A diagnostic approach to IgE-mediated food allergy: A practical algorithm.

A food reaction history is the basis of food allergy diagnoses. Several levels of food allergy diagnostic testing can confirm or refute the presence of food allergy. The choice of food allergy testing modality should be informed by the reaction history and determined by the testing goals. Testing modalities include skin-prick testing, in vitro specific immunoglobulin E testing, component-resolved testing, epitope threshold testing, and basophil activation testing. The goal of food allergy testing may be merely to confirm the diagnosis of food allergy or may be used to guide passive (avoidance) or active (allergen immunotherapy) management. The most appropriate diagnostic path should consider testing predictive value, the goal of the evaluation, patient and family food allergy anxiety, and cost. Peanut allergy testing provides an algorithm for testing pathways.

Long-Term Safety of Facilitated Subcutaneous Immunoglobulin 10% Treatment in US Clinical Practice in Patients with Primary Immunodeficiency Diseases: Results from a Post-Authorization Safety Study.

Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice. Patients with PIDs aged ≥ 16 years who were prescribed and/or had started fSCIG 10% treatment were enrolled. In total, 253 patients were enrolled and included (full analysis set). Participants received fSCIG 10% treatment for a median (interquartile range) of 10.0 (3.5-11.8) months, with the majority of infusions administered every 4 weeks (54.4% [1197/2201 infusions]) and at home (62.6% [1395/2230 infusions]). Overall, 98.5% of infusions were administered without rate reduction, interruption, or discontinuation due to adverse events (AEs). Treatment-related, non-serious AEs were experienced by 52 patients (20.6%, 284 events). Two patients (0.8%) each experienced one treatment-related serious AE (aseptic meningitis and deep vein thrombosis). Development of antibodies against rHuPH20 was uncommon; 14/196 patients (7.1%) tested positive for binding antibodies (titer ≥ 1:160) with no neutralizing antibodies detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs.

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.

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.

Outcome of BMI2+: Motivational Interviewing to Reduce BMI Through Primary Care AAP PROS Practices.

BACKGROUND: Pediatric obesity rates in the United States remain at an all-time high. Pediatric primary care clinicians and registered dietitians can help treat childhood obesity, and motivational interviewing (MI) has shown promising effects in prior trials. METHODS: We randomized 18 pediatric primary care practices to receive the Brief Motivational Interviewing to Reduce BMI or BMI2+ intervention or continue with usual care (UC). Practices were recruited through the American Academy of Pediatrics Pediatric Research in Office Settings network. The intervention comprised 4 components1: in-person and telehealth MI counseling by pediatric clinicians; 4 recommended sessions,2 6 telephone MI counseling sessions from a registered dietitian,3 text message reminders and tailored motivational messages, and4 parent educational materials. The main outcome was the change in the percentage of the 95th percentile of BMI. The study was conducted 2017 through 2021. RESULTS: There was a significant treatment x time interaction (b = 0.017, 95% confidence interval: [0.0066-0.027]) for the main outcome, favoring the UC group, with youth in the intervention arm showing a greater relative increase in their percent of the 95th percentile. CONCLUSIONS: There was no overall benefit of the intervention and, contrary to expectations, youth in the intervention arm gained more weight, based on percent of the distance from the 95th percentile than matched youth from UC practices. The absolute excess weight gain among intervention relative to UC youth was small, approximately 0.5 BMI units and 1 kg over 2 years. We offer several potential explanations for these unexpected findings.

A Cluster Randomized Controlled Trial of a Primary Care Provider-Delivered Social Media Counseling Intervention.

PURPOSE: Evidence and clinical policy support that providers screen and counsel for media use for youth, but most pediatricians lack this training. The purpose of this study was to test a primary care provider (PCP)-delivered intervention to promote safe social media use among youth. METHODS: We enrolled pediatric PCP practices for this clinical trial to test a social media counseling intervention (SMCI) between 2011 and 2013. Youth were recruited during clinic visits; follow-up interviews were conducted at 6 months. Outcomes included media behaviors and caregiver communication. Multivariate regression models examined associations between social media counseling and PCP counseling score. Multivariate logistic regression evaluated four social media behavior outcomes. RESULTS: A total of 120 practices enrolled; PCPs in the SMCI were more likely to provide social media counseling (B = 1.43, 95% confidence interval [CI]: 1.1-1.7). Youth whose PCP received the SMCI were twice as likely to report a decrease in online "friending" of strangers (adjusted odds ratio = 2.23, 95% CI 1.17-4.25) and were more likely to report communication with their caregivers about their social media use (adjusted odds ratio = 1.2; 95% CI: 1.1-1.4) compared to youth whose PCPs were in the active control group. DISCUSSION: Youth whose PCP had received social media counseling training reported a higher receipt of counseling about social media and improved safety behaviors.

Development of a novel shared decision making aid for primary immunodeficiency diseases.

Aim: To describe development of a shared decision making (SDM) aid in treating primary immunodeficiency diseases (PID) with immunoglobulin replacement therapy (IGRT). Materials & methods: Expert engagement and qualitative formative research informed development. IGRT administration features were prioritized using object-case best-worst scaling (BWS) methodology. The aid was assessed by US adults self-reporting PID and revised following interviews/mock treatment-choice discussions with immunologists. Results: Patients participating in interviews (n = 19) and mock treatment-choice discussions (n = 5) deemed the aid useful/accessible and supported the utility of BWS, with content and BWS exercises refined following participant feedback. Conclusion: Formative research led to an improved SDM aid/BWS exercise, and illustrated how the aid may improve treatment decision making. The aid may help less-experienced patients and facilitate efficient SDM.

Shared decision making and developing a decision aid Shared decision making happens when patients and doctors work together to choose treatment options based on a patient's concerns, preferences, goals and values, as well as medical information. The aim of this project was to develop a decision aid to help patients with primary immunodeficiency diseases (PID), in which part of the body's immune system is missing or doesn't function correctly. This will allow patients to better understand and communicate with the healthcare team on their preferences about immunoglobulin treatments, which fight infection by boosting antibody (protein) levels in the blood. The authors talked to experts and reviewed existing information to decide what treatment features the aid should consider. Patients with PID then tested the aid, and changes were made based on their feedback. Doctors specializing in treating PID also provided their feedback. The final aid was judged to be helpful and easy to use by the participants. With further research, this aid could be used to help inexperienced patients better understand what immunoglobulin treatment features are most important to them, and support shared decision-making between patients and their doctors.

Accelerating Food Allergy Research: Need for a Data Commons.

Food allergy is a significant health problem affecting approximately 8% of children and 11% of adults in the United States. It exhibits all the characteristics of a "complex" genetic trait; therefore, it is necessary to look at very large numbers of patients, far more than exist at any single organization, to eliminate gaps in the current understanding of this complex chronic disorder. Advances may be achieved by bringing together food allergy data from large numbers of patients into a Data Commons, a secure and efficient platform for researchers, comprising standardized data, available in a common interface for download and/or analysis, in accordance with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles. Prior data commons initiatives indicate that research community consensus and support, formal food allergy ontology, data standards, an accepted platform and data management tools, an agreed upon infrastructure, and trusted governance are the foundation of any successful data commons. In this article, we will present the justification for the creation of a food allergy data commons and describe the core principles that can make it successful and sustainable.

Cost-effectiveness of a motivational interviewing obesity intervention versus usual care in pediatric primary care offices.

OBJECTIVE: This study aimed to assess the incremental cost-effectiveness ratio (ICER) of a 2-year motivational interviewing (MI) intervention versus usual primary care. METHODS: A national trial was implemented in the Pediatric Research in Office Settings (PROS) network of the American Academy of Pediatrics to evaluate MI versus usual care for children (2-8 years old; baseline BMI 85th-97th percentiles). Health care use, food costs, provider fees, and training costs were assessed, and sensitivity analyses were conducted. Primary outcome was the ICER, calculated as cost per unit change in BMI percentile for intervention versus usual care. RESULTS: At 2 years, 72% of enrolled parent/child dyads were retained; 312 children were included in the analysis. Mean BMI percentile point change was -4.9 and -1.8 for the intervention and control, respectively, yielding an incremental reduction of 3.1 BMI percentile points (95% CI: 1.2-5.0). The intervention cost $1051 per dyad ($658 for training DVD development). Incorporating health care and non-health care costs, the intervention ICER was $363 (range from sensitivity analyses: cost saving, $3159) per BMI percentile point decrease per participant over 2 years. CONCLUSIONS: Training pediatricians, nurse practitioners, and registered dietitians to deliver MI-based interventions for childhood obesity in primary care is clinically effective and acceptably cost-effective. Future work should explore this approach in broader dissemination.

Systemic IgG exposure and safety in patients with primary immunodeficiency: a randomized crossover study comparing a novel investigational wearable infusor versus the Crono pump.

Aim: A novel, Investigational Wearable Infusor (IWI) was evaluated in a randomized, controlled, crossover, open-label study to determine if its delivery of subcutaneous immunoglobulin (IgPro20) achieved a comparable area under the concentration-time curve (AUC) for immunoglobulin G (IgG) versus the Crono S-PID-50 infusion pump (CP). EudraCT: 2016-003798-16. Materials & methods: Patients with primary immunodeficiency (PID) were randomized to receive IgPro20 in Sequence 1 (CP/IWI) or 2 (IWI/CP). The primary end point was AUC for IgG during the final week of each 4-week period. Results: 23 patients were enrolled. Evaluation of area under the concentration-time curve from time 0 (pre-infusion) to 7 days after infusion (AUC0-7 days) (IWI: 1806 h*g/l; CP: 1829 h*g/l) and geometric mean ratio indicated comparable AUCs for IgG for both devices. Conclusion: Similar IgG exposure, indicated by AUC values, can be achieved with IgPro20 using the IWI or CP in PID.

Patients with primary immunodeficiency (PID) are at a higher risk of developing serious infections than healthy individuals. Immunoglobulin G (IgG) replacement therapy reduces this risk, as it raises a patient's antibody levels to help fight off infections. IgG replacement therapy can be performed as an intravenous or subcutaneous (under the skin) infusion. The subcutaneous route is associated with improved quality of life for patients, as therapy can be carried out at home by the patient, allowing for more flexibility, convenience and autonomy. Wearable drug-delivery systems are devices that stick to the body and automatically deliver doses of a drug to the patient. In this study, we investigated whether a novel Investigational Wearable Infusor device could deliver the subcutaneous IgG replacement therapy, IgPro20, in patients with PID. We show that the new infusion device can deliver IgG replacement therapy and allows for similar levels of IgG to be achieved in patients as a comparator device. This wearable drug delivery device simplifies drug administration and could help address some of the challenges associated with self-injection such as complicated infusion preparation, needle phobia and concerns about pain. Trial Registration Number: 2016-003798-16 (EudraCT).

Information needs of patients considering oral immunotherapy for food allergy.

While the historic management of food allergy includes avoidance strategies and allergic reaction treatment, oral immunotherapy (OIT) approaches have become more commonly integrated into therapeutic approaches. International guidelines, phase 3 trials and real-world experience have supported the implementation of this procedure. However, OIT is an elective, rarely curative procedure with inherent risks that necessitates an increased degree of health literacy for the patients and families. Families assume the responsibility of amateur healthcare providers to ensure the daily safe administration of the allergenic food. As such, it is incumbent upon physicians to ensure that families are prepared for this role. A thorough educational and shared decision-making approach is necessary during the counselling and consent process to adequately inform the families. Educated discussion about the efficacy and patient-centred effectiveness, therapeutic alternatives and family goals is required to align physician and patient expectations. A frank discussion about the struggles, practical challenges, risks and contraindications can help to develop an understanding of the risk mitigation strategies employed to maintain safety. Physicians should develop a proactive approach to educate families about this, at times, burdensome procedure. This educational approach should encourage ongoing support starting prior to consent through the maintenance visits. By preparing families for their unique management role, physicians can help ensure the safe and successful integration of OIT into the therapeutic offering for the management of food allergies.

Towards an FDA-cleared basophil activation test.

Food allergy is a global health problem affecting up to 10% of the world population. Accurate diagnosis of food allergies, however, is still a major challenge in medical offices and for patients seeking alternative avenues of diagnosis. A flawless test to confirm or rule out a food allergy does not exist. The lack of optimum testing methods to establish precise clinical correlations remains a major obstacle to effective treatment. Certain IgE measurement methods, including component testing, have received FDA clearance, but they have been used primarily as an analytical tool and not to establish clinical correlations. Most allergy tests are still carried out within the laboratory, and skin tests outside a laboratory setting that are used for food allergy diagnosis rely on non-standardized allergens, according to the FDA definition. Epitope mapping and basophil activation test (BAT) have recently been proposed as a means of establishing better clinical correlations. Yet neither have received FDA clearance for widespread distribution. Of the two methods, the BAT has the advantage of being a functional assay. Over the past few years, several large private practice groups in the United States, have developed BAT as a clinical assay and have started using it in patient care. Given this clinical experience, the vast number of papers published on BAT (more than 1,400 as of 2022) and the trend toward increasing FDA regulation, it is essential to understand the roadmap for regulatory clearance of this assay.

The patient record and the rise of the pediatric EHR.

Medical documentation arose as individual case reports written for teaching purposes. Documentation for patient care later occurred in physicians' personal daybooks and only evolved into the individual patient record in the early 20th century. Dr. Lawrence Weed improved the utility of the patient record by introducing a problem-oriented/subject-object-assessment-plan structure and he and other innovators transformed the patient record into electronic form. Pediatricians built on these innovations to create a child health electronic health record (EHR) for primary care. An American Academy of Pediatrics task force formally specified the child-specific needs of the EHR, but much work remains to integrate the EHR into the pediatric primary care of the future.

Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases.

Aim: This post hoc analysis evaluated the efficacy and overall tolerability of immunoglobulin (Ig) treatment modalities (intravenous Ig [iv.Ig], subcutaneous Ig [sc.Ig] and facilitated sc.Ig [fsc.Ig]). Materials & methods: A total of 30 participants with primary immunodeficiency diseases aged ≥2 years sequentially received iv.Ig, sc.Ig and fsc.Ig during consecutive clinical studies. Results: For iv.Ig, sc.Ig and fsc.Ig, rates of validated acute serious bacterial infections/participant-year (0, 0.09 and 0.04, respectively) and all infections/participant year (4.17, 3.68 and 2.42, respectively) were similarly low; rates of systemic and local causally related adverse events/participant-year were 5.60, 1.93 and 0.88, respectively and 0.13, 0.92 and 1.57, respectively. Conclusion: fsc.Ig provided similar efficacy to iv.Ig and sc.Ig. Clinical Trial registration: NCT00546871, NCT00814320, NCT01175213 (ClinicalTrials.gov).

Long term oral immunotherapy management and assessment of success.

There is limited data addressing the optimal dose, dosing frequency, and duration of OIT maintenance. Using higher maintenance doses, more frequent dosing, and a long dosing duration makes it more likely that sustained unresponsiveness will be achieved but also increases the burden of care on the OIT patient and family. The OIT maintenance regimen should be individualized based on the treatment goals of the patient and family.