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FUNDING Funding sources for the respective studies are as follows: The Norwegian ParkWest study has been funded by the Research Council of Norway (177966), the Western Norway Regional Health Authority (911218), and the Norwegian Parkinson's Disease Association. PINE study was supported by Parkinson's UK (G0502, G0914, and G1302), Scottish Government Chief Scientist Office, BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, and RS MacDonald Trust. The Swedish Medical Research Council, the Swedish Parkinson's Disease Association, the Swedish Parkinson's Foundation, Erling Persson Foundation, Kempe Foundation, and the Västerbotten County Council have funded the NYPUM study. The Research Council of Norway (287842) supported AS, JM-G, and GA. ACKNOWLEDGMENTS The authors would like to thank all of the patients and controls for participation in each of the studies. Equally, we thank all members of each of the study groups and other personnel for their contributions. ; Peer reviewed ; Publisher PDF

PINE was supported by Parkinson's UK (grant numbers G0502, G0914, G1302), Scottish Government Chief Scientist Office, BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, and RS MacDonald Trust. The Norwegian ParkWest study has been funded by the Research Council of Norway (grant number 177966), the Western Norway Regional Health Authority (grant number 911218), Stavanger University Hospital Research Funds (grant number 501611), and the Norwegian Parkinson's Disease Association. Janete Chung and Kristin Aaser Lunde are supported by the Western Norway Regional Health Authority (grant numbers 911859 and 911830). The NYPUM study has been funded by the Swedish Medical Research Council, the Swedish Parkinson's Disease Association, the Swedish Parkinson Foundation, Erling Persson Foundation, Kempe Foundation and the Västerbotten County Council. The funding sources had no role in the design and conduct of the study: collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript: and decision to submit the manuscript for publication. ; Peer reviewed ; Postprint

ACKNOWLEDGMENTS The authors would like to thank all of the patients and controls for participation in each of the studies. Equally, we thank all members of each of the study groups and other personnel for their contributions. Funding sources for the respective studies are as follows: The Norwegian ParkWest study has been funded by the Research Council of Norway (177966), the Western Norway Regional Health Authority (911218), the Norwegian Parkinson's Research Foundation, and Rebergs Legacy. PINE study was supported by Parkinson's UK (G0502, G0914, G1302), Scottish Government Chief Scientist Office, BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, and RS MacDonald Trust. The NYPUM study has been funded by the Swedish Medical Research Council, the Swedish Parkinson's disease Association, the Swedish Parkinson's Foundation, Parkinson Research Foundation, Erling Persson Foundation, Kempe Foundation, the Swedish Brain Foundation (Hjarnfonden), and the Vasterbotten County Council. AAS, JMG and GA are supported by the Research Council of Norway (287842). BLF acknowledges support through donations to the UCLA Clinical Neurogenomics Research Center. CK is supported by the NIH grant F32AG063442. The PEG study was supported by NIH/NIEHS grants R01-ES010544 and U54-ES012078. Publication of this manuscript was supported under the The Michael J. Fox Foundation: 2021 RFA: Accelerating Publication of Parkinson's Disease Replication Data. ; Peer reviewed ; Publisher PDF

OBJECTIVE: This study aimed to determine the prevalence of epilepsy in four European countries (Austria, Denmark, Ireland, and Romania) employing a standard methodology. The study was conducted under the auspices of ESBACE (European Study on the Burden and Care of Epilepsy). METHODS: All hospitals and general practitioners serving a region of at least 50 000 persons in each country were asked to identify patients living in the region who had a diagnosis of epilepsy or experienced a single unprovoked seizure. Medical records were accessed, where available, to complete a standardized case report form. Data were sought on seizure frequency, seizure type, investigations, etiology, comorbidities, and use of antiseizure medication. Cases were validated in each country, and the degree of certainty was graded as definite, probable, or suspect cases. RESULTS: From a total population of 237 757 in the four countries, 1988 (.8%) patients were identified as potential cases of epilepsy. Due to legal and ethical issues in the individual countries, medical records were available for only 1208 patients, and among these, 113 had insufficient clinical information. The remaining 1095 cases were classified as either definite (n = 706, 64.5%), probable (n = 191, 17.4%), suspect (n = 153, 14.0%), or not epilepsy (n = 45, 4.1%). SIGNIFICANCE: Although a precise prevalence estimate could not be generated from these data, the study found a high validity of epilepsy classification among evaluated cases (95.9%). More generally, this study highlights the significant challenges facing epidemiological research methodologies that are reliant on patient consent and retrospective chart review, largely due to the introduction of data protection legislation during the study period. Documentation of the epilepsy diagnosis was, in some cases, relatively low, indicating a need for improved guidelines for assessment, follow-up, and documentation. This study highlights the need to address the concerns and requirements of recruitment sites to engage in epidemiological research.

Objective: This study aimed to determine the prevalence of epilepsy in four European countries (Austria, Denmark, Ireland, and Romania) employing a standard methodology. The study was conducted under the auspices of ESBACE (European Study on the Burden and Care of Epilepsy). Methods: All hospitals and general practitioners serving a region of at least 50 000 persons in each country were asked to identify patients living in the region who had a diagnosis of epilepsy or experienced a single unprovoked seizure. Medical records were accessed, where available, to complete a standardized case report form. Data were sought on seizure frequency, seizure type, investigations, etiology, comorbidities, and use of antiseizure medication. Cases were validated in each country, and the degree of certainty was graded as definite, probable, or suspect cases. Results: From a total population of 237 757 in the four countries, 1988 (.8%) patients were identified as potential cases of epilepsy. Due to legal and ethical issues in the individual countries, medical records were available for only 1208 patients, and among these, 113 had insufficient clinical information. The remaining 1095 cases were classified as either definite (n = 706, 64.5%), probable (n = 191, 17.4%), suspect (n = 153, 14.0%), or not epilepsy (n = 45, 4.1%). Significance: Although a precise prevalence estimate could not be generated from these data, the study found a high validity of epilepsy classification among evaluated cases (95.9%). More generally, this study highlights the significant challenges facing epidemiological research methodologies that are reliant on patient consent and retrospective chart review, largely due to the introduction of data protection legislation during the study period. Documentation of the epilepsy diagnosis was, in some cases, relatively low, indicating a need for improved guidelines for assessment, follow-up, and documentation. This study highlights the need to address the concerns and requirements of recruitment sites to engage in epidemiological research.

INTRODUCTION: Functional dependency in basic activities of daily living (ADLs) is a key outcome in Parkinson's disease (PD). We aimed to define dependency in PD, using the original and MDS versions of the Unified Parkinson's Disease Rating Scale (UPDRS). METHODS: We developed two algorithms to define dependency from items of UPDRS Part 2 and MDS-UPDRS Part 2 relating to basic ADLs (feeding, dressing, hygiene and walking, and getting out of a chair). We validated both algorithms using data from 1110 patients from six community-based PD incidence cohorts, testing concurrent validity, convergent validity, and predictive validity. RESULTS: Our optimal algorithm showed high specificity and moderate to high sensitivity versus Schwab & England <80% (specificity 95% [95% confidence interval (CI) 93-97] and sensitivity 65% [95% CI 55-73] at baseline; 88% [95% CI 85-91] and 85% [95% CI 79-97] respectively at five-years follow-up). Convergent validity was demonstrated by strong associations between dependency defined by the algorithm and cognition (MMSE), quality of life (PDQ39), and impairment (UPDRS part 3) (all p < 0.001). Algorithm-defined dependency status also predicted mortality: HR for mortality in those dependent vs independent at baseline was 1.6 (95%CI 1.2-2.1) and in those dependent vs independent at five-years' follow-up was 2.2 (1.6-3.0). DISCUSSION: We have demonstrated the concurrent validity, convergent validity, and predictive validity of a UPDRS-/MDS-UPDRS-based algorithm to define functional dependency in PD. This can be used for studying dependency in any study where UPDRS or MDS-UPDRS part 2 data have been collected. ; The PICC collaboration was funded by the Chief Scientist Office of the Scottish Government, NHS Education for Scotland, and the Academy of Medical Sciences. The CamPaIGN study has received funding from the Wellcome Trust, the Medical Research Council, the Patrick Berthoud Trust, Parkinson's UK, and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre Dementia and Neurodegeneration Theme (ref. 146281). The ICICLE-PD study was funded by Parkinson's UK (J-0802, G-1301, G-1507) and the, Lockhart Parkinson's Disease Research Fund. The research was supported by the NIHR Newcastle Biomedical Research Unit and Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre Dementia and Neurodegeneration Theme (ref. 146281). The NYPUM study was funded by Swedish Medical Research Council, Parkinson Foundation in Sweden, the Swedish Parkinson Disease Association, University of Umeå, Foundation for Clinical Neuroscience at Umeå University Hospital, Västerbotten County Council (ALF) and King Gustaf V's and Queen Victoria's foundation The Norwegian ParkWest study was funded by the Western Norway Regional Health Authority (grant No 911218), the Research Council of Norway (grant No 177966 and 287842) and the Norwegian Parkinson Research Foundation. The PICNICS study was funded by the Cure Parkinson's Trust, the Van Geest Foundation, the MRC and Parkinson's UK, and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre Dementia and Neurodegeneration Theme (ref. 146281). The PINE study was funded by Parkinson's UK, the Scottish Chief Scientist Office, NHS Grampian endowments, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation and SPRING. C H Williams-Gray holds a RCUK/UKRI Research Innovation Fellowship awarded by the Medical Research Council (MR/R007446/1) and receives support from the Cambridge Centre for Parkinson-Plus.

INTRODUCTION: Due to demographic change, an increase in the frequency of Parkinson's disease (PD) patients is expected in the future and, thus, the identification of modifiable risk factors is urgently needed. We aimed to examine the associations of body mass index (BMI) and waist circumference (WC) with incident PD. METHODS: In 13 of the 23 centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a total of 734 incident cases of PD were identified between 1992 and 2012 with a mean follow-up of 12 years. Cox proportional hazards regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). We modelled anthropometric variables as continuous and categorical exposures and performed subgroup analyses by potential effect modifiers including sex and smoking. RESULTS: We found no association between BMI, WC and incident PD, neither among men nor among women. Among never and former smokers, BMI and waist circumference were also not associated with PD risk. For male smokers, however, we observed a statistically significant inverse association between BMI and PD risk (HR 0.51, 95%CI: 0.30, 0.84) and the opposite for women, i.e. a significant direct association of BMI (HR 1.79, 95%CI: 1.04, 3.08) and waist circumference (HR 1.64, 95%CI: 1.03, 2.61) with risk of PD. CONCLUSION: Our data revealed no association between excess weight and PD risk but a possible interaction between anthropometry, sex and smoking. ; This research has been made possible thanks to a grant of the European Community (5th Framework Programme) to Prof. Paolo Vineis (grant QLK4CT199900927); and a grant of the Compagnia di San Paolo to the ISI Foundation. All authors are independent from founders. Mortality data from the Netherlands are obtained from "Statistics Netherlands". The centers contributing to the NeuroEPIC4PD study are financially supported by: Europe Against Cancer Program of the European Commission (SANCO); ISCIII, Red de Centros RCESP, C03/09; Spanish Ministry of Health (ISCIII RETICC RD06/0020); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research (BMBF); Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra; Spanish Ministry of Health (ISCIII RETICC RD06/0020) Cancer Research U.K.; Medical Research Council, United Kingdom; Stroke Association, United Kingdom; British Heart Foundation; Department of Health, United Kingdom; Food Standards Agency, United Kingdom; Welcome Trust, United Kingdom Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Swedish Cancer Foundation; Swedish Scientific Council; Regional Governments of Skåne and Västerbotten Counties, Sweden; Norwegian Cancer Society; Research Council of Norway; French League against cancer, Inserm, Mutuelle Generale l'Education National and IGR; the Hellenic Health Foundation.

BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking 30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect. ; Mortality data from the Netherlands are obtained from "Statistics Netherlands". In addition we would like to thank for their financial support: Europe Against cancer Program of the European Commission (SANCO); ISCIII, Red de Centros RCESP, C03/09; Spanish Ministry of Health (ISCIII RETICC RD06/0020); Deutsche Krebshilfe; Deutsches Krebsforschungszentrum; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra; Spanish Ministry of Health (ISCIII RETICC RD06/0020)Cancer Research U.K.; Medical Research Council, United Kingdom; Stroke Association, United Kingdom; National Institute of Health Research funding of a Biomedical Research Centre in Cambridge ; British Heart Foundation; Department of Health, United Kingdom; Food Standards Agency, United Kingdom; Wellcome Trust, United Kingdom Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands (The Netherlands); Swedish Cancer; Swedish Research Council; European Research Council, Regional Government of Skåne and Västerbotten, Sweden; Norwegian Cancer Society; Research Council of Norway; French League against cancer, Inserm, Mutuelle Generale l'Education National and IGR. Claudio Ruffmann received funding from 'Fondazione Grigioni per la lotta al Morbo di Parkinson

Objective: This study aimed to determine the prevalence of epilepsy in four European countries (Austria, Denmark, Ireland, and Romania) employing a standard methodology. The study was conducted under the auspices of ESBACE (European Study on the Burden and Care of Epilepsy). Methods: All hospitals and general practitioners serving a region of at least 50 000 persons in each country were asked to identify patients living in the region who had a diagnosis of epilepsy or experienced a single unprovoked seizure. Medical records were accessed, where available, to complete a standardized case report form. Data were sought on seizure frequency, seizure type, investigations, etiology, comorbidities, and use of antiseizure medication. Cases were validated in each country, and the degree of certainty was graded as definite, probable, or suspect cases. Results: From a total population of 237 757 in the four countries, 1988 (.8%) patients were identified as potential cases of epilepsy. Due to legal and ethical issues in the individual countries, medical records were available for only 1208 patients, and among these, 113 had insufficient clinical information. The remaining 1095 cases were classified as either definite (n = 706, 64.5%), probable (n = 191, 17.4%), suspect (n = 153, 14.0%), or not epilepsy (n = 45, 4.1%). Significance: Although a precise prevalence estimate could not be generated from these data, the study found a high validity of epilepsy classification among evaluated cases (95.9%). More generally, this study highlights the significant challenges facing epidemiological research methodologies that are reliant on patient consent and retrospective chart review, largely due to the introduction of data protection legislation during the study period. Documentation of the epilepsy diagnosis was, in some cases, relatively low, indicating a need for improved guidelines for assessment, follow-up, and documentation. This study highlights the need to address the concerns and requirements of recruitment sites to engage in ...

Objective: This study aimed to determine the prevalence of epilepsy in four European countries (Austria, Denmark, Ireland, and Romania) employing a standard methodology. The study was conducted under the auspices of ESBACE (European Study on the Burden and Care of Epilepsy). Methods: All hospitals and general practitioners serving a region of at least 50 000 persons in each country were asked to identify patients living in the region who had a diagnosis of epilepsy or experienced a single unprovoked seizure. Medical records were accessed, where available, to complete a standardized case report form. Data were sought on seizure frequency, seizure type, investigations, etiology, comorbidities, and use of antiseizure medication. Cases were validated in each country, and the degree of certainty was graded as definite, probable, or suspect cases. Results: From a total population of 237 757 in the four countries, 1988 (.8%) patients were identified as potential cases of epilepsy. Due to legal and ethical issues in the individual countries, medical records were available for only 1208 patients, and among these, 113 had insufficient clinical information. The remaining 1095 cases were classified as either definite (n = 706, 64.5%), probable (n = 191, 17.4%), suspect (n = 153, 14.0%), or not epilepsy (n = 45, 4.1%). Significance: Although a precise prevalence estimate could not be generated from these data, the study found a high validity of epilepsy classification among evaluated cases (95.9%). More generally, this study highlights the significant challenges facing epidemiological research methodologies that are reliant on patient consent and retrospective chart review, largely due to the introduction of data protection legislation during the study period. Documentation of the epilepsy diagnosis was, in some cases, relatively low, indicating a need for improved guidelines for assessment, follow-up, and documentation. This study highlights the need to address the concerns and requirements of recruitment sites to engage in epidemiological research.