitant cardiovascular disease, respiratory health, cardiovascular health, prevention, real-world evidence Objective: Patients with chronic obstructive pulmonary disease (COPD) commonly present with cardiovascular disease (CVD). We investigated the association between COPD exacerbations and major cardiovascular (CV) events in a COPD population with a history of CVD.Methods: This population-based and register-based cohort study identified all Danish COPD patients aged >= 40 years who visited a hospital-based, pulmonary outpatient clinic for COPD between 1st January, 2010, and 31st December, 2016, from a nationwide COPD registry. Patients with a history of a major CV event 36-6 months prior to their COPD measurement date and no CV event 6 months before this date were included. During a 6-month assessment period, the risks of a new CV event (hospitalization with fatal/ non-fatal stroke, myocardial infarction, or heart failure) and moderate and severe COPD exacerbations were evaluated. Odds ratios with 95% confidence intervals for CV events and death were estimated using adjusted logistic regression models.Results: Of the 1501 COPD patients included, 55% experienced a COPD exacerbation and 13% experienced both an exacerbation and a CV event during follow-up (6 months). The odds of a CV event were 1.5 times higher in patients with a moderate exacerbation and more than 6-times higher in those with a severe exacerbation vs patients with no exacerbation(s). The majority of CV events occurred within 30 days post exacerbation in patients who experienced both an exacerbation and a CV event. In total, 113 patients died during the study period: 28% of deaths were caused by CVD and 72% by reasons other than CVD, mostly COPD.Conclusion: In patients with known CVD, severe COPD exacerbations are associated with increased odds of major CV events that occur within 30 days post exacerbation, highlighting the need to prevent exacerbations in COPD patients with concomitant CVD to potentially improve both respiratory and CV health.

Heart failure (HF) and diabetes mellitus (DM) are burdensome chronic diseases with high lifetime risks and numerous studies indicate associations between HF and DM. The objective of this study was to investigate the direct and indirect costs of HF patients with and without DM.Patients with a first-time diagnosis of HF from 1998 to 2016 were identified through nationwide Danish registries and stratified according to DM status into HF with or without DM. The economic healthcare cost analysis was based on both direct costs, including hospitalization, procedures, medication and indirect costs including social welfare and lost productivity. The economic burden was investigated prior to, at, and following diagnosis of HF. Patients with concomitant HF and DM were younger (median age 74 vs. 77), had more comorbidities and fewer were female as compared to patients with HF but without DM. The socioeconomic burden of concomitant HF and DM compared to HF alone was substantially higher; 45% in direct costs (€16,237 vs. €11,184), 35% in home care costs (€3123 vs. €2320), 8% in social transfer income (€17,257 vs. €15,994) and they had 27% lower income (€10,136 vs. €13,845). The economic burden peaked at year of diagnosis, but the difference became increasingly pronounced in the years following the HF diagnosis.Patients with concomitant HF and DM had a significantly higher economic burden compared to patients with HF but without DM.

Background and objective: The study aimed to evaluate the direct and indirect costs of systemic sclerosis (SSc) in cases with and without interstitial lung disease (ILD). Methods: Cases diagnosed with SSc (2002–2015) were identified in the Danish National Patient Registry. Cases were matched 1:4 with non-SSc controls from the general population. Data on costs were obtained from national databases. Excess cost was estimated as the annual cost per case subtracting the costs of the control. Results: We identified 1869 cases and 7463 controls. Total excess cost (direct healthcare, elderly care and indirect costs) in the SSc-ILD cohort was €29,725, and €17,905 in the non-ILD SSc cohort. In- and out-patient contacts and forgone earnings were the key drivers of costs in both cohorts. Healthcare costs were higher before and after the diagnosis compared with the controls. Men incurred higher excess healthcare costs than women. Hospitalization and outpatient services were the key drivers of the gender-associated differences. Income from employment decreased more rapidly after diagnosis in the SSc-ILD cohort than in the non-ILD SSc cohort. Public transfer income increased after diagnosis, with the most pronounced difference in the SSc-ILD cohort. Disability pension was the key driver of public transfer income. Conclusion: SSc is associated with a significant individual and societal burden that is evident several years before and after the diagnosis. Total excess costs are higher in SSc-ILD than in the non-ILD SSc underlining the severity of pulmonary involvement. Initiatives to maintain work ability and to reduce hospital admissions may reduce the economic burden of SSc.

Urinary retention (UR) caused by non-neurogenic conditions is a frequent disorder often requiring the use of intermittent catheterization (IC). This study examines the burden of illness among subjects with an IC indication due to non-neurogenic UR. Health-care utilization and costs were extracted from Danish registers (2002–2016) related to the first year after IC training and compared to matched controls. A total of 4,758 subjects with UR due to benign prostatic hyperplasia (BPH) and 3,618 subjects with UR due to other non-neurological conditions were identified. Total health-care utilization and costs per patient-year were significantly higher compared to matched controls (BPH: 12,406 EUR vs 4,363, p < 0.000; other non-neurogenic causes: 12,497 EUR vs 3,920, p < 0.000) and driven mainly by hospitalizations. Urinary tract infections (UTIs) were the most frequent bladder complications often requiring hospitalization. The inpatient costs per patient-year for UTIs were significantly higher for cases than controls (BPH: 479 EUR vs 31, p < 0.000; other non-neurogenic causes: 434 EUR vs 25, p < 0.000). The burden of illness caused by non-neurogenic UR with need for IC was high and essentially driven by hospitalizations. Further research should clarify if additional treatment measures may reduce the burden of illness in subjects suffering from non-neurogenic UR using IC.

Aim: To evaluate survival distributions, long-term socioeconomic consequences, and health care costs in patients with childhood and adolescent onset of brain tumours in a Danish nationwide prospective cohort study. Method: A search of national registries identified 2283 patients (1198 males, 1085 females; mean age 9 years 6 months [SD 5 years 7 months]) diagnosed with a brain tumour between 1980 and 2015 and aged no older than 18 years at diagnosis. These were compared with sex-, age-, and residency-matched comparison individuals. Patients with malignant tumours were compared with those with benign tumours. Survival distributions were estimated by the Kaplan–Meier method and hazard ratio by the Cox proportional hazard model. Socioeconomic data at age 20 and 30 years were assessed. Results: The probability of mortality was highest during the first year after tumour diagnosis. In young adulthood, the patients were generally less likely to be married, had lower grade-point averages, educational levels, and income, were less likely to be in employment, and had higher health care costs than comparison individuals. Patients with malignant tumours had worse outcomes with respect to education, employment, and health care costs than those with benign tumours. Interpretation: A diagnosis of brain tumour in childhood and adolescence adversely affects survival and has negative long-term socioeconomic consequences, especially in patients with malignant tumours. These patients require continuous social support.

IntroductionAs a common chronic disease seen across all ages, asthma has the potential to incur high societal and individual costs from both direct healthcare costs and loss of productivity. Most previous studies use smaller, selected populations to assess the cost of asthma, possibly reducing generalisability. We, therefore, aimed to assess the total, nationwide economic burden of asthma by severity from both an individual and a societal perspective.MethodsThe annual cost of asthma was assessed in a Danish nationwide cohort of patients aged 18–45 during 2014–2016 as excess healthcare costs, loss of income and welfare expenditure compared with controls (matched 1:4) using national registries. Asthma severity was defined as mild-to-moderate (steps 1–3 or step 4 without exacerbations) or severe (step 4 with exacerbations or step 5).ResultsAcross 63 130 patients (mean age 33, 55% female), the annual excess cost of asthma compared with controls was predicted to €4095 (95% CI €3856 to €4334) per patient. Beyond direct costs related to treatment and hospitalisations (€1555 (95% CI €1517 to €1593)), excess indirect costs related to loss of income (€1060 (95% CI €946 to €1171)) and welfare expenditure (eg, sick pay and disability pensions) (€1480 (95% CI €1392 to €1570)) were seen. Crude pooling of excess costs resulted in an annual societal cost of €263 million for all included patients.Severe asthma (4.5%) incurred 4.4 times higher net costs (€15 749 (95% CI 13 928 to €17 638)) compared with mild-to-moderate disease (€3586 (95% CI €3349 to €3824)). Furthermore, patients with severe asthma experienced an annual loss of income of €3695 (95% CI €4106 to €3225) compared with controls.ConclusionIn young adults with asthma, a significant societal and individual financial burden of disease was seen across severities. Expenditure was mainly driven by loss of income and welfare utilisation, rather than direct healthcare costs.

There is insufficient data regarding the excess direct and indirect costs associated with attention deficit hyperactivity disorder (ADHD). Using the Danish National Patient Registry (2002-2016), we identified 83,613 people of any age with a diagnosis of ADHD or who were using central-acting medication against ADHD (primarily methylphenidate, with at least two prescriptions) and matched them to 334,446 control individuals. Additionally, 18,959 partners of patients aged ≥18 years with ADHD were identified, and compared with 74,032 control partners. Direct costs were based on data from the Danish Ministry of Health. Information about the use and costs of drugs were obtained from the Danish Medicines Agency. The frequencies of visits and hospitalizations, and costs of general practice were derived from data from the National Health Security. Indirect costs were obtained from Coherent Social Statistics. The average annual health care costs for people with ADHD and their partners were, respectively, €2636 and €477 higher than those of the matched controls. A greater percentage of people with ADHD and their partners compared with respective control subjects received social services (sick pay or disability pension). Those with ADHD had a lower income from employment than did controls for equivalent periods up to five years before the first diagnosis of ADHD. The additional direct and indirect annual costs (for those aged ≥18 years) including transfers of ADHD compared with controls were €23,072 for people with ADHD and €7,997 for their partners. ADHD has substantial socioeconomic consequences for individual patients, their partners and society.

Objectives There is limited information about the long-term consequences of childhood- and adolescent-onset narcolepsy on educational and social factors. Here, we estimate the long-term socioeconomic consequences and health care costs of narcolepsy. Methods The prospective cohort study included Danish individuals with narcolepsy onset in childhood or adolescence, diagnosed between 1994 and 2015. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. One hundred seventy-one patients were compared with 680 controls (mean index age, 15.2 years; SD, 3.4 years) matched for age, gender, and other sociodemographic characteristics. Results Comparing the narcolepsy patient and control groups at age 20 years we found: (1) no differences in parental educational level; (2) patients had a significantly lower educational level than controls; (3) patients had significantly lower grade-point averages; (4) patients had a lower employment rate and lower-income, even when transfer payments were considered; and (5) patients' initial health care costs were higher. Patients had a higher mortality rate than controls, although the difference was not statistically significant. Conclusion Narcolepsy is associated with a significant influence on educational level, grading, social outcome, and welfare consequences. The development of narcolepsy is independent of parental social level.

Anders Løkke,1,2 Ole Hilberg,1,2 Peter Lange,3,4 Rikke Ibsen,5 Georgios Stratelis,6,7 Sofie de Fine Licht,6 Jesper Lykkegaard8 1Department of Medicine, Little Belt Hospital, Vejle, Denmark; 2Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; 3Medical Department, Copenhagen University Hospital-Herlev, Herlev, Denmark; 4Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark; 5i2Minds, Aarhus, Denmark; 6AstraZeneca Nordic, Södertälje, Sweden; 7Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 8Research Unit for General Practice, Institute of Public Health, University of Southern Denmark, Odense, DenmarkCorrespondence: Anders Løkke, Email Anders.Lokke@rsyd.dkIntroduction: Studies have shown that exacerbation in chronic obstructive pulmonary disease (COPD) increases the risk of further exacerbations. Our aim was to investigate the impact of a single moderate exacerbation on the odds of subsequent exacerbations and death in GOLD B COPD patients.Methods: This hospital-based nationwide, cohort study in Denmark included all patients ≥ 40 years of age with an in- and/or outpatient ICD-10 J44 diagnosis (COPD Register, 2008– 2014). Index was date of first registered modified Medical Research Council (mMRC) score ≥ 2; baseline period was 12 months pre-index. At index, patients were grouped as: B0, no exacerbation; and B1, one moderate exacerbation during the previous year, and followed for three consecutive years in 2008– 2017 for development of moderate- (short-term use of prednisolone or prednisone) and severe (emergency visit or hospitalization) exacerbations and death. Using B0 as reference, the odds ratio (OR) for exacerbation and death in GOLD B1 was estimated with multinominal logistic regression and a Cox model estimated the hazard ratio for exacerbation accounting for recurrent events.Results: In total, 8,453 patients (mean age 70 years, 51% male) were included, of which GOLD B0 4,545 and GOLD B1 3,908 patients. During the 3-year follow-up, 34.1% and 24.9% of GOLD B0 and B1, respectively, had none or one moderate exacerbation whereas 61.9% and 71.2% of B0 and B1, respectively, had a severe trajectory with multiple moderate and/or a severe exacerbation or died. In B1 patients, the OR for 1 moderate, ≥ 2 moderate exacerbations, ≥ 1 severe exacerbation was 1.58 [CI 1.33– 1.87], 2.60 [2.19– 3.08], 2.08 [1.76– 2.45], respectively, and 1.85 [1.57– 2.17] for death compared with B0.Conclusion: One moderate exacerbation in COPD patients with high symptom burden increases the odds of subsequent exacerbations and death during the three following years. The results emphasize the importance of preventing exacerbations in GOLD B patients.Keywords: COPD, exacerbation, dyspnea, GOLD, mortality, epidemiology

People with spinal cord injury (SCI) or multiple sclerosis (MS) are often living with some degree of bladder and/or bowel dysfunction due to acquired neurogenic damage. The objective was to estimate the burden of illness of SCI and MS the first year after diagnosed bladder dysfunction. Data were extracted from registers covering all Danish citizens. People with SCI or MS were indexed at diagnosis of bladder dysfunction. Inclusion period was 2002–2015 and cases and matched controls were followed for one year. A total of 2,132 subjects with SCI and 1,887 subjects with MS were identified. Healthcare utilization and societal costs per patient-year were significantly higher for cases compared to controls driven primarily by inpatient care. Cases with urinary tract infection had significantly higher inpatient costs per patient-year compared to controls (SCI: 544 EUR vs 23, p < 0.05; MS: 497 EUR vs 6, p< 0.05) and medication for constipation was significantly more costly per patient-year (SCI: 178 EUR vs 3, p < 0.05; MS: 78 vs 1, p < 0.05). The study demonstrates heavy societal and personal costs in the first year after bladder dysfunction in people with SCI or MS. This emphasizes the need for medical and social interventions to reduce the burden of illness.

Background and objective: The aims of this national cohort study were: (1) to evaluate mortality in patients with sarcoidosis, stratified by gender, age and systemic corticosteroid (SC) treatment and (2) to characterize comorbidities in this cohort. Methods: Patients diagnosed with sarcoidosis from 2001 to 2015 were identified in the Danish National Patient Registry. Subgroup analyses were performed on cases treated/not treated with SCs within 3 years of the initial sarcoidosis diagnosis (as a proxy for disease severity). The Deyo–Charlson Comorbidity Index was used to evaluate pre-diagnostic comorbidity. Cases were matched (1:4) with controls from the general population. Results: We identified 9795 cases with sarcoidosis. Mean age was 46.5 ± 15.9 years and 55% were male. The adjusted hazard ratio (HR) for death was 1.48 (95% CI 1.31–1.68). Mortality was higher than for controls in all age groups and in both genders. HR for death for cases treated with SCs was 1.78 (95% CI 1.49–2.13) and, for cases receiving no treatment, 1.24 (95% CI 1.04–1.48). Sarcoidosis was the most commonly registered cause of death (13.3%). Conclusion: Patients with sarcoidosis have an increased mortality compared with matched controls. Mortality is particularly high in patients treated with SCs.

Introduction The primary objective was to evaluate the prevalence and incidence of sarcoidosis, and secondly, to evaluate differences in incidence by age at diagnosis, gender, region, calendar year and treatment and to evaluate sarcoidosis-related diagnostic work-up. Methods Patients diagnosed with sarcoidosis from 2001 to 2015 and information on diagnostic procedures three months before and after initial diagnosis were identified in the Danish National Patient Register. Incidence proportion and prevalence proportion were calculated using the total population count of Danish citizens. Results We identified 8545 sarcoidosis cases. Mean age was 46.0 ± 15.0 years, male gender was overrepresented (56.2%) and systemic corticosteroid was initiated in 46% of cases. The prevalence was 77 per 100,000 citizens in 2015. From 2001 to 2015, the incidence varied from 11.3 to 14.8 per 100,000 per year. The age-associated incidence peaked at 30–39 years in both men (23.6 per 100,000 per year) and women (15.0 per 100,000 per year). Incidence varied from 10.4 to 15.7 per 100,000 per year among regions. In particular, the share of bronchoscopies and chest-computed tomography were high in the region with the highest incidence and low in the region with the lowest incidence. Invasive procedures were more frequently performed in patients treated with systemic corticosteroid. Conclusion We find an increasing incidence and prevalence of sarcoidosis, with a peak incidence for both men and women between 30 and 39 years of age. The share of procedures performed seems to correlate well with incidence and disease severity.

Dea Kejlberg Andelius,1 Ole Hilberg,2,3 Rikke Ibsen,4 Anders Løkke2,3 1Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Department of Medicine, Vejle, Little Belt Hospital, Vejle, Denmark; 3Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; 4i2minds, Aarhus, 8000, DenmarkCorrespondence: Dea Kejlberg Andelius Email dea-jensen@hotmail.comBackground: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is mainly caused by smoking, and most patients with COPD are either former or current smokers. The optimal way to slow down disease progression and reduce overall mortality is for patients to stop smoking. Patients with COPD are known to have lower socio-economic status and to be more nicotine-dependent than most other smokers and therefore face difficulties when attempting to quit smoking. Pharmacological smoking cessation treatment is known to be the most effective. However, the extent to which this treatment is actually offered to Danish smokers with COPD is unknown.Aim: The aim of this study was to investigate if patients with COPD were more likely to redeem a prescription for smoking cessation medication compared with matched controls.Materials and Methods: The study was designed as a registry-based, non-interventional case-control study. All Danish patients with COPD (ICD-10-code J 44 chronic obstructive pulmonary disease) diagnosed between 2009 and 2015 were included (130,797 cases). Controls (252,216) were matched on age, gender and geography. Primary outcome was the number of redeemed prescriptions for smoking cessation medication.Results: We found that 12% of patients with COPD redeemed a prescription for smoking cessation medication during the eight-year study period. The odds ratio (OR) for redeeming a prescription on smoking cessation medicine was OR 6.22 for patients with COPD compared with their matched controls. We also found that patients with COPD were more likely to redeem smoking cessation medication if they were younger, female or single.Conclusion: There is substantial room for improvement with respect to pharmacological smoking cessation treatment in Danish patients with COPD. In-depth knowledge of factors contributing to the patients choice of smoking cessation treatment might allow for more personalized guidance of patients with COPD.Keywords: nicotine, bupropion, varenicline, smoking cessation, COPD

Objective Information on societal cost of patients with Borderline Personality Disorder (BPD) and spouses is limited. The aim was to investigate factual societal costs before and after initial BPD diagnosis. Method A register-based cohort study of 2756 patients with incident BPD (ICD F60.3) with spouses and 11 024 matched controls, during 2002-2016. Results Total direct healthcare costs and lost productivity costs amounted €40 441 for patients with BPD, which was more than 16 times higher than the matched controls. Somatic and psychiatric health care costs and costs of lost productivity were increased during 5 years before initial diagnosis of BPD. Before and after initial diagnosis, health care costs and lost productivity were increased among spouses of patients with BPD. Conclusion Patients with BPD differed substantially from the general population with respect to all included costs. The study documented a significant burden on their spouses. Besides the early onset of BPD, which implies that patients are affected before they finish school and enter labor market, the neurocognitive impairment and fundamental symptoms of BPD, e.g. unstable, intense relationships, impulsivity, and lack of stable sense of self together with psychiatric and somatic comorbidity are part of explanation of the excess costs of BPD.

Background Heart failure (HF) imposes a large burden on both the individual and the society. The aim of this study was to investigate the economic burden (either direct or indirect costs) attributed to patients with HF before, at, and after time of diagnosis. Methods and results Using Danish nationwide registries we identified all patients > 18 years with a first-time diagnosis of HF from 1998-2016 and matched them 1:1 with a control group from the background population on age, gender, marital status, and educational level. The economic analysis of the total costs after diagnosis was based on direct costs including hospitalization, procedures, medication, and indirect costs including social welfare and lost productivity to estimate the annual cost of HF. A total of 176 067 HF patients with a median age of 76 (interquartile range 67-84) years and 55% male were included. Patients with HF incurred an average of €17 039 in total annual direct (€11 926) and indirect (€5113) healthcare costs peaking at year of diagnosis compared to €5936 in the control group with the majority attributable to inpatient admissions. The total annual net costs including public transfer after index HF were €11 957 higher in patients with HF compared to controls and the economic consequences were evident more than 2 years prior to the diagnosis of HF. Conclusion Patients with HF impose significantly higher total annual healthcare costs compared to a matched control group with findings evident more than 2 years prior to HF diagnosis.

Background Information on welfare cost of patients with schizophrenia and spouses is limited. Aim The main aim of this study to investigate factual societal mean annual costs per individual during 5 years before and after the initial diagnosis of schizophrenia. Method A register-based cohort study of 12 227 patients with incident schizophrenia (International Classification of Diseases, Tenth Revision F20-F20.99) with spouses and 48 907 matched controls in Denmark during 2002–2016. Results The total annual costs of health care and lost productivity were Euro 43 561 higher for patients with schizophrenia and health care costs and costs of lost productivity were increased during 5 years before the initial diagnosis. The total annual direct health care and indirect costs of lost productivity were Euro 21 888 higher for spouses to patients with schizophrenia than spouses of individuals with no diagnosis of schizophrenia. Also before initial diagnosis, health care costs and lost productivity were increased among spouses of patients with schizophrenia. Conclusion Patients with schizophrenia differed from the general population with respect to all included costs. The study documented a significant burden on spouses. The excess health care costs of schizophrenia are further increased by psychiatric and somatic comorbidity, and the societal costs are 4–10 times higher than chronic neurological disorders such as epilepsy and multiple sclerosis. Early onset of schizophrenia implies that patients are affected before finishing school and before entrance to labor market. Cost savings could be achieved by investments in preventive interventions reaching young people’s needs; in initiatives to reduce hospital admissions caused by medication side effects, substance misuse, and lifestyle factors; and in occupational training.

Background Sarcoidosis is a systemic disease that primarily affects the younger population. Longitudinal studies of the economic burden of sarcoidosis are scarce. This study evaluates overall the economic burden of sarcoidosis in Denmark before and after initial diagnosis. Methods We identified patients with sarcoidosis in the Danish National Patient Registry (1998–2010). All controls were randomly selected and matched concerning age, gender and residence. Data on direct and indirect costs, including frequency of primary and secondary sector contacts and procedures, medication, unemployment benefits and social transfer payments were extracted from national databases for patients and controls. Results We identified 9119 patients with sarcoidosis and 36,432 matching controls. Patients with sarcoidosis had significantly higher rates of health-related contacts, higher usage of medication and more received unemployment and social payments compared with controls. The total health expenses were significantly higher in the sarcoidosis group 11 years before and 11 years after diagnosis than among controls. Income from public transfer payments was significantly higher in the sarcoidosis group five years prior of diagnosis until nine years post diagnosis. Especially women between 40 and 59 years have a lower income than their controls. Conclusion Sarcoidosis has a socioeconomic impact on adults especially during their prime working and providing years and this is evident several years prior to and post diagnosis. The authors advocate that further research should focus on identifying the proportion of patients with sarcoidosis that imposes the largest economic burden. Increased focus on early diagnosis and disease management may reduce the socioeconomic burden of sarcoidosis.

OBJECTIVE Information on societal cost of patients with schizotypal disorder is limited. The aim was to investigate the societal costs of schizotypal disorder before and after initial diagnosis including both patients and their spouses. METHODS A register-based cohort study of 762 patients with incident schizotypal disorder (ICD-10; F21) including their spouses and 3048 matched controls, during 2002 to 2016. Total healthcare costs, home care costs, and costs of lost productivity of patients and spouses were included in the analysis. RESULTS Total costs amounted €47,215 per year for patients with schizotypal disorder, which was fifteen times higher than the matched controls. Of these, 41% were healthcare and home care costs and 59% were costs of lost productivity. Healthcare costs and costs of lost productivity were increased during five years before initial diagnosis of schizotypal disorder. Total costs of spouses to patients were €21,384 compared with € 2519 among spouses of controls. 75% of the total costs of spouses to patients were related to lost productivity. The total costs were higher than the costs of borderline personality disorder, but on the same level as the costs of schizophrenia identified in earlier comparable studies. CONCLUSIONS The total societal costs of patients with schizotypal disorder drawn from national registers differed substantially from the controls representing the general population. As evidence-based recommendations for diagnoses and treatment of patients with schizotypal disorder do not exist, future research should focus on developing effective treatment for this group of patients to reduce cost of illness.

Anders Løkke,1,2 Peter Lange,3,4 Jesper Lykkegaard,5 Rikke Ibsen,6 Maria Andersson,7 Sofie de Fine Licht,8 Ole Hilberg1,2 1Department of Medicine, Little Belt Hospital, Vejle, Denmark; 2Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; 3Medical Department, Copenhagen University Hospital-Herlev, Herlev, Denmark; 4Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark; 5Research Unit for General Practice, Institute of Public Health, University of Southern Denmark, Odense, Denmark; 6i2Minds, Aarhus, Denmark; 7AstraZeneca Nordic, IVS & Health Economics, Södertälje, Sweden; 8AstraZeneca Nordic,Medical & Regulatory, Södertälje, SwedenCorrespondence: Anders LøkkeUniversity of Southern Denmark, Odense, DenmarkEmail Aloekke@gmail.comBackground: Chronic Obstructive Pulmonary Disease (COPD) carries a considerable economic burden, both for individuals and societies. This study aimed to assess direct and indirect costs associated with COPD, and how costs vary across disease severity.Methods: This was a nationwide, population-based cohort study utilizing Danish health registries. Patients; ≥ 40 years of age, with an in- and/or outpatient diagnosis of COPD (ICD-10 J44) in 2008– 2016, were identified in the nationwide Danish COPD Registry. Included patients were matched 1:4 to a population-based non-COPD reference population of 196,623 individuals by sex, year of birth, co-habitation status, and municipality. Patients were grouped by disease severity according to different characteristics including GOLD groups A-D, based on moderate (short-term oral corticosteroid use), presence of severe exacerbations (emergency visit or hospitalization) and symptom score. Index was the date of the first outpatient visit with a symptom score registration. The costs were calculated during a 12 months post-index follow-up.Results: In all, 49,826 patients with COPD (mean age 69.2 years, 52% females) were included. Total annual costs, including direct costs, costs for elderly care, and costs for retirement home, were higher for patients with COPD (€ 28,969) compared with the reference population (€ 10,6913). In GOLD groups A-D, the total direct costs were A: € 8,766, B: € 13,060, C: € 11,113, and D: € 17,749, respectively. A major driver of direct costs was severe exacerbations. The mean costs per moderate and severe exacerbation were € 888 and € 7,091, respectively, during 28 days of follow-up. The costs for non-COPD-related Health Care Resource Utilization were higher than the COPD-related costs in GOLD groups A-C, but not in GOLD group D.Conclusion: In this nationwide real-world study, total direct costs were three-fold higher among patients with COPD compared with the reference population. Severe exacerbations were a major driver of the direct costs. The costs increased with increasing disease severity.Keywords: COPD, exacerbations, symptoms, cost, GOLD

Background: Lung cancer is the leading cause of cancer death worldwide, but the additional economic burden regarding direct and indirect costs is largely unknown. This study provides information on the economic consequences of lung cancer on a national level. Methods: From the Danish National Patient Registry (NPR) and the Danish Civil Registration System (CPR), 53,749 patients with lung cancer were identified and matched with 214,304 controls on age, gender, region of residence and marital status in the period 1998–2010. Direct and indirect costs, health care contacts and frequency, medication and social transfer payments were extracted from national databases. Results: Direct health care cost were higher for lung cancer patients than controls both before and after being diagnosed with lung cancer. At the year of diagnosis, health care cost peaked with cost of €21,497 compared to €2,880 for controls. Average difference in income from employment was €+3,118 in years prior to diagnosis and €+748 after diagnosis in favor of controls. Average difference in total public transfer income was €+1,288 before and €+441 after diagnosis, with higher public transfer income for lung cancer patients. Conclusion: For both genders, lung cancer was associated with significantly higher rates of health-related costs, medication costs, public transfer income, social transfer payments and significantly lower income from employment until retirement (age 65).

Objective: Lung cancer is the leading cause of cancer-related death worldwide. This population-based longitudinal study investigates survival rates and the burden of comorbidity before and after being diagnosed with lung cancer in Denmark. Methods: From the Danish National Patient Registry (NPR) and the Danish Civil Registration System (CPR), 53,749 patients with lung cancer were identified and matched with 214,304 controls on age, gender, region of residence and marital status in the period 1998–2010. From the NPR, data on survival and comorbidity, registered as ICD-10 diagnoses, were extracted. Comorbidity was assessed using the Deyo-Charlson comorbidity score (DCcs) and mortality using Kaplan-Meier survival curves. Results: 1-year survival rate for Danish lung cancer patients was 51.7 % (CI 51.3-52.1) and 5-year survival rate was 14.7 % (CI 14.3-15.0) compared to 96.8 % (CI 96.7-96.8) and 84.0 % (CI 83.9-84.2) for controls respectively. Overall, cases had significantly more comorbidity compared to controls before being diagnosed with lung cancer. Prior to being diagnosed with lung cancer, more cases than controls had been diagnosed with other malignancies (11.4 % vs 6.0 % p

Objectives: The aim of this study was to make a comprehensive economic assessment of the costs of hospital-acquired C. difficile infections (CDI).Methods: We carried out a retrospective matched cohort study utilizing Danish registry data with national coverage to identify CDI cases and matched reference patients without CDI (controls) for economic burden assessment in Denmark covering 2011–2014. Health care costs and public transfer costs were obtained from national registries, and calculated for 1 year prior to, and 2 years after index admission using descriptive statistics and regression analysis.Results: The study included 12,768 CDI patients and 23,272 matched controls. The total health care cost was significantly larger for CDI cases than controls throughout all periods. During the index admission period, cost was €12,867 per CDI case compared to €4,522 (p < 0.001) for controls, which increased to an average of €31,388 and €19,512 (p < 0.001) in Year 1 for the two groups, respectively. Excess costs were found both among infections with onset in hospitals and in the community. Diagnosis compatible with complications increased costs to on average >€91,000 per case. The regression analysis showed that CDI adds a substantial economic burden, but only explains about 1/3 of the crude difference observed in the matched analysis.Discussion: The major economic impact of hospital-acquired CDI with complications underlines the importance of preventing complications in these patients. Our study provides an informed estimate of the potential economic gain per patient by successful intervention, which is likely to be relatively comparable across countries.

OBJECTIVE: To assess the 24-month cost-effectiveness of supervised treatment compared to written advice in knee osteoarthritis (OA).DESIGN: 100 adults with moderate-severe OA not eligible for total knee replacement (TKR) randomized to a 12-week individualized, supervised treatment (exercise, education, diet, insoles and pain medication) or written advice. Effectiveness was measured as change in quality-adjusted life years (QALYs) from baseline to 24 months, including data from baseline, 3, 6, 12 and 24 months, while healthcare costs and transfer payments were derived from national registries after final follow-up. Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. A sensitivity analysis resampling existing data was conducted and the probability of cost-effectiveness was estimated using a 22,665 Euros/QALY threshold. In a sensitivity analysis, cost-effectiveness was calculated for different costs of the supervised treatment (actual cost in study; cost in private practice; and in-between cost).RESULTS: Average costs were similar between groups (6,758 Euros vs 6,880 Euros), while the supervised treatment were close to being more effective (incremental effect (95% CI) of 0.075 (-0.005 to 0.156). In the primary analysis excluding deaths, this led the supervised treatment to be cost-effective, compared to written advice. The sensitivity analysis demonstrated that the results were sensitive to changes in the cost of treatment, but in all scenarios the supervised treatment was cost-effective (ICERs of 6,229 to 20,688 Euros/QALY).CONCLUSIONS: From a 24-month perspective, a 12-week individualized, supervised treatment program is cost-effective compared to written advice in patients with moderate-severe knee OA not eligible for TKR.TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01535001.

Background There is limited information about the long-term outcome of obstructive sleep apnea (OSA) diagnosed in children and adolescents for educational and social factors. Here, we estimate the long-term socioeconomic outcome and health care costs of OSA. Methods The historical case-control cohort study included Danish individuals with OSA diagnosed in childhood or adolescence between 1994 and 2015. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. A total of 5419 were diagnosed during this period; of these we traced 1004 patients who we compared with 4085 controls (mean index age, 10.2 years; Standard Deviation (SD), 5.6 years) until the age of 20 years. Controls were matched for age, gender, and residency. Results Comparing the OSA patient and control groups at age 20 years we found: 1) lower parental educational level; 2) significantly lower educational level also after adjustment for parental educational level; 3) lower school grade-point averages; 4) lower employment rate and lower income, which was not fully compensated when transfer payments were considered; and 5) patients' initial health care costs were higher due to higher morbidity. Patients showed higher mortality rates than controls (Hazard Ratio (HR) = 7.63, 95% CI = 4.87–11.95, P Conclusions OSA in children and adolescent is associated with a significant influence on morbidity, mortality, educational level, grading, social outcome, and welfare consequences.

Introduction: The underlying pathophysiology of idiopathic REM sleep behavior disorder (iRBD) is not fully understood, although the condition is currently recognized as an early-stage alpha-synuclein disorder. We evaluated the morbidity, mortality, and rate of conversion to a neurodegenerative disorder in a national group of patients. Methods: All patients in Denmark with a diagnosis of RBD between 2006 and 2013 were identified from the Danish National Patient Registry (NPR) records. We excluded patients who had received a diagnosis of narcolepsy or any of the following neurodegenerative diseases before their diagnosis of RBD: Parkinson’s disease, multiple system atrophy, progressive supranuclear paralysis, Alzheimer’s, and Lewy body dementia. We used randomly chosen controls matched for age, gender, and municipality. Results: In total, 246 iRBD patients and 982 matched controls were analyzed. The mortality rate was the same in both groups. The morbidity rate was significantly higher in the years before and after an RBD diagnosis, due to a wide variety of disorders in the following major disease groups: mental/behavioral disorders; endocrine/metabolic diseases; diseases of the eye; diseases of the nervous, digestive, musculoskeletal, circulatory, and respiratory systems; abnormal findings not classified elsewhere; external causes; and factors influencing health status. The conversion rate from RBD to a neurodegenerative disease was 13% over the 8 years after a diagnosis of RBD. Conclusions: A diagnosis of RBD is associated with increased morbidity several years before and after a diagnosis is made. Patients have a higher risk of converting to a neurodegenerative disorder than matched controls. Mortality rates are unchanged.