The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy.

OBJECTIVES: Prudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy. METHODS: The guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak. RESULTS: Sixty recommendations were provided for suspected allergy to ß-lactam antibiotics (BLAs) and non-ß-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team. CONCLUSIONS: Accumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non-ß-lactam antibiotics, thereby strongly supporting antimicrobial stewardship.

Influence of added whey proteins and hydrolysates on rheological and textural characteristics of milk chocolate.

In order to improve functional characteristics of standard milk chocolate (C) was enriched by the addition of whey protein concentrate (WPC) and whey proteins hydrolyzed by trypsin (H-WPC) in the amount of 6%. The chocolate samples were analyzed by determination of antioxidant capacity, particle size distribution, textural, rheological, and sensory properties. The obtained results revealed that chocolate enriched by whey protein hydrolysate (H-WPC) possesses higher content of total polyphenols (1007.8 ± 96.8 mg GAE/100 g), increased ability to inhibit ABTS radicals (66.30 ± 1.99%), and increased ability to inhibit DPPH radicals (56.34 ± 3.20%), compared to the standard milk chocolate (C) (877.1 ± 56.0 mg GAE/100g; 48.46 ± 2.11%; 48.07 ± 2.80%, respectively). The additional ingredients do not significantly affect the hardness and enthalpy of chocolates. The hydrolyzed whey proteins increase the viscosity of chocolate (11.81 ± 0.11 Pa·s) to a greater extent than non-hydrolyzed whey proteins (9.17 ± 0.09 Pa·s), relative to the control sample (3.53 ± 0.05 Pa·s). Regardless of the fact that the WPC sample has slightly better rheological characteristics and particle size distribution compared to the H-WPC sample, no major changes in the sensory characteristics of chocolate were observed. Based on the results, whey protein hydrolysate can be marked as an exceptional ingredient for improving the quality of chocolate.

Precautionary Allergen Labelling in Serbia: Market Audit and Consumers' Perception.

Background: Precautionary allergen labels (PAL) should be used to indicate the possibility of allergen presence in the food. This study aimed to determine the prevalence and types of precautionary labeling statements on different pre-packaged food products in retail stores in Belgrade, Serbia, as well as to assess consumers' attitudes and behavior towards PAL statements. Methods: This was a descriptive study. The following characteristics of 1404 pre-packaged foods were analyzed: prevalence of PAL, listed food allergens on PAL, and the types of the advisory terminology. In the group of 275 participants (94 with food allergies, and 181 persons who purchasing food for a household member with food allergy) reading practice of PAL, purchasing practice based on PAL, and the opinion about PAL statements credibility were evaluated. Results: Overall, 33.9% of products had precautionary statements for one or more allergens. "Tree nuts" were the most common allergens listed in the PAL. The most common type of PAL was "May contain traces of x [allergen]" (52.7%). The PAL was always read by half of the participants. Less than half (43.3%) of the participants incorrectly believed that PAL is regulated by national law. A quarter of participants thought that the PAL statements are trustworthy. Conclusion: PAL statements frequently are not user-friendly and are not providing sufficient protection for food allergic patients. To gain buyers' confidence, protect health and provide security, the necessity for the strategies that would regulate PAL by the law exists.

Effect of immobilisation materials on viability and fermentation activity of dairy starter culture in whey-based substrate.

BACKGROUND: The main objectives of the paper were to study influence of immobilisation of dairy starter culture 'Lactoferm ABY 6' on fermentation and probiotic potential of fermented whey-based substrate. RESULTS: Fermentation with free cells takes 1.5 h less than fermentation with encapsulated cells, but samples with encapsulated cells have better characteristics after 28 days of storage. Chitosan coating provides additional protection of cells in bile salt solution (95.86% of viable cells compared to the initial number) and simulated gastric juice (37.8% for pH 2.5) compared to the alginate beads (94.54% in bile salt solution and 36.18% in simulated gastric juice for pH 2.5). Free cells had a drastic reduction in the number of viable cells (83.0% in bile salt solution and no viable cells in simulated gastric juice for pH 2.5). CONCLUSION: Samples with alginate beads and chitosan-coated alginate beads have significantly (P < 0.05) higher viable cell count than samples with free cells, during 4 h monitoring survival at pH 2.5, pH 3.0 and 0.3% bovine bile solution. These beads can be used to improve survival of probiotic cells in fermented whey-based beverage during storage and consummation, which improves the quality of the product.

Effect of different fermentation parameters on L-lactic acid production from liquid distillery stillage.

Expansion of lactic acid applications, predominantly for the preparation of biodegradable polymers increased the research interest for new, economically favourable production processes. Liquid stillage from bioethanol production can be an inexpensive, valuable source of nutrients for growth of lactic acid bacteria. Utilisation of residual biomass with spent fermentation media as a functional animal feed can greatly influence the process value and its ecological aspect. In this paper, the kinetics of lactic acid and biomass production on liquid stillage by Lactobacillus rhamnosus ATCC 7469 was studied. In addition, the impact of temperature, inoculum concentration, shaking and pH control by addition of CaCO(3) was evaluated. Maximal lactic acid yield of 73.4%, as well as high biomass production (3×10(8) CFU ml(-1)) were achieved under selected conditions (41°C, 5% (v/v) of inoculum, 1% (w/v) of CaCO(3), initial pH of 6.5 and shaking rate of 90 rpm). These results were achieved without supplementation of the stillage with nitrogen or mineral sources.

ABCB1 and ABCC3 gene polymorphisms are associated with first-year response to methotrexate in juvenile idiopathic arthritis.

OBJECTIVE: Although methotrexate (MTX) is the most widely prescribed drug in juvenile idiopathic arthritis (JIA), 30% of patients fail to respond to it. To individualize treatment strategies, the genetic determinants of response to MTX should be identified. METHODS: A cohort of 287 patients with JIA treated with MTX was studied longitudinally over the first year of treatment. MTX response was defined as the American College of Rheumatology pediatric 70 criteria (ACRped70). We genotyped 21 single-nucleotide polymorphisms in 13 genes related to MTX polyglutamylation and to cellular MTX uptake and efflux. Potential associations between ACRped70 and genotypes were analyzed in a multivariate model and corrected for these 3 covariates: disease duration prior to MTX treatment, physician's global assessment of disease activity at baseline, and MTX dose at all study visits. RESULTS: MTX response was more often achieved by patients variant for the adenosine triphosphate-binding cassette transporter B1 (ABCB1) gene polymorphism rs1045642 (OR 3.80, 95% CI 1.70-8.47, p = 0.001) and patients variant for the ABCC3 gene polymorphism rs4793665 (OR 3.10, 95% CI 1.49-6.41, p = 0.002) than by patients with other genotypes. Patients variant for the solute carrier 19A1 (SLC19A1) gene polymorphism rs1051266 were less likely to respond to MTX (OR 0.25, 95% CI 0.09-0.72, p = 0.011). CONCLUSION: ABCB1 rs1045642, ABCC3 rs4793665, and SLC19A1 rs1051266 polymorphisms were associated with response to MTX in 287 patients with JIA studied longitudinally. Upon validation of our results in other JIA cohorts, these genetic determinants may help to individualize treatment strategies by predicting clinical response to MTX.

Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis.

OBJECTIVES: Methotrexate (MTX) is a cheap and efficacious drug in juvenile idiopathic arthritis (JIA) treatment. If JIA patients are unresponsive to MTX, early and effective combination treatment with biologicals is required to prevent joint damage. The authors developed a prediction model to identify JIA patients not responding to MTX. METHODS: In a cohort of 183 JIA patients, clinical variables and single nucleotide polymorphisms (SNPs) in genes involved in the mechanism of action of MTX were determined at the start of MTX treatment. These variables were used to construct a prediction model for non-response to MTX treatment during the first year of treatment. Non-response to MTX was defined according the American College of Rheumatology paediatric 70 criteria. The prediction model was validated in a cohort of 104 JIA patients. RESULTS: The prediction model included: erythrocyte sedimentation rate and SNPs in genes coding for methionine synthase reductase, multidrug resistance 1 (MDR-1/ABCB1), multidrug resistance protein 1 (MRP-1/ABCC1) and proton-coupled folate transporter (PCFT). The area under the receiver operating characteristics curve (AUC) was 0.72 (95% CI: 0.63 to 0.81). In the validation cohort, the AUC was 0.65 (95% CI: 0.54 to 0.77). The prediction model was transformed into a total risk score (range 0-11). At a cut-off of ≥3, sensitivity was 78%, specificity 49%, positive predictive value was 83% and negative predictive value 41%. CONCLUSIONS: The prediction model that we developed and validated combines clinical and genetic variables to identify JIA patients not responding to MTX treatment. This model could assist clinicians in making individualised treatment decisions.

High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score.

OBJECTIVE: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire. METHODS: The MTX Intolerance Severity Score (MISS) questionnaire was constructed, consisting of 5 domains: stomach ache, nausea, vomiting, sore mouth, and behavioral symptoms. The domains each consisted of 3 questions pertaining to the presence of a symptom upon, prior to (anticipatory), and when thinking of (associative) MTX intake. The MISS questionnaire was validated in 86 patients by determining its discriminative power between patients with and those without MTX intolerance, identified as such by a gold standard (physician's opinion). Using the MISS questionnaire, the prevalence of MTX intolerance was determined in 297 JIA patients. RESULTS: The MISS questionnaire discriminated well between MTX-intolerant and MTX-tolerant patients. A cutoff score of 6 yielded the best sensitivity (88%) and specificity (80%). MTX intolerance was found in 150 (50.5%) of 297 patients. Of 220 patients receiving oral MTX, 98 (44.5%) experienced MTX intolerance, whereas 67.5% of 77 patients receiving parenteral MTX experienced intolerance to the drug (P = 0.001). CONCLUSION: Our findings indicate that the MISS questionnaire is a highly sensitive and specific tool for the diagnosis of MTX intolerance, and that there is a high prevalence of MTX intolerance among JIA patients. The prevalence of intolerance in patients receiving parenteral MTX exceeds that in patients receiving oral MTX. The frequent occurrence of anticipatory and associative symptoms suggests that classic conditioning plays an important role in MTX intolerance.

Is a positive family history predictive for recurrent acute otitis media in children? An evidence-based case report.

In this evidence-based case report, we studied the clinical question: Is a positive family history of acute otitis media (AOM) predictive for recurrent acute otitis media (rAOM) in children between zero and two years of age? The search yielded 3178 articles, of which only two were relevant and had a high validity regarding our clinical question. Neither of these two studies provided the final answer to our clinical question because they did not report stratified absolute risks for a positive family history. Fortunately, we were able to study the absolute risks in one of the two studies. The absolute risk of rAOM without distinguishing family history was 33 percent; the risk was 27 percent for children without a family history and 45 percent for children with a positive family history. Family history increases the absolute risk, but not in a way that it will help to predict rAOM accurately.