Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 160
Filter
3.
Acta Biomed ; 93(1): e2022014, 2022 03 14.
Article in English | MEDLINE | ID: covidwho-1754151

ABSTRACT

OBJECTIVE: We performed a systematic review and meta-analysis for exploring clinical benefits and safety of tocilizumab in addition to standard of care (SOC) in treating patients with coronavirus disease 2019 (COVID-19). METHODS: An electronic search was carried out in PubMed, EMBASE, Cochrane Library, and Science Direct, as well as in medRxiv preprint server, to identify eligible studies. Only randomized Controlled Trials (RCTs) that compared mortality events and/or adverse events between a tocilizumab + SOC group and a SOC-only control group were included. The primary outcome was 28-day mortality. Secondary outcomes include progression to severe disease, defined as need for mechanical ventilation (MV) or intensive care unit (ICU) admission, and adverse events (AE). RESULTS: A total of nine studies (6,490 participants) could be included in this meta-analysis, with 3,358 participants in the tocilizumab + SOC group and 3,132 participants in the SOC-only group. The overall mortality rate was lower in the tocilizumab group compared to the SOC-only group, though the difference was not statistically significant (odds ratio [OR], 0.87; 95% CI, 0.73-1.04; I2, 15%). This finding was unaffected by subgroup analyses based on initial use of steroids or mechanical ventilation at baseline. Patients receiving tocilizumab were 26% less likely to progress to MV, and this difference was statistically significant (OR, 0.74; 95% CI, 0.64-0.86; I2, 0%). Among patients who were not in ICU at randomization, the tocilizumab group had 34 % lower rate of ICU admission compared to the SOC-only group (OR, 0.66; 95% CI, 0.40-2.14; I2, 29%). The occurrence of serious infections was lower in the tocilizumab group (OR, 0.57; 95% CI, 0.36-0.89; I2, 21%). CONCLUSION: Tocilizumab is generally well-tolerated in COVID-19. Although this drug does not appear to have a significant benefits on survival, it may have a role in preventing progression to intensive care and MV.


Subject(s)
COVID-19 , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Humans , Randomized Controlled Trials as Topic , Standard of Care
4.
JAMA Netw Open ; 5(3): e221744, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1739100

ABSTRACT

Importance: Crisis standards of care (CSOC) scores designed to allocate scarce resources during the COVID-19 pandemic could exacerbate racial disparities in health care. Objective: To analyze the association of a CSOC scoring system with resource prioritization and estimated excess mortality by race, ethnicity, and residence in a socially vulnerable area. Design, Setting, and Participants: This retrospective cohort analysis included adult patients in the intensive care unit during a regional COVID-19 surge from April 13 to May 22, 2020, at 6 hospitals in a health care network in greater Boston, Massachusetts. Participants were scored by acute severity of illness using the Sequential Organ Failure Assessment score and chronic severity of illness using comorbidity and life expectancy scores, and only participants with complete scores were included. The score was ordinal, with cutoff points suggested by the Massachusetts guidelines. Exposures: Race, ethnicity, Social Vulnerability Index. Main Outcomes and Measures: The primary outcome was proportion of patients in the lowest priority score category stratified by self-reported race. Secondary outcomes were discrimination and calibration of the score overall and by race, ethnicity, and neighborhood Social Vulnerability Index. Projected excess deaths were modeled by race, using the priority scoring system and a random lottery. Results: Of 608 patients in the intensive care unit during the study period, 498 had complete data and were included in the analysis; this population had a median (IQR) age of 67 (56-75) years, 191 (38.4%) female participants, 79 (15.9%) Black participants, and 225 patients (45.7%) with COVID-19. The area under the receiver operating characteristic curve for the priority score was 0.79 and was similar across racial groups. Black patients were more likely than others to be in the lowest priority group (12 [15.2%] vs 34 [8.1%]; P = .046). In an exploratory simulation model using the score for ventilator allocation, with only those in the highest priority group receiving ventilators, there were 43.9% excess deaths among Black patients (18 of 41 patients) and 28.6% (58 of 203 patients among all others (P = .05); when the highest and intermediate priority groups received ventilators, there were 4.9% (2 of 41 patients) excess deaths among Black patients and 3.0% (6 of 203) among all others (P = .53). A random lottery resulted in more excess deaths than the score. Conclusions and Relevance: In this study, a CSOC priority score resulted in lower prioritization of Black patients to receive scarce resources. A model using a random lottery resulted in more estimated excess deaths overall without improving equity by race. CSOC policies must be evaluated for their potential association with racial disparities in health care.


Subject(s)
COVID-19/mortality , Health Care Rationing/statistics & numerical data , Residence Characteristics/statistics & numerical data , Standard of Care , Aged , Boston , COVID-19/diagnosis , COVID-19/therapy , Critical Care , Female , Health Priorities , Healthcare Disparities , Hospitalization , Humans , Male , Middle Aged , Organ Dysfunction Scores , Retrospective Studies , Severity of Illness Index , Vulnerable Populations/statistics & numerical data
5.
J Infect Dis ; 225(5): 820-824, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1722476

ABSTRACT

BACKGROUND: Previous reports highlighted the efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs) against coronavirus disease 2019. METHODS: We conducted a prospective study on the clinical outcome and antiviral effects of mAbs added to standard of care therapy in SARS-CoV-2-infected patients with primary antibody defects. RESULTS: Median time of SARS-CoV-2 quantitative polymerase chain reaction (qPCR) positivity was shorter in 8 patients treated with mAbs (22 days) than in 10 patients treated with standard of care therapy only (37 days, P=.026). Median time of SARS-CoV-2 qPCR positivity from mAb administration was 10 days. CONCLUSIONS: The SARS-CoV-2 mAbs treatment was effective and well tolerated in patients with primary antibody defects.


Subject(s)
Antibodies, Viral/therapeutic use , COVID-19/drug therapy , Common Variable Immunodeficiency , Primary Immunodeficiency Diseases/drug therapy , SARS-CoV-2/isolation & purification , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/immunology , Antineoplastic Agents, Immunological , Humans , Prospective Studies , Real-Time Polymerase Chain Reaction , Standard of Care
6.
Chest ; 161(2): e135, 2022 02.
Article in English | MEDLINE | ID: covidwho-1682978
7.
Lancet Respir Med ; 10(4): 327-336, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1665591

ABSTRACT

BACKGROUND: The oral, selective Janus kinase 1/2 inhibitor baricitinib has shown efficacy in studies of hospitalised adults with COVID-19. COV-BARRIER (NCT04421027) was a multinational, phase 3, randomised, double-blind, placebo-controlled trial of baricitinib in patients with confirmed SARS-CoV-2 infection. We aimed to evaluate the efficacy and safety of baricitinib plus standard of care in critically ill hospitalised adults with COVID-19 requiring invasive mechanical ventilation or extracorporeal membrane oxygenation. METHODS: This exploratory trial followed the study design of COV-BARRIER in a critically ill cohort not included in the main phase 3 trial. The study was conducted across 18 hospitals in Argentina, Brazil, Mexico, and the USA. Participants (aged ≥18 years) hospitalised with laboratory-confirmed SARS-CoV-2 infection on baseline invasive mechanical ventilation or extracorporeal membrane oxygenation were randomly assigned (1:1) to baricitinib (4 mg) or placebo once daily for up to 14 days in combination with standard of care. Participants, study staff, and investigators were masked to study group assignment. Prespecified endpoints included all-cause mortality through days 28 and 60, number of ventilator-free days, duration of hospitalisation, and time to recovery through day 28. The efficacy analysis was done in the intention-to-treat population and the safety analysis was done in the safety population. This trial is registered with ClinicalTrials.gov, NCT04421027. FINDINGS: Between Dec 23, 2020, and April 10, 2021, 101 participants were enrolled into the exploratory trial and assigned to baricitinib (n=51) or placebo (n=50) plus standard of care. Standard of care included baseline systemic corticosteroid use in 87 (86%) participants. Treatment with baricitinib significantly reduced 28-day all-cause mortality compared with placebo (20 [39%] of 51 participants died in the baricitinib group vs 29 [58%] of 50 in the placebo group; hazard ratio [HR] 0·54 [95% CI 0·31-0·96]; p=0·030; 46% relative reduction; absolute risk reduction 19%). A significant reduction in 60-day mortality was also observed in the baricitinib group compared with the placebo group (23 [45%] events vs 31 [62%]; HR 0·56 [95% CI 0·33-0·97]; p=0·027; 44% relative reduction; absolute risk reduction 17%). In every six baricitinib-treated participants, one additional death was prevented compared with placebo at days 28 and 60. The number of ventilator-free days did not differ significantly between treatment groups (mean 8·1 days [SD 10·2] in the baricitinib group vs 5·5 days [8·4] in the placebo group; p=0·21). The mean duration of hospitalisation in baricitinib-treated participants was not significantly shorter than in placebo-treated participants (23·7 days [SD 7·1] vs 26·1 days [3·9]; p=0·050). The rates of infections, blood clots, and adverse cardiovascular events were similar between treatment groups. INTERPRETATION: In critically ill hospitalised patients with COVID-19 who were receiving invasive mechanical ventilation or extracorporeal membrane oxygenation, treatment with baricitinib compared with placebo (in combination with standard of care, including corticosteroids) reduced mortality, which is consistent with the mortality reduction observed in less severely ill patients in the hospitalised primary COV-BARRIER study population. However, this was an exploratory trial with a relatively small sample size; therefore, further phase 3 trials are needed to confirm these findings. FUNDING: Eli Lilly and Company.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Adolescent , Adult , Azetidines , COVID-19/drug therapy , Critical Illness , Double-Blind Method , Humans , Purines , Pyrazoles , Respiration, Artificial , SARS-CoV-2 , Standard of Care , Sulfonamides , Treatment Outcome
8.
J Med Econ ; 25(1): 160-171, 2022.
Article in English | MEDLINE | ID: covidwho-1625356

ABSTRACT

AIMS: Estimate the clinical and economic benefits of lenzilumab plus standard of care (SOC) compared with SOC alone in the treatment of patients hospitalized with COVID-19 pneumonia from the United States (US) hospital perspective. MATERIALS AND METHODS: A per-patient cost calculator was developed to report the clinical and economic benefits associated with adding lenzilumab to SOC in newly hospitalized COVID-19 patients over 28 days. Clinical inputs were based on the LIVE-AIR trial, including failure to achieve survival without ventilation (SWOV), mortality, time to recovery, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) use. Base case costs included the anticipated list price of lenzilumab, drug administration, and hospital resource costs based on the level of care required. A scenario analysis examined projected one-year rehospitalization costs. RESULTS: In the base case and all scenarios, lenzilumab plus SOC improved all specified clinical outcomes relative to SOC alone. Lenzilumab plus SOC resulted in estimated cost savings of $3,190 per patient in a population aged <85 years with C-reactive protein (CRP) levels <150 mg/L and receiving remdesivir (base case). Per-patient cost savings were observed in the following scenarios: (1) aged <85 years with CRP <150 mg/L, with or without remdesivir ($1,858); (2) Black and African American patients with CRP <150 mg/L ($13,154); and (3) Black and African American patients from the full population, regardless of CRP level ($2,763). In the full modified intent-to-treat population, an additional cost of $4,952 per patient was estimated. When adding rehospitalization costs to the index hospitalization, a total per-patient cost savings of $5,154 was estimated. CONCLUSIONS: The results highlight the clinical benefits for SWOV, ventilator use, time to recovery, mortality, time in ICU, and time on IMV, in addition to an economic benefit from the US hospital perspective associated with adding lenzilumab to SOC for COVID-19 patients.


Subject(s)
COVID-19 , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Hospitals , Humans , SARS-CoV-2 , Standard of Care , United States
9.
JAMA Netw Open ; 4(12): e2141328, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1592856

ABSTRACT

Importance: Hospitalized patients with COVID-19 pneumonia have high rates of morbidity and mortality. Objective: To assess the efficacy of colchicine in hospitalized patients with COVID-19 pneumonia. Design, Setting, and Participants: The Estudios Clínicos Latino América (ECLA) Population Health Research Institute (PHRI) COLCOVID trial was a multicenter, open-label, randomized clinical trial performed from April 17, 2020, to March 28, 2021, in adults with confirmed or suspected SARS-CoV-2 infection followed for up to 28 days. Participants received colchicine vs usual care if they were hospitalized with COVID-19 symptoms and had severe acute respiratory syndrome or oxygen desaturation. The main exclusion criteria were clear indications or contraindications for colchicine, chronic kidney disease, and negative results on a reverse transcription-polymerase chain reaction test for SARS-CoV-2 before randomization. Data were analyzed from June 20 to July 25, 2021. Interventions: Patients were assigned in a 1:1 ratio to usual care or usual care plus colchicine. Colchicine was administered orally in a loading dose of 1.5 mg immediately after randomization, followed by 0.5 mg orally within 2 hours of the initial dose and 0.5 mg orally twice a day for 14 days or discharge, whichever occurred first. Main Outcomes and Measures: The first coprimary outcome was the composite of a new requirement for mechanical ventilation or death evaluated at 28 days. The second coprimary outcome was death at 28 days. Results: A total of 1279 hospitalized patients (mean [SD] age, 61.8 [14.6] years; 449 [35.1%] women and 830 [64.9%] men) were randomized, including 639 patients in the usual care group and 640 patients in the colchicine group. Corticosteroids were used in 1171 patients (91.5%). The coprimary outcome of mechanical ventilation or 28-day death occurred in 160 patients (25.0%) in the colchicine group and 184 patients (28.8%) in the usual care group (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; P = .08). The second coprimary outcome, 28-day death, occurred in 131 patients (20.5%) in the colchicine group and 142 patients (22.2%) in the usual care group (HR, 0.88; 95% CI, 0.70-1.12). Diarrhea was the most frequent adverse effect of colchicine, reported in 68 patients (11.3%). Conclusions and Relevance: This randomized clinical trial found that compared with usual care, colchicine did not significantly reduce mechanical ventilation or 28-day mortality in patients hospitalized with COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov Identifier: NCT04328480.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/therapy , Colchicine/therapeutic use , Hospitalization , Intubation, Intratracheal , Respiration, Artificial , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Anti-Inflammatory Agents/adverse effects , COVID-19/mortality , COVID-19/pathology , Colchicine/adverse effects , Female , Humans , Inflammation/drug therapy , Inflammation/etiology , Male , Middle Aged , SARS-CoV-2 , Standard of Care
10.
Lancet Respir Med ; 10(3): 255-266, 2022 03.
Article in English | MEDLINE | ID: covidwho-1586183

ABSTRACT

BACKGROUND: Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials. METHODS: In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903. FINDINGS: Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment-time interactions were -0·09 (95% CI -0·19 to 0·00) for namilumab and 0·06 (-0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group. INTERPRETATION: Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation-as measured by CRP concentration-in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19. FUNDING: Medical Research Council.


Subject(s)
COVID-19 , Adolescent , Antibodies, Monoclonal, Humanized , Bayes Theorem , COVID-19/drug therapy , Humans , Infliximab/therapeutic use , SARS-CoV-2 , Standard of Care , Treatment Outcome
11.
Clin Infect Dis ; 73(11): e4166-e4174, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560158

ABSTRACT

BACKGROUND: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. METHODS: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. RESULTS: After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001). CONCLUSIONS: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. CLINICAL TRIALS REGISTRATION: NCT04292899 and EUPAS34303.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Adult , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Cohort Studies , Humans , Retrospective Studies , SARS-CoV-2 , Standard of Care , Treatment Outcome
12.
Ann Intern Med ; 174(9): 1261-1269, 2021 09.
Article in English | MEDLINE | ID: covidwho-1547664

ABSTRACT

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Hydroxychloroquine/therapeutic use , Viral Load/drug effects , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Antibodies, Viral/blood , Biomarkers/blood , COVID-19/complications , COVID-19/mortality , Cause of Death , Female , Hospital Mortality , Humans , Inflammation/virology , Male , Middle Aged , Norway/epidemiology , Oropharynx/virology , Respiratory Insufficiency/virology , SARS-CoV-2/immunology , Severity of Illness Index , Standard of Care , Treatment Outcome
13.
JAMA Netw Open ; 4(11): e2136246, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1540039

ABSTRACT

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.


Subject(s)
COVID-19/therapy , Hospital Mortality , Hospitalization , Immunization, Passive , Plasma , Respiratory Insufficiency , Aged , COVID-19/complications , COVID-19/mortality , Disease Progression , Female , Humans , Italy , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Standard of Care
14.
STAR Protoc ; 2(4): 100943, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1510407

ABSTRACT

During the COVID-19 pandemic, US states developed Crisis Standards of Care (CSC) algorithms to triage allocation of scarce resources to maximize population-wide benefit. While CSC algorithms were developed by ethical debate, this protocol guides their quantitative assessment. For CSC algorithms, this protocol addresses (1) adapting algorithms for empirical study, (2) quantifying predictive accuracy, and (3) simulating clinical decision-making. This protocol provides a framework for healthcare systems and governments to test the performance of CSC algorithms to ensure they meet their stated ethical goals. For complete details on the use and execution of this protocol, please refer to Jezmir et al. (2021).


Subject(s)
COVID-19/therapy , Critical Care/standards , Health Care Rationing/standards , Practice Guidelines as Topic/standards , Standard of Care/ethics , Triage/standards , COVID-19/virology , Critical Care/ethics , Health Care Rationing/ethics , Humans , SARS-CoV-2/isolation & purification , Triage/ethics , Triage/methods
16.
J Infect Dis ; 225(5): 820-824, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1506650

ABSTRACT

BACKGROUND: Previous reports highlighted the efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs) against coronavirus disease 2019. METHODS: We conducted a prospective study on the clinical outcome and antiviral effects of mAbs added to standard of care therapy in SARS-CoV-2-infected patients with primary antibody defects. RESULTS: Median time of SARS-CoV-2 quantitative polymerase chain reaction (qPCR) positivity was shorter in 8 patients treated with mAbs (22 days) than in 10 patients treated with standard of care therapy only (37 days, P=.026). Median time of SARS-CoV-2 qPCR positivity from mAb administration was 10 days. CONCLUSIONS: The SARS-CoV-2 mAbs treatment was effective and well tolerated in patients with primary antibody defects.


Subject(s)
Antibodies, Viral/therapeutic use , COVID-19/drug therapy , Common Variable Immunodeficiency , Primary Immunodeficiency Diseases/drug therapy , SARS-CoV-2/isolation & purification , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/immunology , Antineoplastic Agents, Immunological , Humans , Prospective Studies , Real-Time Polymerase Chain Reaction , Standard of Care
17.
Clin Ther ; 43(11): 1877-1893.e4, 2021 11.
Article in English | MEDLINE | ID: covidwho-1506541

ABSTRACT

PURPOSE: In the Phase III COV-BARRIER (Efficacy and Safety of Baricitinib for the Treatment of Hospitalised Adults With COVID-19) trial, treatment with baricitinib, an oral selective Janus kinase 1/2 inhibitor, in addition to standard of care (SOC), was associated with significantly reduced mortality over 28 days in hospitalized patients with coronavirus disease-2019 (COVID-19), with a safety profile similar to that of SOC alone. This study assessed the cost-effectiveness of baricitinib + SOC versus SOC alone (which included systemic corticosteroids and remdesivir) in hospitalized patients with COVID-19 in the United States. METHODS: An economic model was developed to simulate inpatients' stay, discharge to postacute care, and recovery. Costs modeled included payor costs, hospital costs, and indirect costs. Benefits modeled included life-years (LYs) gained, quality-adjusted life-years (QALYs) gained, deaths avoided, and use of mechanical ventilation avoided. The primary analysis was performed from a payor perspective over a lifetime horizon; a secondary analysis was performed from a hospital perspective. The base-case analysis modeled the numeric differences in treatment effectiveness observed in the COV-BARRIER trial. Scenario analyses were also performed in which the clinical benefit of baricitinib was limited to the statistically significant reduction in mortality demonstrated in the trial. FINDINGS: In the base-case payor perspective model, an incremental total cost of 17,276 US dollars (USD), total QALYs gained of 0.6703, and total LYs gained of 0.837 were found with baricitinib + SOC compared with SOC alone. With the addition of baricitinib, survival was increased by 5.1% and the use of mechanical ventilation was reduced by 1.6%. The base-case incremental cost-effectiveness ratios were 25,774 USD/QALY gained and 20,638 USD/LY gained; a "mortality-only" scenario analysis yielded similar results of 26,862 USD/QALY gained and 21,433 USD/LY gained. From the hospital perspective, combination treatment with baricitinib + SOC was more effective and less costly than was SOC alone in the base case, with an incremental cost of 38,964 USD per death avoided in the mortality-only scenario. IMPLICATIONS: In hospitalized patients with COVID-19 in the United States, the addition of baricitinib to SOC was cost-effective. Cost-effectiveness was demonstrated from both the payor and the hospital perspectives. These findings were robust to sensitivity analysis and to conservative assumptions limiting the clinical benefits of baricitinib to the statistically significant reduction in mortality demonstrated in the COV-BARRIER trial.


Subject(s)
COVID-19 , Adult , Azetidines , COVID-19/drug therapy , Cost-Benefit Analysis , Humans , Purines , Pyrazoles , Quality-Adjusted Life Years , SARS-CoV-2 , Standard of Care , Sulfonamides , United States
18.
Clin Rheumatol ; 41(2): 573-579, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1503887

ABSTRACT

Patients and health workers were at high risk of infection during the Sars-Cov-2 pandemic lockdown. For this reason, other medical and clinical approaches such as Telemedicine were necessary. Despite Telemedicine was born before COVID-19, the pandemic was the opportunity to accelerate a process already underway for at least a decade and to blow all the barriers away. Our aim is to describe the experience of Telemedicine during and immediately after the first lockdown to assure the follow-up in a 'virtual' outpatient clinic dedicated to Rheumatic and Musculoskeletal Diseases (RMDs) and to give an overview of Telemedicine in the rheumatology field. We retrospectively evaluated the patient flow to our rheumatology division from March to September 2020 and, in accordance with local restrictions, three periods were selected. In the 1st period, 96.96% of the outpatient clinic cases were shifted to Telemedicine; these decreased to 52.45% in the 2nd period, while the 3rd period was characterized by the return of the patients at the clinic (97.6%). Diagnostic procedures were postponed during the 1st period, reduced drastically during the 2nd and performed regularly during the third period. Intravenous infusions were maintained as much as possible during the three periods, to assure therapeutic continuity. Shifting stable patients to Telemedicine has the potential to allow continuity of care, while reducing the risk of contagion during a pandemic. In the next future, the integration of Telemedicine as standard of care for specific clinical applications might assure assistance for RMDs patients also in non-pandemic conditions.


Subject(s)
COVID-19 , Telemedicine , Communicable Disease Control , Humans , Pandemics , Retrospective Studies , SARS-CoV-2 , Standard of Care
19.
BMJ ; 375: n2593, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1495418

ABSTRACT

The studyBarker KL, Room J, Knight R, et al. Outpatient physiotherapy versus home-based rehabilitation for patients at risk of poor outcomes after knee arthroplasty: CORKA RCT. Health Technol Assess 2020;24:1-116.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/knee-replacements-home-based-rehabilitation-as-effective-physiotherapy/.


Subject(s)
Arthroplasty, Replacement, Knee/rehabilitation , Home Care Services , Patient Acceptance of Health Care , Physical Therapy Modalities , Standard of Care , Cost-Benefit Analysis , Home Care Services/economics , Humans , Physical Therapy Modalities/economics , Standard of Care/economics , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL