Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 79
Filter
Add filters

Document Type
Year range
1.
Nat Commun ; 12(1): 6055, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1475294

ABSTRACT

COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.


Subject(s)
COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus Protease Inhibitors/administration & dosage , Indoles/administration & dosage , Leucine/administration & dosage , Pyrrolidinones/administration & dosage , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacokinetics , Alanine/administration & dosage , Alanine/adverse effects , Alanine/analogs & derivatives , Alanine/pharmacokinetics , Animals , COVID-19/virology , Chlorocebus aethiops , Coronavirus 229E, Human/drug effects , Coronavirus 229E, Human/enzymology , Coronavirus Protease Inhibitors/adverse effects , Coronavirus Protease Inhibitors/pharmacokinetics , Disease Models, Animal , Drug Design , Drug Synergism , Drug Therapy, Combination , HeLa Cells , Humans , Indoles/adverse effects , Indoles/pharmacokinetics , Infusions, Intravenous , Leucine/adverse effects , Leucine/pharmacokinetics , Mice , Pyrrolidinones/adverse effects , Pyrrolidinones/pharmacokinetics , SARS Virus/drug effects , SARS Virus/enzymology , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Vero Cells
2.
BMJ Qual Saf ; 30(1): 17-26, 2021 01.
Article in English | MEDLINE | ID: covidwho-1430192

ABSTRACT

BACKGROUND: User-testing and subsequent modification of clinical guidelines increases health professionals' information retrieval and comprehension. No study has investigated whether this results in safer care. OBJECTIVE: To compare the frequency of medication errors when administering an intravenous medicine using the current National Health Service Injectable Medicines Guide (IMG) versus an IMG version revised with user-testing. METHOD: Single-blind, randomised parallel group in situ simulation. Participants were on-duty nurses/midwives who regularly prepared intravenous medicines. Using a training manikin in their clinical area, participants administered a voriconazole infusion, a high-risk medicine requiring several steps to prepare. They were randomised to use current IMG guidelines or IMG guidelines revised with user-testing. Direct observation was used to time the simulation and identify errors. Participant confidence was measured using a validated instrument. The primary outcome was the percentage of simulations with at least one moderate-severe IMG-related error, with error severity classified by an expert panel. RESULTS: In total, 133 participants were randomised to current guidelines and 140 to user-tested guidelines. Fewer moderate-severe IMG-related errors occurred with the user-tested guidelines (n=68, 49%) compared with current guidelines (n=79, 59%), but this difference was not statistically significant (risk ratio: 0.82; 95% CI 0.66 to 1.02). Significantly more simulations were completed without any IMG-related errors with the user-tested guidelines (n=67, 48%) compared with current guidelines (n=26, 20%) (risk ratio: 2.46; 95% CI 1.68 to 3.60). Median simulation completion time was 1.6 min (95% CI 0.2 to 3.0) less with the user-tested guidelines. Participants who used user-tested guidelines reported greater confidence. CONCLUSION: User-testing injectable medicines guidelines reduces the number of errors and the time taken to prepare and administer intravenous medicines, while increasing staff confidence. TRIAL REGISTRATION NUMBER: researchregistry5275.


Subject(s)
State Medicine , Adult , COVID-19 , Female , Humans , Infusions, Intravenous , Male , SARS-CoV-2 , Single-Blind Method
3.
J Stroke Cerebrovasc Dis ; 30(12): 106121, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1415617

ABSTRACT

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/administration & dosage , Ischemic Stroke/drug therapy , Thrombolytic Therapy , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Disability Evaluation , Europe , Female , Fibrinolytic Agents/adverse effects , Hospital Mortality , Humans , Infusions, Intravenous , Intracranial Hemorrhages/chemically induced , Iran , Ischemic Stroke/complications , Ischemic Stroke/diagnosis , Ischemic Stroke/mortality , Male , Middle Aged , Risk Assessment , Risk Factors , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Time Factors , Treatment Outcome
4.
J Crohns Colitis ; 15(11): 1846-1851, 2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1387846

ABSTRACT

BACKGROUND AND AIMS: The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. METHODS: Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. RESULTS: A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. CONCLUSIONS: Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.


Subject(s)
Colitis, Ulcerative/drug therapy , Ustekinumab/therapeutic use , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Prospective Studies , Registries , Remission Induction , Ustekinumab/administration & dosage
5.
N Engl J Med ; 385(9): 803-814, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1373469

ABSTRACT

BACKGROUND: Additional interventions are needed to reduce the morbidity and mortality caused by malaria. METHODS: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with Plasmodium falciparum. Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria. Participants received CIS43LS subcutaneously or intravenously at one of three escalating dose levels. A subgroup of participants from Part A continued to Part B, and some received a second CIS43LS infusion. Additional participants were enrolled in Part B and received CIS43LS intravenously. To assess the protective efficacy of CIS43LS, some participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying P. falciparum sporozoites 4 to 36 weeks after administration of CIS43LS. RESULTS: A total of 25 participants received CIS43LS at a dose of 5 mg per kilogram of body weight, 20 mg per kilogram, or 40 mg per kilogram, and 4 of the 25 participants received a second dose (20 mg per kilogram regardless of initial dose). No safety concerns were identified. We observed dose-dependent increases in CIS43LS serum concentrations, with a half-life of 56 days. None of the 9 participants who received CIS43LS, as compared with 5 of 6 control participants who did not receive CIS43LS, had parasitemia according to polymerase-chain-reaction testing through 21 days after controlled human malaria infection. Two participants who received 40 mg per kilogram of CIS43LS and underwent controlled human malaria infection approximately 36 weeks later had no parasitemia, with serum concentrations of CIS43LS of 46 and 57 µg per milliliter at the time of controlled human malaria infection. CONCLUSIONS: Among adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 612 ClinicalTrials.gov number, NCT04206332.).


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antimalarials/therapeutic use , Malaria, Falciparum/prevention & control , Adult , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Protozoan/blood , Antimalarials/administration & dosage , Antimalarials/adverse effects , Antimalarials/pharmacokinetics , Dose-Response Relationship, Drug , Healthy Volunteers , Humans , Infusions, Intravenous/adverse effects , Injections, Subcutaneous/adverse effects , Middle Aged , Plasmodium falciparum/immunology , Plasmodium falciparum/isolation & purification
6.
Rheumatol Int ; 41(10): 1839-1843, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1363732

ABSTRACT

The outcomes of COVID-19 in patients treated with biologic agents are a subject of intense investigation. Recent data indicated that patients under rituximab (RTX) may carry an increased risk of serious disease. We performed an electronic search in Medline and Scopus using the keywords rituximab and COVID-19. We present a rare case of severe, protracted COVID-19 pneumonia in a patient with mixed connective tissue disease (MCTD) who was infected a few days following RTX treatment. In a relevant literature search, we identified 18 cases of patients with rheumatic diseases (6 RA, 8 ANCA vasculitis, 3 systemic sclerosis and 1 polymyositis) treated with RTX who experienced an atypical and/or prolonged course of COVID-19 pneumonia with no evidence of cytokine storm. Our case indicates that RTX may unfavorably affect outcomes following SARS-CoV-2 infection. B cell depletion may dampen the humoral response against the virus; we may hypothesize that B cell-depleted patients may be protected from cytokine storm but on the other hand may have difficulties in virus clearance leading to a protracted course. Taking into account that COVID-19 vaccines are available we may consider delaying RTX infusions at least in patients without life threatening disease, until vaccination is completed.


Subject(s)
Antirheumatic Agents/adverse effects , COVID-19/immunology , Contraindications, Drug , Mixed Connective Tissue Disease/drug therapy , Rituximab/adverse effects , Aged , Antirheumatic Agents/administration & dosage , COVID-19/diagnosis , Fatal Outcome , Female , Humans , Infusions, Intravenous , Male , Rituximab/administration & dosage , SARS-CoV-2
7.
Diabetes Metab Syndr ; 15(5): 102244, 2021.
Article in English | MEDLINE | ID: covidwho-1356196

ABSTRACT

BACKGROUND: We aim to provide a practical guidance on the use of intravenous insulin infusion for managing inpatient hyperglycemia. METHODS AND RESULTS: This document was formulated based on the review of available literature and personal experience of authors. We have used various case scenarios to illustrate variables which should be taken into account when deciding adjustments in infusion rate, including but not restricted to ambient blood glucose level and magnitude of blood glucose change in the previous hour. CONCLUSION: The guidance can be generalized to any situation where dedicated protocols are lacking, trained manpower is not available and resource constraints are present.


Subject(s)
Hospitalization , Hyperglycemia/drug therapy , Insulin/administration & dosage , Blood Glucose/metabolism , Glycemic Control/methods , Glycemic Control/standards , Humans , Hyperglycemia/blood , Infusions, Intravenous , Inpatients , Practice Guidelines as Topic
8.
N Engl J Med ; 385(7): 609-617, 2021 08 12.
Article in English | MEDLINE | ID: covidwho-1354155

ABSTRACT

BACKGROUND: The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation. METHODS: In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily. The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery. RESULTS: Venous thromboembolism occurred in 13 of 102 patients (13%) in the 30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 4 of 98 patients (4%) in the 150-mg abelacimab group, as compared with 22 of 101 patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group. CONCLUSIONS: This trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA EudraCT number, 2019-003756-37.).


Subject(s)
Anticoagulants/therapeutic use , Arthroplasty, Replacement, Knee , Enoxaparin/therapeutic use , Factor XI/antagonists & inhibitors , Postoperative Complications/prevention & control , Venous Thromboembolism/prevention & control , Adult , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Dose-Response Relationship, Drug , Enoxaparin/adverse effects , Factor XI/metabolism , Female , Hemorrhage/chemically induced , Humans , Infusions, Intravenous , Injections, Subcutaneous , Male , Middle Aged , Partial Thromboplastin Time
9.
Cornea ; 40(9): 1204-1206, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1343730

ABSTRACT

PURPOSE: The purpose of this study was to report 2 patients with anterior scleritis manifesting after coronavirus disease 2019 (COVID-19). METHODS: The patients with confirmed COVID-19 developed anterior scleritis after their systemic symptoms were markedly improved. A thorough systemic workup identified no underlying autoimmune diseases. Ocular characteristics and safety and efficacy of systemic immunosuppressive therapy were evaluated. RESULTS: Case 1 was a 67-year-old woman who presented with necrotizing anterior scleritis in both eyes 3 weeks after the onset of COVID-19. One-week treatment with topical betamethasone and oral prednisolone (65 mg daily) did not result in improvement, so she was started on intravenous cyclophosphamide and subcutaneous adalimumab in addition to oral prednisolone. Necrotizing scleritis was gradually improved over 3 months. Case 2 was a 33-year-old man who presented with sectoral anterior scleritis in his right eye 2 weeks after the onset of COVID-19. He was started on topical betamethasone and oral prednisolone (85 mg daily). One week later, all signs and symptoms disappeared, and topical and oral corticosteroids were gradually tapered off over 2 weeks. There was no recurrence of respiratory symptoms or active scleritis in any cases after discontinuation of treatment. CONCLUSIONS: These cases suggest that COVID-19 can be associated with anterior scleritis, which responds to immunosuppressive and biologic agents. Ophthalmologists should consider anterior scleritis in patients with COVID-19 who present with ocular pain and redness during the convalescent phase of the illness.


Subject(s)
COVID-19/diagnosis , Eye Infections, Viral/diagnosis , SARS-CoV-2/isolation & purification , Scleritis/diagnosis , Adalimumab/therapeutic use , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , COVID-19 Nucleic Acid Testing , Cyclophosphamide/therapeutic use , Eye Infections, Viral/drug therapy , Eye Infections, Viral/virology , Female , Humans , Immunosuppressive Agents/therapeutic use , Infusions, Intravenous , Infusions, Subcutaneous , Male , Prednisolone/therapeutic use , SARS-CoV-2/genetics , Scleritis/drug therapy , Scleritis/virology
11.
N Engl J Med ; 385(15): 1382-1392, 2021 10 07.
Article in English | MEDLINE | ID: covidwho-1309482

ABSTRACT

BACKGROUND: Patients with underlying medical conditions are at increased risk for severe coronavirus disease 2019 (Covid-19). Whereas vaccine-derived immunity develops over time, neutralizing monoclonal-antibody treatment provides immediate, passive immunity and may limit disease progression and complications. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, a cohort of ambulatory patients with mild or moderate Covid-19 who were at high risk for progression to severe disease to receive a single intravenous infusion of either a neutralizing monoclonal-antibody combination agent (2800 mg of bamlanivimab and 2800 mg of etesevimab, administered together) or placebo within 3 days after a laboratory diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The primary outcome was the overall clinical status of the patients, defined as Covid-19-related hospitalization or death from any cause by day 29. RESULTS: A total of 1035 patients underwent randomization and received an infusion of bamlanivimab-etesevimab or placebo. The mean (±SD) age of the patients was 53.8±16.8 years, and 52.0% were adolescent girls or women. By day 29, a total of 11 of 518 patients (2.1%) in the bamlanivimab-etesevimab group had a Covid-19-related hospitalization or death from any cause, as compared with 36 of 517 patients (7.0%) in the placebo group (absolute risk difference, -4.8 percentage points; 95% confidence interval [CI], -7.4 to -2.3; relative risk difference, 70%; P<0.001). No deaths occurred in the bamlanivimab-etesevimab group; in the placebo group, 10 deaths occurred, 9 of which were designated by the trial investigators as Covid-19-related. At day 7, a greater reduction from baseline in the log viral load was observed among patients who received bamlanivimab plus etesevimab than among those who received placebo (difference from placebo in the change from baseline, -1.20; 95% CI, -1.46 to -0.94; P<0.001). CONCLUSIONS: Among high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of Covid-19-related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Adolescent , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/ethnology , COVID-19/virology , Child , Double-Blind Method , Drug Therapy, Combination , Female , Hospitalization/statistics & numerical data , Humans , Infusions, Intravenous , Kaplan-Meier Estimate , Male , Middle Aged , Patient Acuity , Risk Factors , SARS-CoV-2/isolation & purification , Viral Load/drug effects , Young Adult
12.
Psychiatry Res ; 303: 114086, 2021 09.
Article in English | MEDLINE | ID: covidwho-1303645

ABSTRACT

Herein we evaluate the impact of COVID-19 restrictions on antidepressant effectiveness of intravenous (IV) ketamine in adults with treatment-resistant depression (TRD). We conducted a case series analysis of adults with TRD (n = 267) who received four ketamine infusions at an outpatient clinic in Ontario, Canada, during COVID-19 restrictions (from March 2020 - February 2021; n = 107), compared to patients who received treatment in the previous year (March 2019 - February 2020; n = 160). Both groups experienced significant and comparable improvements in depressive symptoms, suicidal ideation, and anxiety with repeated ketamine infusions. Effectiveness of IV ketamine was not attenuated during the COVID-19 period.


Subject(s)
COVID-19 , Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Ketamine , Adult , Depression , Depressive Disorder, Major/drug therapy , Depressive Disorder, Treatment-Resistant/drug therapy , Humans , Infusions, Intravenous , Ketamine/therapeutic use , Ontario , Pandemics , SARS-CoV-2
13.
Drug Test Anal ; 13(10): 1727-1734, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1293157

ABSTRACT

BACKGROUND: Currently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has spread worldwide as a severe pandemic and effective therapeutic medications are urgently needed. As reported previously, BD-604 is a fully human monoclonal antibody with strong in vitro and in vivo neutralizing activity to SARS-COV-2. OBJECTIVE: The purpose of this study was to characterize the pharmacokinetic propertie of BD-604 in cynomolgus monkeys. METHODS: To analyze the concentration of BD-604 in cynomolgus monkey serum, an ELISA assay was established, and a systemic validation was performed including accuracy and precision, dilution linearity and hook effect, selectivity, specificity, stability, and parallelism tests. Then, six naïve cynomolgus monkeys (3/sex) were administered BD-604 at a single dose of 10 mg/kg via intravenous infusion (60 min). Blood samples were collected at various time points (0-672 h) and analyzed for serum concentrations of BD-604. RESULTS: The data from validation experiments assure the reproducibility and reliability of the established ELISA assay. Then, the validated method was used to measure BD-604 concentration in cynomolgus monkey serum. The pharmacokinetics parameters including terminal half-life (t1/2 ), peak serum concentration (Cmax ), area under curve from time zero to last timepoint or infinity (AUClast /AUCinf ), apparent volume of distribution (Vz ), clearance rate (CL), and mean residence time (MRT) were calculated and reported. BD-604 showed no marked sex differences at the dose of 10 mg/kg when comparing the AUC0-last and Cmax between female and male cynomolgus monkeys. CONCLUSION: In cynomolgus monkeys, BD-604 possesses pharmacokinetic properties similar to natural IgGs.


Subject(s)
Antibodies, Monoclonal/blood , Antibodies, Neutralizing/blood , SARS-CoV-2/metabolism , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Neutralizing/administration & dosage , CHO Cells , COVID-19 , Cricetinae , Cricetulus , Dose-Response Relationship, Drug , Female , Humans , Infusions, Intravenous , Macaca fascicularis , Male , SARS-CoV-2/drug effects
14.
Medicine (Baltimore) ; 100(19): e25876, 2021 May 14.
Article in English | MEDLINE | ID: covidwho-1262272

ABSTRACT

BACKGROUND: Patients infected with a virus usually lack vitamin C. High-dose vitamin C has an antiviral effect, and has been used by several researchers to treat COVID-19 by intravenous infusion, achieving good results. However, the efficacy and safety of vitamin C in the treatment of patients with COVID-19 remain unclear. Thus, the aim of the present study was to investigate the efficacy of high-dose vitamin C infusion in the treatment of patients with COVID-19. METHODS: Electronic databases were searched, including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure database, Chinese Wanfang database, and Chinese Biomedical Literature database. The aim was to collect randomized controlled trials of high-dose vitamin C infusion in the treatment of patients with COVID-19, with the retrieval time being from the establishment of the database to March 2021. In accordance with the pre-designed inclusion/exclusion criteria, all data were extracted independently by 2 researchers. To assess the risk bias in the studies, the Cochrane collaboration's tool for assessing risk of bias was used to assess the risk bias in the studies, while meta-analysis was performed using Revman 5.3 software. RESULTS: In the present study, a high-quality comprehensive evaluation is provided of high-dose vitamin C infusion in the treatment of patients with COVID-19. CONCLUSION: Further convincing evidence for the clinical treatment of COVID-19 is provided, in addition to evidence-based guidance for clinical practice. PROSPERO REGISTRATION NUMBER: CRD42021246342.


Subject(s)
Ascorbic Acid/therapeutic use , COVID-19/drug therapy , Vitamins/therapeutic use , Ascorbic Acid/administration & dosage , Ascorbic Acid/adverse effects , Dose-Response Relationship, Drug , Humans , Infusions, Intravenous , Interleukin-6/blood , Length of Stay , Randomized Controlled Trials as Topic , Research Design , Respiration, Artificial/statistics & numerical data , SARS-CoV-2 , Vitamins/administration & dosage , Vitamins/adverse effects
15.
J Clin Endocrinol Metab ; 106(10): e4007-e4016, 2021 09 27.
Article in English | MEDLINE | ID: covidwho-1261287

ABSTRACT

CONTEXT: The coronavirus disease 2019 (COVID-19) pandemic has created a need for remote blood glucose (BG) monitoring in the intensive care unit (ICU). OBJECTIVE: To evaluate feasibility and patient safety of a hybrid monitoring strategy of point-of-care (POC) BG plus continuous glucose monitor (CGM) in the ICU. DESIGN: Retrospective analysis. SETTING: ICU of an academic medical center. PATIENTS: Patients with COVID-19 on IV insulin. INTERVENTION: After meeting initial validation criteria, CGM was used for IV insulin titration and POC BG was performed every 6 hours or as needed. MAIN OUTCOME MEASURES: Outcomes included frequency of POC BG, workflow, safety, and accuracy measures. RESULTS: The study included 19 patients, 18 with CGM data, mean age 58 years, 89% on mechanical ventilation, 37% on vasopressors, and 42% on dialysis. The median time to CGM validation was 137 minutes (interquartile range [IQR] 114-206). During IV insulin, the median number of POC values was 7 (IQR 6-16) on day 1, and declined slightly thereafter (71% reduction compared with standard of 24/day). The median number of CGM values used nonadjunctively to titrate IV insulin was 11.5 (IQR 0, 15) on day 1 and increased thereafter. Time in range 70 to 180 mg/dL was 64 ± 23% on day 1 and 72 ± 16% on days 2 through 7, whereas time <70 mg/dL was 1.5 ± 4.1% on day 1 and <1% on days 2 through 7. CONCLUSIONS: This study provides data to support that CGM using a hybrid protocol is feasible, accurate, safe, and has potential to reduce nursing and staff workload.


Subject(s)
Blood Glucose Self-Monitoring/methods , COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Insulin/administration & dosage , SARS-CoV-2 , Adult , Aged , Blood Glucose/analysis , COVID-19/therapy , Comorbidity , Critical Illness/therapy , Diabetes Complications/epidemiology , Diabetes Complications/therapy , Diabetes Complications/virology , Female , Glycemic Control/methods , Humans , Infusions, Intravenous , Intensive Care Units , Male , Middle Aged , Point-of-Care Systems , Retrospective Studies , Treatment Outcome
16.
Medicine (Baltimore) ; 100(22): e26253, 2021 Jun 04.
Article in English | MEDLINE | ID: covidwho-1258821

ABSTRACT

ABSTRACT: Pathophysiological changes are important risk factors for critically ill patients with pneumonia manifesting sub-therapeutic antibiotic exposures during empirical treatment. The effect of coronavirus disease 2019 (COVID-19) on antibiotic dosing requirements is uncertain. We aimed to determine the effect of COVID-19 on ß-lactam pharmacokinetics (PK) and PK target attainment in critically ill patients with a personalized dosing strategy.Retrospective, single-center analysis of COVID-19 ± critically ill patients with pneumonia (community-acquired pneumonia or hospital-acquired pneumonia) who received continuous infusion of a ß-lactam antibiotic with dosing personalized through dosing software and therapeutic drug monitoring. A therapeutic exposure was defined as serum concentration between (css) 4 to 8 times the EUCAST non-species related breakpoint).Data from 58 patients with pneumonia was analyzed. Nineteen patients were tested COVID-19-positive before the start of the antibiotic therapy for community-acquired pneumonia or hospital-acquired pneumonia. Therapeutic exposure was achieved in 71% of COVID-19 patients (68% considering all patients). All patients demonstrated css above the non-species-related breakpoint. Twenty percent exceeded css above the target range (24% of all patients). The median ß-lactam clearance was 49% compared to ß-lactam clearance in a standard patient without a significant difference regarding antibiotic, time of sampling or present COVID-19 infection. Median daily doses were 50% lower compared to standard bolus dosing.COVID-19 did not significantly affect ß-lactam pharmacokinetics in critically ill patients. Personalized ß-lactam dosing strategies were safe in critically ill patients and lead to high PK target attainment with less resources.


Subject(s)
COVID-19/drug therapy , beta-Lactams/administration & dosage , beta-Lactams/pharmacokinetics , Aged , Aged, 80 and over , Body Mass Index , Critical Illness , Dose-Response Relationship, Drug , Drug Monitoring , Female , Humans , Infusions, Intravenous , Male , Metabolic Clearance Rate , Middle Aged , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , beta-Lactams/economics , beta-Lactams/therapeutic use
17.
Pain Med ; 22(7): 1642-1650, 2021 07 25.
Article in English | MEDLINE | ID: covidwho-1258791

ABSTRACT

OBJECTIVES: Cancer-related neuropathic pain (CNP) affects an increasing proportion of cancer patients, given improved survival, but it remains difficult to treat. There are no studies on an extended intravenous ketamine protocol and its synergies with common neuropathy treatments to treat CNP. This study aims to 1) evaluate the safety and effectiveness of an intravenous ketamine protocol to treat refractory CNP and 2) uncover synergies between ketamine and common neuropathy treatments. METHODS: This is a single-center, retrospective review of 57 patients and 192 infusions, with prospective follow-up on 14 enrolled patients during the coronavirus disease 2019 (COVID-19) pandemic. RESULTS: The etiologies of CNP were as follows: 13 from tumor compression, 25 with chemotherapy-induced peripheral neuropathy, 13 from surgery, and 6 from radiation therapy. Overall, 42 of 57 patients (73.7%) were responders, and 71.8% of responders received >3 weeks of pain relief on their last infusion. Analysis of adjuvant treatments revealed that the combination of serotonin-norepinephrine reuptake inhibitors and ketamine resulted in an increase in responders compared with nonresponders (P < 0.01). Adverse events occurred in 32 of 192 infusions (16.7%). All side effects self-resolved or resolved with intervention per the adverse events protocol. During the pandemic, all 14 currently enrolled patients did not receive ketamine infusions. Thirteen of the 14 patients returned to baseline pain, with 61.5% increasing medications. All experienced worsened function, mobility, mood, or anorexia. CONCLUSION: Intravenous ketamine may be a safe and effective adjuvant treatment for CNP, especially with serotonin-norepinephrine reuptake inhibitors. Larger, prospective studies are warranted and should explore parameters to help prognosticate response to ketamine infusions.


Subject(s)
COVID-19 , Ketamine , Neoplasms , Analgesics/therapeutic use , Humans , Infusions, Intravenous , Neoplasms/complications , Neoplasms/drug therapy , Pain Management , Pandemics , Prospective Studies , Retrospective Studies , SARS-CoV-2
18.
Am J Emerg Med ; 49: 189-194, 2021 11.
Article in English | MEDLINE | ID: covidwho-1252391

ABSTRACT

BACKGROUND: Prehospital emergency care of children is challenging. In the era of the COVID-19 pandemic, when medical personnel should use personal protective equipment against aerosol-generating procedures, the efficiency of medical procedures may decrease. The study objective was to evaluate the effectiveness of different intravascular access methods applied by nurses wearing biosafety Level-2 suits in simulated paediatric COVID-19 resuscitation. METHODS: A prospective, randomized, crossover, single-blinded simulation trial was performed. Nursing staff attending Advanced Cardiovascular Life Support courses accredited by the American Heart Association participated in the study. A total of 65 nurses were recruited and randomly assigned to different study groups. They received standard training on intravascular access methods employing distinct devices. The participants wore biosafety Level-2 suits and performed vascular access with the following intraosseous devices: NIO-P, EZ-IO, and Jamshidi needle; intravenous (IV) access was used as a reference method. Both the order of participants and the access methods were random. Each participant performed intravascular access with each of the four methods tested. The effectiveness of the first attempt to obtain intravascular access and the following time parameters were analysed: the time between grasping the intravascular device out of the original packing until infusion line connection. The ease of the procedure was measured with a visual analogue scale (1 - easy; 10 - difficult). RESULTS: The first attempt success rate of intravascular access by using NIO-P and EZ-IO equalled 100% and was statistically significantly higher than that with the Jamshidi needle (80.0%; p = 0.02) and with the IV method (69.2%; p = 0.005). The time required to connect the infusion line varied and amounted to 33 ± 4 s for NIO-P compared to 37 ± 6.7 s for EZ-IO (p<0.001), 43 ± 7 s for Jamshidi (p<0.001), and 98.5 ± 10 s for IV access (p<0.001). The procedure was easiest in the case of NIO-P and EZ-IO (2 ± 1 points; p=1.0) compared with Jamshidi (5 ± 3 points; p<0.001) and IV access (7 ± 2 points; p<0.001). CONCLUSION: The study provides evidence that nurses wearing biosafety Level-2 suits were able to obtain intraosseous access faster and more effectively as compared with IV access during simulated COVID-19 paediatric resuscitation. The most effective method of intravascular access was the NIO-P intraosseous device. Further clinical trials are necessary to confirm the results.


Subject(s)
Education, Nursing , Infusions, Intraosseous/instrumentation , Nurses , Personal Protective Equipment , Resuscitation/instrumentation , Adult , COVID-19/therapy , Cross-Over Studies , Emergency Medical Services/methods , Female , Humans , Infusions, Intravenous , Male , Manikins , Middle Aged , Prospective Studies , Single-Blind Method
19.
Int J Clin Pract ; 75(9): e14341, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1219344

ABSTRACT

OBJECTIVES: One important group of people at higher risk from the SARS-CoV-2(COVID-19) pandemic are those with autoimmune conditions including rheumatoid arthritis/inflammatory bowel disease. To minimise infection risk, many people have been switched from intravenous to subcutaneous biologics including biosimilars. DESIGN: The survey was designed to understand comparative economic issues related to the intravenous infusion vs subcutaneous biologic administration routes for infliximab. The survey focused on direct cost drivers/indirect cost drivers. Acquisition costs of medicines were not included due to data not being available publicly. Wider policy implications linked to the pandemic were also explored. SETTING/PARTICIPANTS: Semistructured single telephone interviews were carried out with twenty key stakeholders across the National Health Service(NHS) from 35 clinical/42 pharmacy/28 commissioning roles. The interviews were undertaken virtually during April 2020. From interview (n = 20) results, a simple cost analysis was developed plus a qualitative analysis of reports on wider policy/patient impacts. RESULTS: Key findings included evidence of significant variation in local infusion tariffs UK wide, with interviewees reporting that not all actual costs incurred are captured in published tariff costs. A cost analysis showed administration costs 50% lower in the subcutaneous compared to infusion routes, with most patients administering subcutaneous medicines themselves. Other indirect benefits to this route included less pressure on infusion unit waiting times/reduced risk of COVID-19 infection plus reduced patient 'out of pocket' costs. However, this was to some extent offset by increased pressure on home-care and community/primary care services. CONCLUSIONS: Switching from infusion to subcutaneous routes is currently driven by the COVID-19 pandemic in many services. A case for biologics (infusion vs subcutaneous) must be made on accurate real-world economic analysis. In an analysis of direct/indirect costs, excluding medicine acquisition costs, subcutaneous administration appears to be the more cost saving option for many patients even without the benefit of industry funded home-care. What's known One important group of people at high risk in COVID-19 pandemic are those with autoimmune conditions, including those with rheumatoid arthritis and inflammatory bowel disease. Depending on the complexity of their condition, some of the patients in this group may be receiving intravenous biologic infusion therapy which under normal circumstances is administered within a hospital or day hospital setting. The National Institute for Health and Care Excellence has published new guidance to ensure that patients having intravenous treatment are assessed for possible switching to the same treatment in subcutaneous form. What's new A cost analysis showed that administration costs for subcutananous routes are 50% lower than for infusion routes, with most patients administering subcutaneous medicines themselves. Other indirect benefits to this route included less pressure on infusion unit waiting times and reduced risk of COVID-19 infection, along with reduced patient costs. Cost savings were partly offset by increased pressure on home-care and community/primary care services.


Subject(s)
Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , COVID-19 , Inflammatory Bowel Diseases , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Biosimilar Pharmaceuticals/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Infusions, Intravenous , Pandemics , SARS-CoV-2 , State Medicine , United Kingdom
20.
Kardiol Pol ; 79(3): 277-286, 2021 03 25.
Article in English | MEDLINE | ID: covidwho-1204474

ABSTRACT

BACKGROUND: Obtaining vascular access is one of the key procedures performed in patients in emergency settings. AIMS: The study was conducted as a meta­analysis and a systematic review and aimed to address the following question: which intravascular access method should be used in patients with COVID­19 when wearing full personal protective equipment (PPE)? METHODS: We performed a systematic search of PubMed, EMBASE, and CENTRAL databases for randomized controlled trials that compared intravascular access methods used by operators wearing full level C PPE. We evaluated procedure duration and the success rate of intraosseous and peripheral intravenous accesses. RESULTS: Eight randomized controlled trials were included in quantitative synthesis. The use of PPE during intravascular access procedures had an impact on procedure duration in the case of intraosseous access (mean difference [MD], 11.69; 95% CI, 6.47-16.92; P <0.001), as well as reduced the success rate of intraosseous access by 0.8% and intravenous access by 10.1%. Under PPE conditions, intraosseous access, compared with peripheral intravenous access, offered a shorter procedure time (MD, -41.43; 95% CI, -62.36 to -24.47; P <0.001). CONCLUSION: This comprehensive meta­analysis suggested that the use of PPE significantly extends the duration of intravascular procedures. However, under PPE conditions, operators were able to obtain intraosseous access in a shorter time and with a higher success rate than in the case of intravenous access.


Subject(s)
Infusions, Intraosseous , Infusions, Intravenous , Personal Protective Equipment , COVID-19 , Humans , Randomized Controlled Trials as Topic
SELECTION OF CITATIONS
SEARCH DETAIL
...