Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.

Persistent symptoms and risk factors predicting prolonged time to symptom-free after SARS­CoV­2 infection: an analysis of the baseline examination of the German COVIDOM/NAPKON-POP cohort.

PURPOSE: We aimed to assess symptoms in patients after SARS-CoV-2 infection and to identify factors predicting prolonged time to symptom-free. METHODS: COVIDOM/NAPKON-POP is a population-based prospective cohort of adults whose first on-site visits were scheduled ≥ 6 months after a positive SARS-CoV-2 PCR test. Retrospective data including self-reported symptoms and time to symptom-free were collected during the survey before a site visit. In the survival analyses, being symptom-free served as the event and time to be symptom-free as the time variable. Data were visualized with Kaplan-Meier curves, differences were tested with log-rank tests. A stratified Cox proportional hazard model was used to estimate adjusted hazard ratios (aHRs) of predictors, with aHR < 1 indicating a longer time to symptom-free. RESULTS: Of 1175 symptomatic participants included in the present analysis, 636 (54.1%) reported persistent symptoms after 280 days (SD 68) post infection. 25% of participants were free from symptoms after 18 days [quartiles: 14, 21]. Factors associated with prolonged time to symptom-free were age 49-59 years compared to < 49 years (aHR 0.70, 95% CI 0.56-0.87), female sex (aHR 0.78, 95% CI 0.65-0.93), lower educational level (aHR 0.77, 95% CI 0.64-0.93), living with a partner (aHR 0.81, 95% CI 0.66-0.99), low resilience (aHR 0.65, 95% CI 0.47-0.90), steroid treatment (aHR 0.22, 95% CI 0.05-0.90) and no medication (aHR 0.74, 95% CI 0.62-0.89) during acute infection. CONCLUSION: In the studied population, COVID-19 symptoms had resolved in one-quarter of participants within 18 days, and in 34.5% within 28 days. Over half of the participants reported COVID-19-related symptoms 9 months after infection. Symptom persistence was predominantly determined by participant's characteristics that are difficult to modify.

Ethical and coordinative challenges in setting up a national cohort study during the COVID-19 pandemic in Germany.

With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic.

Multicenter, cross-sectional study of the costs of illness and cost-driving factors in adult patients with epilepsy.

OBJECTIVE: This study was undertaken to quantify epilepsy-related costs of illness (COI) in Germany and identify cost-driving factors. METHODS: COI were calculated among adults with epilepsy of different etiologies and severities. Multiple regression analysis was applied to determine any epilepsy-related and sociodemographic factors that serve as cost-driving factors. RESULTS: In total, 486 patients were included, with a mean age of 40.5 ± 15.5 years (range = 18-83 years, 58.2% women). Mean 3-month COI were estimated at €4911, €2782, and €2598 for focal, genetic generalized, and unclassified epilepsy, respectively. The mean COI for patients with drug-refractory epilepsy (DRE; €7850) were higher than those for patients with non-DRE (€4720), patients with occasional seizures (€3596), or patients with seizures in remission for >1 year (€2409). Identified cost-driving factors for total COI included relevant disability (unstandardized regression coefficient b = €2218), poorer education (b = €2114), living alone (b = €2612), DRE (b = €1831), and frequent seizures (b = €2385). Younger age groups of 18-24 years (b = -€2945) and 25-34 years (b = -€1418) were found to have lower overall expenditures. A relevant disability (b = €441), DRE (b = €1253), frequent seizures (b = €735), and the need for specialized daycare (b = €749) were associated with higher direct COI, and poorer education (b = €1969), living alone (b = €2612), the presence of a relevant disability (b = €1809), DRE (b = €1831), and frequent seizures (b = €2385) were associated with higher indirect COI. SIGNIFICANCE: This analysis provides up-to-date COI data for use in further health economics analyses, highlighting the high economic impacts associated with disease severity, disability, and disease-related loss of productivity among adult patients with epilepsy. The identified cost drivers could be used as therapeutic and socioeconomic targets for future cost-containment strategies.

Trends in resource utilization and cost of illness in patients with active epilepsy in Germany from 2003 to 2020.

OBJECTIVE: This study was undertaken to calculate epilepsy-related direct, indirect, and total costs in adult patients with active epilepsy (ongoing unprovoked seizures) in Germany and to analyze cost components and dynamics compared to previous studies from 2003, 2008, and 2013. This analysis was part of the Epi2020 study. METHODS: Direct and indirect costs related to epilepsy were calculated with a multicenter survey using an established and validated questionnaire with a bottom-up design and human capital approach over a 3-month period in late 2020. Epilepsy-specific costs in the German health care sector from 2003, 2008, and 2013 were corrected for inflation to allow for a valid comparison. RESULTS: Data on the disease-specific costs for 253 patients in 2020 were analyzed. The mean total costs were calculated at €5551 (±€5805, median = €2611, range = €274-€21 667) per 3 months, comprising mean direct costs of €1861 (±€1905, median = €1276, range = €327-€13 158) and mean indirect costs of €3690 (±€5298, median = €0, range = €0-€11 925). The main direct cost components were hospitalization (42.4%), antiseizure medication (42.2%), and outpatient care (6.2%). Productivity losses due to early retirement (53.6%), part-time work or unemployment (30.8%), and seizure-related off-days (15.6%) were the main reasons for indirect costs. However, compared to 2013, there was no significant increase of direct costs (-10.0%), and indirect costs significantly increased (p < .028, +35.1%), resulting in a significant increase in total epilepsy-related costs (p < .047, +20.2%). Compared to the 2013 study population, a significant increase of cost of illness could be observed (p = .047). SIGNIFICANCE: The present study shows that disease-related costs in adult patients with active epilepsy increased from 2013 to 2020. As direct costs have remained constant, this increase is attributable to an increase in indirect costs. These findings highlight the impact of productivity loss caused by early retirement, unemployment, working time reduction, and seizure-related days off.

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584.

EuroQOL-5D-3L does not adequately map quality-of-life deterioration in severely affected patients with epilepsy.

INTRODUCTION: The steadily increasing impact of health-related quality of life (HRQOL) on reasonable diagnostic and therapeutic decisions makes the correct mapping of HRQOL indispensable in modern epileptology. The aim of this study was to address the reliability of the often-used generic HRQOL screening questionnaire EuroQOL 5-dimension, 3-level (EQ-5D-3L) by comparing its normalized index value (calculated via the time trade-off method) and visual analog scale (VAS) to the gold standard of the extensive Quality of Life in Epilepsy Inventory (QOLIE-31). QOLIE-10 scores were compared with the extensive QOLIE-31 and EQ-5D-3L TTO. METHODS: We conducted a retrospective analysis of a monocentric study of 184 patients with epilepsy. Bivariate Spearman correlation analysis and Fisher's r-to-z transformation were used to compare the strengths of correlations of EQ-5D-3L, QOLIE-10 and QOLIE-31 with different epilepsy-specific domains (disease severity, drug interactions, emotional well-being, stigmatization, seizure-related anxiety, cognitive impairment). RESULTS: The different metrics of EQ-5D-3L, QOLIE-10 and QOLIE-31 showed moderate to very strong intra- and inter-metric correlations for overall HRQOL. Quality of Life in Epilepsy Inventory-31 VAS and EQ-5D-3L VAS did not show any significantly different strengths of correlations with respect to the domains studied. In contrast, the correlation strength of the normalized EQ-5D-3L index value differed significantly from the QOLIE-31 T-score for several domains, for example, for drug-related adverse events, neuropsychological deficits, symptoms of depression and seizure worry. In seizure-free patients, EQ-5D-3L VAS and EQ-5D-3L index values correlated significantly less with the domain of "cognitive impairment" than the QOLIE-31 T-score. In patients without relevant neuropsychological deficits, the strengths of correlations with the assessed domains did not differ significantly between EQ-5D-3L metrics and the QOLIE-31 T-score. The HRQOL mapping probability of QOLIE-10 was inferior to QOLIE-31 and comparable to EQ-5D-3L regarding the analyzed domains. CONCLUSION: In contrast to the EQ-5D-3L VAS, EQ-5D-3L index values do not adequately map health-related quality of life in severely affected patients with epilepsy and therefore should not be used as screening tools. The QOLIE-31 T-score remains the gold standard for HRQOL assessment in patients with epilepsy.

[Care of patients with Parkinson's disease in Germany]. / Versorgung von Parkinson-Patienten in Deutschland.

In Germany various concepts for treating patients with Parkinson's disease (PD) are available, e.g. oral medication with levodopa or deep brain stimulation (DBS), depending on the stage and severity of symptoms and also multidisciplinary management up to intersectoral treatment approaches (e.g. complex PD treatment and integrative care concepts). Nevertheless, in the treatment of patients with PD a comprehensive provision of services and a nationwide standardized collation of treatment quality are so far lacking. This is particularly true for technically complicated procedures, which necessitate a high standard of expertise by the treating physician. Some of these challenges could be overcome by expanding digital approaches (e.g. teleneurological consultation and wearables) and by introducing quality assurance initiatives (e.g. comprehensive registries and certification programs).

Prescription of Benzodiazepines and Related Drugs in Patients with Mild Cognitive Deficits and Alzheimer's Disease.

INTRODUCTION: Benzodiazepines and related drugs (BZDR) should be avoided in patients with cognitive impairment. We evaluated the relationship between a BZDR treatment and the health status of patients with Alzheimer's disease (AD). METHODS: Cross-sectional study in 395 AD patients using bivariate and multiple logistic analyses to assess correlations between the prescription of BZDR and patients' characteristics (cognitive and functional capacity, health-related quality of life (HrQoL), neuropsychiatric symptoms). RESULTS: BZDR were used in 12.4% (n=49) of all participants. In bivariate analyses, the prescription was associated with a lower HrQoL, a higher need of care, and the presence of anxiety. Multivariate models revealed a higher risk of BZDR treatment in patients with depression (OR 3.85, 95% CI: 1.45 - 10.27). Community-dwelling participants and those treated by neurologists/psychiatrists had a lower risk of receiving BZDR (OR 0.33, 95% CI: 0.12 - 0.89 and OR 0.16, 95% CI: 0.07 - 0.36). DISCUSSION: The inappropriate use of BZDR conflicts with national and international guidelines. We suggest evaluating indications and treatment duration and improving the knowledge of alternative therapies in healthcare institutions.

The association between antihypertensive therapy and the incidence of Parkinson's disease in patients followed in general practices in Germany
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AIM: The aim of this study was to investigate the potential association between antihypertensive therapy and the incidence of Parkinson's disease (PD) in patients followed in general practices in Germany. MATERIALS AND METHODS: This study included patients aged ≥ 40 who had received initial diagnoses of PD in 1,203 general practices in Germany between January 2013 and December 2017 (index date). After applying similar inclusion criteria, PD cases were matched to non-PD controls using propensity scores based on age, sex, and treating physician. The primary outcome of the study was the incidence of PD as a function of the use of antihypertensive drugs (diuretics, ß-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers). Logistic regression models were conducted to study the association between the use of antihypertensive drugs and the incidence of PD after adjusting for codiagnoses and antihypertensive cotherapy. RESULTS: The present study included 9,127 patients with PD and 9,127 patients without PD (mean age: 75.8 years; 48.4% women). The at-least-once use of diuretics (44.8% versus 38.4%; odds ratio (OR) = 1.23 (1.15-1.32)) was associated with an increased incidence of PD. However, this effect was not maintained for a therapy duration of at least 3 years, and no association was observed between the diuretic therapy duration and PD incidence. For all other antihypertensive drug classes, we found no significant associations with PD incidence. CONCLUSION: No association was found between antihypertensive therapy duration and PD incidence. Further epidemiological studies are needed to compare the effects of subclasses of antihypertensives on PD.

[Analysis of Different Quality Management Systems in Medical Practices in Saxony]. / Analyse verschiedener Qualitätsmanagementsysteme in Arztpraxen für Sachsen.

INTRODUCTION: Since 1 January 2004, all physicians, psychotherapists and medical care centres on contracts with statutory healthcare in Germany are obliged according to § 135a section 2, no. 2 of the Fifth Social Security Statute Book to introduce and develop an intra-institutional quality management system. Thus, physicians are faced with the question of which quality management system is best suited to their own practice. METHODS: A total of 24 medical practices were chosen by random sampling. The sample was collected in Saxony because the Health Insurance Physicians Unification Saxony provided the necessary information. First, 2 primary units were determined from the basic population. In the following step, a sample was taken for each primary unit using 3 quality management systems. The analysis was carried out with the help of three specially developed questionnaires (physician, employee and patient). The individual questions were developed independently of a quality management system. The basis was formed by the guidelines of the Federal Joint Committee, which describes the concrete contents of the quality categories. A total of 26 quality categories with different questions were available in the 3 survey groups. For the analysis of the data, the arithmetic mean was formed in the individual question complexes. Subsequently, a variance analysis was used to test whether the systems differed statistically significantly on average. Taking into account the costs of the individual quality management systems and their introduction, the effect size was finally analyzed according to η2 and Cohen's d. Finally, a cost-benefit analysis was carried out by researching the direct/indirect costs of the various quality management systems through a literature study. RESULTS: Based on model documents and process support, the "Quality and Development in Practices" had the highest score. Due to a specific family practitioner specialty, "Quality management systems in Saxony medical practices" had the next best scores. The individual quality categories such as the 'range of services' or 'treatment pathways and guidelines' indicate significant differences and sustained effect sizes between quality management systems. CONCLUSION: The assessment of quality management systems shows significant differences. The specific differences between the systems can be explained by the differences in process tools.

Costs of illness in chronic inflammatory demyelinating polyneuropathy in Germany.

INTRODUCTION: Cost of illness studies are essential to estimate societal costs of chronic inflammatory demyelinating polyneuropathy (CIDP) and identify cost-driving factors. METHODS: In total, 108 patients were recruited from 3 specialized neuroimmunological clinics. Costs were calculated for a 3-month period, including direct and indirect costs. The following outcomes were assessed: inflammatory neuropathy cause and treatment disability scale, Mini-Mental State Examination, Beck Depression Inventory, Charlson comorbidity index, EuroQol-5D, World Health Organization quality of life instrument, and socioeconomic status. Univariate and multivariate analyses were applied to identify cost-driving factors. RESULTS: Total quarterly costs were €11,333. Direct costs contributed to 83% of total costs (€9,423), whereas indirect costs accounted for 17% (€1,910) of total costs. The cost of intravenous immunoglobulin (IVIg) was the main determinant of total costs (67%). Reduced health-related quality of life and depressive symptoms were identified as independent predictors of higher total costs. DISCUSSION: CIDP is associated with high societal costs, mainly resulting from the cost of IVIg treatment. Muscle Nerve 58: 681-687, 2018.

Trends in resource utilization and prescription of anticonvulsants for patients with active epilepsy in Germany from 2003 to 2013 - A ten-year overview.

This study evaluated trends in resource use and prescription patterns in patients with active epilepsy over a 10-year period at the same outpatient clinic of a German epilepsy center. We analyzed a cross-sectional patient sample of consecutive adults with active epilepsy over a 3-month period in 2013 and compared them with equally acquired data from the years 2003 and 2008. Using validated patient questionnaires, data on socioeconomic status, course of epilepsy, as well as direct and indirect costs were recorded. A total of 198 patients (mean age: 39.6±15.0years, 49.5% male) were enrolled and compared with our previous assessments in 2003 (n=101) and 2008 (n=151). In the 2013 cohort, 75.8% of the patients had focal epilepsy, and the majority were taking antiepileptic drugs (AEDs) (39.9% monotherapy, 59.1% polytherapy). We calculated epilepsy-specific costs of €3674 per three months per patient. Direct medical costs were mainly due to anticonvulsants (20.9% of total direct costs) and to hospitalization (20.8% of total direct costs). The proportion of enzyme-inducing anticonvulsants and 'old' AEDs decreased between 2003 and 2013. Indirect costs of €1795 in 2013 were mainly due to early retirement (55.0% of total indirect costs), unemployment (26.5%), and days off due to seizures (18.2%). In contrast to our previous findings from 2003 and 2008, our data show a stagnating cost increase with slightly reduced total costs and balanced direct and indirect costs in patients with active epilepsy. These findings are accompanied by an ongoing cost-neutral increase in the prescription of 'newer' and non-enzyme-inducing AEDs. However, the number and distribution of indirect cost components remained unchanged.

Antidepressant medication in a German cohort of patients with Alzheimer's disease
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OBJECTIVE: The use of antidepressant drugs in dementia patients is associated with the risk of adverse events, and the evidence for relevant effects is scarce. We aimed to determine the associations between the prescription of antidepressants and patients' sociodemographic (e.g., age, gender, living situation) and clinical characteristics (e.g., disease severity, neuropsychiatric symptoms). MATERIALS AND METHODS: We included 395 institutionalized and community-dwelling patients with Alzheimer's disease (AD) across all severity stages of dementia in a cross-sectional study design. The patients' clinical characteristics comprised of cognitive status, daily activities, depressive symptoms, further neuropsychiatric symptoms, and health-related quality of life (HrQoL). We conducted multiple logistic regression analyses for the association between the use of antidepressant drugs and the covariates. RESULTS: Approximately 31% of the participants were treated with antidepressant drugs, with a higher chance of being medicated for institutionalized patients (χ2-test: p = 0.010). In the bivariate analyses, the use of antidepressants was significantly associated with higher levels of care, lower cognitive and daily life capacity, higher extent of neuropsychiatric symptoms, and a lower proxy-reported HrQoL. Finally, multiple logistic regression models showed a significantly higher use of antidepressants in patients treated by psychiatrists and neurologists (OR 2.852, 95% CI: 1.223 - 6.652). CONCLUSION: The use of antidepressant drugs in the study population was high, and the suitability of the treatment with antidepressants remains unclear. Participants with diminished cognitive and functional capacity, higher extent of neuropsychiatric symptoms, and those treated by neuropsychiatric specialists were more likely to be treated with antidepressants. The pharmaceutical treatment of patients with these clinical characteristics should be particularly considered in the daily care for dementia patients. Further longitudinal studies should evaluate the appropriateness of indications for antidepressants and the causative direction of correlations with the patients' clinical characteristics.
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Antipsychotic treatment of community-dwelling and institutionalised patients with dementia in Germany.

OBJECTIVE: A restrictive use of antipsychotic drugs in patients with Alzheimer's disease (AD) is recommended due to an increased risk of cerebrovascular events and mortality. We hypothesise that the prescription of antipsychotics is associated with the patients' socio-demographic and clinical status (e.g., dementia severity). METHODS: The prescription of antipsychotics was cross-sectionally evaluated in 272 community-dwelling and 123 institutionalised patients with AD across all severity stages of dementia. The patients' clinical characteristics covered the cognitive status, neuropsychiatric symptoms, daily activities, and quality of life (HrQoL). To determine associations with the use of antipsychotics bivariate and logistic regression analyses were conducted. RESULTS: Totally, 25% of the patients were treated with antipsychotics. significantly less frequently than nursing home inhabitants (15.1% vs. 45.5%). Severely demented patients (MMSE 0-9) received antipsychotics most often (51.5%). Additionally, multiple regression analyses revealed a higher chance of prescription for participants with depressive symptoms (OR 2.3, 95% CI: 1.019-5.160) and those treated by neuropsychiatric specialists (OR 3.4, 95% CI: 1.408-8.328). CONCLUSIONS: Further longitudinal studies are required to assess the appropriateness of indications for antipsychotics and the reasons for a higher use in nursing home inhabitants and patients with severe dementia and depression.

Prevalence, Duration and Severity of Parkinson's Disease in Germany: A Combined Meta-Analysis from Literature Data and Outpatient Samples.

BACKGROUND: Epidemiological data on the prevalence of Parkinson's disease (PD) in Germany are limited. The aims of this study were to estimate the age- and gender-specific prevalence of PD in Germany as well as the severity and illness duration. SUMMARY: A systematic literature search was performed in 5 different databases. European studies were included if they reported age- and gender-specific numbers of prevalence rates of PD. Meta-analytic approaches were applied to derive age- and gender-specific pooled prevalence estimates. Data of 4 German outpatient samples were incorporated to calculate the proportion of patients with PD in Germany grouped by Hoehn and Yahr (HY) stages and disease duration. In the German population, 178,169 cases of PD were estimated (prevalence: 217.22/100,000). The estimated relative illness duration was 40% with less than 5 years, 31% with 5-9 years, and 29% with more than 9 years. The proportions for different HY stages were estimated at 13% (I), 30% (II), 35% (III), 17% (IV), and 4% (V), respectively. Key Message: We provide an up-to-date estimation of age- and gender-specific as well as severity-based prevalence figures for PD in Germany. Further community studies are needed to estimate population-based severity distributions and distributions of non-motor symptoms in PD.

Cost-effectiveness of neurostimulation in Parkinson's disease with early motor complications.

BACKGROUND: Recent research efforts have focused on the effects of deep brain stimulation of the subthalamic nucleus (STN DBS) for selected patients with mild-to-moderate PD experiencing motor complications. OBJECTIVES: We assessed the cost utility of subthalamic DBS compared with the best medical treatment for German patients below the age of 61 with early motor complications of PD. METHODS: We applied a previously published Markov model that integrated health utilities based on EuroQoL and direct costs over patients' lifetime adjusted to the German health care payer perspective (year of costing: 2013). Effectiveness was evaluated using the Parkinson's Disease Questionnaire 39 summary index. We performed sensitivity analyses to assess uncertainty. RESULTS: In the base-case analysis, the incremental cost-utility ratio for STN DBS compared to best medical treatment was 22,700 Euros per quality-adjusted life year gained. The time to, and costs for, battery exchange had a major effect on the incremental cost-utility ratios, but never exceeded a threshold of 50,000 Euros per quality-adjusted life year. CONCLUSIONS: Our decision analysis supports the fact that STN DBS at earlier stages of the disease is cost-effective in patients below the age of 61 when compared with the best medical treatment in the German health care system. This finding was supported by detailed sensitivity analyses reporting robust results. Whereas the EARLYSTIM study has shown STN DBS to be superior to medical therapy with respect to quality of life for patients with early motor complications, this further analysis has shown its cost-effectiveness. © 2016 International Parkinson and Movement Disorder Society.

Costs and cost-driving factors for acute treatment of adults with status epilepticus: A multicenter cohort study from Germany.

OBJECTIVE: To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). METHODS: In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. RESULTS: We evaluated 341 admissions in 316 patients (65.7 ± [standard deviation]18.2 years; 135 male) treated for SE. Mean costs of hospital treatment were €14,946 (median €5,278, range €776-€152,911, €787 per treatment day) per patient per admission, with a mean length of stay (LOS) of 19.0 days (median 14.0, range 1-118). Course of SE had a significant impact on mean costs, with €8,314 in NSE (n = 137, median €4,597, €687 per treatment day, 22.3% of total inpatient costs due to SE), €13,399 in RSE (n = 171, median €7,203, €638/day, 45.0% of total costs, p < 0.001), and €50,488 in SRSE (n = 33, median €46,223, €1,365/day, 32.7% of total costs, p < 0.001). Independent cost-driving factors were SRSE, ventilation, and LOS of >14 days. Overall mortality at discharge was 14.4% and significantly higher in RSE/SRSE (20.1%) than in NSE (5.8%). SIGNIFICANCE: Acute treatment of SE, and particularly SRSE and ventilation, are associated with high hospital costs and prolonged LOS. Extrapolation to the whole of Germany indicates that SE causes hospital costs of >€200 million per year. Along with the demographic change, incidence of SE will increase and costs for hospital treatment and sequelae of SE will rise.

Association of time-to-levodopa with initial Parkinsonian medication: a retrospective cohort study.

OBJECTIVES: To determine the initial distribution of medication in patients with de novo Parkinson's disease (PD), to estimate the share of patients who not receive a recommended initial therapy according to current German guidelines, and to compare the time-to-levodopa. METHODS: We used the Disease Analyzer database (IMS HEALTH), containing basic medical data from ~20 million patients in Germany. The primary outcome was the therapy change rate from initial treatment to levodopa estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to estimate the relationship between time-to-levodopa and confounders for a maximum follow-up of 10 years (between January 2002 and December 2011). Adjusted hazard ratios (HR) and 95% confidence intervals (CI) are presented for change-to-levodopa rate. RESULTS: A representative sample of de-novo patients diagnosed with PD was drawn (n=108,885). 71.8% of patients received levodopa as a first line treatment. 29,708 patients started with other anti-PD substances: 13.3% with dopamine agonists (DA), 3.6% with amantadine, 5.9% with anticholinergics, and 0.8% with monoamine oxidase B (MAO-B) inhibitors. Therefore, the proportion of patients who not receive a recommended initial therapy according to current German guidelines was ~10%. 29.0% of patients not starting with levodopa switched to levodopa within 5 years. After 5 years, more than 80% of PD patients using anticholinergics as their initial treatment remained levodopa-free. MAOB- inhibitors and DAs showed significantly lower proportions of levodopa-free patients after 5 years (35% and 55%, respectively). Compared to MAO-B inhibitors, the HR for switching to levodopa was 0.38 (CI 0.34-0.43; p<0.001) for anticholinergics and 0.85 (CI 0.75-0.97; p=0.017) for nonergot DA. CONCLUSIONS: Surprisingly, initial treatment with anticholinergics is correlated with the longest delay of levodopa treatment among all monotherapies. Our results suggest re-evaluating the comparative effectiveness of all initial PD treatments in head-tohead comparisons.