scholarly journals 22. International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Outcome

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S15-S15
Author(s):  
Ray Y Hachem ◽  
Anne-Marie Chaftari ◽  
Nigo Masayuki ◽  
Nelson Hamerschlak ◽  
Hiba Dagher ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cancer Patients ◽  
Independent Risk Factor ◽  
Panel Member ◽  
Low Flow ◽  
Treatment Modalities ◽  
Research Support ◽  
Review Panel ◽  
All Cause Mortality

Abstract Background Given the limited collaborative international studies that evaluated COVID-19 in patients with cancer in comparison to patients without cancer, we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods We retrospectively collected de-identified data on cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, at 16 centers in Asia, Australia, Europe, North America, and South America. A logistic regression model was used to identify independent predictors of all-cause mortality within 30 days after COVID-19 diagnosis. Results Of the total 4015 COVID-19 confirmed patients entered, we analyzed 3966 patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were older than non-cancer patients (median age, 61 vs 50 years; p< 0.0001); more likely to be pancytopenic , had pulmonary disorders, hypertension, diabetes mellitus. In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms. By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to 6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who were on high flow oxygen (5.9% vs 17.6%; p=0.03). Patients transfused with convalescent plasma within 1 day of diagnosis had a lower 30-day mortality rate than those transfused later (1% vs 7%, p=0.04). Conclusion Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality, as well as convalescent plasma given early after COVID-19 diagnosis. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support) Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Monica Slavin, MBBS,MD, F2G (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Pfizer (Advisor or Review Panel member) Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

scholarly journals 634. Investigational Microbiome Therapeutic SER-109 Reduces Recurrence of Clostridioides difficile Infection (CDI) Compared to Placebo, Regardless of Risk Factors for Recurrence

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S420-S420
Author(s):  
Stuart H Cohen ◽  
Thomas J Louie ◽  
Matthew Sims ◽  
John Pullman ◽  
Elaine E Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Panel Member ◽  
Exploratory Analysis ◽  
Oral Microbiome ◽  
Comorbid Conditions ◽  
Research Support ◽  
Independent Contractor ◽  
Review Panel ◽  
Risk Factors For Recurrence

Abstract Background Several demographic and clinical characteristics, including age, sex, medication use and presence of comorbid conditions are considered risk factors for recurrent CDI (rCDI). We examined the efficacy of an investigational purified oral microbiome therapeutic, SER-109, versus placebo in an exploratory analysis of subgroups of patients with risk factors for recurrence who enrolled in ECOSPOR III, a double-blind, placebo controlled trial. Forest Plot of Relative Risks for Recurrence at Week 8 for Selected Baseline Characteristics in the ITT population Methods Patients with ≥ 3 CDI episodes were treated with SER-109 or placebo (four capsules daily for three days) following standard treatment of CDI. The primary efficacy objective was to demonstrate superiority of SER-109 versus placebo in reducing rCDI up to 8 weeks after treatment. In this exploratory analysis, we analyzed the rate of CDI recurrence among SER-109 treated subjects compared to placebo in subgroups defined by rCDI baseline risk factors: proton-pump inhibitor use, number of CDI recurrences, prior FMT history, presence of comorbid conditions and exposure to non-CDI antibiotics after dosing. We also analyzed the rate of CDI recurrence among SER-109 treated subjects by age (≥ 65 and ≤ 65) and gender, which were pre-specified. Results Of 281 patients screened,182 were enrolled. Overall recurrence rates were lower in SER-109 treated patients compared to placebo (12.4% vs 39.8%, respectively); relative risk (RR), 0.32 [95% CI, 0.18-0.58; P< 0.001 for RR< 1.0:P< 0.001 for RR< 0.833]. Co-morbidities including diabetes, renal disease, malignancy, cardiac disease, COPD/asthma, colitis, or immunocompromised status were observed in most patients in the overall study population; 33.5%, 32.4% and 34.1% had 0, 1, or ≥ 2 comorbidities. SER-109 was consistently observed to show greater benefit than placebo in reducing CDI recurrence in all subgroups regardless of the presence or absence of the rCDI risk factor (Fig 1). Conclusion Regardless of risk factor status, SER-109 reduced recurrence of CDI compared to placebo. Most subjects in ECOSPOR III had co-morbidities consistent with the broad inclusion criteria in this Phase 3 trial. Despite a high proportion of patients with co-morbidities in ECOSPOR III, SER-109 significantly reduced the risk of recurrence compared to placebo. Disclosures Stuart H. Cohen, MD, Seres (Research Grant or Support) Thomas J. Louie, MD, Artugen (Advisor or Review Panel member)Crestone (Consultant, Grant/Research Support)Da Volterra (Advisor or Review Panel member)Finch Therapeutics (Grant/Research Support, Advisor or Review Panel member)MGB Biopharma (Grant/Research Support, Advisor or Review Panel member)Rebiotix (Consultant, Grant/Research Support)Seres Therapeutics (Consultant, Grant/Research Support)Summit PLC (Grant/Research Support)Vedanta (Grant/Research Support, Advisor or Review Panel member) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Kelly Brady, MS, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder)

scholarly journals 1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
Eleni Karantoni ◽  
Yiqi Su ◽  
Anat Stern ◽  
Phaedon D Zavras ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
T Cell ◽  
Panel Member ◽  
Multivariable Model ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Advisory Boards ◽  
Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

scholarly journals 798. Metronidazole Exposure Prior to Clostridiodes difficile Infection (CDI) is a Risk Factor for Severe C. difficile Disease in Cancer Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S442-S443
Author(s):  
Denise Marie A Francisco ◽  
Liangliang Zhang ◽  
Ying Jiang ◽  
Adilene Olvera ◽  
Eduardo Yepez Guevara ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cancer Patients ◽  
Research Study ◽  
Research Support ◽  
Factors Associated ◽  
Patients With Cancer ◽  
Study Investigator ◽  
Severity Levels ◽  
Permutation Analysis

Abstract Background Antibiotic use is a risk factor for CDI. Few studies have correlated use of prior antibiotics with CDI severity in cancer patients. This study identified clinical and microbiology risk factors associated with severe CDI in patients with cancer. We hypothesized that previous antibiotic exposure and microbiome composition at time of CDI presentation, are risk factors for severe disease in cancer patients. Methods This non-interventional, prospective, single-center cohort study examined patients with cancer who had their first episode or first recurrence of CDI between Oct 27, 2016 and Jul 1, 2019. C. difficile was identified using nucleic acid amplification testing. Multivariate analysis was used to determine significant clinical risk factors for severe CDI as defined in the 2018 IDSA/SHEA guidelines. Alpha, and beta diversities were calculated to measure the average species diversity and the overall microbial composition. Differential abundance analysis and progressive permutation analysis were used to single out the significant microbial features that differed across CDI severity levels. Results Patient (n=200) demographics show mean age of 60 yrs., 53% female, majority White (76%) and non-Hispanic (85%). Prior 90 day metronidazole use (Odds Ratio OR 4.68 [1.47-14.91] p0.009) was a significant risk factor for severe CDI. Other factors included Horn’s Index > 2 (OR 7.75 [1.05-57.35] p0.045), Leukocytosis (OR 1.29 [1.16-1.43] p< 0.001), Neutropenia (OR 6.01 [1.34-26.89] p0.019) and Serum Creatinine >0.95 mg/dL (OR 25.30 [8.08-79.17] p< 0.001). Overall, there were no significant differences in alpha and beta diversity between severity levels. However, when identifying individual microbial features, the high presence of Bacteroides uniformis, Ruminococceae, Citrobacter koseri and Salmonella were associated with protection from severe CDI (p< 0.05). Table 1 - Results of multivariate logistic regression analysis of factors associated with severe CDI Figure 1. Microbiome features identified by progressive permutation analysis as seen in a volcano plot. Conclusion A number of risk factors for severe CDI were identified among this population, including prior 90 day metronidazole use. Also, increased relative abundance of Bacteroides uniformis, Ruminococceae, Citrobacter koseri and Salmonella were linked to protection from severe CDI. Reducing metronidazole use in patients with cancer may help prevent subsequent severe CDI. Disclosures Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Kevin W. Garey, PharmD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator) Ryan J. Dillon, MSc, Merck & Co., Inc., (Employee) Engels N. Obi, PhD, Merck & Co. (Employee)

scholarly journals Cardiovascular risk factors during cancer treatment: prevalence, incidence and prognostic relevance

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Caro Codon ◽  
T Lopez-Fernandez ◽  
C Alvarez-Ortega ◽  
P Zamora Aunon ◽  
I Rodriguez Rodriguez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Individual Risk ◽  
Funding Source ◽  
Number Of Patients ◽  
All Cause Mortality

Abstract Background The actual usefulness of CV risk factor assessment in the prognostic evaluation of cancer patients treated with cardiotoxic treatment remains largely unknown. Design Prospective multicenter study in patients scheduled to receive anticancer therapy related with moderate/high cardiotoxic risk. Methods A total of 1324 patients underwent follow-up in a dedicated cardio-oncology clinic from April 2012 to October 2017. Special care was given to the identification and control of CV risk factors. Clinical data, blood samples and echocardiographic parameters were prospectively collected according to protocol, at baseline before cancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years and 2 years after initiation of cancer therapy. Results At baseline, 893 patients (67.4%) presented at least 1 risk factor, with a significant number of patients newly diagnosed during follow-up. Individual risk factors were not related with worse prognosis during a 2-year follow-up. However, a higher Systemic Coronary Risk Estimation (SCORE) was significantly associated with higher rates of severe cardiotoxicity and all-cause mortality [HR 1.79 (95% CI 1.16–2.76) for SCORE 5–9 and HR 4.90 (95% CI 2.44–9.82) for SCORE ≥10 when compared with patients with lower SCORE (0–4)]. Conclusions This large cohort of patients treated with a potentially cardiotoxic regimen showed a significant prevalence of CV risk factors at baseline and significant incidence during follow-up. Baseline cardiovascular risk assessment using SCORE predicted severe cardiotoxicity and all-cause mortality. Therefore, its use should be recommended in the evaluation of cancer patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was partially funded by the Fondo Investigaciones Sanitarias (Spain), Centro de Investigaciόn Biomédica en Red Cardiovascular CIBER-CV (Spain)

Outcomes for and Risk Factors Associated With Vancomycin-ResistantEnterococcus faecalisand Vancomycin-ResistantEnterococcus faeciumBacteremia in Cancer Patients

2007 ◽  
Vol 28 (9) ◽  
pp. 1054-1059 ◽  
Author(s):  
G. Ghanem ◽  
R. Hachem ◽  
Y. Jiang ◽  
R. F. Chemaly ◽  
I. Raad
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Mortality Rate ◽  
Cancer Patients ◽  
Independent Risk Factor ◽  
Response To Therapy ◽  
Aminoglycoside Therapy ◽  
Significant Difference ◽  
Vancomycin Resistant ◽  
And Control

Objective.Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial infection. We sought to compare vancomycin-resistant (VR)Enterococcus faecalisbacteremia and VREnterococcus faeciumbacteremia in cancer patients with respect to risk factors, clinical presentation, microbiological characteristics, antimicrobial therapy, and outcomes.Methods.We identified 210 cancer patients with VRE bacteremia who had been treated between January 1996 and December 2004; 16 of these 210 had VRE. faecalisbacteremia and were matched with 32 patients with VRE. faeciumbacteremia and 32 control patients. A retrospective review of medical records was conducted.Results.Logistic regression analysis showed that, compared with VRE. faecalisbacteremia, VRE. faeciumbacteremia was associated with a worse clinical response to therapy (odds ratio [OR], 0.3 [95% confidence interval (CI), 0.07-0.98];P= .046) and a higher overall mortality rate (OR, 8.3 [95% CI, 1.9-35.3];P= .004), but the VRE-related mortality rate did not show a statistically significant difference (OR, 6.8 [95% CI, 0.7-61.8];P= .09). Compared with control patients, patients with VRE. faecalisbacteremia were more likely to have received an aminoglycoside in the 30 days before the onset of bacteremia (OR, 5.8 [95% CI, 1.2-27.6];P= .03), whereas patients with VRE. faeciumbacteremia were more likely to have received a carbapenem in the 30 days before the onset of bacteremia (OR, 11.7 [95% CI, 3.6-38.6];P<.001). In a multivariate model that compared patients with VRE. faeciumbacteremia and control patients, predictors of mortality included acute renal failure on presentation (OR, 15.1 [95% CI, 2.3-99.2];P= .004) and VRE. faeciumbacteremia (OR, 11 [95% CI, 2.7-45.1];P<.001). No difference in outcomes was found between patients with VRE. faecalisbacteremia and control patients.Conclusions.VRE. faeciumbacteremia in cancer patients was associated with a poorer outcome than was VRE. faecalisbacteremia. Recent receipt of carbapenem therapy was an independent risk factor for VRE. faeciumbacteremia, and recent receipt of aminoglycoside therapy was independent risk factor forE. faecalisbacteremia.

scholarly journals 1050. Phase 3 Trial to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by 23valent Pneumococcal Polysaccharide Vaccine 6 Months Later in At-risk Adults Aged 18–49 Years (PNEU-DAY): A Subgroup Analysis by Baseline Risk Factors

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S616-S617
Author(s):  
Laura Hammitt ◽  
Dean Quinn ◽  
Ewa Janczewska ◽  
Francisco J Pasquel ◽  
Richard Tytus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
Baseline Risk ◽  
Research Support ◽  
Review Panel ◽  
Post Vaccination ◽  
Study Investigator ◽  
Research Grant

Abstract Background Risk factors (RFs) for pneumococcal disease (PD) in immunocompetent individuals include comorbidities, behavioral habits, or living in a community with increased risk of PD transmission. RF stacking of comorbidities is associated with a higher incidence of PD, approaching that of immunocompromised individuals. Pneumococcal vaccination of certain adults is recommended with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) alone/sequentially with pneumococcal conjugate vaccine (PCV). V114, an investigational 15-valent PCV, contains 2 epidemiologically important serotypes (STs), 22F and 33F, in addition to the 13 STs in 13-valent PCV (PCV13). Methods PNEU-DAY was a Phase 3 study evaluating V114 or PCV13 administered on Day 1, and PPSV23 given 6 months later, in adults aged 18–49 years with or without RFs. This subgroup analysis assessed safety, tolerability, and immunogenicity of V114 and PCV13 based on the number of baseline PD RFs, which included chronic liver, lung, and heart disease, diabetes mellitus, tobacco use, and alcohol consumption. Adverse events (AEs; overall and solicited) were collected after each vaccination. Immunogenicity assessment was based on ST-specific opsonophagocytic activity (OPA) at 30 days after each vaccination. Subgroup analyses were conducted by RF group (0, 1, or ≥2 RFs for PD). Results Among the 1515 participants randomized to V114 (n=1135) or PCV13 (n=380), 25.2% had no RFs, 54.7% had 1 RF and 20.1% had ≥2 RFs for PD at baseline. The proportions of participants with solicited AEs following V114/PCV13 and PPSV23 were comparable across the 3 subgroups, with injection-site pain, myalgia, and fatigue being the most common. V114 and PCV13 were immunogenic in all subgroups based on OPA geometric mean titers (GMTs) at 30 days post-vaccination for the 13 shared STs (Figure); in addition, V114 induced a robust immune response to the 2 unique STs (22F, 33F) in all subgroups. PPSV23 following PCV was immunogenic for all 15 STs contained in V114 across all subgroups. Figure. Serotype-specific OPA GMTs at baseline and 30 days post-vaccination with V114 and PCV13 by number of baseline risk factors (per-protocol population) Conclusion V114 administered alone/sequentially with PPSV23 is well tolerated and immunogenic for all 15 vaccine STs, including those not contained in PCV13, in immunocompetent adults aged 18–49 years, regardless of the number of baseline RFs. Disclosures Laura Hammitt, MD, MedImmune (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Novavax (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Francisco J. Pasquel, MD, MPH, Boehringer Ingelheim (Consultant)Dexcom (Grant/Research Support)Eli Lilly & Company (Consultant)Insulet (Grant/Research Support)Merck & Co., Inc. (Consultant, Grant/Research Support) K. Rajender Reddy, MD, BMS (Grant/Research Support)Deciphera (Advisor or Review Panel member)Gilead (Grant/Research Support)Grifols (Grant/Research Support)HCC-TARGET (Grant/Research Support)Intercept (Grant/Research Support)Mallinckrodt (Grant/Research Support, Advisor or Review Panel member)NASH-TARGET (Grant/Research Support)Pfizer (Advisor or Review Panel member)Sequana (Grant/Research Support) Ron Dagan, MD, Medimmune/AstraZeneca (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau) Rachel Dawson, D.O. MPH, Merck & Co., Inc. (Employee, Shareholder) Jennifer McCauley, BSc, Merck & Co., Inc. (Employee) Kyeongmi Cheon, Ph.D., Merck & Co., Inc. (Employee, Shareholder) Alison Pedley, PhD, Merck & Co., Inc. (Employee) Tina Sterling, BS, Merck & Co., Inc. (Employee, Shareholder) Gretchen Tamms, B.S., Merck Sharp and Dohme (Employee, Shareholder) Luwy Musey, MD, Merck & Co., Inc. (Employee) Ulrike K. Buchwald, MD, MS, Merck & Co., Inc. (Employee)TB Alliance (Employee)

scholarly journals 1172. Mucormycosis Treated with Isavuconazole: A matched-Pair Analysis from the FungiScope® Registry

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S611-S612
Author(s):  
Danila Seidel ◽  
Oliver Cornely ◽  
Maria J G T Vehreschild ◽  
Philipp Koehler ◽  
Jon Salmanton-García ◽  
...  
Keyword(s):  
Research Study ◽  
Panel Member ◽  
First Line ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
First Line Therapy ◽  
Line Therapy ◽  
Study Investigator ◽  
All Cause Mortality

Abstract Background Isavuconazole (ISAV) is a novel, broad-spectrum triazole antifungal, available in both intravenous and oral formulations, for the treatment of adult patients with invasive aspergillosis or mucormycosis. In this retrospective case collection study, we compared outcomes for patients with invasive mucormycosis treated with ISAV versus other systemic antifungal therapies, in order to evaluate the real-world effectiveness of ISAV. Methods Proven and probable invasive mucormycosis cases treated with ISAV for a minimum of four consecutive days between 2016 and 2019 were identified from the FungiScope® registry. Matched controls were defined as patients treated with lipid formulations of amphotericin B (lipid-AMB), posaconazole, or a combination of both, as first-line therapy between 2011 and 2019. Case-matching criteria included disease severity, presence of hematological malignancy or allogeneic stem cell transplantation, and surgery for fungal disease. Baseline patient characteristics and clinical outcomes were compared descriptively. Results Each of 30 ISAV cases was matched to 1–3 controls, including 25 ISAV cases each matched to 2 or 3 controls, which resulted in a total of 69 control cases. In 70.0% of ISAV cases (n=21), ISAV was administered as a treatment for invasive mucormycosis in patients who had received prior lipid-AMB. In the remaining cases, ISAV was administered after prior voriconazole treatment (n=3) or as first-line therapy (n=6). All control patients received either lipid-AMB, posaconazole, or a combination of both. Baseline demographic and clinical characteristics and causative pathogens were similar between ISAV cases and controls (Table). Overall response rates (defined as achieving a complete or partial response) at the final assessment were 50.0% (15/30) for ISAV cases and 50.7% (35/69) for controls. All-cause mortality was 43.3% (13/30) in ISAV cases as compared to 46.4% (32/69) in controls (Figure). Table. Demographic and clinical characteristics of 30 isavuconazole cases and 69 control cases Figure. Clinical response at final assessment and all cause mortality for 30 isavuconazole cases and 69 control cases Conclusion In this retrospective analysis of cases from the FungiScope® registry, patients with invasive mucormycosis showed similar overall treatment response and all-cause mortality rates with ISAV compared to treatment with lipid-AMB and/or posaconazole. These data support the effectiveness of isavuconazole in clinical practice. Disclosures Danila Seidel, PhD, Basilea (Other Financial or Material Support, travel grant) Oliver Cornely, Prof., Actelion (Grant/Research Support)Actelion (Other Financial or Material Support, Personal fees)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Other Financial or Material Support, Personal fees)Amplyx (Other Financial or Material Support, Personal fees)Amplyx (Grant/Research Support)Astellas (Grant/Research Support)Astellas (Other Financial or Material Support, Personal fees)Basilea (Other Financial or Material Support, Personal fees)Basilea (Grant/Research Support)Biosys UK Limited (Other Financial or Material Support, Personal fees)Cidara (Other Financial or Material Support, Personal fees)Cidara (Grant/Research Support)Da Volterra (Grant/Research Support)Da Volterra (Other Financial or Material Support, Personal fees)Entasis (Other Financial or Material Support, Personal fees)F2G (Other Financial or Material Support)F2G (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Other Financial or Material Support, Personal fees)Grupo Biotoscana (Other Financial or Material Support, Personal fees)Janssen Pharmaceuticals (Grant/Research Support)Matinas (Other Financial or Material Support, Personal fees)Medicines Company (Grant/Research Support)MedPace (Grant/Research Support)MedPace (Other Financial or Material Support, Personal fees)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche (Other Financial or Material Support, Personal fees)Merck/MSD (Other Financial or Material Support, Personal fees)Merck/MSD (Grant/Research Support)Mylan Pharmaceuticals (Consultant)Nabriva Therapeutics (Other Financial or Material Support, Personal fees)Octapharma (Other Financial or Material Support, Personal fees)Paratek Pharmaceuticals (Other Financial or Material Support, Personal fees)Pfizer (Other Financial or Material Support, Personal fees)Pfizer (Grant/Research Support)PSI (Other Financial or Material Support, Personal fees)Rempex (Other Financial or Material Support, Personal fees)Roche Diagnostics (Other Financial or Material Support, Personal fees)Scynexis (Other Financial or Material Support, Personal fees)Scynexis (Grant/Research Support)Seres Therapeutics (Other Financial or Material Support, Personal fees)Tetraphase (Other Financial or Material Support, Personal fees) Philipp Koehler, MD, Akademie für Infektionsmedizin e.V., (Other Financial or Material Support, Personal fees)Astellas Pharma GmbH (Other Financial or Material Support, Personal fees)Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany (Other Financial or Material Support, Other)Gilead Sciences GmbH (Other Financial or Material Support, Personal fees)GPR Academy Ruesselsheim (Speaker’s Bureau)Miltenyi Biotec GmbH (Other Financial or Material Support, Non-financial support)MSD Sharp & Dohme GmbH (Other Financial or Material Support, Personal fees)Noxxon N.V. (Speaker’s Bureau)University Hospital, LMU Munich (Other Financial or Material Support, Personal fees) Nikolay Klimko, n/a, Astellas (Speaker’s Bureau)Gilead (Speaker’s Bureau)Merck/MSD (Speaker’s Bureau)Pfizer (Speaker’s Bureau) Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member) Martin Hoenigl, MD, SCYNEXIS, Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Farima Barmaki-Rad, n/a, Basilea Pharmaceutica International Ltd. (Employee) Mikael Saulay, n/a, Basilea Pharmaceutica International Ltd. (Employee) Marc Engelhardt, n/a, Basilea Pharmaceutica International Ltd. (Board Member, Consultant, Employee, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Shareholder, Speaker’s Bureau, Independent Contractor, Other Financial or Material Support)Basilea Pharmaceutica International Ltd. (Employee) Kamal Hamed, n/a, Basilea Pharmaceutica International Ltd. (Employee)

scholarly journals 796. Burden of Healthcare-associated (HA) Respiratory Syncytial Virus (RSV) in Hospitalized Adults

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S494-S494
Author(s):  
Alexandra C Hill-Ricciuti ◽  
Edward E Walsh ◽  
William G Greendyke ◽  
Angela Barrett ◽  
Luis Alba ◽  
...  
Keyword(s):  
Risk Factors ◽  
Conditional Logistic Regression ◽  
Panel Member ◽  
Positive Test ◽  
Respiratory Support ◽  
Respiratory Pathogens ◽  
Research Support ◽  
Retrospective Case ◽  
Review Panel ◽  
Syncytial Virus

Abstract Background Little is known about the burden of HA-RSV in hospitalized adults. We assessed risk factors and clinical outcomes in hospitalized adults diagnosed with HA-RSV. Methods A retrospective case-control study was performed from 2017-2020 in two academic hospital systems. HA-RSV cases were &gt;18 years of age, hospitalized &gt;4 days, and developed new or worsening respiratory signs and symptoms that prompted clinicians to test for respiratory pathogens; cases were RSV-positive by PCR assays. Two community-onset (CO) RSV-positive controls (admitted with &gt;2 acute respiratory symptoms), were matched to each HA-RSV case by age, sex, and RSV season. We compared risk factors and outcomes in cases vs. controls. We assessed escalation of respiratory support in HA-RSV cases, defined as new or increased respiratory support from Day -2 to Day +4 of their RSV-positive test. Exact conditional logistic regression compared outcomes of HA-RSV vs. CO-RSV subjects, adjusting for demographic and clinical characteristics. Results 84 cases and 160 controls (both median 64 years) were included; 87% had ≥1 comorbidity. HA-RSV cases were hospitalized for a median of 10 (IQR: 5-17) days prior to their RSV-positive test. CO-RSV controls were more likely to have pulmonary comorbidities than HA-RSV cases (46% vs. 31%, p=0.02). 38% of HA-RSV vs. 15% of CO-RSV subjects were hospitalized ≥15 days after their RSV-positive test (p=0.047). 14% of HA-RSV and 6% of CO-RSV subjects died (p=0.25). Among patients who survived, HA-RSV cases were more likely discharged to a skilled nursing or rehabilitation facility than CO-RSV controls (46% vs. 17%, p=0.04). Of the 44 HA-RSV cases assessed thus far, 25% required escalation of respiratory support; none required initiation of mechanical ventilation. Conclusion HA-RSV was associated with increased morbidity and increased health care resource use during and after hospitalization. RSV vaccines could prevent CO- and HA-RSV infections in adults. Disclosures Edward E. Walsh, MD, GSK (Advisor or Review Panel member)Janssen (Grant/Research Support)Merck (Grant/Research Support)Merck (Grant/Research Support) William G. Greendyke, MD, Merck (Grant/Research Support) Angela Branche, MD, Merck Dohme and Sharpe (Grant/Research Support) Ann Falsey, MD, BioFire Diagnostics (Grant/Research Support)Janssen (Grant/Research Support)Merck (Grant/Research Support)Novavax (Other Financial or Material Support, DSMB member)Pfizer (Grant/Research Support) Matthew R. Phillips, MPH, Merck & Co., Inc. (Employee, Shareholder) Yoonyoung Choi, PhD, MS, RPh, Merck (Employee) Lyn Finelli, DrPH, MS, Merck (Employee) Lisa Saiman, MD, MPH, Merck (Grant/Research Support, Research Grant or Support)Merk Co., Inc (Grant/Research Support, Advisor or Review Panel member)

scholarly journals 889. Early Discontinuations and Adverse Events Among Treatment-Naïve Patients Initiating Integrase Inhibitors in a Real-world Setting

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S535-S536
Author(s):  
Charlotte-Paige M Rolle ◽  
Jamie Castano ◽  
Vu Nguyen ◽  
Kiran Patel ◽  
Federico Hinestrosa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
Integrase Inhibitors ◽  
Research Support ◽  
Review Panel ◽  
Study Investigator ◽  
Treatment Naïve

Abstract Background Cohort studies suggest higher rates of discontinuations (DCs) and adverse events (AEs) with integrase inhibitors (INSTIs) than is reported in clinical trials. Here, we assess DC of different INSTIs in combination with one of two tenofovir prodrugs in the first year following initiation defined as “early DC” in a real-world cohort of treatment-naïve patients. Methods This analysis evaluated treatment-naïve patients at a single center initiating raltegravir (RAL), elvitegravir/cobicistat (EVG/c), dolutegravir (DTG) or bictegravir (BIC) in combination with emtricitabine/tenofovir alafenamide (F/TAF) or emtricitabine/tenofovir disoproxil fumarate (F/TDF) between 10/2007-1/2020. Eligible patients had a minimum follow-up of 1 year. The primary endpoint was incidence of early INSTI DC. Secondary endpoints included AEs and risk factors for early INSTI DC and treatment-related AEs. Results 331 patients were included. Median age was 32 years, 89% were male, 43% were non-White, 8% started RAL-based therapy, 46% started EVG/c-based therapy, 22% started DTG-based therapy and 24% started BIC/F/TAF. 36 discontinued INSTI-based therapy early yielding an incidence rate of 0.17 DCs per person-years (PPY) among RAL patients, 0.14 DCs PPY among EVG/c patients, 0.22 DCs PPY among DTG patients, and 0 DCs PPY among BIC patients, p=0.006. Treatment-related AEs occurred in 27% of RAL patients, 42% of EVG/c patients, 50% of DTG patients, and 43% of BIC patients p=0.607; and were responsible for early DC rates of 0.022 in 3 EVG/c patients and 0.075 in 5 DTG patients. No treatment-related early DCs occurred among RAL or BIC patients. No evaluated factor was significantly associated with early INSTI DC, however DTG use was significantly associated with treatment-related AEs (aOR 3.46, 95% confidence interval: [1.20; 10.82]). Table 1. Risk factors for early integrase inhibitor discontinuation and treatment-related adverse events Conclusion In this cohort, early DCs occurred in 11% initiating INSTI-based therapy, however of these only 2% were treatment-related. These data support use of INSTI-based regimens as preferred options for treatment-naïve patients living with HIV due to their favorable safety and tolerability profiles. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Scientific Research Study Investigator, Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Advisor or Review Panel member, Speaker’s Bureau)Theratechonologies (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member)

scholarly journals 38. Remdesivir Treatment in Patients Hospitalized with COVID-19: A Comparative Analysis of In-Hospital All-Cause Mortality

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S27-S28
Author(s):  
Essy Mozaffari ◽  
Aastha Chandak ◽  
Zhiji Zhang ◽  
Shuting Liang ◽  
Mark Thrun ◽  
...  
Keyword(s):  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
High Flow ◽  
Low Flow ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Risk Of Death ◽  
Study Investigator

Abstract Background Remdesivir (RDV) reduced time to recovery and mortality in some subgroups of hospitalized patients in the NIAID ACTT-1 RCT compared to placebo. Comparative effectiveness data in clinical practice are limited. Methods Using the Premier Healthcare Database, we compared survival for adult non-mechanically ventilated hospitalized COVID-19 patients between Aug-Nov 2020 and treated with RDV within 2 days of hospitalization vs. those who did not receive RDV. Preferential within-hospital propensity score matching with replacement was used. Patients were matched on baseline O2 and 2-month admission period and were excluded if discharged within 3 days of RDV initiation (to exclude anticipated discharges/transfers within 72 hrs consistent with ACTT-1 study). Time to 14- and 28-day mortality was examined separately for patients on high-flow/non-invasive ventilation (NIV), low-flow, and no supplemental O2 using Cox Proportional Hazards models. Results RDV patients (n=27,559) were matched to unique non-RDV patients (n=15,617) (Fig 1). The two groups were balanced; median age 66 yrs and 73% white (RDV); 68 yrs and 74% white (non-RDV), and 55% male. At baseline, 21% required high-flow O2, 50% low-flow O2, and 29% no O2, overall. Mortality in RDV patients was 9.6% and 13.8% on days 14 and 28, respectively. For non-RDV patients, mortality was 14.0% and 17.3% on days 14 and 28, respectively. Kaplan-Meier curves for time to mortality are shown in Fig 2. After adjusting for baseline and clinical covariates, RDV patients on no O2 and low-flow O2 had a significantly lower risk of death within 14 days (no O2, HR: 0.69, 95% CI: 0.57—0.83; low-flow, HR: 0.67, 95% CI: 0.59—0.77) and 28 days (no O2, HR: 0.80, 95% CI: 0.68—0.94; low-flow, HR: 0.76, 95% CI: 0.68—0.86). Additionally, RDV patients on high-flow O2/NIV had a significantly lower risk of death within 14 days (HR: 0.81, 95% CI: 0.70—0.93); but not at 28 days (Fig 3). Fig 1. Study Population Fig 2. Kaplan-Meier curves among matched patients hospitalized for COVID-19, August-November 2020 Fig 3. Cox proportional hazard model* for time to mortality among matched patients hospitalized for COVID-19, August-November 2020 Conclusion In this large study of patients in clinical care hospitalized with COVID-19, we observed a significant reduction of mortality in RDV vs. non-RDV treated patients in those on no O2 or low-flow O2. Mortality reduction was also seen in patients on high-flow O2 at day 14, but not day 28. These data support the use of RDV early in the course of COVID-19 in hospitalized patients. Disclosures Essy Mozaffari, PharmD, MPH, MBA, Gilead Sciences (Employee, Shareholder) Aastha Chandak, PhD, Gilead Sciences (Other Financial or Material Support, Employee of Certara (contracted by Gilead to conduct this study)) Zhiji Zhang, MS, Gilead Sciences (Other Financial or Material Support, Employee of Certara (contracted by Gilead to conduct this study)) Shuting Liang, MPH, Gilead Sciences (Employee) Mark Thrun, MD, Gilead Sciences (Employee, Shareholder) Robert L. Gottlieb, MD, Eli Lilly (Scientific Research Study Investigator, Advisor or Review Panel member)Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Gift in kind to Baylor Scott and White Research Institute for NCT03383419)GSK (Advisor or Review Panel member)Johnson and Johnson (Scientific Research Study Investigator)Kinevant (Scientific Research Study Investigator)Roche/Genentech (Scientific Research Study Investigator) Daniel R. Kuritzkes, MD, Abpro (Consultant)Atea (Consultant, Scientific Research Study Investigator)Decoy (Consultant)Gilead Sciences (Consultant, Grant/Research Support)GSK (Consultant)Janssen (Consultant)Merck (Consultant, Grant/Research Support)Novartis (Scientific Research Study Investigator)Rigel (Consultant)ViiV (Consultant, Grant/Research Support) Paul Sax, MD, Gilead Sciences (Consultant, Grant/Research Support)Janssen (Consultant)Merck (Consultant, Research Grant or Support)ViiV (Consultant, Research Grant or Support) David Wohl, MD, Gilead Sciences (Consultant, Grant/Research Support, Advisor or Review Panel member)Janssen (Consultant, Advisor or Review Panel member)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member)ViiV (Consultant, Grant/Research Support, Advisor or Review Panel member) Roman Casciano, M.Eng, Gilead Sciences (Other Financial or Material Support, Employee of Certara (contracted by Gilead to conduct this study)) Paul Hodgkins, PhD, MSc, Gilead Sciences (Employee, Shareholder) Richard Haubrich, MD, Gilead Sciences (Employee, Shareholder)

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