Direct oral challenge for immediate and non-immediate beta-lactam allergy in children: A real-world multicenter study.

BACKGROUND: Allergy to beta-lactam antibiotics (BLA) is frequently suspected in children, but a drug provocation test (DPT) rules it out in over 90% of cases. Direct oral DPT (DODPT), without skin or other previous tests, is increasingly been used to delabel non-immediate BLA reactions. This real-world study aimed to assess the safety and effectiveness of DODPT in children with immediate and non-immediate reactions to BLAs. METHODS: Ambispective registry study in children (<15 years), attended between 2016 and 2023 for suspected BLA allergy in 15 hospitals in Spain that routinely perform DODPT. RESULTS: The study included 2133 patients with generally mild reactions (anaphylaxis 0.7%). Drug provocation test with the implicated BLA was performed in 2014 patients (94.4%): 1854 underwent DODPT (86.9%, including 172 patients with immediate reactions). One hundred forty-five (7.2%) had symptoms associated with DPT, although only four reactions were severe: two episodes of anaphylaxis and two of drug-induced enterocolitis syndrome, which resolved rapidly with treatment. Of the 141 patients with mild reactions in the first DPT, a second DPT was considered in 87 and performed in 57, with 52 tolerating it without symptoms. Finally, BLA allergy was ruled out in 90.9% of the sample, confirmed in 3.4%, and remained unverified, usually due to loss to follow-up, in 5.8%. CONCLUSIONS: Direct oral DPT is a safe, effective procedure even in immediate mild reactions to BLA. Many reactions observed in DPT are doubtful and require confirmation. Severe reactions are exceptional and amenable to treatment. Direct oral DPT can be considered for BLA allergy delabeling in pediatric primary care.

A Comparative Study between Swedish Interactive Thresholding Algorithm Faster and Swedish Interactive Thresholding Algorithm Standard in Glaucoma Patients.

PURPOSE: To compare the results of the new strategy Swedish Interactive Thresholding Algorithm (SITA) Faster to the results of SITA Standard in patients with glaucoma. METHODS: This was a cross-sectional study of 49 patients with glaucoma and previous experience with standard automated perimetry. Two consecutive tests were performed in random order, one with SITA Standard and another one with SITA Faster, in the studied eye of each patient. Comparisons were made for test time, mean deviation (MD), visual field index (VFI), and number of depressed points in pattern deviation map and total deviation map for every level of significance. RESULTS: The average test time was 56% shorter with SITA Faster (P < 0.001). The intraclass correlation coefficient (ICC) for MD and VFI showed excellent agreement between both strategies, ICC = 0.98 (95% confidence interval [CI]: 0.96, 0.99) and ICC = 0.97 (95% CI: 0.95, 0.99), respectively. For the number of depressed points in total deviation map and pattern deviation map, ICC demonstrated good agreement with values between 0.8 and 0.95. CONCLUSIONS: Our study shows that SITA Faster is a shorter test with strong agreement with SITA Standard parameters. These results suggest that SITA Faster could replace SITA Standard for glaucoma diagnosis.

Egg oral immunotherapy in children (SEICAP I): Daily or weekly desensitization pattern.

BACKGROUND: Studies are required before incorporating egg oral immunotherapy (OIT) into clinical practice. The Spanish Society of Pediatric Allergy, Asthma and Clinical Immunology (SEICAP) conducted a multicenter, randomized controlled study assessing the effectiveness and safety of the OIT using pasteurized egg white (PEW) in egg-allergic children. METHODS: One hundred and one egg-allergic children (6-9 years) were randomized for 1 year: 25 to an egg-free-diet (CG) and 76 to OIT (target dose 3.3 g PEW proteins), PI (30% weekly plus 5% daily increments) or PII (only 30% weekly increments) buildup patterns. Egg skin prick test, sIgE and sIgG4 serum levels, PEW double-blind placebo-controlled food challenge (DBPCFC), and dosing adverse reactions (DARs) were evaluated in all patients from inclusion (T0) until completing 1 year of follow-up (T12). At T12, egg-allergic control patients could start OIT. The effectiveness and safety of OIT and the effect of the buildup pattern were analyzed. RESULTS: At T12, 4/25 (16.0%) CG patients passed the PEW DBPCFC vs 64/76 (84.2%) OIT that reached total desensitization (P = 0.000); 12 egg-allergic control patients started OIT. Finally, 72/88 (81.81%) patients reached total desensitization, 96.15% PI vs 75.80% on PII (P = 0.01). Induction period (121.12 ± 91.43, median 98.00 days) was longer in patients on PII buildup pattern, and those with allergic asthma, minor threshold dose, or higher egg sIgE (P < 0.05). Most patients (89.06%) developed DARs: 74.53% were mild; 21.90% moderate; and 3.5% requiring adrenaline-treatment. Moderate reactions and those requiring adrenaline were more frequent in patients with allergic asthma, PII pattern, or higher egg sIgE serum antibody levels (P < 0.05). CONCLUSIONS: PEW OIT is an effective treatment for children with persistent egg allergy. A 30% weekly plus 5% daily increment pattern could be more effective and safer than one with only 30% weekly increments.

Egg OIT in clinical practice (SEICAP II): Maintenance patterns and desensitization state after normalizing the diet.

BACKGROUND: It is unknown which are the most suitable maintenance pattern and egg consumption to maintain the desensitization state after ending the oral immunotherapy (OIT). This multicenter, randomized, controlled trial compared two OIT maintenance patterns with pasteurized egg white (PEW), evaluating the egg consumption effect on the desensitization state after ending the OIT. METHODS: One hundred and one children with confirmed egg allergy were randomized: 25 to an egg-free diet (CG) and 76 to an OIT year with PEW and two maintenance patterns, 38 patients to daily 3.3 g proteins (AG) and 38 to every two days (BG). PEW challenge (DBPCFC), adverse reactions, and immune markers were assessed at baseline, at the end of the OIT, and at 6 and 12 months later on ad libitum egg consumption (T0, T12, T18, and T24). A questionnaire evaluated the egg consumption at T18. RESULTS: At T12, 64 of 76 (84.21%) OIT patients had reached total desensitization (32 AG and 32 BG) vs 4 of 25 (16.00%) CG who passed the PEW DBPCFC. Thirty (93.75%) AG vs 25 (78.12%) BG patients completed an OIT year. At T18, 27 of 29 (93.1%) AG vs 20 of 24 (83.3%) BG passed the PEW DBPCFC, 96% consuming at least two egg servings/week. At T24, 97.43% OIT patients passed the challenge. Most patients had adverse reactions, more frequent in the BG patients; frequency and severity of reactions decreased through the study. PEW skin prick test wheal and sIgE antibody serum levels similarly decreased in AG or BG, but AG patients had greater increase in PEW sIgG4 (P < 0.05). CONCLUSIONS: Daily OIT maintenance achieves better adherence, effectiveness, and safety. Two egg servings/week ensure maintained desensitization after the end of an OIT year.

[The Catalan Patient Council: the direct voice of the patient in health policies in Catalonia]. / El Consejo Consultivo de Pacientes de Cataluña: la voz directa del paciente en las políticas de salud en Cataluña.

The transition from a more paternalistic model of care focused on the disease and on the medical professional's authority towards a more participatory model centered on the rights and duties of informed patients represents a significant change in public health policy. One of the most widespread methods of social participation in Catalonia today is the tendency to form associations around a particular disease. This kind of organizational participation is a pioneering tool in the debate around public health policy. The Government of the Generalitat de Catalunya undertook to promote the Strategic Plan of patient participation within the public health system. The Department of Health created the Patient Advisory Council of Catalonia (CCPC, as per the acronym in Catalan). This initiative constitutes a permanent consultative and participatory body for patient representatives in the Catalan healthcare system. The CCPC was set up with a solid determination to place the patient at the centre of the healthcare system, including them in the decision-making processes which directly affect them. This patient participation plan has defined and developed 8 different lines approved by the government, with consensus approval between regional government and the organisations. The CCPC has proven itself to be an effective tool for fostering active patient participation in health policy and its relationship with the system has evolved from that of a monologue to becoming the mechanism for dialogue it is today.

Stereoisomeric profiling of drugs of abuse and pharmaceuticals in wastewaters of Valencia (Spain).

The enantiomeric and diastereomeric profiling of chiral pharmaceuticals (ephedrine, norephedrine, atenolol and venlafaxine) and illicit drugs (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)) was undertaken over a period of fourteen consecutive days in three wastewater treatment plants (WWTPs) in the city of Valencia, Spain. Degradation efficiency of WWTPs was found to be compound and enantiomer dependent. Selective enantiomer enrichment was observed for several target analytes. Amphetamine and MDMA were enriched with R(-)-enantiomers. 1S,2S(+)-pseudoephedrine was found to be more readily degradable during activated sludge treatment than its diastereomer 1R,2S(-)-ephedrine. Atenolol underwent enrichment with either S(-)- or R(+)-enantiomer in different WWTPs. This unexpected enantiomeric variation in the stereoselective degradation of atenolol could be attributed to different processes utilized during activated sludge treatment. The application of (enantiomeric) profiling of wastewater revealed usage patterns of chiral drugs in the Valencia region.

Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry to identify contaminants in water: an insight on environmental forensics.

Ultra-high pressure liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QqTOF-MS) acquiring full scan MS data for quantification, and automatic data dependent information product ion spectra (IDA-MS/MS) without any predefinition of the ions by the user was checked for identifying organic contaminants in water samples. The use of a database with more than 2000 compounds achieved high confidence results for a wide number of contaminants based upon retention time, accurate mass, isotopic pattern and MS/MS library searching. More than 20 contaminants, mostly pharmaceuticals, but also mycotoxins and polyphenols were unambiguously identified. Furthermore, the combination of statistical data analysis using principal component analysis (PCA) followed by empirical formula calculation, on-line database searching and MS/MS fragment ion interpretation achieves not only the successful detection of unknown contaminants but also the selection of those relevant to different types of waters. Unknown compounds, such as C20H34O3, were identified in waste water showing the prospects of this technique. A group of 42 currently used pesticides were selected as target compounds to evaluate the quantitative possibilities. Mean recoveries and percentage relative standard deviation (RSD) were 48-79% (4-20% RSD). The limit of detections ranged from 0.02 to 2 ng L(-1), with a validated limit of quantification of 2 ng L(-1) for water after solid-phase (SPE) isolation and concentration. The quantitative data obtained using UHPLC-QqTOF-MS were compared with those obtained using conventional LC-MS/MS with a triple quadrupole (QqQ).

Occurrence and removal efficiency of pesticides in sewage treatment plants of four Mediterranean River Basins.

Removal of contaminants in the sewage treatment plants (STPs) can be incomplete causing their release to the environment. In this paper, the results of an extensive survey on more than 40 pesticides carried out in 2010 and 2011 in 16 STPs of Ebro, Guadalquivir, Jucar and Llobregat Rivers (Spain) are presented. In 2010, of 43 analytes screened, 29 were detected in influent and 28 in effluent samples, meanwhile in 2011, of 50 analytes, 33 and 34 were detected, respectively. Pesticides were in the range of 0.33 ng L(-1) (terbumeton, 2011)-2526.05 ng L(-1) (diuron, 2010) for influent and 0.25 ng L(-1) (terbumeton, 2011)-2821.12 ng L(-1) (carbendazim, 2011) for effluent. Regarding the sludge samples, 11 pesticides were detected in 2010 and 24 in 2011 at concentrations up to 25667.34 ng g(-1) dry weight (dw). Removal efficiencies showed that, in 2010, the elimination ranged from -810% (chlorfenvinphos) to 93% (dimethoate), and in 2011, from -4575% (diazinon) to 97% (chlorfenvinphos). All these data confirm that most of the pesticides are only partially eliminated during the secondary and even tertiary treatments, commonly used in STPs, suggesting that they can be a focal point of contamination to the rivers.

Screening of currently used pesticides in water, sediments and biota of the Guadalquivir River Basin (Spain).

The occurrence of 50 currently used pesticides and their transformation products in surface and waste waters, sediment and fish in the Guadalquivir River Basin was determined in 2010 and 2011. After selective sample extraction, pesticides were identified and quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The contamination profile in water and sediments is marked by the presence of organophosphorus and triazines. Transformation products were even at higher concentrations than parent pesticides. A wider range of pesticides was present in water than in sediments but none of them were detected in fish. The mean concentrations ranged from 0.2 to 13.0 ng/L in water and from 0.1 to 13.2 ng/g d.w. in sediment. The spatial distribution of most pesticides was consistent with the agricultural activities of the area or their urban applications. The waste water treatment plant effluents that impact the river are minor sources for few pesticides but for most of them run-off would be the most important contribution. The temporal distribution showed differences between both sampling campaigns related to the river flow. The low-flow produced a pesticide concentration effect, generating higher levels in water and accumulation in sediments. This forecasts a hazard in future scenarios if the current situation of the climate change and water scarcity evolves to more critical conditions highlighting the need of these monitoring studies.

Risk assessment on the presence of pharmaceuticals in sediments, soils and waters of the Pego-Oliva Marshlands (Valencia, eastern Spain).

This study is focused on the occurrence of 17 pharmaceuticals in waters (34 samples), sediments (16 samples) and soils (23 samples, at two different depths) in a typical Mediterranean coastal wetland (Pego-Oliva marsh, Spain). Soil and sediment samples were extracted by pressurized liquid extraction (PLE). Aqueous extracts from PLE and water samples were concentrated by solid-phase extraction (SPE) and determined by liquid-chromatography tandem mass spectrometry (LC-MS/MS). Pharmaceuticals were detected in concentrations up to 112 ng/L in water samples, up to 15.1 ng/g sediments and up to 8.4 ng/g in soil. In surface waters, ibuprofen and codeine were the compounds more frequently detected (up to 59 ng/L and 63 ng/L, respectively). Ground and tap water samples analyzed were also contaminated with pharmaceuticals. The 94% of sediments and the 80% of agricultural soils were polluted (mostly by carbamazepine and acetaminophen). Diffusion of codeine and fluoroquinolones to deeper soil horizons was observed. Possible relationships between variables were established by Pearson correlations and principal components analysis (PCA). An environmental risk assessment based on the available long-term data was performed. Results showed actual risk for the lowest trophic level, and for fishes, due to the presence of fluoroquinolones and ibuprofen. Nevertheless, the presence of pharmaceuticals in the environment is not limited only to an ecological problem since contamination also affects drinking water, being a potential risk to human health.

Development of an improved method for trace analysis of quinolones in eggs of laying hens and wildlife species using molecularly imprinted polymers.

A sensitive, selective, and efficient method was developed for simultaneous determination of 11 fluoroquinolones (FQs), ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, flumequine, marbofloxacin, norfloxacin, ofloxacin, oxolinic acid, pipemidic acid, and sarafloxacin, in eggs by molecularly imprinted polymer (MIP) and column liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Samples were diluted with 50 mM sodium dihydrogen phosphate at pH 7.4, followed by purification with a commercial MIP (SupelMIP SPE-Fluoroquinolones). Recoveries for the 11 quinolones were in the range of 90-106% with intra- and interday relative standard deviation ranging from 1 to 6% and from 3 to 8%, respectively. Limits of detection (LODs) were 0.12-0.85 ng/g, and limits of quantification (LOQs) were 0.36 and 2.59 ng/g, whereas the decision limit (CC(α)) and detection capability (CC(ß)) ranged from 0.46 to 3.35 ng/g and from 0.59 to 4.12 ng/g, respectively. The calculated relevant validation parameters are in an acceptable range and in compliance with the requirements of Commission Decision 2002/657/EC. Moreover, a comparison to two other sample treatments [solid-phase extraction (SPE) and solvent extraction] has been carried out. The method was applied to lying hens, Japanese quail, and black-headed gull eggs, in which FQs were not found. The method was also applied to study the depletion of sarafloxacin in eggs.

Spatial distribution of illicit drugs in surface waters of the natural park of Pego-Oliva Marsh (Valencia, Spain).

BACKGROUND, AIM AND SCOPE: The Pego-Oliva Marsh is the second most important wetland in the Valencian Community (Spain). It is included in the RAMSAR agreement and represents one key point for migratory birds. Emerging contaminants from the human pressure, such as pharmaceuticals, illicit drugs and personal care product, are not included in the list of priority contaminants of the Water Framework Directive yet, and are neither monitored nor controlled. However, pollution of emerging contaminants can threaten the environment and even human health. In order to understand the status of the emerging contamination and recommend future rationalization of countermeasures, the occurrence of illicit drugs was investigated. MATERIAL AND METHODS: Samples were collected at 23 sites from the main irrigation channels and the marsh. Illicit drugs were extracted using solid phase extraction and determined by liquid chromatography tandem mass spectrometry. The method detection limits ranged from 0.01 to 1.54 ng l(-1) and the recoveries from 57% to 120%. RESULTS AND DISCUSSION: 3,4-Methylenedioxymethamphetamine, ketamine, morphine, benzoylecgonine, cocaine, methadone, 6-acetylmorphine and nor-9-carboxy-tetrahydrocannabinol were detected. The mean concentrations were 0.62, 21.33, 1.30, 1.92, 2.25, 0.32, 0.04 and 0.07 ng l(-1), respectively. The highest concentrations were in the north of Pego-Oliva Marsh. CONCLUSIONS: The pollution status by illicit drugs of the Pego-Oliva Marsh has been established. However, contamination levels in all the area of the natural park were low compared with those reported in other superficial waters.

Occurrence of perfluorinated compounds in water and sediment of L'Albufera Natural Park (València, Spain).

PURPOSE: Perfluorinated compounds (PFCs) are widely distributed from industrialized to remote locations throughout the world. This study demonstrates the spatial distributions of PFCs in water and sediments from the L'Albufera Natural Park (Valencia, Spain). METHODS: Grab water and sediment samples were collected. PFCs were extracted from sediments with acidified acetonitrile by ultrasonication and cleaned up by solid-phase extraction (SPE) and from water by SPE. Determination was carried out by liquid chromatography-tandem mass spectrometry. RESULTS: In 100% of the samples (both water and sediments), perfluorooctane sulfonate (PFOS) and perfluoroctanoic acid (PFOA) were the predominant PFCs. Among the 12 sampling sites, PFOS concentrations in sediments ranged from 0.10 to 4.80 ng/g dry weight and in water from 0.94 to 58.1 ng/L. PFOA concentrations in sediment were from 0.004 to 1.24 ng/g and in water from 0.99 to 120 ng/L. Other perfluorocarboxylic acids (C5, C6, C7, C9, and C10) and perfluorosulfonates (C4 and C10) were also identified in several locations. The sum of all 10 compounds (ΣPFCs) concentration range from 0.99 to 120 ng/L in water and from 0.25 to 17.4 ng/g in sediments. Sediment-water distribution coefficients (log K (D)) were in the range 2.31-4.51 and positively correlated with perfluoroalkyl chain length. CONCLUSIONS: PFC concentrations in water and sediment were both less than those able to cause acute toxicity; low but detectable PFCs pollution in the L'Albufera Natural Park in Valencia was demonstrated. These compounds are bioaccumulative; thus, the risk associated with these exposures requires a deeper evaluation of long-term chronic toxicity.

Comparison of the effectiveness of recent extraction procedures for antibiotic residues in bovine muscle tissues.

Acetonitrile extraction followed by primary-secondary amine dispersive SPE cleanup QuEChERS (quick, easy, cheap, effective, rugged, and safe), was compared to pressurized liquid extraction (PLE) using water at 70 degrees C for 10 min at 1500 psi for the determination of 16 veterinary drugs in bovine muscle tissues by LC/MS/MS. PLE was significantly more effective for the extraction of veterinary drugs (ranging from 69 to 103% with RSD < or = 18%) than QuEChERS (ranging from 19 to 89% with RSD < or = 19%). Linearity of the calibration curves was obtained over the range considered from 10 microg/kg or LOQ to 1000, microg/kg) with r2 > or = 0.99 for all the analytes by both methods. Although an internal standard was used, matrix effects were corrected using matrix- matched standards. LODs were from 5 to 30 microg/kg for PLE and from 10 to 100 microg/kg for QuEChERS. To establish and assess the most efficient conditions for each extraction method, statistical parametric and nonparametric tests were used. PLE with water almost eliminates the use or generation of hazardous wastes. The two methods were applied successfully in a routine analysis during surveys in 2008.

Assessment of the occurrence and distribution of pharmaceuticals in a Mediterranean wetland (L'Albufera, Valencia, Spain) by LC-MS/MS.

The distribution of 17 pharmaceuticals between water and the solid phase (sediments and soils) was studied by utilizing solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two extraction procedures for soils and sediments, prior to the SPE, one based on pressurized liquid extraction (PLE) with hot water and the other on methanol/water ultrasonic extraction, were compared. Absolute recoveries were 71.2-99.3% [relative standard deviation (RSD) <21.4%)] for water, and the method detection limits (MDLs) ranged from 0.3 to 10 ng L(-1). Recoveries were 35.4-105.3% (RSDs <19.1%) and 42.1-97.8% (RSDs <14%) for soil and sediment samples, respectively, using PLE and 20.2-86.5% (RSDs <25.1%) and 30.3-97.4% (RSDs <19.1%) using ultrasonic extraction. Fifteen of the 17 pharmaceuticals were present in the L'Albufera water at concentrations up to 17 µg L(-1). Oxytetracycline and tetracycline were not detected. In sediments, only tetracycline, norfloxacin and diclofenac were not found. The other studied pharmaceuticals were present in the range from less than the method quantification limit (MQL) to 35.83 ng g(-1). Among the 17 target compounds, ofloxacin, ciprofloxacin, norfloxacin, trimethoprim, clofibric acid and diclofenac were not detected in soil samples. The average concentrations ranged from less than the MQL for ibuprofen to 34.91 ng g(-1) for tetracycline. These results indicate that pharmaceuticals could survive the wastewater treatment processes, which could lead to their dissemination in water environments.

Analysis of insecticides in honey by liquid chromatography-ion trap-mass spectrometry: comparison of different extraction procedures.

The feasibility of different extraction procedures was tested and compared for the determination of 12 organophosphorus and carbamates insecticides in honey samples. In this sense, once the samples were pre-treated - essentially dissolved in hot water by stirring - and before they could be analyzed by liquid chromatography-ion trap-second stage mass spectrometry (LC-MS(2)), four different approaches were studied for the extraction step: QuEChERS, solid-phase extraction (SPE), pressurized liquid extraction (PLE) and solid-phase microextraction (SPME). The main aim of this work was to maximise the sensitivity of pesticides and to minimise the presence of interfering compounds in the extract. All pesticides were linear in the range from CC(ß) to 1000× CC(ß) for the four extraction methods (three orders of magnitude). Detection capabilities (CC(ß)) were 0.024-1.155 mg kg(-1) with QuEChERS, 0.010-0.646 mg kg(-1) with SPE, 0.007-0.595 mg kg(-1) with PLE, and 0.001-0.060 mg kg(-1) with SPME. All the target compounds could be recovered by any of the methods, at a CC(ß) fortification level ranged from 28 to 90% for the SPME. In comparison, the PLE method was the most efficient extraction method with recoveries from 82 to 104%. It was followed by the QuEChERS method with recoveries between 78 and 101% and the SPE method with recoveries between 72 and 100%. The repeatability expressed as relative standard deviation (RSDs) was below 20% for all the pesticides by any of the tested extraction methods. Results obtained applying the four extraction techniques to real honey samples are analogous.