Mid- and late-life lifestyle activities as main drivers of general and domain-specific cognitive reserve in individuals with Parkinson's disease: cross-sectional and longitudinal evidence from the LANDSCAPE study.

BACKGROUND: Cognitive reserve (CR) is considered a protective factor for cognitive function and may explain interindividual differences of cognitive performance given similar levels of neurodegeneration, e.g., in Alzheimer´s disease. Recent evidence suggests that CR is also relevant in Parkinson's disease (PD). OBJECTIVE: We aimed to explore the role of life-stage specific CR for overall cognition and specific cognitive domains cross-sectionally and longitudinally in PD. METHODS: The cross-sectional analysis with data from the DEMPARK/LANDSCAPE study included 81 individuals without cognitive impairment (PD-N) and 87 individuals with mild cognitive impairment (PD-MCI). Longitudinal data covered 4 years with over 500 observations. CR was operationalized with the Lifetime of Experiences Questionnaire (LEQ), capturing the complexity of lifestyle activities across distinct life-stages. Cognition was assessed using a comprehensive neuropsychological test battery. RESULTS: Higher LEQ scores, particularly from mid- and late-life, were observed in PD-N compared to PD-MCI [F(1,153) = 4.609, p = .033, ηp2 = 0.029]. They were significantly associated with better cognitive performance (0.200 ≤ ß ≤ 0.292). Longitudinally, linear mixed effect models (0.236 ≤ marginal R2 ≤ 0.441) revealed that LEQ scores were positively related to cognitive performance independent of time. However, the decline in overall cognition and memory over time was slightly more pronounced with higher LEQ scores. CONCLUSIONS: This study emphasizes the association between complex lifestyle activities and cognition in PD. Data indicate that while CR might be related to a delay of cognitive decline, individuals with high CR may experience a more pronounced drop in overall cognition and memory. Future studies will have to replicate these findings, particularly regarding domain-specific effects and considering reverse causal mechanisms.

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.

Quality of life in bariatric patients up to twelve years after surgery - Results from a nationwide retrospective cohort study.

BACKGROUND: Bariatric interventions (BI, including surgical interventions) are effective in patients with massive obesity, i.e., a body mass index (BMI) > 40, and their number has steadily increased during the past decade. Yet, the stability of improvements in quality of life (QoL) in post-interventional patients is understudied and restricted to studies with small samples and short follow-ups. METHODS: Patients with BI between 2004 and 2018 were identified in a health claims database and invited to fill in a survey, comprising sociodemographic and lifestyle information and psychometric scales. QoL was assessed with the Bariatric QoL (BQL) scale with lower scores denoting worse QoL. BMI and excess weight loss (EWL) were calculated for the time soon after intervention (EWL-T1) and when filling the survey (EWL-T2). RESULTS: The majority of n = 2151 patients were female (80.7 %), had a mean age of 54.5 years and a mean BMI of 34.8. The mean EWL-T1 was 79 % (EWL-T2: 64.6 %). The mean BQL score was 47.6 and decreased with BMI (18.5-24.9: 52.6 vs. >40: 38.7), EWL-T2 (>66 %: 51.3 vs. <65 %: 42.1) and years since intervention (3-4: 48.2 vs >8: 45.1, each p < .001). For EWL-T1, the association between higher EWLs and higher BQL scores was stronger in females than in males (p < .005); for EWL at T2, both sexes did not differ in this regard (p = .848). Among normal-weight persons, males scored significantly lower on the BQL than females (44.9 vs. 54.9). CONCLUSIONS: Post-interventional QoL improvements diminish over time and depend on the weight loss, with significant differences between men and women.

Dementia in health claims data: The influence of different case definitions on incidence and prevalence estimates.

OBJECTIVES: The epidemiology of dementia subtypes including Alzheimer's disease (AD) and vascular dementia (VD) and their reliance on different case definitions ("algorithms") in health claims data are still understudied. METHODS: Based on health claims data, prevalence estimates (per 100 persons), incidence rates (IRs, per 100 person-years), and proportions of AD, VD, and other dementias (oD) were calculated. Five algorithms of increasing strictness considered inpatient/outpatient diagnoses (#1, #2), antidementia drugs (#3) or supportive diagnostics (#4, #5). RESULTS: Algorithm 1 detected 213,409 cases (#2: 197,400; #3: 48,688; #4: 3033; #5: 3105), a prevalence for any dementia of 3.44 and an IR of 1.39 (AD: 0.80/0.21, VD: 0.79/0.31). The prevalence decreased by algorithms for any dementia (#2: 3.19; #3: 0.75; #4: 0.04; #5: 0.05) as did IRs (#2: 1.13; #3: 0.18; #4: 0.05, #5: 0.05). Algorithms 1-2, and 4-5 revealed similar proportions of AD (23.3%-26.6%), VD (19.9%-23.2%), and oD (53.1%-53.8%), algorithm 3 estimated 45% (AD), 12.1% (VD), and 43.0% (oD). CONCLUSIONS: Health claims data show lower estimates of AD than previously reported, due to markedly lower prevalent/incident proportions of patients with corresponding codes. Using medication in defining dementia potentially improves estimating the proportion of AD while supportive diagnostics were of limited use.

The interplay of family history of depression and early trauma: associations with lifetime and current depression in the German national cohort (NAKO).

Introduction: Family history of depression and childhood maltreatment are established risk factors for depression. However, how these factors are interrelated and jointly influence depression risk is not well understood. The present study investigated (i) if childhood maltreatment is associated with a family history of depression (ii) if family history and childhood maltreatment are associated with increased lifetime and current depression, and whether both factors interact beyond their main effects, and (iii) if family history affects lifetime and current depression via childhood maltreatment. Methods: Analyses were based on a subgroup of the first 100,000 participants of the German National Cohort (NAKO), with complete information (58,703 participants, mean age = 51.2 years, 53% female). Parental family history of depression was assessed via self-report, childhood maltreatment with the Childhood Trauma Screener (CTS), lifetime depression with self-reported physician's diagnosis and the Mini-International Neuropsychiatric Interview (MINI), and current depressive symptoms with the depression scale of the Patient Health Questionnaire (PHQ-9). Generalized linear models were used to test main and interaction effects. Mediation was tested using causal mediation analyses. Results: Higher frequencies of the childhood maltreatment measures were found in subjects reporting a positive family history of depression. Family history and childhood maltreatment were independently associated with increased depression. No statistical interactions of family history and childhood maltreatment were found for the lifetime depression measures. For current depressive symptoms (PHQ-9 sum score), an interaction was found, with stronger associations of childhood maltreatment and depression in subjects with a positive family history. Childhood maltreatment was estimated to mediate 7%-12% of the effect of family history on depression, with higher mediated proportions in subjects whose parents had a depression onset below 40 years. Abuse showed stronger associations with family history and depression, and higher mediated proportions of family history effects on depression than neglect. Discussion: The present study confirms the association of childhood maltreatment and family history with depression in a large population-based cohort. While analyses provide little evidence for the joint effects of both risk factors on depression beyond their individual effects, results are consistent with family history affecting depression via childhood maltreatment to a small extent.

Potential of Health Insurance Claims Data to Predict Fractures in Older Adults: A Prospective Cohort Study.

Purpose: In older adults, fractures are associated with mortality, disability, loss of independence and high costs. Knowledge on their predictors can help to identify persons at high risk who may benefit from measures to prevent fractures. We aimed to assess the potential of German claims data to predict fractures in older adults. Patients and Methods: Using the German Pharmacoepidemiological Research Database (short GePaRD; claims data from ~20% of the German population), we included persons aged ≥65 years with at least one year of continuous insurance coverage and no fractures prior to January 1, 2017 (baseline). We randomly divided the study population into a training (80%) and a test sample (20%) and used logistic regression and random forest models to predict the risk of fractures within one year after baseline based on different combinations of potential predictors. Results: Among 2,997,872 persons (56% female), the incidence per 10,000 person years of any fracture in women increased from 133 in age group 65-74 years (men: 71) to 583 in age group 85+ (men: 332). The maximum predictive performance as measured by the area under the curve (AUC) across models was 0.63 in men and 0.60 in women and was achieved by combining information on drugs and morbidities. AUCs were lowest in age group 85+. Conclusion: Our study showed that the performance of models using German claims data to predict the risk of fractures in older adults is moderate. Given that the models used data readily available to health insurance providers in Germany, it may still be worthwhile to explore the cost-benefit ratio of interventions aiming to reduce the risk of fractures based on such prediction models in certain risk groups.

[Outpatient medical specialist care (ASV): A multiperspective study on status quo, challenges and perspectives]. / Ambulante Spezialfachärztliche Versorgung (ASV): eine multiperspektivische Studie zu Status quo, Herausforderungen und Perspektiven.

BACKGROUND: In 2012, the so-called ambulatory medical specialist care (ASV) was implemented in accordance with para. 116b of Book V of the German Social Code (SGB V), enabling physicians in outpatient practices and hospitals to treat patients with rare diseases or complex courses of disease in a uniform framework. The implementation, however, is slow. The Joint Federal Committee (G-BA) has therefore commissioned an evaluation of the ASV with the aim to examine the reasons for this and to provide recommendations for further development. METHODS: The health services research study "GOAL-ASV" (Innovation Fund, 01VSF19002) included a multi-perspective design with primary data collection as well as secondary data analyses. Data from the ASV service center and the central association of statutory health insurances and the notification forms of the extended state committees were analyzed. Data from the Robert Koch-Institute, the Federal Joint Committee, the National Association of Statutory Health Insurance Funds and a literature database analysis were used in order to estimate the proportion of insured persons qualifying for ASV. Care was examined by analyzing pseudonymized routine data from the statutory health insurances using selected indicators. Participating and not participating physicians were asked to complete an online survey. RESULTS: Since the start of ASV, 615,531 insured persons have been treated in this form of care. At the time of analysis, 509 teams were operating, with 26,540 physicians treating 102,898 patients by the end of March 2021 in all indications. This comprises less than 9.8 %. of all approx. 1.05 million eligible patients. Especially in the case of rare diseases, a low willingness of participation can be seen. In addition, there was a relevant proportion of multiple uses of physicians within and outside ASV at 31 percent as well as indications of passive participation of doctors. We found significant regional differences in type and scope of the notification procedure as well as the implementation of teams with 13.4 teams per 1 million inhabitants in Schleswig-Holstein and no team in Mecklenburg-Vorpommern. Patient benefits (84 %), interdisciplinary (82 %) and cross-sectoral cooperation (75 %) were cited as motivations for participation. The main barriers reported by the respondents were the complex and laborious notification procedure (60 %), the administrative and documentation effort during participation (50 %), insufficient billing figures (49 %), and a small proportion of patients (32 %) with a consecutively unfavorable assessment of the cost to income ratio due to the current reimbursement system. DISCUSSION: Nearly ten years after its introduction, the ASV has not become established nationwide. The reasons for this probably are the complex notification procedure and the reimburesement system for rare diseases. In the case of rare diseases, the risk of underuse is becoming apparent. CONCLUSION: Strategies to further develop the ASV should, in particular, simplify the notification procedure and reduce the obstacles during participation. The remuneration system should take more account of the specific care required.

Regional Variations in Outpatient Antibiotic Prescribing in Germany: A Small Area Analysis Based on Claims Data.

A comprehensive small area description of regional variations in outpatient antibiotic prescribing in Germany is lacking. Using the German Pharmacoepidemiological Research Database (GePaRD), a claims database covering ~20% of the German population, we determined the age- and sex-standardized prescription rates of antibiotics (number of outpatient prescriptions per 1000 persons/year). We calculated these prescription rates overall and on the level of 401 German districts for the calendar years 2010 and 2018. In 2018, the standardized prescription rate of antibiotics in the total study population was 23% lower than in 2010 (442 vs. 575 per 1000 persons/year). Among 0-17-year-olds, prescription rates across districts ranged from 312 to 1205 in 2010 and from 188 to 710 in 2018 per 1000 persons/year; among adults (≥18 years), they ranged from 388 to 841 in 2010 and from 300 to 693 in 2018 per 1000 persons/year. Despite the overall decline in outpatient antibiotic prescribing between 2010 and 2018, regional variations at the district level remained high in all age groups in Germany. Identifying reasons that explain the persistently high prescription rates in certain regions will be helpful in designing effective and tailored measures to further improve antibiotic stewardship in these regions.

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.

Long-Term Cognitive Decline Related to the Motor Phenotype in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is associated with various non-motor symptoms, including cognitive deterioration. OBJECTIVE: Here, we used data from the DEMPARK/LANDSCAPE cohort to describe the association between progression of cognitive profiles and the PD motor phenotypes: postural instability and gait disorder (PIGD), tremor-dominant (TR-D), and not-determined (ND). METHODS: Demographic, clinical, and neuropsychological six-year longitudinal data of 711 PD-patients were included (age: M = 67.57; 67.4% males). We computed z-transformed composite scores for a priori defined cognitive domains. Analyses were controlled for age, gender, education, and disease duration. To minimize missing data and drop-outs, three-year follow-up data of 442 PD-patients was assessed with regard to the specific role of motor phenotype on cognitive decline using linear mixed modelling (age: M = 66.10; 68.6% males). RESULTS: Our study showed that in the course of the disease motor symptoms increased while MMSE and PANDA remained stable in all subgroups. After three-year follow-up, significant decline of overall cognitive performance for PIGD-patients were present and we found differences for motor phenotypes in attention (ß= -0.08, SE = 0.003, p < 0.006) and memory functions showing that PIGD-patients deteriorate per months by -0.006 compared to the ND-group (SE = 0.003, p = 0.046). Furthermore, PIGD-patients experienced more often difficulties in daily living. CONCLUSION: Over a period of three years, we identified distinct neuropsychological progression patterns with respect to different PD motor phenotypes, with early executive deficits yielding to a more amnestic profile in the later course. Here, in particular PIGD-patients worsened over time compared to TR-D and ND-patients, highlighting the greater risk of dementia for this motor phenotype.

Brain age and Alzheimer's-like atrophy are domain-specific predictors of cognitive impairment in Parkinson's disease.

Recently, it was shown that patients with Parkinson's disease (PD) who exhibit an "Alzheimer's disease (AD)-like" pattern of brain atrophy are at greater risk for future cognitive decline. This study aimed to investigate whether this association is domain-specific and whether atrophy associated with brain aging also relates to cognitive impairment in PD. SPARE-AD, an MRI index capturing AD-like atrophy, and atrophy-based estimates of brain age were computed from longitudinal structural imaging data of 178 PD patients and 84 healthy subjects from the LANDSCAPE cohort. All patients underwent an extensive neuropsychological test battery. Patients diagnosed with mild cognitive impairment or dementia were found to have higher SPARE-AD scores as compared to patients with normal cognition and healthy controls. All patient groups showed increased brain age. SPARE-AD predicted impairment in memory, language and executive functions, whereas advanced brain age was associated with deficits in attention and working memory. Data suggest that SPARE-AD and brain age are differentially related to domain-specific cognitive decline in PD. The underlying pathomechanisms remain to be determined.

Prevalence of multimodal treatment in children and adolescents with ADHD in Germany: a nationwide study based on health insurance data.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) ranks top among neurodevelopmental disorders in children and adolescents. Due to a large number of unfavorable outcomes including psychiatric comorbidities, school problems, and lower socioeconomic status, early and effective treatment of ADHD is essential. Multimodal treatment has become the gold standard in ADHD management, comprising pharmacotherapy and psychosocial interventions, e.g., psychotherapy. Yet, little is known about the prevalence of multimodal treatment in routine care. METHODS: Based on German health claims data for the years 2009-2017, we identified children and adolescents aged 3-17 years diagnosed with ADHD and characterized them cross-sectionally (per calendar year) in terms of treatment status and psychiatric comorbidities. The detection of pharmacotherapy was based on dispensations of drugs to treat ADHD (e.g., methylphenidate); psychotherapeutic treatment was based on corresponding billing codes. Multimodal treatment was assumed if ADHD medication and psychotherapeutic treatment were coded within the same calendar year. Psychiatric comorbidities were based on outpatient and inpatient diagnoses. Prevalences of ADHD and proportions of different treatment options were calculated and standardized by age and sex. RESULTS: In 2017, 91,118 children met the study criteria for ADHD (prevalence: 42.8/1000). Of these, 25.2% had no psychiatric comorbidity, 28.8% had one, 21.6% had two, and 24.5% had three or more. Regarding overall treatment status, 36.2% were treated only pharmacologically, 6.5% received multimodal treatment, and 6.8% were treated with psychotherapy only (neither treatment: 50.2%). With increasing numbers of psychiatric comorbidities, the proportions of patients with multimodal treatment increased from 2.2% (no psychiatric comorbidities) to 11.1% (three or more psychiatric comorbidities) while the proportions of untreated (from 56.8% to 42.7%) or only pharmacologically treated patients (38.4% to 35.0%) decreased. From 2009 to 2017, prevalences were stable and the proportion of patients with only pharmacotherapy decreased from 48% to 36.5%. Concurrently, the proportion of patients with neither pharmacotherapy nor psychotherapy increased from 40.5% to 50.2%. The fraction of patients with multimodal treatment ranged between 6.5% (2017) and 7.4% (2013). CONCLUSIONS: Multimodal treatment, although recommended as the standard of treatment, is rather the exception than the rule. It is, however, increasingly common in ADHD patients with psychiatric comorbidities.

Cognitive profiles of patients with mild cognitive impairment due to Alzheimer's versus Parkinson's disease defined using a base rate approach: Implications for neuropsychological assessments.

INTRODUCTION: Large studies on cognitive profiles of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD-MCI) compared to Parkinson's disease (PD-MCI) are rare. METHODS: Data from two multicenter cohort studies in AD and PD were merged using a unified base rate approach for the MCI diagnosis. Cognitive profiles were compared using scores derived from the Consortium to Establish a Registry for Alzheimer's Disease battery. RESULTS: Patients with AD-MCI showed lower standardized scores on all memory test scores and a language test. Patients with PD-MCI showed lower standardized scores in a set-shifting measure as an executive task. A cross-validated logistic regression with test scores as predictors was able to classify 72% of patients correctly to AD-MCI versus PD-MCI. DISCUSSION: The applied test battery successfully discriminated between AD-MCI and PD-MCI. Neuropsychological test batteries in clinical practice should always include a broad spectrum of cognitive domains to capture any cognitive changes.

A new CERAD total score with equally weighted z-scores and additional executive and non-amnestic "CERAD-Plus" tests enhances cognitive diagnosis in patients with Parkinson's disease: Evidence from the LANDSCAPE study.

INTRODUCTION: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is a renowned cognitive test battery, which has been extended in its German version to the CERAD-Plus including tests of executive functions and processing speed. The most commonly used total score (TS) is based on the restricted CERAD version and reflects the sum of selected raw-values (Chandler et al., 2005). The CERAD-Plus extensions might be of particular diagnostic utility for cognitive assessments in Parkinson's Disease (PD), as executive functions and processing speed belong to the most vulnerable domains in PD. OBJECTIVE: The aim was to develop a CERAD-TS based on the extended CERAD-Plus' age-, gender-, and education-corrected z-scores and to evaluate its diagnostic accuracy compared to the established CERAD-Chandler-TS. METHODS: Baseline data of n = 679 patients with PD (69% male, n = 277 PD without cognitive impairment, n = 307 PD-MCI, n = 95 PD-D) from the multicenter, prospective DEMPARK/LANDSCAPE study were analyzed. ROC-analyses were conducted for four different TS that were either based on the original CERAD or CERAD-Plus, on raw-values or z-scores, and equally-weighted or based on factor scores. AUC-comparisons were conducted to determine the best yet most parsimonious TS. RESULTS: The newly designed CERAD-Plus-TS based on equally-weighted z-scores outperformed both the CERAD-Chandler-TS and cognitive screening instruments when differentiating between individuals with PD of varying cognitive impairment (0.78 ≤ AUC ≤ 0.98). CONCLUSION: Results suggest a high relevance of non-amnestic subscales for the cognitive assessment in PD populations. The proposed CERAD-Plus-TS needs further validation. The extensions might offer diagnostic potential for non-PD populations as well.

Repeated Use of Prescription Drugs in Pediatrics: Comprehensive Overview Based on German Claims Data.

Background: Investigating drug utilization in large and unselected samples of children and adolescents is an important component of public health monitoring. Most existing studies in this field focused on any drug use (i.e., ≥1 prescription of a certain drug) although chronic drug use may be more relevant. This study aimed to provide a comprehensive overview of prevalence and types of prescription drugs used repeatedly in children and adolescents in Germany in 2016. Methods: We used the German Pharmacoepidemiological Research Database (GePaRD)-a claims database covering ∼20% of the German population. We included children and adolescents aged 0-17 years and assessed repeated use of prescription drugs (≥3 prescriptions in 2016) on two levels: therapeutic subgroups (ATC 2nd level) and chemical substances (ATC 5th level). Analyses were stratified by sex and age groups (<2, 2-5, 6-12, and 13-17 years). Results: Overall, 2.5 million children and adolescents were included. In the age groups below 13 years, the prevalence rates of repeated use of prescription drugs (ATC 2nd level) were higher in boys than in girls (113-152 vs. 83-130 per 1,000 person-years), whereas in the age group 13-17 years, they were twice as high in girls than in boys (236 vs. 118 per 1,000 person-years). In boys and girls aged below six years, systemic antibiotics, topical ocular antibiotics, and drugs for constipation were among the most common drugs used repeatedly. For higher ages, methylphenidate, levothyroxine, and combined hormonal contraceptives, were among the most common drugs used repeatedly. Conclusions: Overall, about one in ten children in Germany repeatedly used prescription drugs. This proportion as well as the type of drugs used repeatedly markedly varied by sex and age. For certain drugs, our findings raise concerns regarding appropriateness of prescribing that should be addressed in future studies.

Extrapulmonary symptoms of patients with asthma treated in specialist pulmonary care.

OBJECTIVE: Patients seeking treatment for their asthma are most likely motivated by a change in their experience of symptoms, but primary complaints are not always related to the pulmonary system. This study aimed to determine the frequency of such extrapulmonary symptoms in asthma outpatients and their association with psychopathology and asthma outcomes. METHODS: This cross-sectional study utilized data collected as part of a nationwide, clinical-epidemiological study. The final sample of 572 asthma patients represented all levels of asthma control and severity. Information on demographics and respiratory function was obtained from physicians' documentation. Symptoms were explored using a standardized checklist. RESULTS: Primary symptoms reported by asthma patients were not necessarily airway-related. Patients reported feeling at least occasionally "tired" (72.1%) and "exhausted" (66.8%) more than any other asthma symptom. Hyperventilation and mood symptoms were experienced by 34.4-42.6% of patients. Anxiety or depression diagnoses indicated higher scores in all symptom domains. Controlling for asthma-related factors and psychopathology, fatigue had a small but significant effect on both asthma-related quality of life (AQLQ) (rsp2 = 0.02, P < .001) and asthma control (rsp2 = 0.01, P = .003). Mood symptoms also showed a small but significant effect on AQLQ (rsp2 = 0.02, P < .001). CONCLUSION: Findings suggest that extrapulmonary symptoms are endorsed more frequently than previously reported. Symptoms nonspecific to asthma can play a substantial role in clinical presentation and exclusive focus on airway symptoms may miss important information related to patients' well-being. Surveillance of extrapulmonary symptoms alongside pulmonary function is warranted for an integrated medicine approach to asthma management.

Anticholinergic burden: First comprehensive analysis using claims data shows large variation by age and sex.

PURPOSE: The cumulative effect of medication inhibiting acetylcholine activity-also known as anticholinergic burden (AB)-can lead to functional and cognitive decline, falls, and death. Given that studies on the population prevalence of AB are rare, we aimed to describe it in a large and unselected population sample. METHODS: Using the German Pharmacoepidemiological Research Database (GePaRD) with claims data from ~20% of the German population we analyzed outpatient drug dispensations in 2016. Based on the Anticholinergic Cognitive Burden (ACB) scale, we classified persons into four categories and determined the cumulative AB as continuous variable. RESULTS: Among 16,470,946 persons (54% female), the prevalence of clinically relevant AB (ACB≥3) was 10% (women) and 7% (men). Below age 40 it was highest in persons ≤18 years (6% both sexes). At older ages (50-59 vs. 90-99 years), prevalence of ACB≥3 increased from 7% to 26% (men) and from 10% to 32% (women). Medication classes contributing to the cumulative AB differed by age: antihistamines, antibiotics, glucocorticoids (≤19 years), antidepressants (20-49 years), antidepressants, cardiovascular medication, antidiabetics (50-64 years), and additionally medication for urinary incontinence/overactive bladder (≥65 years). Medication dispensed by general physicians contributed most to the cumulative AB. CONCLUSION: Although a clinically relevant AB is particularly common in older persons, prevalence in younger age groups was up to 7%. Given the risks associated with AB in older persons, targeted interventions at the prescriber level are needed. Furthermore, risks associated with AB in younger persons should be explored.

First-Time Users of ADHD Medication Among Children and Adolescents in Germany: An Evaluation of Adherence to Prescribing Guidelines Based on Claims Data.

Background: Drug utilization studies based on real-world data are vital for the identification of potentially needed improvements to rational prescribing. This is particularly important for the pharmacological treatment of children and adolescents with attention-deficit hyperactivity disorder (ADHD) due to the associated potential side effects and the frequent use. Whereas prevalent use is well-characterized, studies on first-time use of ADHD medication are scarce. This study aimed to evaluate off-label prescribing in first-time users of ADHD medication among children and adolescents in Germany based on three criteria: (i) lack of a documented ADHD diagnosis; (ii) first-time pharmacological treatment with a second-line drug; and (iii) patient age below 6 years. Methods: Based on German claims data, we included children and adolescents aged 0-17 years with a first-time dispensation of any ADHD medication in the period 2015-2017. These first-time users were characterized with regard to sex, age, specialty of the prescribing physician, documentation of an ADHD diagnosis, psychiatric hospitalization, psychiatric comorbidities, and history of other psychopharmacological drugs at first-time use. Results: The study population comprised 18,703 pediatric first-time users of ADHD medication. Of these, 9.8% had no documented ADHD diagnosis. Most of the ADHD drug users received first-line ADHD pharmacotherapy (methylphenidate, atomoxetine), whereas 2.6% were prescribed second-line ADHD medication (lisdexamfetamine, guanfacine, dexamfetamine, multiple ADHD drugs) as first drug. Overall, 1.2% of first-time users were aged below 6 years. A total of 12.7% of the study population met any off-label criterion. Conclusions: About 13% of pediatric first-time users of ADHD medication in Germany received an off-label pharmacotherapy at first-time use. Prescribing ADHD medication without a confirmed ADHD diagnosis was the most common of the three assessed off-label criteria. Off-label prescribing regarding drug choice and age of patients only occurred in a small percentage of initial pharmacological ADHD treatment. Our results suggest the need for improvement in rational prescribing, especially with regard to diagnostic requirements.

[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.