Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

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.).

Anaphylaxis: A 2023 practice parameter update.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations.

BACKGROUND: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology. OBJECTIVE: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD. METHODS: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles. RESULTS: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts. CONCLUSION: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).

Promoting penicillin allergy de-labeling for children attending a hematology clinic.

BACKGROUND: Up to 10% of children are reported to be allergic to penicillin, but many allergy labels are unverified and may require formal testing. Inaccurate drug allergy labels are associated with a range of adverse clinical outcomes. Patients with hematological disorders may experience frequent and severe infections; those who have been incorrectly labeled penicillin allergic may benefit from allergy de-labeling (ADL) efforts to facilitate access to beta-lactam antibiotics. We developed a multidisciplinary, pharmacist-driven process that enabled non-allergist trained providers to assess and de-label penicillin allergies in a pediatric hematology center. METHODS: Volunteers, including physicians, advanced practice providers, nurses, and pharmacists, were trained in skin testing and oral challenge procedures. Patients were identified by review of electronic medical records for penicillin or penicillin-derivative allergy. Patient and family interviews were conducted in cases where a true penicillin allergy was deemed uncertain based on chart review. If allergy could not be de-labeled by chart review or interview alone, patients were offered skin and/or oral challenge testing. RESULTS: Fifty-nine patients were initially labeled as penicillin allergic. Allergy labels of 11 (19%) were removed by chart review only, and 15 (25%) after conducting interviews. A total of two (3%) patients were ineligible due to contraindications, and five (9%) declined participation. Twenty-six patients (44%) underwent allergy testing (50% skin testing, 50% oral challenge) of which 23 (88%) were negative. CONCLUSIONS: ADL was possible in most patients previously identified as penicillin allergic. Testing was well tolerated with no serious adverse effects.

Practice Management Strategies Among Current Members of the American Association of Hip and Knee Surgeons.

BACKGROUND: A survey was conducted at the 2023 Annual Meeting of the American Association of Hip and Knee Surgeons (AAHKS) to assess practice management strategies among current AAHKS members. METHODS: Members of AAHKS used an app to answer both multiple-choice and "yes or no" questions related to a variety of issues related to their practices. RESULTS: The number of AAHKS members in private practice (37%) continues to decline, and 4% are now in private equity-employed practices. Fee for service (30%) and relative value units (30%) are the major forms of compensation. The number of AAHKS members that perform total joint arthroplasties at ambulatory surgery centers continues to increase, and supply chain issues (91%) remain a problem. There has been a decrease in surgeon participation in bundled payment programs and gainsharing arrangements with hospitals. CONCLUSIONS: This member's survey provides valuable information regarding practice patterns. The shift to outpatient surgery has continued. Future surveys will be performed to monitor changes in practice patterns over time.

Diversity of Backgrounds and Academic Accomplishments for Presidents Elected to Hip and Knee Arthroplasty Societies in the United States.

BACKGROUND: Academic accomplishments and demographics for presidents of hip and knee arthroplasty societies are poorly understood. This study compares the characteristics of presidents nominated to serve the Hip Society, Knee Society, and American Association of Hip and Knee Surgeons. METHODS: This was a cross-sectional study of arthroplasty presidents in the United States (1990 to 2022). Curriculum vitae and academic websites were analyzed for demographic, training, bibliometric, and National Institutes of Health (NIH) funding data. Comparisons were made between organizations and time periods (1990 to 2005 versus 2006 to 2022). RESULTS: There were 97 appointments of 78 unique arthroplasty presidents (80%). Most presidents were male (99%) and Caucasian (95%). There was 1 woman (1%) and 5 non-Caucasian presidents (2% Asian, 3% Hispanic). There were no differences in demographics between the 3 arthroplasty organizations and the 2 time periods (P > .05). Presidents were appointed at 55 ± 10 years old, which was on average 24 years after completion of residency training. Most presidents had arthroplasty fellowship training (68%), and the most common were the Hospital for Special Surgery (21%) and Massachusetts General Hospital (8%). The median h-index was 53 resulting from 191 peer-reviewed publications, which was similar between the 3 organizations (P > .05). There were 2 presidents who had NIH funding (2%), and there were no differences in NIH funding between the 3 organizations (P > .05). CONCLUSIONS: Arthroplasty society presidents have diverse training pedigrees, high levels of scholarly output, and similar demographics. There may be future opportunities to promote diversity and inclusion among the highest levels of leadership in total joint arthroplasty.

Same-Day Total Joint Arthroplasty in the United States From 2016 to 2020: The Impact of the Medicare Inpatient Only List and the COVID-19 Pandemic.

BACKGROUND: Same-day total hip arthroplasty (THA) and total knee arthroplasty (TKA) continue to gain popularity in the United States. The present study sought to quantify recent same-day outpatient trends taking into consideration the COVID-19 pandemic as well as the removal of these procedures from the Medicare inpatient only (IPO) list. METHODS: Patients undergoing primary elective TKA and THA were identified using the Nationwide Ambulatory Surgery Sample and the National Inpatient Sample from January 1, 2016, to December 31, 2020. The same-day cohort included Nationwide Ambulatory Surgery Sample and National Inpatient Sample patients with a length of stay = 0 days. The inpatient cohort included patients with length of stay ≥1 day. National estimates were extrapolated using weight functions. RESULTS: From January 2016 to December 2020, the proportion of same-day TKA increased from 1.2 (719) to 62.4% (31,293) and the proportion of same-day THA increased from 2.0 (599) to 54.5% (18,252). Following removal from the Medicare IPO list, same-day TKAs increased from 3.2% (1,895) in December 2017 to 13.8% (9,269) in January 2018, and same-day THAs increased from 10.7% (4,295) in December 2019 to 22.5% (8,708) in January 2020. Between February and March 2020, same-day TKAs increased from 42.4 (26,148) to 44.4% (16,972) and same-day THAs increased from 28.5 (10,729) to 30.2% (7,409). CONCLUSIONS: The proportion of same-day TKA and THA dramatically increased following removal from the Medicare IPO list and in response to the COVID-19 pandemic. By December 2020, same-day TKA and THA accounted for >50% of all cases performed in the United States.

Perioperative Dexamethasone is Associated With a Decreased Risk of Pulmonary Embolism and Deep Vein Thrombosis Following Total Joint Arthroplasty: An Analysis of 70,000 High-Risk Patients.

BACKGROUND: Dexamethasone (DEX) has demonstrated promise with respect to decreasing postoperative thromboembolic complications following total joint arthroplasty (TJA). Therefore, the aim of this study was to investigate the effects of perioperative intravenous DEX on rates of pulmonary embolism (PE) and deep vein thrombosis (DVT) after primary TJA in patients who have a history of venous thromboembolism (VTE). METHODS: Patients who have a history of VTE who underwent primary elective TJA from 2015 to 2021 were identified using a commercial health care database. Patients were divided based on receipt of perioperative intravenous DEX [DEX(+) versus DEX(-)] on the day of index TJA. Patient demographics and hospital factors were collected. The 90-day risk of postoperative complications, readmission, and in-hospital mortality were compared. RESULTS: Overall, 70,147 patients who had a history of VTE underwent TJA, of which 40,607 (57.89%) received DEX and 29,540 (42.11%) did not. The DEX(+) patients were younger (67 ± 9.8 versus 68 ± 9.9 years, P < .001) and had a significantly shorter length of stay compared to the DEX(-) patients (1.8 ± 1.6 versus 2.2 ± 1.8 days, P < .001). The DEX(+) patients demonstrated lower rates of PE (1.37 versus 1.75%, P < .001) and DVT (2.37 versus 3.01%, P < .001) compared to DEX(-) patients. The DEX(+) patients experienced a lower risk of PE (adjusted odds ratio: 0.78, 95% confidence interval: 0.66 to 0.93, P = .006) and DVT (adjusted odds ratio: 0.84, 95% confidence interval: 0.74 to 0.95, P = .006) compared to DEX(-) patients. The DEX(+) patients demonstrated no differences in the odds of surgical site infection, periprosthetic joint infection, or sepsis compared to the DEX(-) patients (P > .05). CONCLUSIONS: The administration of DEX was associated with a decreased risk of PE and DVT in patients who have a history of VTE who underwent TJA. These data warrant further study investigating the postoperative benefits of perioperative DEX administration for high-risk patients undergoing TJA. LEVEL OF EVIDENCE: Level III.

Super-Obesity is Associated With an Increased Risk of Complications Following Primary Total Knee Arthroplasty.

BACKGROUND: Obesity, defined as a body mass index (BMI) ≥ 30, is an ever-growing epidemic, with > 35% of adults in the United States currently classified as obese. Super-obese individuals, defined as those who have a BMI ≥ 50, are the fastest-growing portion of this group. This study sought to quantify the infection risk as well as the incidence of surgical, medical, and thromboembolic complications among super-obese patients undergoing total knee arthroplasty (TKA). METHODS: An all-payer claims database was used to identify patients who underwent elective, primary TKA between 2016 and 2021. Patients who had a BMI ≥ 50 were compared to those who had a normal BMI of 18 to 25. Demographics and the incidence of 90-days postoperative complications were compared between the 2 groups. Univariate analysis and multivariable regression were used to assess differences between groups. RESULTS: In total, 3,376 super-obese TKA patients were identified and compared to 17,659 patients who had a normal BMI. Multivariable analysis indicated that the super-obese cohort was at an increased postoperative risk of periprosthetic joint infection (adjusted odds ratio [aOR] 3.7, 95% confidence interval [CI]: 2.1 to 6.4, P < .001), pulmonary embolism (aOR 2.2, 95%-CI: 1.0 to 5.0, P = .047), acute respiratory failure (aOR 4.1, 95%-CI: 2.7 to 6.1, P < .001), myocardial infarction (aOR 2.5, 95%-CI: 1.1 to 5.8, P = .026), wound dehiscence (aOR 2.3, 95%-CI: 1.4 to 3.8, P = .001), and acute renal failure (aOR 3.2, 95%-CI: 2.4 to 4.2, P < .001) relative to patients who have normal BMI. CONCLUSIONS: Super-obese TKA patients are at an elevated risk of postoperative infectious, surgical, medical, and thromboembolic complications. As such, risk stratification, as well as appropriate medical management and optimization, is of utmost importance for this high-risk group.

Dexamethasone-Associated Hyperglycemia is Not Associated With Infectious Complications After Total Joint Arthroplasty in Diabetic Patients.

BACKGROUND: Postoperative infection is a devastating complication of total joint arthroplasty (TJA). Perioperative use of dexamethasone in patients who have diabetes mellitus (DM) remains controversial due to concern for increased infection risk. This study aimed to evaluate the association between dexamethasone and infection risk among patients who have DM undergoing TJA. METHODS: This was a retrospective cohort study conducted on adult patients who underwent primary, elective total knee arthroplasty (TKA) or total hip arthroplasty (THA) between January 2016 and December 2021 using a large national database. We identified 110,568 TJA patients (TKA: 66.6%; THA: 33.4%), 31.0% (34,298) of which had DM. Patients who received perioperative dexamethasone were compared to those who did not. The primary end points were the 90-day risk of postoperative periprosthetic joint infection, surgical site infection (SSI), and other non-SSI (urinary tract infection, pneumonia, sepsis). RESULTS: When modeling the association between dexamethasone exposure and study outcomes while accounting for the interaction between dexamethasone and morning blood glucose levels, dexamethasone administration conferred no increased odds of postoperative periprosthetic joint infection nor SSI in diabetics. However, dexamethasone significantly lowered the adjusted odds of other postoperative infections in diabetic patients (TKA: adjusted odds ratio = 09, 95% confidence interval = 0.8 to 1.0, P = .030; THA: adjusted odds ratio = 0.7, 95% confidence interval = 0.6 to 0.9, P = .001); specifically in patients with morning blood glucose levels between 110 to 248 mg/dL in TKA and ≤ 172 mg/dL in THA. CONCLUSIONS: This study provides strong evidence against withholding dexamethasone in diabetic patients undergoing TJA based on concern for infection. Instead, short-course perioperative dexamethasone reduced infection risk in select patients. The narrative surrounding dexamethasone should shift away from questions about whether dexamethasone is appropriate for diabetic patients, and instead focus on how best to optimize its use.

The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis.

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline.

How to diagnose IgE-mediated food allergy.

Immunoglobulin E (IgE)-mediated food allergy is an immune response, typically to a food protein. Accurate diagnosis reduces unnecessary dietary restrictions and economic and psychological burden on patients and caregivers but relies on a rigorous clinical history, specific IgE diagnostic tests and, where needed, oral food challenge. Increased awareness is needed around which patients to test for IgE-mediated food allergy, as well as terms commonly associated with IgE-mediated food allergy testing, in order to optimise patient diagnosis and management. Herein, we describe approaches to diagnosis of IgE-mediated food allergy, appropriate interpretation of results and risks of overtesting.

Biodistribution of lentiviral transduced adipose-derived stem cells for "ex-vivo" regional gene therapy for bone repair.

Ex-vivo gene therapy has been shown to be an effective method for treating bone defects in pre-clinical models. As gene therapy is explored as a potential treatment option in humans, an assessment of the safety profile becomes an important next step. The purpose of this study was to evaluate the biodistribution of viral particles at the defect site and various internal organs in a rat femoral defect model after implantation of human ASCs transduced with lentivirus (LV) with two-step transcriptional activation (TSTA) of bone morphogenetic protein-2 (LV-TSTA-BMP-2). Animals were sacrificed at 4-, 14-, 56-, and 84-days post implantation. The defects were treated with either a standard dose (SD) of 5 million cells or a high dose (HD) of 15 million cells to simulate a supratherapeutic dose. Treatment groups included (1) SD LV-TSTA-BMP-2 (2) HD LV-TSTA-BMP-2, (3) SD LV-TSTA-GFP (4) HD LV-TSTA-GFP and (5) SD nontransduced cells. The viral load at the defect site and ten organs was assessed at each timepoint. Histology of all organs, ipsilateral tibia, and femur were evaluated at each timepoint. There were nearly undetectable levels of LV-TSTA-BMP-2 transduced cells at the defect site at 84-days and no pathologic changes in any organ at all timepoints. In conclusion, human ASCs transduced with a lentiviral vector were both safe and effective in treating critical size bone defects in a pre-clinical model. These results suggest that regional gene therapy using lentiviral vector to treat bone defects has the potential to be a safe and effective treatment in humans.

Influence of donor age and comorbidities on transduced human adipose-derived stem cell in vitro osteogenic potential.

Human adipose-derived mesenchymal stem cells (ASCs) transduced with a lentiviral vector system to express bone morphogenetic protein 2 (LV-BMP-2) have been shown to reliably heal bone defects in animal models. However, the influence of donor characteristics such as age, sex, race, and medical co-morbidities on ASC yield, growth and bone regenerative capacity, while critical to the successful clinical translation of stem cell-based therapies, are not well understood. Human ASCs isolated from the infrapatellar fat pads in 122 ASC donors were evaluated for cell growth characteristics; 44 underwent additional analyses to evaluate in vitro osteogenic potential, with and without LV-BMP-2 transduction. We found that while female donors demonstrated significantly higher cell yield and ASC growth rates, age, race, and the presence of co-morbid conditions were not associated with differences in proliferation. Donor demographics or the presence of comorbidities were not associated with differences in in vitro osteogenic potential or stem cell differentiation, except that transduced ASCs from healthy donors produced more BMP-2 at day 2. Overall, donor age, sex, race, and the presence of co-morbid conditions had a limited influence on cell yield, proliferation, self-renewal capacity, and osteogenic potential for non-transduced and transduced (LV-BMP-2) ASCs. These results suggest that ASCs are a promising resource for both autologous and allogeneic cell-based gene therapy applications.

BT595, a 10% Human Normal Immunoglobulin, for Replacement Therapy of Primary Immunodeficiency Disease: Results of a Subcohort Analysis in Children.

PURPOSE: To assess the efficacy, pharmacokinetics, and safety of a new, highly purified 10% IVIg (BT595, Yimmugo®) administered in children with PID. METHODS: This was an open-label, prospective, uncontrolled, multicenter Phase III pivotal trial. Among the 67 subjects in the trial were 18 pediatric patients aged 2 to 17 years with diagnosis of PID included in this analysis. They received doses between 0.2 and 0.8 g/kg body weight for approximately 12 months at intervals of either 3 or 4 weeks. Dosage and dosing interval were based on each patient's pre-trial infusion schedule. The rates of acute serious bacterial infections (SBI), secondary efficacy, safety, and pharmacokinetic outcomes were evaluated. RESULTS: No SBI occurred in the pediatric population. Two hundred sixty infusions were administered to the 18 pediatric patients. The mean (SD) IgG trough level was 8.55 (1.67) g/L at baseline and 8.84 (2.17) g/L at the follow-up visit after the last BT595 infusion. At the single infusions respectively, the average mean IgG trough levels ranged between 8.52 and 10.58 g/L. More than 85% of all infusions administered were not associated with any infusional AE (start during or within 72 h post-infusion). None of the severe or serious AEs were related to the investigational medicinal product (IMP). No premedication was used. Thirteen children reached a maximum infusion rate between > 2.0 and 8 mL/kg/h; no AE with an onset during the infusion occurred at these infusion rates. CONCLUSION: BT595 is effective, convenient, well tolerated, and safe for the treatment of children with PID. TRIAL REGISTRATION: EudraCT: 2015-003652-52; NCT02810444, registered June 23, 2016.

The future of food allergy: Challenging existing paradigms of clinical practice.

The field of food allergy has seen tremendous change over the past 5-10 years with seminal studies redefining our approach to prevention and management and novel testing modalities in the horizon. Early introduction of allergenic foods is now recommended, challenging the previous paradigm of restrictive avoidance. The management of food allergy has shifted from a passive avoidance approach to active interventions that aim to provide protection from accidental exposures, decrease allergic reaction severity and improve the quality of life of food-allergic patients and their families. Additionally, novel diagnostic tools are making their way into clinical practice with the goal to reduce the need for food challenges and assist physicians in the-often complex-diagnostic process. With all the new developments and available choices for diagnosis, prevention and therapy, shared decision-making has become a key part of medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments as well as the evolution of the field of food allergy in the next decade.

Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children.

BACKGROUND: Epicutaneous immunotherapy with investigational Viaskin™ Peanut 250 µg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear whether serologic biomarkers predict response. METHODS: Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE-Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge. RESULTS: Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p < 0.001) and had highest area under the curve (AUC) for predicting ED ≥300 mg and ≥1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE >20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kUA /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg). CONCLUSIONS: Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.

Innovations in the treatment of anaphylaxis: A review of recent data.

PURPOSE OF REVIEW: The current standard of first-line emergency treatment of anaphylaxis is intramuscular (IM) epinephrine, mostly administered through epinephrine autoinjector (EAI) in the outpatient setting. However, undercarriage and underuse of EAIs are common, and delayed epinephrine use is associated with increased morbidity and mortality. Patients, caregivers, and healthcare professionals have expressed a strong desire for small, needle-free devices and products that would offer improved carriage, ease of use, and more convenient, less invasive routes of epinephrine administration. Novel mechanisms of epinephrine administration are under investigation to help address several recognized EAI limitations. This review explores innovative nasal and oral products under investigation for the outpatient emergency treatment of anaphylaxis. FINDINGS: Human studies of epinephrine administered through nasal epinephrine spray, a nasal powder spray, and a sublingual film have been conducted. Data from these studies indicate promising pharmacokinetic results comparable to those of the standard of outpatient emergency care (0.3-mg EAI) and syringe and needle IM epinephrine administration. Several products have shown maximum plasma concentration values higher than those of the 0.3-mg EAI and manual IM injection, although it remains unclear whether this has clinical relevancy in patient outcomes. Generally, these modalities show comparable time to maximum concentrations. Pharmacodynamic changes observed with these products are comparable to or more robust than those seen with EAI and manual IM injection. SUMMARY: Given comparable or superior pharmacokinetic and pharmacodynamic results and safety of innovative epinephrine therapies to those of current standards of care, US Food and Drug Administration approval of these products may help address numerous barriers that EAIs present. The ease of use and carriage and favorable safety profiles of needle-free treatments may make them an attractive alternative to patients and caregivers, potentially addressing injection fears, needle-based safety risks, and other reasons for lack of or delayed use.

Yardstick for managing cough, part 2: In children.

Nationwide statistics in the United States and Australia reveal that cough of undifferentiated duration is the most common complaint for which patients of all ages seek medical care in the ambulatory setting. Management of chronic cough is one of the most common reasons for new patient visits to respiratory specialists. Because symptomatic cough is such a common problem and so much has been learned about how to diagnose and treat cough of all durations but especially chronic cough, this 2-part yardstick has been written to review in a practical way the evidence-based guidelines most of which have been developed from high-quality systematic reviews on how best to manage cough of all durations in adults, adolescents, and children. Chronic cough in children is often benign and self-limiting. Using established and validated protocols and specific pointers (clues in history, findings on examination) can aid the clinician in identifying causes when present and improve outcomes. In this manuscript, part 2 of the 2-part series, we provide evidence-based, expert opinion recommendations on the management of chronic cough in the pediatric patient (<14 years of age).