Pharmacokinetics, pharmacodynamics, and safety of izuforant, an H4R inhibitor, in healthy subjects: A phase I single and multiple ascending dose study.

Izuforant is a selective, and potent histamine H4 receptor (H4R) antagonist developed to treat atopic dermatitis (AD). There is an unmet medical need for therapeutic agents to control inflammation and pruritus. Izuforant is a strong candidate for this task based on the findings of non-clinical studies showing that inhibition of the histamine-mediated signaling pathway via H4R by izuforant results in decreased pruritus and inflammation. This study aimed to evaluate the clinical pharmacokinetic (PK) and pharmacodynamic (PD) profiles of izuforant. Dose-block-randomized, double-blind, placebo-controlled, single- and multiple ascending dose studies were conducted in 64 healthy volunteers. For the single ascending dose (SAD) study, 10-600 mg izuforant was administered to the designated groups. For the multiple ascending dose (MAD) study, 100-400 mg izuforant was administered to three groups. The clinical pharmacokinetic (PK) profile of izuforant was evaluated using plasma and urine concentrations. Blood sampling for the PD assay, which measured imetit-induced eosinophil shape changes (ESC), was also conducted. A one-compartment PK model described the distribution and elimination profiles of izuforant. An imetit-induced ESC inhibition test was established and validated for PD evaluation as a measure of the H4R antagonistic effect. ESC inhibition was observed even at doses as low as 10 mg; however, this inhibition became stronger and lasted longer as the dose increased. All izuforant doses were well tolerated, and no discontinuations due to adverse events (AE) or deaths were reported.

From Research to Practice: The Latest Data on Evolving Treatments for Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) should be on every dermatology practitioner's radar. CSU is a skin disorder marked by wheals, angioedema, or both for more than 6 weeks. Patients with CSU experience unexplained, itchy wheals that appear and disappear, traveling around the body and lasting less than 24 hours per area. Angioedema accompanies wheals for up to 48 hours in around half of cases. CSU is a diagnosis of exclusion, relying heavily on patient history to differentiate CSU symptoms from other causes of urticaria or angioedema. But reassuringly, CSU has a simple diagnostic algorithm and a clear initial treatment path. First-line strategies include non-pharmacologic approaches, and second-generation antihistamines (2gAH) administered up to 4 times their standard dose. Omalizumab and cyclosporine (off-label) are second- and third-line options, respectively. However, many patients will continue to have CSU symptoms despite consistent maximum-dose treatment. Novel therapies, including biologic agents and small molecule drugs targeting mast cell activation and inflammatory mediators, show promise in treating CSU refractory to standard therapy. However, further research is needed to establish their efficacy and safety in clinical practice. J Drugs Dermatol. 2024;23:9(Suppl 2):s5-14.Access the CME Activity.

Rise and fall of decongestants in treating nasal congestion related diseases.

INTRODUCTION: Decongestants are commonly used drugs in clinical practice, and they can relieve nasal congestion caused by factors like influenza, rhinitis, and acute upper respiratory tract infection. AREAS COVERED: In this article, we review the research outcomes about decongestants, which aim to provide beneficial information that can guide the clinical application of decongestants for clinicians. EXPERT OPINION: Although the use of nasal decongestants is increasingly limited, caution rather than prohibition is now advocated. Scientific and accurate use of nasal decongestants can achieve satisfactory clinical effectiveness on nasal congestion, and it is not easy to produce adverse reactions. Patients with severe nasal congestion may use nasal decongestants solely or in combination with nasal corticosteroids or nasal antihistamines to exert a synergistic effect. The concentration, dose, frequency, and time of nasal decongestants determine whether drug-induced rhinitis will occur. Additionally, we recommend patients not to buy nasal sprays with unknown ingredients on the internet or in pharmacy, so as to avoid the risk of rhinitis medicamentosa. For patients with rhinitis medicamentosa, the use of nasal decongestants should be stopped immediately. However, more evidence is still needed to standardize the clinical use of nasal decongestants.

[Modern approaches to rational combination pharmacotherapy of allergic rhinitis]. / Sovremennye podkhody k ratsional'noi kombinirovannoi farmakoterapii allergicheskogo rinita.

Allergic rhinitis (AR) can significantly reduce the quality of life of patients leading to increased fatigue, mood changes, cognitive impairment, and depression. In clinical practice, insufficient effectiveness of initial AR monotherapy is often noted, and a significant proportion of patients referring for medical care have moderate-severe AR. In this regard, the issues of optimization of combined pharmacological treatment of AR are becoming more and more urgent. This paper provides analysis of the opportunities of combined pharmacotherapy within the framework of current management strategy of AR. Based on the results of some studies and known pharmacological properties of medications it is being discussed the advantages of combined use of intranasal corticosteroids and leukotriene receptor antagonists, in particular mometasone furoate and montelukast, in the therapy of AR, including such comorbidities as bronchial asthma, chronic polyposis rhinosinusitis and pharyngeal tonsil hyperplasia. Some aspects of combination therapy with montelukast and second-generation systemic antihistamines as an alternative approach in case of inability to take intranasal corticosteroids, including the reasonability of using a fixed combination of montelukast and levocetirizine, are analyzed from the perspective of rational pharmacotherapy. The problem of interchangeability of brand-name and generic drugs for the treatment of AR is discussed, considering the almost complete absence of studies of their therapeutic equivalence.

Combining dipyridamole and cilostazol with up-dosing antihistamines improves outcomes in chronic spontaneous urticaria with high D-dimer levels: A randomized controlled trial.

In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.

What Are Food Allergies?

This JAMA Patient Page describes the causes, symptoms, risk factors, diagnosis, and treatment of food allergies.

[Recent advances in the practical management of allergic rhinitis.] / Recenti progressi nella gestione pratica della rinite allergica.

Allergic rhinitis (AR) is a widespread disease, and its prevalence is still growing. AR may be associated with other diseases, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on history, physical examination, documentation of sensitization, such as the production of allergen-specific IgE, also using molecular diagnostics in selected patients. Treatments is based on education, engagement, allergen avoidance, non-pharmacological and pharmacological remedies, and allergen-specific immunotherapy (Ait). Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids. This article also aims to discuss new management strategies for AR patients. The self-management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered to intranasal corticosteroids and antihistamines without medical prescription, probiotics and other natural substances, and new formulations (tablets) of Ait.

Evaluation of treatment and long-term management of anaphylaxis in pediatric departments of Greece: a 2-year nationwide survey.

BACKGROUND: Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece. PURPOSE: The aim of the study was to evaluate management of anaphylaxis in Greek pediatric departments. METHODS: We performed a questionnaire-based study of children aged less than 16 years presenting with anaphylaxis in 10 national pediatric hospitals over a period of 2 years. Management of anaphylaxis was assessed prior to and after an informative intervention. RESULTS: In all, 127 cases of anaphylaxis were identified. Epinephrine was administered in almost half of all cases (51.2%), predominantly through intramuscular route (88.5%), while the majority of anaphylaxis patients were treated with antihistamines (92.9%) and corticosteroids (70.1%). Epinephrine was more likely administered by physicians if the elicitor was a drug (P < 0.003). Regarding long-term management, an epinephrine auto-injector was prescribed in 66.9% of patients. Follow-up information was available for most of the patients (92.9%), the majority of whom (76.3%) were referred to an allergist. More than half of these patients (63.6%) had a documented allergy follow-up, which identified a causative allergen in 53.3% of cases. No statistically significant differences were recorded prior to and after the intervention regarding management of anaphylaxis. CONCLUSIONS: This nationwide study highlighted the necessity of further improvement in terms of anaphylaxis treatment and secondary prevention measures. This presupposes appropriate education and training of healthcare professionals, thus contributing to proper and comprehensive care of the pediatric population.

Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVES: We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR. METHODS: The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses. CONCLUSIONS: Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.

Leukotriene receptor antagonists as adjuvant therapy of antihistamines in chronic urticaria: a systematic review and meta-analysis.

Certain guidelines recommend a second-generation H1-antihistamine (AH) as first-line treatment for patients with chronic urticaria (CU). However, some patients show insufficient response to a standard dose of this therapy and might benefit from adding leukotriene receptor antagonists (LTA). Therefore, we aimed to perform a systematic review and meta-analysis comparing LTA plus antihistamines with antihistamines alone. We performed a systematic review and meta-analysis, searching PubMed, EMBASE, and Cochrane Central for randomized clinical trial (RCT) data comparing LTA plus AH treatment to AH alone in patients with CU. Statistical analysis was performed using R Studio 4.3.2. Heterogeneity was assessed with I2 statistics. Three studies comprising 234 patients with urticaria were included. The mean age was 37.23 years in the leukotriene antagonist + antihistamines (LTA + AH) group and 39.14 years in the antihistamines (AH) group. Follow-up ranged from 2 to 18 months between studies. There was no statistically significant difference between groups in terms of TSS level (SMD: -74.82; 95% CI: -222.66 to 73.02; P = 0.32; I2 = 98%), neither in terms of pruritus (MD: -0.07; 95% CI: -0.42 to 0.28; P = 0.70; I2 = 74%). After sensitivity analysis, with the systematic exclusion of each study from the grouped estimates, the result for TSS level did not change. These findings suggest that leukotriene receptor antagonists with antihistamines do not have better outcomes than antihistamines alone regarding TSS and pruritus in patients with CU.

Allergic Rhinitis: A Review.

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.

Targeting histamine receptor 4 in cholinergic urticaria with izuforant (LEO 152020): results from a phase IIa randomized double-blind placebo-controlled multicentre crossover trial.

BACKGROUND: Cholinergic urticaria (CholU) is a common subtype of chronic inducible urticaria, where signs and symptoms (e.g. pruritic wheals and angioedema) are triggered by sweating due to physical exercise, passive warming and by other sweat-inducing situations. While guidelines recommend treatment with second-generation H1 antihistamines, approximately 90% of patients report uncontrolled disease. Targeting the histamine 4 receptor (H4R) has shown promise in preclinical/clinical studies of allergic/inflammatory diseases. Izuforant (LEO 152020) is a selective oral H4R antagonist with expected dual antipruritic and anti-inflammatory effects. OBJECTIVES: To assess the effects of izuforant in adults with CholU, a common type of chronic urticaria driven by histamine and characterized by high skin levels of H4R expression. METHODS: This was a phase IIa randomized double-blind placebo-controlled multicentre crossover trial where patients with CholU with an inadequate response to ≥ 1 standard dose of H1 antihistamine received izuforant 100 mg twice daily or placebo (EUCTR2020-004961-38-DE; NCT04853992). The primary endpoint was change from baseline in Urticaria Activity Score. Exploratory endpoints included CholU activity score over 7 days, urticaria control test, Physician Global Assessment, patient global assessment of severity (PGA-S), provocation tests, Dermatology Life Quality Index and CholU quality of life (CholU-QoL). Pharmacokinetic and pharmacodynamic parameters, and serum biomarkers were assessed, as well as safety and tolerability. RESULTS: Nineteen patients were randomized and included in the full analysis set; 18 completed treatment [mean (SD) age 29.5 (9.8) years; mean (SD) CholU duration 8.0 (6.3) years]. The primary and most of prespecified exploratory endpoints were not met; there were significant improvements in PGA-S for izuforant vs. placebo (P = 0.02), and nonsignificant improvements for other endpoints in quality of life and histamine skin prick test. All adverse events (AEs) experienced with izuforant were considered mild. The most frequently reported (> 1 patient) were nausea (three patients) and upper abdominal pain (two patients), occurring more frequently with izuforant vs. placebo (one patient each). There were no treatment-related serious AEs and no patient receiving izuforant discontinued the study. Treatment with izuforant did not cause downregulation of H4R. CONCLUSIONS: This is the first study to explore the role of H4R as a therapeutic target in urticaria. Targeting H4R with izuforant was well tolerated but did not demonstrate significant improvements vs. placebo in the primary endpoint and all but one prespecified exploratory endpoint in CholU.

Cholinergic urticaria (CholU) is a common subtype of an inflammatory skin condition called chronic inducible urticaria, where signs and symptoms (e.g. hives and swelling in the skin) are triggered by sweating caused by physical exercise, passive warming and other sweat-inducing situations. While guidelines recommend treatment with second-generation H1 antihistamines (a type of medication), approximately 90% of people with the condition report that these medications do not control the disease. Targeting the histamine 4 receptor (H4R) has shown promise in studies of allergic/inflammatory diseases. CholU is driven by histamine (a chemical released in the body) and characterized by high skin levels of H4R. Izuforant is a medication that may reduce itch and inflammation. In our study, which was carried out across multiple sites in Germany, we assessed the effects of izuforant 100 mg in 18 patients with CholU using a range of measures covering symptom control, disease severity, provocation response and quality of life. The primary endpoint (the main result measured at the end of the study to see if the treatment worked) was change from baseline in the post-provocation Urticaria Activity Score, where areas of skin were provoked and the time until common symptoms of CholU appeared (sweating and whealing (hives)) was measured. Overall, the primary endpoint and most of the exploratory endpoints were not met. There were significant improvements in patients' global assessment for izuforant versus placebo. This was the first study to explore the role of H4R as a therapeutic target in urticaria. Our findings suggest that targeting H4R with izuforant was well tolerated but did not demonstrate significant improvements versus placebo in the primary endpoint, and all but one prespecified exploratory endpoint in CholU.

Child with protein losing enteropathy as presentation of collagenous duodenitis and eosinophilic gastroenteritis.

Background: Collagenous duodenitis and gastritis are rare histopathological findings in children. Patients and methods: : We describe a four-year old girl, who presented with non-bloody diarrhea for two months and progressive edema with an albumin of 16g/dl. Results: The diagnosis of a protein losing enteropathy was made. Extensive investigations withheld only an infectious cause of the protein losing enteropathy (cytomegalovirus and adenovirus). However, the patients still required repetitive albumin infusions 3.5 months after onset of symptoms without spontaneous recovery. Therefore, a new endoscopic work-up was performed. Duodenal biopsies revealed collagen deposition, in association with a high number of eosinophils and mast cells throughout different parts of the gastrointestinal tract. Conclusions: The collagen deposition seems to be triggered by an eosinophilic gastrointestinal disorder. Treatment was started with amino acid-based formula, oral iron therapy, an antihistamine, and a proton pomp inhibitor that resulted in persistent normalization of serum albumin already after 1.5 weeks.

Prevalence of chronic respiratory diseases and medication use among children and adolescents in Brazil - a population based cross-sectional study / Prevalência de doenças respiratórias crônicas e uso de medicamentos entre crianças e adolescentes no Brasil - um estudo transversal de base populacional

Abstract Objectives: to describe the prevalence of chronic respiratory diseases and their pharmacological management in children and adolescents in Brazil. Methods: data from the Pesquisa Nacional de Acesso, Uso e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM)(National Access Survey, Use and Promotion of Rational Use of Medicines in Brazil),a population-based cross-sectional study, were analyzed. Household surveys were conducted between September 2013 and February 2014. We included the population under 20 years of age with chronic respiratory diseases. Prevalence of disease, indication of pharmacological treatment, and their use were assessed. Results: the prevalence of chronic respiratory diseases in children aged less than 6 years old was 6.1% (CI95%= 5.0-7.4), 4.7% (CI95%= 3.4-6.4) in those 6-12 years, and 3.9% (CI95%= 2.8-5.4) in children 13 years and older. Children under 6 showed a higher prevalence of pharmacological treatment indication (74.6%; CI95%= 66.0-81.7), as well as medication use (72.6%; CI95%= 62.8-80.7). Of those using inhalers, 56.6% reported using it with a spacer. The most frequent pharmacologic classes reported were short-acting β2 agonists (19.0%), followed by antihistamines (17.2%). Conclusion: children and adolescents who report chronic respiratory diseases living in urban areas in Brazil seem to be undertreated for their chronic conditions. Pharmacological treatment, even if indicated, was not used, an important finding for decision-making in this population.

Resumo Objetivos: descrever a prevalência de doenças respiratórias crônicas e seu manejo farmacológico em crianças e adolescentes no Brasil. Métodos: foram analisados os dados da Pesquisa Nacional de Acesso, Uso e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM), um estudo transversal de base populacional. As pesquisas domiciliares foram realizadas entre setembro de 2013 e fevereiro de 2014. Incluímos a população com menos de 20 anos de idade com doenças respiratórias crônicas. Foi avaliada a prevalência de doença, indicação de tratamento farmacológico e seu uso. Resultados: a prevalência de doenças respiratórias crônicas em menores de 6 anos foi de 6,1% (IC95%= 5,0-7,4), 4,7% (IC95%= 3,4-6,4) naqueles 6-12 anos e 3,9% (IC95%= 2,8-5,4) em crianças com 13 anos ou mais. Crianças menores de 6 anos apresentaram uma maior prevalência de indicação de tratamento farmacológico (74,6%; IC95%= 66,0-81,7), assim como uso de medicamentos (72,6%; IC95%= 62,8-80,7). Dos usuários de inaladores, 56,6% relataram o uso com espaçador. As classes farmacológicas mais frequentemente relatadas foram β2 agonistas de curta ação (19,0%), seguidos por anti-histamínicos (17,2%). Conclusão: crianças e adolescentes que relatam doenças respiratórias crônicas residentes em áreas urbanas no Brasil parecem ser subtratados para suas condições crônicas. O tratamento farmacológico, mesmo quando indicado, não foi utilizado em sua totalidade, um achado importante para a tomada de decisão nessa população.

Pruritus: Diagnosis and Management.

Pruritus is the sensation of itching; it can be caused by dermatologic and systemic conditions. An exposure history may reveal symptom triggers. A thorough skin examination, including visualization of the finger webs, anogenital region, nails, and scalp, is essential. Primary skin lesions indicate diseased skin, and secondary lesions are reactive and result from skin manipulation, such as scratching. An initial evaluation for systemic causes may include a complete blood count with differential, creatinine and blood urea nitrogen levels, liver function tests, iron studies, fasting glucose or A1C level, and a thyroid-stimulating hormone test. Additional testing, including erythrocyte sedimentation rate, HIV screening, hepatitis serologies, and chest radiography, may also be appropriate based on the history and physical examination. In the absence of primary skin lesions, physicians should consider evaluation for malignancy in older patients with chronic generalized pruritus. General management includes trigger avoidance, liberal emollient use, limiting water exposure, and administration of oral antihistamines and topical corticosteroids. If the evaluation for multiple etiologies of pruritus is ambiguous, clinicians may consider psychogenic etiologies and consultation with a specialist.

Profilaxia pós-exposição antirrábica: evidências sobre pré-medicação, administração de soro e esquema vacinal / Anti-rabies post-exposure prophylaxis: evidence on premedication, serum administration and vaccination scheme

A raiva é uma zoonose transmitida ao homem pela inoculação do vírus rábico contido na saliva do animal infectado. A infecção por este vírus causa encefalite aguda com índice de letalidade próximo a 100%.Embora não haja cura para a raiva clínica, a doença é facilmente evitável pelo fornecimento oportuno de profilaxia adequada. A profiaxia antirrábica humana pode ser realizada pré (PrEP) ou pós (PEP) exposição potencial ao virus da raiva. As tecnologias utilizadas para esta profilaxia são as vacinas e os soros. Há diversos esquemas de profilaxia PrEP e PEP utilizados no mundo. No Brasil, há ainda indicação de administração de medicações prévias à infiltração de soro heterólogo, a fim de mitigar potenciais reações anafiláticas. A administração concomitante de vacinas, imunoglobulinas e pré-medicação para hipersensibilidade (anti-histamínicos e corticoides) através da via intramuscular é uma prática instituída no contexto municipal de Campo Grande - MS, ocasionando problemas recorrentes de falta de sítios para administração completa da profilaxia, especialmente em crianças. Quais os cuidados necessários durante a realização de Profilaxia Pós Exposição Antirrábica em situações de limitação de vias de administração e risco de hipersensibilidade? Após análise do conteúdo, a fim de concluir a revisão em tempo oportuno para a tomada de decisão da gestão, a equipe de pesquisa deliberou pela extração de dados somente dos estudos secundários. Os principais achados estão sumarizados em infográfico no APÊNDICE A. É indicada a modernização do Procedimento Operacional Padrão vigente na prefeitura de Campo Grande. A substituição das práticas relacionadas à pré-medicação IM, vacinação IM e administração de soro IM é cientificamente embasada e elimina o problema que originou a questão de pesquisa desta revisão, apresentando benefícios para gestão, profissionais e usuários do SUS.

Synthesis and in vitro characterization of chlorpheneramine-laden liposomes for topical applications.

This study was aimed at synthesizing liposomes for the topical delivery of chlorpheneramine maleate using three-level factorial design. Each experiment consisted of a varying proportion of cholesterol, lecithin and a permeation enhancer mixture of Tween80 and polyethylene glycol (PEG1000), and resultant liposomes were extensively characterized. The drug release study was conducted at 6.0 pH, 37±1ºC temperature and 100 rpm rotation speed utilizing a cellophane membrane pouch in a USP type II dissolution apparatus. Among formulations, L5 was considered as the optimal formulation because of high drug loading (99.05%), 87.71% drug release within 4 hours, high drug loading and the optimized formulation was found to be stable during stability testing. This high drug loading and release was achieved at low level of cholesterol and lecithin (0.1: 0.3g) and high level of permeation enhancer mixture (0.2g) as revealed by the surface plots. The drug release from the optimized formulation followed Fickian diffusion as revealed by Korsmeyers-Peppas kinetic model. In summary, combination of PEG1000 and Tween80 with lecithin and cholesterol can be successfully used to develop liposomes that efficiently incorporated chlorpheneramine. This formulation therefore has the potential to be used as a topical anti-allergic product.

Lactobacillus paracasei L9 improves colitis by expanding butyrate-producing bacteria that inhibit the IL-6/STAT3 signaling pathway.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation that is currently incurable. Increasing evidence indicates that supplementation with probiotics could improve the symptoms of IBD. It is scientifically significant to identify novel and valid strains for treating IBD. It has been reported that the probiotic Lactobacillus paracasei L9 (L9), which is identified from the gut of healthy centenarians, can modulate host immunity and plays an anti-allergic role. Here, we demonstrated that L9 alleviates the pathological phenotypes of experimental colitis by expanding the abundance of butyrate-producing bacteria. Oral administration of sodium butyrate in experimental colitis recapitulates the L9 anti-inflammatory phenotypes. Mechanistically, sodium butyrate ameliorated the inflammatory responses by inhibiting the IL-6/STAT3 signaling pathway in colitis. Overall, these findings demonstrated that L9 alleviates the DSS-induced colitis development by enhancing the abundance of butyrate-producing bacterial strains that produce butyrate to suppress the IL-6/STAT3 signaling pathway, providing new insight into a promising therapeutic target for the remission of IBD.

Comparison of proton pump inhibitors and histamine 2 receptor antagonists for stress ulcer prophylaxis in the intensive care unit.

Proton pump inhibitors (PPIs), followed by histamine 2 receptor antagonists (H2RAs), are the most commonly used drugs to prevent gastrointestinal bleeding in critically ill patients through stress ulcer prophylaxis. The relative efficacy and drug-related adverse events of PPIs and H2RAs remain unclear. In this retrospective, observational, comparative cohort study, PPIs and H2RAs for stress ulcer prophylaxis in critically ill patients were compared using a common data model. After propensity matching, 935 patients from each treatment group (PPI or H2RA) were selected. The PPI group had a significantly higher 90-day mortality than the H2RA group (relative risk: 1.28; P = 0.01). However, no significant inter-group differences in the risk of clinically important gastrointestinal bleeding were observed. Moreover, there were no significant differences between the groups concerning the risk of pneumonia or Clostridioides difficile infection, which are known potential adverse events related to these drugs. Subgroup analysis of patients with high disease severity were consistent with those of the total propensity score-matched population. These findings do not support the current recommendations, which prefer PPIs for gastrointestinal bleeding prophylaxis in the intensive care unit.