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52. List of contributors

Author

Adala, R., primary, Affatato, S., additional, Amendola, L., additional, Anand, A., additional, Ayad, R.B., additional, Battaglia, S., additional, Bettuzi, C., additional, Catani, F., additional, Castiello, E., additional, Comitini, S., additional, Commessatti, M., additional, Devoti, D., additional, Dilip, N., additional, Faaborg-Andersen, C., additional, Fosco, M., additional, Gentile, P., additional, Graceffa, A., additional, Hernigou, P., additional, Indelli, P.F., additional, Innocenti, M., additional, Leonetti, D., additional, Marcucci, M., additional, Mugnai, R., additional, Nam, D., additional, Pipino, G., additional, Poli, P., additional, Ravindran, R., additional, Srinivas, J.V., additional, Tigani, D., additional, Veerappa, Y.A., additional, and Vitantonio, D., additional

Published
2015
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53. International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia

Author

Aliberti, S, Cook, GS, Babu, BL, Reyes, LF, Rodriguez, AH, Sanz, F, Soni, NJ, Anzueto, A, Faverio, P, Sadud, RF, Muhammad, I, Prat, C, Vendrell, E, Neves, J, Kaimakamis, E, Feneley, A, Swarnakar, R, Franzetti, F, Carugati, M, Morosi, M, Monge, E, Restrepo, MI, Aruj, PK, Attorri, S, Barimboim, E, Caeiro, JP, Garzon, MI, Cambursano, VH, Ceccato, A, Chertcoff, J, Lascar, F, Di Tulio, F, Diaz, AC, de Vedia, L, Ganaha, MC, Lambert, S, Lopardo, G, Lopez, V, Luna, CM, Malberti, AG, Morcillo, N, Tartara, S, Pensotti, C, Pereyra, B, Scapellato, PG, Stagnaro, JP, Shah, S, Lotsch, F, Thalhammer, F, Anseeuw, K, Francois, CA, Van Braeckel, E, Vincent, JL, Djimon, MZ, Bashi, J, Dodo, R, Nouer, SA, Chipev, P, Encheva, M, Miteva, D, Petkova, D, Balkissou, AD, Yone, EWP, Ngahane, BHM, Shen, N, Xu, JF, Rico, CAB, Buitrago, R, Paternina, FJP, Ntumba, JMK, Carevic, VV, Jakopovic, M, Jankovic, M, Matkovic, Z, Mitrecic, I, Jacobsson, MLB, Christensen, AB, Bodtger, UCH, Meyer, CN, Jensen, AV, Baunbaek-knudsen, G, Petersen, PT, Andersen, S, Abd El-Wahhab, IES, Morsy, NE, Shafiek, H, Sobh, E, Abdulsemed, KA, Bertrand, F, Brun-Buisson, C, de Montmollin, E, Fartoukh, M, Messika, J, Tattevin, P, Khoury, A, Ebruke, B, Dreher, M, Kolditz, M, Meisinger, M, Pletz, MW, Hagel, S, Rupp, J, Schaberg, T, Spielmanns, M, Creutz, P, Suttorp, N, Siaw-Lartey, B, Dimakou, K, Papapetrou, D, Tsigou, E, Ampazis, D, Bhatia, M, Dhar, R, D'Souza, G, Garg, R, Koul, PA, Mahesh, PA, Jayaraj, BS, Narayan, KV, Udnur, HB, Krishnamurthy, SB, Kant, S, Limaye, S, Salvi, S, Golshani, K, Keatings, VM, Martin-Loeches, I, Maor, Y, Strahilevitz, J, Battaglia, S, Carrabba, M, Ceriana, P, Confalonieri, M, Monforte, AD, Del Prato, B, De Rosa, M, Fantini, R, Fiorentino, G, Gammino, MA, Menzella, F, Milani, G, Nava, S, Palmiero, G, Petrino, R, Gabrielli, B, Rossi, P, Sorino, C, Steinhilber, G, Zanforlin, A, Carone, M, Patella, V, Scarlata, S, Comel, A, Kurahashi, K, Bacha, ZA, Ugalde, DB, Zuniga, OC, Villegas, JF, Medenica, M, van de Garde, EMW, Mihsra, DR, Shrestha, P, Ridgeon, E, Awokola, BI, Nwankwo, ONO, Olufunlola, AB, Olumide, S, Ukwaja, KN, Irfan, M, Minarowski, L, Szymon, S, Froes, F, Leuschner, P, Meireles, M, Ferrao, C, Ravara, SB, Brocovschii, V, Ion, C, Rusu, D, Toma, C, Chirita, D, Dorobat, CM, Birkun, A, Kaluzhenina, A, Almotairi, A, Bukhary, ZAA, Edathodu, J, Fathy, A, Enani, AMA, Mohamed, NE, Memon, JU, Bella, A, Bogdanovic, N, Milenkovic, B, Pesut, D, Borderias, L, Garcia, NMB, Alarcon, HC, Cilloniz, C, Torres, A, Diaz-Brito, V, Casas, X, Gonzalez, AE, Fernandez-Almira, ML, Gallego, M, Gaspar-Garcia, I, del Castillo, JG, Victoria, PJ, Martinez, EL, de Molina, RM, Marcos, PJ, Menendez, R, Pando-Sandoval, A, Aymerich, CP, de la Torre, AL, Garcia-Olive, I, Rello, J, Moyano, S, Sibila, O, Rodrigo-Troyano, A, Sole-Violan, J, Uranga, A, van Boven, JFM, Torra, EV, Pujol, JA, Feldman, C, Yum, HK, Fiogbe, AA, Yangui, F, Bilaceroglu, S, Dalar, L, Yilmaz, U, Bogomolov, A, Elahi, N, Dhasmana, DJ, Ions, R, Skeemer, J, Woltmann, G, Hancock, C, Hill, AT, Rudran, B, Ruiz-Buitrago, S, Campbell, M, Whitaker, P, Youzguin, A, Singanayagam, A, Allen, KS, Brito, V, Dietz, J, Dysart, CE, Kellie, SM, Franco-Sadud, RA, Meier, G, Gaga, M, Holland, TL, Bergin, SP, Kheir, F, Landmeier, M, Lois, M, Nair, GB, Patel, H, Reyes, K, Rodriguez-Cintron, W, Saito, S, Noda, J, Hinojosa, CI, Levine, SM, Angel, LF, Whitlow, KS, Hipskind, J, Sukhija, K, Totten, V, Wunderink, RG, Shah, RD, Mateyo, KJ, Noriega, L, Alvarado, E, Aman, M, Labra, L, Aliberti, S, Cook, G, Babu, B, Reyes, L, H. Rodriguez, A, Sanz, F, Soni, N, Anzueto, A, Faverio, P, Sadud, R, Muhammad, I, Prat, C, Vendrell, E, Neves, J, Kaimakamis, E, Feneley, A, Swarnakar, R, Franzetti, F, Carugati, M, Morosi, M, Monge, E, Restrepo, M, Aliberti, S., Cook, G. S., Babu, B. L., Reyes, L. F., Rodriguez, A. H., Sanz, F., Soni, N. J., Anzueto, A., Faverio, P., Sadud, R. F., Muhammad, I., Prat, C., Vendrell, E., Neves, J., Kaimakamis, E., Feneley, A., Swarnakar, R., Franzetti, F., Carugati, M., Morosi, M., Monge, E., Restrepo, M. I., Aruj, P. K., Attorri, S., Barimboim, E., Caeiro, J. P., Garzon, M. I., Cambursano, V. H., Ceccato, A., Chertcoff, J., Lascar, F., Di Tulio, F., Diaz, A. C., de Vedia, L., Ganaha, M. C., Lambert, S., Lopardo, G., Luna, C. M., Malberti, A. G., Morcillo, N., Tartara, S., Pensotti, C., Pereyra, B., Scapellato, P. G., Stagnaro, J. P., Shah, S., Lotsch, F., Thalhammer, F., Anseeuw, K., Francois, C. A., Van Braeckel, E., Vincent, J. L., Djimon, M. Z., Bashi, J., Dodo, R., Nouer, S. A., Chipev, P., Encheva, M., Miteva, D., Petkova, D., Balkissou, A. D., Yone, E. W. P., Ngahane, B. H. M., Shen, N., Xu, J. -F., Rico, C. A. B., Buitrago, R., Paternina, F. J. P., Ntumba, J. -M. K., Carevic, V. V., Jakopovic, M., Jankovic, M., Matkovic, Z., Mitrecic, I., Jacobsson, M. -L. B., Christensen, A. B., Bodtger, U. C. H., Meyer, C. N., Jensen, A. V., Baunbaek-Knudsen, G., Petersen, P. T., Andersen, S., El-Wahhab, I. E. -S. A., Morsy, N. E., Shafiek, H., Sobh, E., Abdulsemed, K. A., Bertrand, F., Brun-Buisson, C., de Montmollin, E., Fartoukh, M., Messika, J., Tattevin, P., Khoury, A., Ebruke, B., Dreher, M., Kolditz, M., Meisinger, M., Pletz, M. W., Hagel, S., Rupp, J., Schaberg, T., Spielmanns, M., Creutz, P., Suttorp, N., Siaw-Lartey, B., Dimakou, K., Papapetrou, D., Tsigou, E., Ampazis, D., Bhatia, M., Dhar, R., D'Souza, G., Garg, R., Koul, P. A., Mahesh, P. A., Jayaraj, B. S., Narayan, K. V., Udnur, H. B., Krishnamurthy, S. B., Kant, S., Limaye, S., Salvi, S., Golshani, K., Keatings, V. M., Martin-Loeches, I., Maor, Y., Strahilevitz, J., Battaglia, S., Carrabba, M., Ceriana, P., Confalonieri, M., D'Arminio Monforte, A., Del Prato, B., De Rosa, M., Fantini, R., Fiorentino, G., Gammino, M. A., Menzella, F., Milani, G., Nava, S., Palmiero, G., Petrino, R., Gabrielli, B., Rossi, P., Sorino, C., Steinhilber, G., Zanforlin, A., Carone, M., Patella, V., Scarlata, S., Comel, A., Kurahashi, K., Bacha, Z. A., Ugalde, D. B., Zuniga, O. C., Villegas, J. F., Medenica, M., van de Garde, E. M. W., Mihsra, D. R., Shrestha, P., Ridgeon, E., Awokola, B. I., Nwankwo, O. N. O., Olufunlola, A. B., Olumide, S., Ukwaja, K. N., Irfan, M., Minarowski, L., Szymon, S., Froes, F., Leuschner, P., Meireles, M., Ferrao, C., Ravara, S. B., Brocovschii, V., Ion, C., Rusu, D., Toma, C., Chirita, D., Dorobat, C. M., Birkun, A., Kaluzhenina, A., Almotairi, A., Bukhary, Z. A. A., Edathodu, J., Fathy, A., Enani, A. M. A., Mohamed, N. E., Memon, J. U., Bella, A., Bogdanovic, N., Milenkovic, B., Pesut, D., Borderias, L., Garcia, N. M. B., Alarcon, H. C., Cilloniz, C., Torres, A., Diaz-Brito, V., Casas, X., Gonzalez, A. E., Fernandez-Almira, M. L., Gallego, M., Gaspar-Garcia, I., Del Castillo, J. G., Victoria, P. J., Martinez, E. L., de Molina, R. M., Marcos, P. J., Menendez, R., Pando-Sandoval, A., Aymerich, C. P., de la Torre, A. L., Garcia-Olive, I., Rello, J., Moyano, S., Sibila, O., Rodrigo-Troyano, A., Sole-Violan, J., Uranga, A., van Boven, J. F. M., Torra, E. V., Pujol, J. A., Feldman, C., Yum, H. K., Fiogbe, A. A., Yangui, F., Bilaceroglu, S., Dalar, L., Yilmaz, U., Bogomolov, A., Elahi, N., Dhasmana, D. J., Ions, R., Skeemer, J., Woltmann, G., Hancock, C., Hill, A. T., Rudran, B., Ruiz-Buitrago, S., Campbell, M., Whitaker, P., Youzguin, A., Singanayagam, A., Allen, K. S., Brito, V., Dietz, J., Dysart, C. E., Kellie, S. M., Franco-Sadud, R. A., Meier, G., Gaga, M., Holland, T. L., Bergin, S. P., Kheir, F., Landmeier, M., Lois, M., Nair, G. B., Patel, H., Reyes, K., Rodriguez-Cintron, W., Saito, S., Noda, J., Hinojosa, C. I., Levine, S. M., Angel, L. F., Whitlow, K. S., Hipskind, J., Sukhija, K., Totten, V., Wunderink, R. G., Shah, R. D., Mateyo, K. J., Noriega, L., Alvarado, E., Aman, M., Labra, L., Aliberti S., Cook G.S., Babu B.L., Reyes L.F., Rodriguez A.H., Sanz F., Soni N.J., Anzueto A., Faverio P., Sadud R.F., Muhammad I., Prat C., Vendrell E., Neves J., Kaimakamis E., Feneley A., Swarnakar R., Franzetti F., Carugati M., Morosi M., Monge E., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano V.H., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Diaz A.C., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C.A., Van Braeckel E., Vincent J.L., Djimon M.Z., Bashi J., Dodo R., Nouer S.A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A.D., Yone E.W.P., Ngahane B.H.M., Shen N., Xu J.-F., Rico C.A.B., Buitrago R., Paternina F.J.P., Ntumba J.-M.K., Carevic V.V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Jacobsson M.-L.B., Christensen A.B., Bodtger U.C.H., Meyer C.N., Jensen A.V., Baunbaek-Knudsen G., Petersen P.T., Andersen S., El-Wahhab I.E.-S.A., Morsy N.E., Shafiek H., Sobh E., Abdulsemed K.A., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Bhatia M., Dhar R., D'souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Kant S., Limaye S., Salvi S., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., D'Arminio Monforte A., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Menzella F., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., van de Garde E.M.W., Mihsra D.R., Shrestha P., Ridgeon E., Awokola B.I., Nwankwo O.N.O., Olufunlola A.B., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Ravara S.B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C.M., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z.A.A., Edathodu J., Fathy A., Enani A.M.A., Mohamed N.E., Memon J.U., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Garcia N.M.B., Alarcon H.C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., Fernandez-Almira M.L., Gallego M., Gaspar-Garcia I., Del Castillo J.G., Victoria P.J., Martinez E.L., de Molina R.M., Marcos P.J., Menendez R., Pando-Sandoval A., Aymerich C.P., de la Torre A.L., Garcia-Olive I., Rello J., Moyano S., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F.M., Torra E.V., Pujol J.A., Feldman C., Yum H.K., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Ions R., Skeemer J., Woltmann G., Hancock C., Hill A.T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Franco-Sadud R.A., Meier G., Gaga M., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Whitlow K.S., Hipskind J., Sukhija K., Totten V., Wunderink R.G., Shah R.D., Mateyo K.J., Noriega L., Alvarado E., Aman M., and Labra L.

Subjects
0301 basic medicine, Male, Streptococcus pneumonia, antibiotic resistance, Internationality, sputum examination, bronchiectasis, very elderly, Antibiotics, Prevalence, Drug resistance, medicine.disease_cause, Logistic regression, Global Health, Community-Acquired Infections/epidemiology, lung lavage, 0302 clinical medicine, Community-acquired pneumonia, Cost of Illness, Risk Factors, drug resistant Streptococcus pneumoniae pneumonia, 030212 general & internal medicine, Microbial drug resistant, Aged, 80 and over, adult, international cooperation, drug effect, Middle Aged, influenza vaccination, Anti-Bacterial Agents, antiinfective agent, Europe, Community-Acquired Infections, Hospitalization, Global burden of disease, Streptococcus pneumoniae, Infectious Diseases, risk factor, bacterium identification, Female, community acquired infection, influenza, liver disease, pneumococcal vaccination, Pneumococcal infection, hospitalization, medicine.drug, Microbiology (medical), medicine.medical_specialty, Asia, medicine.drug_class, 030106 microbiology, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Article, Anti-Bacterial Agents/pharmacology, 03 medical and health sciences, Internal medicine, Drug Resistance, Bacterial, Pneumonia, Pneumococcal/epidemiology, medicine, Humans, controlled study, human, tetracycline, Hospitalization/statistics & numerical data, Aged, levofloxacin, nonhuman, business.industry, disease association, microbiology, community acquired pneumonia, macrolide, Pneumonia, asthma, South America, Pneumonia, Pneumococcal, vaccination, medicine.disease, major clinical study, antibiotic sensitivity, penicillin derivative, Penicillin, Streptococcus pneumoniae/drug effects, blood examination, Africa, North America, microbiological examination, business
Abstract

Objective: Streptococcus pneumoniae is the most frequent bacterial pathogen isolated in subjects with Community-acquired pneumonia (CAP) worldwide. Limited data are available regarding the current global burden and risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP) in CAP subjects. We assessed the multinational prevalence and risk factors for DRSP-CAP in a multinational point-prevalence study. Design: The prevalence of DRSP-CAP was assessed by identification of DRSP in blood or respiratory samples among adults hospitalized with CAP in 54 countries. Prevalence and risk factors were compared among subjects that had microbiological testing and antibiotic susceptibility data. Multivariate logistic regressions were used to identify risk factors independently associated with DRSP-CAP. Results: 3,193 subjects were included in the study. The global prevalence of DRSP-CAP was 1.3% and continental prevalence rates were 7.0% in Africa, 1.2% in Asia, and 1.0% in South America, Europe, and North America, respectively. Macrolide resistance was most frequently identified in subjects with DRSP-CAP (0.6%) followed by penicillin resistance (0.5%). Subjects in Africa were more likely to have DRSP-CAP (OR: 7.6; 95% CI: 3.34-15.35, p < 0.001) when compared to centres representing other continents. Conclusions: This multinational point-prevalence study found a low global prevalence of DRSP-CAP that may impact guideline development and antimicrobial policies. Published by Elsevier Ltd on behalf of The British Infection Association.

Published
2019

54. Management of suspected COVID-19 patients in a low prevalence region

Author

Alida Benfante, Riccardo Messina, Laura Basile, Francesco Gambino, Sonia Poma, Battaglia S, Stefania Marino, Nicola Scichilone, Marta Maria Zammuto, Roberto Fonte, Stefania Principe, Giovanni Salamone, Scichilone N., Basile L., Battaglia S., Benfante A., Fonte R., Gambino F., Marino S., Messina R., Poma S., Principe S., Salamone G., and Zammuto M.

Subjects
Male, Respiratory Tract Diseases, Disease, Clinical Laboratory Technique, 0302 clinical medicine, COVID-19 Testing, Health care, Prevalence, 030212 general & internal medicine, health-care management, education.field_of_study, respiratory symptoms, Organizational Innovation, Grey zone, Critical Pathway, Italy, Critical Pathways, Female, Coronavirus Infections, Human, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Pneumonia, Viral, Context (language use), Settore MED/10 - Malattie Dell'Apparato Respiratorio, Diagnosis, Differential, 03 medical and health sciences, Betacoronavirus, medicine, Humans, Intensive care medicine, education, Pandemics, Aged, respiratory symptom, Infection Control, Betacoronaviru, business.industry, Coronavirus Infection, Clinical Laboratory Techniques, SARS-CoV-2, Hot Topic, COVID-19, Patient Care Management, COVID-19 Drug Treatment, 030228 respiratory system, Epidemic outbreak, business
Abstract

The spread of the SARS-CoV-2 infection among population has imposed a re-organization of healthcare services, aiming at stratifying patients and dedicating specific areas where patients with suspected COVID-related respiratory disease could receive the necessary health care assistance while waiting for the confirmation of the diagnosis of COVID-19 disease. In this scenario, the pathway defined as a “grey zone” is strongly advocated. We describe the application of rules and pathways in a regional context with low diffusion of the infection among the general population in the attempt to provide the best care to respiratory patients with suspected COVID-19. To date, this process has avoided the worst-case scenario of intra-hospital epidemic outbreak.

Published
2020

55. Correction to: Atypical pathogens in hospitalized patients with community-acquired pneumonia: a worldwide perspective (BMC Infectious Diseases, (2018), 18, 1, (677), 10.1186/s12879-018-3565-z)

Author

Gramegna A., Sotgiu G., Di Pasquale M., Radovanovic D., Terraneo S., Reyes L. F., Vendrell E., Neves J., Menzella F., Blasi F., Aliberti S., Restrepo M. I., Aruj P. K., Attorri S., Barimboim E., Caeiro J. P., Cambursano V. H., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Diaz A. C., de Vedia L., Ganaha M. C., Lambert S., Lopardo G., Luna C. M., Malberti A. G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P. G., Stagnaro J. P., Lotsch F., Vincent J. L., Anseeuw K., Francois C. A., Van Braeckel E., Djimon M. Z., Bashi J., Roger D., Nouer S. A., Chipev P., Encheva M., Miteva D., Petkova D., Dodo B. A., Hugo M. N. B., Shen N., Xu J. -F., Rico C. A. B., Buitrago R., Paternina F. J. P., Jean-Marie K. N., Carevic V. V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Jacobsson M. -L. B., Christensen A. B., HeitmannBodtger U. C., Meyer C. N., Jensen A. V., Baunbaek-knudsen G., Petersen P. T., Andersen S., El-Wahhab I. E. -S. A., Morsy N. E., Shafi ek H., Sobh E., Bertrand F., Brun- Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Dreher M., Kolditz M., Meisinger M., Pletz M. W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Bhatia M., Ampazis D., Dhar R., D'Souza G., Garg R., Koul P. A., Mahesh P. A., Jayaraj B. S., Narayan K. V., Udnur H. B., Krishnamurthy S. B., Golshani K., Keatings V. M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., d'Arminio A., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M. A., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Steinhilber G., Zanforlin A., Kurahashi K., Bacha Z. A., Ugalde D. B., Zuniga O. C., Villegas J. F., Medenica M., van de Garde E. M. W., Mihsra D. R., Ridgeon E., Nwankwo O. N. O., Olufunlola A. B., Olumide S., Ukwaja K. N., Irfan M., Minarowski L., Szymo S., Froes F., Meireles M., Ferrao C., Leuschner P., Ravara S. B., Brocovschii V., Ion C., Rusu D., Chirita D., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z. A. A., Edathodu J., Fathy A., Enani A. M. A., Mohamed N. E., Memon J. U., Bogdanovic N., Milenkovic B., Borderias L., Garcia N. M. B., Alarcon H. C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A. E., FernandezAlmira M. L., Gallego M., Gaspar-GarcIa I., del Castillo J. G., Victoria P. J., Martinez E. L., de Molina R. M., Marcos P. J., Menendez R., Pando-Sandoval A., Aymerich C. P., del la Torre A. L., Garcia-Olive I., Rello J., Moyano S., Sanz F., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J. F. M., Torra E. V., Pujol J. A., Feldman C., Yum H. K., Fiogbe A. A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D. J., Ions R., Skeemer J., Woltmann G., Hancock C., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Allen K. S., Brito V., Dietz J., Dysart C. E., Franco-Sadud R. A., Kellie G. M. S. M., Gaga M., Bergin S. P., Kheir F., Landmeier M., Lois M., Nair G. B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Soni N. J., Noda J., Hinojosa C. I., Levine S. M., Angel L. F., Anzueto A., Whitlow K. S., Hipskind J., Sukhija K., Wunderink R. G., Shah R. D., Mateyo K. J., Gramegna A., Sotgiu G., Di Pasquale M., Radovanovic D., Terraneo S., Reyes L.F., Vendrell E., Neves J., Menzella F., Blasi F., Aliberti S., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Cambursano V.H., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Diaz A.C., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Lotsch F., Vincent J.L., Anseeuw K., Francois C.A., Van Braeckel E., Djimon M.Z., Bashi J., Roger D., Nouer S.A., Chipev P., Encheva M., Miteva D., Petkova D., Dodo B.A., Hugo M.N.B., Shen N., Xu J.-F., Rico C.A.B., Buitrago R., Paternina F.J.P., Jean-Marie K.N., Carevic V.V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Jacobsson M.-L.B., Christensen A.B., HeitmannBodtger U.C., Meyer C.N., Jensen A.V., Baunbaek-knudsen G., Petersen P.T., Andersen S., El-Wahhab I.E.-S.A., Morsy N.E., Shafi ek H., Sobh E., Bertrand F., Brun- Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Bhatia M., Ampazis D., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., d'Arminio A., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Steinhilber G., Zanforlin A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., van de Garde E.M.W., Mihsra D.R., Ridgeon E., Nwankwo O.N.O., Olufunlola A.B., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymo S., Froes F., Meireles M., Ferrao C., Leuschner P., Ravara S.B., Brocovschii V., Ion C., Rusu D., Chirita D., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z.A.A., Edathodu J., Fathy A., Enani A.M.A., Mohamed N.E., Memon J.U., Bogdanovic N., Milenkovic B., Borderias L., Garcia N.M.B., Alarcon H.C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., FernandezAlmira M.L., Gallego M., Gaspar-GarcIa I., del Castillo J.G., Victoria P.J., Martinez E.L., de Molina R.M., Marcos P.J., Menendez R., Pando-Sandoval A., Aymerich C.P., del la Torre A.L., Garcia-Olive I., Rello J., Moyano S., Sanz F., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F.M., Torra E.V., Pujol J.A., Feldman C., Yum H.K., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Ions R., Skeemer J., Woltmann G., Hancock C., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Allen K.S., Brito V., Dietz J., Dysart C.E., Franco-Sadud R.A., Kellie G.M.S.M., Gaga M., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Soni N.J., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Anzueto A., Whitlow K.S., Hipskind J., Sukhija K., Wunderink R.G., Shah R.D., and Mateyo K.J.

Subjects
CAP, Atypical pathogens, Epidemiology, Settore MED/10 - Malattie Dell'Apparato Respiratorio
Abstract

Following publication of the original article [1], the authors identified that they have been incorrectly tagged under the name of their related consortium GLIMP Study Group.

Published
2020

56. Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study

Author

Carugati, Manuela, Aliberti, S., Sotgiu, G., Blasi, F., Gori, A., Menendez, R., Encheva, M., Gallego, M., Leuschner, P., Ruiz-Buitrago, S., Battaglia, S., Fantini, R., Pascual-Guardia, S., Marin-Corral, J., Restrepo, M. I., Aruj, Patricia Karina, Attorri, Silvia, Barimboim, Enrique, Caeiro, Juan Pablo, Garzón, María I, Cambursano, Victor Hugo, Ceccato, Adrian, Chertcoff, Julio, Lascar, Florencia, Tulio, Fernando Di, Díaz, Ariel Cordon, de Vedia, Lautaro, Ganaha, Maria Cristina, Lambert, Sandra, Lopardo, Gustavo, Luna, Carlos M, Malberti, Alessio Gerardo, Morcillo, Nora, Tartara, Silvina, Pensotti, Claudia, Pereyra, Betiana, Scapellato, Pablo Gustavo, Stagnaro, Juan Pablo, Shah, Sonali, Lötsch, Felix, Thalhammer, Florian, Vincent, Jean Louis, Anseeuw, Kurt, Francois, Camille A, Van Braeckel, Eva, Djimon, Marcel Zannou, Bashi, Jules, Roger, Dodo, Nouér, Simone Aranha, Chipev, Peter, Encheva, Milena, Miteva, Darina, Petkova, Diana, Dodo, Balkissou Adamou, Ngahane, Mbatchou, Hugo, Bertrand, Shen, Ning, Xu, Jin-fu, Rico, Carlos Andres Bustamante, Buitrago, Ricardo, Paternina, Fernando Jose Pereira, Jean-Marie, Kayembe Ntumba, Carevic, Vesna Vladic, Jakopovic, Marko, Jankovic, Mateja, Matkovic, Zinka, Mitrecic, Ivan, Jacobsson, Marie-Laure Bouchy, Christensen, Anette Bro, HeitmannBødtger, Uff e Christian, Meyer, Christian Niels, Jensen, Andreas Vestergaard, Baunbæk-knudsen, Gertrud, Petersen, Pelle Trier, Andersen, Stine, El-Wahhab, Ibrahim El-Said Abd, Morsy, Nesreen Elsayed, Shafiek, Hanaa, Sobh, Eman, Bertrand, Fabrice, Brun-Buisson, Christian, de Montmollin, Etienne, Fartoukh, Muriel, Messika, Jonathan, Tattevin, Pierre, Dreher, Michael, Kolditz, Martin, Meisinger, Matthias, Pletz, Mathias W, Hagel, Stefan, Rupp, Jan, Schaberg, Tom, Spielmanns, Marc, Siaw-Lartey, Beatrice, Dimakou, Katerina, Papapetrou, Dimosthenis, Tsigou, Evdoxia, Ampazis, Dimitrios, Bhatia, Mohit, Dhar, Raja, D’Souza, George, Garg, Rajiv, Koul, Parvaiz A, Mahesh, P A, Jayaraj, B S, Narayan, Kiran Vishnu, Udnur, Hirennappa B, Krishnamurthy, Shashi Bhaskara, Golshani, Keihan, Keatings, Vera M, Martin-Loeches, Ignacio, Maor, Yasmin, Strahilevitz, Jacob, Battaglia, Salvatore, Carrabba, Maria, Ceriana, Piero, Confalonieri, Marco, d’Arminio Monforte, Antonella, Del Prato, Bruno, De Rosa, Marino, Fantini, Riccardo, Fiorentino, Giuseppe, Gammino, Maria Antonia, Menzella, Francesco, Milani, Giuseppe, Nava, Stefano, Palmiero, Gerardo, Petrino, Roberta, Gabrielli, Barbra, Rossi, Paolo, Sorino, Claudio, Steinhilber, Gundi, Zanforlin, Alessandro, Kurahashi, Kiyoyasu, Bacha, Zeina Aoun, Ugalde, Daniel Barajas, Zuñiga, Omar Ceballos, Villegas, José F, Medenica, Milic, van de Garde, E M W, Mihsra, Deebya Raj, Shrestha, Poojan, Ridgeon, Elliott, Awokola, Babatunde Ishola, Nwankwo, Ogonna N O, Olufunlola, Adefuye Bolanle, Olumide, Segaolu, Ukwaja, Kingsley N, Irfan, Muhammad, Minarowski, Lukasz, Szymon, Skoczyński, Froes, Felipe, Leuschner, Pedro, Meireles, Mariana, Ferrão, Cláudia, Neves, João, Ravara, Sofia B, da Beira, Cova, Brocovschii, Victoria, Ion, Chesov, Rusu, Doina, Toma, Cristina, Chirita, Daniela, Birkun, Alexei, Kaluzhenina, Anna, Almotairi, Abdullah, Abdulbaqi, Zakeya, Bukhary, Ali, Edathodu, Jameela, Fathy, Amal, Enani, Abdullah Mushira Abdulaziz, Mohamed, Nazik Eltayeb, Memon, Jawed Ulhadi, Bogdanović, Nada, Milenkovic, Branislava, Pesut, Dragica, Borderìas, Luis, Garcia, Noel Manuel Bordon, Alarcón, Hugo Cabello, Cilloniz, Catia, Torres, Antoni, Diaz-Brito, Vicens, Casas, Xavier, González, Alicia Encabo, Fernández-Almira, Maria Luisa, Gallego, Miguel, Gaspar-GarcÍa, Inmaculada, del Castillo, Juan González, Victoria, Patricia Javaloyes, Martínez, Elena Laserna, de Molina, Rosa Malo, Marcos, Pedro J, Menéndez, Rosario, PandoSandova, Ana, Aymerich, Cristina Prat, del la Torre, Alicia Lacoma, García-Olivé, Ignasi, Rello, Jordi, Moyano, Silvia, Sanz, Francisco, Sibila, Oriol, Rodrigo-Troyano, Ana, Solé-Violán, Jordi, Uranga, Ane, van Boven, Job FM, Torra, Ester Vendrell, Pujol, Jordi Almirall, Feldman, Charles, Yum, Ho Kee, Fiogbe, Arnauld Attannon, Yangui, Ferdaous, Bilaceroglu, Semra, Dalar, Levent, Yilmaz, Ufuk, Bogomolov, Artemii, Elahi, Naheed, Dhasmana, Devesh J, Ions, Rhiannon, Skeemer, Julie, Woltmann, Gerrit, Hancock, Carole, Hill, Adam T, Rudran, Banu, Ruiz-Buitrago, Silvia, Campbell, Marion, Whitaker, Paul, Allen, Karen S, Brito, Veronica, Dietz, Jessica, Dysart, Claire E, Kellie, Susan M, Franco-Sadud, Ricardo A, Meier, Garnet, Gaga, Mina, Holland, Thomas L, Bergin, Stephen P, Kheir, Fayez, Landmeier, Mark, Lois, Manuel, Nair, Girish B, Patel, Hemali, Reyes, Katherine, Rodriguez-Cintron, William, Saito, Shigeki, Soni, Nilam J, Noda, Julio, Hinojosa, Cecilia I, Levine, Stephanie M, Angel, Luis F, Anzueto, Antonio, Whitlow, K Scott, Hipskind, John, Sukhija, Kunal, Wunderink, Richard G., Shah, Ray D, Mateyo, Kondwelani John, Carugati, Manuela, Aliberti, S, Sotgiu, G, Blasi, F, Gori, A, Menendez, R, Encheva, M, Gallego, M, Leuschner, P, Ruiz-Buitrago, S, Battaglia, S, Fantini, R, Pascual-Guardia, S, Marin-Corral, J, and Restrepo, M I

Subjects
Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Community-acquired pneumonia, 030106 microbiology, Antimicrobial treatment, Prevalence, Guideline, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Guidelines, Global Health, medicine.disease_cause, Immunocompromised Host, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Internal medicine, Epidemiology, Streptococcus pneumoniae, Pneumonia, Bacterial, Humans, Medicine, 030212 general & internal medicine, Practice Patterns, Physicians', Aged, Aged, 80 and over, business.industry, Correction, General Medicine, Middle Aged, medicine.disease, Anti-Bacterial Agents, Community-Acquired Infections, Hospitalization, Pneumonia, Infectious Diseases, Practice Guidelines as Topic, Pseudomonas aeruginosa, Etiology, Original Article, Female, Guideline Adherence, business
Abstract

An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p

Published
2020

57. Does the frequency of switching inhalers represent a predictive factor of exacerbation in asthma?

Author

Alida Benfante, Nicola Scichilone, Battaglia S, Cinzia Arena, Stefania Principe, Principe S., Battaglia S., Benfante A., Arena C., and Scichilone N.

Subjects
Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Exacerbation, Settore MED/10 - Malattie Dell'Apparato Respiratorio, exacerbation: inhaler, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Adrenal Cortex Hormones, Administration, Inhalation, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Anti-Asthmatic Agents, Intensive care medicine, device, Asthma, Aged, Aged, 80 and over, business.industry, Inhaler, Nebulizers and Vaporizers, Middle Aged, medicine.disease, switch, Predictive factor, Hospitalization, 030228 respiratory system, Pediatrics, Perinatology and Child Health, business
Abstract

Objective: Management of asthma includes monitoring of inhaler technique and level of adherence to treatment. Both factors could be influenced by high frequency of switching inhaler devices. We explored whether switching inhalers is an independent predictive factor of exacerbations. Methods: Data were collected from 2015 to 2017 from the outpatient clinic of asthma at the University of Palermo, Italy. This observational study consisted of two phases: Phase 1 included subjects of at least three visits in the previous year who reported the frequency of inhalers switched; Phase 2 included subjects of at least two visits during the second year, and the rate of switches and exacerbations was recorded. We included adult (24–84 years old) mild/moderate asthmatics under regular inhaled treatment; uncontrolled asthma was defined as poor symptom control, exacerbations (≥2/year) requiring oral corticosteroids (OCS), or serious exacerbations (≥1/year) requiring hospitalization. Results: A total of 109 records were retrieved for the analysis. A significant correlation between the rate of switches in Phase 1 and exacerbations in Phase 2 was found (p = 0.001). Age and the rates of exacerbations in Phase 1 were also independently associated with a higher number of exacerbations in Phase 2 (p < 0.0001). The multivariate regression model showed that the numbers of switches, as well as exacerbations in Phase 1, were independently correlated to the number of exacerbations in Phase 2 (p = 0.003). Conclusions: The frequency of switching inhalers independently affects the risk of exacerbations in asthma. These results imply that changing inhaler requires careful management in clinical practice.

Published
2020

64. Chronic kidney disease in European patients with obstructive sleep apnea: the ESADA cohort study

Author

Marrone, O, Battaglia, S, Steiropoulos, P, Basoglu, O, Kvamme, J, Ryan, S, Pepin, J, Verbraecken, J, Grote, L, Hedner, J, Bonsignore, M, Anttalainen, U, Saaresranta, T, Barbé, F, Tasbakan, S, Bielicki, P, Kumor, M, Dumitrascu, R, Schulz, R, Escourrou, P, Roisman, G, Fietze, I, Penzel, T, Kent, B, Mcnicholas, W, Lévy, P, Pépin, J, Tamisier, R, Lavie, L, Lavie, P, Masa, J, Montserrat, J, Pataka, A, Plywaczewski, R, Sliwinski, P, Pretl, M, Riha, R, Rodenstein, D, Tkacova, R, Varoneckas, G, Vrints, H, Vitols, A., LOMBARDI, CAROLINA, PARATI, GIANFRANCO, ESADA Study Grp, Marrone, O., Battaglia, S., Steiropoulos, P., Basoglu, O., Kvamme, J., Ryan, S., Pepin, J., Verbraecken, J., Grote, L., Hedner, J., Bonsignore, M., Marrone, O, Battaglia, S, Steiropoulos, P, Basoglu, O, Kvamme, J, Ryan, S, Pepin, J, Verbraecken, J, Grote, L, Hedner, J, Bonsignore, M, Anttalainen, U, Saaresranta, T, Barbé, F, Tasbakan, S, Bielicki, P, Kumor, M, Dumitrascu, R, Schulz, R, Escourrou, P, Roisman, G, Fietze, I, Penzel, T, Kent, B, Mcnicholas, W, Lévy, P, Pépin, J, Tamisier, R, Lavie, L, Lavie, P, Lombardi, C, Parati, G, Masa, J, Montserrat, J, Pataka, A, Plywaczewski, R, Sliwinski, P, Pretl, M, Riha, R, Rodenstein, D, Tkacova, R, Varoneckas, G, Vrints, H, and Vitols, A

Subjects
Male, Comorbidity, Body Mass Index, Cohort Studies, Behavioral Neuroscience, 0302 clinical medicine, Risk Factors, Prevalence, obstructive sleep apnea, Aged, 80 and over, Sex Characteristics, Sleep Apnea, Obstructive, Medicine (all), Sleep apnea, General Medicine, Middle Aged, Europe, Hypertension, Cardiology, nephropathy, epidemiology, Female, Glomerular Filtration Rate, Cohort study, Adult, medicine.medical_specialty, Adolescent, Polysomnography, Cognitive Neuroscience, Renal function, Settore MED/10 - Malattie Dell'Apparato Respiratorio, ta3111, Nephropathy, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Obesity, Renal Insufficiency, Chronic, Aged, Heart Failure, hypoxia, business.industry, medicine.disease, Oxygen, Obstructive sleep apnea, Cross-Sectional Studies, 030228 respiratory system, Heart failure, Physical therapy, Human medicine, business, Body mass index, 030217 neurology & neurosurgery, Kidney disease
Abstract

The cross-sectional relationship of obstructive sleep apnea with moderate to severe chronic kidney disease, defined as an estimated glomerular filtration rate = 30) was found in 34% of subjects. The lowest nocturnal oxygen saturation was 81 +/- 10.2%. Chronic kidney disease prevalence in the whole sample was 8.7% or 6.1%, according to the Modification of Diet in Renal Disease or the Chronic Kidney Disease-Epidemiology Collaboration equations, respectively. Subjects with lower estimated glomerular filtration rate were older, more obese, more often female, had worse obstructive sleep apnea and more co-morbidities (P < 0.001, each). With both equations, independent predictors of estimated glomerular filtration rate < 60 were: chronic heart failure; female gender; systemic hypertension; older age; higher body mass index; and worse lowest nocturnal oxygen saturation. It was concluded that in obstructive sleep apnea, chronic kidney disease is largely predicted by co-morbidities and anthropometric characteristics. In addition, severe nocturnal hypoxaemia, even for only a small part of the night, may play an important role as a risk factor for kidney dysfunction.

Published
2016

66. Psycho-social factors associated with mental resilience in the Corona lockdown

Author

Veer, I.M. Riepenhausen, A. Zerban, M. Wackerhagen, C. Puhlmann, L.M.C. Engen, H. Köber, G. Bögemann, S.A. Weermeijer, J. Uściłko, A. Mor, N. Marciniak, M.A. Askelund, A.D. Al-Kamel, A. Ayash, S. Barsuola, G. Bartkute-Norkuniene, V. Battaglia, S. Bobko, Y. Bölte, S. Cardone, P. Chvojková, E. Damnjanović, K. De Calheiros Velozo, J. de Thurah, L. Deza-Araujo, Y.I. Dimitrov, A. Farkas, K. Feller, C. Gazea, M. Gilan, D. Gnjidić, V. Hajduk, M. Hiekkaranta, A.P. Hofgaard, L.S. Ilen, L. Kasanova, Z. Khanpour, M. Lau, B.H.P. Lenferink, D.B. Lindhardt, T.B. Magas, D.Á. Mituniewicz, J. Moreno-López, L. Muzychka, S. Ntafouli, M. O’Leary, A. Paparella, I. Põldver, N. Rintala, A. Robak, N. Rosická, A.M. Røysamb, E. Sadeghi, S. Schneider, M. Siugzdaite, R. Stantić, M. Teixeira, A. Todorovic, A. Wan, W.W.N. van Dick, R. Lieb, K. Kleim, B. Hermans, E.J. Kobylińska, D. Hendler, T. Binder, H. Myin-Germeys, I. van Leeuwen, J.M.C. Tüscher, O. Yuen, K.S.L. Walter, H. Kalisch, R.

Abstract

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics. © 2021, The Author(s).

Published
2021

67. Predicting in-hospital mortality from Coronavirus Disease 2019: A simple validated app for clinical use

Author

Magro, B., Zuccaro, V., Novelli, L., Zileri, L., Celsa, C., Raimondi, F., Gori, Mario, Camma, Giulia, Battaglia, Laura Silvia Carmen Irene, Genova, V. G., Paris, Leonardo, Tacelli, M., Mancarella, Francesco Antonio, Enea, M., Attanasio, M., Senni, M., Marco, F. D., Lorini, L. F., Fagiuoli, Stefano, Bruno, Rosa Anna, Camma, C., Gasbarrini, Antonio, Gori M., Camma G., Battaglia S., Paris L., Mancarella F. A., Fagiuoli S., Bruno R., Gasbarrini A. (ORCID:0000-0002-7278-4823), Magro, B., Zuccaro, V., Novelli, L., Zileri, L., Celsa, C., Raimondi, F., Gori, Mario, Camma, Giulia, Battaglia, Laura Silvia Carmen Irene, Genova, V. G., Paris, Leonardo, Tacelli, M., Mancarella, Francesco Antonio, Enea, M., Attanasio, M., Senni, M., Marco, F. D., Lorini, L. F., Fagiuoli, Stefano, Bruno, Rosa Anna, Camma, C., Gasbarrini, Antonio, Gori M., Camma G., Battaglia S., Paris L., Mancarella F. A., Fagiuoli S., Bruno R., and Gasbarrini A. (ORCID:0000-0002-7278-4823)

Abstract

Backgrounds Validated tools for predicting individual in-hospital mortality of COVID-19 are lacking. We aimed to develop and to validate a simple clinical prediction rule for early identification of in-hospital mortality of patients with COVID-19. Methods and findings We enrolled 2191 consecutive hospitalized patients with COVID-19 from three Italian dedicated units (derivation cohort: 1810 consecutive patients from Bergamo and Pavia units; validation cohort: 381 consecutive patients from Rome unit). The outcome was in-hospital mortality. Fine and Gray competing risks multivariate model (with discharge as a competing event) was used to develop a prediction rule for in-hospital mortality. Discrimination and calibration were assessed by the area under the receiver operating characteristic curve (AUC) and by Brier score in both the derivation and validation cohorts. Seven variables were independent risk factors for in-hospital mortality: age (Hazard Ratio [HR] 1.08, 95% Confidence Interval [CI] 1.07–1.09), male sex (HR 1.62, 95%CI 1.30–2.00), duration of symptoms before hospital admission <10 days (HR 1.72, 95%CI 1.39–2.12), diabetes (HR 1.21, 95% CI 1.02–1.45), coronary heart disease (HR 1.40 95% CI 1.09–1.80), chronic liver disease (HR 1.78, 95%CI 1.16–2.72), and lactate dehydrogenase levels at admission (HR 1.0003, 95%CI 1.0002–1.0005). The AUC was 0.822 (95%CI 0.722–0.922) in the derivation cohort and 0.820 (95%CI 0.724–0.920) in the validation cohort with good calibration. The prediction rule is freely available as a web-app (COVID-CALC: https://sites.google.com/community. unipa.it/covid-19riskpredictions/c19-rp). Conclusions A validated simple clinical prediction rule can promptly and accurately assess the risk for in-hospital mortality, improving triage and the management of patients with COVID-19.

Published
2021

68. Carga y factores de riesgo para la neumonía adquirida en la comunidad de Pseudomonas aeruginosa : un estudio multinacional de prevalencia puntual de pacientes hospitalizados

Author

Restrepo M. I., Babu B. L., Reyes L. F., Chalmers J. D., Soni N. J., Sibila O., Faverio P., Cilloniz C., Rodriguez-Cintron W., Aliberti S., Aruj P. K., Attorri S., Barimboim E., Caeiro J. P., Garzon M. I., Cambursano V. H., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Diaz A. C., de Vedia L., Ganaha M. C., Lambert S., Lopardo G., Luna C. M., Malberti A. G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P. G., Stagnaro J. P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C. A., Van Braeckel E., Vincent J. L., Djimon M. Z., Bashi J., Dodo R., Nouer S. A., Chipev P., Encheva M., Miteva D., Petkova D., Dodo Balkissou A., Pefura Yone E. W., Mbatchou Ngahane B. H., Shen N., Xu J. F., Bustamante Rico C. A., Buitrago R., Pereira Paternina F. J., Kayembe Ntumba J. M., Carevic V. V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Bouchy Jacobsson M. L., Bro Christensen A., Heitmann Bodtger U. C., Niels Meyer C., Vestergaard Jensen A., Baunbaek-Knudsen G., Petersen P. T., Andersen S., Abd El-Wahhab I. E., Elsayed Morsy N., Shafiek H., Sobh E., Abdella Abdulsemed K., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M. W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P. A., Mahesh P. A., Jayaraj B. S., Narayan K. V., Udnur H. B., Krishnamurthy S. B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V. M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A. D., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M. A., Menzella F., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Franzetti F., Carugati M., Morosi M., Monge E., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z. A., Ugalde D. B., Zuniga O. C., Villegas J. F., Medenica M., van de Garde E. M. W., Raj Mihsra D., Shrestha P., Ridgeon E., Awokola B. I., Nwankwo O. N. O., Olufunlola A. B., Olumide S., Ukwaja K. N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Neves J., Ravara S. B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C. M., Birkun A., Kaluzhenina A., Almotairi A., Ali Bukhary Z. A., Edathodu J., Fathy A., Abdulaziz Enani A. M., Mohamed N. E., Memon J. U., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Feldman C., Yum H. K., Borderias L., Bordon Garcia N. M., Cabello Alarcon H., Torres A., Diaz-Brito V., Casas X., Gonzalez A. E., Fernandez-Almira M. L., Gallego M., Gaspar-Garcia I., Del Castillo J. G., Victoria P. J., Martinez E. L., de Molina R. M., Marcos P. J., Menendez R., Pando-Sandoval A., Aymerich C. P., de la Torre A. L., Garcia-Olive I., Rello J., Moyano S., Sanz F., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J. F. M., Torra E. V., Pujol J. A., Fiogbe A. A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D. J., Feneley A., Ions R., Skeemer J., Woltmann G., Hancock C., Hill A. T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K. S., Brito V., Dietz J., Dysart C. E., Kellie S. M., Zablocki C. J., MurphyMurphy R. G., Franco-Sadud R. A., Meier G., Gaga M., Holland T. L., Bergin S. P., Kheir F., Landmeier M., Lois M., Nair G. B., Patel H., Saito S., Noda J., Hinojosa C. I., Levine S. M., Angel L. F., Anzueto A., Whitlow K. S., Hipskind J., Sukhija K., Totten V., Wunderink R. G., Shah R. D., Mateyo K. J., Noriega L., Alvarado E., Aman M., Labra L., Restrepo, M. I., Babu, B. L., Reyes, L. F., Chalmers, J. D., Soni, N. J., Sibila, O., Faverio, P., Cilloniz, C., Rodriguez-Cintron, W., Aliberti, S., Aruj, P. K., Attorri, S., Barimboim, E., Caeiro, J. P., Garzon, M. I., Cambursano, V. H., Ceccato, A., Chertcoff, J., Lascar, F., Di Tulio, F., Diaz, A. C., de Vedia, L., Ganaha, M. C., Lambert, S., Lopardo, G., Luna, C. M., Malberti, A. G., Morcillo, N., Tartara, S., Pensotti, C., Pereyra, B., Scapellato, P. G., Stagnaro, J. P., Shah, S., Lotsch, F., Thalhammer, F., Anseeuw, K., Francois, C. A., Van Braeckel, E., Vincent, J. L., Djimon, M. Z., Bashi, J., Dodo, R., Nouer, S. A., Chipev, P., Encheva, M., Miteva, D., Petkova, D., Dodo Balkissou, A., Pefura Yone, E. W., Mbatchou Ngahane, B. H., Shen, N., Xu, J. F., Bustamante Rico, C. A., Buitrago, R., Pereira Paternina, F. J., Kayembe Ntumba, J. M., Carevic, V. V., Jakopovic, M., Jankovic, M., Matkovic, Z., Mitrecic, I., Bouchy Jacobsson, M. L., Bro Christensen, A., Heitmann Bodtger, U. C., Niels Meyer, C., Vestergaard Jensen, A., Baunbaek-Knudsen, G., Petersen, P. T., Andersen, S., Abd El-Wahhab, I. E., Elsayed Morsy, N., Shafiek, H., Sobh, E., Abdella Abdulsemed, K., Bertrand, F., Brun-Buisson, C., de Montmollin, E., Fartoukh, M., Messika, J., Tattevin, P., Khoury, A., Ebruke, B., Dreher, M., Kolditz, M., Meisinger, M., Pletz, M. W., Hagel, S., Rupp, J., Schaberg, T., Spielmanns, M., Creutz, P., Suttorp, N., Siaw-Lartey, B., Dimakou, K., Papapetrou, D., Tsigou, E., Ampazis, D., Kaimakamis, E., Bhatia, M., Dhar, R., D'Souza, G., Garg, R., Koul, P. A., Mahesh, P. A., Jayaraj, B. S., Narayan, K. V., Udnur, H. B., Krishnamurthy, S. B., Kant, S., Swarnakar, R., Limaye, S., Salvi, S., Golshani, K., Keatings, V. M., Martin-Loeches, I., Maor, Y., Strahilevitz, J., Battaglia, S., Carrabba, M., Ceriana, P., Confalonieri, M., Monforte, A. D., Del Prato, B., De Rosa, M., Fantini, R., Fiorentino, G., Gammino, M. A., Menzella, F., Milani, G., Nava, S., Palmiero, G., Petrino, R., Gabrielli, B., Rossi, P., Sorino, C., Steinhilber, G., Zanforlin, A., Franzetti, F., Carugati, M., Morosi, M., Monge, E., Carone, M., Patella, V., Scarlata, S., Comel, A., Kurahashi, K., Bacha, Z. A., Ugalde, D. B., Zuniga, O. C., Villegas, J. F., Medenica, M., van de Garde, E. M. W., Raj Mihsra, D., Shrestha, P., Ridgeon, E., Awokola, B. I., Nwankwo, O. N. O., Olufunlola, A. B., Olumide, S., Ukwaja, K. N., Irfan, M., Minarowski, L., Szymon, S., Froes, F., Leuschner, P., Meireles, M., Ferrao, C., Neves, J., Ravara, S. B., Brocovschii, V., Ion, C., Rusu, D., Toma, C., Chirita, D., Dorobat, C. M., Birkun, A., Kaluzhenina, A., Almotairi, A., Ali Bukhary, Z. A., Edathodu, J., Fathy, A., Abdulaziz Enani, A. M., Mohamed, N. E., Memon, J. U., Bella, A., Bogdanovic, N., Milenkovic, B., Pesut, D., Feldman, C., Yum, H. K., Borderias, L., Bordon Garcia, N. M., Cabello Alarcon, H., Torres, A., Diaz-Brito, V., Casas, X., Gonzalez, A. E., Fernandez-Almira, M. L., Gallego, M., Gaspar-Garcia, I., Del Castillo, J. G., Victoria, P. J., Martinez, E. L., de Molina, R. M., Marcos, P. J., Menendez, R., Pando-Sandoval, A., Aymerich, C. P., de la Torre, A. L., Garcia-Olive, I., Rello, J., Moyano, S., Sanz, F., Rodrigo-Troyano, A., Sole-Violan, J., Uranga, A., van Boven, J. F. M., Torra, E. V., Pujol, J. A., Fiogbe, A. A., Yangui, F., Bilaceroglu, S., Dalar, L., Yilmaz, U., Bogomolov, A., Elahi, N., Dhasmana, D. J., Feneley, A., Ions, R., Skeemer, J., Woltmann, G., Hancock, C., Hill, A. T., Rudran, B., Ruiz-Buitrago, S., Campbell, M., Whitaker, P., Youzguin, A., Singanayagam, A., Allen, K. S., Brito, V., Dietz, J., Dysart, C. E., Kellie, S. M., Zablocki, C. J., Murphymurphy, R. G., Franco-Sadud, R. A., Meier, G., Gaga, M., Holland, T. L., Bergin, S. P., Kheir, F., Landmeier, M., Lois, M., Nair, G. B., Patel, H., Saito, S., Noda, J., Hinojosa, C. I., Levine, S. M., Angel, L. F., Anzueto, A., Whitlow, K. S., Hipskind, J., Sukhija, K., Totten, V., Wunderink, R. G., Shah, R. D., Mateyo, K. J., Noriega, L., Alvarado, E., Aman, M., Labra, L., Restrepo, M, Babu, B, Reyes, L, Chalmers, J, Soni, N, Sibila, O, Faverio, P, Cilloniz, C, Rodriguez-Cintron, W, Aliberti, S, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Groningen Research Institute for Asthma and COPD (GRIAC), Restrepo M.I., Babu B.L., Reyes L.F., Chalmers J.D., Soni N.J., Sibila O., Faverio P., Cilloniz C., Rodriguez-Cintron W., Aliberti S., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano V.H., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Diaz A.C., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C.A., Van Braeckel E., Vincent J.L., Djimon M.Z., Bashi J., Dodo R., Nouer S.A., Chipev P., Encheva M., Miteva D., Petkova D., Dodo Balkissou A., Pefura Yone E.W., Mbatchou Ngahane B.H., Shen N., Xu J.F., Bustamante Rico C.A., Buitrago R., Pereira Paternina F.J., Kayembe Ntumba J.M., Carevic V.V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Bouchy Jacobsson M.L., Bro Christensen A., Heitmann Bodtger U.C., Niels Meyer C., Vestergaard Jensen A., Baunbaek-Knudsen G., Petersen P.T., Andersen S., Abd El-Wahhab I.E., Elsayed Morsy N., Shafiek H., Sobh E., Abdella Abdulsemed K., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A.D., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Menzella F., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Franzetti F., Carugati M., Morosi M., Monge E., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., van de Garde E.M.W., Raj Mihsra D., Shrestha P., Ridgeon E., Awokola B.I., Nwankwo O.N.O., Olufunlola A.B., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Neves J., Ravara S.B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C.M., Birkun A., Kaluzhenina A., Almotairi A., Ali Bukhary Z.A., Edathodu J., Fathy A., Abdulaziz Enani A.M., Mohamed N.E., Memon J.U., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Feldman C., Yum H.K., Borderias L., Bordon Garcia N.M., Cabello Alarcon H., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., Fernandez-Almira M.L., Gallego M., Gaspar-Garcia I., Del Castillo J.G., Victoria P.J., Martinez E.L., de Molina R.M., Marcos P.J., Menendez R., Pando-Sandoval A., Aymerich C.P., de la Torre A.L., Garcia-Olive I., Rello J., Moyano S., Sanz F., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F.M., Torra E.V., Pujol J.A., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Feneley A., Ions R., Skeemer J., Woltmann G., Hancock C., Hill A.T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Zablocki C.J., MurphyMurphy R.G., Franco-Sadud R.A., Meier G., Gaga M., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Saito S., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Anzueto A., Whitlow K.S., Hipskind J., Sukhija K., Totten V., Wunderink R.G., Shah R.D., Mateyo K.J., Noriega L., Alvarado E., Aman M., and Labra L.

Subjects
Pneumonia, Pseudomonas aeruginosa, Male, antibiotic resistance, Internationality, Cross-sectional study, bacterial colonization, very elderly, Prevalence, Drug Resistance, Drug resistance, Pneumònia adquirida a la comunitat, Pseudomonas aeruginosa community acquired pneumonia, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Tracheostomy, Community-acquired pneumonia, Risk Factors, Epidemiology, 80 and over, Medicine, Community-Acquired Infection, 030212 general & internal medicine, Aged, 80 and over, Cross Infection, adult, article, Bacterial, Middle Aged, Antibiotic coverage, Bronchiectasis, Community-Acquired Infections, hospital patient, priority journal, risk factor, Aged, Cross-Sectional Studies, Drug Resistance, Bacterial, Female, Humans, Logistic Models, Pneumonia, Bacterial, Pseudomonas aeruginosa, Infectious diseases, Human, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Chronic Obstructive, Logistic Model, Admission, Settore MED/10 - Malattie Dell'Apparato Respiratorio, chronic lung disease, Pulmonary Disease, 03 medical and health sciences, Bronchiectasi, Internal medicine, Pseudomonas, controlled study, human, Cross-Sectional Studie, business.industry, Risk Factor, community acquired pneumonia, Pneumonia, medicine.disease, logistic regression analysis, major clinical study, antibiotic sensitivity, hospital admission, 030228 respiratory system, microbiological examination, business, chronic obstructive lung disease
Abstract

Pseudomonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients.

Published
2018

74. Patógenos atípicos en pacientes hospitalizados con neumonía adquirida en la comunidad: una perspectiva mundial

Author

Gramegna A., Sotgiu G., Di Pasquale M., Radovanovic D., Terraneo S., Reyes L. F., Vendrell E., Neves J., Menzella F., Blasi F., Aliberti S., Restrepo M. I., Aruj P. K., Attorri S., Barimboim E., Caeiro J. P., Cambursano V. H., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Diaz A. C., de Vedia L., Ganaha M. C., Lambert S., Lopardo G., Luna C. M., Malberti A. G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P. G., Stagnaro J. P., Lotsch F., Vincent J. L., Anseeuw K., Francois C. A., Van Braeckel E., Djimon M. Z., Bashi J., Roger D., Nouer S. A., Chipev P., Encheva M., Miteva D., Petkova D., Dodo B. A., Hugo M. N. B., Shen N., Xu J. -F., Rico C. A. B., Buitrago R., Paternina F. J. P., Jean-Marie K. N., Carevic V. V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Jacobsson M. -L. B., Christensen A. B., HeitmannBodtger U. C., Meyer C. N., Jensen A. V., Baunbaek-knudsen G., Petersen P. T., Andersen S., El-Wahhab I. E. -S. A., Morsy N. E., Shafi ek H., Sobh E., Bertrand F., Brun- Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Dreher M., Kolditz M., Meisinger M., Pletz M. W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Bhatia M., Ampazis D., Dhar R., D'Souza G., Garg R., Koul P. A., Mahesh P. A., Jayaraj B. S., Narayan K. V., Udnur H. B., Krishnamurthy S. B., Golshani K., Keatings V. M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., d'Arminio A., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M. A., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Steinhilber G., Zanforlin A., Kurahashi K., Bacha Z. A., Ugalde D. B., Zuniga O. C., Villegas J. F., Medenica M., van de Garde E. M. W., Mihsra D. R., Ridgeon E., Nwankwo O. N. O., Olufunlola A. B., Olumide S., Ukwaja K. N., Irfan M., Minarowski L., Szymo S., Froes F., Meireles M., Ferrao C., Leuschner P., Ravara S. B., Brocovschii V., Ion C., Rusu D., Chirita D., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z. A. A., Edathodu J., Fathy A., Enani A. M. A., Mohamed N. E., Memon J. U., Bogdanovic N., Milenkovic B., Borderias L., Garcia N. M. B., Alarcon H. C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A. E., FernandezAlmira M. L., Gallego M., Gaspar-GarcIa I., del Castillo J. G., Victoria P. J., Martinez E. L., de Molina R. M., Marcos P. J., Menendez R., Pando-Sandoval A., Aymerich C. P., del la Torre A. L., Garcia-Olive I., Rello J., Moyano S., Sanz F., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J. F. M., Torra E. V., Pujol J. A., Feldman C., Yum H. K., Fiogbe A. A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D. J., Ions R., Skeemer J., Woltmann G., Hancock C., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Allen K. S., Brito V., Dietz J., Dysart C. E., Franco-Sadud R. A., Kellie G. M. S. M., Gaga M., Bergin S. P., Kheir F., Landmeier M., Lois M., Nair G. B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Soni N. J., Noda J., Hinojosa C. I., Levine S. M., Angel L. F., Anzueto A., Whitlow K. S., Hipskind J., Sukhija K., Wunderink R. G., Shah R. D., Mateyo K. J., Gramegna A., Sotgiu G., Di Pasquale M., Radovanovic D., Terraneo S., Reyes L.F., Vendrell E., Neves J., Menzella F., Blasi F., Aliberti S., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Cambursano V.H., Ceccato A., Chertcoff J., Lascar F., Di Tulio F., Diaz A.C., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Lotsch F., Vincent J.L., Anseeuw K., Francois C.A., Van Braeckel E., Djimon M.Z., Bashi J., Roger D., Nouer S.A., Chipev P., Encheva M., Miteva D., Petkova D., Dodo B.A., Hugo M.N.B., Shen N., Xu J.-F., Rico C.A.B., Buitrago R., Paternina F.J.P., Jean-Marie K.N., Carevic V.V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Jacobsson M.-L.B., Christensen A.B., HeitmannBodtger U.C., Meyer C.N., Jensen A.V., Baunbaek-knudsen G., Petersen P.T., Andersen S., El-Wahhab I.E.-S.A., Morsy N.E., Shafi ek H., Sobh E., Bertrand F., Brun- Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Bhatia M., Ampazis D., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., d'Arminio A., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M.A., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Steinhilber G., Zanforlin A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., van de Garde E.M.W., Mihsra D.R., Ridgeon E., Nwankwo O.N.O., Olufunlola A.B., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymo S., Froes F., Meireles M., Ferrao C., Leuschner P., Ravara S.B., Brocovschii V., Ion C., Rusu D., Chirita D., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z.A.A., Edathodu J., Fathy A., Enani A.M.A., Mohamed N.E., Memon J.U., Bogdanovic N., Milenkovic B., Borderias L., Garcia N.M.B., Alarcon H.C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., FernandezAlmira M.L., Gallego M., Gaspar-GarcIa I., del Castillo J.G., Victoria P.J., Martinez E.L., de Molina R.M., Marcos P.J., Menendez R., Pando-Sandoval A., Aymerich C.P., del la Torre A.L., Garcia-Olive I., Rello J., Moyano S., Sanz F., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F.M., Torra E.V., Pujol J.A., Feldman C., Yum H.K., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Ions R., Skeemer J., Woltmann G., Hancock C., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Allen K.S., Brito V., Dietz J., Dysart C.E., Franco-Sadud R.A., Kellie G.M.S.M., Gaga M., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Soni N.J., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Anzueto A., Whitlow K.S., Hipskind J., Sukhija K., Wunderink R.G., Shah R.D., and Mateyo K.J.

Subjects
medicine.medical_specialty, Atypical pathogens, Epidemiology, Population, Settore MED/10 - Malattie Dell'Apparato Respiratorio, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Community-acquired pneumonia, Internal medicine, Risk Factors, Medicine, lcsh:RC109-216, 030212 general & internal medicine, education, Aged, 80 and over, education.field_of_study, business.industry, Incidence (epidemiology), Atypical pathogen, Healthcare-Associated Pneumonia, Chlamydophila pneumoniae, medicine.disease, Antibiotic coverage, CAP, Pneumonia, Infectious Diseases, 030228 respiratory system, Legionnaires' disease, business, Research Article
Abstract

Background Empirical antibiotic coverage for atypical pathogens in community-acquired pneumonia (CAP) has long been debated, mainly because of a lack of epidemiological data. We aimed to assess both testing for atypical pathogens and their prevalence in hospitalized patients with CAP worldwide, especially in relation with disease severity. Methods A secondary analysis of the GLIMP database, an international, multicentre, point-prevalence study of adult patients admitted for CAP in 222 hospitals across 6 continents in 2015, was performed. The study evaluated frequency of testing for atypical pathogens, including L. pneumophila, M. pneumoniae, C. pneumoniae, and their prevalence. Risk factors for testing and prevalence for atypical pathogens were assessed through univariate analysis. Results Among 3702 CAP patients 1250 (33.8%) underwent at least one test for atypical pathogens. Testing varies greatly among countries and its frequency was higher in Europe than elsewhere (46.0% vs. 12.7%, respectively, p L. pneumophila urinary antigen was the most common test performed worldwide (32.0%). Patients with severe CAP were less likely to be tested for both atypical pathogens considered together (30.5% vs. 35.0%, p = 0.009) and specifically for legionellosis (28.3% vs. 33.5%, p = 0.003) than the rest of the population. Similarly, L. pneumophila testing was lower in ICU patients. At least one atypical pathogen was isolated in 62 patients (4.7%), including M. pneumoniae (26/251 patients, 10.3%), L. pneumophila (30/1186 patients, 2.5%), and C. pneumoniae (8/228 patients, 3.5%). Patients with CAP due to atypical pathogens were significantly younger, showed less cardiovascular, renal, and metabolic comorbidities in comparison to adult patients hospitalized due to non-atypical pathogen CAP. Conclusions Testing for atypical pathogens in patients admitted for CAP in poorly standardized in real life and does not mirror atypical prevalence in different settings. Further evidence on the impact of atypical pathogens, expecially in the low-income countries, is needed to guidelines implementation.

Published
2018

75. The hidden burden of severe asthma: from patient perspective to new opportunities for clinicians

Author

Catherine M. Hawrylowicz, Robert H. Brown, Todor A. Popov, Pierachille Santus, Stefano Centanni, Paolo Solidoro, Maria Gabriella Matera, Angelo Corsico, Andrea Matucci, Enrico Heffler, Gaetano Caramori, Pierluigi Paggiaro, Mina Gaga, Giorgio Walter Canonica, Alberto Papi, Alkis Togias, Paola Rogliani, Fabiano Di Marco, Louis-Philippe Boulet, Antonella Cianferoni, Nicola Scichilone, Alida Benfante, Battaglia S, Mario Cazzola, Peter J. Barnes, Giuseppe De Carlo, Scichilone, Nicola, Barnes, Peter John, Battaglia, Salvatore, Benfante, Alida, Brown, Robert, Canonica, Giorgio Walter, Caramori, Gaetano, Cazzola, Mario, Centanni, Stefano, Cianferoni, Antonella, Corsico, Angelo, De Carlo, Giuseppe, Di Marco, Fabiano, Gaga, Mina, Hawrylowicz, Catherine, Heffler, Enrico, Matera, Maria Gabriella, Matucci, Andrea, Paggiaro, Pierluigi, Papi, Alberto, Popov, Todor, Rogliani, Paola, Santus, Pierachille, Solidoro, Paolo, Togias, Alki, and Boulet, Louis-Philippe

Subjects
severe asthma, medicine.medical_specialty, Severe asthma, precision medicine, Acknowledgement, lcsh:Medicine, Socio-culturale, Review, Disease, biomarkers, patient’s perspective, precision medicine, severe asthma, Medical care, 03 medical and health sciences, Therapeutic approach, 0302 clinical medicine, Medicine, 030212 general & internal medicine, ddc:610, Intensive care medicine, business.industry, lcsh:R, Perspective (graphical), General Medicine, Research opportunities, Biomarkers, patient’s perspective, precision medicine, severe asthma, Biomarkers, Patient’s perspective, Precision medicine, patient’s perspective, Natural history, 030228 respiratory system, business
Abstract

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the “International Course on Severe Asthma” that took place in Palermo, Italy, on May 10–11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient’s needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach.

Published
2020

76. TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model

Author

Moukengue, B. Brown, H.K. Charrier, C. Battaglia, S. Baud'huin, M. Quillard, T. Pham, T.M. Pateras, I.S. Gorgoulis, V.G. Helleday, T. Heymann, D. Berglund, U.W. Ory, B. Lamoureux, F.

Abstract

Background: Osteosarcoma (OS) is the most common primary malignant bone tumour. Unfortunately, no new treatments are approved and over the last 30 years the survival rate remains only 30% at 5 years for poor responders justifying an urgent need of new therapies. The Mutt homolog 1 (MTH1) enzyme prevents incorporation of oxidized nucleotides into DNA and recently developed MTH1 inhibitors may offer therapeutic potential as MTH1 is overexpressed in various cancers. Methods: The aim of this study was to evaluate the therapeutic benefits of targeting MTH1 with two chemical inhibitors, TH588 and TH1579 on human osteosarcoma cells. Preclinical efficacy of TH1579 was assessed in human osteosarcoma xenograft model on tumour growth and development of pulmonary metastases. Findings: MTH1 is overexpressed in OS patients and tumour cell lines, compared to mesenchymal stem cells. In vitro, chemical inhibition of MTH1 by TH588 and TH1579 decreases OS cells viability, impairs their cell cycle and increases apoptosis in OS cells. TH1579 was confirmed to bind MTH1 by CETSA in OS model. Moreover, 90 mg/kg of TH1579 reduces in vivo tumour growth by 80.5% compared to non-treated group at day 48. This result was associated with the increase in 8-oxo-dG integration into tumour cells DNA and the increase of apoptosis. Additionally, TH1579 also reduces the number of pulmonary metastases. Interpretation: All these results strongly provide a pre-clinical proof-of-principle that TH1579 could be a therapeutic option for patients with osteosarcoma. Funding: This study was supported by La Ligue Contre le Cancer, la SFCE and Enfants Cancers Santé. © 2020 The Authors

Published
2020

77. Mental disability management within occupational health surveillance

Author

Buselli, R., Del Guerra, P., Caldi, F., Veltri, A., Battaglia, S., Baldanzi, S., Girardi, M., Sallese, D., Dell'Osso, L., and Cristaudo, A.

Subjects
Psychotherapy, Mental Health, Treatment Outcome, Italy, Mental Disorders, Psychic disability, Health surveillance, Mental disorders, Occupational medicine, Anxiety Disorders, Humans, Occupational Health
Published
2020

78. TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model

Author

Moukengue, B., Brown, H.K., Charrier, C., Battaglia, S., Baud'huin, M., Quillard, T., Pham, T.M., Pateras, I.S., Gorgoulis, V.G., Helleday, T., Heymann, D., Berglund, U.W., Ory, B., Lamoureux, F., Heymann, Dominique, Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of Oncology and Metabolism [Sheffield, UK] (INSERM European Associated Laboratory 'Sarcoma Research Unit'), The University of Sheffield [Sheffield, U.K.], Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm], National and Kapodistrian University of Athens (NKUA), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], University of Sheffield [Sheffield], Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
[SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Research paper, Lung Neoplasms, lcsh:Medicine, Antineoplastic Agents, Apoptosis, Bone Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Mice, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Tumor Cells, Cultured, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, lcsh:R5-920, Osteosarcoma, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, lcsh:R, ROS, DNA, Bone tumours, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Phosphoric Monoester Hydrolases, MTH1, DNA Repair Enzymes, Pyrimidines, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 8-Hydroxy-2'-Deoxyguanosine, DNA damage, lcsh:Medicine (General)
Abstract

Background: Osteosarcoma (OS) is the most common primary malignant bone tumour. Unfortunately, no new treatments are approved and over the last 30 years the survival rate remains only 30% at 5 years for poor responders justifying an urgent need of new therapies. The Mutt homolog 1 (MTH1) enzyme prevents incorporation of oxidized nucleotides into DNA and recently developed MTH1 inhibitors may offer therapeutic potential as MTH1 is overexpressed in various cancers. Methods: The aim of this study was to evaluate the therapeutic benefits of targeting MTH1 with two chemical inhibitors, TH588 and TH1579 on human osteosarcoma cells. Preclinical efficacy of TH1579 was assessed in human osteosarcoma xenograft model on tumour growth and development of pulmonary metastases. Findings: MTH1 is overexpressed in OS patients and tumour cell lines, compared to mesenchymal stem cells. In vitro, chemical inhibition of MTH1 by TH588 and TH1579 decreases OS cells viability, impairs their cell cycle and increases apoptosis in OS cells. TH1579 was confirmed to bind MTH1 by CETSA in OS model. Moreover, 90 mg/kg of TH1579 reduces in vivo tumour growth by 80.5% compared to non-treated group at day 48. This result was associated with the increase in 8-oxo-dG integration into tumour cells DNA and the increase of apoptosis. Additionally, TH1579 also reduces the number of pulmonary metastases. Interpretation: All these results strongly provide a pre-clinical proof-of-principle that TH1579 could be a therapeutic option for patients with osteosarcoma. Funding: This study was supported by La Ligue Contre le Cancer, la SFCE and Enfants Cancers Santé. Key words: Osteosarcoma, Bone tumours, MTH1, ROS, DNA damage

Published
2020

79. Equipo

Author

Battaglia, S. and Daprà, F.

Published
2020

80. PREVALENCE OF ARTERIAL HYPERTENSION AND CHARACTERISTICS OF NOCTURNAL BLOOD PRESSURE PROFILE OF ASTHMA PATIENTS ACCORDING TO THERAPY AND SEVERITY OF THE DISEASE: THE BADA STUDY

Author

Nicola Scichilone, Alida Benfante, Antonino Tuttolomondo, Giuliana Rizzo, Antonio Pinto, Domenico Di Raimondo, Gaia Musiari, Battaglia S, Di Raimondo D., Musiari G., Benfante A., Battaglia S., Rizzo G., Tuttolomondo A., Scichilone N., and Pinto A.

Subjects
cardiovascular risk, Adult, Male, medicine.medical_specialty, Ambulatory blood pressure, Patients, Physiology, Health, Toxicology and Mutagenesis, lcsh:Medicine, Blood Pressure, Disease, 030204 cardiovascular system & hematology, Essential hypertension, Severity of Illness Index, Article, nocturnal dipping of blood pressure, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Diabetes mellitus, Internal medicine, Prevalence, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Contraindication, Aged, Asthma, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, essential hypertension, Odds ratio, asthma, Blood Pressure Monitoring, Ambulatory, Middle Aged, medicine.disease, Nocturnal blood pressure, Circadian Rhythm, Nocturnal dipping of blood pressure, Blood pressure, Hypertension, inhaled corticosteroid therapy, Female, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract

Background: several studies report an increased risk for asthmatic subjects to develop arterial hypertension and the relationship between these two diseases, frequently co-existing, still has some unclear aspects. Methods: The BADA (blood pressure levels, clinical features and markers of subclinical cardiovascular damage of asthma patients) study is aimed to evaluate the prevalence of the cardiovascular comorbidities of asthma and their impact on the clinical outcome. The main exclusion criteria were the presence of other respiratory diseases, current smoking, any contraindication to ambulatory blood pressure monitoring (ABPM). Results: The overall percentage of asthmatics having also hypertension was 75% (30 patients) vs. 45% (18 patients) of the control group (p: 0.012). Reduced level of FEV1 (but not inhaled steroid therapy) was associated to newly-diagnosed hypertension (p: 0.0002), higher day SBP levels (p: 0.003), higher day DBP levels (p: 0.03), higher 24 h-SBP levels (p: 0.005) and higher 24h-DBP levels (p: 0.03). The regression analysis performed taking into account sex, age, diabetes, fasting glucose, and body mass index confirms the independent role played by asthma: odds ratio (OR): 3.66 (CI: 1.29&ndash, 11.1). Conclusions: hypertension is highly prevalent in asthma, the use of ABPM has allowed the detection of a considerable number of unrecognized hypertensives.

Published
2021

81. Multi-Label Random Forest Model for Tuberculosis Drug Resistance Classification and Mutation Ranking

Author

Kouchaki, S, Yang, Y, Lachapelle, A, Walker, T, Walker, SA, Hoosdally, S, Gibertoni Cruz, AL, Carter, J, Grazian, C, Earle, SG, Fowler, P, Iqbal, Z, Hunt, M, Knaggs, J, Smith, GE, Rathod, P, Jarrett, L, Matias, D, Cirillo, DM, Borroni, E, Battaglia, S, Ghodousi, A, Spitaler, A, Cabibbe, A, Tahseen, S, Nilgiriwala, K, Shah, S, Rodrigues, C, Kambli, P, Surve, U, Khot, R, Niemann, S, Merker, M, Hoffmann, H, Todt, K, Plesnik, S, Ismail, N, Omar, SV, Joseph, L, Thwaites, G, Thuong, TNT, Ngoc, NH, Srinivasan, V, Moore, D, Coronel, J, Solano, W, Gao, GF, He, G, Zhao, Y, Liu, C, Ma, A, Zhu, B, Laurenson, I, Claxton, P, Koch, A, Wilkinson, R, Lalvani, A, Posey, J, Gardy, J, Werngren, J, Paton, N, Jou, R, Wu, MH, Lin, WH, Ferrazoli, L, Siqueira de Oliveira, R, Arandjelovic, I, Chaiprasert, A, Comas, I, Roig, CR, Drobniewski, FA, Farhat, MR, Gao, Q, Hee, ROT, Sintchenko, V, Supply, P, van Soolingen, D, Peto, TEA, Crook, D, Clifton, D, Kouchaki, S, Yang, Y, Lachapelle, A, Walker, T, Walker, SA, Hoosdally, S, Gibertoni Cruz, AL, Carter, J, Grazian, C, Earle, SG, Fowler, P, Iqbal, Z, Hunt, M, Knaggs, J, Smith, GE, Rathod, P, Jarrett, L, Matias, D, Cirillo, DM, Borroni, E, Battaglia, S, Ghodousi, A, Spitaler, A, Cabibbe, A, Tahseen, S, Nilgiriwala, K, Shah, S, Rodrigues, C, Kambli, P, Surve, U, Khot, R, Niemann, S, Merker, M, Hoffmann, H, Todt, K, Plesnik, S, Ismail, N, Omar, SV, Joseph, L, Thwaites, G, Thuong, TNT, Ngoc, NH, Srinivasan, V, Moore, D, Coronel, J, Solano, W, Gao, GF, He, G, Zhao, Y, Liu, C, Ma, A, Zhu, B, Laurenson, I, Claxton, P, Koch, A, Wilkinson, R, Lalvani, A, Posey, J, Gardy, J, Werngren, J, Paton, N, Jou, R, Wu, MH, Lin, WH, Ferrazoli, L, Siqueira de Oliveira, R, Arandjelovic, I, Chaiprasert, A, Comas, I, Roig, CR, Drobniewski, FA, Farhat, MR, Gao, Q, Hee, ROT, Sintchenko, V, Supply, P, van Soolingen, D, Peto, TEA, Crook, D, and Clifton, D

Published
2020

82. GenomegaMap: within-species genome-wide d_N/d_S estimation from over 10,000 genomes

Author

Wilson, D, Crook, DW, Peto, TEA, Walker, AS, Hoosdally, SJ, Gibertoni Cruz, AL, Carter, J, Grazian, C, Earle, SG, Kouchaki, S, Lachapelle, A, Yang, Y, Clifton, DA, Fowler, PW, Iqbal, Z, Hunt, M, Knaggs, J, Smith, EG, Rathod, P, Jarrett, L, Matias, D, Cirillo, DM, Borroni, E, Battaglia, S, Ghodousi, A, Spitaleri, A, Cabibbe, A, Tahseen, S, Nilgiriwala, K, Shah, S, Rodrigues, C, Kambli, P, Surve, U, Khot, R, NIemann, S, Kohl, TA, Merker, M, Hoffman, H, Todt, K, Plesnik, S, Ismail, N, Omar, SV, Joseph, L, Thwaites, G, Thoung, TNT, Ngoc, NH, Srinivasan, V, Walker, TM, Moore, D, Coronel, J, Solano, W, Gao, GF, He, G, Zhao, Y, Liu, C, Ma, A, Zhu, B, Laurenson, I, Claxton, P, Koch, A, Wilkinson, R, Lalvani, A, Posey, J, Gardy, J, Werngren, J, Paton, N, Jou, R, Wu, MH, Lin, WH, Ferrazoli, L, Siqueira de Oliveira, R, Arandjelovic, I, Chaipresert, A, Comas, I, Roig, CJ, Drobniewski, FA, Farhat, MR, Gao, Q, Hee, ROT, Sintchenko, V, Wilson, D, Crook, DW, Peto, TEA, Walker, AS, Hoosdally, SJ, Gibertoni Cruz, AL, Carter, J, Grazian, C, Earle, SG, Kouchaki, S, Lachapelle, A, Yang, Y, Clifton, DA, Fowler, PW, Iqbal, Z, Hunt, M, Knaggs, J, Smith, EG, Rathod, P, Jarrett, L, Matias, D, Cirillo, DM, Borroni, E, Battaglia, S, Ghodousi, A, Spitaleri, A, Cabibbe, A, Tahseen, S, Nilgiriwala, K, Shah, S, Rodrigues, C, Kambli, P, Surve, U, Khot, R, NIemann, S, Kohl, TA, Merker, M, Hoffman, H, Todt, K, Plesnik, S, Ismail, N, Omar, SV, Joseph, L, Thwaites, G, Thoung, TNT, Ngoc, NH, Srinivasan, V, Walker, TM, Moore, D, Coronel, J, Solano, W, Gao, GF, He, G, Zhao, Y, Liu, C, Ma, A, Zhu, B, Laurenson, I, Claxton, P, Koch, A, Wilkinson, R, Lalvani, A, Posey, J, Gardy, J, Werngren, J, Paton, N, Jou, R, Wu, MH, Lin, WH, Ferrazoli, L, Siqueira de Oliveira, R, Arandjelovic, I, Chaipresert, A, Comas, I, Roig, CJ, Drobniewski, FA, Farhat, MR, Gao, Q, Hee, ROT, and Sintchenko, V

Abstract

The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters such as dN/dS, but analysing very large datasets poses a major statistical challenge. Here I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: (i) it is fast no matter how large the sample size and (ii) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well-estimated even when genomegaMap’s simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in M. tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species.

Published
2020

83. Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma

Author

Lucarelli, G, Ferro, M, Loizzo, D, Bianchi, C, Terracciano, D, Cantiello, F, Bell, L, Battaglia, S, Porta, C, Gernone, A, Perego, R, Maiorano, E, Cobelli, O, Castellano, G, Vincenti, L, Ditonno, P, Battaglia, M, Lucarelli, Giuseppe, Ferro, Matteo, Loizzo, Davide, Bianchi, Cristina, Terracciano, Daniela, Cantiello, Francesco, Bell, Lauren N., Battaglia, Stefano, Porta, Camillo, Gernone, Angela, Perego, Roberto., Maiorano, Eugenio, Cobelli, Ottavio de, Castellano, Giuseppe, Vincenti, Leonardo, Ditonno, Pasquale, Battaglia, Michele, Lucarelli, G, Ferro, M, Loizzo, D, Bianchi, C, Terracciano, D, Cantiello, F, Bell, L, Battaglia, S, Porta, C, Gernone, A, Perego, R, Maiorano, E, Cobelli, O, Castellano, G, Vincenti, L, Ditonno, P, Battaglia, M, Lucarelli, Giuseppe, Ferro, Matteo, Loizzo, Davide, Bianchi, Cristina, Terracciano, Daniela, Cantiello, Francesco, Bell, Lauren N., Battaglia, Stefano, Porta, Camillo, Gernone, Angela, Perego, Roberto., Maiorano, Eugenio, Cobelli, Ottavio de, Castellano, Giuseppe, Vincenti, Leonardo, Ditonno, Pasquale, and Battaglia, Michele

Abstract

Clear cell renal cell carcinoma (ccRCC) is fundamentally a metabolic disease. Given the importance of lipids in many cellular processes, in this study we delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. Untargeted lipidomic analysis was performed on 20 ccRCC and 20 paired normal tissues, using LC-MS and GC-MS. Different lipid classes were altered in cancer compared to normal tissue. Among the long chain fatty acids (LCFAs), significant accumulations of polyunsaturated fatty acids (PUFAs) were found. Integrated lipidomic and transcriptomic analysis showed that fatty acid desaturation and elongation pathways were enriched in neoplastic tissue. Consistent with these findings, we observed increased expression of stearoyl-CoA desaturase(SCD1) and FA elongase 2 and 5 in ccRCC. Primary renal cancer cells treated with a small molecule SCD1 inhibitor (A939572) proliferated at a slower rate than untreated cancer cells. In addition, after cisplatin treatment, the death rate of tumor cells treated with A939572 was significantly greater than that of untreated cancer cells. In conclusion, our findings delineate a ccRCC lipidomic signature and showed that SCD1 inhibition significantly reduced cancer cell proliferation and increased cisplatin sensitivity, suggesting that this pathway can be involved in ccRCC chemotherapy resistance.

Published
2020

89. Characterization of Genomic Variants Associated with Resistance to Bedaquiline and Delamanid in Naive Mycobacterium tuberculosis Clinical Strains

Author

Battaglia, S., primary, Spitaleri, A., additional, Cabibbe, A. M., additional, Meehan, C. J., additional, Utpatel, C., additional, Ismail, N., additional, Tahseen, S., additional, Skrahina, A., additional, Alikhanova, N., additional, Mostofa Kamal, S. M., additional, Barbova, A., additional, Niemann, S., additional, Groenheit, R., additional, Dean, A. S., additional, Zignol, M., additional, Rigouts, L., additional, and Cirillo, D. M., additional

Published
2020
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90. Characterization of genomic variants associated with resistance to bedaquiline and delamanid in naïve Mycobacterium tuberculosis clinical strains

Author

Battaglia, S, primary, Spitaleri, A, additional, Cabibbe, AM, additional, Meehan, CJ, additional, Utpatel, C, additional, Ismail, N, additional, Tahseen, S, additional, Skrahina, A, additional, Alikhanova, N, additional, Mostofa, Kamal SM, additional, Barbova, A, additional, Niemann, S, additional, Groenheit, R, additional, Dean, AS, additional, Zignol, M, additional, Rigouts, L, additional, and Cirillo, DM, additional

Published
2020
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96. An international perspective on hospitalized patients with viral community-acquired pneumonia

Author

Radovanovic, D., Sotgiu, G., Jankovic, M., Mahesh, P.A., Marcos, P.J., Abdalla, M.I., Di Pasquale, M.F., Gramegna, A., Terraneo, S., Blasi, F., Santus, P., Aliberti, S., Reyes, L.F., Restrepo, M.I., Aruj, P.K., Attorri, S., Barimboim, E., Caeiro, J.P., Garzón, M.I., Cambursano, V.H., Ceccato, A., Chertcoff, J., Cordon Díaz, A., de Vedia, L., Ganaha, M.C., Lambert, S., Lopardo, G., Luna, C.M., Malberti, A.G., Morcillo, N., Tartara, S., Pensotti, C., Pereyra, B., Scapellato, P.G., Stagnaro, J.P., Shah, S., Lötsch, F., Thalhammer, F., Anseeuw, K., Francois, C.A., Van Braeckel, E., Vincent, J.L., Djimon, M.Z., Aranha Nouér, S., Chipev, P., Encheva, M., Miteva, D., Petkova, D., Balkissou, A.D., Pefura Yone, E.W., Mbatchou Ngahane, B.H., Shen, N., Xu, J.F., Bustamante Rico, C.A., Buitrago, R., Pereira Paternina, F.J., Kayembe Ntumba, J.M., Vladic-Carevic, V., Jakopovic, M., Matkovic, Z., Mitrecic, I., Bouchy Jacobsson, M.L., Bro Christensen, A., Heitmann Bødtger, U.C., Meyer, C.N., Vestergaard Jensen, A., El-Said Abd El-Wahhab, I., Elsayed Morsy, N., Shafiek, H., Sobh, E., Abdulsemed, K.A., Bertrand, F., Brun-Buisson, C., de Montmollin, E., Fartoukh, M., Messika, J., Tattevin, P., Khoury, A., Ebruke, B., Dreher, M., Kolditz, M., Meisinger, M., Pletz, M.W., Hagel, S., Rupp, J., Schaberg, T., Spielmanns, M., Creutz, P., Suttorp, N., Siaw-Lartey, B., Dimakou, K., Papapetrou, D., Tsigou, E., Ampazis, D., Kaimakamis, E., Bhatia, M., Dhar, R., D'Souza, G., Garg, R., Koul, P.A., Jayaraj, B.S., Narayan, K.V., Udnur, H.B., Krishnamurthy, S.B., Kant, S., Swarnakar, R., Salvi, S., Limaye, S., Golshani, K., Keatings, V.M., Martin-Loeches, I., Maor, Y., Strahilevitz, J., Battaglia, S., Carrabba, M., Ceriana, P., Confalonieri, M., d'Arminio Monforte, A., Del Prato, B., De Rosa, M., Fantini, R., Fiorentino, G., Gammino, M.A., Menzella, F., Milani, G., Nava, S., Palmiero, G., Petrino, R., Gabrielli, B., Rossi, P., Sorino, C., Steinhilber, G., Zanforlin, A., Franzetti, F., Carone, M., Patella, V., Scarlata, S., Comel, A., Kurahashi, K., Aoun Bacha, Z., Barajas Ugalde, D., Ceballos Zuñiga, O., Villegas, J.F., Medenica, M., van de Garde, E.M.W., Raj Mihsra, D., Shrestha, P., Ridgeon, E., Ishola Awokola, B., Nwankwo, O.N.O., Olufunlola, A.B., Olumide, S., Ukwaja, K.N., Irfan, M., Minarowski, L., Szymon, S., Froes, F., Leuschner, P., Meireles, M., Ferrão, C., Neves, J., Ravara, S.B., Brocovschii, V., Ion, C., Rusu, D., Toma, C., Chirita, D., Dorobat, C.M., Birkun, A., Kaluzhenina, A., Almotairi, A., Bukhary, Z.A.A., Edathodu, J., Fathy, A., Mushira Abdulaziz Enani, A., Eltayeb Mohamed, N., Ulhadi Memon, J., Bella, A., Bogdanovic, N., Milenkovic, B., Pesut, D., Borderìas, L., Bordon Garcia, N.M., Cabello Alarcón, H., Cilloniz, C., Torres, A., Diaz-Brito, V., Casas, X., Encabo González, A., Fernández-Almira, M.L., Gallego, M., Gaspar-GarcÍa, I., González Del Castillo, J., Javaloyes Victoria, P., Laserna Martínez, E., Malo de Molina, R., and Menéndez, R.

Subjects
viruses
Abstract

Background: Who should be tested for viruses in patients with community acquired pneumonia (CAP), prevalence and risk factors for viral CAP are still debated. We evaluated the frequency of viral testing, virus prevalence, risk factors and treatment coverage with oseltamivir in patients admitted for CAP. Methods: Secondary analysis of GLIMP, an international, multicenter, point-prevalence study of hospitalized adults with CAP. Testing frequency, prevalence of viral CAP and treatment with oseltamivir were assessed among patients who underwent a viral swab. Univariate and multivariate analysis was used to evaluate risk factors. Results: 553 (14.9%) patients with CAP underwent nasal swab. Viral CAP was diagnosed in 157 (28.4%) patients. Influenza virus was isolated in 80.9% of cases. Testing frequency and viral CAP prevalence were inhomogeneous across the participating centers. Obesity (OR 1.59, 95%CI: 1.01–2.48; p = 0.043) and need for invasive mechanical ventilation (OR 1.62, 95%CI: 1.02–2.56; p = 0.040) were independently associated with viral CAP. Prevalence of empirical treatment with oseltamivir was 5.1%. Conclusion: In an international scenario, testing frequency for viruses in CAP is very low. The most common cause of viral CAP is Influenza virus. Obesity and need for invasive ventilation represent independent risk factors for viral CAP. Adherence to recommendations for treatment with oseltamivir is poor.

Published
2019

97. DeepAMR for predicting co-occurrent resistance of Mycobacterium tuberculosis

Author

Yang, Y, Walker, TM, Walker, AS, Wilson, DJ, Peto, TEA, Crook, DW, Shamout, F, Zhu, T, Clifton, DA, Arandjelovic, I, Comas, I, Farhat, MR, Gao, Q, Sintchenko, V, Van Soolingen, D, Hoosdally, S, Cruz, ALG, Carter, J, Grazian, C, Earle, SG, Kouchaki, S, Fowler, PW, Iqbal, Z, Hunt, M, Smith, EG, Rathod, P, Jarrett, L, Matias, D, Cirillo, DM, Borroni, E, Battaglia, S, Ghodousi, A, Spitaleri, A, Cabibbe, A, Tahseen, S, Nilgiriwala, K, Shah, S, Rodrigues, C, Kambli, P, Surve, U, Khot, R, Niemann, S, Kohl, T, Merker, M, Hoffmann, H, Molodtsov, N, Plesnik, S, Ismail, N, Omar, SV, Thwaites, G, Thuong, NTT, Nhung, HN, Srinivasan, V, Moore, D, Coronel, J, Solano, W, Gao, GF, He, G, Zhao, Y, Ma, A, Liu, C, Zhu, B, Laurenson, I, Claxton, P, Koch, A, Wilkinson, R, Lalvani, A, Posey, J, Gardy, J, Werngren, J, Paton, N, Jou, R, Wu, M-H, Lin, W-H, Ferrazoli, L, De Oliveira, RS, and Wellcome Trust

Subjects
DRUG-RESISTANCE, Technology, Biochemistry & Molecular Biology, Science & Technology, INFORMATION, MUTATIONS, CRyPTIC Consortium, Bioinformatics, Statistics & Probability, SUSCEPTIBILITY, 06 Biological Sciences, GENE, Biochemical Research Methods, CLASSIFICATION, DIMENSIONALITY REDUCTION, Biotechnology & Applied Microbiology, Physical Sciences, Computer Science, Computer Science, Interdisciplinary Applications, Mathematical & Computational Biology, 08 Information and Computing Sciences, Life Sciences & Biomedicine, Mathematics, 01 Mathematical Sciences
Abstract

Motivation Resistance co-occurrence within first-line anti-tuberculosis (TB) drugs is a common phenomenon. Existing methods based on genetic data analysis of Mycobacterium tuberculosis (MTB) have been able to predict resistance of MTB to individual drugs, but have not considered the resistance co-occurrence and cannot capture latent structure of genomic data that corresponds to lineages. Results We used a large cohort of TB patients from 16 countries across six continents where whole-genome sequences for each isolate and associated phenotype to anti-TB drugs were obtained using drug susceptibility testing recommended by the World Health Organization. We then proposed an end-to-end multi-task model with deep denoising auto-encoder (DeepAMR) for multiple drug classification and developed DeepAMR_cluster, a clustering variant based on DeepAMR, for learning clusters in latent space of the data. The results showed that DeepAMR outperformed baseline model and four machine learning models with mean AUROC from 94.4% to 98.7% for predicting resistance to four first-line drugs [i.e. isoniazid (INH), ethambutol (EMB), rifampicin (RIF), pyrazinamide (PZA)], multi-drug resistant TB (MDR-TB) and pan-susceptible TB (PANS-TB: MTB that is susceptible to all four first-line anti-TB drugs). In the case of INH, EMB, PZA and MDR-TB, DeepAMR achieved its best mean sensitivity of 94.3%, 91.5%, 87.3% and 96.3%, respectively. While in the case of RIF and PANS-TB, it generated 94.2% and 92.2% sensitivity, which were lower than baseline model by 0.7% and 1.9%, respectively. t-SNE visualization shows that DeepAMR_cluster captures lineage-related clusters in the latent space. Availability and implementation The details of source code are provided at http://www.robots.ox.ac.uk/∼davidc/code.php.

Published
2019

98. GenomegaMap: within-species genome-widedN/dSestimation from over 10,000 genomes

Author

Wilson, DJ, Crook, DW, Peto, TEA, Walker, AS, Hoosdally, SJ, Gibertoni Cruz, AL, Carter, J, Grazian, C, Earle, SG, Kouchaki, S, Lachapelle, A, Yang, Y, Clifton, DA, Fowler, PW, Iqbal, Z, Hunt, M, Knaggs, J, Smith, EG, Rathod, P, Jarrett, L, Matias, D, Cirillo, DM, Borroni, E, Battaglia, S, Ghodousi, A, Spitaleri, A, Cabibbe, A, Tahseen, S, Nilgiriwala, K, Shah, S, Rodrigues, C, Kambli, P, Surve, U, Khot, R, Niemann, S, Kohl, TA, Merker, M, Hoffmann, H, Todt, K, Plesnik, S, Ismail, N, Omar, SV, Joseph, L, Thwaites, G, Thuong, TNT, Ngoc, NH, Srinivasan, V, Walker, TM, Moore, D, Coronel, J, Solano, W, Gao, GF, He, G, Zhao, Y, Liu, C, Ma, A, Zhu, B, Laurenson, I, Claxton, P, Koch, A, Wilkinson, R, Lalvani, A, Posey, J, Gardy, J, Werngren, J, Paton, N, Jou, R, Wu, M-H, Lin, W-H, Ferrazoli, L, De Oliveira, RS, Arandjelovic, I, Chaiprasert, A, Comas, I, Roig, CJ, Drobniewski, FA, Farhat, MR, Gao, Q, Hee, ROT, Sintchenko, V, Supply, P, Van Soolingen, D, University of Oxford, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), D.J.W. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101237/Z/13/B) and is a Big Data Institute Robertson Fellow. The CRyPTIC Consortium was supported by grants from the Bill and Melinda Gates Foundation (OPP1133541) and a Wellcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z). F.A.D. was supported by the Imperial Biomedical Research Centre., Members of the CRyPTIC Consortium : Derrick W. Crook, Timothy E.A. Peto, A. Sarah Walker, Sarah J. Hoosdally, Ana L. Gibertoni Cruz, Joshua Carter, Clara Grazian, Sarah G. Earle, Samaneh Kouchaki, Alexander Lachapelle, Yang Yang, David A. Clifton, and Philip W. Fowler, University of Oxford, Zamin Iqbal, Martin Hunt, and Jeffrey Knaggs, European Bioinformatics Institute, E. Grace Smith, Priti Rathod, Lisa Jarrett, and Daniela Matias, Public Health England, Birmingham, Daniela M. Cirillo, Emanuele Borroni, Simone Battaglia, Arash Ghodousi, Andrea Spitaleri, and Andrea Cabibbe, Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Sabira Tahseen, National Tuberculosis Control Program Pakistan, Islamabad, Kayzad Nilgiriwala and Sanchi Shah, The Foundation for Medical Research, Mumbai, Camilla Rodrigues, Priti Kambli, Utkarsha Surve, and Rukhsar Khot, P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, Stefan Niemann, Thomas A. Kohl, and Matthias Merker, Research Center Borstel, Harald Hoffmann, Katharina Todt, and Sara Plesnik, Institute of Microbiology & Laboratory Medicine, IML Red, Gauting, Nazir Ismail, Shaheed Vally Omar, and Lavania Joseph, National Institute for Communicable Diseases, Johannesburg, Guy Thwaites, Thuong Nguyen Thuy Thuong, Nhung Hoang Ngoc, Vijay Srinivasan, and Timothy M. Walker, Oxford University Clinical Research Unit, Ho Chi Minh City, David Moore, Jorge Coronel and Walter Solano, London School of Hygiene and Tropical Medicine and Universidad Peruana Cayetano Heredá, Lima, George F. Gao, Guangxue He, Yanlin Zhao, and Chunfa Liu, China CDC, Beijing, Aijing Ma, Shenzhen Third People’s Hospital, Shenzhen, Baoli Zhu, Institute of Microbiology, CAS, Beijing, Ian Laurenson and Pauline Claxton, Scottish Mycobacteria Reference Laboratory, Edinburgh, Anastasia Koch, Robert Wilkinson, University of Cape Town, Ajit Lalvani, Imperial College London, James Posey, CDC Atlanta, Jennifer Gardy, University of British Columbia, Jim Werngren, Public Health Agency of Sweden, Nicholas Paton, National University of Singapore, Ruwen Jou, Mei-Hua Wu, Wan-Hsuan Lin, CDC Taiwan, Lucilaine Ferrazoli, Rosangela Siqueira de Oliveira, Institute Adolfo Lutz, São Paulo. Authors contributing to the CRyPTIC Consortium are (in alphabetical order): Irena Arandjelovic (Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia), Angkana Chaiprasert (Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand), Iñaki Comas (Instituto de Biomedicina de Valencia [IBV-CSIC], Calle Jaime Roig, Valencia, Spain, FISABIO Public Health, Valencia, Spain, CIBER in Epidemiology and Public Health, Madrid, Spain), Francis A. Drobniewski (Imperial College, London, UK), Maha R. Farhat (Harvard Medical School, Boston, USA), Qian Gao (Shanghai Medical College, Fudan University, Shanghai, China), Rick Ong Twee Hee (Saw Swee Hock School of Public Health, National University of Singapore, Singapore), Vitali Sintchenko (Centre for Infectious Diseases and Microbiology—Public Health, University of Sydney, Sydney, Australia), Philip Supply (Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019—UMR 8204—CIIL—Centre d’Infection et d’Immunité de Lille, F-59000 Lille, France), and Dick van Soolingen (National Institute for Public Health and the Environment [RIVM], Bilthoven, The Netherlands)., Supply, Philip, Consortium, CRyPTIC, University of Oxford [Oxford], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Royal Society (UK), Bill & Melinda Gates Foundation, Newton Fund, Comas, Iñaki [0000-0001-5504-9408], and Comas, Iñaki

Subjects
Natural selection, [SDV]Life Sciences [q-bio], Population genetics, adaptation, Computational biology, Biology, AcademicSubjects/SCI01180, 0601 Biochemistry and Cell Biology, Genome, Coalescent theory, DEAD-box RNA Helicases, Big data, 03 medical and health sciences, 0603 Evolutionary Biology, big data, Parent-dependent mutation, Genetics, dN/dS, Adaptation, Selection, Genetic, Molecular Biology, Allele frequency, Ecology, Evolution, Behavior and Systematics, Silent Mutation, Selection (genetic algorithm), 030304 developmental biology, Evolutionary Biology, 0604 Genetics, 0303 health sciences, Models, Genetic, Phylogenetic tree, 030306 microbiology, AcademicSubjects/SCI01130, natural selection, Mycobacterium tuberculosis, Recombination, Resources, recombination, 3. Good health, [SDV] Life Sciences [q-bio], Genetic Techniques, Mutation (genetic algorithm), parent-dependent mutation, Genome, Bacterial
Abstract

11 págs, 4 figuras y fórmulas matemáticas. Material suplementario en: http://dx.doi.org/10.1093/molbev/msaa069, The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters, such as dN/dS, but analyzing very large data sets poses a major statistical challenge. Here, I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: 1) It is fast no matter how large the sample size and 2) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well estimated even when genomegaMap's simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in Mycobacterium tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species., D.J.W. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101237/Z/13/B) and is a Big Data Institute Robertson Fellow. The CRyPTIC Consortium was supported by grants from the Bill and Melinda Gates Foundation (OPP1133541) and a Wellcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z). F.A.D. was supported by the Imperial Biomedical Research Centre

Published
2019

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