Assessing clinical and psychological features: who are patients showing a nocebo re-action during the drug challenge test?

Summary: The nocebo reaction, namely the undesirable effect of an inert substance (placebo), is a phenomenon rarely investigated in literature. A better knowledge of this reaction may help clinicians in the management of these patients in clinical practice. Patients with drug adverse reactions (ADR) undergoing the drug challenge test are an ideal model for studying the nocebo effect, and the study aims to investigate their clinical and psychological features. One hundred and twenty patients (Mage = 46.59, SD = 15.5; 82% female), of which 90 non responders and 30 with nocebo reactions (25%) were recruited, and completed a battery of psychological measures: State-Trait Anxiety Inventory X1-X2, Beck Depression Inventory II, Symptoms Checklist-90-R, Difficulties in Emotion Regulation Scale, Toronto Alexithymia Scale. Clinical features (individual characteristics and ADR clinical history) were collected by clinicians. The results show that older age (p = 0.002), low level of education (p = 0.039) and a depressive tendency (p = 0.030) appear to be potential risk factors for nocebo effects. Although none of the features related to the previous clinical history appear to represent a risk factor for the nocebo reactions (p minor 0.05), significant correlations between some of the clinical and psychological characteristics considered (p values from 0.005 to 0.042) help to better delineate the profile of these reactive patients. A specific training of the sanitary team about psychological aspects is recommendable.

Canine and feline dermatophytosis due to Microsporum gypseum: a retrospective study of clinical data and therapy outcome with griseofulvin.

OBJECTIVE: Microsporum gypseum is a common inhabitant of the soil, occasionally responsible for human and animal ringworm. Few reports describe the treatment of dermatologic diseases due to M. gypseum. The objective of this study was to evaluate retrospectively cases of M. gypseum infection in dogs and cats. MATERIAL AND METHODS: The occurrence of infection by this dermatophyte was retrospectively evaluated in dermatological specimens from 15,684 dogs and cats dermatologically diseased from Italy. Clinical outcome after treatment with griseofulvin combined with topical enilconazole was evaluated in 41 dogs and, out of label, 10 cats. Furthermore, in vitro susceptibility to griseofulvin and enilconazole was evaluated on 31 clinical isolates of M. gypseum. RESULTS: One hundred and eighty-five specimens out of 15,684 (1.1%) scored positive for M. gypseum. The treatment failed to achieve both mycological and clinical cure in 16 dogs (39%) and four cats (40%), as well as fungal isolates demonstrated a very poor in vitro sensitivity when tested versus griseofulvin: the MIC value was 150 µg/mL. The ED50 value was calculated at 66 µg/mL. CONCLUSION: Blind treatments with griseofulvin in ringworm due to M. gypseum should be avoided.

Relevance of polymer molecular weight to the in vitro/in vivo performances of ocular inserts based on poly(ethylene oxide).

A previous study of the present authors on gel-forming erodible inserts, based on high molecular weight (MW, 400 kDa) poly(ethylene oxide) (PEO), for ocular controlled delivery of ofloxacin (OFX) has been extended to investigate the effects of PEO MW, in the 200-2000 kDa range, on insert properties relevant to therapeutic efficacy. Mucoadhesion has shown a dependence on MW, with a maximum for PEO 400. The in vitro drug release from inserts based on PEO 200, PEO 400 and PEO 900 was mainly controlled by insert erosion, whereas with PEO 2000 it was mainly diffusion-controlled in a first phase, followed by an erosion-controlled phase. The erosion time scale depended directly on MW. Immediately after application in the lower conjunctival sac of the rabbit eye, the inserts based on PEO of whichever MW formed mucoadhesive gels, well tolerated by the animals; then the gels spread over the corneal surface and eroded. PEO 2000 was unsuitable as an insert material, since the resulting gel spilled from the eye, due to excessive swelling. The gel residence time in the precorneal area, the drug permanence time in the aqueous humor at concentrations > MIC and the time to reach the maximal drug concentration in the aqueous humor (C(max)) depended directly on MW, indicating that transcorneal absorption was governed by gel erosion. All inserts increased Cmax and AUCeff (AUC for concentrations > MIC) with respect to the commercial eyedrops. The increases caused by PEO 400 and PEO 900 were similar (3.78- and 3.16-fold, respectively, for Cmax; 11.06- and 12.37-fold, respectively, for AUCeff), whereas smaller increases were produced by PEO 200. The PEO 400 and PEO 900 inserts have shown a potential for a topical treatment of endophthalmitis.

Gel-forming erodible inserts for ocular controlled delivery of ofloxacin.

A new application of high molecular weight (400 kDa) linear poly(ethylene oxide) (PEO) in gel-forming erodible inserts for ocular controlled delivery of ofloxacin (OFX) has been tested in vitro and in vivo. Inserts of 6 mm diameter, 20 mg weight, medicated with 0.3 mg OFX, were prepared by powder compression. The in vitro drug release from inserts was mainly controlled by insert erosion. The erosion time scale was varied by compounding PEO with Eudragit L100 (EUD) 17% neutralized (EUDNa17) or 71% neutralized (EUDNa71). The insert erosion rate depended on the strength of interpolymer interactions in the compounds, and on the hydrophilic-hydrophobic balance of compounds. Immediately after application in the lower conjunctival sac of the rabbit eyes, the inserts based on plain PEO, PEO-EUDNa17 or PEO-EUDNa71 formed mucoadhesive gels, well tolerated by the animals; then the gels spread over the corneal surface and eroded. The gel residence time in the precorneal area was in the order PEO-EUDNa71 < PEO < PEO-EUDNa17. Compared to commercial OFX eyedrops, drug absorption into the aqueous humor was retarded by the PEO-EUDNa71 inserts, and both retarded and prolonged by the PEO-EUDNa17 inserts, while C(max) (maximal concentration in the aqueous) and AUC(eff) (AUC in the aqueous for concentrations > MIC) were barely altered by either insert type. On the other hand, C(max), AUC(eff) and t(eff) (permanence time in the aqueous at concentrations > MIC) were strikingly increased by plain PEO inserts with respect to commercial eyedrops (5.25 +/- 0.56 vs. 1.39 +/- 0.05 microg ml(-1); 693.6 vs. 62.7 microg ml(-1) min; and 290 vs. 148 min, respectively). Bioavailability increase has been ascribed to PEO mucoadhesion and/or increased tear fluid viscosity.