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BackgroundProduction of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and lower-middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A public sector manufacturer in Vietnam assessed the immunogenicity of NDV-HXP-S (COVIVAC) relative to an authorized vaccine. MethodsThis phase 2 stage of a randomised, observer-blind, controlled, phase 1/2 trial was conducted at three community health centers in Thai Binh Province, Vietnam. Healthy males and non-pregnant females, 18 years of age and older, were eligible. Participants were randomised by age (18-59, [≥]60 years) to receive one of three treatments by intramuscular injection twice, 28 days apart: COVIVAC at 3 {micro}g or 6 {micro}g, or AstraZeneca COVID-19 vaccine VAXZEVRIA. Participants and personnel assessing outcomes were masked to treatment. The main outcome was the induction of 50% neutralising antibody titers against vaccine-homologous pseudotyped virus 14 days (day 43) and 6 months (day 197) after the second vaccination by age group. The primary immunogenicity and safety analyses included all participants who received one dose of the vaccine. ClinicalTrials.gov NCT05940194. FindingsDuring August 10-23, 2021, 737 individuals were screened, and 374 were randomised (124-125 per group); all received dose one, and three missed dose two. On day 43, the geometric mean fold rise of 50% neutralising antibody titers for subjects age 18-59 years was 31{middle dot}20 (COVIVAC 3 g N=82, 95% CI 25{middle dot}14-38{middle dot}74), 35{middle dot}80 (COVIVAC 6 g; N=83, 95% CI 29{middle dot}03-44{middle dot}15), 18{middle dot}85 (VAXZEVRIA; N=82, 95% CI 15{middle dot}10-23{middle dot}54), and for subjects age [≥]60 years was 37{middle dot}27 (COVIVAC 3 g; N=42, 95% CI 27{middle dot}43-50{middle dot}63), 50{middle dot}10 (COVIVAC 6 g; N=40, 95% CI 35{middle dot}46-70{middle dot}76), 16{middle dot}11 (VAXZEVRIA; N=40, 95% CI 11{middle dot}73-22{middle dot}13). Among subjects seronegative for anti-S IgG at baseline, the day 43 geometric mean titer ratio of neutralising antibody (COVIVC 6 g/VAXZEVRIA) was 1{middle dot}77 (95% CI 1{middle dot}30-2{middle dot}40) for subjects age 18-59 years and 3{middle dot}24 (95% CI 1{middle dot}98-5{middle dot}32) for subjects age [≥]60 years. On day 197, the age-specific ratios were 1{middle dot}11 (95% CI 0{middle dot}51-2{middle dot}43) and 2{middle dot}32 (0{middle dot}69-7{middle dot}85). Vaccines were well tolerated; reactogenicity was predominantly mild and transient. The percentage of subjects with unsolicited adverse events (AEs) during 28 days after vaccinations was similar among treatments (COVIVAC 3 g 29{middle dot}0%, COVIVAC 6 g 23{middle dot}2%, VAXZEVRIA 31{middle dot}2%); no vaccine-related AE was reported. InterpretationConsidering that induction of neutralising antibodies against SARS-CoV-2 has been correlated with the efficacy of COVID-19 vaccines, including VAXZEVRIA, our results suggest that vaccination with COVIVAC may afford clinical benefit matching or exceeding that of the VAXZEVRIA vaccine. FundingVietnams Institute of Vaccines and Medical Biologicals (including support from Vietnams national COVID-19 vaccine fund and a charitable contribution from the Thien Tam fund of Vin group), Coalition for Epidemic Preparedness Innovations, a charitable contribution from Bayer AG, US National Institutes of Health.
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Coronavirus Infections , Severe Acute Respiratory Syndrome , COVID-19摘要
The inconsistent implementation of disability rights in crisis responses such as the recent COVID-19 pandemic has illuminated the double difficulty that persons with disabilities (PwD) must face. Ableism remains the basis for pandemic responses, leading to a range of irrationalities in collecting and using disability data during critical times. This commentary identifies situational and contextual rationalities in disability data collection and use in Global South. Through vignettes from Indonesia and Vietnam, this commentary illuminates the socio-technical and cultural infrastructure that perpetuates the obscurity of disability rights in the pandemic responses in, respectively, the largest democratic and socialist-communist countries in Southeast Asia. In addition to better listening to the voice of PwD, stronger engagement of organizations of PwD in policy making and programming is advocated for enabling more equitable pandemic preparedness, response, and recovery plans to manifest in future. © The Author(s) 2023.
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Introduction: Intravenous fluids are the most commonly administered drug in critical care but can negatively impact outcomes if used inappropriately. The ROSE (Rescue, Optimization, Stabilization, Evacuation) model consists of four dynamic phases used to guide fluid-related decisions, and it may be used as a construct to direct pharmacistinvolvement in fluid stewardship. During the COVID-19 pandemic, patient-to-pharmacist ratios increased and a more efficient approach to fluid therapy was necessary, as these patients may manifest different fluid needs than more typical ICU patients. Research Question or Hypothesis: When categorizing recommendations by the ROSE model, how does pharmacy-directed fluid stewardship differ in critically ill adults with and without COVID-19? Study Design: IRB-approved, single-center, retrospective, cohort study. Methods: Critically ill adults with and without COVID-19 being followed by the ICU pharmacy team between May and September 2020 were included. Daily pharmacist notes were reviewed for recommendations. The primary outcome was the number of fluid stewardship-related recommendations. Secondary outcomes included the number of recommendations stratified by the ROSE phases. Results were compared between patients with and without COVID-19 using a two-sided t-test. Results: In patients with (n=79) and without (n=350) COVID-19, 1338 and 2597 recommendations were made across 420 and 895 patient days. Fewer fluid stewardship recommendations per patient day were made in the COVID-19 group (0.421 vs 0.556, p=0.003). The COVID-19 group had more recommendations in the rescue (0.029 vs 0.007/patient day, p=0.001) and optimization (0.026 vs 0.02/patient day, p=0.525) phases. The non-COVID-19 group had more recommendations in the stabilization (0.288 vs 0.429/patient day, p<0.001) and evacuation (0.045 vs 0.093/patient day, p=0.005) phases. Conclusion: Despite an important role in COVID-19, fluid stewardship recommendations were more frequent among patients without COVID-19. One explanation may be prolonged length of stay in COVID-19 patients, extending the stabilization and evacuation phases thereby lessening recommendations per patient day. Future research should evaluate outcomes related to pharmacist-directed fluid stewardship.
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Introduction: Volume overload leads to increased mortality and length of stay in critically ill patients. The "Four Rights of Fluid Stewardship" (right patient, drug, dose, and route) is a tool pharmacists can consider when optimizing intravenous fluids to avoid volume overload. Pharmacy-driven fluid stewardship recommendations for critically ill patients with and without coronavirus disease 2019 (COVID-19) have not yet been compared using the Four Rights construct. Research Question or Hypothesis: Due to risk of acute respiratory distress syndrome in COVID-19, pharmacy recommendations related to the Four Rights will occur more often in COVID-19 patients than non-COVID-19 patients. Study Design: Conducted before and during the COVID-19 pandemic, this retrospective, single-center, observational study included all critically ill adults followed on academic rounds. Patients were divided based on COVID-19 diagnosis. Methods: Pharmacy notes for each patient day were reviewed. Fluid stewardship-related recommendations were classified according to pre-determined definitions of the Four Rights. The primary outcome was the mean number of fluid stewardship recommendations per patient day. Secondary outcomes included the mean number of recommendations related to each Right. Outcomes were analyzed in SPSS using two-tailed, independent t-tests with an alpha of 0.05. Results: Recommendations were reviewed for 420 COVID-19 and 895 non-COVID-19 patient days (79 and 350 patients). The COVID-19 and non-COVID-19 groups, respectively, averaged 0.421 and 0.556 fluid stewardship recommendations per patient day (p=0.003), of which 0.143 and 0.217 were related to the right patient (p=0.004), 0.043 and 0.095 to the right drug (p=0.002), 0.062 and 0.062 to the right dose (p=0.977), and 0.176 and 0.184 to the right route (p=0.766). Conclusion: Fluid stewardship recommendations, especially those related to the right patient and drug, were less frequent in COVID-19 patients. This is surprising given the importance of fluid management in COVID-19 pathophysiology. Future research should investigate the relationship between direct patient-pharmacist contact and fluid stewardship recommendations and the impact on patient outcomes.
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Introduction: Intravenous fluids are routinely administered in the intensive care unit (ICU). This includes hidden fluids, which are defined as fluids requisite to routine care, but the volumes of which are not explicitly prescribed (e.g., medication diluents, flushes). With the distinct patient phenotype presented by coronavirus disease 2019 (COVID-19), careful management of fluids is crucial to minimize risks associated with fluid overload. Research Question or Hypothesis: How do pharmacist-driven hidden fluids recommendations differ in critically ill adults with and without COVID-19? Study Design: This single-center, retrospective, IRB-approved, observational study conducted at a community hospital included adult ICU patients with and without COVID-19. Methods: Recommendations made by the pharmacy rounding team were classified based on pre-determined criteria. The primary outcome was the percentage of pharmacy recommendations related to hidden fluids. Secondary outcomes classified the individual types of recommendations. The quantity of recommendations and average per patient day were compared in patients with and without COVID-19 using the Chi-squared test and t-test, respectively, conducted in SPSS with an alpha of 0.05. Results: A total of 420 COVID and 895 non-COVID patient days were reviewed. COVID patients received more pharmacy recommendations per patient day (3.189 vs 2.902, p=0.024), fewer fluid-related recommendations (0.421 vs 0.556, p=0.003), and a similar number of hidden fluids-related recommendations (0.202 vs 0.203, p=0.972). The most common hidden fluids recommendations were: IV to non-IV conversion (n=59 vs 148 recommendations, p=0.268), adjust dose of enteral fluid (n=16 vs 23, p=0.217), discontinue enteral water (n=6 vs 8, p=0.378), adjust volume of parenteral nutrition (n=2 vs 1, p=0.197), change albumin concentration (n=1 vs 0, p=0.144), and concentrate infusions (n=1 vs 2, p=0.959). Conclusion: The average number of hidden fluids-related recommendations was similar in patients with and without COVID-19. The study was limited by its single center and retrospective design. Future research should examine the relationship between hidden fluidsrelated recommendations and patient outcomes.
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Introduction: In the wake of both the unprecedented nationwide ban on elective surgery during the COVID-19 pandemicand the increased mortality of otolaryngologists and neurosurgeons during this same time period, concern regarding thetiming and safety of neurosurgical intervention for sellar-based pathology has been raised within both the neurosurgical andotolaryngology communities. Methods: A retrospective chart review was performed on all patients who underwent operative intervention for sellar-basedpathology from March 12 to July 1 for both 2019 and 2020. Dates were chosen to align with the Virginia State ofEmergency on March 12 and the multiphase reopening of the public which lasted until July 1. Primary endpoints studied forcomparison included case volume, median time to surgery, and COVID-related mortality. Results: In total, a 26.6% decrease in overall surgical case volume occurred in comparison to the previous year. Astatistically significant decrease in frequency of endonasal surgery was seen from 20 in 2019 to 6 in 2020 ( p = 0.04). Whilemedian time to surgery for pituitary adenomas was unchanged from the previous year (26 days), this data does not takeinto account six patients who electively postponed treatment due to fear of receiving medical care during the pandemic.Among 2,795 COVID-19 patients treated in our institution, only one patient had a pituitary tumor. Here, treatment wasdelayed by 81 days. For emergent cases, such as pituitary apoplexy, surgeons increased utilization of the microscope as ameans to reduce the number of personnel exposed. Finally, our practice had no COVID-related mortality for patientsundergoing sellar-based surgery. Conclusion: The COVID-19 pandemic did not delay time to treatment for emergent presentations of vision loss or pituitaryapoplexy. In these instances, our department followed strict institutional policy regarding use of proper PPE, as well asminimization of hospital personnel exposure. On an outpatient basis, the pandemic did cause a noticeable delay in time totreatment;however, patients' outcomes were unaffected. Close patient monitoring was achieved via utilization oftelemedicine to trend hormone levels and assess development of related symptoms. Finally, decreases in overall casevolume are likely due to ongoing cultural avoidance of seeking medical care, while deferment of endonasal surgery may beattributed to a concern for greater mortality for endonasal procedures.
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INTRODUCTION: An emerging body of literature has shown an association between obesity and negative COVID-19 patient outcomes. However, most of these studies have been limited in scale and are not focused on hospitalized patients. Our study aims to report characteristics and outcomes associated with obesity in a large cohort of COVID-19 patients who were admitted during the peak of this pandemic. METHODS: We performed a retrospective single center study at a large tertiary care hospital. All index admissions of adult patients with confirmed COVID-19 between 3/1 and 4/30/2020 were included. A manual chart review was performed to collect data on baseline patient characteristics, medical comorbidities, and clinical outcomes. Patients were stratified into obese and non-obese cohorts for comparison. SAS 9.4 was used for analysis. RESULTS: A total of 1983 patients met our inclusion criteria of which 1031 (51.9%) were obese and 952 (48.9%) were non-obese. Table 1 shows differences in baseline characteristics between these cohorts. Obese patients were younger (58.2 vs. 69.9;P < 0.001), more likely to be female (55% vs. 45%;P < 0.001) and a higher proportion were African American (66% vs. 52%;P < 0.001) compared to non-obese patients. Obese patients were also more likely to be diabetic (41% vs. 35%;P = 0.01) and have obstructive sleep apnea (15% vs. 5%;P < 0.001) and less likely to have cardiovascular disease (25% vs. 33%;P < 0.01) and malignancy (5% vs. 10%;P < 0.01) (Table 2a). Obese patients were found to have lower overall mortality compared to non-obese patients (15% vs. 25%;P < 0.001) however a logistic regression model revealed that this mortality difference was no longer significant when adjusted for patient age (OR 1.05, P = 0.685). This age-adjusted model also demonstrated increased odds of ICU admission (OR 1.39, P = 0.0044) and intubation (OR 1.40, P = 0.0096) in obese patients (Table 2b). There was a strong negative correlation (r2 = 0.2076, P < 0.001) between BMI and age among patients requiring ICU admission (Figure 1). CONCLUSION: Our study suggests that obesity may predispose younger patients with COVID-19 to be hospitalized for their illness. Although obese patients do not have an increased mortality rate, they are at higher risk for requiring ICU admission and intubation during their hospital stay. Recognizing that obesity impacts morbidity in this manner allows medical providers to triage and manage these patients more effectively earlier in their clinical course. (Table Presented).
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Background: There is increasing evidence suggesting that liver dysfunction is a risk factor for severe COVID-19 illness However, due to the low prevalence of liver disease and cirrhosis in the general population, larger studies looking at the impact of these conditions have utilized data from international registries which do not necessarily reflect the US population. Our study aims to assess the association between chronic liver disease and COVID-19 clinical outcomes across a single large inpatient cohort Methods: We performed a retrospective single-center study at a large tertiary care hospital All index admissions of adult patients with confirmed COVID-19 between 3/1/2020 and 4/30/2020 were included A manual chart review was performed to collect data on baseline patient characteristics, medical comorbidities, and clinical outcomes Patients with chronic liver disease (CLD) and cirrhosis were compared to the control group, who had no known underlying liver disease SAS 9 4 was used for analysis Results: A total of 1935 patients met our inclusion criteria of which 1869 (96 6%) had no underlying liver disease, 66 (3 4%) had CLD, and 21 (1 1%) had cirrhosis Table 1 shows baseline patient characteristics There were a higher proportion of males in the CLD and cirrhosis cohorts compared to the control group (67% and 76% vs 50%;p=0 0105) Patients with cirrhosis and chronic liver disease also had a significantly lower average BMI compared to the control group (25 8 and 27 3 vs 31 8;p=0 002) There was no difference in comorbidities between all three cohorts. Patients with cirrhosis had a significantly higher mortality (RR 2 1 [95% CI 1 33-3 62;p=0 0022]) compared to non-cirrhotics There was also a trend towards increased 30-day readmission in the cirrhotic cohort (RR 2 35 [95% CI 0 86-6 42];p=0 0950) however no difference in rate of ICU admission or intubation Patients with CLD did not have an increase in mortality, ICU admission, intubation, or 30-day re-admission compared to the control group Conclusion: Our study demonstrates that cirrhosis is associated with increased mortality in COVID-19 while chronic liver disease in the absence of cirrhosis does not confer the same degree of clinical risk Future studies performed on a larger scale should evaluate how decompensated disease and MELD score may impact this risk profile.(Table Presented).
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Background: Based on current literature there appears to be a high prevalence of liver injury (LI) in patients with COVID-19 However, there are limited large scale studies on risk factors, morbidity, and mortality associated with LI in these patients We aim to determine risk factors and outcomes of patients hospitalized with COVID-19 and LI Methods: We performed a retrospective single-center study at a large tertiary care hospital. All index admissions of adult patients with confirmed COVID19 between 3/1 to 4/30/2020 were included Data on baseline characteristics and clinical outcomes was collected during manual chart review Mild elevation in LFTs (MEL), defined as peak levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB) above upper limit of normal (ULN) but lower than the threshold for LI. LI was defined as peak ALT/AST three times ULN and/or peak ALP/TB two times ULN ULN threshold values of ALT 52, AST 35, TB 1 2, ALP 140 were used Both cohorts were compared with our control group, who had normal LFTs at presentation and throughout the hospitalization SAS 9 4 was used for analysis Results: A total of 1935 patients were included of which 507 (26 2%) had normal LFTs, 1030 (53 2%) had MEL, and 397 (20 5%) had LI Males were more commonly found in the MEL (p=0 0004) and LI groups compared to control (p< 0001) Patients in the MEL cohort were older (p=0 0005) African Americans were more likely to develop LI (p=0 0318) There was no difference in comorbidities between all groups Among patients with LI, 241 (61%) had a hepatocellular pattern, 20 (5%) had a cholestatic pattern, and 135 (34%) had a mixed pattern Patients with LI had an increased risk of mortality (RR 4 26 [95% CI 3 12, 5 81;p< 0001]), ICU admission (RR 5 52 [95% CI 4 07, 7 49;p< 0001]), intubation (RR 11 01 [95% CI 6 97, 17 34]);p< 0001) and 30-day readmission (1 81 [95% CI 1 17, 2 80;p< 0076]) (Table 2, Figure 1) compared to the control group Conclusion: Our study demonstrates that patients with COVID-19 who present with LI have a significantly increased risk of mortality, mechanical ventilation, ICU admission, and 30-day re-admission compared to patients with MEL and normal LFTs This information is important to appropriately manage COVID-19 patients Further research looking at risk prediction models and pooling multi-center data should include liver injury as a key variable.