Search

Your search keyword '"CTR"' showing total 7,529 results
Start Over Author "CTR"

Refine your results

more »

more »

more »

more »

more »

more »
7,529 results on '"CTR"'

1. Seasonal effect on physiological, reproductive and fertility profiles in breeding mithun bulls

Author

P Perumal, N Savino, CTR Sangma, M H Khan, E Ezung, S Chang, and TZT Sangtam

Subjects
Mithun, Seasonal effect, Physiological parameters, Reproductive and fertility parameters, Medicine
Abstract

Objective: To analyse the seasonal effect on physiological parameters, reproductive profiles and in vitro fertility in breeding mithun bulls.Methods: A total of ten adult mithun bulls age of 5 to 6 years old with good body condition (score 5-6) were selected from ICAR-NRC on Mithun, Jharnapani, Nagaland, India. The seasons were categorised into winter, spring, summer and autumn seasons based on the meteorological data and sunshine hours. The physiological parameters, reproductive profiles and in vitro fertility parameters were assessed during different seasons in mithun under the semi-intensive system of management.Results: The statistical analysis revealed that these experimental parameters were differed significantly (P

Published
2017
Full Text
View/download PDF

2. Accuracy of a Cancer Registry Versus Clinical Care Team Chart Abstraction in Identifying Cancer Recurrence

Author

Elsa A. Sutton, MD, Benjamin C. Kamdem Talom, BA, Daniel K. Ebner, MD, MPH, Taylor M. Weiskittel, MS, William G. Breen, MD, Roman O. Kowalchuk, MD, Heather J. Gunn, PhD, Courtney N. Day, MS, Eric J. Moore, MD, Sara J. Holton, CTR, BS Health/Health Care Administration/Management, Kathryn M. Van Abel, MD, Chadi N. Abdel-Halim, MD, David M. Routman, MD, and Mark R. Waddle, MD

Subjects
Medicine (General), R5-920
Abstract

Objective: To evaluate the completeness and reliability of recurrence data from an institutional cancer registry for patients with head and neck cancer. Patients and Methods: Recurrence information was collected by radiation oncology and otolaryngology researchers. This was compared with the institutional cancer registry for continuous patients treated with radiation therapy for head and neck cancer at a tertiary cancer center. The sensitivity and specificity of institutional cancer registry data was calculated using manual review as the gold standard. False negative recurrences were compared to true positive recurrences to assess for differences in patient characteristics. Results: A total of 1338 patients who were treated from January 1, 2010, through December 31, 2017, were included in a cancer registry and underwent review. Of them, 375 (30%) had confirmed cancer recurrences, 45 (3%) had concern for recurrence without radiologic or pathologic confirmation, and 31 (2%) had persistent disease. Most confirmed recurrences were distant (37%) or distant plus locoregional (29%), whereas few were local (11%), regional (9%), or locoregional (14%) alone. The cancer registry accuracy was 89.4%, sensitivity 61%, and specificity 99%. Time to recurrence was associated with registry accuracy. True positives had recurrences at a median of 414 days vs 1007 days for false negatives. Conclusion: Currently, institutional cancer registry recurrence data lacks the required accuracy for implementation into studies without manual confirmation. Longer follow-up of cancer status will likely improve sensitivity. No identified differences in patients accounted for differences in sensitivity. New, ideally automated, data abstraction tools are needed to improve detection of cancer recurrences and minimize manual chart review.

Published
2024
Full Text
View/download PDF

8. The impact of stage-related features in melanoma recurrence prediction: A machine learning approach

Author

Guihong Wan, PhD, Bonnie Leung, BS, Nga Nguyen, MD, MPH, Mia S. DeSimone, MD, MPH, Feng Liu, PhD, Min Seok Choi, MS, Diane Ho, RHIA, CTR, Valerie Laucks, BS, Stacey Duey, MCPH, Ryan J. Sullivan, MD, Genevieve M. Boland, MD, PhD, Nicole R. LeBoeuf, MD, MPH, David Liu, MD, MPH, Alexander Gusev, PhD, Shawn G. Kwatra, MD, Peter K. Sorger, PhD, Kun-Hsing Yu, MD, PhD, and Yevgeniy R. Semenov, MD, MA

Subjects
Dermatology, RL1-803
Published
2023
Full Text
View/download PDF

10. Brief Report: Implementation of a Universal Prescreening Protocol to Increase Recruitment to Lung Cancer Studies at a Veterans Affairs Cancer Center

Author

Jenny J. Xiang, MD, Alicia Roy, BA, Christine Summers, MA, Monica Delvy, BS, Jessica O’Donovan, BA, John Christensen, Christopher Dwy, BS, Lydia Perry, BA, Donna Connery, CTR, Michal G. Rose, MD, Kelsey Sheehan, MD, and Herta H. Chao, MD, PhD

Subjects
Clinical trial, Lung cancer, Accrual, Recruitment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: The oncology clinical trial recruitment process is time, labor, and resource intensive, and poor accrual rates are common. We describe the VA Connecticut Cancer Center experience of implementing a standardized, universal prescreening protocol and its impact on thoracic oncology research recruitment. Methods: Research coordinators prescreened potentially eligible patients with confirmed or suspected cancer from multiple clinical sources and entered relevant patient and research study information into a centralized electronic database. The database provided real-time lists of potential studies for each patient. This enabled the research team to alert the patient's oncologist in advance of clinic visits and to prepare documents needed for enrollment. Clinicians could ensure sufficient time and attention in clinic to the informed consent process, therefore maximizing enrollment opportunities. Patients were also monitored on waitlists for future studies. Results: From March 2017 to December 2020, a total of 1518 patients with lung nodules and suspected or confirmed lung cancers were prescreened. Of these, 379 patients were enrolled to a study, 103 patients declined participation, and 639 were monitored for future studies. Our prescreening protocol identified all new patients with lung cancer who were ultimately added to the cancer registry. We found a substantial increase in study enrollment after prescreening implementation. Conclusions: Universal prescreening was associated with improved patient enrollment to thoracic oncology studies. The protocol was integral in our VA becoming the top accruing VA site for National Cancer Institute’s National Clinical Trials Network studies for 2019 to 2021.

Published
2022
Full Text
View/download PDF

15. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995–2014 (ICBP SURVMARK-2): a population-based study

Author

Arnold, Melina, Rutherford, Mark J, Bardot, Aude, Ferlay, Jacques, Andersson, Therese M-L, Myklebust, Tor Åge, Tervonen, Hanna, Thursfield, Vicky, Ransom, David, Shack, Lorraine, Woods, Ryan R, Turner, Donna, Leonfellner, Suzanne, Ryan, Susan, Saint-Jacques, Nathalie, De, Prithwish, McClure, Carol, Ramanakumar, Agnihotram V, Stuart-Panko, Heather, Engholm, Gerda, Walsh, Paul M, Jackson, Christopher, Vernon, Sally, Morgan, Eileen, Gavin, Anna, Morrison, David S, Huws, Dyfed W, Porter, Geoff, Butler, John, Bryant, Heather, Currow, David C, Hiom, Sara, Parkin, D Max, Sasieni, Peter, Lambert, Paul C, Møller, Bjørn, Soerjomataram, Isabelle, and Bray, Freddie

Published
2019
Full Text
View/download PDF

21. Planning and Management for Excellence and Efficiency of Higher Education. Proceedings of a Round Table at the International Congress on Planning and Management of Educational Development (Mexico City, Mexico, March 26-30, 1990).

Author

United Nations Educational, Scientific and Cultural Organization, Paris (France). Div. of Higher Education and Research., United Nations Educational, Scientific, and Cultural Organization, Caracas (Venezuela). Regional Ctr. for Higher Educ. in Latin America and Caribbean., United Nations Educational, Scientific and Cultural Organization, Paris (France). Div. of Higher Education and Research., and United Nations Educational, Scientific, and Cultural Organization, Caracas (Venezuela). Regional Ctr. for Higher Educ. in Latin America and Caribbean.

Abstract

The 14 papers in this volume address planning and administration of higher education within an international context. Papers are grouped into general studies, regional studies, and national and institutional studies. Included papers are: (1) "Management of Global and Educational Change: Challenges for Higher Education and Graduate Studies" (Gustavo Lopez Ospina); (2) "Accountability for More Efficiency and Effectiveness in Higher Education" (Klaus Huffner); (3) "Training for Planning and Management: Improved Management Systems in Higher Education in Developing Countries" (Kevin M. Lillis); (4) Improving Effectiveness of Higher Education Institutions: Studies of the Management of Change" (International Institute for Educational Planning); (5) "Higher Education: What Procedures for Evaluation?" (William B. Dockrell); (6) "Planning and Management of Higher Education in Latin America and the Caribbean: An Introductory Study" (Jose F. Silvio); (7) "Management and Administration of Higher Education in a Market Economy" (8) "Some Issues and Trends Relevant for Planning and Management of Higher Education in Arab Countries" (Al Awd Galeleldin); (9) "University Governance, Autonomy and Accountability in Brazil: A Couple of Challenges for the Decade" (Jacques Velloso); (10) "Management of Innovation and Change in Higher Education in Developing Countries; Experiences from Tanzania" (I. M. Omari); (11) "Planning and Management of Education in a Period of Crisis: The Example of Higher Education in Rwanda" (Joseph Kalinganire); (12) "Planning and Management for Excellence and Efficiency in Higher Education in India" (T. V. Rao); (13) "Higher Education in Czechoslovakia: Problems and Prospects of Management" (Jana Hendrichova and Ian Kouckij); and (14) "Planning and Managing for Excellence and Efficiency in Higher Education in Britain" (John Eggleston). (Some individual papers contain references.) (DB)

Published
1991

24. Preoperative biliary drainage in severely jaundiced patients with pancreatic head cancer: A retrospective cohort study

Author

Gils, L. van, Verbeek, R., Wellerdieck, N., Bollen, T., Leeuwen, M. van, Schwartz, M., Vleggaar, F., Molenaar, I.Q., Santvoort, H. van, Hooft, J. van, Verdonk, R., Weusten, B., and Reg Acad Canc Ctr Utrecht RAKU

Subjects
Pancreatic Neoplasms, Jaundice, Obstructive, Postoperative Complications, Treatment Outcome, Hepatology, Preoperative Care, Gastroenterology, Humans, Drainage, Jaundice, Bilirubin, Pancreaticoduodenectomy, Retrospective Studies
Abstract

Background: Guidelines recommend against preoperative biliary drainage (PBD) in patients with pancreatic head cancer if bilirubin levels are = 250 and < 250.Methods: Patients were identified from databases of 3 centers. Outcomes were compared in patients with a bilirubin level >= 250 versus = 250. PBD technical success (83% vs. 81%, p = 0.80) and PBD related complications (33% vs. 29%, p = 0.60) did not differ between these groups. Analyzing bilirubin levels >= 250 versus = 250 and < 250. Our study does not support a different approach regarding PBD in patients with severe jaundice.

Published
2022

30. Non-acute chest pain in primary care; referral rates, communication and guideline adherence: a cohort study using routinely collected health data

Author

Bulk, S. van den, Spoelman, W.A., Dijkman, P.R.M. van, Numans, M.E., Bonten, T.N., and Leiden Univ Med Ctr LUMC

Subjects
Chest pain, Communication, Guideline adherence, Routinely collected health data, Family Practice, Primary care, Coronary artery disease, Referral rate
Abstract

Background The prevalence of coronary artery disease is increasing due to the aging population and increasing prevalence of cardiovascular risk factors. Non-acute chest pain often is the first symptom of stable coronary artery disease. To optimise care for patients with non-acute chest pain and make efficient use of available resources, we need to know more about the current incidence, referral rate and management of these patients. Methods We used routinely collected health data from the STIZON data warehouse in the Netherlands between 2010 and 2016. Patients > 18 years, with no history of cardiovascular disease, seen by the general practitioner (GP) for non-acute chest pain with a suspected cardiac origin were included. Outcomes were (i) incidence of new non-acute chest pain in primary care, (ii) referral rates to the cardiologist, (iii) correspondence from the cardiologist to the GP, (iv) registration by GPs of received correspondence and; (v) pharmacological guideline adherence after newly diagnosed stable angina pectoris. Results In total 9029 patients were included during the study period, resulting in an incidence of new non-acute chest pain of 1.01/1000 patient-years. 2166 (24%) patients were referred to the cardiologist. In 857/2114 (41%) referred patients, correspondence from the cardiologist was not available in the GP’s electronic medical record. In 753/1257 (60%) patients with available correspondence, the GP did not code the conclusion in the electronic medical record. Despite guideline recommendations, 37/255 (15%) patients with angina pectoris were not prescribed antiplatelet therapy nor anticoagulation, 69/255 (27%) no statin and 67/255 (26%) no beta-blocker. Conclusion After referral, both communication from cardiologists and registration of the final diagnosis by GPs were suboptimal. Both cardiologists and GPs should make adequate communication and registration a priority, as it improves health outcomes. Secondary pharmacological prevention in patients with angina pectoris was below guideline standards. So, proactive attention needs to be given to optimise secondary prevention in this high-risk group in primary care.

Published
2022

31. Variants in PHF8 cause a spectrum of X-linked neurodevelopmental disorders and facial dysmorphology

Author

Sobering, A.K., Bryant, L.M., Li, D., McGaughran, J., Maystadt, I., Moortgat, S., Graham, J.M., Haeringen, A. van, Ruivenkamp, C., Cuperus, R., Vogt, J., Morton, J., Brasch-Andersen, C., Steenhof, M., Hansen, L.K., Adler, E., Lyonnet, S., Pingault, V., Sandrine, M., Ziegler, A., Donald, T., Nelson, B., Holt, B., Petryna, O., Firth, H., McWalter, K., Zyskind, J., Telegrafi, A., Juusola, J., Person, R., Bamshad, M.J., Earl, D., Tsai, A.C.H., Yearwood, K.R., Marco, E., Nowak, C., Douglas, J., Hakonarson, H., Bhoj, E.J., and Univ Washington Ctr Mendelian Geno

Subjects
histone demethylation, PHF8, Molecular Medicine, orofacial clefting, Genetics (clinical), epigenetic gene regulation, X-linked intellectual disability
Abstract

Loss-of-function variants in PHD Finger Protein 8 (PHF8) cause Siderius X-linked intellectual disability (ID) syndrome, hereafter called PHF8-XLID. PHF8 is a histone demethylase that is important for epigenetic regulation of gene expression. PHF8-XLID is an under-characterized disorder with only five previous reports describing different PHF8 predicted loss-of-function variants in eight individuals. Features of PHF8-XLID include ID and craniofacial dysmorphology. In this report we present 16 additional individuals with PHF8-XLID from 11 different families of diverse ancestry. We also present five individuals from four different families who have ID and a variant of unknown significance in PHF8 with no other explanatory variant in another gene. All affected individuals exhibited developmental delay and all but two had borderline to severe ID. Of the two who did not have ID, one had dyscalculia and the other had mild learning difficulties. Craniofacial findings such as hypertelorism, microcephaly, elongated face, ptosis, and mild facial asymmetry were found in some affected individuals. Orofacial clefting was seen in three individuals from our cohort, suggesting that this feature is less common than previously reported. Autism spectrum disorder and attention deficit hyperactivity disorder, which were not previously emphasized in PHF8-XLID, were frequently observed in affected individuals. This series expands the clinical phenotype of this rare ID syndrome caused by loss of PHF8 function.

Published
2022

33. Editorial 30.4

Author

Maria M. Delgado, Maggie B. Gale, Bryce Lease, and CTR Editorial Team

Subjects
Visual Arts and Performing Arts, State (polity), Political science, media_common.quotation_subject, Political economy, media_common
Abstract

As 2020 draws to a close, theatres all over the world are closed for business. The business of theatre remains in the most precarious state for many decades, with an uncertain future and in the UK,...

Published
2020

34. Real-world experience of switching from intravenous to subcutaneous vedolizumab maintenance treatment for inflammatory bowel diseases

Author

Volkers, A., Straatmijer, T., Duijvestein, M., Sales, A., Levran, A., Schaik, F. van, Maljaars, J., Gecse, K., Ponsioen, C., Grootjans, J., Hanzel, J., Tack, G., Jansen, J., Hoentjen, F., Boer, N. de, Marel, S. van der, Dijkstra, G., Oldenburg, B., Lowenberg, M., Meulen, A. van der, D'Haens, G., IBD Ctr Amsterdam, Dutch Initiative Crohn Colitis, Gastroenterology and Hepatology, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Tytgat Institute for Liver and Intestinal Research, Groningen Institute for Organ Transplantation (GIOT), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Gastroenterology and hepatology, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Hepatology, INDUCTION, Remission Induction, Gastroenterology, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], Antibodies, Monoclonal, Humanized, Inflammatory Bowel Diseases, THERAPY, Treatment Outcome, Crohn Disease, Gastrointestinal Agents, Phobic Disorders, inflammatory bowel disease, REGISTRY, Humans, Colitis, Ulcerative, subcutaneous vedolizumab, Pharmacology (medical), Prospective Studies, real-world evidence, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Abstract

Contains fulltext : 288020.pdf (Publisher’s version ) (Open Access) BACKGROUND: Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions. AIM: To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD METHODS: In this prospective cohort study, patients with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24. RESULTS: We included 82 patients with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) patients with CD and five (9.4%) with UC discontinued SC vedolizumab after a median of 18 (IQR 8-22) and 6 weeks (IQR 5-10), respectively. Four patients with CD switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median serum vedolizumab concentrations increased from 19 μg/ml at the time of the switch to 31 μg/ml 12 weeks after the switch (p

Published
2022

36. Editorial 30.1

Author

CTR Editorial Team

Subjects
Visual Arts and Performing Arts
Published
2020

40. Association between Cerebrovascular Reactivity Monitoring and Mortality Is Preserved When Adjusting for Baseline Admission Characteristics in Adult Traumatic Brain Injury: A CENTER-TBI Study

Author

Zeiler, F.A., Ercole, A., Beqiri, E., Cabeleira, M., Thelin, E.P., Stocchetti, N., Steyerberg, E.W., Maas, A.I.R., Menon, D.K., Czosnyka, M., Smielewski, P., Anke, A., Beer, R., Helbok, R., Bellander, B.M., Nelson, D., Buki, A., Chevallard, G., Chieregato, A., Citerio, G., Czeiter, E., Depreitere, B., Eapen, G., Frisvold, S., Jankowski, S., Kondziella, D., Koskinen, L.O., Meyfroidt, G., Moeller, K., Piippo-Karjalainen, A., Raj, R., Radoi, A., Sahuquillo, J., Ragauskas, A., Rocka, S., Rhodes, J., Rossaint, R., Stevanovic, A., Sakowitz, O., Sundstrom, N., Takala, R., Tamosuitis, T., Tenovuo, O., Vajkoczy, P., Vargiolu, A., Vilcinis, R., Wolf, S., Younsi, A., CTR-TBI High Resolution ICU HR ICU, Public Health, CTR-TBI High Resolution ICU HR ICU, Zeiler, F, Ercole, A, Beqiri, E, Cabeleira, M, Thelin, E, Stocchetti, N, Steyerberg, E, Maas, A, Menon, D, Czosnyka, M, Smielewski, P, and Citerio, G

Subjects
autoregulation, cerebrovascular reactivity, IMPACT, outcome analysis, Adult, Male, 030506 rehabilitation, medicine.medical_specialty, Neurology, Traumatic brain injury, IMPACT, Cerebral autoregulation, cerebrovascular reactivity, Cohort Studies, outcome analysi, 03 medical and health sciences, 0302 clinical medicine, Cerebrovascular reactivity, Patient Admission, outcome analysis, Brain Injuries, Traumatic, medicine, Humans, Autoregulation, Single-Blind Method, Prospective Studies, Mortality, Adult patients, business.industry, autoregulation, Original Articles, Middle Aged, medicine.disease, 3. Good health, Pressure reactivity, Anesthesia, Cerebrovascular Circulation, Female, Human medicine, Neurology (clinical), Neurosurgery, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract

Cerebral autoregulation, as measured using the pressure reactivity index (PRx), has been related to global patient outcome in adult patients with traumatic brain injury (TBI). To date, this has been documented without accounting for standard baseline admission characteristics and intracranial pressure (ICP). We evaluated this association, adjusting for baseline admission characteristics and ICP, in a multi-center, prospective cohort. We derived PRx as the correlation between ICP and mean arterial pressure in prospectively collected multi-center data from the High-Resolution Intensive Care Unit (ICU) cohort of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Multi-variable logistic regression models were analyzed to assess the association between global outcome (measured as either mortality or dichotomized Glasgow Outcome Score-Extended [GOSE]) and a range of covariates (IMPACT [International Mission for Prognosis and Analysis of Clinical Trials] Core and computed tomography [CT] variables, ICP, and PRx). Performance of these models in outcome association was compared using area under the receiver operating curve (AUC) and Nagelkerke's pseudo-R-2. One hundred ninety-three patients had a complete data set for analysis. The addition of percent time above threshold for PRx improved AUC and displayed statistically significant increases in Nagelkerke's pseudo-R-2 over the IMPACT Core and IMPACT Core + CT models for mortality. The addition of PRx monitoring to IMPACT Core +/- CT + ICP models accounted for additional variance in mortality, when compared to models with IMPACT Core +/- CT + ICP alone. The addition of cerebrovascular reactivity monitoring, through PRx, provides a statistically significant increase in association with mortality at 6 months. Our data suggest that cerebrovascular reactivity monitoring may provide complementary information regarding outcomes in TBI.

Published
2019

41. Phytochemical profile of methanolic extracts from Chilca (Baccharis glutinosa) roots and its activity against Aspergillus ochraceus and Fusarium moniliforme

Author

Inifap, Experimental Field Ctr Chiapas, Ocozocoautla , Chiapas, Mexico, Joaquín A. Montes-Molina, E.R. Garrido-Ramírez, Federico Antonio Gutiérrez-Miceli, Teresa Ayora-Talavera, S.A. Lagunas-Rivera, A. Lam-Gutiérrez, and Víctor Manuel Ruíz-Valdiviezo

Subjects
Fusarium, Environmental Engineering, biology, Phytochemical, Traditional medicine, Baccharis, Health, Toxicology and Mutagenesis, Toxicology, biology.organism_classification, Aspergillus ochraceus
Published
2019

42. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Author

Chia, R, Sabir, MS, Bandres-Ciga, S, Saez-Atienzar, S, Reynolds, RH, Gustavsson, E, Walton, RL, Ahmed, S, Viollet, C, Ding, JH, Makarious, MB, Diez-Fairen, M, Portley, MK, Shah, Z, Abramzon, Y, Hernandez, DG, Blauwendraat, C, Stone, DJ, Eicher, J, Parkkinen, L, Ansorge, O, Clark, L, Honig, LS, Marder, K, Lemstra, A, St George-Hyslop, P, Londos, E, Morgan, K, Lashley, T, Warner, TT, Jaunmuktane, Z, Galasko, D, Santana, I, Tienari, PJ, Myllykangas, L, Oinas, M, Cairns, NJ, Morris, JC, Halliday, GM, Van Deerlin, VM, Trojanowski, JQ, Grassano, M, Calvo, A, Mora, G, Canosa, A, Floris, G, Bohannan, RC, Brett, F, Gan-Or, Z, Geiger, JT, Moore, A, May, P, Kruger, R, Goldstein, DS, Lopez, G, Tayebi, N, Sidransky, E, Norcliffe-Kaufmann, L, Palma, JA, Kaufmann, H, Shakkottai, VG, Perkins, M, Newell, KL, Gasser, T, Schulte, C, Landi, F, Salvi, E, Cusi, D, Masliah, E, Kim, RC, Caraway, CA, Monuki, ES, Brunetti, M, Dawson, TM, Rosenthal, LS, Albert, MS, Pletnikova, O, Troncoso, JC, Flanagan, ME, Mao, QW, Bigio, EH, Rodriguez-Rodriguez, E, Infante, J, Lage, C, Gonzalez-Aramburu, I, Sanchez-Juan, P, Ghetti, B, Keith, J, Black, SE, Masellis, M, Rogaeva, E, Duyckaerts, C, Brice, A, Lesage, S, Xiromerisiou, G, Barrett, MJ, Tilley, BS, Gentleman, S, Logroscino, G, Serrano, GE, Beach, TG, McKeith, IG, Thomas, AJ, Attems, J, Morris, CM, Palmer, L, Love, S, Troakes, C, Al-Sarraj, S, Hodges, AK, Aarsland, D, Klein, G, Kaiser, SM, Woltjer, R, Pastor, P, Bekris, LM, Leverenz, JB, Besser, LM, Kuzma, A, Renton, AE, Goate, A, Bennett, DA, Scherzer, CR, Morris, HR, Ferrari, R, Albani, D, Pickering-Brown, S, Faber, K, Kukull, WA, Morenas-Rodriguez, E, Lleo, A, Fortea, J, Alcolea, D, Clarimon, J, Nalls, MA, Ferrucci, L, Resnick, SM, Tanaka, T, Foroud, TM, Graff-Radford, NR, Wszolek, ZK, Ferman, T, Boeve, BF, Hardy, JA, Topol, EJ, Torkamani, A, Singleton, AB, Ryten, M, Dickson, DW, Chio, A, Ross, OA, Gibbs, JR, Dalgard, CL, Traynor, BJ, Scholz, SW, and Amer Genome Ctr

Subjects
hormones, hormone substitutes, and hormone antagonists
Abstract

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

Published
2021

43. Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries

Author

De Backer, Guy Jankowski, Piotr Kotseva, Kornelia and Mirrakhimov, Erkin Reiner, Zeljko Ryden, Lars Tokgozoglu, Lale Wood, David De Bacquer, Dirk Abreu, A. Aguiar, C. and Badariene, J. Bruthans, J. Castro Conde, A. Cifkova, R. and Crowley, J. Davletov, K. De Smedt, D. De Sutter, J. and Deckers, J. W. Dilic, M. Dolzhenko, M. Druais, H. and Dzerve, V. Erglis, A. Fras, Z. Gaita, D. Gotcheva, N. and Grobbee, D. E. Gyberg, V. Ali, H. Hasan Heuschmann, P. and Hoes, A. W. Lalic, N. Lehto, S. Lovic, D. Maggioni, A. P. Mancas, S. Marques-Vidal, P. Mellbin, L. Milicic, D. Oganov, R. Pogosova, N. Stagmo, M. Stoerk, S. and Sundvall, J. Tsioufis, K. Vulic, D. Wood, D. A. and Jennings, C. Adamska, A. Adamska, S. Mellbin, L. and Tuomilehto, J. Schnell, O. Fiorucci, E. Glemot, M. and Larras, F. Missiamenou, V. Maggioni, A. Taylor, C. and Ferreira, T. Lemaitre, K. Raman, L. Sundvall, J. and DeSmedt, D. De Sutter, J. Willems, A. M. De Pauw, M. and Vervaet, P. Bollen, J. Dekimpe, E. Mommen, N. Van Genechten, G. Dendale, P. Bouvier, C. A. Chenu, P. and Huyberechts, D. Persu, A. Dilic, M. Begic, A. Nalbantic, A. Durak Dzubur, A. Hadzibegic, N. Iglica, A. Kapidjic, S. Bico, A. Osmanagic Resic, N. Bajramovic, N. Sabanovic and Zvizdic, F. Vulic, D. Kovacevic-Preradovic, T. and Popovic-Pejicic, S. Djekic, D. Gnjatic, T. Knezevic, T. and Kovacevic-Preradovic, T. Kos, Lj Popovic-Pejicic, S. and Stanetic, B. Topic, G. Gotcheva, N. Georgiev, Borislav and Terziev, A. Vladimirov, G. Angelov, A. Kanazirev, B. and Nikolaeva, S. Tonkova, D. Vetkova, M. Milicic, D. and Bosnic, A. Dubravcic, M. Glavina, M. Mance, M. and Pavasovic, S. Samardzic, J. Batinic, T. Crljenko, K. and Delic-Brkljacic, D. Dula, K. Golubic, K. Klobucar, I. and Kordic, K. Kos, N. Nedic, M. Olujic, D. Sedinic, V. and Blazevic, T. Pasalic, A. Percic, M. Sikic, J. Bruthans, J. Cifkova, R. Hasplova, K. Sulc, P. Wohlfahrt, P. and Mayer, Jr., O. Cvicela, M. Filipovsky, J. Gelzinsky, J. and Hronova, M. Hasan-Ali, H. Bakery, S. Mosad, E. Hamed, H. B. Ibrahim, A. Elsharef, M. A. Kholef, E. F. Shehata, A. and Youssef, M. Elhefny, E. Farid, H. Moustafa, T. M. and Sobieh, M. S. Kabil, H. Abdelmordy, A. Lehto, S. and Kiljander, E. Kiljander, P. Koukkunen, H. Mustonen, J. and Cremer, C. Frantz, S. Haupt, A. Hofmann, U. Ludwig, K. and Melnyk, H. Noutsias, M. Karmann, W. Prondzinsky, R. and Herdeg, C. Hoevelborn, T. Daaboul, A. Geisler, T. and Keller, T. Sauerbrunn, D. Walz-Ayed, M. Ertl, G. Leyh, R. Stoerk, S. Heuschmann, P. Ehlert, T. Klocke, B. and Krapp, J. Ludwig, T. Kaes, J. Starke, C. Ungethuem, K. and Wagner, M. Wiedmann, S. Tsioufis, K. Tolis, P. and Vogiatzi, G. Sanidas, E. Tsakalis, K. Kanakakis, J. and Koutsoukis, A. Vasileiadis, K. Zarifis, J. Karvounis, C. and Crowley, J. Gibson, I. Houlihan, A. Kelly, C. O'Donnell, M. Bennati, M. Cosmi, F. Mariottoni, B. Morganti, M. and Cherubini, A. Di Lenarda, A. Radini, D. Ramani, F. and Francese, M. G. Gulizia, M. M. Pericone, D. Davletov, K. and Aigerim, K. Bekbolat, Z. Amirov, B. Assembekov, B. and Chernokurova, E. Ibragimova, F. Kodasbayev, A. Markova, A. and Asanbaev, A. Toktomamatov, U. Tursunbaev, M. Zakirov, U. and Abilova, S. Arapova, R. Bektasheva, E. Esenbekova, J. and Neronova, K. Asanbaev, A. Baigaziev, K. Toktomamatov, U. and Zakirov, U. Baitova, G. Zheenbekov, T. Erglis, A. and Andrejeva, T. Bajare, I. Kucika, G. Labuce, A. Putane, L. Stabulniece, M. Dzerve, V. Klavins, E. Sime, I. and Badariene, J. Gedvilaite, L. Peciuraite, D. Sileikiene, V. and Skiauteryte, E. Solovjova, S. Sidabraite, R. Briedis, K. and Ceponiene, I. Jurenas, M. Kersulis, J. Martinkute, G. and Vaitiekiene, A. Vasiljevaite, K. Veisaite, R. Plisiene, J. Siurkaite, V. Vaiciulis, Z. Czarnecka, D. Koziel, P. and Podolec, P. Nessler, J. Gomula, P. Mirek-Bryniarska, E. and Bogacki, P. Wisniewski, A. Pajak, A. Wolfshaut-Wolak, R. and Bucko, J. Kaminski, K. Lapinska, M. Paniczko, M. and Raczkowski, A. Sawicka, E. Stachurska, Z. Szpakowicz, M. and Musial, W. Dobrzycki, S. Bychowski, J. Kosior, D. A. and Krzykwa, A. Setny, M. Kosior, D. A. Rak, A. Gasior, Z. and Haberka, M. Gasior, Z. Haberka, M. Szostak-Janiak, K. and Finik, M. Liszka, J. Botelho, A. Cachulo, M. Sousa, J. Pais, A. Aguiar, C. Durazzo, A. Matos, D. and Gouveia, R. Rodrigues, G. Strong, C. Guerreiro, R. and Aguiar, J. Abreu, A. Cruz, M. Daniel, P. Morais, L. and Moreira, R. Rosa, S. Rodrigues, I. Selas, M. Gaita, D. and Mancas, S. Apostu, A. Cosor, O. Gaita, L. Giurgiu, L. Hudrea, C. Maximov, D. Moldovan, B. Mosteoru, S. and Pleava, R. Ionescu, M. Parepa, I. Pogosova, N. and Arutyunov, A. Ausheva, A. Isakova, S. Karpova, A. and Salbieva, A. Sokolova, O. Vasilevsky, A. Pozdnyakov, Y. and Antropova, O. Borisova, L. Osipova, I. Lovic, D. and Aleksic, M. Crnokrak, B. Djokic, J. Hinic, S. Vukasin, T. Zdravkovic, M. Lalic, N. M. Jotic, A. Lalic, K. and Lukic, L. Milicic, T. Macesic, M. Gajovic, J. Stanarcic and Stoiljkovic, M. Djordjevic, D. Kostic, S. Tasic, I. and Vukovic, A. Fras, Z. Jug, B. Juhant, A. Krt, A. and Kugonjic, U. Chipayo Gonzales, D. Gomez Barrado, J. J. and Kounka, Z. Marcos Gomez, G. Mogollon Jimenez, M. V. Ortiz Cortes, C. Perez Espejo, P. Porras Ramos, Y. Colman, R. and Delgado, J. Otero, E. Perez, A. Fernandez-Olmo, M. R. and Torres-LLergo, J. Vasco, C. Barrenada, E. Botas, J. and Campuzano, R. Gonzalez, Y. Rodrigo, M. de Pablo, C. and Velasco, E. Hernandez, S. Lozano, C. Gonzalez, P. and Castro, A. Dalmau, R. Hernandez, D. Irazusta, F. J. and Velez, A. Vindel, C. Gomez-Doblas, J. J. Garcia Ruiz, V. and Gomez, L. Gomez Garcia, M. Jimenez-Navarro, M. Molina Ramos, A. Marzal, D. Martinez, G. Lavado, R. Vidal, A. and Bostrom-Nilsson, V. Kjellstrom, B. Shahim, B. Smetana, S. and Hansen, O. Stensgaard-Nake, E. Deckers, J. W. Klijn, A. J. Mangus, T. J. P. Peters, R. J. G. Reimer, W. Scholte Op and Snaterse, M. Aydogdu, S. Erol, C. Oturk, S. Kaya, C. Tulunay Ahmetoglu, Y. Ergene, O. Akdeniz, B. Cirgamis, D. Kultursay, S. Akkoyun H. Kayikcioglu, M. Catakoglu, A. B. and Cengel, A. Kocak, A. A. Agirbasli, M. A. Aciksari, G. and Cekin, M. E. Kaya, E. B. Kocyigit, D. Ongen, Z. and Ozmen, E. Sansoy, V. Kaya, A. Oktay, V. Temizhan, A. and Unal, S. Yakut, I. Kalkan, A. K. Bozkurt, E. Kasapkara, H. A. Dolzhenko, M. Faradzh, C. Hrubyak, L. Konoplianyk, L. Kozhuharyova, N. Lobach, L. Nesukai, V. Nudchenko, O. and Simagina, T. Yakovenko, L. Azarenko, V. Potabashny, V. and Bazylevych, A. Bazylevych, M. Kaminska, K. Panchenko, L. and Shershnyova, O. Ovrakh, T. Serik, S. Kolesnik, T. and Kosova, H. Adamska, A. Adamska, S. Jennings, C. Atkin, A. Hoye P. Fellowes, D. Lindsay, S. Atkinson, C. and Kranilla, C. Vinod, M. Beerachee, Y. Bennett, C. Broome, M. Bwalya, A. Caygill, Lindsay Dinning, L. Gillespie, A. and Goodfellow, R. Guy, J. Idress, T. Mills, C. Morgan, C. Oustance, N. Singh, N. Yare, M. Jagoda, J. M. and Bowyer, H. Christenssen, V. Groves, A. Jan, A. Riaz, A. and Gill, M. Sewell, T. A. Gorog, D. Baker, M. De Sousa, P. Mazenenga, T. Porter, J. Haines, F. Peachey, T. and Taaffe, J. Wells, K. Ripley, D. P. Forward, H. McKie, H. and Pick, S. L. Thomas, H. E. Batin, P. D. Exley, D. and Rank, T. Wright, J. Kardos, A. Sutherland, S. -B. Wren, L. Leeson, P. Barker, D. Moreby, B. Sawyer, J. and Stirrup, J. Brunton, M. Brodison, A. Craig, J. Peters, S. Kaprielian, R. Bucaj, A. Mahay, K. Oblak, M. and Gale, C. Pye, M. McGill, Y. Redfearn, H. Fearnley, M. and EUROASPIRE V Collaborators Writing Comm Sci Steering Executive Comm Coordinating Ctr Diabet Ctr Data Management Ctr Stat Anal Ctr Cent Lab Study Ctr Org Investigators Other

Abstract

Background and aims: One of the objectives of the ESC-EORP EUROASPIRE V survey is to determine how well European guidelines on the management of dyslipidaemias are implemented in coronary patients. Methods: Standardized methods were used by trained technicians to collect information on 7824 patients from 130 centers in 27 countries, from the medical records and at a visit at least 6 months after hospitalization for a coronary event. All lipid measurements were performed in one central laboratory. Patients were divided into three groups: on high-intensity LDL-C-lowering-drug therapy (LLT), on low or moderate-intensity LLT and on no LLT. Results: At the time of the visit, almost half of the patients were on a high-intensity LLT. Between hospital discharge and the visit, LLT had been reduced in intensity or interrupted in 20.8% of the patients and had been started or increased in intensity in 11.7%. In those who had interrupted LLT or had reduced the intensity, intolerance to LLT and the advice of their physician were reported as the reason why in 15.8 and 36.8% of the cases, respectively. LDL-C control was better in those on a high-intensity LLT compared to those on low or moderate intensity LLT. LDL-C control was better in men than women and in patients with self-reported diabetes. Conclusions: The results of the EUROASPIRE V survey show that most coronary patients have a less than optimal management of LDL-C. More professional strategies are needed, aiming at lifestyle changes and LLT adapted to the need of the individual patient.

Published
2019

44. Protocol for a partially nested randomised controlled trial to evaluate the effectiveness of the scleroderma patient-centered intervention network COVID-19 home-isolation activities together (SPIN-CHAT) program to reduce anxiety among at-risk scleroderma patients

Author

Thombs, B.D., Kwakkenbos, L., Carrier, M.E., Bourgeault, A., Tao, L.D., Harb, S., Gagarine, M., Rice, D., Bustamante, L., Ellis, K., Duchek, D., Wu, Y., Bhandari, P.M., Neupane, D., Carboni-Jimenez, A., Henry, R.S., Krishnan, A., Sun, Y., Levis, B., He, C., Turner, K.A., Benedetti, A., Culos-Reed, N., El-Baalbaki, G., Hebblethwaite, S., Bartlett, S.J., Dyas, L., Patten, S., Varga, J., Fortune, C., Gietzen, A., Guillot, G., Lewis, N., Nielsen, K., Richard, M., Sauve, M., Welling, J., Baron, M., Furst, D.E., Gottesman, K., Malcarne, V., Mayes, M.D., Mouthon, L., Nielson, W.R., Riggs, R., Wigley, F., Assassi, S., Boutron, I., Ells, C., Ende, C. van den, Fligelstone, K., Frech, T., Godard, D., Harel, D., Hinchcliff, M., Hudson, M., Johnson, S.R., Larche, M., Leite, C., Nguyen, C., Pope, J., Portales, A., Rannou, F., Reyna, T.S.R., Schouffoer, A.A., Suarez-Almazor, M.E., Agard, C., Albert, A., Andre, M., Arsenault, G., Benzidia, I., Bernstein, E.J., Berthier, S., Bissonnette, L., Boire, G., Bruns, A., Carreira, P., Casadevall, M., Chaigne, B., Chung, L., Cohen, P., Correia, C., Dagenais, P., Denton, C., Domsic, R., Dubois, S., Dunne, J.V., Dunogue, B., Fare, R., Farge-Bancel, D., Fortin, P.R., Gill, A., Gordon, J., Granel-Rey, B., Gyger, G., Hachulla, E., Hatron, P.Y., Herrick, A.L., Hij, A., Hoa, S., Ikic, A., Jones, N., Fernandes, A.J.D., Kafaja, S., Khalidi, N., Lambert, M., Launay, D., Liang, P., Maillard, H., Maltez, N., Manning, J., Marie, I., Martin, M., Martin, T., Masetto, A., Maurier, F., Mekinian, A., Melchor, S., Nikpour, M., Olagne, L., Poindron, V., Proudman, S., Regent, A., Riviere, S., Robinson, D., Rodriguez, E., Roux, S., Smets, P., Smith, D., Sobanski, V., Spiera, R., Steen, V., Stevens, W., Sutton, E., Terrier, B., Thorne, C., Wilcox, P., Ayala, M.C., Ostbo, N., Scleroderma Patient-ctr Interventi, and SPIN Investigators

Subjects
Coronavirus, COVID-19, Systemic sclerosis, Mental health, Anxiety, RCT, Trial, Scleroderma
Abstract

Objective: Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction.Methods: The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score >= 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via video-conference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention.Ethics and dissemination: The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak.

Published
2020

45. How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? Experiences from the CENTER-TBI study

Author

CTR-TBI Investigators Participants, Timmers, Marjolein, van Dijck, Jeroen T. J. M., van Wijk, Roel P. J., Kompanje, Erwin J. O., Palotie, Aarno, Piippo-Karjalainen, Anna, Pirinen, Matti, Posti, Jussi P., Raj, Rahul, Tenovuo, Olli, Ripatti, Samuli, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, HUS Neurocenter, Neurokirurgian yksikkö, Helsinki Institute for Information Technology, Statistical and population genetics, Department of Mathematics and Statistics, Biostatistics Helsinki, Clinicum, Helsinki University Hospital Area, Department of Public Health, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, and University Management

Subjects
Health-care research, HARMONIZATION, health services administration, education, MULTICENTER, CENTER-TBI, Research ethic committees, European Union, 3111 Biomedicine, CARE, health care economics and organizations, humanities
Abstract

Background The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency. Methods We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. Results From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75-224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074). Conclusion We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.

Published
2020

46. Familial hypocalciuric hypercalcemia type 1 and autosomal-dominant hypocalcemia type 1: prevalence in a large healthcare population

Author

Dershem, Ridge, Gorvin, Caroline M, Metpally, Raghu PR, Krishnamurthy, Sarathbabu, Smelser, Diane T, Hannan, Fadil M, Carey, David J, Thakker, Rajesh V, Breitwieser, Gerda E, and Ctr, Regeneron Genetics

Subjects
0301 basic medicine, Male, Disease, Cohort Studies, 0302 clinical medicine, Sequence Kernel Association Test, Prevalence, Missense mutation, Genetics (clinical), Genes, Dominant, Genetics, Aged, 80 and over, education.field_of_study, Middle Aged, Phenotype, disease associations, familial hypocalciuric hypercalcemia type 1, Female, Calcium-sensing receptor, Adult, Heterozygote, Population, 030209 endocrinology & metabolism, Article, Frameshift mutation, 03 medical and health sciences, disease prevalence, medicine, genomics, Humans, education, Aged, Familial hypocalciuric hypercalcemia, business.industry, serum calcium, medicine.disease, SKAT, United States, calcium sensing receptor, 030104 developmental biology, Hypoparathyroidism, autosomal-dominant hypocalcemia type 1, Mutation, Hypercalcemia, Calcium, business, Delivery of Health Care, Receptors, Calcium-Sensing, Primary hyperparathyroidism
Abstract

The calcium-sensing receptor (CaSR) regulates serum calcium concentrations. CASR loss- or gain-of-function mutations cause familial hypocalciuric hypercalcemia type 1 (FHH1) or autosomal-dominant hypocalcemia type 1 (ADH1), respectively, but the population prevalence of FHH1 or ADH1 is unknown. Rare CASR variants were identified in whole-exome sequences from 51,289 de-identified individuals in the DiscovEHR cohort derived from a single US healthcare system. We integrated bioinformatics pathogenicity triage, mean serum Ca concentrations, and mode of inheritance to identify potential FHH1 or ADH1 variants, and we used a Sequence Kernel Association Test (SKAT) to identify rare variant-associated diseases. We identified predicted heterozygous loss-of-function CASR variants (6 different nonsense/frameshift variants and 12 different missense variants) in 38 unrelated individuals, 21 of whom were hypercalcemic. Missense CASR variants were identified in two unrelated hypocalcemic individuals. Functional studies showed that all hypercalcemia-associated missense variants impaired heterologous expression, plasma membrane targeting, and/or signaling, whereas hypocalcemia-associated missense variants increased expression, plasma membrane targeting, and/or signaling. Thus, 38 individuals with a genetic diagnosis of FHH1 and two individuals with a genetic diagnosis of ADH1 were identified in the 51,289 cohort, giving a prevalence in this population of 74.1 per 100,000 for FHH1 and 3.9 per 100,000 for ADH1. SKAT combining all nonsense, frameshift, and missense loss-of-function variants revealed associations with cardiovascular, neurological, and other diseases. In conclusion, FHH1 is a common cause of hypercalcemia, with prevalence similar to that of primary hyperparathyroidism, and is associated with altered disease risks, whereas ADH1 is a major cause of non-surgical hypoparathyroidism.

Published
2020

47. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Author

Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjornsson, Gardar, Fatemifar, Ghazaleh, Hedman, Asa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Arnlov, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Doerr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engstrom, Gunnar, Esko, Tonu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Gudbjartsson, Daniel F, Gutmann, Rebecca, Haggerty, Christopher M, van der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Kober, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, Maerz, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, Stott, David J, Svensson, Per, Tammesoo, Mari-Liis, Taylor, Kent D, Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tyl, Benoit, Uitterlinden, Andre G, Veluchamy, Abirami, Voelker, Uwe, Voors, Adriaan A, Wang, Xiaosong, Wareham, Nicholas J, Waterworth, Dawn, Weeke, Peter E, Weiss, Raul, Wiggins, Kerri L, Xing, Heming, Yerges-Armstrong, Laura M, Yu, Bing, Zannad, Faiez, Zhao, Jing Hua, Hemingway, Harry, Samani, Nilesh J, McMurray, John JV, Yang, Jian, Visscher, Peter M, Newton-Cheh, Christopher, Malarstig, Anders, Holm, Hilma, Lubitz, Steven A, Sattar, Naveed, Holmes, Michael V, Cappola, Thomas P, Asselbergs, Folkert W, Hingorani, Aroon D, Kuchenbaecker, Karoline, Ellinor, Patrick T, Lang, Chim C, Stefansson, Kari, Smith, J Gustav, Vasan, Ramachandran S, Swerdlow, Daniel I, Lumbers, R Thomas, Abecasis, Goncalo, Backman, Joshua, Bai, Xiaodong, Balasubramanian, Suganthi, Banerjee, Nilanjana, Baras, Aris, Barnard, Leland, Beechert, Christina, Blumenfeld, Andrew, Cantor, Michael, Chai, Yating, Coppola, Giovanni, Damask, Amy, Dewey, Frederick, Economides, Aris, Eom, Gisu, Forsythe, Caitlin, Fuller, Erin D, Gu, Zhenhua, Gurski, Lauren, Guzzardo, Paloma M, Habegger, Lukas, Hahn, Young, Hawes, Alicia, van Hout, Cristopher, Jones, Marcus B, Khalid, Shareef, Lattari, Michael, Li, Alexander, Lin, Nan, Liu, Daren, Lopez, Alexander, Manoochehri, Kia, Marchini, Jonathan, Marcketta, Anthony, Maxwell, Evan K, McCarthy, Shane, Mitnaul, Lyndon J, O'Dushlaine, Colm, Overton, John D, Padilla, Maria Sotiropoulos, Paulding, Charles, Penn, John, Pradhan, Manasi, Reid, Jeffrey G, Schleicher, Thomas D, Schurmann, Claudia, Shuldiner, Alan, Staples, Jeffrey C, Sun, Dylan, Toledo, Karina, Ulloa, Ricardo H, Widom, Louis, Wolf, Sarah E, Yadav, Ashish, Ye, Bin, Ctr, Regeneron Genetics, Shah, Sonia [0000-0001-5860-4526], Henry, Albert [0000-0001-7422-2288], Roselli, Carolina [0000-0001-5267-6756], Lin, Honghuang [0000-0003-3043-3942], Chaffin, Mark D. [0000-0002-1234-5562], Helgadottir, Anna [0000-0002-1806-2467], Verweij, Niek [0000-0002-4303-7685], Almgren, Peter [0000-0002-0473-0241], Chen, Xu [0000-0002-7299-3238], Ghanbari, Mohsen [0000-0002-9476-7143], Giedraitis, Vilmantas [0000-0003-3423-2021], Gross, Stefan [0000-0003-4121-7161], Guðbjartsson, Daníel F. [0000-0002-5222-9857], Hyde, Craig L. [0000-0002-6939-287X], Ingelsson, Erik [0000-0003-2256-6972], Jukema, J. Wouter [0000-0002-3246-8359], Kleber, Marcus E. [0000-0003-0663-7275], Koekemoer, Andrea [0000-0001-8222-3547], Langenberg, Claudia [0000-0002-5017-7344], Lindgren, Cecilia M. [0000-0002-4903-9374], Lovering, Ruth C. [0000-0002-9791-0064], Luan, Jian’an [0000-0003-3137-6337], Magnusson, Patrik [0000-0002-7315-7899], Mahajan, Anubha [0000-0001-5585-3420], Mordi, Ify R. [0000-0002-2686-729X], Morris, Andrew D. [0000-0002-1766-0473], Nagle, Michael W. [0000-0002-4677-7582], Nelson, Christopher P. [0000-0001-8025-2897], Palmer, Colin N. A. [0000-0002-6415-6560], Rice, Kenneth M. [0000-0002-3071-7278], Rotter, Jerome I. [0000-0001-7191-1723], Salomaa, Veikko [0000-0001-7563-5324], van Setten, Jessica [0000-0002-4934-7510], Svensson, Per [0000-0003-0372-6272], Taylor, Kent D. [0000-0002-2756-4370], Teder-Laving, Maris [0000-0002-5872-1850], Teumer, Alexander [0000-0002-8309-094X], Tyl, Benoit [0000-0001-5297-8412], Uitterlinden, Andre G. [0000-0002-7276-3387], Völker, Uwe [0000-0002-5689-3448], Wiggins, Kerri L. [0000-0003-2749-1279], Hemingway, Harry [0000-0003-2279-0624], Yang, Jian [0000-0003-2001-2474], Visscher, Peter M. [0000-0002-2143-8760], Lubitz, Steven A. [0000-0002-9599-4866], Sattar, Naveed [0000-0002-1604-2593], Cappola, Thomas P. [0000-0002-9630-7204], Asselbergs, Folkert W. [0000-0002-1692-8669], Kuchenbaecker, Karoline [0000-0001-9726-603X], Ellinor, Patrick T. [0000-0002-2067-0533], Vasan, Ramachandran S. [0000-0001-7357-5970], Lumbers, R. Thomas [0000-0002-9077-4741], Apollo - University of Cambridge Repository, Chaffin, Mark D [0000-0002-1234-5562], Guðbjartsson, Daníel F [0000-0002-5222-9857], Hyde, Craig L [0000-0002-6939-287X], Jukema, J Wouter [0000-0002-3246-8359], Kleber, Marcus E [0000-0003-0663-7275], Lindgren, Cecilia M [0000-0002-4903-9374], Lovering, Ruth C [0000-0002-9791-0064], Luan, Jian'an [0000-0003-3137-6337], Mordi, Ify R [0000-0002-2686-729X], Morris, Andrew D [0000-0002-1766-0473], Nagle, Michael W [0000-0002-4677-7582], Nelson, Christopher P [0000-0001-8025-2897], Palmer, Colin NA [0000-0002-6415-6560], Rice, Kenneth M [0000-0002-3071-7278], Rotter, Jerome I [0000-0001-7191-1723], Taylor, Kent D [0000-0002-2756-4370], Uitterlinden, Andre G [0000-0002-7276-3387], Wiggins, Kerri L [0000-0003-2749-1279], Visscher, Peter M [0000-0002-2143-8760], Lubitz, Steven A [0000-0002-9599-4866], Cappola, Thomas P [0000-0002-9630-7204], Asselbergs, Folkert W [0000-0002-1692-8669], Ellinor, Patrick T [0000-0002-2067-0533], Vasan, Ramachandran S [0000-0001-7357-5970], Lumbers, R Thomas [0000-0002-9077-4741], Palmer, Colin N A [0000-0002-6415-6560], Cardiovascular Centre (CVC), University of Queensland [Brisbane], University College of London [London] (UCL), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University Medical Center Groningen [Groningen] (UMCG), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Framingham Heart Study, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), deCODE genetics [Reykjavik], Karolinska Institutet [Stockholm], Pfizer, University of Pennsylvania [Philadelphia], University of Groningen [Groningen], Imperial College London, Lund University [Lund], Herlev and Gentofte Hospital, Massachusetts General Hospital [Boston], Department of Neurobiology, Care Sciences and Society [Stockholm, Sweden] (Division of Family Medicine), Dalarna University, Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, Department of Biostatistics, University of Washington [Seattle], Emory University School of Medicine, Emory University [Atlanta, GA], The University of Texas Medical School at Houston, Department of Molecular and Functional Genomics, Geisinger, Danville, PA, Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY, Novartis Institutes for BioMedical Research (NIBR), University of Liverpool, Universität Heidelberg [Heidelberg], Medizinische Fakultät Mannheim, The Alan Turing Institute, Ninewells Hospital and Medical School [Dundee], Universität Greifswald - University of Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Minnesota System, Regeneron Pharmaceuticals [Tarrytown], Department of Clinical Sciences, Cardiovascular Epidemiology, Skane University Hospital [Lund], Institute of Genomics [Tartu, Estonia], University of Tartu, Robertson Centre for Biostatistics, University of Glasgow, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Uppsala University, Brigham & Women’s Hospital [Boston] (BWH), University of Maryland School of Medicine, University of Maryland System, School of Science and Engineering (Reykjavik University), Carver College of Medicine, University of Iowa, Geisinger Health System [Danville, PA, USA], Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford Cardiovascular Institute, Uppsala Universitet [Uppsala], Leiden University Medical Center (LUMC), Einthoven Laboratory for Experimental Vascular Medicine (ELEVM - LEIDEN), Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Glenfield Hospital, University Hospitals Leicester, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Big Data Institute, University of Oxford [Oxford], University of Iowa [Iowa City], The Wellcome Trust Centre for Human Genetics [Oxford], Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Medical University Graz, Skane University Hospital [Malmo], Vanderbilt University School of Medicine [Nashville], University of Edinburgh, Université médicale de Vienne, Autriche, National Institute for Health and Welfare [Helsinki], University of Turku, Birmingham Women's and Children's NHS Foundation Trust, Kaiser Permanente, Harbor UCLA Medical Center [Torrance, Ca.], Los Angeles Biomedical Research Institute (LA BioMed), University Medical Center [Utrecht], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Seattle Epidemiologic Research and Information Center [Seattle], Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Department of Cardiology, Södersjukhuset, Stockholm, Estonian Genome and Medicine, Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], Aalborg University [Denmark] (AAU), Institut de Recherches SERVIER (IRS), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, GlaxoSmithKline, Glaxo Smith Kline, Northeastern Ohio Medical University (NEOMED), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Department of Cardiovascular Sciences [Leicester], University of Leicester, Queensland Brain Institute, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, University of Dundee, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Atherosclerosis Risk in Communities Study (ARIC)The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC- 55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694 and RC2 HL102419, National Human Genome Research Institute contract U01HG004402, and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT- CHF)This project was funded by a grant from the European Commission (FP7‐242209‐ BIOSTAT‐CHF, EudraCT 2010–020808–29). Cardiovascular Health Study (CHS) This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, HHSN268200960009C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and U01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. deCODE Heart Failure Study (deCODE) We at deCODE thank the women and men of Iceland that have participated in our studies and our colleagues that contributed to data collection and processing. DiscovEHR We acknowledge and thank all participants in Geisinger’s MyCode Community Health Initiative for their support and permission to use their health and genomic information in the DiscovEHR collaboration. This work was supported by the Regeneron Genetics Center and Geisinger. Estonian Genome Center at the University of Tartu (EGCUT) This study was supported by Estonian Research Council Grant IUT20-60, EU, H2020 grant 692145, European Union through the European Regional Development Fund (Project No. 2014-2020.4.01.15-0012) GENTRANSMED. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) The EPHESUS was supported by Pfizer, Inc. The European Prospective Investigation of Cancer, Norfolk study (EPIC-Norfolk) The EPIC-Norfolk Study is supported by programme grants from the Medical Research Council UK (G1000143) and Cancer Research UK (C864/A14136) and with additional support from the European Union, Stroke Association, British Heart Foundation, Research into Ageing, Department of Health, The Wellcome Trust and the Food Standards Agency. NJW and CL also acknowledge support from the Medical Research Council, UK (MC_UU_12015/1, MC_PC_13048). We thank all EPIC participants and staff for their contribution to the study, and thank staff from the Technical, Field Epidemiology and Data Functional Group Teams of the Medical Research Council Epidemiology Unit in Cambridge, UK, for carrying out sample preparation, DNA provision and quality control, genotyping and data handling work. Framingham Heart Study (FHS) This work was conducted using data and resources from the Framingham Heart Study (FHS) of the National Heart Lung and Blood Institute and Boston University School of Medicine. The study was supported by the National Heart, Lung and Blood Institute’s Framingham Heart Study (Contract No. N01-HC-25195 and HHSN268201500001I) and its contract with Affymetrix, Inc for genotyping services (Contract No.N02-HL-6-4278). The work was also supported by R01 HL093328, R01 HL105993, and R01 HL71039 (PI: Ramachandran). FINRISK V.S. has been supported by the Finnish Foundation for Cardiovascular Research. Genetics of Diabetes Audit and Research Tayside Scotland GoDARTS) The Wellcome Trust United Kingdom Type 2 Diabetes Case Control Collection (supporting GoDARTS) was funded by the Wellcome Trust (072960/Z/03/Z, 084726/Z/08/Z, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z) and as part of the EU IMI-SUMMIT programme. We acknowledge the support of the Health Informatics Centre, University of Dundee, for managing and supplying the anonymized data and NHS Tayside, the original data owner. The Genetic Risk Assessment of Defibrillator Events (GRADE) NIH-NHLBI R01 HL77398 (Genetic Modulators of Sudden Death). S.L. is supported by NIH grant 1R01HL139731 and American Heart Association 18SFRN34250007. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study We extend our appreciation to the participants of the LURIC study, without their collaboration, this article would not have been written. We thank the LURIC study team who were either temporarily or permanently involved in patient recruitment as well as sample and data handling, in addition to the laboratory staff at the Ludwigshafen General Hospital and the Universities of Freiburg and Ulm, Germany. LURIC has received funding from the 7th Framework Program (RiskyCAD, grant agreement number 305739 and Atheroremo, grant agreement number 201668) of the European Union. Malmö Diet and Cancer Study (MDCS) J. Gustav Smith was supported by grants from the Swedish Heart-Lung Foundation (2016- 0134 and 2016-0315), the Swedish Research Council (2017-02554), the European Research Council (ERC-STG-2015-679242), the Crafoord Foundation, Skåne University Hospital, the Scania county, governmental funding of clinical research within the Swedish National Health Service, a generous donation from the Knut and Alice Wallenberg foundation to the Wallenberg Center for Molecular Medicine in Lund, and funding from the Swedish Research Council (Linnaeus grant Dnr 349-2006-237, Strategic Research Area Exodiab Dnr 2009-1039) and Swedish Foundation for Strategic Research (Dnr IRC15- 0067) to the Lund University Diabetes Center. The Malmo Diet and Cancer Study was made possible by grants from the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, and the Malmo city council. Penn Heart Failure Study (PHFS) The study was supported by NIH grants (NIH R01L088577 and NIH R01H105993). Prevention of REnal and Vascular ENd-stage Disease (PREVEND) The Prevention of Renal and Vascular Endstage Disease Study (PREVEND) genetics is supported by the Dutch Kidney Foundation (Grant E033), the EU project grant GENECURE (FP-6 LSHM CT 2006 037697), the National Institutes of Health (grant LM010098), the Netherlands organisation for health research and development (NWO VENI grant 916.761.70), and the Dutch Inter University Cardiology Institute Netherlands (ICIN). Niek Verweij was supported by NWO VENI grant 016.186.125. PROspective Study of Pravastatin in the Elderly at Risk for vascular disease (PROSPER)The PROSPER study was supported by an investigator-initiated grant obtained from Bristol- Myers Squibb. Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). J.W.J. is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Study of Health in Pomerania (SHIP) SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID)SOLID-TIMI 52 was funded by GlaxoSmithKline. TwinGene (TwinGene) TwinGene received funding from the Swedish Research Council (M-2005-1112), GenomEUtwin (EU/QLRT-2001-01254, QLG2-CT-2002-01254), NIH DK U01-066134, The Swedish Foundation for Strategic Research (SSF) and the Heart and Lung foundation no. 20070481. TwinGene is part of the Swedish Twin Registry which is managed by Karolinska Institutet and receives funding through the Swedish Research Council (2017–00641). UK Biobank (UKBiobank) This research has been conducted using the UK Biobank Resource under Application Number 15422. This work was supported in part by grants to R.T.L. from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant no. 116074, MRC Proximity to Discovery Award Scheme, the American Heart Association Institute for Precision Mecidine, Pfizer Ltd, the University College London British Heart Foundation Research Accelerator (AA/18/6/34223), and was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A. H. is supported by the British Heart Foundation Cardiovascular Biomedicine PhD studentship. R.T.L is supported by a UK Research and Innovation Rutherford Fellowship and was previously supported by a National Institutes of Health Research Clinical Lectureship. Uppsala Longitudinal Study of Adult Men (ULSAM) J.Ä. is supported by the Swedish Research Council and the Swedish Heart Lung foundation. C.M.L is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford, by Widenlife and NIH (5P50HD028138- 27). Women’s Genome Health Study (WGHS) The WGHS is supported by the National Heart, Lung, and Blood Institute (HL043851 and HL080467, HL099355) and the National Cancer Institute (CA047988 and UM1CA182913), with collaborative scientific support and funding for genotyping provided by Amgen., Epidemiology, Internal Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland

Subjects
0301 basic medicine, Dánartíðni, Epidemiology, LOCI, 45/43, General Physics and Astronomy, Muscle Proteins, Genome-wide association study, Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Bioinformatics, Genome-wide association studies, DISEASE, Ventricular Function, Left, Coronary artery disease, 0302 clinical medicine, Risk Factors, Atrial Fibrillation, IMPUTATION, Medicine, Blóðrásarsjúkdómar, 692/308/174, lcsh:Science, 2. Zero hunger, RISK, Multidisciplinary, Microfilament Proteins, article, Atrial fibrillation, Mendelian Randomization Analysis, CATALOG, 3. Good health, OBESITY, Erfðarannsóknir, Cardiomyopathies, Medical Genetics, Cyclin-Dependent Kinase Inhibitor p21, Science, 631/208/205/2138, Heart failure, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 631/443/592/2727, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, RESOURCE, Humans, Mortality, METAANALYSIS, Genetic association, Medicinsk genetik, Adaptor Proteins, Signal Transducing, Heart Failure, HYPERTENSION, business.industry, Case-control study, Klinisk medicin, 692/699/75/230, General Chemistry, Cardiovascular genetics, medicine.disease, R1, 030104 developmental biology, Case-Control Studies, lcsh:Q, Morbidity, Clinical Medicine, business, Apoptosis Regulatory Proteins, Carrier Proteins, Genome-Wide Association Study
Abstract

Publisher's version (útgefin grein), Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies., We acknowledge the contribution from the EchoGen Consortium.

Published
2020

48. Superior Long-term Survival for Simultaneous Pancreas-Kidney Transplantation as Renal Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort

Author

Esmeijer, K., Hoogeveen, E.K., Boog, P.J.M. van den, Konijn, C., Mallat, M.J.K., Baranski, A.G., Dekkers, O.M., Fijter, J.W. de, and Dutch Transplant Ctr

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Urology, 030209 endocrinology & metabolism, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Diabetes mellitus, Internal Medicine, medicine, Humans, Diabetic Nephropathies, 030212 general & internal medicine, Renal replacement therapy, Survivors, Survival analysis, Kidney transplantation, Dialysis, Aged, Netherlands, Advanced and Specialized Nursing, business.industry, Mortality rate, Hazard ratio, Graft Survival, Middle Aged, medicine.disease, Combined Modality Therapy, Kidney Transplantation, Survival Analysis, Transplantation, Diabetes Mellitus, Type 1, Kidney Failure, Chronic, Female, Pancreas Transplantation, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, Follow-Up Studies
Abstract

OBJECTIVE In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients. RESEARCH DESIGN AND METHODS We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016. We used multivariable Cox regression analyses adjusted for recipient age and sex, dialysis modality and vintage, transplantation era, and donor age to compare all-cause mortality between deceased- or living-donor kidney and SPK transplant recipients. Separately, we analyzed mortality between regions where SPK transplant was the preferred intervention (80% SPK) versus regions where a kidney transplant alone was favored (30% SPK). RESULTS Of 996 transplanted patients, 42%, 16%, and 42% received a deceased- or living-donor kidney or SPK transplant, respectively. Mean (SD) age at transplantation was 50 (11), 48 (11), and 42 (8) years, respectively. Median (95% CI) survival time was 7.3 (6.2; 8.3), 10.5 (7.2; 13.7), and 16.5 (15.1; 17.9) years, respectively. SPK recipients with a functioning pancreas graft at 1 year (91%) had the highest survival (median 17.4 years). Compared with deceased-donor kidney transplant recipients, adjusted hazard ratios (95% CI) for 10- and 20-year all-cause mortality were 0.79 (0.49; 1.29) and 0.98 (0.69; 1.39) for living-donor kidney and 0.67 (0.46; 0.98) and 0.79 (0.60; 1.05) for SPK recipients, respectively. A treatment strategy favoring SPK over kidney transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 (0.40; 0.78) and 0.69 (0.52; 0.90), respectively. CONCLUSIONS Compared with living- or deceased-donor kidney transplantation, SPK transplant was associated with improved patient survival, especially in recipients with a long-term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mortality rate.

Published
2020

49. 5-fluorouracil decreases rates of persistent and reappearing actinic keratoses: The VAKCC Trial

Author

Moniyka Sachar and Moniyka Sachar1, Julia A Siegel1, Joanna L Walker1, Susan M Swetter2, George Stricklin3, Martin A Weinstock1, For The VAKCC Trial Group 1 VA Med Ctr, Brown Univ, Providence, RI 2 VA Healthcare Syst, Palo Alto, CA 3 VA Healthcare Syst, Nashville, TN

Abstract

Moniyka Sachar1, Julia A Siegel1, Joanna L Walker1, Susan M Swetter2, George Stricklin3, Martin A Weinstock1, for the VAKCC Trial Group 1 VA Med Ctr, Brown Univ, Providence, RI2 VA Healthcare Syst, Palo Alto, CA3 VA Healthcare Syst, Nashville, TN Keratinocyte carcinoma (KC) is the most common cancer in the United States, with over 5 million cases treated annually. KC treatment is associated with the potential for substantial morbidity as well as significant costs, estimated at $4.8 billion per year from 2007 to 2011. Actinic keratoses (AKs) are known precursors to squamous cell carcinoma (SCC) and therefore may be a target for KC prevention. Topical 5-fluoruracil (5-FU) has been shown to reduce AK count, but its role as AK prophylaxis (vs. treatment) is unclear. In this double-blind, placebo-controlled trial, veterans with two or more prior KCs were randomized to apply topical 5-FU or vehicle control cream to the face and ears twice daily for up to 4 weeks. Complete skin exams were performed by study dermatologists at enrollment and every 6 months, and clinically diagnosed AKs were marked, photographed, and later used to track AKs over time. This allowed distinction between new AKs and persistent AKs. Among participants in the placebo group who had had no AK treatments with cryotherapy on the face and ears from baseline to 6 months (n=161), only 15% (174/1160) of AKs persisted from baseline to 6 months, demonstrating a high rate of spontaneous regression. In the subset of the treatment group who had also not received cryotherapy on the face and ears during this time (n=152), only 5% (59/1177) of AKs persisted from baseline to 6 months—one third of the placebo group. At 6 months, the mean number of persistent AKs per subject was 1.09 in the placebo group and 0.39 in the treatment group (p

Published
2020
Full Text
View/download PDF

50. Building a disaster behavioral health response to a radiological nuclear disaster

Author

Ashley Pearson, Bs, Mpa, Cbcp, Ctr and Cts Elena Cherepanov

Subjects
business.industry, General Medicine, Public relations, Public opinion, Multidisciplinary approach, Radiological weapon, Political science, Environmental health, Preparedness, Health care, Emergency Medicine, Nuclear disaster, Safety, Risk, Reliability and Quality, business, Safety Research, Psychosocial, Inclusion (education)
Abstract

The analysis of psychological reactions to the past nuclear plants disasters, such as Three Mile Island, Pennsylvania (1979), Chernobyl, Ukraine (1986), and Fukushima, Japan (2011), allows for a development of adequate preparedness and response protocols. The systemic, long-term, and future-oriented impact of radionuclear-type event calls for inclusion of the behavioral health module into comprehensive and multidisciplinary disaster response planning. It is important to incorporate the psychosocial education and focused trainings for responders, public officials, healthcare workers, teachers, and spiritual leaders into established systems of readiness on local, state, and federal levels. Inaccurate or misleading information perpetuates misconceptions and contributes to further victimization of survivors. Building strong partnerships with media can assist in supporting the survivors, gathering testimonies, and mobilizing aid resources by bringing public attention to the problem and shaping public opinion.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results