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Background: Red meat allergy has historically been understood as a rare disease of atopic children, but the discovery of the "α-Gal syndrome," which relates to IgE to the oligosaccharide galactose-α-1,3-galactose (α-Gal), has challenged that notion., Objective: To describe the clinical and immunologic characteristics of a large group of subjects with self-reported allergy to mammalian meat., Methods: This was an observational study of 261 children and adults (range, 5-82 years) who presented for evaluation for allergic reactions to mammalian meat. Results were based on serum assays and a detailed questionnaire., Results: α-Gal specific IgE ≥ 0.35 IU/mL was detected in 245 subjects and symptom onset occurred ≥2 hours after eating mammalian meat in 211 (81%). Component testing supported a diagnosis of α-Gal syndrome in 95%, pork-cat syndrome in 1.9%, and primary beef allergy in 1.1%. Urticaria was reported by 93%, anaphylaxis by 60%, and gastrointestinal symptoms by 64%. Levels of IgE and IgG specific to α-Gal were similar in subjects who reported early- or delayed-onset symptoms, and in those with and without anaphylaxis. Levels of α-Gal specific IgE and severity of reactions were similar among those with and without traditional atopy, and among children (n = 35) and adults (n = 226). Blood group B trended toward being under-represented among α-Gal-sensitized subjects; however, α-Gal specific IgE titers were high in symptomatic cases with B-antigen., Conclusions: The α-Gal syndrome is a regionally common form of food allergy that has a characteristic but not universal delay in symptom onset, includes gastrointestinal symptoms, can develop at any time in life, and is equally common in otherwise nonatopic individuals., (Copyright © 2019. Published by Elsevier Inc.)

Background: Voriconazole is well established as standard treatment for invasive aspergillosis (IA). In 2017, isavuconazole, a new antifungal from the azole class, with a broader pathogen spectrum, was introduced in Sweden. A model has therefore been developed to compare the cost-effectiveness of isavuconazole and voriconazole in the treatment of possible IA in adults in Sweden., Methods: The cost-effectiveness of isavuconazole versus voriconazole was evaluated using a decision-tree model. Patients with possible IA entered the model, with 6% assumed to actually have mucormycosis. It was also assumed that pathogen information would become available during the course of treatment for only 50% of patients, with differential diagnosis unavailable for the remainder. Patients who were considered unresponsive to first-line treatment were switched to second-line treatment with liposomal amphotericin-B. Data and clinical definitions included in the model were taken from the published randomised clinical trial comparing isavuconazole with voriconazole for the treatment of IA and other filamentous fungi (SECURE) and the single-arm, open-label trial and case-control analysis of isavuconazole for the treatment of mucormycosis (VITAL). A probabilistic sensitivity analysis was used to estimate the combined parameter uncertainty, and a deterministic sensitivity analysis and a scenario analysis were performed to test the robustness of the model assumptions. The model followed a Swedish healthcare payer perspective, therefore only considering direct medical costs., Results: The base case analysis showed that isavuconazole resulted in an incremental cost-effectiveness ratio (ICER) of 174,890 Swedish krona (SEK) per additional quality adjusted life-year (QALY) gained. This was mainly due to the efficacy of isavuconazole against IA and mucormycosis, as opposed to voriconazole, which is only effective against IA. Sensitivity and scenario analyses of the data showed that the average ICER consistently fell below the willingness to pay (WTP) threshold of 1,000,000 SEK. The probability of isavuconazole being cost-effective at a WTP of 170,000 SEK per QALY gained was 50% and at a WTP of 500,000 SEK per QALY gained was 100%., Conclusions: This model suggests that the treatment of possible IA with isavuconazole is cost-effective compared with treatment with voriconazole from a Swedish healthcare payer perspective.

Objectives: Voriconazole, amphotericin B (AmB) formulations, and isavuconazole are all included in guideline recommendations for treatment of patients with invasive aspergillosis (IA) but the relative efficacy of isavuconazole versus AmB formulations has not been directly compared. We aimed to estimate the relative efficacy of isavuconazole compared with AmB deoxycholate (AmB-D), liposomal AmB (L-AmB), and voriconazole for the treatment of patients with proven/probable IA., Methods: Nine literature databases were screened for randomized controlled trials comparing treatments with any of voriconazole, AmB-D, L-AmB and isavuconazole for treatment of proven/probable IA. Articles meeting the criteria were included in a meta-analysis to determine the efficacy of AmB-D, L-AmB and voriconazole relative to isavuconazole based on all-cause mortality (ACM) and overall response using a fixed-effects model., Results: Four articles were identified that compared L-AmB with AmB-D (Study 1), standard-dose L-AmB (3-5 mg/kg/day) with high-dose L-AmB (10 mg/kg/day; Study 2), voriconazole with AmB-D (Study 3), and isavuconazole with voriconazole (Study 4). In the network meta-analysis, isavuconazole was statistically superior to AmB-D on both ACM (odds ratio [95% credible intervals] shown as natural log, 1.00 [0.26, 1.74]) and overall response (-1.39 [-2.21, -0.63]). Differences between isavuconazole, and standard-dose L-AmB, high-dose L-AmB and voriconazole were not statistically significant for either ACM (0.18 [-1.17, 1.53], 0.50 [-1.11, 2.13] and 0.32 [-0.19, 0.84], respectively) or overall response (-0.99 [-2.21, 0.29], -0.89 [-2.41, 0.65] and 0.06 [-0.43, 0.57], respectively)., Conclusions: This data suggests that the efficacy of isavuconazole for treatment of IA is superior to AmB-D and comparable with both L-AmB and voriconazole.

Aim: Invasive mold diseases (IMDs) are associated with significant morbidity and mortality. Approved treatments include voriconazole (VORI), liposomal amphotericin B (L-AMB), posaconazole (POSA) and isavuconazole (ISAV). A UK-based economic model was developed to explore the cost of treating IMDs with ISAV versus L-AMB followed by POSA., Materials & Methods: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration & monitoring, and hospitalization costs were evaluated from the healthcare system perspective., Results: Per-patient costs were UK£14,842 with ISAV versus UK£18,612 with L-AMB followed by POSA. Savings were driven by drug acquisition, and administration & monitoring costs., Conclusion: ISAV has the potential to reduce IMD treatment costs relative to L-AMB followed by POSA.

Aim: Mucormycosis is a fungal infection associated with high mortality. Until recently, the only licensed treatments were amphotericin B (AMB) formulations. Isavuconazole (ISAV) is a new mucormycosis treatment. A UK-based economic model explored treatment costs with ISAV versus liposomal AMB followed by posaconazole., Materials & Methods: As a matched case-control analysis showed similar efficacy for ISAV and AMB, a cost-minimization approach was taken. Direct costs - drug acquisition, monitoring and administration, and hospitalization costs - were estimated from the National Health Service perspective., Results: Per-patient costs for ISAV and liposomal AMB + posaconazole were UK£26,810 and UK£41,855, respectively, with savings primarily driven by drug acquisition and hospitalization costs., Conclusion: ISAV may reduce costs compared with standard mucormycosis therapy.

Chronic hand eczema places a heavy burden on patients, often affecting their ability to work. This paper compares the cost-of-illness and treatment approaches for patients with refractory chronic hand eczema, in relation to whether the disease was occupational or unrelated to work factors. Data from 2 surveys, comprising 310 patients with chronic hand eczema insured by German statutory health insurance (SHI) (including work-impaired patients, work-unaffected patients and non-working patients) and known work-related chronic hand eczema insured by occupational health insurance (OHI). Annual healthcare costs of managing work-impaired patients (SHI) and patients with work-related chronic hand eczema (OHI) were €3,164 and €3,309, respectively, approximately double the costs of managing non-working and work-unaffected (SHI) patients. This analysis shows that the costs associated with chronic hand eczema are affected by the correlation of chronic hand eczema with work, with costs being higher for occupational patients with chronic hand eczema.

Evaluation of the tympanic bulla (TB) in cases of otitis media in the rabbit can be a diagnostic challenge, although a feature often associated with the condition is the accumulation of fluid or material within the TB. Randomly selected TB from 40 rabbit cadavers were filled with a water-based, water-soluble jelly lubricant. A dorsoventral radiograph and single computed tomography (CT) slice were taken followed by an ultrasound (US) examination. Image interpretation was performed by blinded operators. The content of each TB was determined (fluid or gas) using each technique and the cadavers were frozen and sectioned for confirmation. CT was the most accurate diagnostic method, but US produced better results than radiography. Given the advantages of US over the other imaging techniques, the results suggest that further work is warranted to determine US applications in the evaluation of the rabbit TB and clinical cases of otitis media in this species., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The allergist is frequently called on to evaluate patients after episodes of anaphylaxis to determine the cause and implement preventive measures that will reduce the patient's risk from future episodes. The etiology of anaphylaxis can be the result of numerous causes that may go undiagnosed if a thorough evaluation is not performed. We present a 71-year-old man with no history of food allergy or atopy who presented to the emergency room and then our allergy clinic for evaluation after suffering anaphylaxis after a meal of grits and shrimp. The underlying diagnosis, which was subsequently determined, requires a high index of suspicion and should be included in the differential diagnosis of any patient presenting with unexplained anaphylaxis.

Background: A multidisciplinary outpatient department was set up in the northern part of the Netherlands because of a local lack of adequate treatment and care for Huntington's disease (HD)patients. Outreaching multidisciplinary care is a novel way to optimise functioning and quality of life of HD patients. The vast majority of patients want to stay home as long as possible. Huntington's disease is a devastating neurodegenerative disorder leading to complete disability and long term residence in a specialised institution. In this paper we outline this new type of treatment and give the results of 1.5 year, we also present the results of an inquiry on the appreciation of the working method., Methods: In the first project half (1.5 yr) 28 patients were seen as had been anticipated. The multidisciplinary team consisting of an institutional physician, a psychologist, a speech and language therapist, a social worker, an occupational therapist and a case manager, assesses the stage of the disease and formulates, coordinates and implements the individual care and treatment plan in the home situation. After 1.5 year a questionnaire on the appreciation of the department was sent to patients, caregivers, healthcare professionals, the lay organisation and Dutch "experts in the field"., Results: For the 28 HD patients a total of 242 problems and actions were verbalised in the care plan, which was accepted by the majority of the patients. Especially informal caregivers, the lay organisation and the Dutch "experts in the field" were enthusiastic on the outreaching and multidisciplinary nature of the department. The verdict over the continuance of the clinic was positive and unanimous., Conclusions: We concluded that coordinating outreaching multidisciplinary care from an outpatient clinic into the dwelling place of the patient is feasible and appreciated.

Background: It is broadly assumed that costs caused by chronic hand eczema (CHE) are significant. However, there is a lack of cost-of-illness studies on CHE., Objectives: To determine the direct and indirect costs of CHE under routine conditions in Germany from the societal perspective., Methods: A cross-sectional survey was conducted in 24 outpatient practices and clinics across Germany. Patients with CHE refractory to potent topical steroids and insured by statutory health insurance were eligible. Clinical and cost data were collected using standardized questionnaires. Severity classes were defined according to a photographic guide and physician global assessment (PGA). Four treatment stages were defined based on the German CHE guidelines: topical treatments only (stage I), additionally ultraviolet (UV) radiation therapy (II), systemic therapy (III) and inpatient treatment (IV). Bivariate associations between costs and severity as well as treatment stage were assessed., Results: Two hundred and twenty-three patients with CHE (mean age 45·7years, 56% women) enrolled in the study, of whom 63·2% were treated only with topical treatments, 15·7% additionally with UV radiation and 11·7% with systemic treatments. Of all patients, 9·4% had been admitted to hospital. Total costs per year and patient were €2128, including €1742 direct costs and €386 indirect costs. The total costs increased with treatment stages I-IV (P<0·001): €1044, €2307, €2697 and €8407, respectively. Accordingly, costs also correlated with clinical severity., Conclusions: Patients with CHE refractory to topical steroids incur marked costs to society. The costs increase disproportionately with escalating treatment stages, especially in patients admitted to hospital. Hence, new treatments may help to reduce the societal costs of CHE., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Otitis media in the rabbit commonly results in fluid accumulation in the tympanic bulla. Radiographic detection of fluid in the tympanic bulla is only moderately sensitive in the dog and cat. The purpose of this study was to investigate the accuracy of radiographic detection of fluid in the rabbit tympanic bulla for three different radiographic projections. Forty rabbit cadavers were used. Half of the tympanic bullae were randomly allocated to be filled with soft tissue material. Following this procedure, each specimen was radiographed in three projections: dorsoventral (DV), rostro 40 degrees ventral-caudodorsal (R40 degrees V-CdDO), and left and right latero 40 degrees ventral-laterodorsal (Lat40 degrees V-LatDO). After imaging, each specimen was frozen and sectioned to determine the content of the tympanic bullae. Images were interpreted and scored independently by two board-certified radiologists. There was no significant difference in sensitivity or specificity between the three projections when compared with the gross findings following sectioning, but observer confidence was highest for the DV projection. Accuracy of radiographic fluid detection was similar to that reported in the dog and cat. The DV and R40 degrees V-CdDO allow comparison of both tympanic bullae on a single radiograph, but the DV was subjectively easier to position, while the Lat40 degrees V-LatDO requires two radiographs for comparison.

Introduction: Randomization is the most optimal design for evaluating program-effectiveness. In practice, however, conducting a randomized controlled trial is not always feasible. For a non-randomized study into the effect of a parent management training, predefined intervention and control groups of families were matched on six key characteristics. The quality of this match was then compared with the quality which is to be expected from a randomized study., Methods: The performance of matching intervention and control families for predefined and randomized groups was evaluated by simulating new hypothetical intervention and control groups. The Mahalanobis metric was used to assess the distance between families in the intervention and the control groups and pairwise matching was performed. The global distance between these groups was used as measure of the balance of covariates in all matched pairs, with a smaller distance indicating a higher match quality., Results: In the ideal situation, when predefined groups are actually equal to randomized groups, the expected probability of a more equal balance of characteristics in the former groups than in the latter groups is 0.50. Using the data obtained in our study, and our predefined groups, this expected probability was 0.34., Conclusion: Even when randomized groups are more balanced than predefined groups, using the latter groups for analyses might still be acceptable when the differences in group means are small. Findings suggest that matching can be a viable alternative to randomization for situations in which randomization is not feasible due to pragmatic constraints. However, a more accurate judgment on the value of the results obtained in this study requires results from similar analyses performed in other studies for comparison.