Amoxicillin is the most common antibiotic prescribed in children with increasing use over time. While up to 10% of children are labelled as amoxicillin allergic, most children can tolerate ...amoxicillin after allergy evaluation. It is well documented that the label of amoxicillin allergy in children is associated with adverse health outcomes such as antibiotic‐resistant infections. However, it remains controversial how best to assess children for amoxicillin allergy. While in general it is recommended that skin testing be done prior to drug provocation test in the evaluation of amoxicillin allergy, there is increasing evidence that drug provocation testing could be done in lower risk children without skin testing prior. The goal of this article as a narrative review is to review the strengths and limitations of skin testing prior to drug provocation test in children who have a history of either immediate or non‐immediate, reactions to amoxicillin.
Background
Chronic spontaneous urticaria (CSU), a long‐lasting disease in children, impacts their quality of life. We report the results of a phase 2b dose‐finding trial of ligelizumab (NCT03437278) ...and a high‐affinity humanized monoclonal anti‐IgE antibody, in adolescents with CSU, supported by modeling and simulation analyses, mitigating challenges in pediatric drug development.
Methods
This multicenter, double‐blind, placebo‐controlled trial, randomized H1‐antihistamine‐refractory adolescent CSU patients (12–18 years) 2:1:1 to ligelizumab 24 mg, 120 mg, or placebo every 4 weeks for 24 weeks. Patients on placebo transitioned to ligelizumab 120 mg at week 12. Integrating data from the previous adult and present adolescent trial of ligelizumab, a nonlinear mixed‐effects modeling described the longitudinal changes in ligelizumab pharmacokinetics, and its effect on weekly Urticaria Activity Score (UAS7).
Results
Baseline UAS7 (mean ± SD) was 30.5 ± 7.3 (n = 24), 29.3 ± 7.7 (n = 13), and 32.5 ± 9.0 (n = 12) for patients (median age, 15 years) on ligelizumab 24 mg, 120 mg, and placebo, respectively. Change from baseline in UAS7 at week 12 with ligelizumab 24 mg, 120 mg, and placebo was −15.7 ± 10.9, −18.4 ± 12.3, and −13.0 ± 13.0, respectively. Ligelizumab was well‐tolerated. The modeling analysis showed that body weight, but not age, affected ligelizumab's apparent clearance. No significant differences between adolescents and adults were detected on the model‐estimated maximum effect and potency.
Conclusions
Ligelizumab exhibited efficacy and safety in adolescent CSU patients, consistent with that in adults. The PK and potency of ligelizumab were not impacted by age, and the same dose of ligelizumab can be used for treating adolescents and adults with CSU. Our study shows how modeling and simulation can complement pediatric drug development.
Background
Children are often diagnosed with an antibiotic allergy, with little investigation to confirm whether it is a true allergy. Recent studies support the use of oral challenges to confirm ...antibiotic allergy. Yet, little is known about families' perceptions of these challenges, or experiences of living with a misdiagnosis, often for many years.
Objective
To describe how families with a child previously labelled as “antibiotic allergic,” but who has subsequently been delabelled, perceive the experience of misdiagnosis and subsequent delabelling.
Methods
We performed semi‐structured interviews with parents whose children had recently completed a graded oral challenge for antibiotic allergy. Interview transcripts were analysed concurrently, but independently, by two investigators, using content analysis.
Results
A total of 15 parents (14 individual interviews; 1 mother‐father dyad) participated. Children were, on average, 5.04 ± 4.5 years and were first diagnosed in infancy (mean age: 1.82 ± 1.48 years) subsequent to a rash (14/14; 100%), and commonly at a walk‐in clinic (6/14; 42.9%). We identified four themes: (1) A red, raised rash results in a quick diagnosis despite a lack of testing, (2) sensitive care allays concerns, (3) delabelling brings relief, but also mystery and calls for proper diagnoses, and (4) quick diagnoses are reckless, but manageable through downward comparisons.
Conclusion and Clinical Relevance
These findings underscore the importance of a careful physical examination and clinical history of the patient, but also an ongoing dialogue to support families, both of which would ideally begin at the time of initial investigation.
SARS-CoV-2 has caused a worldwide pandemic that began with an outbreak of pneumonia cases in the Hubei province of China. Knowledge of those most at risk is integral for treatment, guideline ...implementation, and resource allocation. We conducted a systematic review and meta-analysis to evaluate comorbidities associated with severe and fatal cases of COVID-19. A search was conducted on PubMed and EmBase on 20 April 2020. Pooled estimates were collected using a random-effects model. Thirty-three studies were included in the systematic review and twenty-two in the meta-analysis. Of the total cases 40.80% (95%CI: 35.49%, 46.11%) had comorbidities, while fatal cases had 74.37% (95%CI: 55.78%, 86.97%). Hypertension was more prevalent in severe 47.65% (95%CI: 35.04%, 60.26%) and fatal 47.90% (95%CI: 40.33%, 55.48%) cases compared to total cases 14.34% (95%CI: 6.60%, 28.42%). Diabetes was more prevalent among fatal cases 24.89% (95%CI: 18.80%, 32.16%) compared to total cases 9.65% (95%CI: 6.83%, 13.48%). Respiratory diseases had a higher prevalence in fatal cases 10.89% (95%CI: 7.57%, 15.43%) in comparison to total cases 3.65% (95%CI: 2.16%, 6.1%). Studies assessing the mechanisms accounting for the associations between severe cases and hypertension, diabetes, and respiratory diseases are crucial in understanding this new disease, managing patients at risk, and developing policies and guidelines that will reduce future risk of severe COVID-19 disease.
Oral immunotherapy for milk allergy Yeung, Joanne P; Kloda, Lorie A; McDevitt, Jason ...
Cochrane database of systematic reviews,
11/2012, Volume:
2012, Issue:
11
Journal Article
Peer reviewed
Open access
Background
The mainstay of treatment of IgE‐mediated cow milk allergy (IMCMA) is an avoidance diet, which is especially difficult with a ubiquitous food like milk. Milk oral immunotherapy (MOIT) may ...be an alternative treatment, through desensitization or induction of tolerance.
Objectives
We aim to assess the clinical efficacy and safety of MOIT in children and adults with IMCMA as compared to a placebo treatment or avoidance strategy.
Search methods
We searched 13 databases for journal articles, conference proceedings, theses and unpublished trials, without language or date restrictions, using a combination of subject headings and text words. The search is up‐to‐date as of October 1, 2012.
Selection criteria
Only randomised controlled trials (RCT) were considered for inclusion. Blinded and open trial designs were included. Children and adults with IMCMA were included. MOIT administered by any protocol were included.
Data collection and analysis
A total of 2111 unique records were identified and screened for potential inclusion. Studies were selected, data extracted and methodological quality assessed independently by two reviewers. We attempted to contact the study investigators to inquire about data not published that was required for the analysis. Statistical heterogeneity was assessed using the I² test. We estimated a pooled risk ratio (RR) for each outcome using a Mantel‐Haenzel fixed‐effect model if statistical heterogeneity was low as evaluated by an I² value less than 50%.
Main results
Of 157 records reviewed, 16 were included, representing five trials. In general, the studies were small and had inconsistent methodological rigor. Overall, the quality of evidence was rated as low. Each study used a different MOIT protocol. A total of 196 patients were studied (106 MOIT, 90 control) and all were children. Three studies were blinded and two used an avoidance diet control. Sixty‐six patients (62%) in the MOIT group were able to tolerate a full serving of milk (about 200 mL) compared to seven (8%) of the control group (RR 6.61, 95% CI 3.51 to 12.44). In addition, 27 (25%) in the MOIT group could ingest a partial serving of milk (10 to 184 mL) while none could in the control group (RR 9.34, 95% CI 2.72 to 32.09). None of the studies assessed the patients following a period off immunotherapy. Adverse reactions were common (97 of 106 MOIT patients had at least one symptom), although most were local and mild. Because of variability in reporting methods, adverse effects could not be combined quantitatively. For every 11 patients receiving MOIT, one required intramuscular epinephrine. One patient required it on two occasions.
Authors' conclusions
Studies to date have involved small numbers of patients and the quality of evidence is generally low. The current evidence shows that MOIT can lead to desensitization in the majority of individuals with IMCMA although the development of long‐term tolerance has not been established. A major drawback of MOIT is the frequency of adverse effects, although most are mild and self‐limited. The use of parenteral epinephrine is not infrequent. Because there are no standardized protocols, guidelines would be required prior to incorporating desensitization into clinical practice.
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