Hospitalization characteristics and outcomes of patients with cancer and COVID-19 at a comprehensive cancer center.

Purpose: Several studies have confirmed increased mortality among patients with both COVID-19 and cancer. It remains important to continue to report observations of morbidity and mortality from COVID-19 in this vulnerable population. The purpose of this study is to describe the hospitalization characteristics and outcomes of patients with both cancer and COVID-19 admitted to our comprehensive cancer center.

A juvenile case of cerebellar arteriovenous malformation with gradual onset of dysphoria and headache.

A 25-year-old woman was admitted because of frequent vomiting and headache which had lasted over one week. She had initially clear consciousness but slowly progressive mild headache and dysphoria. Emergency cranial CT revealed a 4 cm haematoma in the left cerebellar hemisphere.

A safety grading scale to support dose escalation and define stopping rules for healthy subject first-entry-into-man studies: some points to consider from the French Club Phase I working group.

Aim: To propose a relevant grading scale for clinical adverse events or laboratory results, electrocardiogram (ECG) and vital sign findings supporting both dose escalation and stopping decisions in first-entry-into-man (FIM) studies conducted in young healthy subjects.

Methods: A three-level scale was used for the proposed grading system. The grading is directly derived from the observed severity of discontinuous variables, as are most of clinical adverse events.

Pharmacodynamic markers in the early clinical assessment of otamixaban, a direct factor Xa inhibitor.

This manuscript reports the assessment of pharmacodynamic (PD) markers of anti-coagulation in the first-in-man study with the novel direct Factor Xa (FXa) inhibitor, otamixaban, with a brief description of safety and pharmacokinetic (PK) findings. The study comprised ten consecutive parallel groups of healthy male subjects (6 active, 2 placebo per group). Eight groups received escalating intravenous doses of otamixaban as 6-hour infusions (1.

Acute, recurrent fosfomycin-induced liver toxicity in an adult patient with cystic fibrosis.

We report a very unusual adverse effect--fosfomycin-induced repeat liver toxicity--in a female adult with cystic fibrosis (CF).

[Myelopathy revealing lupus. Two cases and review of the literature].

Introduction: Myelopathy is a rare manifestation of systemic lupus erythematosus, occurring most often during the course of the disease.

Exegesis: We report two cases of women with myelopathy as the first manifestation of systemic lupus erythematosus; both had an unusual course. We review the literature for previously reported cases.

Pharmacokinetics, pharmacodynamics, and safety of a platelet GPIIb/IIIa antagonist, RGD891, following intravenous administration in healthy male volunteers.

The pharmacokinetics (PK), pharmacodynamics (PD), and safety of a platelet GPIIb/IIIa receptor antagonist, RGD891, and its active metabolite, RGD039, were evaluated after administration of various intravenous regimens of RGD891 to healthy male volunteers in two Phase I studies. Plasma and urine concentrations of RGD891 and RGD039 were measured by validated LC/MS/MS methods with minimum quantifiable limit (MQL) of 1 ng/mL and 10 ng/mL, respectively. PD activity was assessed by percent inhibition of ADP (20 microM)-induced platelet aggregation.

Laboratory data in healthy volunteers: reference values, reference changes, screening and laboratory adverse event limits in Phase I clinical trials.

Objective: Laboratory data are key evaluation procedures for Phase I clinical pharmacology for two reasons. Firstly, laboratory data are used within the screening process to exclude subjects with asymptomatic diseases, which could result in increased danger to themselves or confuse interpretation of the study results. Secondly, during study implementation, safety evaluation and in particular maximum tolerated dose determination have to be done by a case-by-case analysis, sometimes using laboratory adverse events (LAEs).

Adverse events in phase-I studies: a report in 1015 healthy volunteers.

Objective: This report describes all clinical, laboratory and electrocardiographical adverse events detected in healthy volunteers in a phase-I centre over a 10-year period: 54 phase-I studies are involved, including 1015 healthy young volunteers (993 males) who received 1538 treatments (23 different active drugs or placebo) corresponding to 12143 days of follow-up. This updates a similar report published previously in the European Journal of Clinical Pharmacology.

Methods: Adverse events were defined as all events noted in case-report forms.

Critical limits to define a lab adverse event during phase I studies: a study in 1134 subjects.

Objective: The first goal of phase I drug development is the determination of maximal tolerated dose, which must be established by case-by-case analysis, sometimes using a laboratory adverse event. Since no accurate rule defining lab adverse events, has been validated yet, we propose a new "combined method" based on combination of two thresholds: inclusion values and magnitude of variation. Using this combined method, the label "lab adverse event" is applied if any lab value exceeds the inclusion threshold and is associated with a variation from baseline exceeding the variation threshold defined from reference change limit.

Bioavailability Study of Menorest®, a New Estrogen Transdermal Delivery System, Compared with a Transdermal Reservoir System.

The aim of this study was to compare the bioavailability and plasma profiles of estradiol and estrone after repeated applications of 2 types of estradiol transdermal systems: a new adhesive matrix system (Menorest®) compared with a reference membrane/reservoir system (Estraderm®) and to evaluate their short term safety. This was an open, randomised, crossover study, with 2 treatment periods of 10.5 days separated by a 10-day washout period and with a 1-week follow-up.

Upper limit of plasma alanine amino transferase during phase I studies.

In Phase I clinical studies, the maximum tolerated dose has to be determined by a case by case analysis sometimes using a laboratory adverse effect, e.g. an increase in alanine amino transferase (ALT).

[Critical value of bilirubin in the selection of healthy volunteers in for phase I].

10% of young male healthy volunteers have a total bilirubin value over 20 mumol/l; thus such a value appears not relevant as screening cut off point in clinical pharmacology. This study was intended to confirm if a 27 mumol/l cut off point previously defined by the authors does not support a risk. This study dealt with 487 subjects who had together measurements of total bilirubin value and lab.

Adverse events in phase one studies: a study in 430 healthy volunteers.

All the clinical, laboratory and electrocardiographic adverse events detected during 24 Phase I studies in the same unit over a 5 y period are reported here. 430 healthy male volunteers were involved, corresponding to 5488 days of follow-up. The overall incidence of adverse events was 13.

[Diagnostic significance of low thyrotropin in internal medicine].

In an attempt to determine the significance of low plasma thyrotropin (TSH) concentrations in internal medicine and the usefulness of systematic TSH assays in hospitals, 732 consecutive TSH measurements were performed in first-admission patients. TSH concentrations below 0.15 mU/l were found in 33 patients (4.

Selection of healthy volunteers for phase I studies.

Healthy volunteers selection is one of the foundations for phase I results. Safety for volunteers, quality of data and reliability for study results depend on healthy volunteers selection. The selection aim is not to choose normal subjects but to exclude every people with diseases or risk factors which could result in increased danger for themselves or confuse the interpretation of study results.

Laboratory screening method for selection of healthy volunteers.

The aim of laboratory screening in Phase I is to exclude subjects with subclinical illness, who might be at increased risk in the study, and who might also adversely influence interpretation of the results. A new method for laboratory screening, based on Bayesian probability theory, is proposed, which consists of: 1. Drawing up a list of diseases to be excluded.