Edward M. Kilbane

Bio: Edward M. Kilbane is an academic researcher from United States Department of the Navy. The author has contributed to research in topics: Pneumonia & Absolute risk reduction. The author has an hindex of 2, co-authored 2 publications receiving 850 citations.

Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment?

Abstract: This review of 8 controlled studies published in English-language medical literature between 1918 to 1925 found that transfusion with influenza-convalescent human blood products may have reduced ri...

Meta-analysis: Convalescent blood products for spanish influenza pneumonia : A future H5N1 treatment? Commentary

Abstract: Background: Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics. Purpose: To determine whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia. Data Sources: Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched. Study Selection: Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group. Data Extraction: Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality. Data Synthesis: Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. The overall crude case-fatality rate was 16% (54 of 336) among treated patients and 37% (452 of 1219) among controls. The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% Cl, 15% to 27%]). The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after <4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after ≥4 days of pneumonia complications). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41 % [Cl, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients. Limitations: Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed. Conclusions: Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.

Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)

Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.

Rapid cloning of high-affinity human monoclonal antibodies against influenza virus

Abstract: Pre-existing neutralizing antibody provides the first line of defence against pathogens in general. For influenza virus, annual vaccinations are given to maintain protective levels of antibody against the currently circulating strains. Here we report that after booster vaccination there was a rapid and robust influenza-specific IgG+ antibody-secreting plasma cell (ASC) response that peaked at approximately day 7 and accounted for up to 6% of peripheral blood B cells. These ASCs could be distinguished from influenza-specific IgG+ memory B cells that peaked 14-21 days after vaccination and averaged 1% of all B cells. Importantly, as much as 80% of ASCs purified at the peak of the response were influenza specific. This ASC response was characterized by a highly restricted B-cell receptor (BCR) repertoire that in some donors was dominated by only a few B-cell clones. This pauci-clonal response, however, showed extensive intraclonal diversification from accumulated somatic mutations. We used the immunoglobulin variable regions isolated from sorted single ASCs to produce over 50 human monoclonal antibodies (mAbs) that bound to the three influenza vaccine strains with high affinity. This strategy demonstrates that we can generate multiple high-affinity mAbs from humans within a month after vaccination. The panel of influenza-virus-specific human mAbs allowed us to address the issue of original antigenic sin (OAS): the phenomenon where the induced antibody shows higher affinity to a previously encountered influenza virus strain compared with the virus strain present in the vaccine. However, we found that most of the influenza-virus-specific mAbs showed the highest affinity for the current vaccine strain. Thus, OAS does not seem to be a common occurrence in normal, healthy adults receiving influenza vaccination.

COVID-19: combining antiviral and anti-inflammatory treatments

Abstract: 400 www.thelancet.com/infection Vol 20 April 2020 5 WHO. Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks. 2014. http://apps.who.int/iris/rest/ bitstreams/604045/retrieve (accessed Feb 20, 2020). 6 Arabi Y, Balkhy H, Hajeer AH. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus 2015; 4: 709. 7 Hung IF, To KK, Lee CK, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis 2011; 52: 447–56. 8 Hung IFN, To KKW, Lee CK, et al. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest 2013; 144: 464–73. 9 Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis 2015; 211: 80–90. 10 Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 2006; 145: 599–609. 15 Schoofs T, Klein F, Braunschweig M, et al. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science 2016; 352: 997–1001. 12 Lu CL, Murakowski DK, Bournazos S, et al. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 2016; 352: 1001–04. 13 WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. 2020. https://www.who. int/docs/default-source/coronaviruse/clinical-management-of-novel-cov. pdf (accessed Feb 20, 2020). 14 Clark DR, Jonathan EM, JKB. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; published online Feb 7. https://doi.org/10.1016/S0140-6736(20)30317-2.

Convalescent plasma as a potential therapy for COVID-19.

Abstract: 398 www.thelancet.com/infection Vol 20 April 2020 Control and Nursing in Guangdong Second Provincial General Hospital, have undergone intensive training to become familiar with the requirements for infection control in the negative pressure isolation wards. Herein, cameras cover the entire ward except for the privacy area. The infection control observer monitors medical staff in real time via computer monitors in a separate area (figure). The main responsibilities of the observer are to maintain the normal operation of the negative pressure isolation wards, supervise the implementation of disinfection, ensure a sufficient supply of protective materials, arrange specimens for inspection, and relieve anxiety of the medical personnel while treating patients. The observers pay attention to the medical staff not only during their time in the negative pressure ward, but also during the putting on or taking off of protective equipment when they enter or leave the ward. Although the health-care providers have attended multiple training sessions and emergency drills, in operation (especially in high-stress negative pressure wards) some steps might be omitted or overlooked, thus incurring potential exposure to nosocomial infection. For example, when a nurse helped an elderly patient pull up a zipper in the negative pressure ward, the zipper unexpectedly ripped the nurse’s glove. The nurse became nervous, and anxious to continue her procedures. Discovering this situation on screen, the observer immediately soothed the nurse and sent another staff member into the ward to assist. Following the occupational exposure process, the observer then instructed the nurse to remove her gloves carefully, disinfect her hands, and dispose of the ripped gloves. The observer also systematically assessed the risks for the nurse and arranged a quarantine room for medical observation to ensure full safety before she was allowed to return to the negative pressure ward. The observing system, as a proactive infection control tool, provides immediate prevention against nosocomial infection in negative pressure isolation wards, which offers creative assistance to combat the COVID-19 outbreak. Guangdong Second Provincial General Hospital plans to incorporate artificial intelligence image recognition into the observing system, aiming to enhance the sensitivity and accuracy of instant detection. Implementing and improving the observing system might be a promising endeavor for controlling nosocomial infection of the COVID-19 outbreak and other acute infectious diseases.