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[Pharmacology of glucocorticoids].

Although Nobel Prize was attributed to three searchers more than 60 years ago for their discovery of corticosteroids, this therapeutic class remains one of the most prescribed nowadays.

The mechanism of action of corticosteroids has not been known since very long and active fundamental research is still very intensive in order to design new drugs able to have all the inhibitory properties without the agonist properties at the level of gene transcription. These new concepts would allow better tolerability. After recording structure-activity properties of steroids, all the pharmacological aspects are reviewed in order to better understand the mechanisms of adverse drug side effects and try to understand them best. All the improvements concerning local topics, especially in the field of dermatology and asthma, have already been a major step towards better tolerance.

The most frequent indications of corticosteroids are reviewed knowing that most of them are without an official market access labelling. Prescribing corticosteroids is always weighing the balance between benefits and risks mainly due to side effects and dependence.

Omalizumab versus 'Usual Care': Results from a Naturalistic Longitudinal Study in Routine Care.

It is unclear how far the superior efficacy of omalizumab, established in randomized controlled clinical trials of patients with severe allergic asthma (SAA), translates into routine practice and when compared to matched controls.

Methods: New-onset omalizumab-treated (OT) patients with SAA (n = 53) were compared to a matched control group of usual-care (UC) patients (n = 53). Treatment and procedures were naturalistic. Subsequent to a baseline assessment, patients were followed up over at least 6 months with at least two follow-up assessments. Primary clinical outcomes were the number of asthma attacks, persistence of asthma symptoms and degree of control [asthma control test (ACT), Global Initiative for Asthma]. Secondary outcome criteria were quality of life (Euro-Qol 5D) and number of medications. For each outcome we compared within-group effects from baseline to 6-month follow-up as well as between-group effects.

Results: OT patients showed significant improvements in number [effect size (ES) = 0.03] and frequency (ES = 0.04) of asthma attacks as well as asthma control (ES = 0.09), whereas controls revealed no significant improvements in these measures. Further improvements in the OT group were found for 'perceived control always' (ACT, p = 0.006), no impairment (ACT, p = 0.02), reduction of sickness days (p = 0.002) and number of medications needed (p = 0.001).

Conclusions: Substantial beneficial effects of omalizumab, similar to those observed in controlled trials and after marketing studies, were confirmed, particularly with regard to the reduction of asthma attacks, persistence of symptoms, asthma control and reduction of concomitant asthma medications. This study provides a tougher test and generalizable evidence for the effectiveness of omalizumab in routine care.

Identification of budesonide metabolites in human urine after oral administration.

Budesonide (BUD) is a glucocorticoid widely used for the treatment of asthma, rhinitis, and inflammatory bowel disease. Its use in sport competitions is prohibited when administered by oral, intravenous, intramuscular, or rectal routes. However, topical preparations are not prohibited. Strategies to discriminate between legal and forbidden administrations have to be developed by doping control laboratories. For this reason, metabolism of BUD has been re-evaluated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with different scan methods.

Urine samples obtained after oral administration of 3 mg of BUD to two healthy volunteers have been analyzed for metabolite detection in free and glucuronide metabolic fractions. Structures of the metabolites have been studied by LC-MS/MS using collision induced dissociation and gas chromatography-mass spectrometry (GC/MS) in full scan mode with electron ionization. Combination of all structural information allowed the proposition of the most comprehensive picture for BUD metabolism in humans to this date. Overall, 16 metabolites including ten previously unreported compounds have been detected. The main metabolite is 16α-hydroxy-prednisolone resulting from the cleavage of the acetal group. Other metabolites without the acetal group have been identified such as those resulting from reduction of C20 carbonyl group, oxidation of the C11 hydroxyl group and reduction of the A ring. Metabolites maintaining the acetal group have also been identified, resulting from 6-hydroxylation (6α and 6β-hydroxy-budesonide), 23-hydroxylation, reduction of C6-C7, oxidation of the C11 hydroxyl group, and reduction of the C20 carbonyl group.

Metabolites were mainly excreted in the free fraction. All of them were excreted in urine during the first 24 h after administration, and seven of them were still detected up to 48 h after administration for both volunteers.

Recurrent Anaphylactic Reactions: An Uncommon Debut of Lymphocytic Hypophysitis.

We report on a 24-year-old male, with exercise-induced asthma and intermittent abdominal pain since puberty, who suffered from recurrent anaphylactic reactions. He also complained of occasional headaches.

After extensive studies he was eventually diagnosed with idiopathic anaphylaxis, once the following diagnoses had been excluded: allergic origin [foods (including ω5-gliadin), latex and drugs], hydatidosis, carcinoid syndrome, systemic mastocytosis, autonomic epilepsy, hereditary angioedema, pheocromocitoma, Meckel diverticle, medullar thyroid carcinoma, leukemia, hyper-IgE and hypereosinophilic syndromes. Given the frequency and severity of the attacks, we started off-label treatment with omalizumab, initially well tolerated. Some days after the second dose the patient started to develop recurrent urticaria. Because of these new symptoms, blood work was repeated, and elevated TSH, decreased T4, positive antithyroid antibodies and decreased cortisol levels with normal ACTH were found. The antiadrenal autoantibodies were negative. The MRI showed a slight thickening of the infundibulum, without pituitary adenoma. Suspecting an autoimmune hypophysitis, we looked for antipituitary antibodies; the result was positive.

A clinical picture of recurrent anaphylactic reactions, the result of complicated adrenal crises in an asthmatic patient, was a manifestation of lymphocytic hypophysitis, a rare chronic inflammatory disease of autoimmune etiology. One year after replacement therapy had been started, the patient remained asymptomatic.

Clinical and cost effectiveness of mobile phone supported self monitoring of asthma: multicentre randomised controlled trial.

OBJECTIVE: To determine whether mobile phone based monitoring improves asthma control compared with standard paper based monitoring strategies.
DESIGN: Multicentre randomised controlled trial with cost effectiveness analysis.
SETTING: UK primary care.
PARTICIPANTS: 288 adolescents and adults with poorly controlled asthma (asthma control questionnaire (ACQ) score ≥ 1.5) from 32 practices.

INTERVENTION: Participants were centrally randomised to twice daily recording and mobile phone based transmission of symptoms, drug use, and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring.

MAIN OUTCOME MEASURES: Changes in scores on asthma control questionnaire and self efficacy (knowledge, attitude, and self efficacy asthma questionnaire (KASE-AQ)) at six months after randomisation. Assessment of outcomes was blinded. Analysis was on an intention to treat basis.

RESULTS: There was no significant difference in the change in asthma control or self efficacy between the two groups (ACQ: mean change 0.75 in mobile group v 0.73 in paper group, mean difference in change -0.02 (95% confidence interval -0.23 to 0.19); KASE-AQ score: mean change -4.4 v -2.4, mean difference 2.0 (-0.3 to 4.2)). The numbers of patients who had acute exacerbations, steroid courses, and unscheduled consultations were similar in both groups, with similar healthcare costs. Overall, the mobile phone service was more expensive because of the expenses of telemonitoring.

CONCLUSIONS: Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines standards. The mobile technology was not cost effective.
TRIAL REGISTRATION: Clinical Trials NCT00512837.

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