Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

The impact of telemonitoring on adherence to nasal corticosteroid treatment in children with seasonal allergic rhinoconjunctivitis.

BACKGROUND: Adherence to controller therapy in allergic diseases is low. Telemonitoring has been proposed to improve adherence to treatment in chronic diseases. However, this strategy has never been tested in allergic rhinoconjunctivitis. OBJECTIVE: To test whether Internet-based telemonitoring during the grass-pollen season of children with allergic rhinoconjunctivitis may enhance adherence to treatment. METHODS: Children and adolescents, 5-18 years old, with moderate-to-severe seasonal allergic rhinoconjunctivitis to grass pollen requiring daily administration of nasal corticosteroid (NCS) (mometasone) were recruited (April 2013) in a paediatric allergy practice. Participants were randomized to Internet-based monitoring (AllergyMonitor(™) , AM) or to usual care (no diary at all, controls) and followed from 13 May (T0) to 15 June 2013 (T2). An intermediate visit (T1) was performed between 31 May and 2 June. Optimal adherence to therapy was expressed as the use of at least 0.190 g/day of mometasone, corresponding to 1 puff/nostril/day, and it was measured by canister weights during (T1) and at the end (T2) of the study period. Main secondary outcomes included the reported disease severity (validated self-questionnaire) and quality of life (AdoIRQLQ questionnaire), disease knowledge (multiple-choice questionnaire), nasal flow and resistance at baseline and at T2. RESULTS: The use of mometasone, expressed as both optimal adherence rate (48.4% vs. 12.5%; P = 0.002) and average daily use (0.20 ± 0.12 g/day vs. 0.15 ± 0.07 g/day; P = 0.037), was higher in the AM group (n = 31) than among controls (n = 32). Disease knowledge improved among the patients using AM (83.3% vs. 68.3%; P < 0.001) but not among controls (68.2% vs. 67.7% right answers; P > 0.05). No differences were observed in the reported severity of disease, nasal flow and resistance and quality of life both at baseline and at follow-up visits. CONCLUSIONS: Internet-based telemonitoring improves adherence to NCS treatment and disease knowledge among children and adolescents with seasonal allergic rhinoconjunctivitis.

Pilot study on the short-term prediction of symptoms in children with hay fever monitored with e-Health technology.

Forecasting symptoms of pollen-related allergic rhinoconjunctivitis at the level of individual patients would be useful to improve disease control and plan pharmacological intervention. Information Technology nowadays facilitates a more efficient and easier monitoring of patients with chronic diseases. We aimed this study at testing the efficiency of a model to short-term forecast symptoms of pollen-AR at the "individual" patient level. We analysed the data prospectively acquired from a group of 21 Italian children affected by pollen-related allergic rhinoconjunctivitis and recorded their symptoms and medication "Average Combined Score" (ACS) on a daily basis during April-June 2010-2011 through an informatics platform (Allergymonitor™). The dataset used for prediction included 15 variables in four categories: (A) date, (B) meteo-climatic, (C) atmospheric concentration of 5 pollen taxa, and (D) intensity of the patient's IgE sensitization. A Partial Least Squares Discriminant Analysis approach was used in order to predict ACS values above a fixed threshold value (0.5). The best performing predicting model correctly classified 77.8% ± 10.3% and 75.5% ± 13.2% of the recorded days in the model and test years, respectively. In this model, 9/21 patients showed ≥ 80% correct classification of the recorded days in both years. A better performance was associated with a higher degree of patient's atopic sensitization and a time lag > 1. Symptom forecasts of seasonal allergic rhinitis are possible in highly polysensitised patients in areas with complex pollen exposure. However, only predictive models tailored to the individual patient's allergic susceptibility are accurate enough. Multicenter studies in large population samples adopting the same acquisition data system on smart phones are now needed to confirm this encouraging outcome.

Factors predicting the outcome of allergen-specific nasal provocation test in children with grass pollen allergic rhinitis.

Background: Nasal provocation testing (NPT) is a reference methodology to identify the culprit allergen in patients with allergic rhinitis. Selecting the right allergen for NPT is particularly difficult in poly-sensitized patients with seasonal allergic rhinitis (SAR). Predictors of NPT outcomes may facilitate the proper use of this test or even substitute it. Objective: To identify predictors of grass pollen NPT outcome from an array of clinical data, e-diary outcomes, and allergy test results in poly-sensitized pediatric patients with SAR. Methods: Poly-sensitized, SAR patients with grass pollen allergy, participating in the @IT.2020 pilot project in Rome and Pordenone (Italy), participated in a baseline (T0) visit with questionnaires, skin prick testing (SPT), and blood sampling to measure total (ImmunoCAP, TFS, Sweden) and specific IgE antibodies to grass pollen extracts and their major allergenic molecules (ESEP, Euroimmun Labordiagnostika, Germany). During the pollen season, patients filled the AllergyMonitor® e-diary app measuring their symptoms, medication intake, and allergy-related well-being via the Visual Analogue Scale (VAS). After the pollen season (T1), patients answered clinical questionnaires and underwent a nasal provocation test (NPT) with grass pollen extract. Results: We recruited 72 patients (age 14.3 ± 2.8 years, 46 males) sensitized to grass and/or other pollens, including olive (63; 87.5%) and pellitory (49; 68.1%). Patients positive to grass pollen NPT (61; 84.7%), compared to the negative ones, had worse VAS values in the e-diary, larger SPT wheal reactions, and higher IgE levels, as well as specific activity to timothy and Bermuda grass extracts, rPhl p 5 and nCyn d 1. A positive NPT to grass pollen was predicted by an index combining the specific activity of IgE towards Phl p 5 and Cyn d 1 (AUC: 0.82; p < 0.01; best cut-off ≥7.25%, sensitivity 70.5%, specificity: 90.9%). VAS results also predicted NPT positivity, although with less precision (AUC: 0.77, p < 0.01; best cut-off ≥7, sensitivity: 60.7%, specificity: 81.8%). Conclusions: An index combining the specific activity of IgE to rPhl p 5 and nCyn d 1 predicted with moderate sensitivity and high specificity the outcome of a grass pollen NPT in complex, poly-sensitized pediatric patients with seasonal allergic rhinitis. Further studies are needed to improve the index sensitivity and to assess its usefulness for NPT allergen selection or as an alternative to this demanding test procedure.

Lack of efficacy of topical furfuryl palmitate in pediatric atopic dermatitis: a randomized double-blind study.

INTRODUCTION: Atopic dermatitis is a common disease in children. It is usually treated with topical steroids and/or calcineurin inhibitors in association with emollients but topical antioxidants have been recently introduced as a therapeutic option for children. The aim of this study was to evaluate the efficacy and tolerability of furfuryl palmitate, a new antioxidant molecule, in a multicenter, randomized, double-blind, vehicle-controlled study. PATIENTS AND METHODS: Children with atopic dermatitis were randomized into 2 groups treated for 2 weeks. One group of children (n = 60) was treated with a basic emollient cream and the other (n = 57) was treated with the same cream enriched with furfuryl palmitate. RESULTS: In both groups, there was a significant reduction (P < .001) in atopic dermatitis-measured using the SCORAD index-after 14 days. The reduction in the per-protocol analysis was higher for the basic cream. Treatment success was defined as a reduction of 20% or more in the SCORAD index from baseline to day 14. Patients who used treatment not permitted by the protocol were also considered treatment failures. The intention-to-treat analysis showed 70% positive results for the basic treatment and 29% for the treatment containing furfuryl palmitate (P < .0001) with a number needed to treat of 2.4 (95% confidence interval, 1.6-4.6). The emollient cream without furfuryl palmitate was observed to be more efficacious by pediatricians and parents, and no differences were reported between the 2 products in terms of tolerability. CONCLUSIONS: Both products proved to be efficacious in treating atopic dermatitis in children, but the emollient cream not containing furfuryl palmitate showed better clinical efficacy.

Non-indigenous macrozoobenthic species on hard substrata of selected harbours in the Adriatic Sea.

The intense shipping traffic characterising the Adriatic Sea favours the spread of marine organisms. Yet, a study of 12 Adriatic ports (4 on the western side and 8 on the eastern side of the basin) found that non-indigenous species (NIS) accounted for only 4% of the benthic communities settled on hard substrates. The cirripeds Amphibalanus amphitrite and Balanus trigonus, found in 8 harbours, were the most common invaders followed by Amphibalanus eburneus, the ascidian Styela plicata, and the bivalve Magallana gigas. The highest percentage of NIS was recorded in Venice and Ploce, the harbours with the least rich native communities; the lowest percentage was retrieved in Trieste, Koper, Pula, and Rijeka, the harbours hosting the highest species diversity. In contrast, the ports of Bari and Ancona showed both high NIS percentages and highly diversified communities.

Ossicular chain mobilisation versus reconstruction in surgery for isolated malleus and/or incus fixation: systematic review and meta-analysis.

OBJECTIVE: To compare post-operative audiometric outcomes for the two prevailing surgical approaches for isolated malleus and/or incus fixation: ossicular mobilisation with preservation of the ossicular chain, and disruption and reconstruction of the ossicular chain. METHODS: A search was conducted, in December 2016, of PubMed, Scopus, and Cumulative Index to Nursing and Allied Health Literature articles written in English. Papers presenting original data regarding post-operative audiometric outcomes in patients who underwent surgical treatment for malleus and/or incus fixation with a mobile and intact stapes were included. A risk of bias assessment was performed on the 14 selected papers and a tier system was developed. Meta-analysis was accomplished by comparing pooled rates of surgical success by chi-square test and calculating odds ratios by logistical regression. Analysis was performed using Revman5 and R software.Results and conclusionAnalysis of the literature revealed no differences in audiometric outcomes between ossicular chain mobilisation and ossicular chain reconstruction in patients with isolated malleus and/or incus fixation. A large, prospective study comparing both short- and long-term hearing results for ossicular chain mobilisation and ossicular chain reconstruction in this population may identify whether a difference in outcomes exists between the two approaches.

Synthesis and antibacterial evaluation of 2-(substituted phenylureido)-4-thiocyanatobenzothiazoles.

The synthesis and antibacterial evaluation of a number of 2-(substituted phenylureido)-4-thiocyanatobenzothiazoles are described. The more active compounds against the test organisms in vitro generally were those substituted with halogens on the phenyl and benzothiazole rings.

Soft tissue overgrowth in bone-anchored hearing aid patients: use of 8.5 mm abutment.

OBJECTIVE: To review outcomes following implantation of an 8.5 mm bone-anchored hearing aid abutment, as regards post-operative management of scalp soft tissue overgrowth. STUDY DESIGN: Retrospective chart review of paediatric and adult patients implanted with bone-anchored hearing aids between 2003 and 2008 who subsequently underwent revision surgery for excessive soft tissue growth. SETTING: A tertiary referral centre and a private otology and neurotology clinic. SUBJECTS: A total of 80 patients underwent bone-anchored hearing aid placement between 2003 and 2008. Of these patients, 14 had significant scalp soft tissue overgrowth unresponsive to first-line, nonsurgical local wound care. RESULTS: Fourteen patients underwent an average of 2.1 surgical procedures each for soft tissue overgrowth around their bone-anchored hearing aid abutment. The mean time between initial implantation and revision surgery was 13.6 months. Of these 14 patients, 11 were eventually fitted with an 8.5 mm abutment. Following placement of the longer abutment, only one patient required additional surgical reduction of soft tissue overgrowth (mean follow-up time 11.8 months). All patients were able to use their bone-anchored hearing aid. CONCLUSION: The 8.5 mm bone-anchored hearing aid abutment is successful in preventing the need for additional surgical intervention in the small but significant number of patients with post-implantation soft tissue overgrowth. Early consideration should be given to this option when first-line soft tissue care is inadequate.

Cooperative cataloging from the participants' point of view: a record of SUNY'S and Countway's experiences.

This paper describes the procedures and practices adopted for the cooperative cataloging program between NLM, Countway, and the Upstate Medical Center, Syracuse. Catalogers were trained by NLM, and the two libraries communicated data and queries by means of TWX and, later, IBM terminals. A description is given of how books are selected for cataloging, and details are given as to how conflicts in cataloging practice are settled. Further results of such cooperation are given, such as the addition of Upstate's holding symbol in Current Catalog. Statistics of work done are given, and impending changes are mentioned.

Characterization of 5-[5-(4-chlorophenyl-2-furanyl)]dihydro-2(3H)-furanone as a nonsteroidal antiinflammatory drug.

5-[5-(4-Chlorophenyl-2-furanyl)]dihydro-2(3H)-furanone (F-1044), a nonsteroidal antiinflammatory drug related to orpanoxin, lacks the usual acid moiety of such agents. F-1044 had antiinflammatory activity equivalent to ibuprofen's and orpanoxin's in the carrageenin-induced paw edema model in normal and adrenalectomized rats. Antiinflammatory activity was also expressed in the guinea pig UV-induced erythema and rat established arthritis models. F-1044 was a more potent analgesic than ibuprofen and orpanoxin in the rat paw pressure assay. In contrast to the reference agents, F-1044 raised the pain threshold of both the yeast-injected and non-injected paws, suggesting a central component to its analgesic action. F-1044 was more potent than ibuprofen and orpanoxin in the rat brewer's yeast pyresis model. Based on its low activity in inhibiting bradykinin-induced bronchoconstriction in guinea pigs and low gastric irritation activity in rats. F-1044 appears to have a mechanisms of action that involves more than simple inhibition of prostaglandin synthesis. Thus F-1044 is a nonsteroidal antiinflammatory agent with unique chemical and pharmacological features.

Confidential enquiry into avoidable vehicle accident deaths in the province of Modena, Italy.

The authors describe the methods and results of a kind of study confidential enquiries into avoidable deaths very rarely performed in the Mediterranean area. After assessing some quali/ quantitative evaluation criteria, an independent expert panel investigated the quality of each step in emergency health care. Information was collected by clinical and forensic reports (clinical method). Of 102 cases, 4 were avoidable deaths and 18 probably avoidable. These results, which are comparable with other similar ones found in Italy (autoptic method) and abroad, have been useful in highlighting some health care errors: in particular, in on-site care and in emergency department diagnosis and treatment. Other avoidable factors emerging were the inappropriateness of transporting severe trauma cases to a small hospital lacking proper equipment and trained staff, and the importance of staff training in first emergency care of severe trauma on ambulance. This situation had been highlighted previously and led to implementation of trauma centres. The methods implemented turned out to be quite statistically reproducible and have been used in local health care planning, especially in the rearrangement of ambulance deployment and emergency staff training.

5-phenyl-2-furamidines: a new chemical class of potential antidepressants.

A series of 5-phenyl-2-furamidines has been synthesized and evaluated for antidepressant activities. Substitution in the phenyl ring with a nitro (4) or an amino (12) group in the ortho-position resulted in an increase in antidepressant activity. Both 4 and 12 antagonized tetrabenazine-induced ptosis in rodents and inhibited norepinephrine (noradrenaline) uptake into crude synaptosomes of whole mouse brain at doses or concentrations comparable to those of the tricyclic antidepressants. However, these compounds did not possess the anticholinergic and antihistaminic activities common to tricyclic antidepressants. In addition, they lacked monoamine oxidase inhibitory activity. The 5-phenyl-2-furamidines represent a new chemical class of antidepressants and may be useful for depressive patients who cannot tolerate the compromising side effects of the tricyclic antidepressants and monoamine oxidase inhibitors.