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over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context.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.

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.

Food allergen ladders: A need for standardization.

INTRODUCTION: The process of gradually reintroducing food allergens into an individual's diet is referred to as food allergen "ladders". There remain many questions regarding the foods chosen, structure and composition of the ladder, and medical and safety considerations. The COVID-19 pandemic has propelled us into an era where medicine is increasingly practiced via online platforms, highlighting the need for standardized food allergen ladder approaches for successful and safe introduction of food allergens. METHODS: We performed a search of currently published food allergen ladders and obtained published information and clinical expertise to summarize current knowledge and suggest future standardized approaches for using food allergen ladders. RESULTS: There are currently a limited number of published milk, egg, wheat, and soy ladders. We suggest the following points should be considered when developing food ladders: (1) Food allergen: dose, time, and temperature of heating of the food allergen, simplicity of the ladder and recipes, the possible role of the wheat matrix, and testing for allergenic protein levels to standardize doses; (2) Nutritional factors: health and nutritional value of the foods in the ladder, taste, texture, and cultural appropriateness of foods should be considered; and (3) Medical aspects: consideration of which patients are safe to undergo ladders outside of the clinical setting, other safety aspects and risk factors for severe reactions, number of days suggested per steps, and availability and provision of rescue medication. Written instructions and recipes should be provided to families who wish to use food allergen ladders. DISCUSSION: Food allergen ladders used for gradual reintroduction of food allergens into a food allergic individual's diet are increasingly being used internationally. Standardization regarding the foods included in the ladder and medical considerations are required to practice patient-centered care, best assist patients and families, and ensure safety.

Electrophysiological and Behavioral Responses of Adult Vine Weevil, Otiorhynchus sulcatus (Coleoptera: Curculionidae), to Host Plant Odors.

Vine weevil, Otiorhynchus sulcatus F. (Coleoptera: Curculionidae), is an economically important pest species in many soft-fruit and ornamental crops. Economic losses arise from damage to the roots, caused by larvae, and to the leaves, caused by adults. As adults are nocturnal and larvae feed below ground, infestations can be missed initially, with controls applied too late. In the absence of a vine weevil sex or aggregation pheromone, the development of an effective semiochemical lure for better management of this pest is likely to focus on host-plant volatiles. Here, we investigate the electrophysiological and behavioral responses of adult vine weevils to volatile organic compounds (VOCs) originating from their preferred host plant Euonymus fortunei, and synthetic VOCs associated with this host when presented individually or as blends. Consistent electroantennographic responses were observed to a range of generalist VOCs. Behavioral responses of weevils to VOCs, when presented individually, were influenced by concentration. Vine weevil adults showed directional movement toward a mixture of seven plant volatiles, methyl salicylate, 1-octen-3-ol, (E)-2-hexenol, (Z)-3-hexenol, 1-hexanol, (E)-2-pentenol, and linalool, even though no, or negative, responses were recorded to each of these compounds presented individually. Similarly, vine weevils showed directional movement toward a 1:1 ratio mixture of (Z)-2-pentenol and methyl eugenol. Results presented here point to the importance of blends of generalist compounds and their concentrations in the optimization of a lure.

Screening for tuberculosis in migrants and visitors from high-incidence settings: present and future perspectives.

In most settings with a low incidence of tuberculosis (TB), foreign-born people make up the majority of TB cases, but the distribution of the TB risk among different migrant populations is often poorly quantified. In addition, screening practices for TB disease and latent TB infection (LTBI) vary widely. Addressing the risk of TB in international migrants is an essential component of TB prevention and care efforts in low-incidence countries, and strategies to systematically screen for, diagnose, treat and prevent TB among this group contribute to national and global TB elimination goals.This review provides an overview and critical assessment of TB screening practices that are focused on migrants and visitors from high to low TB incidence countries, including pre-migration screening and post-migration follow-up of those deemed to be at an increased risk of developing TB. We focus mainly on migrants who enter the destination country via application for a long-stay visa, as well as asylum seekers and refugees, but briefly consider issues related to short-term visitors and those with long-duration multiple-entry visas. Issues related to the screening of children and screening for LTBI are also explored.

Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study.

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.

Tuberculosis notifications in Australia, 2014.

In 2014, the National Notifiable Diseases Surveillance System received 1,339 tuberculosis (TB) notifications, representing a rate of 5.7 per 100,000 population. Australia has achieved and maintained good tuberculosis (TB) control since the mid-1980s, sustaining a low annual TB incidence rate of approximately 5 to 6 cases per 100,000 population. The number of multi-drug resistant TB (MDR-TB) cases diagnosed in Australia is low by international standards, with approximately 1-2% of notifications per year being classified as MDR-TB. Australia's overseas-born population continued to represent the majority (86%) of TB notifications and Australia's Aboriginal and Torres Strait Islander population continue to record TB rates around 6 times higher than the Australian born non Indigenous population. Whilst Australia has achieved excellent and sustained control of TB in Australia, sustained effort is still required to reduce rates further and contribute to the achievement of the World Health Organization's goal to end the global TB epidemic by 2035.

Towards tuberculosis elimination: an action framework for low-incidence countries.

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

The epidemiology of tuberculosis in children in Australia, 2003-2012.

OBJECTIVE: To describe the burden of and trends in paediatric tuberculosis (TB) in Australia between 2003 and 2012. DESIGN: A retrospective analysis of TB data from the National Notifiable Diseases Surveillance System (NNDSS) on TB in children (under 15 years of age) during the 10-year period, 2003-2012. RESULTS: TB notifications in Australia during the study period included 538 children (range, 37-66 cases per year), representing 4.6% of the total TB case load during the period (range, 3.8%-5.8% each year). Place of birth was recorded for 524 patients (97.4%); of these, 230 (43.9%) were born in Australia, 294 (56.1%) overseas. The average annual notification rate was 1.31 (95% CI, 1.20-1.43) cases per 100 000 child population. The rate was higher for overseas-born than for Australian-born children (9.57 [95% CI, 8.51-10.73] v 0.61 [95% CI, 0.53-0.69] cases per 100 000 children. The overall rate was highest among those aged 0-4 years. The annual notification rate was three times higher for Indigenous children than for non-Indigenous Australian-born children. Of 427 patients (79.4% of total) for whom the method of case detection was recorded, 37.0% were detected by contact screening, 8.7% by post-arrival immigration screening, and 54.3% by passive case detection. Pulmonary TB was the most common diagnostic classification (64.7% of patients). The most common risk factors were close contact with a TB case and recent residence in a country with a high incidence of TB. Treatment outcomes were satisfactory; 89.4% of children had completed treatment or were cured. CONCLUSIONS: The burden of paediatric TB in Australia is low but has not changed over the past decade. The highest rates are among children born overseas, emphasising the important role of immigration screening as Australia aspires to eliminate TB.

Tuberculosis notifications in Australia, 2012 and 2013.

The National Notifiable Diseases Surveillance System received 1,317 tuberculosis (TB) notifications in 2012 and 1,263 notifications in 2013. This represents a rate of 5.8 per 100,000 population in 2012 and 5.5 per 100,000 population in 2013 and a reversal of the upward trend in TB incidence reported since 2007. In 2012 and 2013, Australia's overseas-born population continued to represent the majority of TB notifications with an incidence rate of 19.5 per 100,000 and 18.4 per 100,000 respectively. The incidence of TB in the Australian-born Indigenous population has fluctuated over the last decade; however, it remained reasonably steady in 2012 and 2013 with an incidence rate of 4.5 per 100,000 and 4.6 per 100,000 respectively. The incidence of TB in the Australian-born non-Indigenous population has continued to remain low at 0.7 per 100,000 in 2012 and 0.8 per 100,000 in 2013. Australia continued to record only a small number of multi-drug resistant TB cases nationally (2012: n=20; 2013: n=22) of which nearly all were identified in the overseas-born population. This report demonstrates excellent and sustained control of TB in Australia and reflects Australia's commitment to reducing the global burden of TB.

Further studies on sex pheromones of female Lygus and related bugs: development of effective lures and investigation of species-specificity.

Mirid bugs (Heteroptera: Miridae) are important pests of many crops worldwide. In previous work by others and ourselves, several species of Lygus bugs were shown to produce blends of three compounds, hexyl butyrate, (E)-2-hexenyl butyrate, and (E)-4-oxo-2-hexenal. These have been proposed as components of the female-produced sex pheromones, but attraction of males to synthetic lures has been difficult to demonstrate. We studied the volatiles released by females of four species: Lygus rugulipennis, Lygus pratensis, Lygocoris pabulinus, and Liocoris tripustulatus. Analyses of volatiles from individual, undisturbed insects showed that the three compounds were produced in species-specific blends, by females only, or in greater quantities by females than by males. The three compounds were loaded into pipette tips, which released the defined blends over at least 30 days. Traps baited with the blend for L. rugulipennis caught more males than traps baited with virgin females, with all three compounds required for maximum attractiveness. Traps baited with the specific blends for each of the four species caught males of three of the species, indicating considerable cross-attraction. There is evidence that other, non-chemical factors, such as time-of-day of production of pheromone, contribute to species-specificity of attraction. This is the first report of consistent attraction of Lygus bugs to synthetic lures in the field.

Tuberculosis notifications in Australia, 2011.

The National Notifiable Diseases Surveillance System received 1,385 tuberculosis (TB) notifications in 2011, representing a rate of 6.2 cases per 100,000 population. While Australia has maintained a rate of 5 to 6 cases per 100,000 for TB since the mid-1980s, there has been a steady increase in incidence over the past decade. In 2011, Australia's overseas-born population continued to represent the majority of TB notifications (88%) with a notification rate of 20.2 per 100,000. The incidence of TB in the Australian-born Indigenous population has fluctuated over the last decade and showed no clear trend; however, in 2011 the notification rate was 4.9 per 100,000, which is a notable decrease from the 7.5 per 100,000 recorded in 2010. The incidence of TB in the Australian-born non-Indigenous population has continued to remain low at 0.9 per 100,000. Australia continued to record only a small number of multi-drug-resistant TB (MDR-TB) cases nationally (n=25), all of which were identified in the overseas-born population. To ensure that Australia can retain its low TB rate and work toward reducing rates further, it is essential that Australia maintains good centralised national TB reporting to monitor trends and identify at-risk populations, and continues to contribute to global TB control initiatives.

The impact of prolonged violent video-gaming on adolescent sleep: an experimental study.

Video-gaming is an increasingly prevalent activity among children and adolescents that is known to influence several areas of emotional, cognitive and behavioural functioning. Currently there is insufficient experimental evidence about how extended video-game play may affect adolescents' sleep. The aim of this study was to investigate the short-term impact of adolescents' prolonged exposure to violent video-gaming on sleep. Seventeen male adolescents (mean age = 16 ± 1 years) with no current sleep difficulties played a novel, fast-paced, violent video-game (50 or 150 min) before their usual bedtime on two different testing nights in a sleep laboratory. Objective (polysomnography-measured sleep and heart rate) and subjective (single-night sleep diary) measures were obtained to assess the arousing effects of prolonged gaming. Compared with regular gaming, prolonged gaming produced decreases in objective sleep efficiency (by 7 ± 2%, falling below 85%) and total sleep time (by 27 ± 12 min) that was contributed by a near-moderate reduction in rapid eye movement sleep (Cohen's d = 0.48). Subjective sleep-onset latency significantly increased by 17 ± 8 min, and there was a moderate reduction in self-reported sleep quality after prolonged gaming (Cohen's d = 0.53). Heart rate did not differ significantly between video-gaming conditions during pre-sleep game-play or the sleep-onset phase. Results provide evidence that prolonged video-gaming may cause clinically significant disruption to adolescent sleep, even when sleep after video-gaming is initiated at normal bedtime. However, physiological arousal may not necessarily be the mechanism by which technology use affects sleep.

Are There Hidden Dangers Associated With Milk and Egg Dietary Advancement Therapy?

Dietary advancement therapies (DATs) constitute a continuum spanning extensively heated item ingestion, progressive milk or egg ladders, and oral immunotherapy (OIT). These represent an evolution in food allergy management from strict avoidance to an active therapy that may modulate the immune system to develop tolerance to particular forms of the allergen. Many egg or milk individuals are tolerant to baked egg or milk at baseline, and regular consumption (at home ingestion) of baked milk or egg is a safe process with potential quality of life and immunologic benefit. Milk and egg ladders, developed for non-IgE mediated allergy, are increasingly being adapted to IgE-mediated allergy as a potentially safe at-home option for gradual dietary advancement. However, data are limited regarding how safe and effective these approaches are or what patient is best suited for which DAT. It is also unclear whether extensively heated allergen consumption and ladders are susceptible to the same patient-specific factors that affect day-to-day tolerance and safety in OIT. Several recent events involving near-fatal or fatal reactions to milk or egg products (all among patients with asthma) have highlighted that DATs are not risk-free, and that physician guidance in these therapies is essential. Such guidance may include obtaining informed consent before starting any DAT and instituting the same safe dosing rules for OIT across any form of DAT. This rostrum discusses practical concerns about the safety of DAT, and considerations regarding how clinicians can maximize patient protection while defining the safety and efficacy of real-world implementation of these concepts.

Synthesis of compounds related to the anti-migraine drug eletriptan hydrobromide.

Eletriptan hydrobromide (1) is a selective serotonin (5-HT(1)) agonist, used for the acute treatment of the headache phase of migraine attacks. During the manufacture of eletriptan hydrobromide the formation of various impurities were observed and identified by LC-MS. To control the formation of these impurities during the preparation of active pharmaceutical ingredients, the structure of the impurities must be known. Major impurities of the eletriptan hydrobromide synthesis were prepared and characterized by using various spectroscopic techniques, i.e., mass spectroscopy, FTIR , (1)H NMR, (13)C NMR/DEPT, and further confirmed by co-injection in HPLC. The present study will be of great help in the synthesis of highly pure eletriptan hydrobromide related compounds.

Evaluation of the Safety Profile of the ASFV Vaccine Candidate ASFV-G-ΔI177L.

African swine fever (ASF) is the cause of a recent pandemic that is posing a threat to much of the world swine production. The etiological agent, ASF virus (ASFV), infects domestic and wild swine, producing a variety of clinical presentations depending on the virus strain and the genetic background of the pigs infected. No commercial vaccine is currently available, although recombinant live attenuated vaccine candidates have been shown to be efficacious. In addition to determining efficacy, it is paramount to evaluate the safety profile of a live attenuated vaccine. The presence of residual virulence and the possibility of reversion to virulence are two of the concerns that must be evaluated in the development of live attenuated vaccines. Here we evaluate the safety profile of an efficacious live attenuated vaccine candidate, ASFV-G-ΔI177L. Results from safety studies showed that ASFV-G-ΔI177L remains genetically stable and phenotypically attenuated during a five-passage reversion to virulence study in domestic swine. In addition, large-scale experiments to detect virus shedding and transmission confirmed that even under varying conditions, ASFV-G-ΔI177L is a safe live attenuated vaccine.

A comparative examination of tuberculosis immigration medical screening programs from selected countries with high immigration and low tuberculosis incidence rates.

BACKGROUND: Tuberculosis (TB) in migrants is an ongoing challenge in several low TB incidence countries since a large proportion of TB in these countries occurs in migrants from high incidence countries. To meet these challenges, several countries utilize TB screening programs. The programs attempt to identify and treat those with active and/or infectious stages of the disease. In addition, screening is used to identify and manage those with latent or inactive disease after arrival. Between nations, considerable variation exists in the methods used in migration-associated TB screening. The present study aimed to compare the TB immigration medical examination requirements in selected countries of high immigration and low TB incidence rates. METHODS: Descriptive study of immigration TB screening programs. RESULTS: 16 out of 18 eligible countries responded to the written standardized survey and phone interview. Comparisons in specific areas of TB immigration screening programs included authorities responsible for TB screening, the primary objectives of the TB screening program, the yield of detection of active TB disease, screening details and aspects of follow up for inactive pulmonary TB. No two countries had the same approach to TB screening among migrants. Important differences, common practices, common problems, evidence or lack of evidence for program specifics were noted. CONCLUSIONS: In spite of common goals, there is great diversity in the processes and practices designed to mitigate the impact of migration-associated TB among nations that screen migrants for the disease. The long-term goal in decreasing migration-related introduction of TB from high to low incidence countries remains diminishing the prevalence of the disease in those high incidence locations. In the meantime, existing or planned migration screening programs for TB can be made more efficient and evidenced based. Cooperation among countries doing research in the areas outlined in this study should facilitate the development of improved screening programs.

Is premigration health screening for tuberculosis worthwhile?

OBJECTIVE: To determine whether premigration screening for tuberculosis is worth undertaking in visa applicants, and whether screening resources are being appropriately directed towards intending migrants at highest risk of tuberculosis. DESIGN, SETTING AND PARTICIPANTS: A 12-month survey of all intending migrants with tuberculosis necessitating treatment detected during the premigration health assessment process, whose medical examinations were submitted to the Department of Immigration and Citizenship's Global Health Branch for assessment by a Medical Officer of the Commonwealth between 1 July 2009 and 30 June 2010. MAIN OUTCOME MEASURES: Individuals diagnosed with active tuberculosis; proportions diagnosed by sputum smear and culture tests or clinically, and with susceptibility test results; distribution of visa types among people diagnosed. RESULTS: In premigration assessments, 519 people were diagnosed with active tuberculosis (prevalence, 137 per 100,000 in examined population). The top source countries for people with tuberculosis were the Philippines (21.8%), India (16.8%), Vietnam (16.2%) and China (8.3%). Positive sputum smear test results were submitted for 67 cases (12.9%). Positive culture test results were obtained in 230 cases (44.3%), but only 95 of these (41.3%) had susceptibility test results, with 83 fully susceptible. Four people had multidrug-resistant tuberculosis (prevalence, 1.06 per 100 000 population). Five people had both active tuberculosis and HIV infection. Of all those diagnosed with tuberculosis, 162 (31.2%) were intending students, 82 (15.8%) were intending visitors, and 53 (10.2%) were applicants for humanitarian (refugee and Special Humanitarian Program) visas. CONCLUSIONS: Premigration health screening of intending migrants is identifying substantial numbers of people who would have required treatment for tuberculosis after arrival in Australia. The high proportion of students, visitors and refugee and humanitarian entrants with tuberculosis validates the current screening program. The screening is of benefit to the applicants, whose tuberculosis is treated earlier than it otherwise would have been, and to the Australian population, by averting exposure to people with active tuberculosis.

CSACI position statement: transition recommendations on existing epinephrine autoinjectors.

Epinephrine is the first line treatment for anaphylaxis, an acute potentially life-threatening allergic reaction. It is typically administered intramuscularly in the anterolateral thigh at a dose of 0.01 mg/kg of 1:1000 (1 mg/ml) solution to a maximum initial dose of 0.5 mg. Currently in Canada, epinephrine autoinjectors (EAI) are available in three doses, 0.15 mg, 0.30 mg, and 0.50 mg. There are currently no published studies comparing 0.3 mg and 0.5 mg EAIs in the paediatric or adult populations to compare clinical effectiveness. However, as weight increases above 30 kg, the percentage of the recommended 0.01 mg/kg epinephrine dose from an existing 0.3 mg EAI decreases resulting in potential underdosing. As such, The Canadian Society of Allergy and Immunology (CSACI) recommends that for those who weigh ≥ 45 kg, physicians could consider prescribing the 0.50 mg EAI based on shared decision making with patients.