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1.
N Engl J Med ; 388(19): 1755-1766, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37163622

RESUMO

BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).


Assuntos
Anafilaxia , Dessensibilização Imunológica , Hipersensibilidade a Amendoim , Pré-Escolar , Humanos , Lactente , Alérgenos/efeitos adversos , Anafilaxia/etiologia , Arachis/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Amendoim/complicações , Hipersensibilidade a Amendoim/terapia , Administração Cutânea
2.
J Allergy Clin Immunol ; 153(6): 1621-1633, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38597862

RESUMO

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.


Assuntos
Consenso , Técnica Delphi , Dessensibilização Imunológica , Hipersensibilidade Alimentar , Consentimento Livre e Esclarecido , Humanos , Dessensibilização Imunológica/métodos , Administração Oral , Hipersensibilidade Alimentar/terapia , Hipersensibilidade Alimentar/imunologia
3.
J Infect Dis ; 229(3): 763-774, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38035854

RESUMO

BACKGROUND: Chronic inflammation persists in some people living with human immunodeficiency virus (HIV) during antiretroviral therapy and is associated with premature aging. The glycoprotein 120 (gp120) subunit of HIV-1 envelope sheds and can be detected in plasma, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasma soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, linked to CD4 depletion in vitro, contribute to chronic inflammation, immune dysfunction, and subclinical cardiovascular disease in participants of the Canadian HIV and Aging Cohort Study with undetectable viremia. METHODS: Cross-sectional assessment of sgp120 and anti-cluster A antibodies was performed in 386 individuals from the cohort. Their association with proinflammatory cytokines and subclinical coronary artery disease was assessed using linear regression models. RESULTS: High levels of sgp120 and anti-cluster A antibodies were inversely correlated with CD4+ T cell count and CD4/CD8 ratio. The presence of sgp120 was associated with increased levels of interleukin 6. In participants with detectable atherosclerotic plaque and detectable sgp120, anti-cluster A antibodies and their combination with sgp120 levels correlated positively with the total volume of atherosclerotic plaques. CONCLUSIONS: This study showed that sgp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of people living with HIV, contributing to the development of premature comorbid conditions.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Viremia , Estudos de Coortes , Estudos Transversais , Canadá , Infecções por HIV/tratamento farmacológico , Anticorpos Anti-HIV , Glicoproteínas , Proteína gp120 do Envelope de HIV
4.
Transfusion ; 64(4): 606-614, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38511889

RESUMO

BACKGROUND: The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. This study evaluates the cost-effectiveness of convalescent plasma and its impact on quality-of-life to provide insight into its potential as an alternative treatment in resource-constrained settings. METHODS: Individual patient data on health outcomes and resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L were measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses costs from this population. RESULTS: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality-adjusted life day was -0.078. DISCUSSION: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID-19.


Assuntos
COVID-19 , Adulto , Humanos , COVID-19/terapia , Qualidade de Vida , Bisoprolol , Análise Custo-Benefício , Soroterapia para COVID-19 , Canadá/epidemiologia
5.
Pediatr Allergy Immunol ; 35(5): e14130, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693814

RESUMO

While the early introduction of food allergens in the infant diet has been shown to be effective at preventing the development of food allergy (FA), its implementation in real life has been associated with various challenges. Interventions aimed at correcting skin barrier dysfunction have been explored in recent decades as a distinct or complementary mean to prevent allergic sensitization through the skin and subsequent development of FA. Studies assessing the application of emollient from birth have yielded conflicting results, and meta-analyses have demonstrated either no effect or only a slight positive effect on FA prevention. However, a careful review of the clinical trials reveals that different emollients were used, which may have explained some of the discrepancies between study results. Emollient application protocols also varied widely between studies. While firm conclusions cannot be drawn with regard to their overall efficacy at preventing FA, the available data provide valuable insight into the characteristics that could be associated with a more effective intervention. Namely, successful trials tended to use emollients with an acidic pH of 5.5, applied over the entire body, and combined with topical corticosteroids in affected areas. Consensus on the optimal strategy to restore skin barrier function could help improve the homogeneity and clinical relevance of future trials on this topic. In the meantime, clinicians should avoid products associated with worse outcomes.


Assuntos
Emolientes , Hipersensibilidade Alimentar , Pele , Humanos , Hipersensibilidade Alimentar/prevenção & controle , Emolientes/administração & dosagem , Pele/efeitos dos fármacos , Pele/imunologia , Lactente , Alérgenos/imunologia , Alérgenos/administração & dosagem , Ensaios Clínicos como Assunto , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Recém-Nascido
6.
Eur J Pediatr ; 183(9): 3843-3851, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38884821

RESUMO

PURPOSE: Hyperemesis gravidarum has the potential to affect the long-term health of offspring. We examined whether maternal hyperemesis gravidarum was associated with the risk of hospitalization for childhood morbidity. METHODS: We conducted a longitudinal cohort study of 1,189,000 children born in Quebec, Canada, between April 2006 and March 2021. The main exposure measure was maternal hyperemesis gravidarum requiring hospitalization in the first or second trimester. The outcome was any pediatric admission between birth and 16 years of age, with follow-up ending in March 2022. We used Cox regression models adjusted for maternal and socioeconomic factors to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between maternal hyperemesis gravidarum and childhood hospitalization. RESULTS: Among 1,189,000 children, 6904 (0.6%) were exposed to maternal hyperemesis gravidarum. Hospitalization rates at age 16 years were higher for children exposed to hyperemesis gravidarum than unexposed children (47.6 vs 43.9 per 100 children). Relative to no exposure, hyperemesis gravidarum was associated with a 1.21 times greater risk of any hospitalization before 16 years (95% CI 1.17-1.26). Hyperemesis gravidarum was associated with hospitalization for neurologic (HR 1.50, 95% CI 1.32-1.71), developmental (HR 1.51, 95% CI 1.29-1.76), digestive (HR 1.40, 95% CI 1.30-1.52), and allergic disorders (HR 1.39, 95% CI 1.24-1.56). When contrasted with preeclampsia, hyperemesis gravidarum was a stronger risk factor for these outcomes. CONCLUSIONS: Maternal hyperemesis gravidarum is associated with an increased risk of childhood hospitalization, especially for neurologic, developmental, digestive, and atopic disorders. WHAT IS KNOWN: • Hyperemesis gravidarum is associated with neurodevelopmental disorders in offspring. • However, the effect of hyperemesis gravidarum on other childhood morbidity is unclear. WHAT IS NEW: • In this longitudinal cohort study of 1.2 million children, maternal hyperemesis gravidarum was associated with a greater risk of hospitalization before age 16 years. • Exposure to hyperemesis gravidarum was associated with developmental, neurologic, atopic, and digestive morbidity in childhood.


Assuntos
Hospitalização , Hiperêmese Gravídica , Humanos , Hiperêmese Gravídica/epidemiologia , Feminino , Gravidez , Estudos Longitudinais , Adolescente , Criança , Hospitalização/estatística & dados numéricos , Pré-Escolar , Lactente , Masculino , Quebeque/epidemiologia , Recém-Nascido , Adulto , Fatores de Risco , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos de Coortes
7.
J Allergy Clin Immunol ; 151(3): 595-606, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36872039

RESUMO

Continuing insight into the molecular mechanisms of atopic disorders has enabled the development of biologics to precisely target these diseases. Food allergy (FA) and eosinophilic gastrointestinal disorders (EGIDs) are driven by similar inflammatory molecular mechanisms and exist along the same atopic disease spectrum. Therefore, many of the same biologics are being investigated to target key drivers of mechanisms shared across the disease states. The enormous potential of biologics for the treatment of FA and EGIDs is highlighted by the significant increases in the number of ongoing clinical trials (more than 30) evaluating their use in these disease states, as well as by the recent US Food and Drug Administration approval of dupilumab for the treatment of eosinophilic esophagitis. Here we discuss past and current research into the use of biologics in FA and EGIDs and their potential role in improving treatment options in the future, with the need to have biologics widely clinically available.


Assuntos
Produtos Biológicos , Enterite , Esofagite Eosinofílica , Hipersensibilidade Alimentar , Estados Unidos , Humanos , Criança
8.
J Allergy Clin Immunol ; 152(2): 309-325, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37295474

RESUMO

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.


Assuntos
Anafilaxia , COVID-19 , Hipersensibilidade Imediata , Humanos , Vacinas contra COVID-19/efeitos adversos , Abordagem GRADE , Consenso , Excipientes de Vacinas , COVID-19/prevenção & controle , Excipientes
9.
Clin Exp Allergy ; 53(1): 25-38, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36200952

RESUMO

The 21st century has seen the propulsion of research in the field of food allergy, which has driven real changes in the clinical approach. Allergen immunotherapy has been recommended for the active management of food allergy. Data have shown promising additional methods of treatment, including biologics. Efforts have been devoted to the risk stratification of food allergy and the standardization of the assessment of food-allergic severity. Alternative routes of administration of epinephrine are under investigation to minimize any mechanical issue and the fear of injections. Evidence-based guidelines have been published by the main international societies in the field of anaphylaxis and food allergy management and new updates are in preparation. In the coming years, treatment options that are currently in pre-clinical or early clinical evaluation will hopefully lead to safe and effective disease-modifying therapies for food allergy in clinical practice. The identification of reliable biomarkers and the standardization of definitions and measurement approaches, alongside a shared decision-making with patients and families, will be key for the development of personalized care and to help minimize the substantial burden of food allergy.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Humanos , Imunoglobulina E , Hipersensibilidade Alimentar/terapia , Hipersensibilidade Alimentar/tratamento farmacológico , Alimentos , Anafilaxia/diagnóstico , Anafilaxia/etiologia , Anafilaxia/prevenção & controle , Alérgenos
10.
Transfus Med ; 33(1): 21-25, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35633145

RESUMO

Faced with an evolving pandemic and a lack of clarity of the role of convalescent plasma for patients with COVID-19, the CONCOR-1 trial was launched. In 14 months the trial was designed, launched, completed, and submitted for publication. In total, 72 sites in three countries served by four blood suppliers randomised 940 patients. Many enablers facilitated the trial including: three study principal investigators to distribute the trial workload, diverse steering committee members, an international data safety monitoring committee, multiple statisticians and methodologists, virtual meeting platforms, REDCap data platform, pausing of non-COVID-19 trials, rapid approval pathways for institutional review boards and regulators, centralised institutional review boards in many locations, restriction of use of convalescent plasma to trial participants and the incredible dedication by research personnel. In future pandemics, we need to be prepared for rapid launch of trials. The protocols, consent forms, data collection tools, and procedures need to be in draft form ready for use at all times. We were well-prepared for blood shortages but should have anticipated the need to conduct trials with convalescent plasma. In this short article, we detail our lessons learned to inform researchers faced with the next pandemic pathogen.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Bisoprolol , Imunização Passiva/métodos , Soroterapia para COVID-19
11.
Cancer ; 128(8): 1684-1691, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35100438

RESUMO

BACKGROUND: Health outcomes of children in families affected by cancer are poorly understood. The authors assessed the risk of hospitalization in children who have a sibling with cancer. METHODS: This was a longitudinal cohort study in which 1600 children who had a sibling with cancer were matched to 32,000 children who had unaffected siblings in Quebec, Canada, from 2006 to 2020. The exposure of interest was having a sibling with cancer. Outcomes included hospitalization for pneumonia, asthma, fracture, and other morbidities any time after the sibling was diagnosed with cancer. The children were followed over time, and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the impact of having a sibling with cancer on the risk of hospitalization before age 14 years, adjusted for patient characteristics. RESULTS: Children who had a sibling with cancer had an increased risk of hospitalization compared with unaffected children (HR, 1.15; 95% CI, 1.02-1.29). Conditions associated with a greater risk of hospitalization included pneumonia, hemangioma, other skin conditions, sleep apnea, and inflammatory bowel disease. The risk of hospitalization was greatest for children whose older sibling had cancer (HR, 1.16; 95% CI, 1.01-1.32) and for children whose sibling had hematopoietic cancer (HR, 1.22; 95% CI, 1.01-1.48). CONCLUSIONS: Children who have a sibling with cancer are at risk of hospitalization for conditions such as pneumonia, inflammatory bowel disease, and other morbidities. Families affected by childhood cancer may benefit from additional support to facilitate care for all children in the family. LAY SUMMARY: Little is known about the health of children who have a brother or sister with cancer. The authors studied the types of hospitalization experienced by children who have siblings with cancer. The results indicated that having a sibling with cancer increased the chance of being hospitalized for pneumonia and other conditions that could have been preventable. The results also indicated that children who had an older sibling with cancer or a sibling with blood cancer had a greater chance of being hospitalized. The findings highlight the importance of providing timely care for children in families affected by childhood cancer.


Assuntos
Neoplasias , Irmãos , Adolescente , Criança , Estudos de Coortes , Hospitalização , Humanos , Estudos Longitudinais , Masculino , Neoplasias/epidemiologia , Neoplasias/terapia
12.
Allergy ; 77(6): 1815-1826, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34822184

RESUMO

BACKGROUND: The Food Allergy Quality of Life Questionnaire Parent Form (FAQLQ-PF) is the most widely used quality of life questionnaire in food allergy. The objective of this study was to develop a mapping algorithm to convert FAQLQ-PF scores into health state utilities. METHODS: The Short-Form Six-Dimensions version 2 (SF-6Dv2) and FAQLQ-PF questionnaires were collected from an academic center oral immunotherapy referral cohort. Utility estimates were derived from the SF-6Dv2 using the food allergy preference set. Candidate mapping algorithm models were developed using seven regression methods starting from either the total average score, the average scores of each of the three domains or the individual item scores of FAQLQ-PF. The process was repeated twice, including only section A, common to all age groups, or including all age-applicable sections of the FAQLQ-PF. The mean absolute error (MAE) and root mean squared error (RMSE) were used to select the best fitting model. An independent cohort from a previous national online survey was used for external validation. RESULTS: In the index cohort, 1000 of 1257 respondents had completed both questionnaires. The lowest MAE (0.0791) and RMSE (0.1020) were recorded when entering individual item scores in a categorical regression model. The model including only FAQLQ-PF section A was found to be most consistent when tested in the external validation cohort (n = 248) (MAE of 0.0898). CONCLUSION: The FAQLQ-PF was mapped onto SF-6Dv2 utilities with good predictive accuracy in two independent cohorts. This will enable calculation of health utility for cost-effectiveness analyses in food allergy.


Assuntos
Hipersensibilidade Alimentar , Qualidade de Vida , Análise Custo-Benefício , Hipersensibilidade Alimentar/diagnóstico , Humanos , Pais , Inquéritos e Questionários
13.
Allergy ; 77(9): 2770-2777, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35466405

RESUMO

BACKGROUND: The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) is a commonly used patient-reported outcome measure in food allergy (FA) research. It was developed before FA treatment clinical trials were commonplace and is used as a secondary outcome measure in pivotal FA treatment trials. We examined the psychometric properties of the FAQLQ-PF and its relevance to children with peanut allergy engaged in an epicutaneous immunotherapy (EPIT) clinical trial. METHODS: Analysis was performed on 26 universally answered items of the FAQLQ-PF, from assessments undertaken during the phase 3 PEPITES study (baseline, Month 12), which examined the safety and efficacy of EPIT for children with peanut allergy aged 4-11 years. Item response theory (IRT) was used to assess psychometric parameters of the FAQLQ-PF (i.e., discrimination, difficulty, and information). Confirmatory factor analysis was also employed; reliability was assessed using McDonald's omega (ω) and Cronbach's alpha (α). RESULTS: A total of 23 of 26 items presented very high discrimination levels (>1.7), and all 26 fell within the recommended difficulty threshold (between -1.5 and 1.5). The items contributed a reasonable information level for their respective factors/subdomains. The measure also presented a marginally acceptable model fit for the 3-factor structure (e.g., comparative fit index = 0.88, Tucker-Lewis index = 0.87) and good reliability levels across time points (ω and α > 0.90). CONCLUSIONS: Herein, we present a novel reanalysis of the FAQLQ-PF items using IRT. The longitudinal performance of individual items and subscales was corroborated, and items with the highest discrimination were identified, showing that the tool is suitable for longitudinal measurements in FA treatment trials.


Assuntos
Hipersensibilidade Alimentar , Hipersensibilidade a Amendoim , Criança , Dessensibilização Imunológica/efeitos adversos , Hipersensibilidade Alimentar/terapia , Humanos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários
14.
Allergy ; 77(6): 1852-1862, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35001400

RESUMO

BACKGROUND: There is substantial interest in immunotherapy and biologicals in IgE-mediated food allergy. METHODS: We searched six databases for randomized controlled trials about immunotherapy alone or with biologicals (to April 2021) or biological monotherapy (to September 2021) in food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis. RESULTS: We included 36 trials about immunotherapy with 2126 mainly child participants. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5.-21.4, high certainty); cow's milk (RR 5.7, 1.9-16.7, moderate certainty) and hen's egg allergy (RR 8.9, 4.4-18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300 mg or 1000 mg peanut protein was 2. Oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0-1.2, low certainty) or severe reactions in peanut allergy (RR 1,6, 0.7-3.5, low certainty), but may increase (mild) adverse reactions in cow's milk (RR 3.9, 2.1-7.5, low certainty) and hen's egg allergy (RR 7.0, 2.4-19.8, moderate certainty). Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8-3.8, moderate certainty). Results were unclear for other allergies and administration routes. There were too few trials of biologicals alone (3) or with immunotherapy (1) to draw conclusions. CONCLUSIONS: Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow's milk and hen's egg allergy. More research is needed about quality of life, cost and biologicals.


Assuntos
Hipersensibilidade a Ovo , Hipersensibilidade Alimentar , Alérgenos , Animais , Bovinos , Galinhas , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Feminino , Hipersensibilidade Alimentar/terapia , Humanos , Imunoglobulina E , Qualidade de Vida
15.
Allergy ; 77(6): 1736-1750, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741557

RESUMO

BACKGROUND: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. METHODS: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. RESULTS: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. CONCLUSION: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Alérgenos/análise , Anafilaxia/diagnóstico , Anafilaxia/etiologia , Anafilaxia/prevenção & controle , Animais , Ovos , Hipersensibilidade Alimentar/diagnóstico , Rotulagem de Alimentos , Humanos
16.
Int Arch Allergy Immunol ; 183(9): 980-984, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35675786

RESUMO

BACKGROUND: Peanut specific IgE (sIgE) can lead to false-positive results. OBJECTIVE: We aimed to assess whether peanut sIgE to total IgE (tIgE) ratio improves accuracy in predicting clinical reactivity to peanut compared to peanut sIgE alone, which has not been explored in the adult population so far. METHOD: A retrospective chart review was performed for adults who underwent peanut oral food challenge (OFC) and/or oral immunotherapy (OIT) at the Centre Hospitalier de l'Université de Montréal's allergy clinic between January 2017 and July 2021. Patients with positive peanut OFC and/or undergoing OIT were considered peanut-allergic. Patients with negative OFC were considered peanut-tolerant. Peanut sIgE to tIgE ratios were calculated and performance characteristics of the sIgE to tIgE ratio were compared to sIgE alone by using receiver operator characteristics curves. RESULTS: Forty-two patients were included (52% male) with a median age of 26 years (range 14-54). Forty-five percent had atopic dermatitis. Median sIgE levels were 2.64 kUA/L (range 0.1-100), median tIgE levels were 154 kUA/L (range 19-3,400), and median sIgE to tIgE ratio was 0.66% (range 0.04-38.3). Twenty-four patients (57%) were classified as peanut-allergic and 18 (43%) as peanut tolerant. The area under the curve for peanut sIgE was 0.921 compared to 0.926 for peanut sIgE/tIgE (p not statistically significant). CONCLUSIONS: We found that there was no significant benefit in using peanut sIgE to tIgE ratio over sIgE alone to predict peanut reactivity in an adult population. Larger prospective studies are needed to further confirm these findings.


Assuntos
Arachis , Hipersensibilidade a Amendoim , Adolescente , Adulto , Alérgenos , Feminino , Humanos , Imunoglobulina E , Masculino , Pessoa de Meia-Idade , Hipersensibilidade a Amendoim/diagnóstico , Estudos Retrospectivos , Adulto Jovem
17.
Transfusion ; 62(12): 2525-2538, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36285763

RESUMO

BACKGROUND: Equitable allocation of scarce blood products needed for a randomized controlled trial (RCT) is a complex decision-making process within the blood supply chain. Strategies to improve resource allocation in this setting are lacking. METHODS: We designed a custom-made, computerized system to manage the inventory and allocation of COVID-19 convalescent plasma (CCP) in a multi-site RCT, CONCOR-1. A hub-and-spoke distribution model enabled real-time inventory monitoring and assignment for randomization. A live CCP inventory system using REDCap was programmed for spoke sites to reserve, assign, and order CCP from hospital hubs. A data-driven mixed-integer programming model with supply and demand forecasting was developed to guide the equitable allocation of CCP at hubs across Canada (excluding Québec). RESULTS: 18/38 hospital study sites were hubs with a median of 2 spoke sites per hub. A total of 394.5 500-ml doses of CCP were distributed; 349.5 (88.6%) doses were transfused; 9.5 (2.4%) were wasted due to mechanical damage sustained to the blood bags; 35.5 (9.0%) were unused at the end of the trial. Due to supply shortages, 53/394.5 (13.4%) doses were imported from Héma-Québec to Canadian Blood Services (CBS), and 125 (31.7%) were transferred between CBS regional distribution centers to meet demand. 137/349.5 (39.2%) and 212.5 (60.8%) doses were transfused at hubs and spoke sites, respectively. The mean percentages of total unmet demand were similar across the hubs, indicating equitable allocation, using our model. CONCLUSION: Computerized tools can provide efficient and immediate solutions for equitable allocation decisions of scarce blood products in RCTs.


Assuntos
COVID-19 , Humanos , COVID-19/terapia , Canadá , Quebeque
18.
Pediatr Allergy Immunol ; 33(2): e13728, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35212046

RESUMO

BACKGROUND: Children whose mothers have autoimmune disease may be at risk of developing immune-mediated disorders. We assessed the association between maternal autoimmune disease and risk of autoimmune disease, allergy, and cancer in offspring. METHODS: We analyzed a cohort of 1,011,623 children born in Canada between 2006 and 2019. We identified mothers who had autoimmune diseases and assessed hospitalizations for autoimmune disease, allergy, and cancer in offspring between birth and 14 years of age. We estimated hazard ratios (HR) for the association of maternal autoimmune disease with child hospitalization in adjusted Cox regression models. We used within-sibling analysis to control for genetic and environmental confounders. RESULTS: A total of 20,354 children (2.0%) had mothers with an autoimmune disease. Compared with no autoimmune disease, maternal autoimmune disease was associated with the risk of childhood hospitalization for autoimmune disease (HR 1.96, 95% CI 1.66-2.31) and allergy (HR 1.30, 95% CI 1.21-1.40), but was not significantly associated with cancer (HR 1.31, 95% CI 0.96-1.80). Type 1 diabetes, celiac disease, inflammatory arthritis, and systemic lupus erythematosus were among specific maternal autoimmune diseases most strongly associated with childhood hospitalization for autoimmune disease and allergy. The associations disappeared after controlling for genetic and environmental confounders in the within-sibling analysis. CONCLUSIONS: Maternal autoimmune disease is associated with an increased risk of autoimmune disease and allergy hospitalization in offspring, but the relationship appears to be confounded by genetic and environmental factors. Prenatal exposure to immunologic or pharmacologic products is not likely a direct cause of immune-mediated disease in children.


Assuntos
Doenças Autoimunes , Hipersensibilidade , Neoplasias , Efeitos Tardios da Exposição Pré-Natal , Doenças Autoimunes/epidemiologia , Criança , Estudos de Coortes , Feminino , Hospitalização , Humanos , Hipersensibilidade/epidemiologia , Neoplasias/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores de Risco
19.
BMC Med Educ ; 22(1): 616, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35962381

RESUMO

BACKGROUND: Multiple mini-interviews (MMI) are used to assess non-academic attributes for selection in medicine and other healthcare professions. It remains unclear if different MMI station formats (discussions, role-plays, collaboration) assess different dimensions. METHODS: Based on station formats of the 2018 and 2019 Integrated French MMI (IFMMI), which comprised five discussions, three role-plays and two collaboration stations, the authors performed confirmatory factor analysis (CFA) using the lavaan 0.6-5 R package and compared a one-factor solution to a three-factor solution for scores of the 2018 (n = 1438) and 2019 (n = 1440) cohorts of the IFMMI across three medical schools in Quebec, Canada. RESULTS: The three-factor solution was retained, with discussions, role-plays and collaboration stations all loading adequately with their scores. Furthermore, all three factors had moderate-to-high covariance (range 0.44 to 0.64). The model fit was also excellent with a Comparative fit index (CFI) of 0.983 (good if > 0.9), a Tucker Lewis index of 0.976 (good if > 0.95), a Standardized Root Mean Square Residual of 0.021 (good if < .08) and a Root Mean Square Error of 0.023 (good if < 0.08) for 2018 and similar results for 2019. In comparison, the single factor solution presented a lower fit (CFI = 0.819, TLI = 0.767, SRMR = 0.049 and RMSEA = 0.070). CONCLUSIONS: The IFMMI assessed three dimensions that were related to stations formats, a finding that was consistent across two cohorts. This suggests that different station formats may be assessing different skills, and has implications for the choice of appropriate reliability metrics and the interpretation of scores. Further studies should try to characterize the underlying constructs associated with each station format and look for differential predictive validity according to these formats.


Assuntos
Critérios de Admissão Escolar , Faculdades de Medicina , Canadá , Humanos , Psicometria , Reprodutibilidade dos Testes
20.
J Allergy Clin Immunol ; 147(1): 233-243, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32980425

RESUMO

BACKGROUND: Omalizumab has been shown to improve the safety and feasibility of oral immunotherapy (OIT), but the optimal dosage strategy is unknown. OBJECTIVE: Our aim was to identify determinants of omalizumab dose-related efficacy in the context of OIT. METHODS: The study sample consisted of a clinical cohort of 181 patients treated with omalizumab-enabled oral immunotherapy at 3 centers. Patients received omalizumab for at least 2 months before an initial food escalation (IFE) with a mix of up to 6 allergens. Progression through IFE steps was assessed with survival analysis. Continued food dose tolerance with omalizumab weaning was also documented. RESULTS: Omalizumab dosage per weight alone was strongly associated with progression through the IFE (χ2 = 28.18; P < .0001), whereas the standard dosage per weight and total IgE level used for asthma was not (χ2 = 0.001; P = .97). When the values at time of IFE were estimated through pharmacokinetics and pharmacodynamics simulation, IFE outcome was best predicted by a model that includes levels of free allergen-specific IgE and their interaction with blocking omalizumab-IgE complexes and free omalizumab levels in serum (χ2 = 65.84; degrees of freedom [df] = 2; P < .0005). The occurrence of immediate-type reactions to food dosing subsequent to weaning of omalizumab was associated with a greater ratio of specific IgE level to total IgE level at baseline (geometric mean 0.39 vs 0.16 in those without symptom; P < .0001). CONCLUSION: In the context of OIT and IgE-mediated disease, omalizumab dosages should be adjusted for body weight alone, independently of total IgE level. The fraction of allergen-specific/total IgE may be useful to predict patients at greater risk of food dosing reactions subsequent to weaning.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade Alimentar , Omalizumab , Administração Oral , Adolescente , Criança , Feminino , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/tratamento farmacológico , Humanos , Imunoglobulina E/sangue , Masculino , Omalizumab/administração & dosagem , Omalizumab/farmacocinética
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