The emergence of task-relevant representations in a nonlinear decision-making task.

This paper describes the relationship between performance in a decision-making task and the emergence of task-relevant representations. Participants learnt two tasks in which the appropriate response depended on multiple relevant stimuli and the underlying stimulus-outcome associations were governed by a latent feature that participants could discover. We divided participants into good and bad performers based on their overall classification rate and computed behavioural accuracy for each feature value. We found that participants with better performance had a better representation of the latent feature space. We then used representation similarity analysis on Electroencephalographic (EEG) data to identify when these representations emerge. We were able to decode task-relevant representations in a time window emerging 700 ms after stimulus presentation, but only for participants with good task performance. Our findings suggest that, in order to make good decisions, it is necessary to create and extract a low-dimensional representation of the task at hand.

Cross-reactivity and Tolerability of Ertapenem in Patients With IgE-Mediated Hypersensitivity to ß-Lactams.

BACKGROUND AND OBJECTIVE: Administration of carbapenems to ß-lactam-allergic patients has always been considered potentially harmful because of a 47.4% rate of cross-reactivity to imipenem reported in a single study. Nevertheless, recent studies have shown that the rate of cross-reactivity of imipenem and meropenem with penicillins is lower than 1%. The aim of this study was to evaluate the possibility of using ertapenem in patients with an established IgE-mediated ß-lactam allergy. PATIENTS AND METHODS: We studied all participants who came to our allergy unit and had a clinical history of immediate hypersensitivity reactions to ß-lactams. The inclusion criteria were a positive skin test result to at least 1 ß-lactam molecule and/or positive specific IgE (when available). All participants underwent immediate-type skin tests with several ß-lactam molecules including ertapenem. Challenges with intravenous ertapenem were performed on 2 different days in patients with negative skin test results. RESULTS: We examined 49 patients with a clinical history of immediate reactions to ß-lactams. All the patients had positive skin tests and/or positive specific IgE to at least 1 ß-lactam reagent and negative carbapenem skin tests. Thirty-six patients agreed to undergo the challenges and 35 tolerated the full dose of ertapenem. CONCLUSIONS: The practice of avoiding carbapenems in patients with ß-lactam allergy should be abandoned considering the very low rate of cross-reactivity. ß-Lactam-allergic patients who need ertapenem therapy should undergo skin tests and, if negative, a graded challenge to assess tolerability.

Cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins.

BACKGROUND AND OBJECTIVE: 13-Lactams are the most commonly used antibiotics but they can cause hypersensitivity reactions. We sought to estimate cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins. METHODS: We studied 97 patients with a clinical history of nonimmediate reactions to a penicillin and a positive patch test result to at least 1 of the penicillins tested. All patients also underwent patch testing with several cephalosporins. Patients with a negative patch test to a cephalosporin underwent test dosing in order to assess tolerability. RESULTS: We recorded 129 reactions. The most commonly involved drugs were aminopenicillins, and the most widely reported symptoms were delayed urticaria and maculopapular exanthema. Seventeen patients had positive patch test results for cephalosporins, mostly for cephalexin (n=10), cefaclor (n=9), and cefuroxime axetil (n=5). All the patients-except 4 who experienced an exanthema after the challenge test with cephalexin-tolerated a therapeutic dose of the cephalosporin tested without any adverse effects. CONCLUSIONS: Our data show that cross-reactivity between penicillins and cephalosporins may be as high as 10.9% for first-generation cephalosporins and 1.1% for third-generation cephalosporins, possibly due to the involvement of similar side chains. Patch tests are a useful diagnostic tool to assess cross-reactivity, but a graded challenge is mandatory because a negative patch test does not always mean tolerability.

Italian study on buckwheat allergy: prevalence and clinical features of buckwheat-sensitized patients in Italy.

Buckwheat allergy is considered a rare food allergy outside of Asia. In Europe, buckwheat has been described mainly as a hidden allergen. Data on the prevalence of buckwheat hypersensitivity in non-Asian countries is very poor. The aim of this multicenter study was to evaluate the prevalence of buckwheat sensitization and its association with other sensitizations among patients referred to allergy clinics in different geographic areas of Italy. All patients referred to 18 Italian allergy clinics from February through April 2011 were included in the study and evaluated for sensitization to buckwheat and other allergens depending on their clinical history. A total of 1,954 patients were included in the study and 61.3 percent of them were atopic. Mean prevalence of buckwheat sensitization was 3.6 percent with significant difference between Northern (4.5 percent), Central (2.2 percent) and Southern (2.8 percent) regions. This is, to our knowledge, the largest epidemiological survey on buckwheat allergy reported outside of Asia. Buckwheat is an emerging allergen in Italy, being more frequently associated to sensitization in Northern regions.

Profilin desensitization in two patients with plant-derived food allergy.

Profilins are "panallergens", responsible for many cross-reactivities between inhalant, latex and plant-derived food allergens. We evaluated the effectiveness and the safety of sublingual desensitization treatment (SLIT) in two patients with allergic respiratory and food diseases. Skin prick tests, IgE and IgG4 assays to pollens, some plant-derived foods, profilin, non-lipid specific transfer protein and PR 10 proteins were performed. The patients also underwent double-blind placebo-controlled challenge (DBPCFC) with the culprit foods and profilin and then a SLIT with it. Both the patients had positive SPT, specific IgE and DBPCFCs with profilin and some vegetables referred in anamnesis. They therefore underwent SLIT with profilin extract. At the end of treatment, the patients had negative DBPCFCs with culprit foods and a decrease of specific IgE levels for profilin and vegetable foods. Profilin desensitization allowed our patients to manage their diet without restriction, eating several foods previously not tolerated.

The clinical meaning of positive latex sIgE in patients with food/pollen adverse reactions.

Natural rubber latex allergy (NRL-A) is an international problem of public health. About 50-60% of NRL-A patients may present adverse reactions after ingestion of cross-reacting vegetable foods. This condition, called "Latex-fruit Syndrome", is a matter of research. The aim of our study is to distinguish between clinical/subclinical latex-fruit syndrome and cross-sensitization to latex and food/pollen allergens on the basis of latex recombinant allergens. We studied 51 patients with food hypersensitivity and serological evidence of NRL sensitization. The subjects underwent an accurate allergological evaluation (skin prick test with latex, food and pollen extracts, specific IgE to latex and recombinant allergens, challenge provocation tests). The patients were divided in two groups: group A) 34 patients with clinical and serological latex and fruit/vegetable allergies; group B) 17 patients allergic to fruits/vegetables and/or pollens, with serological, but not clinical NRL-A. All the latex challenge tests resulted positive in group A patients and only two patients of group B presented positive cutaneous challenge tests. Moreover, specific IgE-antibodies were detected to rHev b 5, to rHev b 6.01, to rHev b 6.02 and to rHev b 8 (and other profilins) of group A patients, while in group B we observed a monosensitization to Hev b8, probably linked to a cross-sensitization to pollens and foods. At the present state of knowledge, we need a multi-parametric approach based on a combination of clinical history, diagnostic tests (CRD) and latex challenge tests to make diagnosis of latex-fruit syndrome.

Tolerability of aztreonam in patients with cell-mediated allergy to ß-lactams.

BACKGROUND: Cross-reactivity between aztreonam and ß-lactams is poor, but tolerability of aztreonam has been assessed in a few groups of patients suffering from IgE-mediated allergy to ß-lactams. The aim of this study was to assess the cross-reactivity of aztreonam with other ß-lactams and its tolerability in patients with cell-mediated allergy to these drugs. METHODS: We studied 78 patients with cell-mediated allergy to ß-lactams who underwent skin prick, immediate and delayed-reading intradermal tests as well as patch tests with penicilloyl-polylysine, minor determinant mixture, semi-synthetic penicillins, cephalosporins, aztreonam and imipenem. Patients with negative allergy testing with aztreonam underwent an intramuscular test dosing and were observed for 3 h. RESULTS: Our patients experienced 94 non-immediate reactions; delayed-onset urticaria (34 cases), maculopapular exanthema (13 cases), urticaria/angioedema (15 cases) and itching erythema (13 cases) were the most reported symptoms. Amoxicillin (35 cases), ampicillin (28 cases) and bacampicillin (18 cases) were the most involved drugs. All patients had a positive patch test and/or a positive delayed-reading intradermal test to at least 1 ß-lactam antibiotic and none had a positive patch or delayed-reading intradermal test to aztreonam. Then, 65 patients underwent intramuscular test dosing with aztroenam, and none of them had a clinical reaction. CONCLUSIONS: Our data confirm the lack of cross-reactivity between ß-lactams and aztreonam in patients with cell-mediated allergy to these drugs. Delayed-reading intradermal tests and patch tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in ß-lactam-allergic patients.

Allergic and non-allergic drug hypersensitivity reactions in children.

Adverse drug reactions (ADR) are an important medical problem. The aim of this study is to investigate the clinical characteristics of children with ADR and to assess the tolerability of alternative drugs in children (under 16 yrs of age) with a history of ADR. We studied 278 children (132 males and 146 females). Patients were studied by recording personal history and performing in vivo skin testing, in vitro laboratory tests and challenge tests. Patients who had experienced mild adverse reactions underwent challenge tests without any premedication; patients with a clinical history of moderate reactions, received a premedication with sodium chromolyn 30 min before the oral challenge; patients with a clinical history of severe reactions or undergoing parenteral challenges, were given an antihistamine 30 minutes before. A total of 660 adverse events were reported with 126 different drugs involved. Antimicrobial agents were the most involved drugs (51.7%). Non-steroidal anti-inflammatory drugs were involved in 22.7% of episodes. The most reported symptoms were cutaneous. Allergy testing was negative in 272 patients. A diagnosis of drug allergy was reported for 6 patients. A total of 669 challenge tests were performed. 639 were negative at first attempt while 22 were positive. Eight were repeated using a different premedication and resulted negative. Hypersensitivity drug reactions in children are mainly non-allergic. A premedication with sodium cromolyn or with oral H1-antihistamines may be useful in preventing ADR.

Cross-reactivity and tolerability of imipenem in patients with delayed-type, cell-mediated hypersensitivity to beta-lactams.

BACKGROUND: Administration of imipenem-cilastatin to patients with IgE-mediated hypersensitivity to beta-lactams has always been considered potentially harmful. Recent studies have demonstrated the tolerability of carbapenems (imipenem-cilastatin and meropenem) in patients with IgE-mediated hypersensitivity to beta-lactams; there are no studies on this topic regarding patients with cell-mediated allergy to beta-lactams. The aim of this study is to assess cross-reactivity and tolerability of imipenem in patients with cell-mediated allergy to beta-lactams. METHODS: From our database we selected 73 patients with cell-mediated allergy to beta-lactams, diagnosed by means of immediate-type skin tests, delayed reading intradermal tests, patch tests and detection of specific IgE. Patients with negative patch tests with imipenem-cilastatin underwent an intramuscular test dosing. RESULTS: Our patients had a total of 94 nonimmediate reactions to penicillins. All patients had positive patch tests and/or delayed reading intradermal tests for at least one of the penicillin reagent tested and negative immediate-type skin tests and specific IgE. Four patients out of 73 had a positive patch tests to at least one penicillin reagent and imipenem-cilastatin showing cross-reactivity. Sixty-four patients underwent the imipenem-cilastatin intramuscular test dosing and none of them had a clinical reaction. CONCLUSIONS: Our rate of cross-reactivity between imipenem-cilastatin and other beta-lactams was 5.5%. This result is different from previous findings and this may be explained by the fact that we investigated patients with cell-mediated allergy to beta-lactams. Patients with cell-mediated allergy to beta-lactams should undergo patch tests and a tolerance challenge test before treatment with imipenem-cilastatin.

Sublingual desensitization in patients with wasp venom allergy: preliminary results.

The aim of this paper is to assess in an open prospective pilot case-control study the tolerability, safety and efficacy of an ultra-rush sublingual immunotherapy (SLIT) protocol with Vespula venom in wasp allergic patients compared to subcutaneous immunotherapy (SCIT). Forty-one wasp allergic patients were treated with sublingual (SLIT group) or subcutaneous (SCIT group) ultrarush immunotherapy with Vespula venom extract. All patients underwent skin tests and serum specific IgE and IgG4 detection before enrollment and after 6, 12 and 24 months of immunotherapy. The SLIT group consisted of 21 (6 females and 15 males) patients who received increasing doses of Vespula venom (Aquagen, ALK-Abellò) until the final dose of 30 drops of extract in 3 hours, containing 100,000 SQ-U/ml. The maintenance dose was of 10 drops of pure venom extract 3 times a week, for a total dose of 100,000 SQ-U weekly (corresponding to 100 microgram of venom extract). The SCIT group consisted of 20 patients (16 males and 4 females) who were treated with subcutaneous ultrarush immunotherapy with Vespula venom extract (Pharmalgen, Alk-Abellò). Patients received 101.1 microgram of Vespula venom in 3 hours and were treated with 100 microgram of wasp venom monthly. During the ultrarush sublingual treatment 2 patients (9.5%) experienced mild side-effects. Specific IgE and specific IgG to wasp venom did not show any significant modification. Four patients were field-stung by a wasp during the treatment (for a total of 6 stings). Two patients (3 stings), with a previous clinical history of a grade III and IV reaction, did not experience any reaction. One patient, with a previous grade II reaction, showed a large local reaction. The fourth patient, with a previous grade III reaction, was re-stung twice (after 12 and 24 months) with two systemic reactions (SR) (mild throat constriction). During the ultrarush SCIT phase, 3 (15%) patients experienced side-effects: 2 of them showed a large local reaction and 1 had headache and stomach ache. Specific IgE showed a significant (P = 0.001) increase after 6 months of treatment and then returned to baseline levels while specific IgG showed a significant (P = 0.001) increase after 6, 12 and 24 months in comparison with baseline. Nine patients were field-stung during the treatment: 8 of them experienced large local reactions; one patient (11%) experienced an SR (dizziness). Our results, even if in a small number of patients, suggest that in patients with Hymenoptera sting allergy SLIT could be efficacious with a good tolerability profile when compared to SCIT. Larger studies are needed to assess efficacy, safety and tolerability profile of wasp venom SLIT.