Corticosteroids in the Management of Pregnant Patients With Coronavirus Disease (COVID-19).

Recent evidence supports the use of an early, short course of glucocorticoids in patients with COVID-19 who require mechanical ventilation or oxygen support. As the number of coronavirus disease 2019 (COVID-19) cases continues to increase, the number of pregnant women with the disease is very likely to increase as well. Because pregnant women are at increased risk for hospitalization, intensive care unit admission, and mechanical ventilation support, obstetricians will be facing the dilemma of initiating maternal corticosteroid therapy while weighing its potential adverse effects on the fetus (or neonate if the patient is postpartum and breastfeeding). Our objective is to summarize the current evidence supporting steroid therapy in the management of patients with acute respiratory distress syndrome and COVID-19 and to elaborate on key modifications for the pregnant patient.

How conducting a clinical trial affects physicians' guideline adherence and drug preferences.

CONTEXT: General practitioners are frequently involved in clinical trials sponsored by pharmaceutical companies but the effects of participation on their prescribing patterns have not been evaluated. OBJECTIVE: To determine how conducting a company-sponsored clinical trial influenced physicians' adherence to international treatment recommendations and their prescribing of the pharmaceutical company's drugs. DESIGN, SETTING, AND PATIENTS: Observational cohort study in Funen County, Denmark, comparing 10 practices that were conducting a trial on asthma medicine with 165 control (non-trial-conducting) practices. The study population included 5439 patients treated with asthma drugs from the trial-conducting practices and 59,574 patients from the control practices. Practices conducted the trial between April 26, 2001, and October 7, 2002. MAIN OUTCOME MEASURES: Adherence to guidelines measured as use of inhaled corticosteroids among asthma patients. Prevalence of use of the company's drugs and the trial sponsor's share of the total volume of asthma drugs prescribed. RESULTS: The baseline proportion of asthma patients using inhaled corticosteroids was 68.5% in trial-conducting and 69.1% in control practices. Conducting the trial did not influence guideline adherence (odds ratio [OR] after 2 years, 1.00; 95% confidence interval [CI], 0.84-1.19). In trial-conducting practices, the sponsoring company's share of the total prescribed volume of asthma drugs increased compared with control practices (6.7%; 95% CI, 3.0%-11.7%). This could be attributed to a significantly higher preference for the company's inhaled corticosteroids (OR, 1.26; 95% CI, 1.04-1.54) and trends toward increased prescribing of the company's other asthma drugs. CONCLUSION: Conducting a trial sponsored by a pharmaceutical company had no significant impact on physicians' adherence to international treatment recommendations but increased their use of the trial sponsor's drugs.

Simultaneous determination of glucocorticoids in plasma or urine by high-performance liquid chromatography with precolumn fluorimetric derivatization by 9-anthroyl nitrile.

A new method for simultaneous determination of glucocorticoids (GCs) in plasma or urine by high-performance liquid chromatography (HPLC) with fluorimetric detection has been developed. Following extraction with ethyl acetate using a reversed-phase disposable cartridge, the six GCs [cortisol (F), cortisone (E), prednisolone (PL), prednisone (PN), 6beta-hydroxycortisol (6beta-OHF) and 6beta-hydroxyprednisolone (6beta-OHP)] and an internal standard (6beta-hydroxycotortisone) were derivatized by treatment with 9-anthroyl nitrile (9-AN) in a mixture of basic catalysts (triethylamine and quinuclidine) to give the fluorescent esters through the 21-hydroxyl group. The GC derivatives so obtained were then cleaned by a straight-phase disposable cartridge and chromatographed on a straight-phase column with an isocratic HPLC technique. The fluorescence derivatives of the GCs, including the internal standard, were separated as clear single peaks and no interfering peaks were observed on the chromatograms. The lower limits of detection for F, E, PL and PN in plasma or urine were 0.1 ng/ml and those for 6beta-OHF and 6beta-OHP in plasma or urine were 0.5 ng/ml, at a signal-to-noise ratio of 3. The analytical recovery of known amounts of the GCs added to plasma or urine were almost 100%. This method can be applied to the determination of plasma or urinary F in renal transplant patients who received PL and can be applied for other metabolic investigations in relation to the change in blood pressure via 11beta-hydroxysteroid dehydrogenase or in hepatic metabolizing via CYP3A4.

[Hypersensitivity to glucocorticoids: reflections on a published case report sample]. / Hypersensibilités aux glucocorticoïdes: réflexions à partir d'un échantillon de cas rapportés dans la littérature.

Hypersensitivity reactions associated with glucocorticoid treatment are rare but well known; the purpose of this study was to identify the responsible constituent (the excipient or the glucocorticoid). 32 cases published from 1970 have been analysed. In 75 per cent of cases, the patients received the glucocorticoid (hydrocortisone and methylprednisolone principally) by the intravenous route. Clinical manifestations reported were respiratory or cutaneous, with a short interval to onset. Skin tests were performed in 20 patients, but cutaneous challenge identified an agent responsible for hypersensitivity in only three cases. The heterogeneity of the test results in these 32 cases makes it difficult to identify a unifying explanation for the reactions, or propose a therapeutic schedule.

Temporal and individual variations in the dose of glucocorticoid used for the treatment of salt-losing congenital virilizing adrenal hyperplasia due to 21-hydroxylase deficiency.

The dose of glucocorticoid was evaluated in the treatment of 19 patients with salt-losing congenital adrenal hyperplasia due to complete or nearly complete 21-hydroxylase deficiency. In most cases, follow-up was from infancy to puberty. The dose of steroid was expressed as oral cortisol (mg/m2 body surface area/24 hours); the equivalent doses of the various glucocorticoid preparations was as follows: 100 mg oral cortisol = 120 mg oral cortisone acetate = 25 mg oral prednisone = 50 mg intramuscular cortisol = 60 mg intramuscular cortisone acetate. The dose of glucocorticoid producing good laboratory and clinical control varied significantly with age. The dose fell from 26 mg/m2/24 hours in early infancy to 19 mg/m2/24 hours between 6 and 8 years of age, and then rose to 23-24 mg/m2/hour in adolescence. In addition to these age-related changes, there were large individual variations at each age. Indeed, the values from 4 of the 19 patients were not included in the calculation of the mean because they were more than 3 SD either above or below the mean. For the rest of the patients, the coefficient of variation ranged from 14.5% to 37.2%. It is concluded that glucocorticoid therapy must be adjusted carefully to the age and needs of each patient.

Effects of gonadectomy and sex hormone therapy on the endotoxin-stimulated hypothalamo-pituitary-adrenal axis: evidence for a neuroendocrine-immunological sexual dimorphism.

Bacterial lipopolysaccharide (LPS) stimulates the hypothalamo-pituitary-adrenal axis by a mechanism involving the release of cytokines, which activate the CRH-ACTH system and, as a result, increase glucocorticoid secretion. In the present study we investigated the possibility that endogenous sex hormones modulate the in vivo endotoxin-stimulated adrenal and immune responses in adult BALB/c mice. In preliminary experiments we determined that the maximal glucocorticoid release in response to LPS (50 micrograms, ip) administration was reached 2 h after treatment. The endotoxin effect on the adrenal and immune responses was then tested in male, randomly cycling female, 20-day-gonadectomized and 20-day-gonadectomized mice treated with either testosterone or estradiol. In addition, in vitro experiments were performed to determine whether 1) LPS exerts any direct effect on basal and ACTH-stimulated corticosterone release, and 2) adrenal function is influenced by bilateral gonadectomy and sex steroid therapy. Our results indicate that 1) randomly cycling female mice have significantly more pronounced corticosterone secretion than males 2 h after endotoxin injection, although the tumor necrosis factor responses were similar; 2) the response of the hypothalamo-pituitary-adrenal axis to endotoxin stimulation in female mice was invariable throughout the different stages of the normal estrous cycle; 3) gonadectomy leads to enhanced (P < 0.05) adrenal and immune responses to LPS stimulation compared to the responses in shams; 4) the endotoxin-elicited adrenal and immune overresponses observed in gonadectomized mice are reversed by testosterone treatment, regardless of sex; 5) LPS does not directly modify spontaneous and ACTH-stimulated adrenal corticosterone secretion; and 6) gonadectomy alone or combined with sex steroid therapy does not increase the in vitro adrenal response to ACTH stimulation. Our findings further suggest an evident neuroendocrine-immunological sexual dimorphism during the acute phase of inflammatory processes.

Ranking of glucocorticoid creams and ointments.

20 corticosteroids ointments and 19 corticosteroid creams available on the Swedish market in January 1977 were tested for their blanching effect. Three ointments and three creams showing pronounced blanching were tested only without occlusion. Hydrocortisone preparations were tested only with occlusion. Other preparations were tested with and without occlusion. All ointments and creams were tested at four randomized sites on the flexor aspect of the forearm in each of 11 or 12 subjects. When used occlusion was applied for 6 hours. Repeated readings were made, using scores 0, 1, 2, and 3. The reading at the time when most preparations showed blanching were analysed statistically. The scores for blanching showed a Poisson distribution when the mean score was less than or equal to 1. Classification of preparations according to blanching was facilitated by the fact that statistical methods for Poisson distribution could be used. A ranking of corticosteroids based on vasoconstriction was obtained, and four different groups for ointments and four for creams emerged. The arbitrary nature of any ranking and grouping of steroids is evident from the data presented.

[Classification of corticoids]. / Classification des corticoïdes

A pharmacological classification of corticoids can be carried out, based on the ratio of their glucocorticoid and mineralocorticoid activities. Their large number is due to the fact that they are practically all synthetic, and that minimal modifications in their structure gives rise to new drugs with variable gluco and mineralocorticoid activity.