Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

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.

Quality of life and cost-effectiveness of convalescent plasma compared to standard care for hospitalized COVID-19 patients in the CONCOR-1 trial.

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.

Skin-centered strategies in food allergy prevention.

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.

Hyperemesis gravidarum and the risk of offspring morbidity: a longitudinal cohort study.

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.

Long-term outcomes of patients with toxic shock syndrome: A matched cohort study.

OBJECTIVES: We examined long-term outcomes of toxic shock syndrome. METHODS: We conducted a matched cohort study of 630 patients with toxic shock syndrome and 5009 healthy controls between 2006 and 2021 in Quebec, Canada. Outcomes included hospitalization for renal, cardiovascular, hepatic, and other morbidity during 15 years of follow-up. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the risk of these outcomes over time, comparing patients with toxic shock syndrome relative to matched controls. RESULTS: Compared with healthy controls, rehospitalization rates at 15 years were higher for men with toxic shock syndrome (52.0 vs 30.0 per 100) but not for women (38.7 vs 45.6 per 100). In men, toxic shock syndrome was associated with an elevated risk of renal (HR 17.43, 95% CI 6.35-47.82), cardiovascular (HR 2.57; 95% CI 1.52-4.34), and hepatic hospitalization (HR 19.83, 95% CI 4.72-83.34). In women, toxic shock syndrome was associated with renal hospitalization (HR 4.71, 95% CI 1.94-11.45). Streptococcal toxic shock was associated with a greater risk of rehospitalization than staphylococcal toxic shock. CONCLUSIONS: Toxic shock syndrome is associated with rehospitalization up to 15 years later, especially in men. These patients may benefit from continued follow-up to prevent long-term morbidity.

Impact of Exacerbation History on Dupilumab Efficacy in Children with Uncontrolled Moderate-to-Severe Asthma: LIBERTY ASTHMA VOYAGE Study.

Purpose: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 inflammation in multiple diseases. This post hoc analysis of the Phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959) evaluated the efficacy of dupilumab in children aged 6 to 11 years with moderate-to-severe asthma with a type 2 inflammatory phenotype (blood eosinophil count ≥150 cells/µL or fractional exhaled nitric oxide [FeNO] ≥20 ppb) and a history of 1, 2, or ≥3 prior exacerbations. The impact of baseline type 2 biomarker levels on the efficacy of dupilumab in this population was also investigated. Patients and Methods: Patients were stratified by the number of exacerbations in the prior year (1, 2, or ≥3) and level of FeNO or blood eosinophil count at baseline. Endpoints included rate of severe exacerbations, percentage of non-exacerbators, and change from baseline in both lung function parameters (pre- and post-bronchodilator [BD] percent predicted forced expiratory volume in 1 s (ppFEV1) and ppFEV1/forced vital capacity [FVC] ratio) and Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) score. Results: A total of 350 patients were included in this analysis. Across patients with 1, 2, or ≥3 prior exacerbations and different levels of type 2 biomarkers, dupilumab reduced the risk of severe asthma exacerbations vs placebo by 53.0-96.0% and improved both pre-BD ppFEV1 and pre-BD FEV1/FVC ratio at Week 52. Dupilumab led to significant reductions in ACQ-7-IA scores in all groups of patients by Week 52. Conclusion: In children with uncontrolled, moderate-to-severe asthma with a type 2 phenotype, dupilumab consistently reduced the risk of asthma exacerbations, improved lung function, and reduced ACQ-7-IA scores, regardless of exacerbation history.

Age-Related Food Aversion and Anxiety Represent Primary Patient Barriers to Food Oral Immunotherapy.

BACKGROUND: Although oral immunotherapy (OIT) for food allergy is a reasonable treatment option, barriers to this procedure's implementation have not been extensively evaluated from a patient perspective. OBJECTIVE: We evaluated the barriers patients face during OIT administration, including anxiety and taste aversion, and the role of health care professionals, especially dietitians. METHODS: A survey in Canada and the United States involved families currently enrolled in food OIT programs. RESULTS: Of responses from 379 participants, fear of reaction was the most common barrier to OIT initiation, with 45.6% reporting it being a "very significant" barrier with other fears reported. However, taste aversion represented the prominent obstacle to continuation. Taste aversion was associated with a slower buildup (P = .02) and a reduction in dose (P = .002). Taste aversion was a strongly age-dependent barrier for initiation (P < .001) and continuation (P < .002), with older children over 6 years of age reporting it as a very significant barrier (P < .001). Boredom was reported as a concern for specific allergens such as peanut, egg, sesame, and hazelnuts (P < .05), emphasizing the need for diverse food options. Notably, 59.9% of respondents mixed OIT foods with sweet items. Despite these dietary concerns, dietitians were underutilized, with only 9.5% of respondents having seen a dietitian and the majority finding dietitian support helpful with greater certainty about the exact dose (P < .001). CONCLUSIONS: Taste aversion and anxiety represent primary patient-related barriers to OIT. Taste aversion was highly age dependent, with older patients being more affected. Dietitians and psychology support were underutilized, representing a critical target to improve adherence and OIT success.

Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in Children With Cow's Milk Allergy: A Randomized Clinical Trial.

Importance: No approved treatment exists for allergen-specific immunoglobulin E (IgE)-mediated cow's milk allergy (CMA), a common childhood food allergy. Objective: To assess dose, efficacy, and safety of epicutaneous immunotherapy with Viaskin milk in children with IgE-mediated CMA. Design, Setting, and Participants: A phase 1/2, 2-part, randomized, double-blind, placebo-controlled dose-ranging clinical trial in children aged 2 to 17 years with IgE-mediated CMA was conducted between November 2014 through December 2017. It took place at 17 trial sites in the US and Canada. Current CMA was confirmed by double-blind, placebo-controlled food challenge at study entry. Part A assessed the short-term safety of 150 µg, 300 µg, or 500 µg of Viaskin milk; part B evaluated the efficacy and safety of the 3 doses vs placebo over 12 months of treatment. Of the 308 screened participants with physician-diagnosed CMA, 198 met eligibility criteria (including an eliciting dose 300 mg or less) and were randomized. Intervention: Safety of Viaskin milk (150-µg, 300-µg, or 500-µg doses) was evaluated over a 3-week period (part A). In part B, 180 additional participants were randomized to receive Viaskin milk at doses of 150 µg, 300 µg, or 500 µg or placebo (1:1:1:1) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of treatment responders, defined as a 10-fold or more increase in the cumulative reactive dose of cow's milk protein (reaching at least 144 mg) or a cumulative reactive dose of cow's milk protein at 1444 mg or more at the month 12 double-blind, placebo-controlled food challenge. Results: A total of 95.5% of the randomized participants (mean [SD] age, 8 [4.17] years; 124 of 198 were male [62.6%]) completed treatment. The highest response rate was observed in participants who received Viaskin milk at the 300-µg dose with 24 of 49 responders (49.0%) overall vs 16 of 53 responders (30.2%) in the placebo group (odds ratio, 2.19; 95% CI, 0.91-5.41; P = .09), highest in the 2 to 11 years age group (22 of 38 [57.9%] vs 13 of 40 [32.5%]; P = .04). Most treatment-emergent adverse events were mild or moderate application-site reactions. One participant in the 500-µg Viaskin milk dose group experienced treatment-related anaphylaxis. Conclusions and Relevance: In this randomized clinical trial, 12 months of daily epicutaneous immunotherapy with a dose of Viaskin milk at 300 µg was associated with a statistically significant treatment response in 2- to 11-year-old children with IgE-mediated CMA. Treatment-related anaphylaxis and treatment-related discontinuation rates were low. Further research is needed to explore Viaskin milk as a viable treatment option for children with IgE-mediated CMA. Trial Registration: ClinicalTrials.gov Identifier: NCT02223182.

An overview of current clinical practice and international oral immunotherapy guidelines: A focus on Spanish, European, and Canadian guidelines.

Oral immunotherapy (OIT) is a recent and evolving therapeutic option for the treatment of immunoglobulin E (IgE) mediated food allergies. Clinical practice guidelines are starting to emerge to establish the parameters of this new clinical offer. A comparative analysis reveals several areas of consensus, such as the need for an accurate diagnosis with immunoglobulin E testing and, if necessary, open food challenge before initiating therapy; a list of specific contraindications; the importance of performing OIT in an adequate setting with appropriate level of expertise; the possibility to use grocery products to perform OIT; and the need to adapt protocols to patient needs. Certain discrepancies among the guidelines also underscore various areas of uncertainty, which makes it important that decisions to pursue the treatment be reached by using a shared decision-making approach that involves patients and caregivers. Gaps of knowledge remain with regard to treatment of adolescents and adults, and optimal performance measures in practice. These guidelines are expected to evolve in the coming years as new scientific and experiential knowledge is gained.