Role of the community pharmacist in detecting frailty and spatio-temporal disorientation among community-dwelling older people in France.

BACKGROUND: Many older community-dwelling subjects may be frail and/or disoriented, putting them at risk of adverse outcomes. We investigated the prevalence of frailty and spatiotemporal disorientation among patients aged > 65 years collecting regular medication at a community pharmacy. METHODS: Prospective, cross-sectional study of geriatric evaluation in 218 community pharmacies in France. Regular customers aged > 65 years attending the pharmacy to receive ≥ 1 prescription drug were eligible. Spatio-temporal disorientation was assessed using a 4-item screening test; subjects were considered disoriented if they had ≥ 1 incorrect answers. Frailty was evaluated using the Short Emergency Geriatric Assessment (SEGA) grid. Subjects were considered as not frail (score < 8), or frail/very frail (score of 8 or more). RESULTS: 4090 subjects were included, average age 77.5 ± 7.6 years, 60.1% females. Overall, 1025 (25%) were frail/very frail, and 384 (9.4%) were disoriented in space or time. On average, subjects were taking 5.4 ± 3.5 medications per day. Among non-frail patients, 116/3065 (3.8%) were disoriented, of whom 87 (87/116, 75%) managed their medication alone. Among frail/very frail patients, 268/1025 (26.1%) were disoriented, of whom 46 (46/268, 16.8%) managed their medication alone. The majority of patients (77.9%) collected their medication alone at the pharmacy, but significantly fewer frail patients came to collect their drugs alone (p < 0.001). CONCLUSION: It is feasible for community pharmacists to detect disorientation and frailty among older patients. A quarter of subjects were frail/very frail, and 3.2% were disoriented yet managing their drugs alone. Additional social support should be envisaged for these subjects.

IPADAM "Pharmaceutical interventions on the issue of pharmaceutical records and self-medication" quanti survey in 482 French pharmacies.

OBJECTIVES: This study aims to: (i) quantify the number of pharmaceutical interventions (PIs) linked to spontaneous requests for the two oral target molecules, ibuprofen and pseudoephedrine (ii) analyse the causes and proposed solutions (iii) quantify the number of registrations in the patient's pharmaceutical record and identify the various causes of non-registration. METHODS: The study was conducted over a 2 weeks' period in the months of February and April 2014 in 482 pharmacies affiliated to the training supervisor associations of 8 French Faculties of Pharmacy. Data regarding spontaneous requests for the target molecules was collected, with due respect to a patient care flow chart at the pharmacy, by incorporating the systematic proposal for registration of the medication in the patient's pharmaceutical record. Each PI was the subject of a notification made with reference to a standardized grid. RESULTS: A total of 12,160 dispensations were made over the two weeks of the study. Overall 815 of them gave rise to an PI (6.7%), justified in almost half of the cases by a contraindication. The alternative proposed by the dispensing pharmacist was accepted in more than 9 out of 10 cases. In half of the cases, the dispensing pharmacist had access to the patient's French healthcare card; more than 2/3 of the dispensations thus led to the registration of the medication in the patient's pharmaceutical record. CONCLUSION: The pairing of the two tools, these being the notification grid and the pharmaceutical record, aims to maximize dispensation security while patients are being guided in their approach to self-medication.

[Bladder located gastric heterotopy: a case report confronting embryology to histopathology]. / Hétérotopie gastrique de siège vésical: un cas clinique au carrefour de l'embryologie et de l'histopathologie.

We report a case of bladder located gastric heterotopy, which has never been described, to our mind in the scientific literature. We discuss the diagnosis and the physiopathological mechanisms that may have been involved in the genesis of such a lesion.

Anti-inflammatory action of methimazole.

The anti-inflammatory activity of 1-methylimidazole-2-thiol (methimazole), the most widely used antithyroid drug, was investigated. Methimazole had a marked inhibitory action on prostaglandin H synthase (IC50 = 10 mumol/l), inhibiting the peroxidase (IC50 = 330 mumol/l), although the cyclo-oxygenase was slightly activated. Methimazole was less potent than indometacin (IC50 = 1.7 mumol/l) on prostaglandin H synthase, but was more potent than acetylsalicylic acid (IC50 = 160 mumol/l). Methimazole has been found to trap superoxide (O2.-) radicals and to decrease the level of blood prostaglandin E2.

Sensitive microanalysis of imipramine and desipramine in single rat thyroids by gas chromatography-mass spectrometry.

A new sensitive method for the quantitative determination of imipramine and desipramine in single rat thyroids using gas chromatography-mass spectrometry with selected ion monitoring, after enzymatic hydrolysis and liquid-liquid extraction has been developed. The technique was deemed suitable for microanalysis of single rat thyroids and for other solid tissues, using smaller sample sizes than usually required for traditional determination methods. The quantification was linear from 10 to 200 nmol/l (i.e., from 0.25 to 5 microg/g) for imipramine and from 100 nmol/l to 2000 nmol/l (i.e., from 2.4 to 47 microg/g) for desipramine, and the limits of detection (less than 25 ng/g tissue for both compounds) were better than those previously reported. Recoveries, repeatability and reproducibility of this technique were satisfactory. It has been successfully applied in a preliminary study of the concentration-time profiles of imipramine and desipramine in the thyroid of rats treated with either of these drugs.

Spectroscopic analysis of charge transfer complex formation and peroxidase inhibition with tricyclic antidepressant drugs: potential anti-thyroid action.

Inspection of the chemical structures of tricyclic antidepressant drugs indicates that they might interfere with the synthesis of thyroid hormones. This iatrogenic potential was demonstrated in vitro by the spectrophotometric detection in both the visible and UV regions of the formation of a complex between antidepressants and iodine. The values of Kc, the formation constant of the drug-iodine complex, were calculated. The concentration of antidepressant which led to a 50% inhibition (IC50) of horseradish peroxidase was also determined. The anti-thyroid activity of drugs can be evaluated from these two parameters, Kc and IC50. The results were compared to those obtained with methimazole, a reference anti-thyroid agent. Antidepressants derived from imipramine appeared to have anti-thyroid activity. This result is now awaiting confirmation in animal experiments.

Synthesis and antithyroid activity of 1,4,5-trialkyl 2-thioimidazole derivatives.

A series of compounds based on the structure of MTI (1-methyl-2-thioimidazole) were synthesized by condensation of alpha-hydroxyketones and alkylthioureas. The alpha-hydroxyketones were obtained by a radical reaction in the presence of sodium and the alkyl ester, while the alkylthioureas were prepared by nucleophilic addition of ammonia on an alkylisothiocyanate. The antithyroid activity of the 13 compounds prepared was evaluated in vitro by determination of the concentrations which led to a 50% inhibition (IC50) of the activity of thyroid peroxidase, and in vivo by assay of thyroid hormones levels and histological examination of the thyroid gland in rats treated chronically with the compounds. 1-methyl-4,5-dipropyl 2-thioimidazole (compound 10) was found to have the highest antithyroid activity of the 13 compounds synthesized.

Antithyroid action of ketoconazole: in-vitro studies and rat in-vivo studies.

Inspection of the chemical structure of ketoconazole indicates that it may have antithyroid activity. The antithyroid action of this drug was demonstrated in-vitro and in-vivo. In-vitro, it was found to form a complex with iodine (formation constant Kc 141 L mol-1), and to inhibit lactoperoxidase (IC50 2 x 10(-4) M). Its effects in-vivo in the rat were assessed by assay of circulating-thyroxine, and from the histological appearance of the thyroid gland. Thyroid gland weight was increased in rats treated with ketoconazole.

Synthesis and antithyroid activity of pyridine, pyrimidine and pyrazine derivatives of thiazole-2-thiol and 2-thiazoline-2-thiol.

A series of compounds was synthesized by linking various derivatives of pyridine, pyrimidine or pyrazine to thiazole-2-thiol or to its partially hydrogenated derivative 2-thiazoline-2-thiol. The reactions of the compounds with molecular iodine and lactoperoxidase were examined in vitro. Their antithyroid activity was also examined in vivo in the rat. T4 and TSH levels were determined, and the thyroid gland was examined histologically. 2-(3-Hydroxy-2-pyridyl)-2-thiothiazoline had the highest antithyroid activity of the compounds tested (Kc = 14931.mol(-1),IC(50)0.65 x 10(-4) M, activity of thyroid gland).

[Antibacterial sulfonamides, antiparasitic and antifungal derivatives of imidazole: evaluation of their antithyroid effects in the rat]. / Sulfamides antibactériens, antiparasitaires et antifongiques dérivés de l'imidazole: évaluation des effets antithyroïdiens sur le rat.

Antithyroid action of some antibacterial, antiparasitic or antifungal agents, was studied by 2 in vitro and 3 in vivo experimentations in the rat. These drugs can upset thyroid hormone synthesis by forming a molecular complex with iodine, and/or by inhibiting thyroid peroxidase activity. Rats treated with these drugs showed an hypothyroidism, demonstrated both by a decrease in T4 concentration and an hyperactivity of thyroid gland by positive feed-back, whose consequence was the presence of cylindrical cells. We noticed this iatrogenic hypothyroidism with all the drugs experimented, by an increase in thyroid gland weight. But the increase of rats body weight, which should have appeared, was not shown. The use of anabolic steroid is now forbidden, therefore, such drugs could be used for breeding animals, in order to gain body weight. Detection of use of these drugs in breeding, to obtain this side effect, should be advised.

Sites of action of 2-thiazoline-2-thiol on biogenesis of thyroid hormones.

2-Thiazoline-2-thiol is an antithyroid agent that strongly reduces thyroid hormone levels. Synthesis of these hormones is catalyzed in vivo by thyroid peroxidase. The interaction of this drug with molecular iodine and its effect on peroxidase activity were investigated. Iodine and 2-thiazoline-2-thiol form a complex of the charge transfer type of 1:1 stoichiometry characterized by a formation constant of 2,527 l.mole-1 at 20 degrees C. This drug was found to inhibit both horseradish peroxidase and lactoperoxidase (used as a model of thyroid peroxidase) in a competitive manner, giving inhibition constants of 5.7 mM and 0.13 mM, respectively. T3 and T4 levels were reduced significantly after a three-week administration of this drug to a group of 10 rats. Histological examination of the thyroid gland showed the presence of a cylindrical epithelium, which is indicative of hyperactivity of the gland. The results indicated that 2-thiazoline-2-thiol acts on both molecular iodine and thyroid peroxidase.

Spectroscopic analysis of charge transfer complex formation between neuroleptics and iodine.

Molecular interactions between iodine and various neuroleptics were investigated by UV/Vis spectroscopy. Iodine was found to form charge transfer complexes in a 1:1 stoichiometry and of n-sigma type with these molecules. The values of the formation constants Kc of these iodinated complexes indicate a strong donor-acceptor interaction. These drugs can therefore be expected to interfere with thyroid metabolism.