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  1. Article ; Online: Assessment of epinephrine efficacy in out-of-hospital cardiac arrest.

    Bonzi, Mattia / Peta, Jacopo / Fusco, Alessandra / Bosco, Paola

    Internal and emergency medicine

    2019  Volume 14, Issue 7, Page(s) 1155–1157

    MeSH term(s) Cardiopulmonary Resuscitation ; Epinephrine ; Humans ; Out-of-Hospital Cardiac Arrest
    Chemical Substances Epinephrine (YKH834O4BH)
    Language English
    Publishing date 2019-08-07
    Publishing country Italy
    Document type Journal Article ; Comment
    ZDB-ID 2454173-4
    ISSN 1970-9366 ; 1828-0447
    ISSN (online) 1970-9366
    ISSN 1828-0447
    DOI 10.1007/s11739-019-02158-5
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  2. Article ; Online: La predizione del ricovero ospedaliero in triage:<br> strumenti e metodi di valutazione a confronto.<br>Revisione sistematica.

    Salvato, Mauro / Binda, Filippo / Iotti, Marco / Bosco, Paola / Laquintana, Dario

    Assistenza infermieristica e ricerca : AIR

    2020  Volume 39, Issue 3, Page(s) 139–146

    Abstract: The prediction fo Hospitalization in triage: a comparison of instruments and methods of evaluation. A systematic revision.: Introduction: Overcrowding in the emergency department causes called-boarding, in addition to the increase of the waiting ... ...

    Title translation The prediction of hospitalization in triage: a comparison of instruments and methods of evaluation. A systematic revision.
    Abstract . The prediction fo Hospitalization in triage: a comparison of instruments and methods of evaluation. A systematic revision.
    Introduction: Overcrowding in the emergency department causes called-boarding, in addition to the increase of the waiting times, high costs and unsatisfied patients. Boarded patients are those admitted to an inpatient unit in the hospital that continue to wait in the emergency department for a bed to become available. The adoption of tools and methods to help the clinician to predict the admission in the triage phase could significantly improve patients flow.
    Aim: To analyze and compare different tools and methods and to predict the hospitalization in the triage phase for adult patients.
    Methods: A systematic review was conducted by querying the PubMed and Cochrane databases, limited to the last 10 years articles.
    Results: Ten longitudinal observational studies analyzed the variables associated with admission, predictive ability of the clinical judgment of the triage nurse, predictive ability of validated objective scores, and cross compared the various methods of predicting admission. The variable most associated with admission was advanced age; both the clinical judgment of the triage nurse and the various scores showed a good predictive ability; the association of the clinical judgment of the triage nurse with one of the scores would offer more accurate predictions.
    Discussion: The ability to predict admission in the triage, through the use of validated scores and the clinical judgment of the triage nurse, could be the first step to reduce the boarding phenomenon and to improve the flow in the emergency department.
    MeSH term(s) Adult ; Emergency Service, Hospital/organization & administration ; Hospitalization ; Humans ; Nurses/organization & administration ; Patient Admission ; Triage/methods
    Language Italian
    Publishing date 2020-10-19
    Publishing country Italy
    Document type Comparative Study ; Journal Article ; Systematic Review
    ZDB-ID 1480438-4
    ISSN 2038-1778 ; 1120-3803
    ISSN (online) 2038-1778
    ISSN 1120-3803
    DOI 10.1702/3454.34431
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  3. Article ; Online: Quality of dying in hospital general wards: a cross-sectional study about the end-of-life care.

    Binda, Filippo / Clari, Marco / Nicolò, Gabriella / Gambazza, Simone / Sappa, Barbara / Bosco, Paola / Laquintana, Dario

    BMC palliative care

    2021  Volume 20, Issue 1, Page(s) 153

    Abstract: Background: In the last decade, access to national palliative care programs have improved, however a large proportion of patients continued to die in hospital, particularly within internal medicine wards.: Objectives: To describe treatments, symptoms ...

    Abstract Background: In the last decade, access to national palliative care programs have improved, however a large proportion of patients continued to die in hospital, particularly within internal medicine wards.
    Objectives: To describe treatments, symptoms and clinical management of adult patients at the end of their life and explore whether these differ according to expectation of death.
    Methods: Single-centre cross-sectional study performed in the medical and surgical wards of a large tertiary-level university teaching hospital in the north of Italy. Data on nursing interventions and diagnostic procedure in proximity of death were collected after interviewing the nurse and the physician responsible for the patient. Relationship between nursing treatments delivered and patients' characteristics, quality of dying and nurses' expectation about death was summarized by means of multiple correspondence analysis (MCA).
    Results: Few treatments were found statistically associated with expectation of death in the 187 patients included. In the last 48 h, routine (70.6%) and biomarkers (41.7%) blood tests were performed, at higher extent on patients whose death was not expected. Many symptoms classified as severe were reported when death was highly expected, except for agitation and respiratory fatigue which were reported when death was moderately expected. A high Norton score and absence of anti-bedsore mattress were associated with unexpected death and poor quality of dying, as summarized by MCA. Quality of dying was perceived as good by nurses when death was moderately and highly expected. Physicians rated more frequently than nurses the quality of dying as good or very good, respectively 78.6 and 57.8%, denoting a fair agreement between the two professionals (k = 0.24, P <  0.001). The palliative care consultant was requested for only two patients.
    Conclusion: Staff in medical and surgical wards still deal inadequately with the needs of dying people. Presence of hospital-based specialist palliative care could lead to improvements in the patients' quality of life.
    MeSH term(s) Adult ; Cross-Sectional Studies ; Hospitals ; Humans ; Patients' Rooms ; Quality of Life ; Terminal Care
    Language English
    Publishing date 2021-10-12
    Publishing country England
    Document type Journal Article
    ISSN 1472-684X
    ISSN (online) 1472-684X
    DOI 10.1186/s12904-021-00862-8
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  4. Article: Pattern of Visits in a Metropolitan Emergency Department in Lombardia (Italy): January 2019-December 2020.

    Gambazza, Simone / Galazzi, Alessandro / Binda, Filippo / Passeri, Onorina / Bosco, Paola / Costantino, Giorgio / Laquintana, Dario

    Healthcare (Basel, Switzerland)

    2021  Volume 9, Issue 7

    Abstract: During the Coronavirus disease 2019 (COVID-19), a general decrease in the presentations to emergency departments (ED) was reported. However, we suspect that there was a lower number but an unchanged pattern of ED visits for urgent conditions in 2020 ... ...

    Abstract During the Coronavirus disease 2019 (COVID-19), a general decrease in the presentations to emergency departments (ED) was reported. However, we suspect that there was a lower number but an unchanged pattern of ED visits for urgent conditions in 2020 compared to 2019. This retrospective study assessed the change in the number of presentations in the ED of a tertiary level university hospital in Milano (Lombardia, Italy). Compared to 2019, a significant drop in ED presentations occurred (-46.4%), and we recorded a -15.7% difference in the proportion of patients admitted with white codes. The pattern of hourly presentations to the ED was unchanged, with overcrowding during the working daytime. COVID-19 changed ED flows, likely causing an overall reduction in the number of deferrable conditions. However, the pattern associated with urgent conditions did not change abruptly in 2020.
    Language English
    Publishing date 2021-06-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2721009-1
    ISSN 2227-9032
    ISSN 2227-9032
    DOI 10.3390/healthcare9070791
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  5. Article ; Online: Prospective comparison of AMB, GAP AND START scores and triage nurse clinical judgement for predicting admission from an ED: a single-centre prospective study.

    Salvato, Mauro / Solbiati, Monica / Bosco, Paola / Casazza, Giovanni / Binda, Filippo / Iotti, Marco / Calegari, Jessica / Laquintana, Dario / Costantino, Giorgio

    Emergency medicine journal : EMJ

    2021  Volume 39, Issue 12, Page(s) 897–902

    Abstract: Background: It is postulated that early determination of the need for admission can improve flow through EDs. There are several scoring systems which have been developed for predicting patient admission at triage, although they have not been directly ... ...

    Abstract Background: It is postulated that early determination of the need for admission can improve flow through EDs. There are several scoring systems which have been developed for predicting patient admission at triage, although they have not been directly compared. In addition, it is not known if these scoring systems perform better than clinical judgement. Therefore, the aim of this study was to validate existing tools in predicting hospital admission during triage and then compare them with the clinical judgement of triage nurses.
    Methods: To conduct this prospective, single-centre observational study, we enrolled consecutive adult patients who presented between 30 September 2019 and 25 October 2019 at the ED of a large teaching hospital in Milan, Italy. For each patient, triage nurses recorded all of the variables needed to perform Ambulatory (AMB), Glasgow Admission Prediction (GAP) and Sydney Triage to Admission Risk Tool (START) scoring. The probability of admission was estimated by the triage nurses using clinical judgement and expressed as a percentage from 0 to 100 with intervals of 5. Nurse estimates were dichotomised for analysis, with ≥50% likelihood being a prediction of admission. Receiver operating characteristic curves were generated for accuracy of the predictions. Area under the curve (AUC) with 95% CI for each of the scores and for the nursing judgements was also calculated.
    Results: A total of 1710 patients (844 men; median age, 54 years (IQR: 34-75)) and 35 nurses (15 men; median age, 37 years (IQR: 33-48)) were included in this study. Among these patients, 310 (18%) were admitted to hospital from the ED. AUC values for AMB, GAP and START scores were 0.77 (95% CI: 0.74 to 0.79), 0.72 (95% CI: 0.69 to 0.75) and 0.61 (95% CI: 0.58 to 0.64), respectively. The AUC for nurse clinical judgement was 0.86 (95% CI: 0.84 to 0.89).
    Conclusion: AMB, GAP and START scores provided moderate accuracy in predicting patient admission. However, all of the scores were significantly worse than the clinical judgement of the triage nurses.
    MeSH term(s) Adult ; Male ; Humans ; Middle Aged ; Triage ; Prospective Studies ; Clinical Reasoning ; Emergency Service, Hospital ; Patient Admission ; Risk Factors
    Language English
    Publishing date 2021-12-30
    Publishing country England
    Document type Observational Study ; Journal Article
    ZDB-ID 2040124-3
    ISSN 1472-0213 ; 1472-0205
    ISSN (online) 1472-0213
    ISSN 1472-0205
    DOI 10.1136/emermed-2020-210814
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  6. Article ; Online: Case management programs in emergency department to reduce frequent user visits: a systematic review.

    Di Mauro, Raffaele / Di Silvio, Valentina / Bosco, Paola / Laquintana, Dario / Galazzi, Alessandro

    Acta bio-medica : Atenei Parmensis

    2019  Volume 90, Issue 6-S, Page(s) 34–40

    Abstract: Background and aim: Inappropriate visits to the Emergency Department (ED) by frequent users (FU) are a common phenomenon because this service is perceived as a rapid and concrete answer to any health and social issue not necessarily related to urgent ... ...

    Abstract Background and aim: Inappropriate visits to the Emergency Department (ED) by frequent users (FU) are a common phenomenon because this service is perceived as a rapid and concrete answer to any health and social issue not necessarily related to urgent matters. Could Case Management (CM) programs be a suitable solution to address the problem? The purpose is to examine how CM programs are implemented to reduce the number of FU visits to the ED.
    Methods: PubMed, CINAHL and EMBASE were consulted up to December 2018. This review follows PRISMA guidelines for systematic review, as first outcomes were considered the impact of CM interventions on ED utilization, costs and composition of teams.
    Results: Fourteen studies were included and they showed patients with common characteristics but the FU definition wasn't the same. Twelve studies provided a reduction of ED utilization and seven studies a cost reduction. The main tool used is the individual care plan with telephone contact, supportive group therapy, facilitated contacts with healthcare providers and informatics system for immediate identification. The CM team composition is heterogeneous, even if nurses are considered the most used professional figures.
    Conclusions: In contrast with a standardized method, a customized approach of CM program helps frequent users in finding an appropriate answer to their needs, thus decreasing inappropriate visits to the ED.
    MeSH term(s) Adult ; Aged ; Case Management ; Emergency Service, Hospital/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged
    Language English
    Publishing date 2019-07-08
    Publishing country Italy
    Document type Journal Article ; Systematic Review
    ZDB-ID 2114240-3
    ISSN 2531-6745 ; 0392-4203
    ISSN (online) 2531-6745
    ISSN 0392-4203
    DOI 10.23750/abm.v90i6-S.8390
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  7. Article ; Online: Management of patients with cervical spine trauma in the emergency department: a systematic critical appraisal of guidelines with a view to developing standardized strategies for clinical practice.

    Gesu, Elisa / Bellone, Pietro / Bonzi, Mattia / Bertani, Giulio Andrea / Brignolo Ottolini, Barbara / Bosco, Paola / Conte, Giorgio / Ferrari, Matteo / Fiorelli, Elisa Maria / Kurihara, Hayato / Solbiati, Monica / Solimeno, Luigi Piero / Costantino, Giorgio

    Internal and emergency medicine

    2021  Volume 16, Issue 8, Page(s) 2277–2296

    Abstract: Several guidelines on the evaluation of patients with suspected cervical spine trauma in the Emergency Department (ED) exist. High heterogeneity between different guidelines has been reported. Aim of this study was to find areas of agreement and ... ...

    Abstract Several guidelines on the evaluation of patients with suspected cervical spine trauma in the Emergency Department (ED) exist. High heterogeneity between different guidelines has been reported. Aim of this study was to find areas of agreement and disagreement between guidelines, to identify topics in which further research is needed and to provide an evidence-based cervical spine trauma algorithm for ED physicians. The three most relevant guidelines published on cervical spine trauma in the last 10 years were selected screening websites of the main scientific societies and through the comparison of a normalized Google Scholar and SCOPUS citation index. We compared the selected guidelines through seven a-priori defined questions. In case of disagreement between the guidelines or if the quality of evidence appeared low, evidence from published systematic reviews on the topic was added to build an evidence-based algorithm for approach to spinal trauma in the ED. The three selected guidelines were: NICE 2016, Eastern Association for the Surgery of Trauma 2009 and American Association of Neurological Surgeons and Congress of Neurological Surgeons 2013. We found complete agreement on one question, partial agreement for one questions, no agreement for two questions, while agreement was not assessable for 3 questions. The agreement between different guidelines and the evidence on which recommendations are based is low. An attempt to build an evidence-based algorithm has been made. More studies are needed on many topics.
    MeSH term(s) Cervical Cord/injuries ; Emergency Service, Hospital/organization & administration ; Emergency Service, Hospital/standards ; Guidelines as Topic/standards ; Humans ; Reference Standards ; Wounds and Injuries/complications ; Wounds and Injuries/therapy
    Language English
    Publishing date 2021-10-05
    Publishing country Italy
    Document type Journal Article ; Systematic Review
    ZDB-ID 2454173-4
    ISSN 1970-9366 ; 1828-0447
    ISSN (online) 1970-9366
    ISSN 1828-0447
    DOI 10.1007/s11739-021-02838-1
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  8. Article ; Online: Correction to: Management of patients with cervical spine trauma in the emergency department: a systematic critical appraisal of guidelines with a view to developing standardized strategies for clinical practice.

    Gesu, Elisa / Bellone, Pietro / Bonzi, Mattia / Bertani, Giulio Andrea / Brignolo Ottolini, Barbara / Bosco, Paola / Conte, Giorgio / Ferrari, Matteo / Fiorelli, Elisa Maria / Kurihara, Hayato / Solbiati, Monica / Solimeno, Luigi Piero / Costantino, Giorgio

    Internal and emergency medicine

    2021  Volume 17, Issue 2, Page(s) 627

    Language English
    Publishing date 2021-12-20
    Publishing country Italy
    Document type Published Erratum
    ZDB-ID 2454173-4
    ISSN 1970-9366 ; 1828-0447
    ISSN (online) 1970-9366
    ISSN 1828-0447
    DOI 10.1007/s11739-021-02897-4
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  9. Article: Un nuovo modello di gestione dei pazienti "non urgenti" in Pronto Soccorso.

    Longo, Marcella / Pavan, Anna / Patriarca, Matteo / Speccher, Laura / Grillo, Paolo / Monzani, Valter / Porro, Fernando / Bosco, Paola / Passeri, Onorina / Macchi, Luigi

    Igiene e sanita pubblica

    2012  Volume 68, Issue 5, Page(s) 707–717

    Abstract: Emergency Department visits for nonurgent conditions are very widespread and new strategies to provide timely and appropriate medical care for these patients are required. The "Fondazione IRCCS Ca 'Grande" Hospital in Milan, in collaboration with the ... ...

    Title translation A new Emergency Department case management model for nonurgent patients.
    Abstract Emergency Department visits for nonurgent conditions are very widespread and new strategies to provide timely and appropriate medical care for these patients are required. The "Fondazione IRCCS Ca 'Grande" Hospital in Milan, in collaboration with the local health authorities have evaluated a new case management model in which patients classed as nonurgent at triage are diverted to a "continuity of care" outpatient office within the emergency department. This model, based on the integration of hospital and community-based primary healthcare, was effective and led to a significant reduction in waiting times in the ED and to a more appropriate use of resources.
    MeSH term(s) Case Management/organization & administration ; Continuity of Patient Care/organization & administration ; Diagnosis-Related Groups ; Emergency Service, Hospital/organization & administration ; Emergency Service, Hospital/utilization ; Health Services Misuse/prevention & control ; Hospitals, Urban/organization & administration ; Humans ; Italy ; Models, Theoretical ; Outpatient Clinics, Hospital/organization & administration ; Pilot Projects ; Retrospective Studies ; Time Management ; Triage/organization & administration
    Language Italian
    Publishing date 2012-09
    Publishing country Italy
    Document type English Abstract ; Journal Article
    ISSN 0019-1639
    ISSN 0019-1639
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  10. Article ; Online: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

    Kunkle, Brian W / Grenier-Boley, Benjamin / Sims, Rebecca / Bis, Joshua C / Damotte, Vincent / Naj, Adam C / Boland, Anne / Vronskaya, Maria / van der Lee, Sven J / Amlie-Wolf, Alexandre / Bellenguez, Céline / Frizatti, Aura / Chouraki, Vincent / Martin, Eden R / Sleegers, Kristel / Badarinarayan, Nandini / Jakobsdottir, Johanna / Hamilton-Nelson, Kara L / Moreno-Grau, Sonia /
    Olaso, Robert / Raybould, Rachel / Chen, Yuning / Kuzma, Amanda B / Hiltunen, Mikko / Morgan, Taniesha / Ahmad, Shahzad / Vardarajan, Badri N / Epelbaum, Jacques / Hoffmann, Per / Boada, Merce / Beecham, Gary W / Garnier, Jean-Guillaume / Harold, Denise / Fitzpatrick, Annette L / Valladares, Otto / Moutet, Marie-Laure / Gerrish, Amy / Smith, Albert V / Qu, Liming / Bacq, Delphine / Denning, Nicola / Jian, Xueqiu / Zhao, Yi / Del Zompo, Maria / Fox, Nick C / Choi, Seung-Hoan / Mateo, Ignacio / Hughes, Joseph T / Adams, Hieab H / Malamon, John / Sanchez-Garcia, Florentino / Patel, Yogen / Brody, Jennifer A / Dombroski, Beth A / Naranjo, Maria Candida Deniz / Daniilidou, Makrina / Eiriksdottir, Gudny / Mukherjee, Shubhabrata / Wallon, David / Uphill, James / Aspelund, Thor / Cantwell, Laura B / Garzia, Fabienne / Galimberti, Daniela / Hofer, Edith / Butkiewicz, Mariusz / Fin, Bertrand / Scarpini, Elio / Sarnowski, Chloe / Bush, Will S / Meslage, Stéphane / Kornhuber, Johannes / White, Charles C / Song, Yuenjoo / Barber, Robert C / Engelborghs, Sebastiaan / Sordon, Sabrina / Voijnovic, Dina / Adams, Perrie M / Vandenberghe, Rik / Mayhaus, Manuel / Cupples, L Adrienne / Albert, Marilyn S / De Deyn, Peter P / Gu, Wei / Himali, Jayanadra J / Beekly, Duane / Squassina, Alessio / Hartmann, Annette M / Orellana, Adelina / Blacker, Deborah / Rodriguez-Rodriguez, Eloy / Lovestone, Simon / Garcia, Melissa E / Doody, Rachelle S / Munoz-Fernadez, Carmen / Sussams, Rebecca / Lin, Honghuang / Fairchild, Thomas J / Benito, Yolanda A / Holmes, Clive / Karamujić-Čomić, Hata / Frosch, Matthew P / Thonberg, Hakan / Maier, Wolfgang / Roshchupkin, Gennady / Ghetti, Bernardino / Giedraitis, Vilmantas / Kawalia, Amit / Li, Shuo / Huebinger, Ryan M / Kilander, Lena / Moebus, Susanne / Hernández, Isabel / Kamboh, M Ilyas / Brundin, RoseMarie / Turton, James / Yang, Qiong / Katz, Mindy J / Concari, Letizia / Lord, Jenny / Beiser, Alexa S / Keene, C Dirk / Helisalmi, Seppo / Kloszewska, Iwona / Kukull, Walter A / Koivisto, Anne Maria / Lynch, Aoibhinn / Tarraga, Lluís / Larson, Eric B / Haapasalo, Annakaisa / Lawlor, Brian / Mosley, Thomas H / Lipton, Richard B / Solfrizzi, Vincenzo / Gill, Michael / Longstreth, W T / Montine, Thomas J / Frisardi, Vincenza / Diez-Fairen, Monica / Rivadeneira, Fernando / Petersen, Ronald C / Deramecourt, Vincent / Alvarez, Ignacio / Salani, Francesca / Ciaramella, Antonio / Boerwinkle, Eric / Reiman, Eric M / Fievet, Nathalie / Rotter, Jerome I / Reisch, Joan S / Hanon, Olivier / Cupidi, Chiara / Andre Uitterlinden, A G / Royall, Donald R / Dufouil, Carole / Maletta, Raffaele Giovanni / de Rojas, Itziar / Sano, Mary / Brice, Alexis / Cecchetti, Roberta / George-Hyslop, Peter St / Ritchie, Karen / Tsolaki, Magda / Tsuang, Debby W / Dubois, Bruno / Craig, David / Wu, Chuang-Kuo / Soininen, Hilkka / Avramidou, Despoina / Albin, Roger L / Fratiglioni, Laura / Germanou, Antonia / Apostolova, Liana G / Keller, Lina / Koutroumani, Maria / Arnold, Steven E / Panza, Francesco / Gkatzima, Olymbia / Asthana, Sanjay / Hannequin, Didier / Whitehead, Patrice / Atwood, Craig S / Caffarra, Paolo / Hampel, Harald / Quintela, Inés / Carracedo, Ángel / Lannfelt, Lars / Rubinsztein, David C / Barnes, Lisa L / Pasquier, Florence / Frölich, Lutz / Barral, Sandra / McGuinness, Bernadette / Beach, Thomas G / Johnston, Janet A / Becker, James T / Passmore, Peter / Bigio, Eileen H / Schott, Jonathan M / Bird, Thomas D / Warren, Jason D / Boeve, Bradley F / Lupton, Michelle K / Bowen, James D / Proitsi, Petra / Boxer, Adam / Powell, John F / Burke, James R / Kauwe, John S K / Burns, Jeffrey M / Mancuso, Michelangelo / Buxbaum, Joseph D / Bonuccelli, Ubaldo / Cairns, Nigel J / McQuillin, Andrew / Cao, Chuanhai / Livingston, Gill / Carlson, Chris S / Bass, Nicholas J / Carlsson, Cynthia M / Hardy, John / Carney, Regina M / Bras, Jose / Carrasquillo, Minerva M / Guerreiro, Rita / Allen, Mariet / Chui, Helena C / Fisher, Elizabeth / Masullo, Carlo / Crocco, Elizabeth A / DeCarli, Charles / Bisceglio, Gina / Dick, Malcolm / Ma, Li / Duara, Ranjan / Graff-Radford, Neill R / Evans, Denis A / Hodges, Angela / Faber, Kelley M / Scherer, Martin / Fallon, Kenneth B / Riemenschneider, Matthias / Fardo, David W / Heun, Reinhard / Farlow, Martin R / Kölsch, Heike / Ferris, Steven / Leber, Markus / Foroud, Tatiana M / Heuser, Isabella / Galasko, Douglas R / Giegling, Ina / Gearing, Marla / Hüll, Michael / Geschwind, Daniel H / Gilbert, John R / Morris, John / Green, Robert C / Mayo, Kevin / Growdon, John H / Feulner, Thomas / Hamilton, Ronald L / Harrell, Lindy E / Drichel, Dmitriy / Honig, Lawrence S / Cushion, Thomas D / Huentelman, Matthew J / Hollingworth, Paul / Hulette, Christine M / Hyman, Bradley T / Marshall, Rachel / Jarvik, Gail P / Meggy, Alun / Abner, Erin / Menzies, Georgina E / Jin, Lee-Way / Leonenko, Ganna / Real, Luis M / Jun, Gyungah R / Baldwin, Clinton T / Grozeva, Detelina / Karydas, Anna / Russo, Giancarlo / Kaye, 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    Nature genetics

    2019  Volume 51, Issue 3, Page(s) 414–430

    Abstract: Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We ... ...

    Abstract Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10
    MeSH term(s) Aged ; Alzheimer Disease/genetics ; Amyloid beta-Peptides/genetics ; Case-Control Studies ; Female ; Genetic Loci/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Testing/methods ; Genome-Wide Association Study/methods ; Haplotypes/genetics ; Humans ; Immunity/genetics ; Lipid Metabolism/genetics ; Lipids/genetics ; Male ; tau Proteins/genetics
    Chemical Substances Amyloid beta-Peptides ; Lipids ; tau Proteins
    Language English
    Publishing date 2019-02-28
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-019-0358-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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