ABSTRACT
We report 4 cases of Health Workers (HW) suspected of having contracted Ebola Virus Disease (EVD), transported from the Alliance for International Medical Action (ALIMA) Ebola Treatment Centre (ETC) in N'Zerekore, Guinea to the Treatment Centre for Carers run by the medical corps of the French army in Conakry, the capital of Guinea, which was established on 17 January 2015 and closed on 7 July 2015. In total more than 500 HWs have died from EVD since the epidemic began. This mortality has had significant effects on the ability of local services to respond appropriately to the disaster. The HWs were transported by air in the "Human Stretcher Transit Isolator-Total Containment (Oxford) Limited" (HSTI-TCOL) negative pressure isolation pod. Medical evacuation of patients with suspected, potentially fatal, infectious diseases is feasible with the use of a light isolator for patients without critical dysfunctions.
Subject(s)
Air Ambulances , Health Personnel , Hemorrhagic Fever, Ebola/epidemiology , Infectious Disease Transmission, Patient-to-Professional , Patient Isolation/methods , Disease Outbreaks , Guinea/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/therapy , Hemorrhagic Fever, Ebola/transmission , Humans , Patient Isolation/standardsABSTRACT
BACKGROUND: Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies. METHODS AND FINDINGS: Inclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in "cycle threshold" [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A "target value" of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%-32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%-91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 µmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 µmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 µmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 µmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated. CONCLUSIONS: In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, are not as firm as they could have been if we had used randomization. On the other hand, we learned about how to quickly set up and run an Ebola trial, in close relationship with the community and non-governmental organizations; we integrated research into care so that it improved care; and we generated knowledge on EVD that is useful to further research. Our data illustrate the frequency of renal dysfunction and the powerful prognostic value of low Ct values. They suggest that drug trials in EVD should systematically stratify analyses by baseline Ct value, as a surrogate of viral load. They also suggest that favipiravir monotherapy merits further study in patients with medium to high viremia, but not in those with very high viremia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02329054.
Subject(s)
Amides/therapeutic use , Antiviral Agents/therapeutic use , Hemorrhagic Fever, Ebola/drug therapy , Pyrazines/therapeutic use , Adolescent , Adult , Child , Child, Preschool , Ebolavirus/genetics , Feasibility Studies , Female , Guinea , Hemorrhagic Fever, Ebola/diagnosis , Historically Controlled Study , Humans , Infant , Male , RNA, Viral/blood , Reverse Transcriptase Polymerase Chain Reaction , Therapies, Investigational , Treatment Outcome , Viral Load , Young AdultABSTRACT
[This corrects the article DOI: 10.1371/journal.pmed.1001967.].
ABSTRACT
BACKGROUND: Postanesthesia Care Unit (PACU) is an environment associated with an important workload which is susceptible to lead to task interruption (TI), leading to task-switching or concurrent multitasking. The objective of the study was to determine the predictors of the reaction of the nurses facing TI and assess those who lead to an alteration of the initial task. METHODS: We conducted a prospective observational study into the PACU of a university hospital during February 2017. Among 18 nurses, a selected one was observed each day, documenting for each TI the reaction of the nurse (task switching or concurrent multitasking), and the characteristics associated with the TI. We performed classification tree analyses using C5.0 algorithm in order to select the main predictors of the type of multitasking performed and the alteration of the initial task. RESULTS: We observed 1119 TI during 132 hours (8.5 TI/hour). The main reaction was concurrent multitasking (805 TI, 72%). The short duration of the task interruption (one minute or less) was the most important predictor leading to concurrent multitasking. Other predictors of response to TI were the identity of the task interrupter and the number of nurses present. Regarding the consequences of the task switching, long interruption (more than five minutes) was the most important predictor of the alteration of the initial task. CONCLUSIONS: By analysing the predictors of the type of multitasking in front of TI, we propose a novel approach to understanding TI, offering new perspective for prevention strategies.
Subject(s)
Task Performance and Analysis , Workload , Humans , Prospective Studies , Time FactorsABSTRACT
BACKGROUND: Successful extubation is difficult to predict. Ultrasound measurement of the diaphragm thickening fraction (DTF) might help predict weaning failure after cardiothoracic surgery. METHODS: We assessed the predictive performance of diaphragm ultrasound in a derivation cohort of 50 prospectively included cardiothoracic surgery subjects ready for a weaning trial and in a validation cohort of 39 subjects ventilated for ≥ 48 h. DTF was assessed by ultrasound during pressure support ventilation (PSV) then during a T-piece spontaneous breathing trial (SBT). DTF was the percentage change in diaphragm thickness between expiration and inspiration and DTFmax, the higher DTF value of the 2 hemidiaphragms. DTFmax during SBT (static study) and the difference in DTFmax between PSV and SBT (dynamic study) were analyzed. RESULTS: In the derivation cohort, DTFmax during SBT was 25.6 ± 17.3% in subjects with successful extubation and 65.2 ± 17.3% in those with weaning failure (difference 39.7 [95% CI 27.4-51.9], P < .01). During SBT, DTFmax ≥ 50% was associated with weaning failure (area under the receiver operating characteristic curve [AUC] 0.94 ± 0.05). In the dynamic study, a ≥ 40% DTFmax increase was associated with weaning failure (AUC 0.91 ± 0.06). In the validation cohort, DTFmax during SBT was 20.3 ± 17.1% in subjects with successful extubation and 82.0 ± 51.6% in those with weaning failure (difference 61.8 [95% CI 41.6-82.0], P < .01). During SBT, DTFmax ≥ 50% predicted weaning failure (AUC 0.99 ± 0.02). In the dynamic study, a ≥ 40% increase in DTFmax predicted weaning failure (AUC 0.81 ± 0.09). CONCLUSIONS: Measuring DTFmax during SBT and the DTFmax change when switching from PSV to SBT may help predict weaning failure after cardiothoracic surgery. The study was registered on ANZCTR. CLINICAL TRIAL REGISTRATION NUMBER: U1111-1180-1999.
Subject(s)
Airway Extubation , Diaphragm , Diaphragm/diagnostic imaging , Humans , Predictive Value of Tests , Respiration, Artificial , Ultrasonography , Ventilator WeaningABSTRACT
Abstract Background: Postanesthesia Care Unit (PACU) is an environment associated with an important workload which is susceptible to lead to task interruption (TI), leading to task-switching or concurrent multitasking. The objective of the study was to determine the predictors of the reaction of the nurses facing TI and assess those who lead to an alteration of the initial task. Methods: We conducted a prospective observational study into the PACU of a university hospital during February 2017. Among 18 nurses, a selected one was observed each day, documenting for each TI the reaction of the nurse (task switching or concurrent multitasking), and the characteristics associated with the TI. We performed classification tree analyses using C5.0 algorithm in order to select the main predictors of the type of multitasking performed and the alteration of the initial task. Results: We observed 1119 TI during 132 hours (8.5 TI/hour). The main reaction was concurrent multitasking (805 TI, 72%). The short duration of the task interruption (one minute or less) was the most important predictor leading to concurrent multitasking. Other predictors of response to TI were the identity of the task interrupter and the number of nurses present. Regarding the consequences of the task switching, long interruption (more than five minutes) was the most important predictor of the alteration of the initial task. Conclusions: By analysing the predictors of the type of multitasking in front of TI, we propose a novel approach to understanding TI, offering new perspective for prevention strategies.
Subject(s)
Humans , Task Performance and Analysis , Workload , Time Factors , Prospective StudiesABSTRACT
OBJECTIVE: Transesophageal echocardiography (TEE) has proven its efficiency in assessing hemodynamics in patients by its ability to evaluate cardiac function and fluid responsiveness. Classically, it requires quantitative measurements, whereas in routine practice TEE is used in our unit especially as a qualitative procedure. We assessed the accuracy of this qualitative central hemodynamic evaluation obtained by TEE at the bedside. DESIGN AND SETTING: Prospective study conducted in a medical ICU between September 2004 and April 2005. All TEE examinations performed in consecutive patients hospitalized for septic shock and mechanically ventilated for an associated acute lung injury were eligible for evaluation. Intensivists trained in echocardiography were asked to classify (a) respiratory changes in the superior vena cava (SVC), (b) left ventricular (LV) systolic function, (c) right ventricular (RV) end-diastolic size, and (d) shape and kinetics of the interventricular septum (IVS). A post-hoc quantitative evaluation was then performed by a trained investigator unaware of the patients' status. RESULTS: We evaluated 83 examinations in 30 patients. Qualitative evaluation was easily able to distinguish patients with significant or nonsignificant SVC respiratory changes, normal, moderately or markedly depressed LV systolic function, and nondilated or dilated right ventricle. Acute cor pulmonale was also well recognized. CONCLUSION: By its ability accurately to evaluate hemodynamic status qualitative TEE could be useful for intensivists in managing circulatory failure in septic shock, rendering the more time-consuming quantitative evaluation useless.
Subject(s)
Echocardiography, Transesophageal , Shock, Septic/diagnostic imaging , Aged , Analysis of Variance , Diastole , Female , Heart Ventricles/diagnostic imaging , Humans , Male , Point-of-Care Systems , Prospective Studies , Severity of Illness Index , Systole , Vena Cava, Inferior/diagnostic imaging , Vena Cava, Superior/diagnostic imagingABSTRACT
The 2014 Ebola epidemic has shown the importance of accurate and rapid triage tools for patients with suspected Ebola virus disease (EVD). Our objective was to create a predictive score for EVD. We retrospectively reviewed all suspected cases admitted to the Ebola treatment center (ETC) in Nzérékoré, Guinea, between December 2, 2014, and February 23, 2015. We used a multivariate logistic regression model to identify clinical and epidemiological factors associated with EVD, which were used to create a predictive score. A bootstrap sampling method was applied to our sample to determine characteristics of the score to discriminate EVD. Among the 145 patients included in the study (48% male, median age 29 years), EVD was confirmed in 76 (52%) patients. One hundred and eleven (77%) patients had at least one epidemiological risk factor. Optimal cutoff value of fever to discriminate EVD was 38.5°C. After adjustment on presence of a risk factor, temperature higher than 38.5°C (odds ratio [OR] = 18.1, 95% confidence interval [CI] = 7.6-42.9), and anorexia (OR = 2.5, 95% CI = 1.1-6.1) were independently associated with EVD. The score had an area under curve of 0.85 (95% CI = 0.78-0.91) for the prediction of laboratory-confirmed EVD. Classification of patients in a high-risk group according to the score had a lower sensitivity (71% versus 86%) but higher specificity (85% versus 41%) than the existing World Health Organization algorithm. This score, which requires external validation, may be used in high-prevalence settings to identify different levels of risk in EVD suspected patients and thus allow a better orientation in different wards of ETC.
Subject(s)
Hemorrhagic Fever, Ebola/epidemiology , Models, Biological , Adolescent , Adult , Female , Guinea/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Sensitivity and Specificity , Socioeconomic Factors , Young AdultABSTRACT
OBJECTIVE: We tested the hypothesis that ventilation in the prone position might improve homogenization of tidal ventilation by reducing time-constant inequalities, and thus improving alveolar ventilation. We have recently reported in ARDS patients that these inequalities are responsible for the presence of a "slow compartment," excluded from tidal ventilation at supportive respiratory rate. DESIGN: In 11 ARDS patients treated by ventilation in the prone position because of a major oxygenation impairment (PaO(2)/FIO(2)=100 mm Hg) we studied mechanical and blood gas changes produced by a low PEEP (6+/-1 cm H(2)O), ventilation in the prone position, and the two combined. RESULTS: Ventilation in the prone position significantly reduced the expiratory time constant from 1.98+/-0.53 s at baseline with ZEEP to 1.53+/-0.34 s, and significantly decreased PaCO(2) from 55+/-11 mm Hg at baseline with ZEEP to 50+/-7 mm Hg. This improvement in alveolar ventilation was accompanied by a significant improvement in respiratory system mechanics, and in arterial oxygenation, the latter being markedly increased by application of a low PEEP (PaO(2)/FIO(2) increasing from 64+/-19 mm Hg in supine position with ZEEP to 137+/-88 mm Hg in prone with a low PEEP). CONCLUSION: In severely hypoxemic patients, prone position was able to improve alveolar ventilation significantly by reducing the expiratory time constant.
Subject(s)
Prone Position/physiology , Pulmonary Alveoli/physiopathology , Respiration, Artificial , Respiratory Distress Syndrome/physiopathology , Respiratory Mechanics , Analysis of Variance , Blood Gas Analysis , Female , Humans , Lung Compliance/physiology , Male , Middle Aged , Positive-Pressure Respiration , Prospective Studies , Statistics, NonparametricABSTRACT
INTRODUCTION: We conducted a prospective observational study from January 1995 to December 2004 to evaluate the impact on recovery of a major advance in renal replacement therapy, namely continuous veno-venous haemodiafiltration (CVVHDF), in patients with refractory septic shock. METHOD: CVVHDF was implemented after 6-12 hours of maximal haemodynamic support, and base excess monitoring was used to evaluate the improvement achieved. Of the 60 patients studied, 40 had improved metabolic acidosis after 12 hours of CVVHDF, with a progressive improvement in all failing organs; the final mortality rate in this subgroup was 30%. In contrast, metabolic acidosis did not improve in the remaining 20 patients after 12 hours of CVVHDF, and the mortality rate in this subgroup was 100%. The crude mortality rate for the whole group was 53%, which is significantly lower than the predicted mortality using Simplified Acute Physiology Score II (79%). CONCLUSION: Early CVVHDF may improve the prognosis of sepsis-related multiple organ failure. Failure to correct metabolic acidosis rapidly during the procedure was a strong predictor of mortality.
Subject(s)
Hemofiltration/methods , Multiple Organ Failure/etiology , Multiple Organ Failure/therapy , Sepsis/complications , Acid-Base Imbalance/blood , Acid-Base Imbalance/etiology , Acid-Base Imbalance/therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Electrolytes/blood , Female , Humans , Lactic Acid/blood , Male , Middle Aged , Phosphates/blood , Prospective Studies , Shock, Septic/complications , Shock, Septic/therapy , Survival Analysis , Treatment OutcomeABSTRACT
OBJECTIVE: In mechanically ventilated patients inspiratory increase in pleural pressure during lung inflation may produce complete or partial collapse of the superior vena cava. Occurrence of this collapse suggests that at this time external pressure exerted by the thoracic cavity on the superior vena cava is greater than the venous pressure required to maintain the vessel fully open. We tested the hypothesis that measurement of superior vena caval collapsibility would reveal the need for volume expansion in a given septic patient. DESIGN AND SETTING: Prospective data collection for 66 successive patients in septic shock admitted in a medical intensive care unit and mechanically ventilated for an associated acute lung injury. MEASUREMENTS AND RESULTS: We simultaneously measured superior vena caval collapsibility by echocardiography and cardiac index by the Doppler technique at baseline and after a 10 ml/kg volume expansion by 6% hydroxyethyl starch in 30 min. The threshold superior vena caval collapsibility of 36%, calculated as (maximum diameter on expiration-minimum diameter on inspiration)/maximum diameter on expiration, allowed discrimination between responders (defined by an increase in cardiac index of at least 11% induced by volume expansion) and nonresponders, with a sensitivity of 90% and a specificity of 100%. CONCLUSIONS: Superior vena cava measurement should be systematically performed during routine echocardiography in septic shock as it gives an accurate index of fluid responsiveness.