Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders.

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.

Validity of the Finnish Care Register for Social Welfare in a nationwide cohort of people with Alzheimer's disease.

AIMS: To assess the validity and completeness of the Care Register for Social Welfare among community-dwelling people with Alzheimer's disease in Finland. METHODS: The study was carried out in the Medication Use and Alzheimer's disease (MEDALZ) study population, which includes 70,719 people who received a clinically verified diagnosis of Alzheimer's disease between 2005 and 2011 and the people matched with them for comparison (n=282,862). The data were linked to the Care Register for Social Welfare, which contains data on care periods for nursing homes and sheltered housing with 24-h assistance during the time period 1994-2015. The validity of the Care Register for Social Welfare was analysed in relation to the Prescription Register among people with Alzheimer's disease aged >65 years (n=25,640) who fulfilled the definitions of long-term care in certain inpatient care units (nursing homes, institutional care for people with dementia and rehabilitation institutions), although, in Finland, drug purchases should not be recorded in the register during long-term care. RESULTS: The required level of assistance at discharge was recorded for 99.7% of people, diagnoses for 5.1% of the care periods and the discharge date for 100% of the completed care periods. Depending on the definition of long-term care, 6-10% of all long-term care periods included drug purchases during the study period. CONCLUSIONS: The validity of the Care Register for Social Welfare is high, but some limitations should be considered when using the data. Combining health and social care registers provides a potentially more comprehensive database on the utilisation and costs of services.

Application of Healthcare 'Big Data' in CNS Drug Research: The Example of the Neurological and mental health Global Epidemiology Network (NeuroGEN).

Neurological and psychiatric (mental health) disorders have a large impact on health burden globally. Cognitive disorders (including dementia) and stroke are leading causes of disability. Mental health disorders, including depression, contribute up to one-third of total years lived with disability. The Neurological and mental health Global Epidemiology Network (NeuroGEN) is an international multi-database network that harnesses administrative and electronic medical records from Australia, Asia, Europe and North America. Using these databases NeuroGEN will investigate medication use and health outcomes in neurological and mental health disorders. A key objective of NeuroGEN is to facilitate high-quality observational studies to address evidence-practice gaps where randomized controlled trials do not provide sufficient information on medication benefits and risks that is specific to vulnerable population groups. International multi-database research facilitates comparisons across geographical areas and jurisdictions, increases statistical power to investigate small subpopulations or rare outcomes, permits early post-approval assessment of safety and effectiveness, and increases generalisability of results. Through bringing together international researchers in pharmacoepidemiology, NeuroGEN has the potential to be paradigm-changing for observational research to inform evidence-based prescribing. The first focus of NeuroGEN will be to address evidence-gaps in the treatment of chronic comorbidities in people with dementia.

Incidence of muscle relaxant use in relation to diagnosis of Parkinson's disease.

Background Parkinson's disease is the second most common neurodegenerative disorder. Motor and non-motor symptoms seem to precede the diagnosis of Parkinson's disease. Objective To evaluate the incidence of muscle relaxant use in community-dwelling persons with and without Parkinson's disease from 4 years before to 4 years after the diagnosis of Parkinson's disease. Method Nationwide register-based cohort included all community-dwelling Finnish persons who received reimbursement of Parkinson's disease drugs between 2000 and 2015 (N = 17,450) and comparison persons without Parkinson's disease who were matched for age, gender and region of residence (N = 122,694). Data on muscle relaxant use during 1995-2016 were collected from the Prescription Register. Results The incidence of muscle relaxant use was higher among persons with Parkinson's disease in comparison to persons without Parkinson's disease from 3 years before the diagnosis until 6 months after the diagnosis. The largest difference in incidence rates was observed at the time of the diagnosis (incidence rate ratio = 2.04, 95% confidence interval = 1.81-2.30). Tizanidine was the most frequently initiated muscle relaxant. Conclusions The incidence of muscle relaxant use starts increasing years before the diagnosis of Parkinson's disease but declines after that. It is important to identify the causes of muscle symptoms to avoid unnecessary muscle relaxant use and consequent adverse effects and events.

Predictors of high hospital care and medication costs and cost trajectories in community-dwellers with Alzheimer's disease.

Objectives: We studied the determinants of high healthcare costs (highest decile of hospital care and medication costs) and cost trajectories among all community-dwellers with clinically verified Alzheimer's disease (AD), diagnosed during 2005-2011 in Finland (N = 70,531). Methods: The analyses were done separately for hospital care costs, medication costs and total healthcare costs that were calculated for each 6-month period from 5 years before to 3 years after AD diagnosis. Results: Total healthcare costs were driven mainly by hospital care costs. The definition of "high-cost person" was time-dependent as 63% belonged to the highest 10% at some timepoint during the study period and six distinct cost trajectories were identified. Strokes, cardiovascular diseases, fractures and mental and behavioural disorders were most strongly associated with high hospital care costs. Conclusions: Although persons with AD are often collectively considered as expensive patient group, there is large temporal and inter-individual variation in belonging to the highest decile of hospitalization and/or medication costs. It would be important to assess whether hospitalization rate could be decreased by, e.g., comprehensive outpatient care with more efficient management of comorbidities. In addition, other interventions that could decrease hospitalization rate in persons with dementia should be studied further in this context. Key messages Persons with AD had large individual fluctuation in hospital care costs and medication costs over time. Hospital care costs were considerably larger than medication costs, with fractures, cardiovascular diseases and mental and behavioural disorders being the key predictors. Antidementia medication was associated with lower hospital care costs.

Use of Antiepileptic Drugs and Dementia Risk-an Analysis of Finnish Health Register and German Health Insurance Data.

OBJECTIVES: To evaluate the association between regular antiepileptic drug (AED) use and incident dementia. DESIGN: Case-control analysis. SETTING: Finnish public health register and German health insurance data. PARTICIPANTS: Individuals with dementia of any type (German data, N=20,325) and Alzheimer's disease (AD; Finnish data, N=70,718) were matched with up to four control persons without dementia. MEASUREMENTS: We analyzed the association between regular AED use and dementia. To address potential protopathic bias, a lag time of 2 years between AED use and dementia diagnosis was introduced. Odds ratios (ORs) were calculated by applying conditional logistic regression, adjusted for potential confounding factors such as comorbidities and polypharmacy. RESULTS: Regular AED use was more frequent in individuals with dementia than controls. Regular use of AEDs was associated with a significantly greater risk of incident dementia (adjusted OR=1.28, 95% confidence interval (CI)=1.14-1.44) and AD (adjusted OR=1.15, 95% CI=1.09-1.22) than no AED use. We also detected a trend toward greater risk of dementia with higher exposure. When AEDs with and without known cognitive adverse effects (CAEs) were compared, a significantly greater risk of dementia was observed for substances with known CAEs (dementia: OR=1.59, 95% CI=1.36-1.86; AD: OR=1.19, 95% CI=1.11-1.27). CONCLUSION: AEDs, especially those with known CAEs, may contribute to incident dementia and AD in older persons.

Does routinely collected patient-reported outcome data represent the actual case-mix of elective coronary revascularization patients?

Aims: Patient-reported outcomes (PROs) are valuable for effectiveness evaluation, but it is unknown whether the patient views obtained represent the actual case mix. We studied the representativeness of the responses obtained to a routinely administered health-related quality of life (HRQoL) questionnaire in a cardiology unit. Methods and results: Elective coronary artery bypass grafting (CABG; n = 404) and percutaneous coronary intervention (PCI; n = 738) patients operated during June 2012 to August 2014 in the Heart Center, Kuopio University Hospital. The characteristics of the patients with a baseline (n = 260 and 290 for CABG and PCI, respectively) or both baseline and follow-up HRQoL measurements (n = 203 and 189 for CABG and PCI, respectively) were compared with those who did not respond (n = 144 and 448 for CABG and PCI). Baseline questionnaires were less likely obtained from older CABG patients (odds ratio 0.51, 95% confidence interval 0.28-0.91) and those with more severe disease (0.20, 0.05-0.79). Among PCI patients, women (0.64, 0.45-0.91), smokers (0.74, 0.53-1.04), and those with more severe disease (0.26, 0.13-0.52) or more hospital days were underrepresented. Conclusion: Routinely collected PROs in cardiac patients may be biased towards younger and healthier patients. This needs to be recognized when evaluating the representativeness of such data. The routine collection of these data should be adequately resourced.

Hospital care and drug costs from five years before until two years after the diagnosis of Alzheimer's disease in a Finnish nationwide cohort.

AIMS: The aim of our study was to investigate costs related to hospital care and drugs utilizing register-based data from five years before until two years after the diagnosis of Alzheimer's disease (AD) in a nationwide cohort. METHODS: Finnish nationwide MEDALZ cohort includes all incident cases with clinically verified diagnosis of AD diagnosed during 2005-2011. The study population included 70,718 persons with AD and age-, gender- and region-of-residence-matched control persons. Data of medical care costs was derived from the prescription register and hospital discharge register. Costs of hospital care were calculated according to Finnish healthcare system unit costs. Costs in six month periods before and after the diagnosis per person-years were analyzed. RESULTS: Persons with AD had higher mean total medical care costs per person-years starting from 0.5-1 years before the diagnosis of AD and remained at a higher level until two years after the diagnosis. The difference in mean total medical care costs was at its highest at six months after the diagnosis (cost difference €5088). After that, persons with AD had costs that reached approximately double those without AD. Hospital care costs constituted the major share (78-84%) of the total medical care costs in both persons with and without AD, whereas drug costs had a minor role. Increase in drug costs was caused by anti-dementia drugs. CONCLUSIONS: Costs of hospital stays constituted the most significant portion of medical care costs for persons with AD. Further research should be focused on the causes of hospitalization periods.

Health condition and physical function as predictors of adherence in long-term strength and balance training among community-dwelling older adults.

AIM: Strength and balance training (SBT) has remarkable health benefits, but little is known regarding exercise adherence in older adults. We examined the adherence to strength and balance training and determinants of adherence among ≥75 year old adults. METHODS: 182 community-dwelling individuals (aged 75-98 years, 71% female) began group-based SBT as part of a population-based Geriatric Multidisciplinary Strategy for the Good Care of the Elderly study. Training was offered once a week for 2.3 years. Adherence was defined as the proportion of attended sessions relative to offered sessions. Participants were classified based on their adherence level into low (≤33.3%), moderate (33.4-66.5%) and high (≥66.6%) adherers. RESULTS: The mean length of training was 19 ± 9 months, and 68% continued participation for at least two years. The mean training adherence was 55 ± 29% for all participants and 18%, 53% and 82% for low, moderate and high adherers, respectively. High adherence was predicted by female sex; younger age; better cognition; independence in Instrumental Activities of Daily Living; higher knee extension strength; faster walking speed; and better performance on the Berg Balance Scale and Timed Up and Go tests. Poorer self-perceived health and the use of a walking aid were related to low adherence. CONCLUSIONS: Long-term continuation of training is possible for older community-dwelling adults, although poorer health and functional limitations affect training adherence. Our findings have implications for tailoring interventions and support for older adults to optimize their exercise adherence.

Associations across spatial patterns of disease incidences, socio-demographics, and land use in Finland 1991-2010.

AIMS: The epidemiological aim was to draw a general picture of spatial patterns of diseases, socio-demographics, and land use in Finland to detect possible under-recognized associations between the patterns. The methodological purpose was to compare and combine two statistical techniques to approach the data from different viewpoints. METHODS: Two different statistical methods, the self-organizing map and principal coordinates of neighbor matrices with variation partitioning, were used to search for spatial patterns of 15 non-infectious diseases and 17 direct or indirect risk factors. The dataset was gathered from five Finnish registries and pooled over the years 1991-2010. The statistical unit in the analyses was a municipality (n=303). RESULTS: Variables referring to urban living were related to low incidences of all other diseases but cancer, whereas variables referring to rural living were related to low incidences of cancer and high incidences of other diseases, especially coronary heart disease (CHD), hypertension, diabetes, asthma/chronic obstructive pulmonary disease, and serious mental illnesses at the municipal level. The relationships between diseases other than cancer and risk factors related to socio-demographics and land use variables were stronger than those between cancer and risk factors. CONCLUSIONS: The structuration of spatial patterns was dominated by CHD together with land use features and unemployment rate. The relationship between unemployment and spatial health inequalities was emphasized. On the basis of the present study, it is suggested that large heterogeneous datasets are clustered and analyzed simultaneously with more than one statistical method to recognize the most significant and generalizable results.

Hospital admissions, outpatient visits and healthcare costs of community-dwellers with Alzheimer's disease.

BACKGROUND: Detailed data on the health care service use of people with Alzheimer's disease (AD) are scarce. METHODS: We assessed the health care service use of all community-dwelling persons with clinically verified AD diagnosis, residing in Finland on December 31, 2005 (n = 27,948) in comparison to matched cohort without AD. Hospitalization data during 2006-2009 were extracted from the National Hospital Discharge Register. RESULTS: Comorbidity-adjusted incidence rate ratios; IRR (95% CI) were 1.25 (1.22-1.28) for inpatient admissions and 0.72 (0.68-0.77) for outpatient visits. People with AD had more general health care admissions (IRR, 95%CI 1.73, 1.67-1.80) but less admissions to specialty units 0.82 (0.79-0.85) than the non-AD group, with psychiatry being the only specialty with more admissions in the AD group. People with AD had 16 more hospital days/person-year. CONCLUSIONS: It would be important to assess whether inpatient hospitalizations of AD patients could be decreased by better targeting of outpatient services and whether other conditions are underdiagnosed or undertreated among persons with AD.

Antidementia drug use among community-dwelling individuals with Alzheimer's disease in Finland: a nationwide register-based study.

The objective of this study was to investigate the prevalence of acetylcholinesterase inhibitor (AChEI) and memantine use, duration of treatment, concomitant use of these drugs, and factors associated with the discontinuation of AChEI therapy during 2006-2009. We utilized data from a nationwide sample of community-dwelling individuals with a clinically verified Alzheimer's disease diagnosed during the year 2005 (n=6858) as a part of the MEDALZ-2005 study. During the 4-year follow-up, 84% used AChEI and 47% used memantine. Altogether, 22% of the sample used both drugs concomitantly. The median duration of the first AChEI use period was 860 (interquartile range 295-1458) days and 1103 (interquartile range 489-1487) days for the total duration of AChEI use. Although 20% of the AChEI users discontinued the use during the first year, over half of them restarted later. The risk of discontinuation was higher for rivastigmine [hazard ratio 1.34 (confidence interval 1.22-1.48)] and galantamine users [hazard ratio 1.23 (confidence interval 1.15-1.37)] compared with donepezil users in the adjusted model. In conclusion, median time for AChEI use was over 3 years and every fifth Alzheimer's disease patient used AChEI and memantine concomitantly during the follow-up. The low rate of discontinuation is consistent with the Finnish Care Guideline but in contrast to the results reported from many other countries.

Association of serum 25-hydroxyvitamin D3 and D2 with academic performance in childhood: findings from a prospective birth cohort.

BACKGROUND: Higher total serum 25-hydroxyvitamin D (25(OH)D) concentrations have been associated with better cognitive function mainly in cross-sectional studies in adults. It is unknown if the associations of different forms of 25(OH)D (25(OH)D(3) and 25(OH)D(2)) are similar. METHODS: Prospective cohort study (n=3171) with serum 25(OH)D(3) and 25(OH)D(2) concentrations measured at mean age of 9.8 years and academic performance at age 13-14 years (total scores in English, mathematics and science) and 15-16 years (performance in General Certificates of Education examinations). RESULTS: Serum 25(OH)D(3) concentrations were not associated with any educational outcomes. Higher 25(OH)D(2) concentrations were associated with worse performance in English at age 13-14 years (adjusted SD change per doubling in 25(OH)D(2) (95% CI) -0.05 (-0.08 to -0.01)) and with worse academic performance at age 15-16 years (adjusted OR for obtaining ≥5 A*-C grades (95% CI) 0.91 (0.82 to 1.00)). CONCLUSION: The null findings with 25(OH)D(3) are in line with two previous cross-sectional studies in children. It is possible that the positive association of 25(OH)D with cognitive function seen in adults does not emerge until later in life or that the results from previous cross-sectional adult studies are due to reverse causality. The unexpected inverse association of 25(OH)D(2) with academic performance requires replication in further studies. Taken together, our findings do not support suggestions that children should have controlled exposure to sunlight, or vitamin D supplements, in order to increase academic performance.

The association of serum 25-hydroxyvitamin D3 and D2 with depressive symptoms in childhood--a prospective cohort study.

BACKGROUND: Depression in adolescence is common and early onset predicts worse outcome in adulthood. Studies in adults have suggested a link between higher total 25-hydroxyvitamin D [25(OH)D] concentrations and lower risk of depression. OBJECTIVES: To investigate (a) the association between serum 25(OH)D(2) and 25(OH)D(3) concentrations and depressive symptoms in children, and (b) whether the associations of 25(OH)D(2) and 25(OH)D(3) are different from, and independent of, each other. METHODS: Prospective cohort study with serum 25(OH)D(2) and 25(OH)D(3) concentrations measured at mean age of 9.8 years and depressive symptoms assessed with the Mood and Feelings Questionnaire by a trained interviewer at the mean ages of 10.6 years (n = 2,759) and 13.8 years (n = 2,752). RESULTS: Higher concentrations of 25(OH)D(3) assessed at mean age 9.8 years were associated with lower levels of depressive symptoms at age 13.8 years [adjusted risk ratio (RR; 95% confidence interval (CI)): 0.90 (0.86-0.95)], but not at age 10.6 years [adjusted RR (95% CI): 0.98 (0.93-1.03)] and with increased odds of decreasing symptoms between age 10.6 and 13.8 years [adjusted RR (95% CI): 1.08 (1.01-1.16)]. Serum 25(OH)D(2) concentrations were not associated with depressive symptoms. CONCLUSIONS: This is the first study in children to suggest that the association between 25(OH)D(3) concentrations and depression emerges in childhood. The association is independent of a wide range of potential confounding factors, and appears to be stronger with greater time separation between assessment of 25(OH)D(3) and assessment of depressive symptoms. Confirmation of our findings in large prospective studies and trials would be valuable.