The short-term and long-term adverse effects of melatonin treatment in children and adolescents: a systematic review and GRADE assessment.

Background: Currently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to provide clinicians and guideline panels with a systematic assessment of serious-and non-serious adverse events seen in continuation of melatonin treatment and the impact on pubertal development and bone health following long-term administration in children and adolescents with chronic insomnia. Methods: We searched PubMed, Embase, Cinahl and PsycINFO via Ovid, up to March 17, 2023, for studies on melatonin treatment among children and adolescents (aged 5-20 years) with chronic insomnia. The language was restricted to English, Danish, Norwegian, and Swedish. Outcomes were non-serious adverse events and serious adverse events assessed 2-4 weeks after initiating treatment and pubertal development and bone health, with no restriction on definition or time of measurement. Observational studies were included for the assessment of long-term outcomes, and serious and non-serious adverse events were assessed via randomised studies. The certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The protocol is registered with the Danish Health Authority. Findings: We identified 22 randomised studies with 1350 patients reporting on serious-and non-serious adverse events and four observational studies with a total of 105 patients reporting on pubertal development. Melatonin was not associated with serious adverse events, yet the number of patients experiencing non-serious adverse events was increased (Relative risk 1.56, 95% CI 1.01-2.43, 17 studies, I2 = 47%). Three studies reported little or no influence on pubertal development following 2-4 years of treatment, whereas one study registered a potential delay following longer treatment durations (>7 years). These findings need further evaluation due to several methodological limitations. Interpretation: Children who use melatonin are likely to experience non-serious adverse events, yet the actual extent to which melatonin leads to non-serious adverse events and the long-term consequences remain uncertain. This major gap of knowledge on safety calls for caution against complacent use of melatonin in children and adolescents with chronic insomnia and for more research to inform clinicians and guideline panels on this key issue. Funding: The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.

Subjective sleep assessment compared to polysomnography in mechanically ventilated critically ill ICU patients.

Sleep deprivation is expected in the intensive care unit (ICU) and is associated with delirium and increased mortality. Polysomnography (PSG) is the gold standard for sleep assessment, but practical issues limit the method. Hence, many ICUs worldwide use subjective sleep assessment (SSA) for sleep monitoring, but the agreement between SSA and PSG is unknown. The hypothesis was that the level of agreement between SSA and PSG was low and that total sleep time (TST) assessed with SSA would be overestimated compared to PSG in this existing cohort database. In this sub-analysis, 30 consecutive study participants underwent 15-h PSG recordings during two consecutive nights. The attending nurse performed an hourly subjective observer rating of sleep quantity during both nights, and the agreement between SSA and PSG was determined along with mean TST. Primary outcome: The level of agreement between SSA and PSG determined by Bland-Altman analysis. Secondary outcome: (1) The overall mean TST estimated by SSA compared to PSG in all study participants enrolled in the main study during both study nights, (2) TST for all study participants evaluated hourly during both study nights, (3) TST assessed with SSA compared to PSG in study participants sedated with dexmedetomidine during the second night and for study participants treated with placebo or non-sedation the first and second nights. The level of agreement between SSA and PSG was low. Mean TST estimated by SSA during the time interval 4.00 p.m. to 7.00 a.m. was 481 min (428;534, 95% CI) vs. PSG at 437 min (386;488, 95% CI) (p = .05). When sedated with dexmedetomidine, TST estimated using SSA was 650 min (571;729, 95% CI) versus PSG which was 588 min (531;645, 95% CI) (p = 0.56). For participants treated with placebo or non-sedation TST estimated with SSA was 397 min (343;450, 95% CI) versus PSG at 362 min (302;422, 95% CI) versus (p = 0.17). In mechanically ventilated critically ill ICU patients, the level of agreement between SSA and PSG was low, and there was a significant overestimation of mean TST. SSA should only be used under awareness that it is imprecise and overestimates TST.

Estimates of epilepsy prevalence, psychiatric co-morbidity and cost.

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.

Welfare consequences of early-onset Borderline Personality Disorder: a nationwide register-based case-control study.

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.

Socioeconomic and humanistic burden of illness of excessive daytime sleepiness severity associated with obstructive sleep apnoea in the European Union 5.

OBJECTIVE/BACKGROUND: Evaluate the impact of excessive daytime sleepiness (EDS) severity on burden of illness among adults with obstructive sleep apnoea (OSA) in European Union 5 (EU5) countries (France, Germany, Italy, Spain, United Kingdom). PATIENTS/METHODS: This retrospective observational study used data from the 2017 EU5 National Health and Wellness Survey, a self-administered, internet-based, non-screening survey. Respondents who self-reported both having experienced OSA in the last 12 months and having had their OSA diagnosed by a physician were considered to have OSA. Respondents completed the Epworth Sleepiness Scale (ESS) and were consequently categorised into 4 groups: OSA-with-EDS (ESS >10) subdivided by EDS severity (mild [ESS = 11-12], moderate [ESS = 13-15], severe [ESS = 16-24]), and OSA-without-EDS (ESS ≤10). Bivariate and multivariable analyses examined group differences in health-related quality of life (HRQoL), work productivity and activity impairment, and health care utilisation. RESULTS: The analysis included 2008 respondents with OSA: n = 661 (32.9%) with EDS (29.5% mild, 34.5% moderate, 36.0% severe) and n = 1347 without EDS. Compared with the OSA-without-EDS group, the OSA-with-EDS subgroups generally had higher rates of obesity, depression, and other reported comorbidities. Greater severity of EDS was associated with worse self-reported HRQoL (all domains, P < 0.001) and work productivity and activity impairment (absenteeism, P = 0.031; presenteeism, overall work impairment, and non-work activity impairment, P < 0.001), as well as increased numbers of health care provider visits (P < 0.001). CONCLUSIONS: Compared to patients with OSA but without EDS, those with EDS had substantially higher socioeconomic and humanistic burden of disease, which was more profound among those reporting greater EDS.

Costs of schizotypal disorder: A matched-controlled nationwide register-based study of patients and spouses.

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.

Health, social, and economic consequences of rapid eye movement sleep behavior disorder: a controlled national study evaluating societal effects.

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.

Long-term employment, education, and healthcare costs of childhood and adolescent onset of epilepsy.

OBJECTIVE: Childhood- and adolescent-onset epilepsy may have a significant impact on long-term educational and vocational status, which in turn has consequences for individuals' socioeconomic status. We estimated the factual long-term socioeconomic consequences and healthcare costs of individuals with diagnosed epilepsy. METHODS: The prospective cohort study included Danish individuals with epilepsy onset before the age of 18 years, diagnosed between 2002 and 2016. Healthcare costs and socioeconomic data were obtained from nationwide administrative and health registers. The prediction was made with a general estimating equation (GEE). A total of 15,329 individuals were found with the diagnosis during this period and were followed until the age of 30 years. These were compared with 31,414 controls. We used 30 years as this represent an age where most has finalized their education, and as such represent the final educational level. Patients and their controls were subdivided into debut age groups of 0-5 and 6-18 years. Individuals were matched for age, gender, and residential location. RESULTS: Compared with control groups, patients with epilepsy at the age of 30 years tended to have the following: 1) parents with lower educational attainment; 2) a significantly lower educational level when controlling for parental education attainment; 3) lower grade-point averages; 4) a lower probability of being in employment and lower income, even when transfer payments were considered; and 5) elevated healthcare costs, including those for psychiatric care. It was also noted that the long-term educational consequences for patients with epilepsy were associated with parental educational level. Differences were more pronounced for those with early (0-5 years) rather than later (6-18 years) onset epilepsy. CONCLUSIONS: Epilepsy is associated with severe long-term socioeconomic consequences: lower educational level, school grades, employment status, and earned income. The presence of epilepsy is associated with parental educational level. LIMITATIONS: SIGNIFICANT OUTCOMES.

Long-term health and socioeconomic outcome of obstructive sleep apnea in children and adolescents.

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 < 0.001). CONCLUSIONS: OSA in children and adolescent is associated with a significant influence on morbidity, mortality, educational level, grading, social outcome, and welfare consequences.

Welfare consequences for people diagnosed with attention deficit hyperactivity disorder (ADHD): A matched nationwide study in Denmark.

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.

Societal Costs of Schizophrenia in Denmark: A Nationwide Matched Controlled Study of Patients and Spouses Before and After Initial Diagnosis.

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

Long-term health and socioeconomic consequences of childhood and adolescent-onset of narcolepsy.

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.

Welfare consequences for people diagnosed with nonepileptic seizures: A matched nationwide study in Denmark.

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.

Assessment of diurnal melatonin, cortisol, activity, and sleep-wake cycle in patients with and without diabetic retinopathy.

OBJECTIVE: To assess the diurnal melatonin, cortisol, and activity/rest levels, as well as sleep quality, in patients with and without nonproliferative diabetic retinopathy (DR). METHODS: We included 25 diabetic patients with DR and 29 without DR. A total of 21 healthy subjects constituted the control group. We assessed the circadian rhythm by actigraphy and diurnal salivary melatonin and cortisol measurements. Sleep quality was evaluated by actigraphy and the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires. Light exposure was quantified by actigraphy. The primary outcome was peak salivary melatonin level. Secondary outcomes were mean melatonin and cortisol levels during dark hours, activity-rest rhythm, sleep quality, as well as level of white, red, green, and blue light exposure. RESULTS: Peak melatonin concentration at 04:00 and mean nocturnal melatonin level were significantly reduced in all diabetic patients, regardless of retinopathy stage (p < 0.001). Levels of light exposures during dark hours were not significantly different in patients with and without DR and healthy controls. Only patients with DR showed increased intradaily variability in their activity-rest interval, indicating circadian misalignment (p = 0.04). Neither the objective actigraphic sleep quality parameters nor the subjective PSQI or ESS scores were significantly different between healthy controls and diabetic patients. CONCLUSIONS: Reduced nocturnal melatonin concentration and increased fragmentation of activity-rest intervals revealed circadian rhythm disturbance in diabetic patients with DR.

Long-term health and socioeconomic consequences of childhood and adolescent onset of meningococcal meningitis.

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.

Welfare consequences for people with epilepsy and their partners: A matched nationwide study in Denmark.

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.

Polysomnographic indicators of mortality in stroke patients.

PURPOSE: The purpose of the study was to assess polysomnographic indicators of increased mortality risk in patients with stroke or a transient ischemic attack (TIA). METHODS: We performed polysomnographies in 63 acute stroke/TIA patients. Mortality data were collected from a national database after a 19-37-month follow-up period. RESULTS: Of the 57 stroke and 6 TIA patients, 9 stroke patients died during follow-up. All nine had moderate or severe sleep-related breathing disorders (SRBDs). Binarily divided, the group with the highest apnea hypopnea index (AHI) had an almost 10-fold higher mortality risk (hazard ratio (HR) 9.71; 95 % confidence interval (CI) 1.20-78.29; p = 0.033) compared to the patients with the lowest AHI. The patients with the longest versus shortest nocturnal wake time had a higher mortality (HR 8.78; 95 % CI 1.1-71.8; p = 0.0428). Lung disease increased mortality (HR 9.92; 95 % CI 2.00-49.23; p = 0.005), and there was a trend toward a higher mortality risk with atrial fibrillation/flutter (HR 3.63; 95 % CI 0.97-13.51; p = 0.055). CONCLUSIONS: In stroke patients, the AHI and nocturnal wake time are indicators of increased mortality risk. SRBDs in stroke patients should receive increased attention.

Welfare costs in patients with rheumatoid arthritis and their partners compared with matched controls: a register-based study.

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.

Socioeconomic evaluation of vagus stimulation: A controlled national study.

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.

Socioeconomic outcome of epilepsy surgery: A controlled national study.

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.