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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: Obesity is associated with increased societal costs, primarily due to its comorbidities. The objective of this study was to estimate the 3-year attributable societal costs of the first event of cardiovascular comorbidities among people with obesity. Methods: We used an incidence-based cohort study based on Danish national registries. Attributable costs of each event were calculated as the difference between costs of individuals with an event and costs incurred by matched controls. Results: We identified 58,597 individuals with a diagnosis of obesity. On average, 2,038 individuals were diagnosed annually with one or more than ten cardiovascular comorbidities between 2007 and 2013. The 3-year attributable societal costs (health-care costs plus productivity loss) for patients of working age ranged from 8,164 EUR for other ischemic heart disease to 32,203 EUR for hemorrhagic stroke. In the incidence year, costs were mainly driven by health-care costs, while productivity loss and income transfer payments were the primary drivers in subsequent years. Conclusion: The onset of obesity-related cardiovascular comorbidities affected health-care costs and work ability to an extent where sick pay and disability pension were required. Our study demonstrates the need to intensify obesity and cardiovascular disease risk factor management to prevent costly and debilitating obesity-related comorbidities.

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.

ObjectivesTo assess the effect of a systematic, fast-track transition from oncological treatment to specialised palliative care at home on symptom burden, to explore intervention mechanisms through patient and intervention provider characteristics and to assess long-term survival and place of death.MeasuresThe effect of a systematic, fast-track transition from oncological treatment to specialised palliative care at home on patient symptom burden was studied in the Domus randomised clinical trial. Participants had incurable cancer and limited treatment options. The intervention was provided by specialised palliative home teams (SPT) based in hospice or hospital and was enriched with a psychological intervention for patient and caregiver dyad. Symptom burden was measured with Edmonton Symptom Assessment System (ESAS-r) at baseline, 8 weeks and 6 months follow-up and analysed with mixed models. Survival and place of death was analysed with Kaplan-Meier and Fisher’s exact tests.ResultsThe study included 322 patients. Tiredness was significantly improved for the Domus intervention group at 6 months while the other nine symptom outcomes were not significantly different from the control group. Exploring the efficacy of intervention provider demonstrated significant differences in favour of the hospice SPT on four symptoms and total symptom score. Patients with children responded more favourably to the intervention. The long-term follow-up demonstrated no differences between the intervention and the control groups regarding survival or home deaths.ConclusionsThe Domus intervention may reduce tiredness. Moreover, the intervention provider and having children might play a role concerning intervention efficacy. The intervention did not affect survival or home deaths.Trial registration numberNCT01885637

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.

Background Current estimates of lifetime costs of smoking are largely based on model analyses using etiologic fractions for a variety of diseases or Markov chain models. Direct estimation studies based on individual data for health costs by smoking status over a lifetime are non-existent. Methods We estimated lifetime costs in a societal perspective of 18-year-old daily-smokers (continuing smoking throughout adult life) and never-smokers in Denmark, as well as lifetime public expenditures in the two groups. Main outcomes were lifetime net public expenditures and lifetime health costs according to OECD definitions and lifetime earned incomes. Estimates of these outcomes were based on registries containing individual-level data. Confounder-adjusted differences between daily-smokers and never-smokers were interpreted as smoking-attributable lifetime public expenditures and costs. Results The net lifetime public expenditure is, on average, €20 520 higher for male 18-year-old daily-smokers than for never-smokers, but €9771 lower, for female daily-smokers compared with never-smokers. In male 18-year-old daily-smokers, average lifetime health costs are €9921 higher and average lifetime earned incomes are €91 159 lower than for never-smokers. The corresponding figures are €5849 higher and €23 928 lower, respectively, for women. Conclusion 18-year-old male daily-smokers are net public spenders over their lifetime compared with never-smokers, while the opposite applies for women. In Denmark, smoking is associated with higher lifetime health costs for society and losses in earned incomes—both for men and women.

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: To date, there are no nationwide studies of the social and economic burden of psoriasis to patients in Denmark. Incentives for health care management based on patient-related outcomes and value (IMPROVE) in psoriasis and psoriatic arthritis is a project aimed at assisting movement from activity-based to outcome-based health care management. One of the key objectives in IMPROVE is to describe the disease-associated socioeconomic burden of psoriasis. Methods: A case-matched study of the impact of psoriasis on patients’ income, employment and health care costs in Denmark was performed. The IMPROVE study was a retrospective analysis of patients with a hospital diagnosis of psoriasis identified from the Danish National Patient Registry (NPR). In total, 13,025 psoriasis patients and 25,629 matched controls were identified from the NPR. Data from psoriasis patients and matched controls were compared for social and economic factors including income, employment, health care costs and risk of comorbidities. Results: Psoriasis was associated with increased health care costs (mean annual costs +116% compared to control, p < 0.001), peaking in the year of referral to hospital for psoriasis and sustained thereafter. Both direct and indirect costs were significantly higher for patients with psoriasis than controls (p < 0.001). In the years before and immediately following hospital diagnosis, the rates of employment were lower in psoriasis patients than controls. Comorbidities, including cardiovascular (odds ratio 1.93 [95% CI 1.77–2.09]) and psychiatric conditions (odds ratio 2.61 [95% CI 2.30–2.97]), were more prevalent in patients with psoriasis than controls. Conclusion: In Denmark, psoriasis has a significant impact on health care costs, income and employment, and is associated with a range of comorbidities.

Background: People with type 2 diabetes are at increased risk of developing diabetes-related complications and the augmented societal costs increase with the severity of complications. The objective was to estimate the short-term attributable societal costs of the first event of specific diabetes-related complications amongst people with type 2 diabetes. Methods: The study was based on national registry data covering all patients with type 2 diabetes in Denmark. Attributable costs of each event were calculated as the difference between costs of patients with the specific event and costs incurred by their controls. Results were reported for the incidence year and the following two years. Results: On average, 13,054 patients were identified annually from 2007 to 2013 with one or more of 17 specific first-incident diabetes-related complications. The attributable healthcare costs amounted to 114 million EUR annually in the incidence year alone. Costs were highest in the incidence year but were significantly higher also in the 2nd and 3rd year, driven particularly by increased indirect costs. Conclusions: Short-term excess costs of treating specific first-incident diabetes-related complications are massive for society. Our study highlights the importance of strengthening primary prevention within type 2 diabetes to minimize the risk of developing costly diabetes-related complications.

Background While hospitals remain the most common place of death in many western countries, specialised palliative care (SPC) at home is an alternative to improve the quality of life for patients with incurable cancer. We evaluated the cost-effectiveness of a systematic fast-track transition process from oncological treatment to SPC enriched with a psychological intervention at home for patients with incurable cancer and their caregivers. Methods A full economic evaluation with a time horizon of six months was performed from a societal perspective within a randomised controlled trial, the DOMUS trial (Clinicaltrials.gov: NCT01885637). The primary outcome of the health economic analysis was a incremental cost-effectiveness ratio (ICER), which is obtained by comparing costs required per gain in Quality-Adjusted Life Years (QALY). The costs included primary and secondary healthcare costs, cost of intervention and informal care from caregivers. Public transfers were analysed in seperate analysis. QALYs were measured using EORTC QLQ-C30 for patients and SF-36 for caregivers. Bootstrap simulations were performed to obtain the ICER estimate. Results In total, 321 patients (162 in intervention group, 159 in control group) and 235 caregivers (126 in intervention group, 109 in control group) completed the study. The intervention resulted in significantly higher QALYs for patients when compared to usual care (p-value = 0.026), while being more expensive as well. In the 6 months observation period, the average incremental cost of intervention compared to usual care was €2015 per patient (p value p-value = 0.026). Thereby, the ICER was €118,292/QALY when adjusting for baseline costs and quality of life. For the caregivers, we found no significant differences in QALYs between the intervention and control group (p-value = 0.630). At a willingness to pay of €80,000 per QALY, the probability that the intervention is cost-effective lies at 15% in the base case scenario. Conclusion This model of fast-track SPC enriched with a psychological intervention yields better QALYs than usual care with a large increase in costs. Trial registration The trial was prospectively registered 25.6.2013. Clinicaltrials.gov Identifier: NCT01885637.

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.

We estimated the long-term socioeconomic consequences and health care costs of Neisseria meningitidis meningitis (NM). The prospective cohort study included Danish individuals with onset of NM in childhood and adolescence, diagnosed between 1980 and 2009. Health care costs and socioeconomic data were obtained from nationwide administrative and health registers. Two thousand nine hundred two patients were compared with 11,610 controls matched for age, gender, and other sociodemographic characteristics. In the follow-up analysis at the age of 30 years, 1028 patients were compared with 4452 controls. We found that (1) NM caused increased mortality at disease onset, but after adequate treatment, the mortality rate was similar to that of the general population; (2) neurological and eye diseases were more frequently observed in patients; (3) patients had significantly lower grade-point averages; (4) patients had lower income even when transfer payments were taken into account; and (5) patients' initial health care costs were elevated.Conclusion: NM has significant influence on mortality, morbidity, education, and income. We suggest that the management of patients with previous meningococcal meningitis should focus on early educational and social interventions to improve social and health outcomes. What is known: • Meningococcal meningitis is a severe infectious disease affecting children and adolescents with high rates of mortality and complications. What is new: • Meningococcal meningitis causes increased mortality at disease onset, but after adequate treatment the mortality rate is similar to that of the general population. • Meningococcal meningitis in childhood and adolescence has a major long-term effect on morbidity, health care costs, education, employment, and income.

CONTEXT: Avoidable hospital admissions are important negative indicators of quality of end-of-life care. Specialized palliative care (SPC) may support patients remaining at home.OBJECTIVES: Therefore, the purpose of this study was to investigate if SPC at home could prevent hospital admissions in patients with incurable cancer.METHODS: These are secondary results of Domus: a randomized controlled trial of accelerated transition to SPC with psychological intervention at home (Clinicaltrials.gov: NCT01885637). Participants were patients with incurable cancer and limited antineoplastic treatment options and their caregivers. They were included from the Department of Oncology, Rigshospitalet, Denmark, between 2013 and 2016. The control group received usual care. Outcomes were hospital admissions, causes thereof, and patient and caregiver perceptions of place of care (home, hospital, etc.) at baseline, four weeks, eight weeks, and six months.RESULTS: During the study, 340 patients were randomized and 322 were included in modified intention-to-treat analyses. Overall, there were no significant differences in hospital admissions between the groups. The intervention group had more admissions triggered by worsened general health (22% vs. 16%, P = 0.0436) or unmanageable home situation (8% vs. 4%, P = 0.0119). After diagnostics, admissions were more often caused by clinical symptoms of cancer without progression in the intervention group (11% vs. 7%, P = 0.0493). The two groups did not differ significantly in overall potentially avoidable admissions. Both groups felt mostly safe about their place of care.CONCLUSION: The intervention did not prevent hospital admissions. Likely, any intervention effects were outweighed by increased identification of problems in the intervention group leading to hospital admissions. Overall, patients and caregivers felt safe in their current place of care.

This study aimed to evaluate all-cause mortality in relation to the use of benzodiazepines, antidepressants and antipsychotics in obstructive sleep apnoea (OSA) patients and matched controls.Patients with a diagnosis of OSA and no pre-index use of psychotropic medication (n = 38,735) were compared with control subjects (n = 75,941) matched by age, gender, marital status and community location. National register data were used to obtain information on diagnoses (the Danish National Patient Registry), mortality (the Central Person Register) and psychotropic medication use (the Danish Register on Medicinal Product Statistics).All-cause mortality was higher in patients with OSA than in control subjects. Mortality hazard ratios were higher for OSA patients and controls who were prescribed serotonergic antidepressant drugs (HR = 1.808, SD = 0.015, p = 0.001 in OSA patients; HR = 2.607, SD = 0.158, p 0.001 in controls), tricyclic antidepressants (HR = 1.846, SD = 0.166, p 0.001; HR = 2.087, SD = 0.172, p 0.001), benzodiazepines (HR = 2.590, SD = 0.040, p 0.001); (HR = 3.705, SD = 0.085, p 0.001), benzodiazepine-like drugs (HR = 1.980, SD = 0.087, p 0.001; HR = 2.227, SD = 0.083, p 0.001), first-generation antipsychotics (HR = 2.894, SD = 0.268, p 0.001; HR = 1.210, SD = 0.509, NS), and second-generation antipsychotics (HR = 2.069, SD = 0.182, p 0.001; HR = 1.355, SD = 0.171, NS), compared with those who did not receive the drugs. Interaction analysis suggested that similar or slightly lower mortality was associated with selective serotonin re-uptake inhibitors, benzodiazepines and second-generation antipsychotics in OSA compared with controls when comorbidities were taken into consideration.All-cause mortality was higher in OSA patients and especially controls treated with benzodiazepines, antidepressants or antipsychotics than in untreated controls. The findings were not controlled for psychiatric comorbidity and the results may have partly been attributable to confounding by indication. The results raised the possibility that the use of psychotropic medication may have deleterious health consequences, but the risk did not seem to be higher in OSA than in controls.

Uncertainty exists regarding cardiovascular (CV) safety of sulphonylureas (SUs) as reflected in package labels and treatment guidelines. This study evaluated clinical treatment practice for SUs by analysing prescription patterns for SUs relative to patient history of CV disease (CVD). Patients in Denmark initiating treatment with SU or other anti-hyperglycaemic drugs during 2006-12 were retrospectively identified using national health registries. Pre-existing (previous 12 years) overall CVD, coronary heart disease (CHD) and myocardial infarction (MI) were subsequently identified. Proportion of patients with pre-existing CVD was compared between new users of SU and new users of other anti-hyperglycaemic drugs. In total, 50,425 (42.2% females, mean ± SD age 63.3 ± 13.5 years) and 190,438 (46.5% females, age 60.3 ± 15.0 years) patients initiated treatment with SU or other anti-hyperglycaemic drugs, respectively, during 2006-12. The number of patients initiating SU treatment decreased by 63% during 2006-12. The proportion of patients with pre-existing CVD varied between 46.9% and 49.8% among new SU users versus 39.9% and 44.8% among new users of other anti-hyperglycaemic drugs. Corresponding proportions for CHD (17.9-19.9% versus 15.4-16.9%) and MI (6.3-7.5% versus 5.8-6.2%) showed the same pattern. Excluding new gliclazide users (9.6% of all new SU users) from the SU definition did not alter the results. Despite a potentially increased CV risk associated with use of SUs, pre-existing CVD did not decrease clinicians' relative prescriptions of SUs.

Objectives The objective of the study was to evaluate the morbidities and mortality in a national group of middle-aged and elderly narcolepsy patients before and after the first diagnosis of the condition. Methods From the Danish National Patient Registry (NPR), 1174 patients (45.1% males) aged 20–59 years and 339 patients (44.8% males) aged 60+ who received a diagnosis of narcolepsy between 1998 and 2014 were compared, respectively, with 4716 and 1353 control citizens matched for age, gender and geography, who were randomly chosen from the Danish Civil Registration System Statistics. In the NPR, all morbidities are grouped into major WHO classes. Results Middle-aged and elderly patients had more health contacts before and after their narcolepsy diagnosis with respect to several disease domains: infections, neoplasm, endocrine/metabolic diseases/diabetes, mental/psychiatric, neurological (including epilepsy), eye, cardiovascular (hypertension, ischemic heart disease), respiratory (upper-airway infections, sleep apnea), gastrointestinal, musculoskeletal (including discopathies) and skin diseases. Narcolepsy patients had lower reproductive rates. Furthermore, patients showed significantly more health contacts due to the evaluation and control contacts for disease and symptoms. Patients suffered from significantly more multiple diseases than did controls. The 17-year hazard ratio mortality rates were 1.35 (95% CI, 0.94–1.95, p = 0.106) among 20–59 year-olds, and 1.38 (1.12–1.69, p = 0.002) among those aged 60+ years. Conclusion There are higher rates of morbidity in several disease domains before and after a diagnosis of narcolepsy. Elderly narcolepsy patients have higher mortality rates.

Aims and Objectives Based on class-I studies, sodium oxybate is regarded as a first-line treatment for both EDS and cataplexy. The cost-effectiveness of sodium oxybate is largely unknown, though. In this study, we estimate the cost-effectiveness of sodium oxybate as treatment for patients with narcolepsy as compared to standard treatment, by calculating incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) for patients in a Swedish setting. Materials and Methods Calculations were performed using a Markov model with a 10-year time horizon. The study population consisted of adult patients treated for narcolepsy with cataplexy. Healthcare utilization and quality-adjusted life years (QALYs) for each treatment alternative were calculated assuming no treatment effect on survival. Sensitivity analyses were performed for treatment effectiveness and healthcare cost parameters. Results The cost per additional quality-adjusted life year was estimated at SEK 563,481. The cost-effectiveness measure was demonstrated to be particularly sensitive to the duration of the relative quality-of-life improvements accruing to patients treated with sodium oxybate. Conclusions The estimated cost per additional QALY for the sodium oxybate treatment alternative compared with standard treatment was estimated above the informal Swedish willingness-to-pay threshold (SEK 500,000). The estimated cost per additional QALY obtained here is likely to overestimate the true cost-effectiveness ratio as potentially beneficial effects on productivity of treatment with sodium oxybate were not included (due to lack of data).

Purpose: We aimed to evaluate the excess direct and indirect costs associated with epilepsy.Methods: From the Danish National Patient Registry (1998-2013), we identified people within all ages with an epilepsy diagnosis and matched them to control individuals. Additionally, partners of people with epilepsy were identified, who were compared with control partners. Direct costs included frequencies and costs of hospitalizations and weighted outpatient use according to diagnosis-related group, and specific outpatient costs based on data from the Danish Ministry of Health. The use and costs of drugs were based on data from the Danish Medicines Agency. The frequencies of visits and hospitalizations, and costs from general practice were derived from data from the National Health Security. Indirect costs included labor supply-based income data, and all social transfer payments obtained from Coherent Social Statistics.Results: A greater percentage of people with epilepsy and their partners compared with respective control subjects received social services (sick pay or disability pension). Those with epilepsy had a lower employment rate than did controls for equivalent periods up to eight years before the diagnosis was made. Mortality was significantly higher in people with epilepsy than in control individuals (hazard ratio 2.38 (95% CI: 2.34, 2.41). The additional direct and indirect annual costs of epilepsy compared with controls were 11,223 for persons with epilepsy and 2,494 for their partners.Conclusion: Epilepsy has major socioeconomic consequences for individual patients, their partners and society. (C) 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Objective We aimed to evaluate the excess direct and indirect costs associated with nonepileptic seizures. Methods From the Danish National Patient Registry (2011–2016), we identified 1057 people of any age with a diagnosis of psychogenic nonepileptic seizures (PNESs) and matched them with 2113 control individuals. Additionally, 239 partners of patients with PNES aged ≥ 18 years were identified and compared with 471 control partners. Direct costs included frequencies and costs of hospitalizations and outpatient use weighted by diagnosis-related group, and specific outpatient costs based on data from the Danish Ministry of Health. The use and costs of drugs were based on data from the Danish Medicines Agency. The frequencies of visits and hospitalizations and costs of general practice were derived from National Health Security data. Indirect costs included labor supply-based income data, and all social transfer payments were obtained from Coherent Social Statistics. Results A higher percentage of people with PNES and their partners compared with respective control subjects received welfare benefits (sick pay, disability pension, home care). Those with PNES had a lower employment rate than did controls for equivalent periods up to three years before the diagnosis was made. The additional direct and indirect annual costs for those aged ≥ 18 years, including transfers to patients with PNES, compared with controls, were €33,697 for people with PNES and €15,121 for their partners. Significance Psychogenic nonepileptic seizures have substantial socioeconomic consequences for individual patients, their partners, and society.

OBJECTIVE: Specialized palliative care (SPC) interventions increasingly include patient-caregiver dyads, but their effects on dyadic coping are unknown. We investigated whether an SPC and dyadic psychological intervention increased aspects of dyadic coping in patients with advanced cancer and their caregivers, whether dyad characteristics moderated effects and whether aspects of dyadic coping mediated significant intervention effects on caregivers' anxiety and depression.METHODS: We randomized 258 patients with incurable cancer and their caregivers to care as usual or accelerated transition from oncological treatment to home-based SPC and dyadic psychological support. In secondary outcome analyses, using mixed-effects models, we estimated intervention effects and 95% confidence intervals (CIs) for communication of stress and common coping, and moderation by dyad type and demographics. In path analyses, we investigated whether stress communication and common coping mediated intervention effects on caregivers' symptoms of anxiety and depression. (Clinicaltrials.gov NCT01885637).RESULTS: The intervention significantly increased common coping in patients and caregivers in couples (estimated difference, 0.68; 95% CI, 0.11 to 1.24) and stress communication by partner caregivers (0.97; 0.24 to 1.24). We found some support for different intervention effects for spouses and other dyads, but no evidence of mediation.CONCLUSIONS: Specialized palliative care and dyadic psychological intervention may affect aspects of dyadic coping. Common coping and stress communication did not mediate the previously found significant intervention effects on caregiver anxiety and depression, indicating that other mechanisms may have been central in the intervention.

Nonepileptic seizures (NES, psychogenic NES-PNES) are associated with significant morbidities. We evaluated the morbidities and mortality in a national group of children, adolescent, and adult patients before and after a first diagnosis of PNES. Methods: From the Danish National Patient Registry (1998–2013), we identified 1057 people of all ages with a diagnosis of NES and matched them with 2113 control individuals by age, gender, and geography. Comorbidities were calculated three years before and after diagnoses. Results: Patients with PNES showed increased comorbidities 3 years before and after diagnosis in almost all the diagnostic domains. The strongest associations were identified with other neurological diseases (after diagnosis, Hazard Ratio (HR): 38.63; 95% Confidence Interval (CI): 21.58–69.13; P < 0.001), abnormal clinical and laboratory findings (HR: 46.59; 95 CI: 27.30–79.52; P < 0.001), other health-related factors (HR: 12.83; 95%CI: 8.45–19.46; P < 0.001), and psychiatric comorbidities (HR: 15.45; 95% CI: 9.81–24.33). Epilepsy was identified in 8% of the patients with PNES. We found especially frequent comorbidity involving overweight, depression, anxiety, dissociative somatoform condition, other convulsions, lipothymias, reports of pain and other symptoms in several organ systems, and several reports of minimal traumas to the head, trunk, and extremities. Mortality was higher in patients with NES than in controls (HR: 3.21; 95% CI: 1.92–5.34; P < 0.001). Conclusion: Morbidity is more frequent in several domains, including neurological, psychiatric, and other diseases, before and after a diagnosis of NES. Mortality is significantly higher in patients with PNES as compared to controls.

Background and purpose In the world today 10–20 million people are still living with late effects of poliomyelitis (PM), but the long-term consequences of the disease are not well known. The aim of this study was to describe lifelong morbidity and mortality among Danes who survived PM. Methods Data from official registers for a cohort of 3606 Danes hospitalized for PM in the period 1940–1954 were compared with 13 762 age- and gender-matched controls. Results Compared with controls, mortality was moderately increased for both paralytic as well as non-paralytic PM cases; Hazard Ratio, 1.31 (95% confidence interval, 1.18–1.44) and 1.09 (95% confidence interval, 1.00–1.19), respectively. Hospitalization rates were approximately 1.5 times higher among both paralytic and non-paralytic PM cases as compared with controls. Discharge diagnoses showed a broad spectrum of diseases. There were no major differences in morbidities between paralytic and non-paralytic PM cases. Conclusions Poliomyelitis has significant long-term consequences on morbidity and mortality of both paralytic and non-paralytic cases.

OBJECTIVE: To estimate long-term socioeconomic consequences and health care costs of epilepsy with onset in childhood and adolescence.METHODS: A historical prospective cohort study of Danish individuals with epilepsy, age up to 20 years at time of diagnosis between January 1981 and December 2012. Information about marital status, parenthood, educational level, employment status, income, use of the health care system, and cost of medicine was obtained from nationwide administrative and health registers.RESULTS: We identified 12,756 and 28,319 people with diagnosed with epilepsy, ages 0-5 and 6-20 years at onset, respectively. Using follow-up data for a maximum of 30 years, 1,394 of those ages 0-5 years at onset were compared with 2,897 controls persons without epilepsy, and 10,195 of those ages 6-20 years at onset were compared with 20,678 controls without epilepsy. Compared with people without the epilepsy, those with epilepsy tended to have a lower level of education, to be less likely to be married, to be more likely to live alone, and to have higher divorce and unemployment rates, lower employment rates, and people with epilepsy were more likely to receive disability pension and social security. Income was lower from employment, which in part was compensated by social security, sick pay, disability pension and unemployment benefit, sick pay (public-funded), disability pension, and other public transfers. Predicted health care costs 30 years after epilepsy onset were significantly higher among persons with epilepsy onset at 0-5 and 6-20 years, including costs for outpatient and inpatient services (hospital services), emergency room use, primary health care sector (general practice), and use of medication.SIGNIFICANCE: The long-term negative effects on all aspects of health care and social domains, including marital status, parental socioeconomic status, educational level, employment status, and use of welfare benefits compared with controls without epilepsy calls for increased awareness on childhood- and adolescent-onset epilepsy.

Background and purpose Dementia causes morbidity, disability and mortality, and as the population ages the societal burden will grow. The direct health costs and indirect costs of lost productivity and social welfare of dementia were estimated compared with matched controls in a national register based cohort study. Methods Using records from the Danish National Patient Registry (1997–2009) all patients with a diagnosis of Alzheimer's disease, vascular dementia or dementia not otherwise specified and their partners were identified and compared with randomly chosen controls matched for age, gender, geographical area and civil status. Direct health costs included primary and secondary sector contacts, medical procedures and medication. Indirect costs included the effect on labor supply. All cost data were extracted from national databases. The entire cohort was followed for the entire period – before and after diagnosis. Results In all, 78 715 patients were identified and compared with 312 813 matched controls. Patients' partners were also identified and matched with a control group. Patients had lower income and higher mortality and morbidity rates and greater use of medication. Social- and health-related vulnerability was identified years prior to diagnosis. The average annual additional cost of direct healthcare costs and lost productivity in the years before diagnosis was 2082 euros per patient over and above that of matched controls, and 4544 euros per patient after the time of diagnosis. Conclusions Dementias cause significant morbidity and mortality, consequently generating significant socioeconomic costs.

Worldwide 10-20 million individuals are living with disabilities after acute poliomyelitis. However, very little is known about the socio-economic consequences and health care costs of poliomyelitis. We carried out a historical register-based study including 3606 individuals hospitalised for poliomyelitis in Copenhagen, Denmark 1940-1954, and 13,795 age and gender-matched Danes. Participants were followed from 1980 until 2012, and family, socio-economic conditions and health care costs were evaluated in different age groups using chi-squared tests, boot-strapped t tests or hazard ratios (HR) calculated in Cox-regression models. The analyses were performed separately for paralytic and non-paralytic polio survivors and their controls, respectively. Compared with controls a higher percentage of paralytic polio survivors remained childless, whereas no difference was observed for non-paralytic polio survivors. The educational level among paralytic as well as non-paralytic polio survivors was higher than that among their controls, employment rate at the ages of 40, 50 and 60 years was slightly lower, whereas total income in the age intervals of 31-40, 41-50 and 51-60 years were similar to controls. Paralytic and non-paralytic polio survivors had a 2.5 [HR = 2.52 (95 % confidence interval (CI); 2.29-2.77)] and 1.4 [HR = 1.35 (95 % CI; 1.23-1.49)]-fold higher risk, respectively, of receiving disability pension compared with controls. Personal health care costs were considerably higher in all age groups in both groups of polio survivors. Individuals with a history of poliomyelitis are well educated, have a slightly lower employment rate, an income similar to controls, but a considerably higher cost in the health care system.

ObjectiveTo assess the 24-month cost-effectiveness of total knee replacement (TKR) plus non-surgical treatment compared with non-surgical treatment with the option of later TKR if needed.Methods100 adults with moderate-to-severe knee osteoarthritis found eligible for TKR by an orthopaedic surgeon in secondary care were randomised to TKR plus 12 weeks of supervised non-surgical treatment (exercise, education, diet, insoles and pain medication) or to supervised non-surgical treatment alone. Including quality-adjusted life years (QALYs) data from baseline, 3, 6, 12 and 24 months, effectiveness was measured as change at 24 months. Healthcare costs and transfer payments were derived from national registries. Incremental healthcare costs, and incremental cost-effectiveness ratios (ICERs) were calculated. A probabilistic sensitivity analysis was conducted and the probability of cost-effectiveness was estimated at the 22 665 Euros/QALY threshold defined by the National Institute for Health and Care Excellence.ResultsTKR plus non-surgical treatment was more expensive (mean of 23 076 vs 14 514 Euros) but also more effective than non-surgical treatment (mean 24-month improvement in QALY of 0.195 vs 0.056). While cost-effective in the unadjusted scenario (ICER of 18 497 Euros/QALY), TKR plus non-surgical treatment was not cost-effective compared with non-surgical treatment with the option of later TKR if needed in the adjusted (age, sex and baseline values), base-case scenario (ICER of 32 611 Euros/QALY) with a probability of cost-effectiveness of 23.2%. Including deaths, TKR plus non-surgical treatment was still not cost-effective (ICERs of 46 277 to 64 208 Euros/QALY).ConclusionsFrom a 24-month perspective, TKR plus non-surgical treatment does not appear to be cost-effective compared with non-surgical treatment with the option of later TKR if needed in patients with moderate-to-severe knee osteoarthritis and moderate intensity pain in secondary care in Denmark. Results were sensitive to changes, highlighting the need for further confirmatory research also assessing the long-term cost-effectiveness of TKR.Trial registration numberClinicalTrials.gov (NCT01410409).

BACKGROUND: Specialised palliative care trials often fail to address intervention effects on caregiver anxiety and depression, particularly in bereavement. We evaluate effects of specialised palliative care and dyadic psychological intervention on caregiver anxiety and depression in a randomised controlled trial (RCT).METHODS: Patients with incurable cancer and limited antineoplastic treatment options and their caregivers, recruited from a university hospital oncology department, were randomised (1:1) to care as usual or accelerated transition from oncological treatment to home-based specialised palliative care. We assessed caregivers' symptoms of anxiety and depression with the Symptom Checklist-92 up to six months after randomisation and 19 months into bereavement, and estimated intervention effects in mixed effects models.RESULTS: The 'Domus' trial enrolled 258 caregivers. The intervention significantly attenuated increases in caregivers' symptoms of anxiety overall (estimated difference, -0.12; 95% confidence interval, -0.22 to -0.01, p = 0.0266), and symptoms of depression at eight weeks (-0.17; -0.33 to -0.02; p = 0.0314), six months (-0.27; -0.49 to -0.05; p = 0.0165), and in bereavement at two weeks (-0.28; -0.52 to -0.03; p = 0.0295) and two months (-0.24; -0.48 to -0.01; p = 0.0448).CONCLUSIONS: This first RCT evaluating specialised palliative care with dyadic psychological support significantly attenuated caregiver anxiety and depression before and during bereavement. (Clinicaltrials.gov: NCT01885637).

Background: The focus of specialized palliative care is to improve quality of life for patients with incurable cancer and their relatives including an increased opportunity to make their own choice of place of care and death. Aim: To investigate whether a systematic fast-track transition from oncological treatment to specialized palliative care at home for patients with incurable cancer reinforced with a psychological dyadic intervention could result in more time spent at home and death at home. Secondary aims were to investigate effects on quality of life, symptomatology and survival. Design: A prospective, single-centre, randomized controlled trial ( Clinicaltrials.gov : NCT01885637). Setting/participants: In all, 340 patients with incurable cancer and no or limited antineoplastic treatment options. Results: No statistically significant difference was found regarding number of deaths (4%, p = 0.460) and time spent at home (3%, p = 0.491). The secondary outcomes indicated that the intervention resulted in improved quality of life (−11.6 ± 25.5, p = 0.005, effect size = −0.44, 95% confidence interval = −0.77; −0.11), social functioning (−15.8 ± 31.4, p = 0.001, effect size = −0.50, 95% confidence interval = −0.84; −0.17) and emotional functioning (−9.1 ± 21.2, p = 0.039, effect size = −0.43, 95% confidence interval = −0.76; −0.10) after 6 months. A linear mixed-effect regression model confirmed a possible effect on emotional and social functioning at 6 months. Regarding survival, no differences were found between groups ( p = 0.605). No adverse effects were seen as consequence of the intervention. Conclusions: The main findings indicated that the intervention had no effect on time spent at home or place of death. However, the intervention resulted in a weak improvement of quality of life, social functioning and emotional functioning after 6 months.

We aimed to evaluate all-cause mortality of middle-aged and elderly subjects diagnosed with dementia and treated with psychotropic drugs as compared with controls subjects. Using data from the Danish National Patient Registry, n=26,821 adults with a diagnosis of dementia were included. They were compared with 44,286 control subjects with a minimum follow-up of four years and matched on age, gender, marital status, and community location. Information about psychotropic medication use (benzodiazepines, antidepressants, antipsychotics) was obtained from the Danish Medicinal Product Statistics. All-cause mortality was higher in patients with dementia as compared to control subjects. Mortality hazard ratios were increased for subjects prescribed serotonergic antidepressant drugs (respectively, HR=1.355 (SD=0.023), P=0.001 in patients; HR=1.808 (0.033), P

BACKGROUND: Limited data exist on the economic consequences of implementing targeted therapy (TT) for metastatic renal cell carcinoma (RCC) in a real-world setting.OBJECTIVE: To analyze health care and productivity costs for TT implementation in a national cohort of patients.DESIGN, SETTING, AND PARTICIPANTS: Costs were measured per patient per year during a 2-yr follow-up during 2002-2005 (immunotherapy only) and 2006-2009 (TT implementation). All Danish patients with a diagnosis code for RCC and a procedure code for TT or immunotherapy were linked to the Danish National Patient Registry (contains information on all contacts with primary and secondary health sector). Health care and productivity costs were retrieved from the Danish case-mix system and Coherent Social Statistics, respectively. Drug costs were calculated separately from procedure codes and retail prices.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Generalized linear models were used to analyze costs adjusted for age, gender, and civil status.RESULTS AND LIMITATIONS: A total of 439 patients were included for 2006-2009 and 192 for 2002-2005. Comparison of the health care cost per patient per year between 2006-2009 and 2002-2005 revealed lower inpatient costs (€11 899 vs €19 944, adjusted relative risk [RR] 0.64), higher outpatient costs (€14 308 vs €6209, RR 2.39), lower radiotherapy costs (€194 vs €633, RR 0.31), higher radiology costs (€676 vs €191, RR 3.73), and higher separately calculated drug costs (€12 040 vs €3103, RR 3.82, all pCONCLUSIONS: A different pattern of health care costs were observed but total health care costs per patient per year did not significantly differ after implementation of TT for patients with mRCC.PATIENT SUMMARY: In this nationwide study, we found changes in the pattern of health care costs for patients with metastatic kidney cancer after implementation of targeted therapy compared to an immunotherapy control period; however, total health care costs and income from employment were without significant changes.

Objective: To evaluate the socioeconomic impact of obesity by estimating the direct and indirect costs associated with obesity in Denmark, based on individual level data. Methods: Costs were assessed for different BMI groups, and the relative risks for change in direct and indirect costs per BMI point above 30 were estimated. A fourth analysis estimated the odds ratio for comorbidities per BMI point above 30. Individual data on income, social transfer payments, healthcare costs and diagnoses were retrieved from national registries. Results: One BMI point above 30 was associated with a 2% decrease in income, a 3% increase in social transfer payments, and a 4% increase in healthcare costs. In absolute numbers, income contributed to most of the total economic burden. One BMI point above 30 was also associated with increased comorbidity, which explains the increase in both direct and indirect costs. Conclusion: Obesity is associated with increased comorbidity, giving rise to an increase in both direct and indirect costs. Especially income is affected, which emphasizes the importance of including both measures when evaluating the total socioeconomic burden of obesity. Our findings draw attention to the potential for saving public resources and preventing loss of income by preventing obesity.

BACKGROUND: The aim of this study was to analyse the additional treatment costs of acute patients admitted to a Danish hospital who suffered an adverse event (AE) during in-hospital treatment.METHODS: A matched case-control design was utilised. Using a combination of trigger words and patient record reviews 91 patients exposed to AEs were identified. Controls were identified among patients admitted to the same department during the same 20-month period. The matching was based on age, gender, and main diagnosis. Cost data was extracted from the Danish National Cost Database for four different periods after beginning of the admission.RESULTS: Patients exposed to an AE were associated with higher mean cost of EUR 9505 during their index admission (p = 0.014). For the period of 6 months from the beginning of the admission minus the admission itself they were associated with higher mean cost of EUR 4968 (p = 0.016). For the period from the 7th month until the end of the 12th month there was no statistically significant difference (p = 0.104). For the total period of 12 month, patients exposed to an AE were associated with statistically significant higher mean cost of EUR 13,930 (p = 0.001).CONCLUSIONS: AEs are associated with significant hospital costs. Our findings suggest that a follow-up period of 6 months is necessary when investigating the costs associated with AEs among acute patients. Further research of specific types of AEs and the costs of preventing these types of AEs would improve the understanding of the relationship between adverse events and costs.

A recurring argument for bariatric surgery is cost savings due to sustained weight loss and reductions in comorbidities. However, studies prompting this argument tend to focus only on health care costs, and in some of them, cost changes after surgery have been modelled. The aim of this study was to generate real-world evidence on the socio-economic impact of bariatric surgery, by evaluating the effect on both direct and indirect costs. Using real-world data from national registries, predictions of health care costs, social transfer payments and income were performed for a surgically treated individual and compared to those for a similar but non-surgically treated individual 3 years before and after surgery. Secondly, the relative risks for health care costs, social transfer payments and income of a surgical group compared with a non-surgical group were estimated. The non-surgical group was defined as being eligible for bariatric surgery but not undergoing it. Bariatric surgery was associated with higher, but insignificantly so, health care costs, primarily due to an increase in somatic inpatient services. A significant decrease in costs of drugs was seen, especially for anti-diabetic medication. Bariatric surgery had a slight positive effect on social transfer payments and no significant effect on income. There are no cost savings of bariatric surgery in the short run. Further real-world evidence over a longer period of time is needed to examine whether the higher health care costs will eventually be counterbalanced, making bariatric surgery a profitable intervention in a socio-economic perspective.

Background While cardiac rehabilitation in patients with ischaemic heart disease and heart failure is considered cost-effective, this evidence may not be transferable to heart valve surgery patients. The aim of this study was to investigate the cost-effectiveness of cardiac rehabilitation following heart valve surgery. Design We conducted a cost-utility analysis based on a randomised controlled trial of 147 patients who had undergone heart valve surgery and were followed for 6 months. Methods Patients were randomised to cardiac rehabilitation consisting of 12 weeks of physical exercise training and monthly psycho-educational consultations or to usual care. Costs were measured from a societal perspective and quality-adjusted life years were based on the EuroQol five-dimensional questionnaire (EQ-5D). Estimates were presented as means and 95% confidence intervals (CIs) based on bootstrapping. Costs and effect differences were presented in a cost-effectiveness plane and were transformed into net benefit and presented in cost-effectiveness acceptability curves. Results No statistically significant differences were found in total societal costs (-1609 Euros; 95% CI: -6162 to 2942 Euros) or in quality-adjusted life years (-0.000; 95% CI -0.021 to 0.020) between groups. However, approximately 70% of the cost and effect differences were located below the x-axis in the cost-effectiveness plane, and the cost-effectiveness acceptability curves showed that the probability for cost- effectiveness of cardiac rehabilitation compared to usual care is at minimum 75%, driven by a tendency towards costs savings. Conclusions Cardiac rehabilitation after heart valve surgery may not have improved health-related quality of life in this study, but is likely to be cost-effective for society, outweighing the extra costs of cardiac rehabilitation.

Background and aim Opioid analgesics are often effective for pain management, but may cause constipation. The aim of this study was to determine healthcare resource use and costs in non-cancer and cancer patients with opioid-induced constipation (OIC). Methods This was a nationwide register-based cohort study including patients ≥18years of age initiating ≥4 weeks opioid therapy (1998–2012) in Denmark. Ameasure of OIC was constructed based on data from Danish national health registries, and defined as ≥1 diagnosis of constipation, diverticulitis, mega colon, ileus/subileus, abdominal pain/acute abdomen or haemorrhoids and/or ≥2 subsequent prescription issues of laxatives. Total healthcare resource utilization and costs (including pharmacy dispense, inpatient-, outpatient-, emergency room- and primary care) were estimated according to OIC status, opioid treatment dosage and length, gender, age, marital status, and comorbidities using Generalised Linear Model. Results We identified 97 169 eligible opioid users (77 568 non-cancer and 19 601 patients with a cancer diagnosis). Among non-cancer patients,15% were classified with OIC,10% had previous constipation, and 75% were without OIC. Patients characteristics of non-cancer OIC patients showed a higher frequency of strong opioid treatment (69% versus 41%), long-term opioid treatment (1189 days versus 584 days), advanced age (73 years versus 61 years), and cardiovascular disease (31%versus 19%) compared to those without OIC (P < 0.001 for all comparisons). Non-cancer patients with OIC had 34% higher total healthcare costs compared to those without OIC (P < 0.001) after adjusting for age, gender, opioid usage, marital status and comorbidities. Among cancer patients, 35% were classified with OIC,14% had previous constipation, and 51% were without OIC. A higher proportion of cancer patients with OIC were continuous opioid users (85% versus 83%) and strong opioid users (97% versus 85%), compared to those without OIC (P P < 0.001). Total healthcare costs were 25% higher for cancer patients with versus without OIC (P < 0.001) after adjusting for age, gender, opioid usage, marital status and comorbidities. Conclusions The results of this nationwide study based on real life data suggested that both non-cancer patients and cancer patients suffering from opioid-induced constipation (OIC) may have higher healthcare resource utilization and higher associated costs compared to those without OIC. Implications Reducing the number of OIC patients has potential cost savings for the health care system. Special attention should be on patients at potential high risk of OIC, such as strong and long-term opioid treatment, advanced age, and concomitant cardiovascular disease.

Aim Use of medication and polypharmacy is common as the population ages and its disease burden increases. We evaluated the association of antidepressants, benzodiazepines, antipsychotics and combinations of psychotropic drugs with all-cause mortality in patients with Parkinson's disease (PD) and a matched group without PD. Method We identified 5861 PD patients and 31,395 control subjects matched by age, gender and marital status, and obtained register data on medication use and vital status between 1997 and 2007. Results All-cause mortality was significantly higher with the use of most groups of psychotropic medication in PD patients and controls. Hazard ratios were as follows for the medication types: selective serotonin reuptake inhibitors or serotonin-noradrenalin reuptake inhibitors, PD HR = 1.19, 95% CI = 1.04−1.36; Control HR = 1.77, 95% CI = 1.64−1.91; benzodiazepines, PD HR = 1.17, 95% CI = 0.99−1.38; Control HR = 1.39, 95% CI = 1.29−1.51; benzodiazepine-like drugs, PD HR = 1.33, 95% CI = 1.11−1.59; Control HR = 1.27, 95% CI = 1.18−1.37; first-generation antipsychotics, PD HR = 1.89, 95% CI = 1.42−2.53; Control HR = 2.12, 95% CI = 1.82−2.47; second-generation antipsychotics, PD HR = 1.46, 95% CI = 1.20−1.76; Control HR = 2.00, 95% CI 1.66−2.43; and combinations of these drugs compared with non-medicated PD patients and controls. Discontinuation of medication was associated with decreased mortality in both groups. Conclusions The use of psychotropic medication in the elderly is associated with increased mortality, independent of concurrent neurodegeneration due to PD. Confounding by indication may partly explain the higher hazard ratios in medicated controls compared with medicated PD patients. Our findings indicate that neurodegeneration should not be a separate contraindication per se for the use of psychotropic drug in patients with PD, but its use should be based on careful clinical evaluation and follow-up.

ObjectivesIn year 2016, Danish national guidelines included a mandatory switch of patients with inflammatory rheumatic diseases treated with originator etanercept (ETA) to biosimilar SB4 in routine care. We aimed to explore if switching lead to increased healthcare utilisation and costs.MethodsObservational cohort study. Adult patients who switched from ETA to SB4 were identified in the Danish nationwide DANBIO registry. In the National Patient Registry, we identified health utilisation (hospital admissions/hospital days/outpatient visits/prescription medication use) and comorbidities. Estimation of health utilisation included average use and costs 1 year before/after switch, changes after the switch, and whether patient characteristics affected changes. Analyses were by adjusted two-step gamma distributed regression models, and for changes over time a generalized estimation equations (GEE) model was applied. Impact of comorbidities was explored as interaction terms in the model. Medication costs of ETA and SB4 were not included in model.Results1620 patients were included (mean age 55 years (SD 14.7), 40% male). Costs before and after switching were mainly driven by outpatient visits (67%/72% of all costs). Monthly fluctuations of costs were similar before/after switch. After switching, use (8%) and costs (7%) of outpatient services increased, whereas costs of admissions (55%) and medication (5%) decreased. Patients with longer ETA treatment duration had an increase in use and costs of healthcare resources, whereas gender and comorbidities had no impact. Higher age was associated with an increase in costs of inpatient services.ConclusionWe demonstrated no obvious changes in overall use and costs of healthcare services following switch from originator to biosimilar etanercept.

Background Little is known about the diagnostic patterns of obstructive sleep apnoea (OSA) in children. A study was undertaken to evaluate morbidity and mortality in childhood OSA. Methods 2998 patients aged 0–19 years with a diagnosis of OSA were identified from the Danish National Patient Registry. For each patient we randomly selected four citizens matched for age, sex and socioeconomic status, thus providing 11 974 controls. Results Patients with OSA had greater morbidity at least 3 years before their diagnosis. The most common contacts with the health system arose from infections (OR 1.19, 95% CI 1.01 to 1.40); endocrine, nutritional and metabolic diseases (OR 1.30, 95% CI 0.94 to 1.80); nervous conditions (OR 2.12, 95% CI 1.65 to 2.73); eye conditions (OR 1.43, 95% CI 1.07 to 1.90); ear, nose and throat (ENT) diseases (OR 1.61, 95% CI 1.33 to 1.94); respiratory system diseases (OR 1.78, 95% CI 1.60 to 1.98); gastrointestinal diseases (OR 1.34, 95% CI 1.09 to 1.66); skin conditions (OR 1.32, 95% CI 1.02 to 1.71); congenital malformations (OR 1.56, 95% CI 1.31 to 1.85); abnormal clinical or laboratory findings (OR 1.21, 95% CI 1.06 to 1.39); and other factors influencing health status (OR 1.29, 95% CI 1.16 to 1.43). After diagnosis, OSA was associated with incidences of endocrine, nutritional and metabolic diseases (OR 1.78, 95% CI 1.29 to 2.45), nervous conditions (OR 3.16, 95% CI 2.58 to 3.89), ENT diseases (OR 1.45, 95% CI 1.14 to 1.84), respiratory system diseases (OR 1.94, 95% CI 1.70 to 2.22), skin conditions (OR 1.42, 95% CI 1.06 to 1.89), musculoskeletal diseases (OR 1.29, 95% CI 1.01 to 1.64), congenital malformations (OR 1.83, 95% CI 1.51 to 2.22), abnormal clinical or laboratory findings (OR 1.16, 95% CI 1.06 to 1.27) and other factors influencing health status (OR 1.35, 95% CI 1.20 to 1.51). The 5-year death rate was 70 per 10 000 for patients and 11 per 10 000 for controls. The HR for cases compared with controls was 6.58 (95% CI 3.39 to 12.79; p Conclusions Children with OSA have significant morbidities several years before and after their diagnosis.

STUDY OBJECTIVES To identify the factual morbidity and mortality of narcolepsy in a controlled design. SETTING National Patient Registry. PATIENTS All national diagnosed patients (757) with health information at least 3 years prior to and after diagnose of narcolepsy. CONTROLS Randomly selected four citizens (3,013) matched for age, sex, and socioeconomic status from the Danish Civil Registration System Statistics. RESULTS Increased morbidity prior to narcolepsy diagnosis included (odds ratio, 95% confidence interval):- diseases of the endocrine, nutritional, and metabolic systems (2.10, 1.32-3.33); nervous system (5.27, 3.65-7.60); musculoskeletal system (1.59, 1.23-2.05); and other abnormal symptoms and laboratory findings (1.66, 1.25-2.22). After the diagnosis, narcolepsy patients experienced diseases of the endocrine, nutritional, and metabolic (2.31, 1.51-3.54), nervous (9.19, 6.80-12.41), musculoskeletal (1.70, 1.28-2.26), eye (1.67, 1.03-2.71), and respiratory systems (1.84, 1.21-2.81). Specific diagnoses were diabetes (2.4, 1,2-4.7, P < 0.01), obesity (13.4, 3.1-57.6, P < 0.001), sleep apnea (19.2, 7.7-48.3, P < 0.001), other sleep disorders (78.5, 11.8-523.3, P < 0.001), chronic obstructive pulmonary disease (2.8, 1.4-5.8, P < 0.01), lower back pain (2.5, 1.4-4.2, P < 0.001), arthrosis/arthritis (2.5, 1.3-4.8, P < 0.01), observation of neurological diseases (3.5, 1.9-6.5, P < 0.001), observation of other diseases (1.7, 1.2-2.5, P < 0.01), and rehabilitation (5.0, 1.5-16.5, P < 0.005). There was a trend towards greater mortality in narcolepsy (P = 0.07). CONCLUSIONS Patients with narcolepsy present higher morbidity several years prior to diagnose and even higher thereafter. The mortality rate due to narcolepsy was slightly but not significantly higher.

We aimed to evaluate the total costs to patients and their partners of sleep apnoea and obesity hypoventilation syndrome (OHS) and their treatment, as this is poorly described in families. Using data from the Danish National Patient Registry and other public databases, all patients and their partners with a diagnosis of sleep apnoea (n=30,278) or OHS (n=1562) were included. They were compared with age-, sex- and community location-matched citizens at a ratio 1:4 (120,506 and 6241 control subjects, respectively). Direct and indirect costs were evaluated for patients and their partners. Sleep apnoea and OHS patients and their partners had higher rates of health-related contact, medication use and unemployment, and lower income levels. Excess yearly direct net health and foregone earnings (indirect costs) were €2174 and €7981 prior to diagnosis, and €3988 and €12,022 after diagnosis for sleep apnoea and OHS, respectively. The comparable annual mean excess health-related costs for spouses were €1965 and €2862 before diagnosis, and €2307 and €3079 after diagnosis, for sleep apnoea and OHS patients, respectively. These socioeconomic consequences were present up to 12 years before first diagnosis, and increased as the disease advanced. Sleep-disordered breathing has major socioeconomic consequences for patients and their spouses years before and after diagnosis.

PURPOSE: We aimed to determine the health costs and social outcomes in terms of education, employment and income level after insertion of a vagus nerve stimulator (VNS) in patients with epilepsy.METHODS: This is a case-control study using Danish health care and socioeconomic register data. The analysis of the effect involved a comparison of the health care costs, occupation and income status of VNS-treated epilepsy patients with those of a control group of epilepsy patients who had a VNS implanted during the 12 months before the index date (pre-period) and during the two years after the index date (post-period).RESULTS: 101 patients who had undergone VNS implantation and 390 control patients were included. VNS implantation was associated with fewer inpatient admissions and emergency room visits and less frequent use of prescription medication compared with epilepsy patients without VNS implantation. VNS implantation was not associated with changes in occupational status (including employment and income). In fact, the number of people on disability pension increased during the period.CONCLUSIONS: VNS implantation in people with epilepsy is associated with reduced health care use, but not with occupational or social status.

ObjectivesTo comprehensively study the comorbidities, healthcare and public transfer (allowance) costs in patients with psoriatic arthritis (PsA) before and after diagnosis.MethodsNationwide cohort study, using data from Danish registries from January 1998 through December 2014. A total of 10 525 patients with PsA and 20 777 matched general population comparator (GPC) subjects were included. Societal costs, employment status and occurrence of comorbidities in patients with PsA both before and after diagnosis were compared with GPC subjects.ResultsAt baseline, patients with PsA had significantly more comorbidities, including cardiovascular disease (OR 1.70 95% CI 1.55 to 1.86), respiratory diseases (OR 1.73 95% CI 1.54 to 1.96) and infectious diseases (OR 2.03 95% CI 1.69 to 2.42) compared with GPC subjects. At all time points, patients with PsA had higher total healthcare and public transfer costs; they also had lower income (p.36 (95% CI 1.24 to 1.49) compared with GPC subjects. The RR increased to 1.60 (95% CI 1.49 to 1.72) at the time of diagnosis and was 2.69 (95% CI 2.40 to 3.02) 10 years after diagnosis, where 21.8% of the patients with PsA received disability pension.ConclusionsOur findings are suggestive of health inequity for patients with PsA and call for individual preventive measures and societal action.

Total hip and knee replacement (THA and TKA) are successful operations based on patient-reported outcomes and short-term socioeconomic evaluations. However, other data have shown problems regarding persistent pain and function. No detailed large-scale, long-term socioeconomic data exist on income and total health expenses before and after THA and TKA compared with a matched reference population (RP).From the unique nationwide Danish registers, a total of 128,109 patients undergoing primary THA and TKA were followed from up to 12 years before to up to 12 years after surgery. The economic analysis of the total costs before and after surgery were divided into annual healthcare costs (outpatient services, inpatient admissions, prescription drugs and physician office visits), home care and loss of income and compared with a matched RP.Healthcare costs increased by about 10,000 € in the year of surgery followed by an increase of about 6,000 €/yr/patient in both operations due to a loss of employment income, a need for home care and the use of medications, also compared with an RP. Survival was slightly better for patients than for the RP, suggesting that severe co-morbidities have only a limited role in explaining the increased costs.The healthcare costs and income of patients undergoing THA and TKA are comparable to those of their matched RP until three years before the operation, but TKA and THA patients continuously have higher healthcare costs and lower income levels than the RP after surgery. These data should be taken into account in future studies of patient expectations and strategies for enhanced rehabilitation.none.none.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with significant morbidity, mortality, and costs for the individual patient and for society. The purpose of this study was to examine welfare costs in patients with RA including their partners before and after initial diagnosis. Data were collected from population-based registers in the period from 1998 to 2009. A total of 25,547 Danish patients with a diagnosis of RA and 15,660 of their partners were identified and compared with 101,755 randomly selected age- and gender-matched controls and 62,681 control partners. The direct and indirect costs were calculated for patients and their partners and compared to matched controls. These included inpatient and outpatient treatment, medication, income from employment and social transfer payments. Patients with RA had statistically significantly more inpatient and outpatient costs than control subjects, i.e., treatment (€346 vs. €211), hospitalization (€1261 vs. €778), and medication use (€654 vs. €393). The costs associated with the patients were present 11 years before diagnosis of RA (€1592) compared with control subjects (€1172). Furthermore, income from employment was lower for patients (€14,023) than for control subjects (€17,196). Being a partner to a patient with RA was associated with high total welfare costs. This register-based study shows that RA has significant welfare costs for patients, their partners, and society. The differences in total health costs exist up to 11 years before the diagnosis of RA is established.

Purpose: Epilepsy is associated with significant morbidities and mortality. We aimed to evaluate the 30-year morbidities and mortality in a national group of patients after a first diagnosis of epilepsy. Methods: From the Danish National Patient Registry (NPR), in total, 3123 patients with epilepsy aged 0-5years and 5018 patients aged 6-20years diagnosed in 1998-2002 were identified and compared with, respectively, 6246 and 10,036 persons matched for age, gender, and place of living with randomly chosen citizens from the Danish Civil Registration System Statistics. In the NPR, all morbidities in the following 30years were grouped into major WHO disease classes. Key findings: Patients with epilepsy had significantly higher rates of comorbidities including almost all health-related comorbidities compared with controls. Mortality rates were elevated: the hazard ratio (5%; 95% CI) was 14.46 (11.8; 17.7, p

PURPOSE: Epilepsy surgery has been a standard treatment for refractory epilepsies that cannot be controlled by standard medical treatment. We aimed to evaluate the health and social consequences of resective surgery relative to controls from a study of national data.METHODS: Using the Danish National Patient Registry we identified all subjects with an epilepsy diagnosis between 1996 and 2009 and compared them with a group of patients with an epilepsy diagnosis who had had neither epilepsy surgery nor a vagus stimulation diagnosis by the index date, and who were matched by gender, index year for epilepsy diagnosis, and index year for epilepsy surgery. We considered all the health and social information available in the Danish health, medication and social registers. The duration of follow-up was three years.RESULTS: 254 epilepsy patients and 989 controls were analyzed. Surgery patients were more severely affected by their disease as indicated by health care use and social impact before the surgical procedure. Patients who underwent epilepsy surgery had a significantly lower costs associated with the use of medication, outpatient services, inpatient admissions, and accident and emergency visits after surgery. The surgical intervention had no significant effects on social status in terms of occupation and educational level.CONCLUSION: Although epilepsy surgery was followed by a reduction in inpatient and outpatient health care use, medication and use of accident and emergency facilities, suggesting a positive effect on the epileptic disease, there was no significant effect on social outcome measures.

OBJECTIVES: Epilepsy is associated with a significant burden to patients and society. We calculated the factual excess in direct and indirect costs associated with childhood- and adolescent-onset epilepsy.METHODS: Using records from the Danish National Patient Registry (1998-2002), we identified 3123 and 5018 patients with epilepsy aged 0-5years and 6-20years at the time of diagnosis, respectively. The two age groups of patients with epilepsy were matched to 6246 and 10,036 control persons without epilepsy, respectively, by gender, age, and geography. The controls were randomly chosen from the Danish Civil Registration System. Welfare costs included outpatient services, inpatient admissions, and emergency room visits based on the Danish National Patient Registry and information from the primary health-care sector based on data from the Danish Ministry of Health. This allowed the total health-care cost of epilepsy to be estimated. The use and costs of drugs were based on data from the Danish Medicines Agency. The frequencies of visits to outpatient clinics and hospitalizations and costs from primary sectors were based on data obtained from the National Patient Registry.RESULTS: Children with epilepsy had higher welfare costs than controls. The highest cost was found one year after diagnosis, with higher costs up to 10years after diagnosis compared with controls. Children aged 0-5years incurred greater health-care costs than those aged 6-20years.CONCLUSION: Epilepsy has major socioeconomic consequences for the individual person with epilepsy and for society.

Background Previous studies suggest that a greater proportion of neck injury patients, whose injuries were sustained through whiplash accidents, become chronic due to a component of sickness-focusing. However, it is also possible that some of those with neck injuries were already more frail prior to the injury, resulting in more consequences from a certain intensity of injury. The objective of this study was to compare co-morbidity and mortality in people with a registered neck injury diagnosis, evaluated prior to and after the neck injury, to people without a registered neck injury evaluated at the same time-points. Methods From a hospital patient registry over a 12-year period, we identified those with the diagnosis ‘cervical-column distortion’ and matched four controls for each of them on sex, age, marital status and county of residence. For calculations of co-morbidity, those with an injury at year 1, who thus had no prior data, and for those at year 12 who did not have post data, were not included. The same applied to their individually matched controls. Health data for up to 3 years prior to and up to 3 years after the year of injury were recorded. Results We identified 94,224 cases and 373,341 controls. Those with registered neck injuries had 1.2-2.0 times more co-morbidities than controls after the injury, but had already had about the same (1.3-1.8 more co-morbidities) number of co-morbidities prior to the injury. Mortality up to 12 years was approximately the same in the two groups. Conclusions Those people having a registered neck injury had more co-morbidity diagnoses both before and after the injury than those without a registered neck injury. This suggests that the co-morbidities observed after the injury may be partly related to already existing general high health care-seeking and/or a low health status, rather than being entirely the consequence of the injury.

We estimated the rate of compliance with oral bisphosphonates among Danish women and examined its association with health care resource use and cost. Approximately 30 % of Danish females aged >55 who take bisphosphonates are noncompliant, and noncompliance is significantly associated with increased health care resource use and cost.INTRODUCTION: Two objectives of this study were to estimate the rate of oral bisphosphonate compliance among Danish women and to examine the association of noncompliance with health care resource use and cost.METHODS: Women ≥55 with an index prescription claim for an oral bisphosphonate were identified from Danish national health registries between 2003 and 2008. Compliance was measured as the medication possession ratio (MPR) during the first 12 months post-index. Cost and health care resource use were collected for the following 12 months.RESULTS: Among the 38,234 women meeting the study inclusion criteria, 29.9 % were noncompliant (MPR CONCLUSIONS: Approximately 30 % of Danish females aged 55 or older who take bisphosphonates are noncompliant. Noncompliance is significantly associated with increased health care resource use and cost.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that imposes a great burden on the patient, the patient's family and society. However, we lack information about the total disease burden at a national level, especially regarding costs before and after diagnosis and the consequences for spouses. We aimed to estimate the factual direct and indirect costs of ALS in a national sample. Using records from the Danish National Patient Registry (1998-2009), 2,394 patients with ALS were identified and subsequently compared with 9,575 randomly chosen control subjects matched for age, gender and geographic area/civil status. Direct costs, including frequencies of primary and sector contacts and procedures, and medication from primary and secondary sectors, were obtained from the Danish Ministry of Health, the Danish Medicines Agency, and the National Health Security. Indirect costs included labour supply and social transfer payments, and were based on income data derived from Coherent Social Statistics. Patients with a diagnosis of ALS had poor survival. The average (95 % CI) 5-year survival rate was 0.278 (0.358-0.298) compared with 0.865 (0.858-0.872) among controls. Patients with ALS had significantly higher rates of health-related contact and medication use and higher socioeconomic costs. They also had very low employment rates, while those in employment had a lower income level than control subjects. The annual mean excess health-related cost waseuro18,918 for each ALS patient. However, spouses showed no excess health usage; in fact, their employment and income rates were higher, and the net cost was reduced by -euro3,420. We conclude that ALS has serious mortality, health and socioeconomic consequences for patients. However, the consequences for spouses are complex; they tend to compensate for the social consequences to patients by increasing their net income after ALS diagnosis.