[Show abstract][Hide abstract] ABSTRACT: Introduction: The systematic application of human factors engineering (HFE) principles to the development of drug-device combination products, including epinephrine auto-injectors (EAIs), has the potential to improve the effectiveness and safety of drug administration. Areas covered: A PubMed search was performed to assess the role of HFE in the development of drug-device combination products. The following keywords were used in different combinations: 'human factors engineering,' 'human factors,' 'medical products,' 'epinephrine/adrenaline auto-injector,' 'healthcare' and 'patient safety.' This review provides a summary of HFE principles and their application to the development of drug-device combination products as advised by the US FDA. It also describes the HFE process that was applied to the development of Auvi-Q, a novel EAI, highlighting specific steps that occurred during the product-development program. Expert opinion: For drug-device combination products, device labeling and usability are critical and have the potential to impact clinical outcomes. Application of HFE principles to the development of drug-delivery devices has the potential to improve product quality and reliability, reduce risk and improve patient safety when applied early in the development process. Additional clinical and real-world studies will confirm whether the application of HFE has helped to develop an EAI that better meets the needs of patients at risk of anaphylaxis.
Expert Opinion on Drug Delivery 12/2014; · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model.Methods
The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively.Key findingsEpimean(standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P > 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P < 0.05) than after placebo RDSTs administration (reflecting endogenous adrenaline levels).Conclusion
Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings.
[Show abstract][Hide abstract] ABSTRACT: This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).
[Show abstract][Hide abstract] ABSTRACT: Anaphylaxis is a serious allergic or hypersensitivity reaction, which is rapid in onset and sometimes can prove fatal. Although H2-antihistamines are often administered for emergency treatment in anaphylaxis, there is uncertainty about their effectiveness in this disease.
To assess the benefits and harms of H2-antihistamines in the treatment of anaphylaxis.
A systematic review was performed of randomized controlled trials and quasi-randomized controlled trials comparing H2-antihistamines with placebo or no intervention in patients with anaphylaxis.
The authors failed to identify any eligible studies for inclusion in this systematic review.
When H2-antihistamines are recommended for anaphylaxis treatment, the status of the evidence base supporting their use should be described. Well-designed randomized controlled trials investigating the role of H2-antihistamines in anaphylaxis treatment are urgently needed.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 02/2014; 112(2):126-31. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction. They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice. For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available. ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research. IN ADDITION TO CONFIRMING THE ALIGNMENT OF MAJOR ANAPHYLAXIS GUIDELINES, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public.
The World Allergy Organization journal. 01/2014; 7(1):9.
[Show abstract][Hide abstract] ABSTRACT: Although anaphylaxis is recognized as an important life-threatening condition, data are limited regarding its prevalence and characteristics in the general population.
We sought to estimate the lifetime prevalence and overall characteristics of anaphylaxis.
Two nationwide, cross-sectional random-digit-dial surveys were conducted. The public survey included unselected adults, whereas the patient survey captured information from household members reporting a prior reaction to medications, foods, insect stings, or latex and idiopathic reactions in the previous 10 years. In both surveys standardized questionnaires queried anaphylaxis symptoms, treatments, knowledge, and behaviors.
The public survey included 1,000 adults, of whom 7.7% (95% CI, 5.7% to 9.7%) reported a prior anaphylactic reaction. Using increasingly stringent criteria, we estimate that 5.1% (95% CI, 3.4% to 6.8%) and 1.6% (95% CI, 0.8% to 2.4%) had probable and very likely anaphylaxis, respectively. The patient survey included 1,059 respondents, of whom 344 reported a history of anaphylaxis. The most common triggers reported were medications (34%), foods (31%), and insect stings (20%). Forty-two percent sought treatment within 15 minutes of onset, 34% went to the hospital, 27% self-treated with antihistamines, 10% called 911, 11% self-administered epinephrine, and 6.4% received no treatment. Although most respondents with anaphylaxis reported 2 or more prior episodes (19% reporting ≥5 episodes), 52% had never received a self-injectable epinephrine prescription, and 60% did not currently have epinephrine available.
The prevalence of anaphylaxis in the general population is at least 1.6% and probably higher. Patients do not appear adequately equipped to deal with future episodes, indicating the need for public health initiatives to improve anaphylaxis recognition and treatment.
The Journal of allergy and clinical immunology 10/2013; · 12.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Few anaphylaxis education materials have been prospectively evaluated in randomized controlled trials.
Our objective was to evaluate the American Academy of Allergy, Asthma & Immunology Anaphylaxis Wallet Card (AAAAI-AWC) as an anaphylaxis education mini-handout for health care professionals.
We performed a randomized controlled study of the AAAAI-AWC with residents in general pediatrics at Miami Children's Hospital. Participants in the intervention group completed a pretest about anaphylaxis, heard a 3-minute PowerPoint presentation based on the AAAAI-AWC, reviewed the AAAAI-AWC, and discussed it with the presenter. After this, participants took a post-test immediately and a follow-up test 4 weeks later. Participants in the control group took the pretest, were handed an AAAAI-AWC, studied it briefly, then took the post-test immediately and the follow-up test 4 weeks later.
Fifty-five residents participated. Regardless of the amount of time spent studying the AAAAI-AWC, when the pretests were compared with the post-tests and follow-up tests, residents in both the intervention and control groups were more likely to recognize anaphylaxis symptoms (P < .05), name asthma as the most common comorbid disease in children with fatal or near-fatal anaphylaxis (P < .05), and recall the names of epinephrine auto injectors (P < .05) and the epinephrine doses available in these auto injectors (P < .05). When the pretests were compared with the post-tests and the follow-up tests, residents in the intervention group were more likely than controls to identify the body organ systems involved in severe or fatal anaphylaxis correctly (P < .05).
The AAAAI-AWC is a practical, concise anaphylaxis education mini-handout for pediatric residents, a time-challenged group of health care professionals.
The Journal of Allergy and Clinical Immunology: In Practice. 03/2013; 1(2):181–185.
[Show abstract][Hide abstract] ABSTRACT: Background
Auvi-Q is a novel epinephrine autoinjector (EAI) that provides audio and visual cues for patients at risk for life-threatening allergic reactions.
We tested the preference for Auvi-Q or EpiPen with regard to method of instruction, preference to carry, device size, and device shape.
This large, multicenter, simulated-use study evaluated whether adults (aged 18-65 years), caregivers (parents/guardians aged 18-65 years of children aged 5-17 years), and children (aged 11-17 years), with and without experience in using an EAI, had a preference for the current design of Auvi-Q or the current design of EpiPen. Participants were given a scenario that involved anaphylaxis and were instructed to simulate use of an EAI. They received and tested each device individually according to the randomization assignment. After testing both devices, they completed a survey to indicate their preference for Auvi-Q versus EpiPen.
Among all 693 participants combined, Auvi-Q was preferred over EpiPen on all study end points (P < .001). For experienced and inexperienced participants in all 3 groups (adults, caregivers, and children), Auvi-Q was preferred over EpiPen for method of instruction, preference to carry, and device size (all P < .001). The preference for Auvi-Q device shape was not significant among experienced children (P = .10); however, it was significant for inexperienced children (P = .04) and highly significant for experienced and inexperienced adults and caregivers (P < .001).
In this large multicenter, simulated-use study, Auvi-Q was preferred over EpiPen by experienced and inexperienced adults, caregivers, and children.
The Journal of Allergy and Clinical Immunology: In Practice. 02/2013; 1(3):266–272.e3.
[Show abstract][Hide abstract] ABSTRACT: To determine if chronic pulmonary diseases adversely impact selected outcomes in hospitalised patients who have various allergic conditions including anaphylaxis.
A population-based cohort study.
A statewide hospital inpatient discharge database from Texas, USA, covering the years 2004-2007 was analysed. Patients with anaphylaxis and other allergic conditions were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Within each group of patients (the overall group with various selected allergic conditions and the subgroup with anaphylaxis), the exposure variables were 11 chronic pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis.
Admission to an intensive care unit, a prolonged (>3 days) hospital stay, receipt of mechanical ventilation and death in hospital. Logistic regression was used to calculate adjusted OR and 95% CI for these four outcomes.
30 390 patients with allergic conditions were identified, of whom 2410 had anaphylaxis. The following results pertain to the subcohort of patients with anaphylaxis. Median age was 50 years (range 0-95 years) and 1470 (61%) were female. The hospital mortality was 2.7%. Although asthma was not associated with hospital mortality (OR=1.27, 95% CI 0.55 to 2.90), asthmatics had more than twice the odds of non-asthmatics of receiving mechanical ventilation (OR=2.45, 95% CI 1.81 to 3.33). Chronic bronchitis, COPD, emphysema and interstitial lung diseases (ILDs) were also associated with an increased risk of requiring mechanical ventilation. Chronic bronchitis and COPD were associated with a prolonged length of stay: OR=2.69 (95% CI 1.45 to 4.98) and OR=1.86 (95% CI 1.30 to 2.66), respectively. ILD was the only chronic pulmonary disease associated with an elevated risk of hospital mortality: OR=8.71 (95% CI 1.48 to 51.20).
In this unique analysis of a large database, we found that asthma, COPD and other chronic pulmonary diseases increased the risk of adverse outcomes among hospitalised patients with anaphylaxis.
[Show abstract][Hide abstract] ABSTRACT: Patients with severe or difficult-to-treat asthma account for substantial asthma morbidity, mortality, and healthcare burden despite comprising only a small proportion of the total asthma population. TENOR, a multicenter, observational, prospective cohort study was initiated in 2001. It enrolled 4,756 adults, adolescents and children with severe or difficult-to-treat asthma who were followed semi-annually and annually for three years, enabling insight to be gained into this understudied population. A broad range of demographic, clinical, and patient self-reported assessments were completed during the follow-up period. Here, we present key findings from the TENOR registry in relation to asthma control and exacerbations, including the identification of specific subgroups found to be at particularly high-risk. Identification of the factors and subgroups associated with poor asthma control and increased risk of exacerbations can help physicians design individual asthma management, and improve asthma-related health outcomes for these patients.
Current respiratory care reports. 12/2012; 1(4):259-269.