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.

Epidemiología del derrame pleural paraneumónico en la infancia durante la implementación de la vacuna antineumocócica conjugada de 13 serotipos / Epidemiology of pediatric parapneumonic pleural effusion during 13-valent pneumococcal conjugate vaccine implementation

Introducción: La incidencia del derrame pleural paraneumónico, incluyendo el empiema, ha sufrido variaciones en las últimas décadas, que se han relacionado con la implantación de distintos tipos de vacuna antineumocócica conjugada. Métodos: Se han revisado retrospectivamente los datos de los 10 hospitales públicos de la provincia de Alicante (España), que abarcan una población de 279.000 niños menores de 15 años, entre 2010 y 2018. Se desglosaron los derrames menores de 10mm (DP−) y los de 10mm o más (DP+). Resultados: Se han analizado 366 episodios de derrame pleural paraneumónico, 178 DP− (48,6%) y 188 DP+ (51,4%), con una mediana de edad de 4 años (rango intercuartílico: 2-7 años) y una evidente estacionalidad con máximo en invierno y mínimo en verano. Se identificó al agente etiológico por cultivo en 34 pacientes (9,3%), destacando Streptococcus pneumoniae (24 pacientes) seguido por Streptococcus pyogenes (7 pacientes). El serotipo de S. pneumoniae más frecuente fue el 19A (6 pacientes) y se han identificado 3 fallos vacunales. La tasa anual media de incidencia fue de 14,3 casos por 100.000 menores de 15 años (7,0 para DP− y 7,3 para DP+), sin cambios significativos a lo largo del tiempo, aunque sí se apreciaron diferencias marcadas de la incidencia entre los distintos departamentos sanitarios. Conclusiones: No hemos encontrado variaciones temporales en la incidencia del derrame paraneumónico pese a la implementación de la vacuna antineumocócica conjugada de 13 serotipos. Es destacable la variabilidad de la incidencia entre departamentos vecinos sin motivo aparente.(AU)

Introduction: The reported incidence of parapneumonic pleural effusion, including empyema, has shown fluctuations in the last decades. It has been related to the implementation of different types of conjugate pneumococcal vaccines. Methods: We have retrospectively reviewed data from all 10 public hospitals in Alicante Province (Spain) covering a population of 279,000 children under 15 years of age, between 2010 and 2018. Effusions less than 10mm (PE−) and those of 10mm or more (PE+) were separated. Results: A total of 366 episodes of parapneumonic pleural effusion have been analyzed, 178 PE− (48.6%) and 188 PE+ (51.4%), with a median age of 4 years (interquartile range: 2-7 years) and marked seasonality with the maximum in winter and the minimum in summer. A culture proven bacterial agent was identified in 34 patients (9.3%), mainly Streptococcus pneumoniae (24 patients) followed by Streptococcus pyogenes (7 patients). The most frequent S. pneumoniae serotype was 19A (6 patients) and 3 vaccine failures were observed. The mean annual incidence rate was 14.3 cases per 100,000 children under 15 years of age (7.0 for PE− and 7.3 for PE+). No significant changes were observed in incidence over time, but noticeable differences in incidence were observed in different health departments. Conclusions: We have not found temporal variations in incidence of parapneumonic effusion despite the implementation of the 13-valent pneumococcal conjugate vaccine. The unexplained disparity in incidence between close departments is noteworthy.(AU)

Epidemiology of pediatric parapneumonic pleural effusion during 13-valent pneumococcal conjugate vaccine implementation.

INTRODUCTION: The reported incidence of parapneumonic pleural effusion, including empyema, has shown fluctuations in the last decades. It has been related to the implementation of different types of conjugate pneumococcal vaccines. METHODS: We have retrospectively reviewed data from all 10 public hospitals in Alicante Province (Spain) covering a population of 279,000 children under 15 years of age, between 2010 and 2018. Effusions less than 10 mm (PE-) and those of 10 mm or more (PE+) were separated. RESULTS: A total of 366 episodes of parapneumonic pleural effusion have been analyzed, 178 PE- (48.6%) and 188 PE+ (51.4%), with a median age of 4 years (interquartile range: 2-7 years) and marked seasonality with the maximum in winter and the minimum in summer. A culture proven bacterial agent was identified in 34 patients (9.3%), mainly Streptococcus pneumoniae (24 patients) followed by Streptococcus pyogenes (7 patients). The most frequent S. pneumoniae serotype was 19A (6 patients) and 3 vaccine failures were observed. The mean annual incidence rate was 14.3 cases per 100,000 children under 15 years of age (7.0 for PE- and 7.3 for PE+). No significant changes were observed in incidence over time, but noticeable differences in incidence were observed in different health departments. CONCLUSIONS: We have not found temporal variations in incidence of parapneumonic effusion despite the implementation of the 13-valent pneumococcal conjugate vaccine. The unexplained disparity in incidence between close departments is noteworthy.

Positive drug provocation with beta-lactam antibiotics in children: A single test may not be enough.

BACKGROUND: Drug provocation tests (DPTs) are considered the gold standard for diagnosing beta-lactam allergy. However, positive results tend to be mild and difficult to interpret. This study aimed to describe pediatric patients with a presumedly positive or inconclusive DPT, assess the decision to repeat the DPT, and describe its outcome. METHODS: Retrospective review of all presumedly positive or inconclusive DPTs performed in six pediatric allergy clinics from 2017 to 2019. We describe the interpretation of results, focusing on the decision to repeat the DPT and its outcome. RESULTS: Of 439 children challenged with a beta-lactam, 26 (5.9%) with a presumedly positive or inconclusive result were included in this study. Most were girls (n = 16, 61.5%), and the median age was 5 years (range 1-13). The initial DPT used amoxicillin (n = 13, 50.0%), amoxicillin-clavulanic acid (n = 12, 46.2%), or cefadroxil (n = 1, 3.8%). Reactions were early (n = 11, 42.3 %), delayed (n = 14, 53.8 %), or not registered (n = 1, 3.8 %), but mild in all cases. A second confirmatory DPT was proposed in 19 patients (73.1%) and performed in 17 patients (65.4%). Nine DPTs were performed from 1 day to 4 months after the first DPT, and the remaining eight took place 6 months to 2 years later. Fifteen children tolerated the drug in the second DPT: 88.2% of those reevaluated and 57.5% of the whole study group. CONCLUSION: The positive predictive value of DPT may be lower than expected. Given the mildness of observed reactions, a second confirmatory DPT is warranted within a few weeks or months.

Positive drug provocation with beta-lactam antibiotics in children: A single test may not be enough

Background: Drug provocation tests (DPTs) are considered the gold standard for diagnosing beta-lactam allergy. However, positive results tend to be mild and difficult to interpret. This study aimed to describe pediatric patients with a presumedly positive or inconclusive DPT, assess the decision to repeat the DPT, and describe its outcome.Methods: Retrospective review of all presumedly positive or inconclusive DPTs performed in six pediatric allergy clinics from 2017 to 2019. We describe the interpretation of results, focusing on the decision to repeat the DPT and its outcome.Results: Of 439 children challenged with a beta-lactam, 26 (5.9%) with a presumedly positive or inconclusive result were included in this study. Most were girls (n = 16, 61.5%), and the median age was 5 years (range 1–13). The initial DPT used amoxicillin (n = 13, 50.0%), amoxicillin-clavulanic acid (n = 12, 46.2%), or cefadroxil (n = 1, 3.8%). Reactions were early (n = 11, 42.3 %), delayed (n = 14, 53.8 %), or not registered (n = 1, 3.8 %), but mild in all cases. A second confirmatory DPT was proposed in 19 patients (73.1%) and performed in 17 patients (65.4%). Nine DPTs were performed from 1 day to 4 months after the first DPT, and the remaining eight took place 6 months to 2 years later. Fifteen children tolerated the drug in the second DPT: 88.2% of those reevaluated and 57.5% of the whole study group.Conclusion: The positive predictive value of DPT may be lower than expected. Given the mildness of observed reactions, a second confirmatory DPT is warranted within a few weeks or months (AU)

Population-Based Cohort of Children With Parapneumonic Effusion and Empyema Managed With Low Rates of Pleural Drainage.

Introduction: The most appropriate treatment for parapneumonic effusion (PPE), including empyema, is controversial. We analyzed the experience of our center and the hospitals in its reference area after adopting a more conservative approach that reduced the use of chest tube pleural drainage (CTPD). Methods: Review of the clinical documentation of all PPE patients in nine hospitals from 2010 to 2018. Results: A total of 318 episodes of PPE were reviewed; 157 had a thickness of <10 mm. The remaining 161 were 10 mm or thicker and were subdivided into three increasing sizes: PE+1, PE+2, and PE+3. There was a strong relationship between the size of the effusion and complicated effusion/empyema, defined by its appearance on imaging studies or by the physical or bacteriological characteristics of the pleural fluid. The size of effusion was also strongly related to the duration of fever and intravenous treatment and was the best independent predictor of the length of hospital stay (LHS) (p < 0.001). CTPD was placed in 2.9% of PE+1 patients, 19.3% of PE+2, and 63.9% of PE+3 (p < 0.001). The referral of patients with PE+1 decreased over time (p = 0.033), as did the use of CTPD in the combined PE+1/PE+2 group (p = 0.018), without affecting LHS (p = 0.814). There were no changes in the use of CTPD in the PE+3 group (p = 0.721). Conclusions: The size of the PPE is strongly correlated with its severity and with LHS. Most patients can be treated with antibiotics alone.

Isotropic/Anisotropic NMR Editing by Resolution-Enhanced NMR Spectroscopy.

Modern resolution-enhanced NMR techniques can monitor the in situ discrimination of co-existing isotropic and anisotropic contributions of small molecules dissolved in weakly aligning PMMA/CDCl3 media. The simultaneous sign-sensitive determination of accurate Δδiso-aniso (1 H), Δδiso-aniso (13 C) and/or isotropic 1 JCH and anisotropic 1 TCH coupling constants (and consequently 1 H-13 C residual dipolar couplings and 1 H/13 C residual chemical shift anisotropies) can be performed from spectral-aliased heteronuclear single-quantum correlation spectra.

2JHH-resolved HSQC: Exclusive determination of geminal proton-proton coupling constants.

The measurement of two-bond proton-proton coupling constants (2JHH) in prochiral CH2 groups from the F2 dimension of 2D spectra is not easy due to the usual presence of complex multiplet J patterns, line broadening effects and strong coupling artifacts. These drawbacks are particularly pronounced and frequent in AB spin systems, as those normally exhibited by the pair of diastereotopic CH2 protons. Here, a novel 2JHH-resolved HSQC experiment for the exclusive and accurate determination of the magnitude of 2JHH from the doublet displayed along the highly-resolved indirect F1 dimension is described. A pragmatic 2JHH NMR profile affords a fast overview of the full range of existing 2JHH values. In addition, a 2JHH/δ(13C)-scaled version proves to be an efficient solution when severe signal overlapping complicate a rigorous analysis. The performance of the method is compared with other current techniques and illustrated by the determination of challenging residual dipolar 2DHH coupling constants of small molecules dissolved in weakly orienting media.

1JCH NMR Profile: Identification of Key Structural Features and Functionalities by Visual Observation and Direct Measurement of One-Bond Proton-Carbon Coupling Constants.

A user-friendly NMR interface for the visual and accurate determination of experimental one-bond proton-carbon coupling constants (1JCH) in small molecules is presented. This intuitive 1JCH profile correlates directly to δ(1H), and 1JCH facilitates the rapid identification and assignment of 1H signals belonging to key structural elements and functional groups. Illustrative examples are provided for some target molecules, including terminal alkynes, strained rings, electronegative substituents, or lone-pair-bearing heteronuclei.

Structural discrimination from in situ measurement of 1 DCH and 2 DHH residual dipolar coupling constants.

A fast residual dipolar coupling constant-assisted strategy involving the simultaneous determination of scalar and total coupling constants from a single 1 JCH /2 JHH -resolved NMR spectrum is reported. It is shown that the concerted use of the directly measured 1 DCH (for all CHn multiplicities) and 2 DHH residual dipolar couplings allows an on-the-fly assignment of diastereotopic CH2 protons, as well as of an efficient discrimination between diastereoisomeric structures of strychnine which contains six stereocenters. Copyright © 2017 John Wiley & Sons, Ltd.

Extending long-range heteronuclear NMR connectivities by HSQMBC-COSY and HSQMBC-TOCSY experiments.

The detection of long-range heteronuclear correlations presenting J(CH) coupling values smaller than 1-2Hz is a challenge in the structural analysis of small molecules and natural products. HSQMBC-COSY and HSQMBC-TOCSY pulse schemes are evaluated as complementary NMR methods to standard HMBC/HSQMBC experiments. Incorporation of an additional J(HH) transfer step in the basic HSQMBC pulse scheme can favor the sensitive observation of traditionally missing or very weak correlations and, in addition, facilitates the detection of a significant number of still longer-range connectivities to both protonated and non-protonated carbons under optimum sensitivity conditions. A comparative (1)H-(13)C study is performed using strychnine as a model compound and several examples are also provided including (1)H-(15)N applications.

Ultra high-resolution HSQC: application to the efficient and accurate measurement of heteronuclear coupling constants.

A rapid NMR data acquisition strategy in terms of enhanced resolution per time unit for the simple and efficient determination of multiple coupling constants is described. The use of (13)C spectral aliasing combined by broadband (1)H homodecoupling allows accurate measurements from ultra high resolved 2D HSQC cross-peaks.

Burden of Severe 2009 Pandemic Influenza A (H1N1) Infection in Children in Southeast Spain

Introduction: Most of the published studies on patients admitted with 2009 pandemic influenza are not population based. We have compiled the clinical information regarding all children admitted with 2009pandemic influenza A (H1N1) infection during the season 2009-2010 in our defined population, in order to have an unbiased view of the most severe side of the clinical spectrum of the infection and to quantify its burden. Methods: Children <15 years-old admitted to any of 3 hospitals in South-East Spain with 2009 pandemic influenza A (H1N1) detected by means of reverse transcriptase polymerase chain reaction. High quality data were extracted from clinical records specially designed for the pandemic. Results: Eighty two children fulfilled the inclusion (..) (AU)

Introducción: Pocos artículos sobre pacientes ingresados por la gripe pandémica de 2009 tienen una perspectiva poblacional. Hemos revisado la información clínica de todos los ninos que han requerido hos- ˜ pitalización por gripe pandémica A (H1N1) 2009 durante la temporada 2009-2010 en nuestra población, para obtener una visión no sesgada de la faceta más grave de esta gripe y cuantificar su impacto. Métodos: Se incluyeron los ninos menores de 15 a ˜ nos ingresados en 3 hospitales del sureste de Espa ˜ na˜ con infección por influenza A (H1N1) 2009 confirmada por reacción en cadena de la polimerasa. Los datos se obtuvieron de registros específicos disenados durante la pandemia. ˜ Resultados: Ochenta y dos ninos cumplieron los criterios de inclusión. La tasa de hospitalización fue de ˜ 68/100.000 ninos <15 a ˜ nos; 131/100.000 en los menores de 5 a ˜ nos y 234/100.000 en menores de 1 a ˜ no. ˜ Se estimó que el 0,7% de los ninos que padecieron la gripe pandémica requirió ingreso (1,7% en menores (..) (AU)

Burden of severe 2009 pandemic influenza A (H1N1) infection in children in Southeast Spain.

INTRODUCTION: Most of the published studies on patients admitted with 2009 pandemic influenza are not population based. We have compiled the clinical information regarding all children admitted with 2009 pandemic influenza A (H1N1) infection during the season 2009-2010 in our defined population, in order to have an unbiased view of the most severe side of the clinical spectrum of the infection and to quantify its burden. METHODS: Children <15 years-old admitted to any of 3 hospitals in South-East Spain with 2009 pandemic influenza A (H1N1) detected by means of reverse transcriptase polymerase chain reaction. High quality data were extracted from clinical records specially designed for the pandemic. RESULTS: Eighty two children fulfilled the inclusion criteria. The hospitalization rate was 68 per 100,000 children <15 years-old; in those <5 years-old the rate was of 131 and in <1 year-old, 234 per 100,000. An estimated 0.7% of the children who suffered from pandemic influenza were admitted (1.7% in <5 years-old). Intensive care was required for 5% of the hospitalized patients living in the study area. Mortality was roughly estimated about 1 per 100,000 children <15 years-old and was associated with the presence of very severe comorbidities or co-infections. Only 20% of the admitted children were ≥ 5 years-old and without risk factors. The disease followed a generally benign course despite the modest use of oseltamivir (49% of the patients). CONCLUSIONS: Clinical and epidemiological data are very similar to those observed in other places and in interpandemic seasons with a high influenza activity.

Calculating the prevalence of atopy in children.

BACKGROUND: Atopy is an important risk factor for asthma, rhinitis, atopic eczema and urticaria. For this reason, several studies have been done to determine the prevalence of atopy in the paediatric population. The important differences among these studies do not allow the extrapolating of results. In this study, we calculate the prevalence of atopy and atopy-related diseases in a paediatric population using a different methodology. METHODS: Retrospective study among children referred for drug allergy in which the latter was discarded. We evaluated the prevalence of atopy (measured by allergen sensitisation), asthma, rhinitis, urticaria, atopic eczema and their characteristics. RESULTS: Three hundred and forty-two patients were studied for adverse drug reaction. This was discarded in 325/342 patients. 20 % of the children in the sample were atopic. Atopy prevalence increased with age. Some atopy related disease was observed in 83/325 (25.5 %) children. Among these children allergen sensitisation increased from 42.3 % in the 0-3 years age group to 93.3 % in the 7-14 age group (p < 0.0001). Prevalence of asthma was 11.5 %, 10.2 % and 7 % in the 0-3, 4-6 and 7-14 age groups, respectively. Prevalence of rhinoconjunctivitis increased through age groups with a prevalence of 20 % among the 7 to 14-year old children. CONCLUSION: The use of this type of methodology seems to be correct to estimate the prevalence of atopy. Prevalence of allergen sensitisation is very high among 7 to 14-year old children with asthma and/or rhinoconjunctivitis.

Calculating the prevalence of atopy in children

Background: Atopy is an important risk factor for asthma, rhinitis, atopic eczema and urticaria. For this reason, several studies have been done to determine the prevalence of atopy in the paediatric population. The important differences among these studies do not allow the extrapolating of results. In this study, we calculate the prevalence of atopy and atopy-related diseases in a paediatric population using a different methodology. Methods: Retrospective study among children referred for drug allergy in which the latter was discarded. We evaluated the prevalence of atopy (measured by allergen sensitisation), asthma, rhinitis, urticaria, atopic eczema and their characteristics. Results: Three hundred and forty-two patients were studied for adverse drug reaction. This was discarded in 325/342 patients. 20 % of the children in the sample were atopic. Atopy prevalence increased with age. Some atopy related disease was observed in 83/325 (25.5 %) children. Among these children allergen sensitisation increased from 42.3 % in the 0-3 years age group to 93.3 % in the 7-14 age group (p < 0.0001). Prevalence of asthma was 11.5 %, 10.2 % and 7 % in the 0-3,4-6 and 7-14 age groups, respectively. Prevalence of rhinoconjunctivitis increased through age groups with a prevalence of 20 % among the 7 to 14-year old children. Conclusion: The use of this type of methodology seems to be correct to estimate the prevalence of atopy. Prevalence of allergen sensitisation is very high among 7 to 14-year old children with asthma and/or rhinoconjunctivitis (AU)

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