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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.

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: There is an average 5 day delay between a COVID-19 infection and symptom onset. Evidence suggests between 35% and 50% of all transmissions occur within this time-frame. Presymptomatic COVID-19 detection, therefore, serves a crucial role in containing the spread of COVID-19. An early COVID-19 detection algorithm were developed in the COVID-Red trial, which based on anomalies in biophysical markers, measured via a bracelet, predicts COVID-19 infection. Method: This paper is an economic evaluation of the anomaly detection model developed in the COVID-Red trial with a health sector perspective. The primary outcome is the incremental cost effectiveness ratio (ICER), where the effectiveness is measured as early COVID-19 detection. Data on healthcare utilisation and COVID-19 testing are collected through biweekly surveys, structured phone interviews and a daily symptom diary. All data is self reported. Results: COVID-19 can be detected 3.50 days earlier using an anomaly detection model, as opposed to a deterministic approach. The associated costs are ­≈54€ and ≈50€, on average, in the intervention and control group respectively. The ICER is 1.15€, and implies a marginal cost of 1.15€ per days of early detection. Conclusion: The anomaly detection model detects COVID-19 3.5 earlier than otherwise possible, with a marginal cost of 4€. The ICER is 1.15€. Compared to the existing test strategies, the bracelet and algorithm combination is expensive. It can be considered inexpensive amongst, for example, healthcare workers where structured COVID-19 screenings are common. Trial registration: Dutch Trial Register, NL9320. Registered 18/02/2021, https://clinicaltrialregister.nl/en/trial/23180

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.

Background The Domus study, a randomized controlled trial (RCT), evaluated the effect of home-based specialized palliative care (SPC) reinforced with a psychological intervention for the patient-caregiver dyad on increasing advanced cancer patients’ time spent at home, as opposed to hospitalized, and the number of home deaths. As palliative care extends to include support for patients’ families and may thus assist caregivers and decrease demands on them, in this study we evaluated a secondary outcome, caregiver burden. Material and Methods Patients with incurable cancer and their caregivers were randomized (1:1) to care as usual or home-based SPC. Caregiver burden was assessed using the Zarit Burden Interview (ZBI) at baseline and 2, 4, 8 weeks and 6 months after randomization. Intervention effects were assessed in mixed effects models. Results A total of 258 caregivers were enrolled. Eleven per cent of informal caregivers experienced severe caregiver burden at baseline. Caregiver burden increased significantly over time in both groups (p = 0.0003), but no significant effect of the intervention was seen on overall caregiver burden (p = 0.5046) or burden subscales measuring role and personal strain. Conclusion In line with the majority of previous RCTs, the Domus intervention was not able to significantly reduce caregiver burden. Future interventions should consider targeting only caregivers reporting the greatest caregiver burden.

As clinical practice variation has been problematized as a symptom of suboptimal care and inefficient resource spending, consistency in the delivery of healthcare is a recurring policy goal. We examine a case where the introduction of a new treatment is most likely to provide consistency in healthcare delivery because it was introduced with a national clinical practice guideline representing consensus about best clinical practice among leading clinicians, and because care delivery was highly centralized to few high-volume treatment units. Despite the consensus on best clinical practice and care centralization, this study shows pronounced regional variation in patient outcomes and treatment costs that increased over time. Using a mixed-methods design, we find that the lack of consistency in care was largely unrelated to patient-specific characteristics, but seemed to reflect structural differences in the regional organization and financing of healthcare delivery. We conclude that the value of clinical practice guidelines is undermined when structural barriers limit the ability of clinicians and clinical managers to scale up treatment, and that some degree of decentralization may be a tool to maintain treatment intensity when the treatment effect is dependent on a high treatment intensity.

The aim of this study was to evaluate lifetime income, educational level and workforce participation in patients with childhood-onset inherited retinal dystrophies (IRD). The registry-based study using national, Danish databases on education, income, employment and social benefits in a cohort of 515 patients with childhood-onset IRD and without severe systemic comorbidities matched 1:4 to an age- and sex to a control sample of the Danish background population. Socio-economic status was modelled with focus on grade mark points after primary education, highest attained education at 30 years or age, employment and unemployment rate, disability pension and lifetime income. At 30 years of age, the proportion of those who had primary education as the highest achieved level was higher in the IRD group (35.4% versus 18.7%) and they were more likely to be receiving a disability pension (OR 11.77) or be unemployed (OR 6.63). Those at work had the same number of work hours as the control group, and the same proportion had obtained a Master or PhD degree (14%). At 30 years of age, income earnings were lower in the IRD group and the lifetime income was reduced by 30%. A few among those with childhood-onset IRD were able to obtain high educational levels, and many were assigned a disability pension from early adulthood or were unemployed, resulting in a markedly reduced lifetime income although grade mark points from primary education were comparable, suggesting that the difference was not explained by intellectual differences between the groups.

ObjectivesWe investigated machinelearningbased identification of presymptomatic COVID-19 and detection of infection-related changes in physiology using a wearable device.DesignInterim analysis of a prospective cohort study.Setting, participants and interventionsParticipants from a national cohort study in Liechtenstein were included. Nightly they wore the Ava-bracelet that measured respiratory rate (RR), heart rate (HR), HR variability (HRV), wrist-skin temperature (WST) and skin perfusion. SARS-CoV-2 infection was diagnosed by molecular and/or serological assays.ResultsA total of 1.5 million hours of physiological data were recorded from 1163 participants (mean age 44±5.5 years). COVID-19 was confirmed in 127 participants of which, 66 (52%) had worn their device from baseline to symptom onset (SO) and were included in this analysis. Multi-level modelling revealed significant changes in five (RR, HR, HRV, HRV ratio and WST) device-measured physiological parameters during the incubation, presymptomatic, symptomatic and recovery periods of COVID-19 compared with baseline. The training set represented an 8-day long instance extracted from day 10 to day 2 before SO. The training set consisted of 40 days measurements from 66 participants. Based on a random split, the test set included 30% of participants and 70% were selected for the training set. The developed long short-term memory (LSTM) based recurrent neural network (RNN) algorithm had a recall (sensitivity) of 0.73 in the training set and 0.68 in the testing set when detecting COVID-19 up to 2 days prior to SO.ConclusionWearable sensor technology can enable COVID-19 detection during the presymptomatic period. Our proposed RNN algorithm identified 68% of COVID-19 positive participants 2 days prior to SO and will be further trained and validated in a randomised, single-blinded, two-period, two-sequence crossover trial.Trial registration numberISRCTN51255782; Pre-results.

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.

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.

Patients in intensive care units (ICUs) are at risk of stress-related gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP), including proton pump inhibitors, is widely used in the attempt to prevent this. In this secondary analysis of Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, we assessed 1-year outcomes in the pantoprazole vs. placebo groups.In the SUP-ICU trial, 3298 acutely admitted ICU patients at risk of GI bleeding were randomly allocated, stratified for site, to pantoprazole or placebo. In this secondary analysis, we assessed clinically important GI bleedings in ICU and 1-year mortality, health care resource use (e.g. readmission with GI bleeding, use of home care and general practitioner), health care costs, and employment status for the Danish participants using registry data.Among the 2099 Danish participants, 2092 had data in the registries; 1045 allocated to pantoprazole and 1047 to placebo. The number of clinically important GI bleedings in ICU was 1.9 percentage points [95% CI 0.3-3.5] lower in the pantoprazole group vs. the placebo group, but none of the 1-year outcomes differed statistically significantly between groups, including total health care costs (€1954 [- 2992 to 6899]), readmission with GI bleeding (- 0.005 admissions [- 0.016 to 0.005]), 1-year mortality (- 0.013 percentage points [- 0.051 to 0.026]), and employment (- 0.178 weeks [- 0.390 to 0.034]).Among ICU patients at risk of GI bleeding, pantoprazole reduced clinically important GI bleeding in ICU, but this did not translate into a reduction in 1-year mortality, health care resource use or improvements in employment status.

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.

Introduction Knee osteoarthritis (OA) is associated with chronic knee pain and functional disability that negatively affect the ability to carry out normal daily activities. Patients are offered a large variety of non-surgical treatments, often not in accordance with clinical guidelines. This observational study will provide a comprehensive overview of treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon, including timing and order of treatment modalities, predictors of treatment outcomes, cost-effectiveness of treatment pathways and patients’ views on different treatment pathways. Methods and analysis Patients with primary referrals to an orthopaedic surgeon due to knee OA are consecutively invited to participate and fill out a questionnaire prior to their consultation with an orthopaedic surgeon. Follow-up questionnaires will be obtained at 6 and 24 months after inclusion. Based on a prospective cohort study design, including questionnaires and register data, we will (1) describe treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon; (2) describe the characteristics of patients choosing different treatment pathways; (3) develop predictive models for patient-self-determined classifications of good and poor treatment outcomes; (4) evaluate the cost-effectiveness of treatment pathways that live up to clinical guidelines versus pathways that do not; based on a qualitative study design using semistructured individual interviews, we will (5) describe the patients’ perspectives on treatment pathways for knee OA. Ethics and dissemination The study is approved by the Danish regional ethical committee (journal number H-17017295) and the Danish Data Protection Agency (journal number AHH-2017–072). Data will be anonymised and handled in line with the General Data Protection Regulation and the Danish Data Protection Act. The study results will be submitted to international open-access peer-reviewed journals and disseminated at conferences. Trial registration number NCT03746184, pre-results.

BackgroundTherapeutic management of inflammatory bowel diseases (IBD) is rapidly evolving, with an expanding armoury of biological drugs at our disposal. However, real-world findings about treatment persistence and the impact of biologicals on surgery remain inconsistent.AimsThis study aimed to investigate trends in biological use and surgery rates in a nationwide cohort of biological-naïve IBD patients.MethodsPatients with IBD who initiated biological treatment between 2011 and 2018 were identified in the Danish National Patient Registry. Data on use of biologicals, surgeries and healthcare costs were retrieved and analysed for time trends.ResultsBetween 2011 and 2018, a total of 6,036 IBD (51% ulcerative colitis (UC), 49% Crohn's disease (CD)) patients received biological treatment for the first time. Cumulative use of biologicals increased from 5.0% to 10.8% among UC and 8.9%-14.5% among CD patients. Infliximab remained the most-prescribed first-line biological for UC and CD. Treatment persistence was 44.3% and 16.9% after 1 and 3 years in UC, compared to 59.9% and 33.6% in CD patients. Overall, 32.8% of patients switched to a second biological. Surgery rates decreased in both UC (P = 0.015) and CD (P = 0.008) patients and remained significant for UC in the Cox regression model (P = 0.002). Outpatient and surgical costs also fell among both UC and CD patients.ConclusionsPersistence rates for first-line biologicals among IBD patients were low and one-third switched treatment. Surgery rates and direct costs decreased over time, but whether this is related to the use of biologicals has yet to be determined. Background: Therapeutic management of inflammatory bowel diseases (IBD) is rapidly evolving, with an expanding armoury of biological drugs at our disposal. However, real-world findings about treatment persistence and the impact of biologicals on surgery remain inconsistent. Aims: This study aimed to investigate trends in biological use and surgery rates in a nationwide cohort of biological-naïve IBD patients. Methods: Patients with IBD who initiated biological treatment between 2011 and 2018 were identified in the Danish National Patient Registry. Data on use of biologicals, surgeries and healthcare costs were retrieved and analysed for time trends. Results: Between 2011 and 2018, a total of 6,036 IBD (51% ulcerative colitis (UC), 49% Crohn's disease (CD)) patients received biological treatment for the first time. Cumulative use of biologicals increased from 5.0% to 10.8% among UC and 8.9%-14.5% among CD patients. Infliximab remained the most-prescribed first-line biological for UC and CD. Treatment persistence was 44.3% and 16.9% after 1 and 3 years in UC, compared to 59.9% and 33.6% in CD patients. Overall, 32.8% of patients switched to a second biological. Surgery rates decreased in both UC (P = 0.015) and CD (P = 0.008) patients and remained significant for UC in the Cox regression model (P = 0.002). Outpatient and surgical costs also fell among both UC and CD patients. Conclusions: Persistence rates for first-line biologicals among IBD patients were low and one-third switched treatment. Surgery rates and direct costs decreased over time, but whether this is related to the use of biologicals has yet to be determined.

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.

Technological innovation creates new treatment opportunities, while also putting healthcare budgets under strain. To deal with the rising costs of hospital medicines, the regional governments in Denmark have developed a new model for prioritising the adoption and use of hospital medicine. Marking a shift from previous policies, the new model formalises the evaluation of clinical benefit, adds an assessment of treatment costs and ensures a relatively high degree of direct stakeholder involvement. In international comparison, the new model is ambitious in terms of stakeholder involvement and adherence with principles advocated to ensure procedural justice and fair decision-making processes. However, these procedural innovations have also created new challenges. Notably, the newly formed assessment body, the Danish Medicines Council, is faced with a very high caseload and limited options to prioritise the use of its analytical resources.

The paper analyses a case of contract reversal in the market for ambulance services. The paper suggests that the sociology of markets-literature provides insights into market institutions of importance to relations between government and contractors that will benefit contracting out theory. Building on document analysis and interviews with 19 key stakeholders, it is demonstrated how a regional government in Denmark tried to wrestle the service provision from a long-time private provider and create a competitive market, only to discover that the implementation of the new contract was beset by obstacles largely stemming from informal norms in the market and attempts of the existing provider to hamper market entry for challenger firms. The result was a contract reversal: from private provision to government-provided service delivery. The paper contributes to the contracting out literature by providing a more elaborate understanding of the institutional conditions under which contract reversals can take place.

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.

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.

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.

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.

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.

Information regarding welfare consequences of early onset of Borderline Personality Disorder (BPD) is limited. This nationwide study aimed to estimate the educational and employment outcome and health care costs of patients with early-onset BPD compared with matched controls. All patients ( 19 years) with first diagnosis of BPD in the Danish Patient Register (NPR) during the period 1983-2015 were included. Health care costs and socioeconomic variables were extracted from national registers. A total of 171 patients was compared with 677 controls. At the age of 20 years, BPD patients had reached a statistically significantly lower educational level (including lower primary school grades) and employment status compared with the controls. When adjusting for the parents' educational level, BPD patients were nearly 22 times more likely to be unemployed (OR = 21.7, 95% CI 11.9, 39.6), and nearly 15 times more likely to be on disability pension (OR = 14.8, 95% CI 5.0, 43.9) than controls. Furthermore, the total health care costs were more than 8 times higher in the BPD group. Early onset of BPD was associated with lower educational and vocational outcome and increased health care costs as early as at the age of 20 years. Even after controlling for parents' lower socioeconomic status, the patients have poorer outcome than the control group. This underlines that initiatives to support patients in finishing school and secondary education is highly needed. Future prevention and early intervention programs should target patients with early-onset BPD and their families.

Study Objectives Parkinson’s disease (PD) causes significant socioeconomic burdens. One of the strongest predictors of PD is rapid eye movement (REM) sleep behavior disorder (RBD; when there is no known other cause of RBD, referred to as idiopathic RBD [iRBD]), but there is no information about its factual welfare burden. We estimated the direct and indirect total costs of iRBD in a national sample of patients, based on a national register-based cohort study with matched controls. Methods Using records from the Danish National Patient Registry, patient’s diagnosis with RBD from 2006 to 2016 were identified. We excluded patients with a prior diagnosis of narcolepsy, PD, and other neurodegenerative diseases. We identified and compared randomly chosen controls matched for age, gender, geographic area, and civil status. Direct costs included frequencies of primary and secondary sector contacts and procedures, and medication. Indirect costs included the effect on labor supply. Social-transfer payments were included to illustrate the effect on national accounts. Results A total of 246 iRBD patients and 982 matched controls were registered. iRBD patients had significantly higher rates of health-related contacts and of medication use, and higher socioeconomic costs than controls. The total additional direct net healthcare costs after the diagnosis (general practitioner services, hospital services, and medication) and indirect costs (loss of labor market income) was €13,088 for patients compared with controls. Patients already exhibited a negative social- and health-related status several years before the first diagnosis. Conclusions Diagnoses of iRBD have major socioeconomic consequences for patients, their partners, and society.