Impact of the COVID-19 pandemic on the diagnosis, management and prognosis of infective endocarditis
2020; Elsevier BV; Volume: 27; Issue: 4 Linguagem: Inglês
10.1016/j.cmi.2020.11.022
ISSN1469-0691
AutoresLaura Escolà‐Vergé, Guillermo Cuervo, Arístides de Alarcón, Dolores Sousa, Laura Varela Barca, Núria Fernández-Hidalgo, Arístides de Alarcón, Encarnación Gutiérrez‐Carretero, Rafael Luque‐Márquez, Blanca Anaya Baz, Luis Eduardo López-Cortés, Zaira Palacios Baena, María Victoria García López, Guillermo Ojeda, Antonio Plata, José María Reguera Iglesias, Ricardo Vivancos Delgado, Carmen Hidalgo-Tenorio, Sergio Sequera, Ch, María Carmen Fariñas, Claudia González-Rico, J.F. Gutiérrez-Díez, Gonzalo Cabezón, Javier López, José Alberto San Román, Benito Almirante, Laura Escolà‐Vergé, Rubén Fernández García, Núria Fernández-Hidalgo, M. T. Gonzalez-Alujas, Olga Maisterra, Gerard Oristrell, M.N. Pizzi, Pau Rello, Remedios Ríos, Albert Roque, Antonia Sambola, Toni Soriano, Guillermo Cuervo, Inmaculada Grau, Sara Grillo, Lourdes Mateu, Maria Lluïsa Pedro-Botet Montoya, Núria Vallejo, Marta Hernández‐Meneses, José M. Miró, Eduard Quintana, A J Barros, Mercè Gurguí, Alba Rivera, María Laura Castelo Corral, Efrén Sánchez Vidal, Dolores Sousa, Pérez Rodríguez, Dolores Sousa, Milagros Suárez, M Fernandez, Laura Varela Barca, Laura Vidal Bonet, Lara García-Álvarez, José A. Oteo, Adrián Jerónimo Baza, Carmen Olmos, Isidre Vilacosta, Laura Domínguez-Pérez, Francisco López‐Medrano, Javier T Solera, José Luis Moya Mur, Enrique Navas, Andrea Kallmeyer Mayor, Ana María Pello, Luis Nieto Roca, María Aguilera García, Carmen de las Cuevas Torres, Carmen Sáez Béjar, Daniel de Castro, Fernándo Domínguez, António Ramos, Patricia Muñoz García, María Olmedo, Maricela Valerio Minero, Elisa García Vázquez, Alicia Hernández Torres, Encarnación Moral Escudero, Miguel Ángel Goenaga Sánchez, Xavier Kortajarena Urkola, Karlos Reviejo Jaka, Elena Bereciartúa, Josune Goikoetxea, Regino Rodríguez, Martín Reyes Acevedo,
Tópico(s)Cardiac Structural Anomalies and Repair
ResumoOn 13 March, Spain declared a state of emergency and lockdown for COVID-19. In this context, organizational changes included, among others, the prohibition of holding face-to-face clinical meetings, the cancellation of non-urgent surgeries and the redistribution of medical teams to face the emergency. The aim of this study was to evaluate the impact of the COVID-19 pandemic on the diagnosis, management and prognosis of infective endocarditis (IE) patients in Spanish referral centres. We hypothesize that during the COVID-19 pandemic, fewer IE episodes have been diagnosed, and fewer surgeries during the active phase of infection have been performed. This multicentre retrospective observational study was conducted at 26 Spanish referral centres for IE and cardiac surgery. Investigators were asked to complete a questionnaire about the organizational changes during the COVID-19 pandemic. They were also asked to collect retrospectively from their prospective IE registry clinical and outcome data for all consecutive definite IE episodes in adult patients (≥18 years) treated during the first month after the establishment of the state of emergency in Spain (14 March to 13 April) and for those patients treated during the same period in 2019. The main outcomes were the number of definite IE episodes treated and the rate of surgeries performed when indicated [[1]Habib G. Lancellotti P. Antunes M.J. Bongiorni M.G. Casalta J.P. Del Zotti F. et al.2015 ESC guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European society of cardiology (ESC). Endorsed by: European association for cardio-thoracic surgery (EACTS), the European association of nuclear medicine (EANM).Eur Heart J. 2015; 36: 3075-3128Crossref PubMed Scopus (3228) Google Scholar]. Comparisons between groups (2019 vs. 2020) were performed using the chi-squared test or Fisher's exact test for qualitative variables, as appropriate, and the two-sample Wilcoxon rank-sum (Mann–Whitney U) test for continuous variables. This study was approved by the Ethics Committee of the Hospital Universitari Vall d'Hebron (PR(AG)312-2020). Fig. 1 shows the distribution of participating hospitals and the burden of laboratory-confirmed COVID-19 episodes by region for 14 March and 13 April 2020. Twenty-five out of 26 participating centres suffered significant organizational changes (Table S1). Notably, in 23 periodic endocarditis team meetings were cancelled. The medical staff in charge of IE patients suffered different degrees of modification in 19. Strikingly, in six centres patients were attended by professionals without experience in the management of IE. Fourteen reported fewer transfer requests and four refused patient transfer for surgery. Eighteen reported alterations in the realization of echocardiograms due to lower availability. Cardiac surgeries were cancelled in eight, mostly (7/8) non-urgent surgeries. The length of admission was intentionally reduced in 12, enhancing outpatient antibiotic therapy (10). After finishing antimicrobial therapy, fewer control blood cultures were performed in seven, and 20 centres prioritized telematic control. Compared with 2019, there was a 34% reduction in the absolute number of definite IE episodes in 2020 (from 136 to 90 cases) (Table 1). We found no differences in the percentage of patients transferred from other hospitals or in the transfer delay, but less patients were transferred in the first two weeks of April in 2020 compared with 2019 (3.3% vs. 26.7%, p 0.009). In the second period (2020), there was a non-significantly lower rate of infections due to Staphylococcus aureus (21.3% vs. 12.2%, p 0.079) and a higher percentage of episodes of unknown aetiology (0.7% vs. 8.9%, p 0.003). Interestingly, there were no differences in the percentages of community acquisition between periods in S. aureus episodes (15/29 (52%) in 2019 vs. 6/11 (55%) in 2020). The percentage of patients undergoing a transoesophageal echocardiogram did not differ between periods. There were no differences in the percentage of indications for surgery, but in 2020 fewer surgeries were performed when indicated (79% in 2019 vs. 65% in 2020, p 0.042). In-hospital mortality was similar in both periods (∼20%), but in 2020 survivors were discharged earlier to continue treatment on an outpatient basis. During follow-up, fewer control blood cultures were performed in 2020.Table 1Comparison of clinical characteristics and outcomes of 226 patients with definite infective endocarditis treated at 26 Spanish referral centres between 14 March and April 13 2019 and 20202019 (n = 136)2020 (n = 90)aOne patient in the series had been reported in a previous article [3].pDemographicsAge in years, median (IQR)69.6 (60.2–79.4)70.3 (62.5–78.2)0.645Male sex88 (64.7)59 (65.6)0.896ComorbiditiesCharlson comorbidity index, median (IQR)2 (1–3)2 (1–4)0.635Calendar admissionFrom 14 March to 31 March103 (75.7)70 (77.8)0.723From 1 April to 13 April33 (24.3)20 (22.2)Transferred from another hospital45 (33.1)30 (33.3)0.969Transfer from 14 March to 31 March33/45 (73.3)29/30 (96.7)0.009Transfer from 1 April to 13 April12/45 (26.7)1/30 (3.3)n = 45n = 30Days from admission to transfer, median (IQR)7 (2–11)8 (2–12)0.922Type of IENative valve IE77 (56.6)45 (50)0.329Prosthetic valve IE50 (36.8)41 (45.6)0.187Intracardiac electronic device9 (6.6)4 (4.4)0.492Type of acquisitionCommunity acquired94 (69.1)62 (68.9)0.971Nosocomial healthcare-associated infection30 (22.1)17 (18.9)0.565Non-nosocomial healthcare-associated infection12 (8.8)11 (12.2)0.408AetiologyOral streptococci31 (22.8)20 (22.2)0.920Staphylococcus aureus29 (21.3)11 (12.2)0.079 MSSA25/29 (86.2)10/11 (90.9) MRSA4/29 (13.8)1/11 (9.1)Enterococci26 (19.1)13 (14.4)0.363Coagulase-negative staphylococci21 (15.4)18 (20)0.375Streptococcus gallolyticus (formerly S. bovis)6 (4.4)5 (5.6)0.757HACEK group5 (3.7)00.160Non-HACEK Gram-negative bacilli4 (2.9)5 (5.6)0.489Candida albicans01 (1.1)0.398Otherb2019: Gemella morbillorum in 3, Corynebacterium striatum in 2, Aerococcus sanguinicola in 1, Bartonella henselae 1, Coxiela burnetii in 1, Finegoldia magna in 1, Ganulicatella adicens in 1, Lactococcus garviae in 1, Rothia dentocariosa in 1, Enterococcus faecalis and Staphylococcus aureus in 1.2020: Abiotrophia defectiva in 2, Cutibacterium acnes in 2, Aerococcus urinae in 1, Lactobacillus jensenii in 1, Paenibacillu pabuli in 1, Staphylococcus epidermidis and Staphylococcus hominis in 1, and Streptococcus gallolyticus and Streptococcus oralis in 1.13 (9.6)9 (10)0.913Unknown aetiology1 (0.7)8 (8.9)0.003Performance of TEE126 (92.7)80 (88.9)0.330Local cardiac complications (some patients had >1 complication)68 (50)42 (46.7)0.624 Perivalvular abscess35 (51.5)22 (52.4)0.926 Valve perforation25 (36.8)13 (31)0.533 Pseudoaneurysm11 (16.2)8 (19.1)0.699 Fistula7 (10.3)3 (7.1)0.739 Prosthetic dehiscence6 (8.8)6 (14.3)0.530 Prosthetic leak3 (4.4)3 (7.1)0.673Peripheral emboli (some patients had embolisms in >1 location)60 (44.1)45 (50)0.385 Central nervous system29 (50.9)24 (54.6)0.714 Spleen17 (29.8)19 (43.2)0.165 Osteoarticular13 (22.8)8 (18.2)0.570 Kidney6 (10.5)6 (13.6)0.632 Lung6 (10.5)00.034 Vessels5 (8.8)3 (6.8)1SARS-CoV-2 infectionNA11 (12.2)Duration of antibiotic treatment, days, median (IQR)n = 132n = 86Overall (n = 218)cEight patients were not included in the analysis. 2019: 2 with suppressive treatment (a native IE due to S. oralis with local cardiac complications not operated due to patient rejection, and an intracardiac device infection due to E. faecalis not operated due to high surgical risk), and 2 still on treatment due to infective endocarditis caused due to B. henselae and C. burnetii, respectively. 2020: 4 with suppressive treatment (a native IE due to S. gordonii with local cardiac complications not operated due to high surgical risk, a prosthetic IE due to S. gallolyticus with local cardiac complications not operated due to comorbidities, a prosthetic IE due to S. epidermidis with local cardiac complications not operated due to comorbidities, and a prosthetic IE due to E. coli not operated due to favourable outcome with medical treatment).42 (32–48.5)41.5 (29–46)0.275n = 102n = 67Survivors (n = 169)dFifty-seven patients were excluded from the analysis. 2019: 30 who died during infective endocarditis antimicrobial treatment (28 during hospitalization and 2 after discharge), 2 who underwent suppressive treatment, and 2 were still on treatment for infective endocarditis caused by B. henselae and C. burnetii, respectively. 2020: 19 who died during infective endocarditis antimicrobial treatment (18 during hospitalization and 1 after discharge) and 4 who underwent suppressive treatment.43 (36–52)42 (34–48)0.347n = 102n = 61Survivors excluding 6 patients who received dalbavancin (N = 163)43 (36–52)44 (37–48)0.752Use of dalbavancin as continuation treatment06 (6.7)0.004Surgery indicated according to 2015 ESC guidelines108 (79.4)65 (72.2)0.212Indications for surgery (some patients had > 1 indication)Heart failure54/108 (50)32/65 (49.2)0.922Uncontrolled infection49/108 (45.4)35/65 (53.8)0.280Prevention of embolism20/108 (18.5)8/65 (12.3)0.283Intracardiac electronic device infection9/108 (8.3)4/65 (6.2)0.769Surgery performed, if indicated85/108 (78.7)42/65 (64.6)0.042Indications for surgery in not operated patients (some patients had > 1 indication)Heart failure9/23 (39.1)9/23 (39.1)1Uncontrolled infection11/23 (47.8)15/23 (65.2)0.234Prevention of embolism4/23 (17.4)1/23 (4.3)0.346Intracardiac electronic device infection2/23 (8.7)00.489Reasons for no surgery, if indicatedHigh-risk patient11/23 (47.8)12/23 (52.2)0.768Poor vital prognosis due to comorbidities6/23 (26.1)7/23 (30.4)0.743Good outcome without surgery4/23 (17.4)4/23 (17.4)1Patient's rejection2/23 (8.7)00.489In-hospital mortality (n = 224)eTwo patients from the 2020 period were not included because they had not been discharged at the time of the analysis.28/136 (20.6)18/88 (20.4)0.981No indication for surgery3/28 (10.7)1/25 (4)0.613Surgery indicated and performed16/85 (18.8)10/42 (23.8)0.512Surgery indicated and not performed9/23 (39.1)7/21 (33.3)0.690N = 108N = 70Length of stay in survivors, days, median (IQR) (n = 178)fForty-eight patients were excluded from the analysis. 2019: 28 patients who died during hospitalization. 2020: 18 patients who died during hospitalization and 2 patients who had finished endocarditis treatment but were still hospitalized were not included in the analysis.41 (30–54.5)34 (24–45)0.018Hospital discharge (n = 178)fForty-eight patients were excluded from the analysis. 2019: 28 patients who died during hospitalization. 2020: 18 patients who died during hospitalization and 2 patients who had finished endocarditis treatment but were still hospitalized were not included in the analysis.Home66/108 (61.1)33/70 (47.1)0.067Outpatient parenteral antimicrobial therapy25/108 (23.2)22/70 (31.4)0.221Transferred to the hospital from which the patient was referred10/108 (9.3)10/70 (14.3)0.300Transferred to a rehabilitation clinic7/108 (6.5)5/70 (7.1)1Control blood culture performed during follow-up (n = 166)gSixty patients were excluded from the analysis: 2019: 28 patients who died during hospitalization, 3 patients from which it was not possible to obtain this information, 2 who underwent suppressive treatment, 2 who died after discharge during endocarditis treatment, 1 patient with C. burnetii endocarditis, and 1 patient with B. henselae endocarditis. 2020: 18 patients who died during hospitalization, 4 who underwent suppressive treatment, and 1 who died after discharge during endocarditis treatment.78/99 (78.8)41/67 (61.2)0.014n = 99n = 67Number of samples taken on separated days (n = 166)gSixty patients were excluded from the analysis: 2019: 28 patients who died during hospitalization, 3 patients from which it was not possible to obtain this information, 2 who underwent suppressive treatment, 2 who died after discharge during endocarditis treatment, 1 patient with C. burnetii endocarditis, and 1 patient with B. henselae endocarditis. 2020: 18 patients who died during hospitalization, 4 who underwent suppressive treatment, and 1 who died after discharge during endocarditis treatment.1 (1–2)1 (0–1)<0.001n = 108n = 70Duration of follow-up of survivors at hospital discharge, days, median (IQR) (n = 178)fForty-eight patients were excluded from the analysis. 2019: 28 patients who died during hospitalization. 2020: 18 patients who died during hospitalization and 2 patients who had finished endocarditis treatment but were still hospitalized were not included in the analysis.304.5 (216.5–368)44.5 (28–60)<0.001Number of patients followed-up ≥30 days (n = 178)fForty-eight patients were excluded from the analysis. 2019: 28 patients who died during hospitalization. 2020: 18 patients who died during hospitalization and 2 patients who had finished endocarditis treatment but were still hospitalized were not included in the analysis.104/108 (96.3)50/70 (71.4)<0.001Mortality during first month of follow-up (after hospital discharge) (n = 154)10/104 (9.6)2/50 (4)0.339Mortality during follow-up (after hospital discharge) (n = 178)fForty-eight patients were excluded from the analysis. 2019: 28 patients who died during hospitalization. 2020: 18 patients who died during hospitalization and 2 patients who had finished endocarditis treatment but were still hospitalized were not included in the analysis.13/108 (12)3/70 (4.3)0.077Relapse during follow-up for survivors (n = 169)dFifty-seven patients were excluded from the analysis. 2019: 30 who died during infective endocarditis antimicrobial treatment (28 during hospitalization and 2 after discharge), 2 who underwent suppressive treatment, and 2 were still on treatment for infective endocarditis caused by B. henselae and C. burnetii, respectively. 2020: 19 who died during infective endocarditis antimicrobial treatment (18 during hospitalization and 1 after discharge) and 4 who underwent suppressive treatment.2/102 (2)hOne relapse 151 days after antimicrobial treatment (an operated S. epidermidis prosthetic endocarditis) and one relapse 27 days after antimicrobial treatment (an A. sanguinicola native endocarditis not operated although indicated).3/67 (4.5)iOne relapse 42 days after finishing antimicrobial treatment (an operated P. aeruginosa prosthetic endocarditis), one relapse 37 days after finishing antimicrobial treatment (an operated E. faecalis native endocarditis), and one relapse 16 days after finishing antimicrobial treatment (a prosthetic endocarditis due to S. epidermidis with surgical indication but not operated due to comorbidities).0.386Data are expressed as n (%) or median (IQR) as appropriate. IQR, interquartile range; MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus; HACEK, Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella spp.; TEE, transoesophageal echocardiogram; NA, not applicable.a One patient in the series had been reported in a previous article [[3]Pericàs J.M. Hernandez-Meneses M. Sheahan T.P. Quintana E. Ambrosioni J. Sandoval E. et al.Hospital Clínic Cardiovascular Infections Study GroupCOVID-19: from epidemiology to treatment.Eur Heart J. 2020 Jun 7; 41: 2092-2112https://doi.org/10.1093/eurheartj/ehaa462Crossref PubMed Scopus (59) Google Scholar].b 2019: Gemella morbillorum in 3, Corynebacterium striatum in 2, Aerococcus sanguinicola in 1, Bartonella henselae 1, Coxiela burnetii in 1, Finegoldia magna in 1, Ganulicatella adicens in 1, Lactococcus garviae in 1, Rothia dentocariosa in 1, Enterococcus faecalis and Staphylococcus aureus in 1.2020: Abiotrophia defectiva in 2, Cutibacterium acnes in 2, Aerococcus urinae in 1, Lactobacillus jensenii in 1, Paenibacillu pabuli in 1, Staphylococcus epidermidis and Staphylococcus hominis in 1, and Streptococcus gallolyticus and Streptococcus oralis in 1.c Eight patients were not included in the analysis. 2019: 2 with suppressive treatment (a native IE due to S. oralis with local cardiac complications not operated due to patient rejection, and an intracardiac device infection due to E. faecalis not operated due to high surgical risk), and 2 still on treatment due to infective endocarditis caused due to B. henselae and C. burnetii, respectively. 2020: 4 with suppressive treatment (a native IE due to S. gordonii with local cardiac complications not operated due to high surgical risk, a prosthetic IE due to S. gallolyticus with local cardiac complications not operated due to comorbidities, a prosthetic IE due to S. epidermidis with local cardiac complications not operated due to comorbidities, and a prosthetic IE due to E. coli not operated due to favourable outcome with medical treatment).d Fifty-seven patients were excluded from the analysis. 2019: 30 who died during infective endocarditis antimicrobial treatment (28 during hospitalization and 2 after discharge), 2 who underwent suppressive treatment, and 2 were still on treatment for infective endocarditis caused by B. henselae and C. burnetii, respectively. 2020: 19 who died during infective endocarditis antimicrobial treatment (18 during hospitalization and 1 after discharge) and 4 who underwent suppressive treatment.e Two patients from the 2020 period were not included because they had not been discharged at the time of the analysis.f Forty-eight patients were excluded from the analysis. 2019: 28 patients who died during hospitalization. 2020: 18 patients who died during hospitalization and 2 patients who had finished endocarditis treatment but were still hospitalized were not included in the analysis.g Sixty patients were excluded from the analysis: 2019: 28 patients who died during hospitalization, 3 patients from which it was not possible to obtain this information, 2 who underwent suppressive treatment, 2 who died after discharge during endocarditis treatment, 1 patient with C. burnetii endocarditis, and 1 patient with B. henselae endocarditis. 2020: 18 patients who died during hospitalization, 4 who underwent suppressive treatment, and 1 who died after discharge during endocarditis treatment.h One relapse 151 days after antimicrobial treatment (an operated S. epidermidis prosthetic endocarditis) and one relapse 27 days after antimicrobial treatment (an A. sanguinicola native endocarditis not operated although indicated).i One relapse 42 days after finishing antimicrobial treatment (an operated P. aeruginosa prosthetic endocarditis), one relapse 37 days after finishing antimicrobial treatment (an operated E. faecalis native endocarditis), and one relapse 16 days after finishing antimicrobial treatment (a prosthetic endocarditis due to S. epidermidis with surgical indication but not operated due to comorbidities). Open table in a new tab Data are expressed as n (%) or median (IQR) as appropriate. IQR, interquartile range; MSSA, methicillin-sensitive Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus; HACEK, Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella spp.; TEE, transoesophageal echocardiogram; NA, not applicable. In concordance with our data, a recent study carried out in Marseille and Brussels shows a 33% decrease of IE diagnosed during the first months of 2020 compared with the same period of time in 2019 [[2]Cosyns B. Motoc A. Arregle F. Habib G. A plea not to forget infective endocarditis in COVID-19 era.JACC Cardiovasc Imaging. 2020; 13: 2470-2471Crossref PubMed Scopus (13) Google Scholar]. Several factors could explain this decline. The strict instructions to stay at home, people's fear of infection in medical facilities, the possible confusion of IE symptoms with those of SARS-CoV-2 infection and the prescription of oral antibiotics without further examinations may have caused a decrease in the number of hospital consultations. Other possible causes could be the decrease in the number of cases transferred from other facilities in April 2020 and decrease in usual hospital activity, possibly leading to a slight decrease in nosocomial IE episodes. On the other hand, in contrast to our study, they report a higher rate of complications in 2020 and a striking in-hospital mortality rate (31% in 2019 and 61% in 2020) [[2]Cosyns B. Motoc A. Arregle F. Habib G. A plea not to forget infective endocarditis in COVID-19 era.JACC Cardiovasc Imaging. 2020; 13: 2470-2471Crossref PubMed Scopus (13) Google Scholar]. However, the follow-up in our study was too short to ensure that long-term mortality and relapses will not increase. This study has several limitations. First, only referral centres for IE and cardiac surgery were included, so we cannot determine the impact of the COVID-19 pandemic in community hospitals. Second, follow-up in the 2020 period is shorter than in 2019, so long-term mortality and relapses may be underestimated, especially in non-operated patients and in those treated with outpatient antimicrobial therapy. Third, the relatively small sample size precludes any sub-analysis in regions with high and low incidences of COVID-19. In conclusion, the COVID-19 pandemic has led to important organizational changes in the main Spanish referral centres for endocarditis. In addition, fewer definite IE cases were diagnosed and treated than in the previous year, and fewer cardiac surgeries have been performed, although these changes did not have an impact on the in-hospital mortality. Future studies should evaluate the long-term impact of these changes as well as the evolution of the epidemiology of IE in the post-COVID-19 era. Writing – Original Draft: L.E. and N.F.; Writing – Review and Editing: L.E., G.C., A. A., D.S., L.V.B., N.F.; Conceptualization: L.E., N.F.; Investigation: L.E., G.C., A. A., D.S., L.V.B., N.F. and IE COVID-19 investigators; Methodology: L.E. and N.F.; Formal Analysis: L.E. and N.F.; Project Administration:: L.E. and N.F. Conflict of interest: None declared. Funding: No specific funding was provided to conduct this study. We warmly thank Iván Adán for logistic support. The following is the Supplementary data to this article: Download .docx (.02 MB) Help with docx files Multimedia component 1 Participating sites and IE COVID-19 investigators: Andalucía: Arístides de Alarcón, MD, PhD, Encarnación Gutiérrez-Carretero, MD, Rafael Luque-Márquez, MD (University Hospital Virgen del Rocío, Sevilla (GAMES affiliated hospital)). Blanca Anaya Baz, PharmD, PhD, Luis Eduardo López-Cortés, MD, PhD, Zaira Palacios Baena, MD, PhD (Hospital Universitario Virgen Macarena, Sevilla (GAMES affiliated hospital)). María Victoria García López, MD, Guillermo Ojeda Burgos, MD, PhD (Hospital Universitario Virgen de la Victoria, Málaga (GAMES affiliated hospital)). Antonio Pláta Ciézar, MD, PhD, José María Reguera Iglesias, MD, Ricardo Vivancos Delgado, MD (Hospital Regional Universitario de Málaga, Málaga (GAMES affiliated hospital)). Carmen Hidalgo-Tenorio, MD, PhD, Sergio Sequera, Ch (Hospital Universitario Virgen de las Nieves, Granada (GAMES affiliated hospital)). Cantabria: María Carmen Fariñas, MD, PhD, Claudia González-Rico, MD, José Francisco Gutiérrez-Díez, MD (Hospital Universitario Marqués de Valdecilla, Santander (GAMES affiliated hospital)). Castilla y León: Gonzalo Cabezón, MD, Javier López, MD, PhD, Alberto San Román, MD, PhD (Hospital Clínico de Valladolid, Valladolid (ENDOVAL affiliated hospital)). Cataluña: Benito Almirante, MD, PhD, Laura Escolà-Vergé, MD, PhD, Rubén Fernández, MD, Nuria Fernández-Hidalgo, MD, PhD, MSc, Maria Teresa Gonzàlez-Alujas, MD, Olga Maisterra, MD, PhD, Gerard Oristrell, MD, María Nazarena Pizzi, MD, PhD, Pau Rello, MD, Remedios Ríos, MD, Albert Roque, MD, Antonia Sambola, MD, PhD, Toni Soriano, MD (Hospital Universitari Vall d'Hebron, Barcelona). Guillermo Cuervo, MD, PhD, Immaculada Grau, MD, PhD, Sara Grillo, MD (Bellvitge University Hospìtal, L'Hospitalet de Llobregat (GAMES affiliated hospital)). Lourdes Mateu Pruñonosa, MD, PhD, Maria Lluïsa Pedro-Botet Montoya, MD, PhD, Nuria Vallejo Camazón, MD (Hospital Universitari Germans Trias i Pujol, Badalona). Marta Hernández-Meneses, MD, Jose M. Miro, MD, PhD, Eduard Quintana, MD, PhD (Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona (GAMES affiliated hospital)). Antonio José Barros, MD, Mercè Gurgui, MD, PhD, Alba Rivera, MD (Hospital de la Santa Creu i Sant Pau, Barcelona (GAMES affiliated hospital)). Galicia: María Laura Castelo Corral, MD, Efrén Sánchez Vidal, MD, Dolores Sousa, MD, PhD (Complexo Hospitalario Universitario A Coruña, A Coruña (GAMES affiliated hospital)). María Teresa Pérez-Rodríguez, MD, Adrián Sousa, MD, Milagros Suárez, MD (Complexo Hospitalario Universitario de Vigo, Vigo). Islas Baleares: Maria Àngels Ribas Fernández, MD, Laura Varela Barca, MD, Laura Vidal Bonet, MD (Hospital Universitari Son Espases, Palma de Mallorca (GAMES affiliated hospital)). La Rioja: Lara García-Álvarez, PhD José A Oteo, MD, PhD (Hospital San Pedro, Logroño (GAMES affiliated hospital)). Madrid: Adrián Jerónimo Baza, MD, Carmen Olmos, MD, PhD, Isidre Vilacosta MD, PhD (Hospital Clínico San Carlos, Madrid (ENDOVAL affiliated hospital)). Laura Domínguez-Pérez, MD, Francisco López-Medrano, MD, PhD, Javier T Solera Rallo, MD (Hospital 12 de Octubre, Madrid (GAMES affiliated hospital)). José Luis Moya Mur, MD, Enrique Navas Elorza, MD, PhD (Hospital Universitario Ramón y Cajal, Madrid (GAMES affiliated hospital)). Andrea Kallmeyer Mayor, MD, Ana María Pello, MD, PhD, Luis Nieto Roca, MD (Fundación Jiménez Díaz Quirón Salud, Madrid (GAMES affiliated hospital)). María Aguilera García, MD, Carmen de las Cuevas Torres, MD, Carmen Sáez Béjar, MD, PhD (Hospital Universitario La Princesa, Madrid (ENDOVAL affiliated hospital)). Daniel de Castro Campos, MD, Fernando Domínguez, MD, PhD, Antonio Ramos-Martínez, MD, PhD (Hospital Puerta de Hierro, Majadahonda (GAMES affiliated hospital)). Patricia Muñoz García, MD, PhD, María Olmedo Samperio, MD, Maricela Valerio Minero, MD (Hospital General Universitario Gregorio Marañón, Madrid (GAMES affiliated hospital)). Murcia: Elisa García Vázquez, MD, PhD, Alicia Hernández Torres, MD, PhD, Encarnación Moral Escudero, MD, PhD (Hospital Clínico Universitario Virgen de la Arrixaca, Murcia (GAMES affiliated hospital)). País Vasco: Miguel Ángel Goenaga Sánchez, MD, Xavier Kortajarena Urkola, MD, Karlos Reviejo Jaka, MD (Hospital Universitario Donostia, Donostia (GAMES affiliated hospital)). Elena Bereciartua, MD, Josune Goikoetxea, MD, Regino Rodríguez, MD (Hospital Universitario Cruces, Barakaldo (GAMES affiliated hospital)). Martín Reyes Acevedo (Ataulfo Argenta 135, San Borja, Lima 41, Perú).
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