Aplicación, comprobación y corrección a partir de un checklist elaborado con algunas de las recomendaciones («hacer y no hacer») de los grupos de trabajo de la SEMICYUC / Application, verification and correction from an elaborate checklist with some of the recommendations («do and do not do») of the SEMICYUC working groups

Objetivo Con algunas de las recomendaciones de los grupos de trabajo de la SEMICYUC elaboramos un checklist y lo aplicamos en 2 periodos. Analizamos su comportamiento como herramienta de mejora en la seguridad. Diseño Estudio longitudinal, comparativo pre- y postintervención. Ámbito Unidad de Cuidados Intensivos de un hospital universitario de 400 camas. Pacientes Serie de casos aleatorios en 2 periodos separados por 6 meses. Intervenciones Elaboramos un checklist con 24 indicadores seleccionados que aplicamos de forma aleatoria a 50 pacientes. La verificación fue conducida por un profesional no relacionado con el cuidado (prompter). Analizamos los resultados y el índice de cumplimiento y realizamos medidas correctoras con formación. Con 6 meses de preparación, aplicamos de nuevo el checklist aleatorio a 50 pacientes (periodo postintervención) y comparamos el índice de cumplimiento entre ambos. Resultados No observamos diferencias en características demográficas ni en la evolución entre periodos. El índice de cumplimiento en el periodo basal fue de 0,86±0,12 y en el periodo de postintervención de 0,91±0,52; p=0,023. Obtuvimos un índice de cumplimiento aceptable de los 24 indicadores, pero en el basal en 5 recomendaciones el índice de cumplimiento fue menor a 0,85. Estos incumplimientos detectados se trabajaron formativamente en la segunda fase. En el checklist postintervención observamos una mejoría en el cumplimiento de las recomendaciones. Conclusiones El checklist utilizado para comprobar el cumplimiento de una selección de recomendaciones de la SEMICYUC aplicado y moderado por un prompter fue un instrumento útil que permitió establecer puntos de mejora en la atención de los pacientes de una unidad de cuidados intensivos, aumentando la calidad y la seguridad. (AU)

Objective Based on some of the recommendations of the SEMICYUC working groups, we developed a checklist and applied it in 2 periods, analyzing their behavior as a tool for improving safety. Design A comparative pre- and post-intervention longitudinal study was carried out. Setting The Intensive Care Unit (ICU) of a 400-bed university hospital. Patients Random cases series in 2 periods separated by 6 months. Interventions We developed a checklist with 24 selected indicators that were randomly applied to 50 patients. Verification was conducted by a professional not related to care (prompter). We analyzed the results and compliance index and carried out corrective measures with training. With 6 months of preparation, we again applied the random checklist to 50 patients (post-intervention period) and compared the compliance indexes between the two timepoints. Results There were no differences in demographic characteristics or evolution between the periods. The compliance index at baseline was 0.86±0.12 versus 0.91±0.52 in the post-intervention period (P=.023). An acceptable compliance index was obtained with the 24 indicators, though at baseline the compliance index was<0.85 for 5 recommendations. These detected non-compliances were worked upon through training in the second phase of the study. The post-intervention checklist evidenced improvement in compliance with the recommendations. Conclusions The checklist used to assess compliance with a selection of recommendations of the SEMICYUC applied and moderated by a prompter was seen to be a useful instrument allowing us to identify points for improvement in the management of Intensive Care Unit patients, increasing the quality and safety of care. (AU)

Application, verification and correction from an elaborate checklist with some of the recommendations («do and do not do¼) of the SEMICYUC working groups. / Aplicación, comprobación y corrección a partir de un checklist elaborado con algunas de las recomendaciones («hacer y no hacer¼) de los grupos de trabajo de la SEMICYUC.

OBJECTIVE: Based on some of the recommendations of the SEMICYUC working groups, we developed a checklist and applied it in 2 periods, analyzing their behavior as a tool for improving safety. DESIGN: A comparative pre- and post-intervention longitudinal study was carried out. SETTING: The Intensive Care Unit (ICU) of a 400-bed university hospital. PATIENTS: Random cases series in 2 periods separated by 6 months. INTERVENTIONS: We developed a checklist with 24 selected indicators that were randomly applied to 50 patients. Verification was conducted by a professional not related to care (prompter). We analyzed the results and compliance index and carried out corrective measures with training. With 6 months of preparation, we again applied the random checklist to 50 patients (post-intervention period) and compared the compliance indexes between the two timepoints. RESULTS: There were no differences in demographic characteristics or evolution between the periods. The compliance index at baseline was 0.86±0.12 versus 0.91±0.52 in the post-intervention period (P=.023). An acceptable compliance index was obtained with the 24 indicators, though at baseline the compliance index was<0.85 for 5 recommendations. These detected non-compliances were worked upon through training in the second phase of the study. The post-intervention checklist evidenced improvement in compliance with the recommendations. CONCLUSIONS: The checklist used to assess compliance with a selection of recommendations of the SEMICYUC applied and moderated by a prompter was seen to be a useful instrument allowing us to identify points for improvement in the management of Intensive Care Unit patients, increasing the quality and safety of care.

ECLIM-SEHOP, a new platform to set up and develop international academic clinical trials for childhood cancer and blood disorders in Spain.

INTRODUCTION: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. METHODS: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. RESULTS: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. CONCLUSIONS: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.

Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV-HCV co-infected patients: final results of the Spanish BOC HIV-HCV Study.

INTRODUCTION: Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC+pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1. METHODS: This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug. RESULTS: From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients). CONCLUSIONS: Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC+PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.

Effects of oral exposure to silver nanoparticles on the sperm of rats.

It has been demonstrated that exposure to silver nanoparticles (AgNPs) can induce toxicological effects in rodents. In this study, we investigated whether sub-chronic oral exposure to different doses of polyvinil pyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) (50, 100 and 200mg/kg/day) could induce harmful effects on epididymal sperm rat parameters. Sperm motility, viability and morphology were examined. Moreover, a histological evaluation of testis and epididymis was also performed. High doses of PVP-AgNPs showed higher sperm morphology abnormalities, while a progressive, but not significant effect, was observed in other sperm parameters. The current results suggest that oral sub-chronic exposure to PVP-AgNPs induces slight toxicological effects in sperm rat parameters.

Lean techniques to improve the flow of critically ill patients in a health region with its epicenter in the intensive care unit of a reference hospital. / Técnicas «Lean¼ para la mejora del flujo de los pacientes críticos de una región sanitaria con epicentro en el servicio de medicina intensiva de un hospital de referencia.

OBJECTIVE: To analyze whether the application of Lean techniques to improve the flow of critically ill patients in a health region with its epicenter in the intensive care unit (ICU) of a reference hospital. DESIGN: Observational study with pre and post intervention analysis. SETTING: ICU of a reference hospital. PATIENTS: We design projects and a value stream map of flow and compared pre and post intervention. INTERVENTIONS: We recorded demographic data, patient transfers by EMS for lack of beds and delay times in the discharge from ICU to ward. Multidisciplinary meetings and perform daily visual panel, with high priority ICU discharge. We promote temporary relocation of critically ill patients in other special areas of the hospital. We performed a professional satisfaction questionnaire with pre and post implementation of process. We make a statistical analysis of pre and post-intervention comparisons. RESULTS: We planned for 2013 and progressively implemented in 2014. Analysis of patients entering the critical process flow 1) evaluate patients who must transfer for lack of beds, focusing on a diagnosis: pre 10/22 vs. 3/21 post (P=.045); 2) analysis of time delay in the discharge from the ICU to ward: 360.8±163.9minutes in the first period vs. 276.7±149.5 in the second (P=.036); and 3) personal professional satisfaction questionnaire, with 6.6±1.5 points pre vs. 7.5±1.1 in post (P=.001). Analysis of indicators such as the ICU acquired infections, length of ICU stay, the rate of re-admissions and mortality, with no significant differences between the two periods. CONCLUSIONS: The application of Lean techniques in the critically ill process had a positive impact on improving patient flow within the health region, noting a decrease of transfers outside the region due to lack of beds, reduced delayed discharge from ICU to conventional ward and increased satisfaction of ICU professionals.

Transmitted drug resistance to rilpivirine in newly diagnosed antiretroviral naive adults.

We characterized transmitted drug resistance to rilpivirine and the predicted efficacy of first-line rilpivirine-containing regimens in antiretroviral-naive Spanish patients. International Antiviral Society-USA mutations were detected in 138 of 2781 patients (4.9%), E138A (3.4%) being the most prevalent. Using the Stanford Algorithm, 121 patients (4.4%) showed low-level or intermediate resistance. No differences in the predicted efficacy of first-line non-nucleoside reverse transcriptase inhibitor-based regimens were observed. As rilpivirine becomes more widely used in clinical practice, the evolution of its transmitted drug resistance will need to be monitored. In addition, the exact role of E138A singletons on rilpivirine activity as part of first-line regimens merits further evaluation.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients.

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Predictive factors of mortality in severe community-acquired pneumonia: a model with data on the first 24h of ICU admission.

OBJECTIVE: To construct a model of factors predicting mortality in severe community-acquired pneumonia (SCAP) with data on the first 24h after admission to the intensive care unit (ICU). DESIGN: A prospective, observational study was carried out. SETTING: The ICU of a university hospital. PATIENTS: ICU-admitted patients with SCAP were studied prospectively. INTERVENTIONS: Admission pneumonia scores were calculated, and clinical variables were registered during the first 24h. Relationships between predictors of mortality at 28 days were assessed by means of a multivariate logistic regression model. RESULTS: A total number of 242 SCAP patients were evaluated. The SAPS II severity score was 37.2±15.5 points. Bivariate analysis showed high mortality to be more frequent in elderly patients, as well as in patients with high SAPS II scores, neoplastic disease or chronic renal failure. The other prognostic factors related to increased mortality included mechanical ventilation, acute respiratory distress syndrome (ARDS), acute renal failure, bacteremia, and septic shock. Mortality at 28 days was 23.1% (56 patients). Multivariate analysis of the risk factors generated a new predictive model of mortality applicable within the first 24h after ICU admission and comprising 5 main factors: age, CURB severity score 3-4, septic shock, ARDS, and acute renal failure. CONCLUSIONS: Age in years, CURB score 3-4, septic shock, ARDS, and acute renal failure during the first 24h of ICU admission were found to be independent predictors of mortality in SCAP patients.

Macrolide-based regimens in absence of bacterial co-infection in critically ill H1N1 patients with primary viral pneumonia.

PURPOSE: To determine whether macrolide-based treatment is associated with mortality in critically ill H1N1 patients with primary viral pneumonia. METHODS: Secondary analysis of a prospective, observational, multicenter study conducted across 148 Intensive Care Units (ICU) in Spain. RESULTS: Primary viral pneumonia was present in 733 ICU patients with pandemic influenza A (H1N1) virus infection with severe respiratory failure. Macrolide-based treatment was administered to 190 (25.9 %) patients. Patients who received macrolides had chronic obstructive pulmonary disease more often, lower severity on admission (APACHE II score on ICU admission (13.1 ± 6.8 vs. 14.4 ± 7.4 points, p < 0.05), and multiple organ dysfunction syndrome less often (23.4 vs. 30.1 %, p < 0.05). Length of ICU stay in survivors was not significantly different in patients who received macrolides compared to patients who did not (10 (IQR 4-20) vs. 10 (IQR 5-20), p = 0.9). ICU mortality was 24.1 % (n = 177). Patients with macrolide-based treatment had lower ICU mortality in the univariate analysis (19.2 vs. 28.1 %, p = 0.02); however, a propensity score analysis showed no effect of macrolide-based treatment on ICU mortality (OR = 0.87; 95 % CI 0.55-1.37, p = 0.5). Moreover, the sensitivity analysis revealed very similar results (OR = 0.91; 95 % CI 0.58-1.44, p = 0.7). A separate analysis of patients under mechanical ventilation yielded similar results (OR = 0.77; 95 % CI 0.44-1.35, p = 0.4). CONCLUSION: Our results suggest that macrolide-based treatment was not associated with improved survival in critically ill H1N1 patients with primary viral pneumonia.

Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years.

OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/µL, 19% CD4 < 200/µL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/µL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.

Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.

OBJECTIVES: Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. METHODS: Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. RESULTS: HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P < 0.001) and HDLc (r = 0.216; P = 0.005). CONCLUSIONS: HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.

[Recommendations of the Infectious Diseases Work Group (GTEI) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Infections in Critically Ill Patients Study Group (GEIPC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) for the diagnosis and treatment of influenza A/H1N1 in seriously ill adults admitted to the Intensive Care Unit]. / Recomendaciones del Grupo de Trabajo Enfermedades Infecciosas (GTEI) de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y el Grupo de Estudio de Infecciones en el Paciente Crítico (GEIPC) de la Sociedad Española de Enfermedades Infecciosas y Microbiología clínica (SEIMC) para el diagnóstico y tratamiento de la gripe A/H1N1 en pacientes adultos graves hospitalizados en las Unidades de Cuidados Intensivos.

The diagnosis of influenza A/H1N1 is mainly clinical, particularly during peak or seasonal flu outbreaks. A diagnostic test should be performed in all patients with fever and flu symptoms that require hospitalization. The respiratory sample (nasal or pharyngeal exudate or deeper sample in intubated patients) should be obtained as soon as possible, with the immediate start of empirical antiviral treatment. Molecular methods based on nucleic acid amplification techniques (RT-PCR) are the gold standard for the diagnosis of influenza A/H1N1. Immunochromatographic methods have low sensitivity; a negative result therefore does not rule out active infection. Classical culture is slow and has low sensitivity. Direct immunofluorescence offers a sensitivity of 90%, but requires a sample of high quality. Indirect methods for detecting antibodies are only of epidemiological interest. Patients with A/H1N1 flu may have relative leukopenia and elevated serum levels of LDH, CPK and CRP, but none of these variables are independently associated to the prognosis. However, plasma LDH> 1500 IU/L, and the presence of thrombocytopenia <150 x 10(9)/L, could define a patient population at risk of suffering serious complications. Antiviral administration (oseltamivir) should start early (<48 h from the onset of symptoms), with a dose of 75 mg every 12h, and with a duration of at least 7 days or until clinical improvement is observed. Early antiviral administration is associated to improved survival in critically ill patients. New antiviral drugs, especially those formulated for intravenous administration, may be the best choice in future epidemics. Patients with a high suspicion of influenza A/H1N1 infection must continue with antiviral treatment, regardless of the negative results of initial tests, unless an alternative diagnosis can be established or clinical criteria suggest a low probability of influenza. In patients with influenza A/H1N1 pneumonia, empirical antibiotic therapy should be provided due to the possibility of bacterial coinfection. A beta-lactam plus a macrolide should be administered as soon as possible. The microbiological findings and clinical or laboratory test variables may decide withdrawal or not of antibiotic treatment. Pneumococcal vaccination is recommended as a preventive measure in the population at risk of suffering severe complications. Although the use of moderate- or low-dose corticosteroids has been proposed for the treatment of influenza A/H1N1 pneumonia, the existing scientific evidence is not sufficient to recommend the use of corticosteroids in these patients. The treatment of acute respiratory distress syndrome in patients with influenza A/H1N1 must be based on the use of a protective ventilatory strategy (tidal volume <10 ml / kg and plateau pressure <35 mmHg) and positive end-expiratory pressure set to high patient lung mechanics, combined with the use of prone ventilation, muscle relaxation and recruitment maneuvers. Noninvasive mechanical ventilation cannot be considered a technique of choice in patients with acute respiratory distress syndrome, though it may be useful in experienced centers and in cases of respiratory failure associated with chronic obstructive pulmonary disease exacerbation or heart failure. Extracorporeal membrane oxygenation is a rescue technique in refractory acute respiratory distress syndrome due to influenza A/H1N1 infection. The scientific evidence is weak, however, and extracorporeal membrane oxygenation is not the technique of choice. Extracorporeal membrane oxygenation will be advisable if all other options have failed to improve oxygenation. The centralization of extracorporeal membrane oxygenation in referral hospitals is recommended. Clinical findings show 50-60% survival rates in patients treated with this technique. Cardiovascular complications of influenza A/H1N1 are common. Such problems may appear due to the deterioration of pre-existing cardiomyopathy, myocarditis, ischemic heart disease and right ventricular dysfunction. Early diagnosis and adequate monitoring allow the start of effective treatment, and in severe cases help decide the use of circulatory support systems. Influenza vaccination is recommended for all patients at risk. This indication in turn could be extended to all subjects over 6 months of age, unless contraindicated. Children should receive two doses (one per month). Immunocompromised patients and the population at risk should receive one dose and another dose annually. The frequency of adverse effects of the vaccine against A/H1N1 flu is similar to that of seasonal flu. Chemoprophylaxis must always be considered a supplement to vaccination, and is indicated in people at high risk of complications, as well in healthcare personnel who have been exposed.