Food-specific sublingual immunotherapy is well tolerated and safe in healthy dogs : a blind, randomized, placebo-controlled study

Background: Food allergies are increasing in prevalence but no treatment strategies are currently available to cure dogs with food allergy. Over the past decade, experimental food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a potential treatment for food allergies in human medicine. However, FA-SLIT has not been investigated in dogs. Therefore, the objective of this study was to prospectively evaluate the safety, tolerability and dispenser sterility of FA-SLIT in healthy dogs before testing it in food allergic dogs. Eight experimental healthy beagle dogs, never orally exposed to peanut, were randomized in two groups to receive SLIT with peanut or placebo for 4 months. Subjects were monitored daily for local and systemic adverse effects. Blood samples for complete blood count and serum biochemistry, and urine for urinalysis were collected and the dogs' body weight was recorded at day 0, 35 and 119 of the SLIT treatment. Sera for the determination of peanut-specific IgG and IgE were collected at day 0, 35, 49, 70, 91, 105 and 119. Intradermal tests were performed before (day 0) and after (day 119) the experiment. The content of each dispenser used to administer treatment or placebo was tested for sterility after usage. In order to assess the presence or absence of sensitization, dogs were challenged 6 months after the end of the study with 2000 mu g of peanut extract daily for 7 to 14 days. Results: All dogs completed the study. The treatment did not provoke either local or systemic side-effects. Peanut-specific IgG significantly increased in treatment group. Even though a significant increase in peanut-specific IgE was also seen, intradermal tests were negative in all dogs before and after the experiment, and the challenge test did not trigger any adverse reactions in the treated dogs, which shows the protocol did not cause sensitization to peanut, but nevertheless primed the immune system as indicated by the humoral immune response. All dispenser solutions were sterile. Conclusions: Our results demonstrate that the used peanut-SLIT protocol is well tolerated and safe in healthy dogs. Further studies should evaluate tolerability, safety and efficacy in dogs with food allergy

Food allergen-specific sublingual immunotherapy modulates peripheral T cell responses of dogs with adverse food reactions

Food allergen-specific sublingual immunotherapy (FA-SLIT) is a novel, safe and effective approach in dogs with adverse food reactions (AFR) to reduce their clinical symptoms. However, little is known about the specific immune components which mediate this reduction in clinical symptoms. In humans, regulatory T cells seem to play an important role in this desensitisation process. Here, we investigated changes in peripheral T cell responses of dogs with AFR upon FA-SLIT. Five dogs received a dose escalation of FA-SLIT over a six-month period. An oral food challenge was performed at the beginning and end of the study to assess the efficacy of the FA-SLIT. Using in vitro allergen-recall assays, we assessed the proliferation of T cell subsets before and at the end of the treatment. FA-SLIT significantly increased the percentage of proliferating CD4-CD8- double-negative (DN) T cells, while the percentage of allergen-specific CD4-CD8+ and CD4+CD8+ double-positive (DP) T cells decreased upon treatment. These findings indicate that sublingual immunotherapy in dogs activates DN T cells, which might be important for the desensitisation of dogs with adverse food reactions. However, further research is needed to corroborate these findings and to further elucidate the mechanism of action of FA-SLIT in dogs with AFR

Exploration of gender norms and socialization among early adolescents : the use of qualitative methods for the global early adolescent study

Purpose: The Global Early Adolescent Study (GEAS) was launched in 2014 with the primary goal of understanding the factors in early adolescence that predispose young people to subsequent sexual risks, and conversely, those that promote healthy sexuality across different cultural contexts. The present article describes the methodology that was used for the first phase of GEAS, which consisted of conducting qualitative research to understand the gendered transitions into adolescence and the role that gender norms play within the key relationships of adolescents. Researchers from each of the sites that had completed data collection were also elicited for their feedback on the key strengths, challenges, and lessons learned from conducting research among 11- to 14-year-old adolescents. The purpose of this article is to present the description of each of the methods that were used in GEAS, as well as the researchers' perspectives of using the methods among early adolescents in their sites. Methods: The GEAS is being implemented through a collaboration of university and nongovernmental institutions from 15 cities: Assiut (Egypt) Baltimore (U.S.), Blantyre (Malawi), Cape Town (South Africa), Cochabomba (Bolivia), Cuenca (Ecuador), Edinburgh (Scotland), Ghent (Belgium), Hanoi (Vietnam), Ile-Ife (Nigeria), Kinshasa (DRC), Nairobi (Kenya), New Delhi (India), Ouaga-dougou (Burkina Faso), and Shanghai (China). Approximately 30 in-depth interviews among adolescents and 30 in-depth interviews with their parent/guardian were conducted at each site, with adults and adolescents interviewed separately. To build trust and increase engagement among the adolescent participants, we used two different visual research methods: (1) timeline exercise which was small group based and (2) the Venn diagram exercise which was conducted individually and used at the start of the in-depth interview. Results: The visual aspects of both the timeline and the Venn diagrams not only helped to produce data for the purposes of the study, but also were a successful way of engaging the adolescent participants across sites. While the narrative interviews produced extremely rich data, researchers did notice that there were a few challenges among the younger adolescents. Challenges were related to the length of the interview, comprehension of questions, as some of the questions were either too abstract or asked adolescents about an experience they had not yet had and therefore could not address or articulate. Conclusions: Conducting the first phase of GEAS revealed important insights for research with participants who are in this developmental phase of early adolescence. Methods that involve greater engagement and those that are visual were shown to work well irrespective of the cultural setting

Suicidality in patients with obsessive-compulsive and related disorders (OCRDs): A meta-analysis

© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/Introduction Previous meta-analyses showed that OCD is associated with a substantial risk of suicidal behaviours. Conclusive rates of suicidal ideation (current and lifetime) and suicide attempts based on pooled prevalence rates have not so far been calculated using meta-analysis for the other DSM-5 Obsessive-Compulsive Related Disorders (OCRDs). Objectives This meta-analysis aims to separately calculate the pooled prevalence rates of lifetime suicide attempts and current or lifetime suicidal ideation in BDD, Hoarding Disorder (HD), Skin Picking Disorder (SPD) and Trichotillomania (TTM) and to identify factors associated with increased suicide rates. Methods Our protocol was pre-registered with PROSPERO (CRD42020164395). A systematic review and meta-analysis following PRISMA reporting guidelines was performed by searching in PubMed/Medline, PsycINFO, Web of Science and CINAHL databases from the date of the first available article to April 20th, 2020. Stata version 15 was used for the statistical analysis. Given the small number of studies in TTM and SPD, the two grooming disorders were grouped together. Meta-analyses of proportions based on random effects (Der-Simonian and Laird method) were used to derive the pooled estimates. Results Thirty-nine studies (N=4559 participants) were included: 23 for BDD, 8 for HD, 7 for Grooming Disorders. For BDD, the pooled prevalence of lifetime suicide attempts, current and lifetime suicidal ideation was, respectively 35.2% (CI:23.4-47.8), 37.2% (CI:23.8-51.6) and 66.1% (CI:53.5-77.7). For HD, the pooled prevalence of lifetime suicide attempts, current and lifetime suicidal ideation was 24.1% (CI:12.8-37.6), 18.4% (CI:10.2-28.3) and 38.3% (CI:35.0-41.6), respectively. For Grooming Disorders, the pooled prevalence of lifetime suicide attempts and current suicidal ideation were 13.3% (CI:5.9-22.8) and 40.4% (CI:35.7-45.3), respectively (no data available for lifetime suicidal ideation). Conclusions The OCRDs as a group are associated with relatively high rates of suicidal behaviour. Through indirect comparisons, we infer that BDD has the greatest risk. Comorbid substance abuse, possibly reflecting poor underlying impulse control, is associated with higher rates of suicidal behaviour in BDD. Our data emphasize the need for clinicians to consider the risk of suicidal behaviour in the management of patients presenting with all forms of OCRDs.Peer reviewe

A double blind, randomized, placebo controlled trial of the efficacy, quality of life and safety of food allergen-specific sublingual immunotherapy in client owned dogs with adverse food reactions : a small pilot study

Background - Food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a novel and successful approach for desensitizing human patients to specific food allergens. It has not been tested in dogs. Objective - To investigate the efficacy, quality of life (QoL), tolerability and safety of FA-SLIT in dogs with adverse food reactions (AFR). Methods - Dogs with proven AFR were randomized to treatment (T group; n = 7) or placebo (P group; n = 6) to receive either FA- SLIT (based on the results of a food elimination trial) or glycerinated saline, respectively. The treatment was continued daily for 6 months with fortnightly dosage escalations. To evaluate the treatment, pruritus Visual Analog Scale (pVAS), Canine Atopic Dermatitis Extent and Severity Index (CADESI-04), QoL, faecal consistency scores, owner assessment, overall tolerability scores and blood analyses were assessed. Results - Eleven dogs completed the study, two dogs in the T group were withdrawn by the owner after FA-SLIT exacerbated clinical signs of AFR. Statistical tests showed significant protection against food challenge induced clinical signs following FA- SLIT therapy, as indicated by reduced pVAS and CADESI scores (P < 0.05). The QoL did not differ between groups. The treatment was rated as effective or quite effective by 80% of the owners, whereas placebo was rated as ineffective by all owners. Conclusions and clinical importance - FA- SLIT was effective, well tolerated and safe. No severe adverse events were recorded; erythema and pruritus were reported in association with only 0.7% of the dispensed doses. Larger clinical trials with more extended maintenance immunotherapy periods will be needed to provide more precise estimates of efficacy and frequency of adverse events