Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Health State Utilities and Disease Duration in Systemic Sclerosis: Is There an Association?

ObjectiveHealth state utility values (HSUV) are used as weightings to calculate quality-adjusted life years in economic evaluations. Evidence suggests that patients' perceptions of a new diagnosis for a chronic disease, while initially poor, may improve over time. The objective of this study was to examine the association between disease duration and direct HSUV scores in patients with systemic sclerosis (SSc).MethodsOur study included patients with SSc from a US SSc center. An interviewer administered direct HSUV techniques including the visual analog scale (VAS), time tradeoff (TTO), and standard gamble (SG). We calculated the Short Form 6D HSUV from the Medical Outcomes Study Short Form-36. Additional clinical and demographic variables were collected.ResultsThe mean age of the SSc sample (n = 223) was 51 years (SD 16) with the majority being women (84%). Median disease duration was 5 years (interquartile range 1.5-9). Mean (SD) HSUV scores were 0.67 (0.19) for the VAS, 0.76 (0.28) for the TTO, 0.84 (0.22) for the SG, and 0.65 (0.13) for the SF-6D. In patients with early disease (defined as ≤ 2 yrs, n = 78), the mean HSUV values were 0.64 (VAS), 0.70 (TTO), 0.80 (SG), and 0.63 (SF-6D) versus for those with a longer disease duration: 0.69, 0.79, 0.87, and 0.67, respectively. In multivariate analysis, the SG measure showed a significant and positive association with disease duration measured as a continuous variable and using a threshold of 2 years (p = 0.047 and p = 0.023, respectively).ConclusionGreater disease duration showed a positive association with a direct measure (SG) of utility elicitation after a period of 2 years

Pharmacokinetics of repeated i.v. bolus administration of high doses of r-met-Hu interleukin-2 in advanced cancer patients

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Monoclonal immunoradiometric assay and polyclonal radioimmunoassay compared for measuring neuron-specific enolase in patients with lung cancer

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A preliminary evaluation of calcitonin and PDN-21 as tumor markers for lung cancer

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Evaluation of squamous cell carcinoma antigen as a new marker for lung cancer

SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Circadian and seasonal variations of hematopoiesis in cord blood.

Cord blood hematopoietic progenitors undergo circadian and seasonal variations. The lowest values are obtained between 4:00 and 12:00, as well as between May and August. This represents the first observation of such rhythms before birth.Journal Articleinfo:eu-repo/semantics/publishe