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May 2020

Nivel de dímero D en plasma

Efficacy and Safety of Active Vitamin D Supplementation in Chronic Spontaneous Urticaria Patients.

By Selected articles

Ahmed Mohamed A, Hussein MS, Salah EM, Eldemery A, Darwish MM, Ghaith DM, Attala RA, El Borolossy R.

J Dermatolog Treat. 2020 Apr 29:1-22. doi: 10.1080/09546634.2020.1762838. [Epub ahead of print]

Chronic spontaneous urticaria is one of the most common cutaneous disorders, characterized by the recurrence of transient wheals, angioedema or both for more than 6 weeks. Vitamin D has a main role in bone homeostasis, but also has immunomodulatory action in innate and adaptive immunity. Some studies have shown that vitamin D plays also a role in the improvement of clinical symptoms of chronic urticaria.

The aim of this study was to assess the association between serum levels of vitamin D and chronic spontaneous urticaria and to evaluate its efficacy and safety.

The study included 77 participants with chronic spontaneous urticaria and 67 healthy controls. They were randomized to receive 0,25 ug of alfacalcidol daily or placebo for 12 weeks.

Participants with chronic spontaneous urticaria had a significantly lower serum vitamin D than healthy controls at the beginning of the study. 12 weeks after administration of alfacalcidol, participants with chronic spontaneous urticaria showed a significant higher level of serum vitamin D compared to placebo. Additionally, mean serum level of IL6, CRP and TNFa significantly also decreased in these participants.

Although vitamin D deficiency is more common in people with chronic spontaneous urticaria, supplementation with alfacalcidol may have a beneficial role as add-on therapy of chronic spontaneous urticaria with no relevant side effects.

This document is only available for registered healthcare professionals


International expert consensus on the management of allergic rhinitis (AR) aggravated by air pollutants: Impact of air pollution on patients with AR: Current knowledge and future strategies.

By Selected articles

Naclerio R, Ansotegui IJ, Bousquet J, Canonica GW, D’Amato G, Rosario N, Pawankar R, Peden D, Bergmann KC, Bielory L, Caraballo L, Cecchi L, Cepeda SAM, Chong Neto HJ, Galán C, Gonzalez Diaz SN, Idriss S, Popov T, Ramon GD, Ridolo E, Rottem M, Songnuan W, Rouadi P.

World Allergy Organ J. 2020 Apr 3;13(3):100106. doi: 10.1016/j.waojou.2020.100106. eCollection 2020 Mar.

Exposition to pollution and climate change worsen symptoms in people with allergic rhinitis. The aim of this study was to summarize the conclusions of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution.

Epidemiological and clinical studies have shown that co-exposure to aeroallergens and pollutants have an immunological effect that induces inflammatory responses with recruitment of inflammatory cells, cytokines and interleukins. In addition, allergic rhinitis symptoms can be mediated by a neurogenic component upon contact with environmental irritants. Other studies that included specific pollutants exposure and allergen challenge propose that pollution can exacerbate allergic airway disease and increase responsiveness.

Although there have been advances in the understanding of the mechanistic ways of airway inflammation, there is lack of evidence about the benefits of management of allergic rhinitis aggravated by pollution. Fexofenadine, a non-sedating oral antihistamine as shown to improve allergic rhinitis symptoms aggravated by pollution, however, more studies with other related antihistamines in mitigating symptoms resulting from co-exposure to pollution and allergens are needed.

Nevertheless, an individual and careful approach with avoidance measures and conventional pharmacotherapy can improve symptoms caused by allergic rhinitis and air pollution.

This document is only available for registered healthcare professionals

vitamina modulador rinitis

Defining biomarkers to predict symptoms in subjects with and without allergy under natural pollen exposure.

By Selected articles

Gökkaya M, Damialis A, Nussbaumer T, Beck I, Bounas-Pyrros N, Bezold S, Amisi MM, Kolek F, Todorova A, Chaker A, Aglas L, Ferreira F, Redegeld FA, Brunner JO, Neumann AU, Traidl-Hoffmann C, Gilles S.

J Allergy Clin Immunol. 2020 Apr 6. pii: S0091-6749(20)30419-X. doi: 10.1016/j.jaci.2020.02.037. [Epub ahead of print]

The exposition to airborne pollen is the main cause of seasonal allergic rhinitis. This exposition induces local and systemic allergic immune responses in sensitized and non-sensitized individuals. The mechanisms of action of the expression of symptoms under natural pollen exposure is not fully understood. The aim of this study was to monitor the humoral immune response under natural pollen exposure to categorise and understand nasal biomarkers for in-season symptom severity and to identify protective factors.

50 participants with seasonal allergic rhinitis and non-allergic rhinitis were included from November 2015 to October 2016. Immune monitoring to compare humoral immune response kinetics and cross-sectional and interseasonal differences in levels of serum and nasal, total and Bet v 1-specific immunoglobulin isotypes, immunoglobulin free light chains, cytokines and chemokines was performed every 4 weeks out of season and bi-weekly within the main pollen season. Nasal immune variables were registered with non-supervised principal component analysis and single immune variables were correlated with in-season severity by Spearman test.

Participants with seasonal allergic rhinitis had symptoms in 0 to 13 days after airborne pollen exposure, depending on the pollen type. 4 out of 7 non-allergic participants also exhibited in-season symptoms. Non-allergic participants had lower cumulative symptoms than participants with seasonal allergic rhinitis but followed the pollen exposure with similar kinetics. Seasonal allergic rhinitis participants had higher levels of nasal eotaxin-2, MDC and MCP-1, non-allergic participants had higher levels of IL-7. Non-supervises principal component analysis and Spearman correlations identified nasal IL-8, IL-33, Bet v 1-specific IgG4 and sIgE antibodies a prognostic for seasonal symptom severity.

Nasal IL-8, IL-33, sIgG3 and sIgE could be predictive biomarkers for pollen-specific symptom expression, irrespective of atopy, while nasal pollen-specific IgA and IgG isotypes seem to be potentially protective within the humoral compartment.

This document is only available for registered healthcare professionals

skin microdyalisis

Chronic urticaria in the real-life clinical practice setting in the UK: results from the non-interventional multicentre AWARE study.

By Selected articles

Savic S, Leeman L, El-Shanawany T, Ellis R, Gach JE, Marinho S, Wahie S, Sargur R, Bewley AP, Nakonechna A, Randall R, Fragkas N, Somenzi O, Marsland A.

Clin Exp Dermatol. 2020 Apr 4. doi: 10.1111/ced.14230. [Epub ahead of print]

Chronic urticaria is a group of skin conditions that include chronic spontaneous urticaria and chronic inducible urticaria. Symptoms include itchy wheals and/or angioedema for a period longer than 6 weeks. The objective of this study was to provide information demonstrating the real-life burden of chronic urticaria in the UK.

The non-interventional AWARE study (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) collected data from a representative sample of chronic urticaria patients worldwide. A subset of UK patients aged 18-75 diagnosed with H1-antihistamine-refractory chronic spontaneous urticaria was analysed.

Baseline analysis included 252 UK patients, mostly female (77,8%) with moderate-to-severe disease activity and a spontaneous component to their chronic urticaria. Comorbidities included depression/anxiety (24,6%), asthma (23,8%) and allergic rhinitis (12,7%). 57,9% of the patients had undergone a treatment. Their mean Dermatology Life Quality Index score was 9,5 with report of reduction in work productivity and activity. These patients referred a high need to use healthcare resources. Chronic spontaneous urticaria severity was linked to gender, obesity, anxiety and diagnosis.

Only 28,5% of UK patients completed all nine study visits, which limits analysis of long-term treatment patterns and disease impact. Chronic urticaria patients reported high rates of healthcare resource use and impairment in quality of life, work productivity and activity at baseline, which highlights the need to ensure appropriate management to optimise patient quality of life and reduce the socioeconomic burden of chronic urticaria in the UK.

This document is only available for registered healthcare professionals

Urticaria cronica angioedema

Urticaria and Angioedema Across the Ages

By Selected articles

Saini S, Shams M, Bernstein JA, Maurer M.

J Allergy Clin Immunol Pract. 2020 Apr 13. pii: S2213-2198(20)30329-9. doi: 10.1016/j.jaip.2020.03.030. [Epub ahead of print]

Chronic urticaria symptoms include itchy wheals, angioedema, or both, caused by the release of histamine, prostaglandin metabolites, leukotrienes, platelet activating factor and other proinflammatory mediators, which in turn lead to vasodilation and extravasation, sensory nerve activation and cellular infiltration.

Chronic urticaria is a common clinical condition that impairs quality of life of people and represent an important health burden. International Consensus guidelines have been published that recommend the use of standard terminology and definitions for different types of chronic urticaria, such as chronic spontaneous urticaria and chronic inducible urticaria. However, there is a lack in the understanding of mechanistic pathways and treatment in some more vulnerable populations, such as children, elderly people and pregnant or lactating women.

40-50% of the patients are effectively treated with monotherapy with a non-sedating H1-antihistamine or 2-4 times the recommended dose of a non-sedating H1-antihistamine. Biologics like omalizumab or immunosuppressants such as cyclosporin are used when patients fail to respond to simpler treatments. There is evidence that omalizumab can be safely used in the vulnerable populations, however cyclosporin has a greater toxicity and is not appropriate in these populations.

Additional therapies for vulnerable chronic urticaria patients are needed.

This document is only available for registered healthcare professionals

Terapia combinada de azelastina intranasal y propionato de fluticasona

Adherence to Prescribed E-Diary Recording by Patients With Seasonal Allergic Rhinitis: Observational Study.

By Selected articles

Di Fraia M, Tripodi S, Arasi S, Dramburg S, Castelli S, Villalta D, Buzzulini F, Sfika I, Villella V, Potapova E, Perna S, Brighetti MA, Travaglini A, Verardo P, Pelosi S, Zicari AM, Matricardi PM.

J Med Internet Res. 2020 Mar 16;22(3):e16642. doi: 10.2196/16642.

Seasonal allergic rhinitis affects patients exposed to pollens to which they are sensitized. The etiological diagnosis and therapy of allergic rhinitis require an evidence that exposure to the sensitizing pollen triggers allergic symptoms. Electronic clinical diaries can demonstrate this association as patients can record disease severity scores and pollen exposure. However, there is a lack of adherence in patients who have spontaneously downloaded an e-diary application.

The aim of the study @IT-2020 project was to evaluate adherence of patients with seasonal allergic rhinitis to symptom recording via e-diary clearly prescribed by a specialist within a blended care approach. Italian children and adults with seasonal allergic rhinitis were included and instructed to record their symptoms, medication intake and general conditions daily through a mobile app (Allergy.Monitor) during pollen season.

A total of 101 children and 93 adults with seasonal allergic rhinitis were included and showed a slow decline in the adherence to device use during monitoring: from 90% at the end of the first week to 70 to 80% from the seventh week onward. At the individual level, the adherence evaluated in the second and third weeks predicted with enough confidence the overall participant adherence to recording.

If prescribed and motivated by an allergist in a blended care setting, the adherence to daily recording in an e-diary is very high, which supports their use in addition to face-to-face visits for diagnosis and treatment of seasonal allergic rhinitis. The proper use of mobile health technology in monitoring seasonal allergic rhinitis strengthens the blended care approach.

This document is only available for registered healthcare professionals

interacciones contaminacion rinitis

Clinical symptoms and biomarkers of Bermuda grass-induced allergic rhinitis using the nasal allergen challenge model.

By Selected articles

Rawls M, Thiele J, Adams DE, Steacy LM, Ellis AK.

Ann Allergy Asthma Immunol. 2020 Mar 12. pii: S1081-1206(20)30147-2. doi: 10.1016/j.anai.2020.03.003. [Epub ahead of print]

Allergic rhinitis is an immunoglobulin E (IgE) mediated inflammatory disorder of the nose. Its prevalence ranges from 10 to 30% in North America. Grass pollens are common allergens that can provoke allergic rhinitis symptoms, such as sneezing, nasal itching, congestion and postnasal drip. Uncontrolled allergic rhinitis symptoms can have a negative impact on sleep quality, work productivity, driving ability and academic performance. Antihistamines and nasal corticoids are the usual treatments to reduce symptoms severity. This study objective was to evaluate whether Bermuda grass allergens can provoke allergic rhinitis symptoms in sensitized participants and to determine if nasal allergen challenge model is adequate to study this type of allergic rhinitis.

The study included 22 participants sensitized to Bermuda grass and 12 nonallergic participants, who completed a titrated nasal allergen challenge with increasing allergen concentrations at a screening visit. Total nasal symptom score (TNSS) and peak nasal inspiratory flow were registered before allergen exposure and 10 minutes after each concentration.

At titrated nasal allergen challenge, 19 of 22 sensitized participants met the criteria for positive allergic response when challenged. During single-dose nasal allergen challenge, sensitized participants had significantly greater TNSS between 15 min and 3 hours after nasal allergen challenge than nonallergic participants. Likewise, allergic participants had a significantly increased number of nasal lavage eosinophils at both 1 and 6 hours after nasal allergen challenge. Also, Bermuda grass specific IgE was significantly increased in Bermuda grass allergic participants at nasal allergen challenge than at screening visit.

In conclusion, Bermuda grass induces allergic rhinitis symptoms in sensitized participants and the model of nasal allergen challenge is adequate to study this type of allergic rhinitis.

This document is only available for registered healthcare professionals

Diagnosis and treatment of urticaria in primary care

Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020.

By Selected articles

Maurer M, Eyerich K, Eyerich S, Ferrer M, Gutermuth J, Hartmann K, Jakob T, Kapp A, Kolkhir P, Larenas-Linnemann D, Park HS, Pejler G, Sánchez-Borges M, Schäkel K, Simon D, Simon HU, Weller K, Zuberbier T, Metz M.

Int Arch Allergy Immunol. 2020 Mar 30:1-13. doi: 10.1159/000507218. [Epub ahead of print] Review.

Chronic urticaria is a heterogeneous persistent, severely debilitating and often poorly controlled disease. Recent studies have shown that the prevalence of CU and its sub forms may be more heterogeneous than previously thought.

This update on chronic urticaria focuses on its prevalence and pathogenesis, the expanding spectrum of patient-reported outcome measures for assessing disease activity, impact and control, as well as future treatment options.

Chronic urticaria is a mast cell-driven disease which presents with transient wheals (hives), angioedema, or both, without any definite triggers and reoccurrence of signs and symptoms for more than six weeks. It is common in both children and adults; its prevalence is increasing with substantial differences across geographical regions.

The objective of treatment in chronic urticaria is complete disease control with absence of signs and symptoms, as well as normalization of quality of life. Specialists can monitor by using sets of patient-reported outcome measures. Antihistamines and omalizumab are the only currently licensed treatments for chronic urticaria. Some inhibit the effects of signals that drive mast cells activation and accumulation, others inhibit intracellular pathways of mast cells activation and degranulation, or silence mast cells by binding to inhibitory receptors.

This document is only available for registered healthcare professionals

enfermedades de la piel

The role of eosinophils in chronic spontaneous urticaria

By Selected articles

Altrichter S, Frischbutter S, Fok JS, Kolkhir P, Jiao Q, Skov PS, Metz M, Church MK, Maurer M.

J Allergy Clin Immunol. 2020 Mar 26. pii: S0091-6749(20)30406-1. doi: 10.1016/j.jaci.2020.03.005. [Epub ahead of print]

Chronic spontaneous urticaria is a mast-cell driven skin disease characterized by the recurrence of transient wheals, angioedema or both for more than 6 weeks. Recent studies have suggested that eosinophils may also have a major role in symptomatology. In urticaria, it is usually observed a peripheral blood eosinopenia, opposed to other allergic and inflammatory conditions. Histological studies have shown the presence of eosinophils and eosinophil granules in urticaria lesions. They may enhance urticaria in three ways: first, eosinophil-derived stem cell factor (SCF) promotes the recruitment and local maturation of mast cells in the tissues. Second, eosinophil proteins, such as major basic protein, eosinophil cationic protein and eosinophil peroxidase can provoke mast cell degranulation. And third, activated eosinophils also express tissue factor, the main initiator of the coagulation cascade leading to thrombin formation. Eosinophil infiltration may contribute to tissue edema of skin in urticaria but can also, together with increased mast cells, prime the skin for further healing.

Treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL5 humanized antibodies mepolizumab, reslizumab and benralizumab, have shown to reduce chronic spontaneous urticaria.

This document is only available for registered healthcare professionals

enfoque rinitis alergica

Allergen immunotherapy: what is the added value of real-world evidence from retrospective claims database studies?

By Selected articles

Devillier P, Demoly P, Molimard M.

Expert Rev Respir Med. 2020 Mar 4:1-8. doi: 10.1080/17476348.2020.1733417. [Epub ahead of print]

Allergen immunotherapy (AIT) is the only disease-modifying treatment available for allergic rhinitis. It works by inducing allergen-specific immune tolerance and by preventing the development of new allergen sensitization. Studies have shown that AIT has proven long-term efficacy in people with allergic rhinitis, however there is a lack of studies of real-world evidence.

In this review, retrospective studies from France and Germany have confirmed the sustained benefits of grass and pollen AIT. When compared to standard of care, AIT improved allergic rhinitis symptom control after treatment cessation (reduced allergic rhinitis symptomatic medication use), as well as asthma control and decreased the risk of developing asthma.

Real-world evidence studies have advantages over randomizes clinical trials, such as evaluation of a broader patient population that mirrors clinical practice, greater generalizability and enabling the assessment of long-term safety and effectiveness. In particular real-world evidence of AIT in people with allergic rhinitis and asthma confirm and build on the efficacy findings of regular studies, and their results can be used to guide clinical management and assist counselling of patients, so much so that recent guidance supports the inclusion of real-world evidence data in updated guidelines.

This document is only available for registered healthcare professionals


Co-occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria.

By Selected articles

Asero R, Marzano AV, Ferrucci S, Lorini M, Carbonelli V, Cugno M.

Clin Exp Immunol. 2020 Mar 2. doi: 10.1111/cei.13428. [Epub ahead of print]

Chronic spontaneous urticaria (CSU) is the recurrent manifestation of wheals sometimes associated with angioedema for more than 6 weeks. It is a usual and potentially disabling disease. Its pathogenesis shows a complex and unclear connection between immunoglobulin G (IgG) and immunoglobulin E (IgE)-mediated autoimmunity, which leads to mast cell and basophil degranulation and formation of wheals.

The aim of this study was to assess the IgG and IgE reactivity to autoantigens in people with chronic spontaneous urticaria and to evaluate its effects on response to the anti-IgE monoclonal antibody omalizumab.

The study included 20 participants who underwent omalizumab treatment (300 g /month). Urticaria activity score 7 (UAS7) was registered at baseline and 1, 3 and 4 months after treatment initiation to categorize early-, late- or non-responders. At baseline, sera from the 20 participants and 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors, tissue factor and thyroglobulin by ELISA. Antibody levels were compared with those of controls and analysed according to response.

There were 18 omalizumab responders (11 early and 7 late) and 2 non-responders. More than half of the participants had contemporary IgE and IgG to at least one of the four autoantigens. Late responders had higher levels of anti-TF IgG and IgE. 25% of the participants had levels of anti-high and low affinity IgE receptors (anti-FcεRI IgE), which suggests that it could be a novel auto-allergen in chronic spontaneous urticaria.

In conclusion, autoimmune responses sustained by both IgE and IgG antibody classes were detected in more than half of the participants with chronic spontaneous urticaria. Such autoimmune responses may co-exist and possibly influence the clinical response to anti-IgE therapy, especially in late responders to omalizumab.

This document is only available for registered healthcare professionals


Identification of antigenic epitopes of thyroperoxidase, thyroglobulin and interleukin-24. Exploration of cross-reactivity with environmental allergens and possible role in urticaria and hypothyroidism.

By Selected articles

Sánchez A, Cardona R, Munera M, Sánchez J.

Immunol Lett. 2020 Apr;220:71-78. doi: 10.1016/j.imlet.2020.02.003. Epub 2020 Feb 3.

Chronic spontaneous urticaria is characterized by hives and angioedema that significantly affects quality of life. People with urticaria have higher self-reactive autoantibodies IgE and IgG than healthy people. Other proteins implicated in the pathogenesis of urticaria include thyroperoxidase (TPO), interleukin 24 (IL24) and thyroglobulin (Tg). The reason why these proteins are recognized by specific autoantibodies in people with urticaria is unknown.

The aim of this study was to compare the sequences of TPO, Tg and IL24 with some prevalent allergens through in silico analysis.

The amino acid sequences of IL24, TPO and Tg were compared between them and with 22 environmental allergens. To explore the degree of protein identity and cover, researchers carried out phylogenetic studies and multiple pairing. Proteins without 3D structure reported in the database were modelled and compared by homology. Residues conserved and accessible to the solvent were located in the 3D model to identify possible areas of cross-reactivity and antigen binding.

Five epitopes for TPO, six for IL24 and six for Tg were predicted with the 3D model built. The amino acid sequences of allergens from different sources (Dermatophagoides pteronyssinus, Blomia tropicalis, Betula verrucosa, Cynodon dactylon, Aspergillus fumigatus, Canis domesticus, Felis domesticus) were also compared with the human proteins. The cover and alignments between allergens and human proteins were low.

In conclusion, there are possible linear and conformational epitopes of TPo, Tg and IL24 that can be the target of IgE and IgG binding in patients with urticaria. These epitopes aren’t found in common allergens, which indicates that autoreactivity to the human proteins is not through cross-reactivity.

This document is only available for registered healthcare professionals


Clinically significant differences in patient-reported outcomes evaluations in chronic spontaneous urticaria.

By Selected articles

Baiardini I, Canonica GW, La Grutta S, Braido F.

Curr Opin Allergy Clin Immunol. 2020 Feb 18. doi: 10.1097/ACI.0000000000000636. [Epub ahead of print]

Chronic spontaneous urticaria is a common skin disorder that affects up to 1% of the world population, with more women affected. Its symptoms include repeated occurrence of itchy wheals, angioedema or both, for over 6 weeks. The objective of this review was to highlight the conceptual and practical knowledge for interpreting score changes in patient-reported outcomes (PROs) that have been validated for chronic spontaneous urticaria.

Guidelines recommend assessing PROs as Health-Related Quality of Life, disease activity and disease control to detect the impact of urticaria and the overall treatment effect. In order to have this, it is fundamental to determine the minimal important difference (MID) to evaluate if changes in questionnaire scores represent a perceived improvement or deterioration for patients. MID are collected into two categories, distribution-based and anchor-based.

For most chronic spontaneous urticaria questionnaires, a MID has been defined according to the results of various approaches. The majority of studies analysed in this review used anchor-based methods. The available information regarding MIDs across validated tools for people with chronic spontaneous urticaria helps to interpret measurement scores and allows the implementation of PROs in routine practices.

This document is only available for registered healthcare professionals

rinitis alérgica

Multidisciplinary Real-World Experience With Bilastine, a Second Generation Antihistamine

By Articles about Bilastine

Lynde CW, Sussman G, Dion PL, Guenther L, Hébert J, Rao J, Leek TV, Waserman S.


J Drugs Dermatol. 2020 Feb 1;19(2):145-154. doi: 10.36849/JDD.2020.4835.

Allergic conditions, such as seasonal allergic rhinitis, perennial allergic rhinitis (PAR), and urticaria (both acute and chronic) are frequently treated with H1-antihistamines. However, first-generation H1-antihistamines cause impairment and potentially interfere with restful sleep, cause hangovers or “morning after” effects, impair learning and memory, and reduce work efficiency. Second generation antihistamines, such as bilastine have shown to decrease allergy symptoms effectively without causing night-time sleep disturbances and related adverse events.

Bilastine is a prescription medicine. It is not derived from nor is it a metabolite of another antihistamine, has a rapid one-hour onset of action and provides sustained efficacy. Bilastine does not penetrate the brain, is scarcely metabolized and does not interact with cytochrome P450. For the treatment of allergic conditions in adults and children over 12 years of age, a daily oral dose of bilastine 20 mg is recommended.

This real world case project was developed to help optimize patient care and supported with evidence from the literature. It included patients between 9 and 76 years old with seasonal allergic rhinitis, perennial allergic rhinitis and chronic and acute urticaria as well as urticarial vasculitis and pruritus associated with inflammatory skin conditions.

The presented cases using bilastine showed positive outcomes for the patients, relieving symptoms with safety and good tolerance.

This document is only available for registered healthcare professionals

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