Childhood and adolescence factors and multiple sclerosis: results from the German National Cohort (NAKO).

BACKGROUND: Multiple Sclerosis (MS) represents the most common inflammatory neurological disease causing disability in early adulthood. Childhood and adolescence factors might be of relevance in the development of MS. We aimed to investigate the association between various factors (e.g., prematurity, breastfeeding, daycare attendance, weight history) and MS risk. METHODS: Data from the baseline assessment of the German National Cohort (NAKO) were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between childhood and adolescence factors and risk of MS. Analyses stratified by sex were conducted. RESULTS: Among a total of 204,273 participants, 858 reported an MS diagnosis. Male sex was associated with a decreased MS risk (HR 0.48; 95% CI 0.41-0.56), while overweight (HR 2.03; 95% CI 1.41-2.94) and obesity (HR 1.89; 95% CI 1.02-3.48) at 18 years of age compared to normal weight were associated with increased MS risk. Having been breastfed for ≤ 4 months was associated with a decreased MS risk in men (HR 0.59; 95% CI 0.40-0.86) compared to no breastfeeding. No association with MS risk was observed for the remaining factors. CONCLUSIONS: Apart from overweight and obesity at the age of 18 years, we did not observe considerable associations with MS risk. The proportion of cases that can be explained by childhood and adolescence factors examined in this study was low. Further investigations of the association between the onset of overweight and obesity in childhood and adolescence and its interaction with physical activity and MS risk seem worthwhile.

Overall survival in 92,991 colorectal cancer patients in Germany: differences according to type of comorbidity.

BACKGROUND: Poorer survival in cancer patients with vs. without comorbidity has been reported for various cancer sites. For patients with colorectal cancer (CRC), limited data are available so far. METHODS: Patients with CRC diagnosed between 2010 and 2018 were identified in a health claims database covering 20% of the German population. We assessed the prevalence of comorbidities at cancer diagnosis and categorized the patients into the groups: 'none', 'somatic only', 'mental only' or 'both' types of comorbidities. Hazard ratios (HR, with 95% confidence intervals) for five-year overall survival were estimated by Cox proportional hazard models, adjusted for age, sex and stage at diagnosis (advanced vs. non-advanced). RESULTS: We included 92,991 patients (females: 49.1%, median age: 72 years) with a median follow-up of 30 months. The proportions assigned to the groups 'none', 'somatic only', 'mental only' or 'both' were 24.7%, 65.5%, 1.4% and 8.4%. Overall, 32.8% of the patients died during follow-up. Compared to patients without comorbidities ('none'), the adjusted HR regarding death from any cause was 1.11 (95% CI: 1.07-1.14) in the group 'somatic only', 1.74 (95% CI: 1.58-1.92) in the group 'mental only' and 1.92 (95% CI: 1.84-2.00) in the group 'both'. For patients with 'mental only' comorbidities, the adjusted HR was higher in males than in females (HR = 2.19, 95% CI: 1.88-2.55 vs. HR = 1.55, 95% CI: 1.37-1.75). CONCLUSIONS: Our results suggest that patients with CRC and with mental comorbidities, particularly males, have a markedly lower overall survival compared to those without any or only somatic comorbidities.

Stability of individual dementia diagnoses in routine care: Implications for epidemiological studies.

PURPOSE: Epidemiological and health care research frequently rely on diagnoses from routine care, but the intra-individual stability of diagnoses of Alzheimer's disease (AD), vascular dementia (VD) or other forms of dementia (oD) in patients over time is understudied. More data on the diagnostic stability is needed to appraise epidemiological findings from such studies. METHODS: Using health claims data of the years 2004-2016 from the German Pharmacoepidemiological Research Database, 160 273 patients aged ≥50 with incident dementia were identified and followed for 4 years. According to the incident ICD-10 codes patients were assigned to the categories AD, VD or oD. Changes between categories during follow-up were calculated. RESULTS: Overall, 18.8% had incident AD (VD: 21.5%, oD: 59.7%). Fifteen thousand eight hundred forty-two patients had only one dementia diagnosis during 4 years (AD: 7.4%, VD: 12.4%, oD: 9.8%). Among those with more than one diagnosis, the incident diagnosis matched the last diagnosis in 65.1% (AD), 53.9% (VD) and 73.8% (oD) of patients. Changes in the diagnostic category were higher in patients with AD (mean: 5.1) than in patients with VD (3.6) or oD (3.3). Patients with stable AD diagnoses during the observation period were younger (median: 76 vs. 79 years) and had less inpatient treatment days (median: 14 days) than patients with changes from an AD diagnosis to another category or from another category to AD (27 days). CONCLUSIONS: While health claims data are feasible for estimating the incidence of dementia in general, the substantial number of changes in dementia diagnoses during the course of the disease warrant caution on the interpretation of epidemiological data on specific dementia types.

How often are antidepressants prescribed off-label among older adults in Germany? A claims data analysis.

AIM: To estimate the extent of off-label prescribing of antidepressants in older adults and to characterize patients with off-label vs on-label prescriptions of antidepressants using a large German health claims database. METHODS: Using data from the German Pharmacoepidemiological Research Database (GePaRD), we conducted a cross-sectional study in adults aged 65 years or older with a dispensation of an antidepressant between 1 January 2009 and 31 December 2015 after a period of 365 days without such a dispensation. We assessed the overall and annual proportion of off-label prescriptions of antidepressants by class and individual substance. RESULTS: Among 263 276 incident users of antidepressants, the proportion of off-label prescribing was 43.6% (95% CI 43.4-43.8%) with little variation between 2009 and 2015 (42.2-44.4%). The proportion of off-label use was higher in men (49%) than women (41%). While the proportion of off-label prescriptions was highest for tri- and tetracyclic antidepressants with 56.2% (amitriptyline 54.6%, maximum 65.9% for trimipramine), it amounted to 41.8% for selective serotonin reuptake inhibitors (citalopram 41.6%, maximum 46.0% for escitalopram) and was 51.2% for mirtazapine. Indicators of overall morbidity were similar in both groups, eg, pain was coded in 72% of off-label users vs 77% of on-label users (insomnia 20% vs 24%). CONCLUSION: Our study suggests a high prevalence of off-label antidepressant use among older adults in Germany, which was not restricted to certain classes of antidepressants or individual antidepressants. Given the unclear risk-benefit ratio, studies investigating the safety of off-label use among older adults for individual antidepressants are urgently needed.

[Guidelines for the Neuropsychological Assessment of Patients with Parkinson's Disease]. / Empfehlungen zur neuropsychologischen Diagnostik beim Morbus Parkinson.

BACKGROUND: Presence of mild cognitive impairment is currently the best predictor for the development of Parkinson's disease dementia. Diagnostic criteria for both Parkinson's with mild cognitive impairment and Parkinson's disease dementia have been suggested by the Movement Disorder Society. However, not all cognitive tests recommended are available in the German language with proper standard values. OBJECTIVES: To define evidence-based guidelines for neuropsychological assessment of patients with Parkinson's disease in German. METHODS: Two systematic literature searches were conducted. First, articles that presented international guidelines (consensus papers or reviews) for the application of standardized neuropsychological assessments for the diagnosis of cognitive impairment in Parkinson's disease were selected. Of those, only neuropsychological assessments in German language with normative values referring either to a German, Austrian, or Swiss population were considered. Second, articles comparing test performances of healthy controls vs. Parkinson's disease and/or different cognitive Parkinson's disease subtypes (e.g. no cognitive impairment, Parkinson's with mild cognitive impairment, Parkinson's disease dementia) were selected. Effect sizes for group differentiation were calculated. RESULTS: Out of 127 full-text articles reviewed, 48 tests were identified during the first literature search. In the second search, 1716 articles were reviewed and 23 papers selected. The strongest effect sizes for group discrimination were revealed for tests assessing executive function, attention, and visuo-cognitive abilities. Based on the results of the two literature searches, consensus guidelines were defined by the authors, allowing for Level-II diagnosis for Parkinson's with mild cognitive impairment and Parkinson's disease dementia. CONCLUSIONS: The presented guidelines may have the potential to standardize and improve the neuropsychological assessment of Parkinson's disease patients in German speaking countries.

Incidence of second primary malignancies in metastatic castration-resistant prostate cancer: results from observational studies in three countries.

Aim: This reports some of the first incidence rate (IR) estimates of second primary malignancies (SPMs) in men with metastatic castration-resistant prostate cancer (mCRPC) in three countries. Patients & methods: Claims data from the German Pharmacoepidemiological Research Database; registry data from the Prostate Cancer Data Base Sweden; and combined registry-claims data from the US Surveillance, Epidemiology and End Results-Medicare database were analyzed to obtain overall survival and incidence of SPMs in men with mCRPC. Results: SPMs occurred in 308 German (n = 2360), 273 Swedish (n = 2849) and 172 US (n = 2234) men with mCRPC. IRs of SPMs were 79.0 (95% CI: 70.4-88.4), 101.7 (95% CI: 90.3-114.5) and 59 (95% CI: 50-68) per 1000 person-years in German, Swedish and US cohorts, respectively. Conclusion: These studies report some of the first IR estimates of SPMs in men with mCRPC, providing a historical risk estimate of SPM in this patient population.

Linkage of Routine Data to Other Data Sources in Germany: A Practical Example Illustrating Challenges and Solutions.

Routine data have a high potential for epidemiological and health care research but lack information, for instance, on the cause of death. Often detailed information, such as on lifestyle factors is also missing. In Germany, obtaining the missing information by linkage to data sources is challenging, mainly due to strict data protection regulations. One key challenge arises from the fact that routine data users usually have no access to person identifiers which would be necessary for record linkage. A second key challenge is that sensitive information (i. e., the cause of death) should not be transferred to an institution that holds person identifiers. In this paper, we illustrate these key challenges and present corresponding solutions based on a practical example where claims data from statutory health insurance providers are linked to an epidemiological cancer registry to obtain cause of death information. We describe the approval procedures necessary for the record linkage, the dataflow between the involved institutions and explain the rationale of the dataflow in view of the key challenges. Finally, we generalize the questions that need to be addressed when a record linkage is planned and point to additional potential challenges. Overall, we illustrate that a linkage between routine data and other data sources in Germany is feasible, but specific restrictions and hurdles need to be taken into consideration.

Cognitive decline in Parkinson's disease: the impact of the motor phenotype on cognition.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function. METHODS: Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration. RESULTS: Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314). CONCLUSION: The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.

Potential Explanations for Increasing Methylphenidate Use in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder in Germany From 2004 to 2013.

BACKGROUND: Despite a decreasing population of children and adolescents, the cumulative total amount of dispensed methylphenidate (MPH), the first-choice treatment of attention-deficit/hyperactivity disorder (ADHD) in this age group, has increased dramatically in Germany. We investigated potential reasons for this increase such as changes in the ADHD prevalence over time and other potential explanations including the cumulative amount of dispensed MPH per person. METHODS: Based on German claims data, we calculated standardized annual ADHD prevalence rates, proportions of ADHD cases treated with MPH and/or psychotherapy, and mean cumulative defined daily doses of ADHD drugs for 3- to 17-year-old children and adolescents from 2004 to 2013. RESULTS: The ADHD prevalence increased continuously from 2004 to 2011 and remained stable thereafter. In ADHD cases, there was little variation in the proportion of individuals treated with drugs and in the frequency of psychotherapeutic treatment during the whole study period. The annual cumulative mean amount of MPH defined daily doses increased by approximately 30% from 2004 to 2008. CONCLUSIONS: Our analyses suggest that the increase in MPH use in Germany was mainly influenced by an increasing ADHD prevalence and increasing amounts of dispensed MPH per person.

Psychiatric Symptoms in Patients With Dementia: Do Caregivers and Doctors See the Same Thing?

PURPOSE: Neuropsychiatric symptoms (NPS) are common in Alzheimer Disease (AD). Treatment could be optimized by supplementing the clinician's impression of a patient with information from the caregiver. Yet the agreement between caregivers and physicians on the presence of NPS in patients with AD is understudied. METHODS: Data were obtained from a 2-staged survey in neurology outpatient offices. At stage 1, patients (n=403) were documented by their physicians, including an assessment on the presence of NPS. At stage 2, patients' CGs (n=171) were asked about the presence of NPS in the patients, based on questions from the Neuropsychiatric Inventory. Caregivers were screened for depression with the Depression Screening Questionnaire. PATIENTS: The study sample comprised patients with mild or moderate AD. RESULTS: NPS frequency varied between 52.6% [95% confidence interval (CI), 44.9%-60.3%] and 67.2% (95% CI, 59.7%-74.2%, reported by CGs) and 34.2% (95% CI, 26.8%-42.1%) and 50.9% (95% CI, 42.9%-58.9%, reported by physicians). Apathy, depression, aggression, and irritability occurred most frequently according to both sources. κ values were lowest for euphoria (κ=0.03; 95% CI, -0.08 to 0.25), and highest for depression (κ=0.26; 95% CI, 0.11-0.43). CG depression was associated with an increased probability (odds ratio=2.9; 95% CI, 1.2-6.7) of disagreement between caregivers and physicians on the patient's mental status. CONCLUSION: NPS, though very prevalent in dementia patients, are perceived differently by caregivers and physicians. This divergence increases depending on the psychological health of caregivers.

Anticholinergic burden before and after hospitalization in older adults with dementia: Increase due to antipsychotic medications.

OBJECTIVES: To evaluate changes in the use of antipsychotics and medications with anticholinergic activity (MACs) during hospitalization in older adults with dementia and factors associated with antipsychotic prescriptions and increased anticholinergic burden (ACB). METHODS AND DESIGN: This retrospective cohort study included all patients aged 65 years or older with a discharge diagnosis of dementia hospitalized at the university hospital of Udine, Italy, from 2012 to 2014. Medications dispensed within 3 months before and after hospitalization were identified in community-pharmacy dispensations while those prescribed at discharge were collected from Hospital Electronic Medical Records (EMR). ACB was assessed using the Anticholinergic Cognitive Burden score. RESULTS: Among 1908 patients included, at discharge, 37.0% used one or more antipsychotic (9.4% before and 12.6% after hospitalization), 68.6% used one or more MAC (49.1% and 45.7%, respectively), and ACB of 38.4% of patients increased at discharge mainly because of a higher use of antipsychotics with anticholinergic activity (33% at discharge vs 12% before hospitalization). Prescription of antipsychotics at discharge was associated with prior treatment with antipsychotics (adjusted odds ratio [aOR] 4.85; 95%CI, 3.37-6.97), psychiatric conditions, (4.39; 3.47-5.54) and discharge from surgical department (2.17; 1.32-3.55). An increased ACB was associated with psychiatric conditions (1.91; 1.52-2.39), discharge from surgical (1.75; 1.09-2.80) or medical department (1.50; 1.04-2.17), and with cardiac insufficiency (1.41; 1.00-1.99). CONCLUSIONS: ACB was higher at discharge, and antipsychotics were the main drivers of this increase. Clinicians treating older adults with dementia should be aware of the risks associated with antipsychotics and that some of these medications may increase the risk of anticholinergic effects.

First-degree relatives of cancer patients: a target group for primary prevention? A cross-sectional study.

BACKGROUND: Persons with a first-degree relative (FDR) with cancer are at increased cancer risk. We investigated preventive behaviour, cancer risk perception and readiness to change an unhealthy lifestyle in persons with and without an FDR with cancer. METHODS: Using an online questionnaire, we conducted a cross-sectional study in Germany including persons (≥35 years) with an FDR with colorectal, lung, prostate, breast, stomach or cervical/uterine cancer (n = 621) and persons without cancer in FDRs (n = 303). Quota sampling ensured similar age and sex distributions in both groups. RESULTS: Unfavourable lifestyle factors were equally common in both groups. The proportion perceiving an increased cancer risk significantly differed (p < 0.0001) with 4% among respondents without cancer in FDRs and 18% (colorectal cancer) to 30% (stomach cancer) among cancer patients' relatives. The proportion of smokers ready to quit smoking was significantly higher among those perceiving an increased vs. a lower cancer risk (64 vs. 46%, p = 0.04). There was a similar association for readiness to increase physical activity and consumption of fruits/vegetables and to reduce alcohol consumption. CONCLUSIONS: Given the increased risk perception and motivation to change an unhealthy lifestyle, our study provides a strong rationale for research on the effectiveness of lifestyle interventions in cancer patients' relatives.

Psychometric Properties of an Abbreviated Version of the Apathy Evaluation Scale for Parkinson Disease (AES-12PD).

BACKGROUND: Apathy is a frequent symptom in Parkinson's disease (PD), substantially aggravating the course of PD. Regarding the accumulating evidence of the key role of apathy in PD, time-efficient assessments are useful for fostering progress in research and treatment. The Apathy Evaluation Scale (AES) is widely used for the assessment of apathy across different nosologies. OBJECTIVE: To facilitate the application of the AES in PD, we reduced the AES to two-thirds its length and validated this abbreviated version. DESIGN: Data sets of 339 PD patients of the DEMPARK/LANDSCAPE study without dementia and depression were randomly split into two samples. Data of sample 1 were used to develop a brief version of the AES (AES-12PD). A cross-validation was conducted in sample 2 and in a subsample of 42 PD patients with comorbid dementia and depressive symptomatology. Receiver operating characteristic analysis was applied to determine the optimal cutoff of the AES-12PD as an indicator of apathy. RESULTS: The AES-12PD featured high internal consistency that was better compared to the AES. The abbreviated scale was well differentiated from motor impairment and cognitive deficits. The AES-12PD cutoff of 27/28 was the optimal cutoff for apathy in PD patients without dementia and depression. The cutoff of 25/26 indicated apathy in PD patients with comorbid dementia and depression. CONCLUSION: Results confirm a high internal consistency and good discriminant validity of the AES-12PD. The AES-12PD represents a reliable tool for the efficient assessment of apathy that can be applied in PD patients with and without dementia and depression.

Incidence of Multiple Sclerosis in Germany: A Cohort Study Applying Different Case Definitions Based on Claims Data.

BACKGROUND: Data on the incidence of multiple sclerosis (MS) on the national level is scarce. We aimed to estimate the incidence of MS in Germany and to compare different MS case definitions based on claims data. METHODS: We conducted a cohort study with the German Pharmacoepidemiological Research Database in 2012 and calculated age- and gender-standardized incidence rates (sIRs) for 3 case definitions. In addition, the effect of stepwise reduction of the look-back period without MS diagnosis on the incidence rate was evaluated. RESULTS: Our cohort comprised 4,175,877 individuals. The first case definition based on ICD-10 diagnoses yielded an sIR of 21.8 (95% CI 20.2-23.5) per 100,000 person years, whereas the second and third case definitions with additional requirements for drug treatment and diagnostic tests resulted in lower sIRs of 10.1 (9.1-11.3) and 6.6 (5.8-7.6) respectively. We observed a higher incidence for shorter look-back periods. CONCLUSION: The incidence of MS in Germany might be substantially higher than suggested in earlier studies. In addition, our study highlights the importance of a look-back period of at least 36 months to identify incident MS cases based on claims data.

Extent and risks of antidepressant off-label use in children and adolescents in Germany between 2004 and 2011.

PURPOSE: So far, only little is known about antidepressant off-label use in pediatric patients. This is the first study examining the prevalence and the risks of off-label antidepressant prescriptions in minors over time in Germany and analyzing patterns regarding age, sex, drug class, and type of off-label use. METHODS: We used claims data of about two million individuals (<18 y) to calculate the share of off-label antidepressant prescriptions for the years 2004 to 2011, stratified by age, sex, and drug class. Off-label prescriptions were analyzed regarding underlying diagnoses, the prescribing doctor's specialty, and the type of off-label use. Incidence rates of adverse events were calculated for off- and on-label use, and the risk of suicidal events associated with off- or on-label use was examined in a nested case-control study. RESULTS: The prevalence of off-label prescriptions decreased from 58.0% to 40.9%. Selective serotonin reuptake inhibitors were more frequently prescribed off-label than tricyclic antidepressants (37.7% vs 17.5% in 2011). The most common type of off-label use was off-label use by age, followed by off-label use by indication, and off-label use by contraindication. Adverse events were rare with no significant differences between on- and off-label use. CONCLUSIONS: Although off-label antidepressant use in minors decreased over time, it is still common. However, this rather indicates a lack of approved drugs for the treatment of depression in this population than inappropriate medical treatment. This is supported by the fact that off-label use was not associated with a higher risk of adverse events than on-label use.

Outpatient antidepressant drug use in children and adolescents in Germany between 2004 and 2011.

PURPOSE: Recent studies on the utilization of antidepressant drugs in minors are scarce, methodologically limited, and do not factor in off-label use sufficiently. Beyond that, little is known about the short treatment durations that have been observed for many young antidepressant users. The present study examined antidepressant use in pediatric patients aged 0 to 17 years over time, investigated changes regarding the prescribed drugs, analyzed underlying diagnoses, and assessed the rate of off-label use. METHODS: We used claims data of roughly two million individuals to calculate annual prevalence and incidence rates of antidepressant prescriptions for the years 2004 to 2011. Analyses were stratified by age, sex, and drug type. For antidepressant users, numbers of prescriptions, frequencies of disorders/diseases, and specialties of the prescribing physicians were examined. The share of off-label prescriptions was calculated for each year. RESULTS: The prescription prevalence of antidepressants ranged between 1.7 and 2.1 per 1000 minors. The use of tricyclic antidepressants decreased from 0.9 to 0.6 prescriptions per 1000 minors, while the use of selective serotonin reuptake inhibitors increased from 0.5 to 1.1. Of the patients with an antidepressant prescription, 46.4% only received one prescription. Depression was by far the most frequent diagnosis among all antidepressant users as well as among subjects with only one prescription. In 2011, 36.3% of all prescriptions were off-label. CONCLUSIONS: The high proportion of single prescriptions, even in patients with a diagnosed depression, and the high rate of off-label use are particularly noteworthy and should be further investigated in future studies. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Outpatient antipsychotic drug use in children and adolescents in Germany between 2004 and 2011.

Studies from different countries showed increasing use of antipsychotics in pediatric patients. However, these studies were methodologically limited and could not assess underlying diagnoses and off-label use sufficiently. This is the first study to examine antipsychotic prescriptions in a representative sample of minors over a long period, looking at changes regarding substances and drug classes, underlying diagnoses, and the rate of off-label use. Claims data of about two million pediatric subjects were used to calculate annual prevalences and incidence rates of antipsychotic prescriptions for the years 2004-2011. Analyses were stratified by sex, age, and drug type. Numbers of prescriptions, frequencies of diseases/disorders, the prescribing physicians' specialties, and the share of off-label prescriptions were examined. During the study period, the prevalence of antipsychotic prescriptions ranged between 2.0 and 2.6 per 1000 minors. Antipsychotic prescriptions in children younger than 6 years decreased from 2.42 per 1000 subjects in 2004 to 0.48 in 2011. Among antipsychotic users, 47.0 % had only one prescription and hyperkinetic disorder was, by far, the most frequent diagnosis. The annual share of off-label prescriptions varied between 61.0 and 69.5 %. Antipsychotics were mainly prescribed to manage aggressive and impulsive behaviors in hyperkinetic disorder patients. This explains the high share of off-label prescriptions but raises concerns, since efficacy and safety of antipsychotics in this indication have not been sufficiently investigated. The decreasing antipsychotic use in younger children and the high proportion of antipsychotic users with one-time prescriptions are striking and should be further investigated in the future.

Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study.

OBJECTIVE: Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. METHODS: Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. RESULTS: 269 patients with PD-MCI (age 67.8±7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. CONCLUSIONS: This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia.

Validating mortality in the German Pharmacoepidemiological Research Database (GePaRD) against a mortality registry.

PURPOSE: The study aimed at validating the status and date of death of a large electronic health insurance database against data of a mortality registry, using a probabilistic record linkage. METHODS: Data were obtained from one local health insurance company contributing to the German Pharmacoepidemiological Research Database (GePaRD). Furthermore, data of the Bremen Mortality Index (BreMI) containing all information from death certificates were used as reference information. Both data sources were probabilistically linked. The study sample consisted of insurants dying in 2005 or 2006. RESULTS: Of 3245 deaths in GePaRD, 83.7% were successfully linked to BreMI records. The linkage success did not differ between men and women, age groups or insurance status groups. Date of death was accurate in 97.1% of all linked deaths. CONCLUSIONS: The accuracy of the status of death in GePaRD is likely to be underestimated in this study because of factors related to the record linkage procedure leading to failure of the probabilistic record linkage approach and the limited completeness of BreMI. A previous validation study comparing aggregate mortality information in GePaRD with German national statistics did not indicate an overreporting of deaths in GePaRD. Thus, a higher accuracy of the status of death in GePaRD than estimated here can be assumed. Copyright © 2016 John Wiley & Sons, Ltd.