tag:blogger.com,1999:blog-24556929126158224312024-03-18T17:18:07.345-03:00Allergy, Asthma and ImmunologyA blog that publishes updates and open access scientific papers about allergy, asthma and immunology.
Editor: Juan Carlos Ivancevich, MD. Specialist in Allergy & Immunologyivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.comBlogger4095125tag:blogger.com,1999:blog-2455692912615822431.post-37578129357490318882024-03-18T17:17:00.004-03:002024-03-18T17:17:17.594-03:00Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://dm5migu4zj3pb.cloudfront.net/volumes/134/6/134-6-cover.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="402" data-original-width="300" height="97" src="https://dm5migu4zj3pb.cloudfront.net/volumes/134/6/134-6-cover.jpg" width="72" /></a></span></div><span style="font-family: arial;">Joulia R, Puttur F, Stölting H, Traves WJ, Entwistle LJ, Voitovich A, Garcia Martín M, Al-Sahaf M, Bonner K, Scotney E, Molyneaux PL, Hewitt RJ, Walker SA, Yates L, Saglani S, Lloyd CM. <i><a href="https://www.jci.org/articles/view/173676" target="_blank">J Clin Invest. 2024 Mar 15;134(6):e173676. doi: 10.1172/JCI173676.</a></i></span><p></p><p><br /></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://dm5migu4zj3pb.cloudfront.net/manuscripts/173000/173676/medium/JCI173676.ga.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><span style="font-family: arial;"><img border="0" data-original-height="707" data-original-width="700" height="400" src="https://dm5migu4zj3pb.cloudfront.net/manuscripts/173000/173676/medium/JCI173676.ga.jpg" width="396" /></span></a></div><span style="font-family: arial;">Allergic asthma generally starts during early life and is linked to substantial tissue remodeling and lung dysfunction. Although angiogenesis is a feature of the disrupted airway, the impact of allergic asthma on the pulmonary microcirculation during early life is unknown. Here, using quantitative imaging in precision-cut lung slices (PCLSs), we report that exposure of neonatal mice to house dust mite (HDM) extract disrupts endothelial cell/pericyte interactions in adventitial areas. <span><a name='more'></a></span>Central to the blood vessel structure, the loss of pericyte coverage was driven by mast cell (MC) proteases, such as tryptase, that can induce pericyte retraction and loss of the critical adhesion molecule N-cadherin. Furthermore, spatial transcriptomics of pediatric asthmatic endobronchial biopsies suggests intense vascular stress and remodeling linked with increased expression of MC activation pathways in regions enriched in blood vessels. These data provide previously unappreciated insights into the pathophysiology of allergic asthma with potential long-term vascular defects.</span><p></p><p style="text-align: center;"><a href="https://www.jci.org/articles/view/173676/pdf" target="_blank"><span style="font-family: arial;"><b>PDF</b></span></a></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-80638626017168295332024-03-18T16:41:00.004-03:002024-03-18T16:42:07.277-03:00Dexamethasone protects against asthma via regulating Hif-1α-glycolysis-lactate axis and protein lactylation<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://ars.els-cdn.com/content/image/1-s2.0-S1567576923X00186-cov150h.gif" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><span style="font-family: arial;"><img border="0" data-original-height="150" data-original-width="113" height="84" src="https://ars.els-cdn.com/content/image/1-s2.0-S1567576923X00186-cov150h.gif" width="63" /></span></a></div><p></p><p><span style="font-family: arial;">Chen N, Xie QM, Song SM, Guo SN, Fang Y, Fei GH, Wu HM. <i><a href="https://www.sciencedirect.com/science/article/abs/pii/S1567576924003096" target="_blank">Int Immunopharmacol. 2024 Mar 8;131:111791. doi: 10.1016/j.intimp.2024.111791. </a></i></span></p><p><span style="font-family: arial;"><br /></span></p><p><b><span style="font-family: arial;"><br /></span></b></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><b><span style="font-family: arial;">Purpose</span></b></p><p><span style="font-family: arial;">Asthma can not be eradicated till now and its control primarily relies on the application of corticosteroids. Recently, glycolytic reprogramming has been reportedly contributed to asthma, this study aimed to reveal whether the effect of corticosteroids on asthma control is related to their regulation of glycolysis and glycolysis-dependent protein lactylation.</span></p><p><b><span style="font-family: arial;">Methods</span></b></p><p><span style="font-family: arial;">Ovalbumin (OVA) aeroallergen was used to challenge mice and stimulate human macrophage cell line THP-1 following dexamethasone (DEX) treatment. Airway hyperresponsiveness, airway inflammation, the expressions of key glycolytic enzymes and pyroptosis markers, the level of lactic acid, real-time glycolysis and oxidative phosphorylation (OXPHOS), and protein lactylation were analyzed.</span></p><p><b><span style="font-family: arial;">Results</span></b></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://ars.els-cdn.com/content/image/1-s2.0-S1567576924003096-ga1_lrg.jpg" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><span style="font-family: arial;"><img border="0" data-original-height="886" data-original-width="1292" height="274" src="https://ars.els-cdn.com/content/image/1-s2.0-S1567576924003096-ga1_lrg.jpg" width="400" /></span></a></div><span style="font-family: arial;">DEX significantly attenuated OVA-induced eosinophilic airway inflammation, including airway hyperresponsiveness, leukocyte infiltration, goblet cell hyperplasia, Th2 cytokines production and pyroptosis markers expression. Meanwhile, OVA-induced Hif-1α-glycolysis axis was substantially downregulated by DEX, which resulted in low level of lactic acid. Besides, key glycolytic enzymes in the lungs of asthmatic mice were notably co-localized with F4/80-positive macrophages, indicating metabolic shift to glycolysis in lung macrophages during asthma. <span><a name='more'></a></span>This was confirmed in OVA-stimulated THP-1 cells that DEX treatment resulted in reductions in pyroptosis, glycolysis and lactic acid level. Finally, protein lactylation was found significantly increased in the lungs of asthmatic mice and OVA-stimulated THP-1 cells, which were both inhibited by DEX.</span><p></p><p><b><span style="font-family: arial;">Conclusion</span></b></p><p><span style="font-family: arial;">Our present study revealed that the effect of DEX on asthma control was associated with its suppressing of Hif-1α-glycolysis-lactate axis and subsequent protein lactylation, which may open new avenues for the therapy of eosinophilic asthma.</span></p><p><b><span style="font-family: arial;">Highlights</span></b></p><p></p><ul style="text-align: left;"><li><span style="font-family: arial;">Hif-1α-glycolysis and protein lactylation are increased in asthmatic mice.</span></li><li><span style="font-family: arial;">DEX attenuates OVA-induced Hif-1α-glycolysis and pyroptosis in vivo and in vitro.</span></li><li><span style="font-family: arial;">DEX suppresses OVA-induced protein lactylation in vivo and in vitro.</span></li></ul><div><span style="font-family: arial;"><br /></span></div><p></p><div><span style="font-family: arial;"><br /></span></div><p><br /></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-69617604159232259322024-03-18T11:37:00.004-03:002024-03-18T11:37:16.347-03:00Practical Use of Upadacitinib in Patients with Severe Atopic Dermatitis in a Real-World Setting: A Systematic Review<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://www.tandfonline.com/action/showCoverImage?doi=10.1080/dcci20.v017.i00" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><span style="font-family: arial;"><img border="0" data-original-height="283" data-original-width="200" height="100" src="https://www.tandfonline.com/action/showCoverImage?doi=10.1080/dcci20.v017.i00" width="71" /></span></a></div><span style="font-family: arial;">Luciano Ibba, Luigi Gargiulo, Carlo Alberto Vignoli, Giovanni Fiorillo, Mario Valenti, Antonio Costanzo & Alessandra Narcisi . <i><a href="https://www.tandfonline.com/doi/full/10.2147/CCID.S329442" target="_blank">Clinical, Cosmetic and Investigational Dermatology, 17:, 593-604, DOI: 10.2147/CCID.S329442 </a></i></span><p></p><p><b><span style="font-family: arial;"><br /></span></b></p><p><b><span style="font-family: arial;"><br /></span></b></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://www.tandfonline.com/cms/asset/d100a7a0-5a98-4def-808a-d3a46d20f55a/dcci_a_12301217_f0001_c.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><span style="font-family: arial;"><img border="0" data-original-height="500" data-original-width="436" height="400" src="https://www.tandfonline.com/cms/asset/d100a7a0-5a98-4def-808a-d3a46d20f55a/dcci_a_12301217_f0001_c.jpg" width="349" /></span></a></div><span style="font-family: arial;">Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies. <span><a name='more'></a></span>Of these, 214 were excluded after reviewing their titles and abstracts. We then conducted a full-text review of 25 studies, of which 17 met our inclusion criteria and were therefore included in our systematic review. The analysis of real-world studies showed high effectiveness of upadacitinib, in terms of both clinical signs and subjective symptoms, in different patient populations, including those resistant to other treatments. No new significant safety concerns have emerged as compared to randomized clinical trials.</span><p></p><p style="text-align: center;"><b><a href="https://www.tandfonline.com/doi/epdf/10.2147/CCID.S329442?needAccess=true" target="_blank"><span style="font-family: arial;">PDF</span></a></b></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-44664396127128013342024-03-17T11:12:00.005-03:002024-03-17T11:12:35.864-03:00A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://images.journals.lww.com/apallergy/XLargeThumb.01607935-202403000-00000.CV.jpeg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="214" data-original-width="160" height="157" src="https://images.journals.lww.com/apallergy/XLargeThumb.01607935-202403000-00000.CV.jpeg" width="118" /></a></span></div><span style="font-family: arial;"><br />Bhatia D, Mehta H, Bishnoi A, Srivastava N, Vinay K, Parsad D, Kumaran MS. <i><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10932479/" target="_blank">Asia Pac Allergy. 2024 Mar;14(1):5-11. doi: 10.5415/apallergy.0000000000000132.</a></i></span><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><b><span style="font-family: arial;">Background:</span></b></p><p><span style="font-family: arial;">Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive.</span></p><p><b><span style="font-family: arial;">Objective:</span></b></p><p><span style="font-family: arial;">To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients.</span></p><p><b><span style="font-family: arial;">Methods:</span></b></p><p><span style="font-family: arial;">This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response. <span></span></span></p><a name='more'></a><span style="font-family: arial;">Serological markers, serum IgE, and anti-TPO were correlated with baseline disease severity and antihistamine response.</span><p></p><p><b><span style="font-family: arial;">Results:</span></b></p><p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10932479/bin/pa9-14-05-g004.jpg" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><span style="font-family: arial;"><img border="0" data-original-height="194" data-original-width="800" height="98" src="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10932479/bin/pa9-14-05-g004.jpg" width="400" /></span></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="background-color: white; color: #333333; text-align: start;"><span style="font-family: arial; font-size: xx-small;">Comparison of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein A-IV <br />among antihistamine responders, nonresponders, and healthy controls.</span></span></td></tr></tbody></table><span style="font-family: arial;">C5a levels were significantly higher in cases as compared to controls (P = 0.004). Significantly higher IL-9 levels were observed in antihistamine responders than nonresponders (P = 0.008). Baseline urticaria severity demonstrated a statistically significant positive and negative correlations with IL-9 (ρ = 0.277, P = 0.007) and apo A-IV (ρ = −0.271, P = 0.008) levels, respectively. Levels of serum IgE (P = 0.031) and anti-TPO (P = 0.039) were significantly higher in antihistamine nonresponders compared to responders.</span></p><p><b><span style="font-family: arial;">Conclusions:</span></b></p><p><span style="font-family: arial;">IL-9 and apo A-IV might be potential novel biomarkers to predict urticaria severity. Higher IL-9 might be a predictor of antihistamine response. Elevated anti-TPO and serum IgE might predict poor antihistamine response.</span></p><p style="text-align: center;"><a href="chrome-extension://dagcmkpagjlhakfdhnbomgmjdpkdklff/enhanced-reader.html?openApp&pdf=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC10932479%2Fpdf%2Fpa9-14-05.pdf" target="_blank"><span style="font-family: arial; font-size: medium;"><b>PDF</b></span></a></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-69759437598667462292024-03-17T11:00:00.002-03:002024-03-17T11:01:21.509-03:00The autologous serum skin test (ASST) predicts the response to anti-IgE treatment in Chronic Spontaneous Urticaria patients: a prospective study<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: left;"><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJpoGZVBjAAWF67m420BK2OJuwEryHh5OKK8HFH5Gme_0PgI4gdavgkcYeuJgciC_GHJoizKMpxmExSidWBop_4ASJ1W_oQyzyGTrEgXTrwNScvM2X42-W7KS2GNpcmHJCB2waq7lOzoW0uj_Sj4VHBYdBu-aeXkxSwei5YOfOzhdd1-PmGXcEuba5I8o/s468/volume--5722imhp1.jpg" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="468" data-original-width="364" height="138" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJpoGZVBjAAWF67m420BK2OJuwEryHh5OKK8HFH5Gme_0PgI4gdavgkcYeuJgciC_GHJoizKMpxmExSidWBop_4ASJ1W_oQyzyGTrEgXTrwNScvM2X42-W7KS2GNpcmHJCB2waq7lOzoW0uj_Sj4VHBYdBu-aeXkxSwei5YOfOzhdd1-PmGXcEuba5I8o/w108-h138/volume--5722imhp1.jpg" width="108" /></a></span></div><span style="font-family: arial;"><br />Palladino A, Villani F, Pinter E, Visentini M, Asero R. <i><a href="http://www.eurannallergyimm.com/cont/online-first/1326/original-articlebrthe-autologous-serum-skin-test-asst.asp?pgg=1" target="_blank">Eur Ann Allergy Clin Immunol. 2024 Mar 14. doi: 10.23822/EurAnnACI.1764-1489.337.</a></i></span></div><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><span style="font-family: arial;"><b>Background.</b> Chronic spontaneous urticaria (CSU), characterized by recurrent itchy wheals and angioedema for > 6 weeks, is a quite common disease that may heavily impair the quality of life. Omalizumab, an anti-IgE mAb, has much improved the management of CSU but patients' response to the drug may vary and predictive markers are still largely missing. We investigated the predictive value of the autologous serum skin test (ASST) on omalizumab response. </span></p><p><span style="font-family: arial;"><b>Methods.</b> 15 patients with severe CSU eligible for omalizumab treatment were prospectively studied submitting them to ASST and to complete blood count, D-dimer, anti-thyroid peroxidase antibodies, and total IgE measurement before the start of the treatment. </span></p><p><span style="font-family: arial;"><b></b></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiChKYmS1YnLV4grYA6sMIyig9a9VCn0LTMmD4D9sDWaeMoCci46QML-1GUPjkXP0MI39QHjUeNmw2q3Wc_GBT7kpaFfelScSKKGRqXErXcp8BoHDWbjRi5mDBixCIvA0X9AHIinacDCa7apphSJc0-bKFFyvFCvRVuLx4LfiBCXHG7jH0ssxmr7hwi1Bg/s762/ST.png" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><span style="font-family: arial;"><img border="0" data-original-height="246" data-original-width="762" height="103" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiChKYmS1YnLV4grYA6sMIyig9a9VCn0LTMmD4D9sDWaeMoCci46QML-1GUPjkXP0MI39QHjUeNmw2q3Wc_GBT7kpaFfelScSKKGRqXErXcp8BoHDWbjRi5mDBixCIvA0X9AHIinacDCa7apphSJc0-bKFFyvFCvRVuLx4LfiBCXHG7jH0ssxmr7hwi1Bg/s320/ST.png" width="320" /></span></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-family: arial; font-size: x-small;">Summary table of the differences between the means of the two <br />groups of patients divided
according to the response to therapy.</span></td></tr></tbody></table><span style="font-family: arial;"><b>Results.</b> 14/15 (93%) responded brilliantly to omalizumab at 3 months assessment. 7 responded in less than 1 month ("early responders") and 7 only after multiple administrations ("late responders"). Of 9 patients scoring positive on ASST, 7 (78%) were late, and 2 (22%) early responders to omalizumab (p = 0.021). <span></span></span><p></p><a name='more'></a><span style="font-family: arial;">Of 6 patients scoring negative on ASST, 5 were early omalizumab responders and 1 did not respond. The PPV and NPV of the ASST for a "late" response to omalizumab were 78% and 100%, respectively. Total IgE were significantly higher in early responders. </span><b style="font-family: arial;">Conclusions.</b><span style="font-family: arial;"> Although larger prospective studies are needed to confirm these results, this study confirms previous retrospective investigations that the positive ASST appears to predict a slow response to omalizumab in CSU patients.</span><p style="text-align: center;"><a href="http://www.eurannallergyimm.com/cont/online-first/1326/original-articlebrthe-autologous-serum-skin-test-asst-5784allasp1.pdf" target="_blank"><span style="font-family: arial;"><b>PDF</b></span></a></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-2520310196901204332024-03-17T10:31:00.005-03:002024-03-17T10:31:41.580-03:00Pharmacists’ Attitudes Towards Long-Term Use of Nasal Decongestants: A Cross-Sectional Study<span style="font-family: arial;"><div class="separator" style="clear: both; text-align: center;"><a href="https://www.tandfonline.com/doi/cover-img/10.1080/djmd20.v013.i00" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="252" data-original-width="200" height="167" src="https://www.tandfonline.com/doi/cover-img/10.1080/djmd20.v013.i00" width="133" /></a></div><br />Mokhatrish MM, Almatrafi SD, Aldrees TM, Aldriweesh TA, AlGhamdi FM, Al-Dosary AS, Alhumaydani NK, Aldakkan OZ, Alrudian N, Ali AH. <a href="https://www.dovepress.com/pharmacists-attitudes-towards-long-term-use-of-nasal-decongestants-a-c-peer-reviewed-fulltext-article-JMDH" target="_blank"> J Multidiscip Healthc. 2024;17:1079-1090<br />https://doi.org/10.2147/JMDH.S451835</a></span><div><span style="font-family: arial;"><br /></span></div><div><div><span style="font-family: arial;"><b>Background:</b> Rhinitis medicamentosa is a nonallergic inflammation of the nasal mucosa caused by topical decongestants overuse. It mainly affects young and middle-aged adults. Therefore, the aim of this study was to investigate the attitudes of pharmacists regarding the utilization of over-the-counter intranasal decongestants.</span></div><div><span style="font-family: arial;"><b>Methods:</b> An online cross-sectional study was conducted from November 2021 to January 2022. The target population of the study included pharmacists who work in community pharmacies in Saudi Arabia. Binary logistic regression analysis was used to identify predictors of having positive attitude towards controlling the use of decongestant.</span></div><div><span style="font-family: arial;"><b><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://www.dovepress.com/getfile_article_fulltext.php?filename=article_fulltext%2Fs451000%2F451835/img/JMDH_A_451835_O_F0001g.jpg" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="648" data-original-width="750" height="276" src="https://www.dovepress.com/getfile_article_fulltext.php?filename=article_fulltext%2Fs451000%2F451835/img/JMDH_A_451835_O_F0001g.jpg" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="background-color: white; color: #555555; font-size: 11.4844px; text-align: left;">Most prevalent symptoms of patients asking for NDs</span><span style="background-color: white; color: #555555; font-size: 11.4844px; text-align: left;">.</span></td></tr></tbody></table>Results:</b> A total of 220 participants were included in this study. Around 15.0% of them reported that ND come with a physician prescription. The majority of the participants (87.3%) reported that the less than 5 days is the maximum safe duration for the use of NDs. Overall, the study participants demonstrated moderately positive attitude towards controlling the use of decongestant with a mean attitude score of 2.5 (standard deviation: 1.2) out of 5; which represents 50.0% of the maximum score.<span><a name='more'></a></span> Binary logistic regression analysis identified that pharmacists aged 31– 40 years were two-folds more likely to have positive attitude towards controlling the use of decongestant compared to others (p< 0.05). Around 45.9% of them reported that they recommend other over-the-counter treatments like nasal irrigation, nasal steroids, or antihistamine if they see a patient with RM asking for ND with or without prescription.</span></div><div><span style="font-family: arial;"><b>Conclusion:</b> The majority of pharmacists in Saudi Arabia demonstrated sufficient awareness and understanding on the adverse effects associated with the excessive use of NDs. Rhinitis medicamentosa can be avoided by appropriate measures, highlighting the importance of raising awareness about the excessive use of decongestants among healthcare professionals and patients alike.</span></div></div><div><span style="font-family: arial;"><br /></span></div><div style="text-align: center;"><a href="https://www.dovepress.com/getfile.php?fileID=97526" target="_blank"><span style="font-family: arial;">PDF</span></a></div>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-50275857139744193542024-03-15T11:33:00.001-03:002024-03-15T11:33:45.101-03:00Component-specific clusters for diagnosis and prediction of allergic airway diseases<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://onlinelibrary.wiley.com/cms/asset/8f42fc49-a0ff-4cd3-9d23-3a74799e01f6/cea.v54.3.cover.jpg" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="782" data-original-width="595" height="117" src="https://onlinelibrary.wiley.com/cms/asset/8f42fc49-a0ff-4cd3-9d23-3a74799e01f6/cea.v54.3.cover.jpg" width="89" /></a></span></div><span style="font-family: arial;">Howard R, Fontanella S, Simpson A, Murray CS, Custovic A, Rattray M. <i><a href="https://onlinelibrary.wiley.com/doi/10.1111/cea.14468" target="_blank">Clin Exp Allergy. 2024; 00: 1-11. doi:10.1111/cea.14468</a></i></span><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><b><span style="font-family: arial;">Background</span></b></p><p><span style="font-family: arial;">Previous studies which applied machine learning on multiplex component-resolved diagnostics arrays identified clusters of allergen components which are biologically plausible and reflect the sources of allergenic proteins and their structural homogeneity. Sensitization to different clusters is associated with different clinical outcomes.</span></p><p><b><span style="font-family: arial;">Objective</span></b></p><p><span style="font-family: arial;">To investigate whether within different allergen component sensitization clusters, the internal within-cluster sensitization structure, including the number of c-sIgE responses and their distinct patterns, alters the risk of clinical expression of symptoms.</span></p><p><b><span style="font-family: arial;">Methods</span></b></p><p><span style="font-family: arial;">In a previous analysis in a population-based birth cohort, by clustering component-specific (c-s)IgEs, we derived allergen component clusters from infancy to adolescence. In the current analysis, we defined each subject's within-cluster sensitization structure which captured the total number of c-sIgE responses in each cluster and intra-cluster sensitization patterns. <span></span></span></p><a name='more'></a><span style="font-family: arial;">Associations between within-cluster sensitization patterns and clinical outcomes (asthma and rhinitis) in early-school age and adolescence were examined using logistic regression and binomial generalized additive models.</span><p></p><p><b><span style="font-family: arial;">Results</span></b></p><p><span style="font-family: arial;"></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://onlinelibrary.wiley.com/cms/asset/b4ff946c-edfb-41b4-9de4-9093f09e7e1d/cea14468-fig-0003-m.jpg" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="650" data-original-width="1384" height="150" src="https://onlinelibrary.wiley.com/cms/asset/b4ff946c-edfb-41b4-9de4-9093f09e7e1d/cea14468-fig-0003-m.jpg" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span face=""Open Sans", icomoon, sans-serif" style="background-color: white; color: #1c1d1e; font-size: 12px; text-align: start;">Odds ratios and 95% CIs from univariable logistic regression for <br />the associations between the responses to the House Dust <br />Mite(HDM)and Grass/cat clusters at age 5 and current asthma, <br />rhinitis and wheeze at age 5. </span></td></tr></tbody></table><span style="font-family: arial;">Intra-cluster sensitization patterns revealed specific associations with asthma and rhinitis (both contemporaneously and longitudinally) that were previously unseen using binary sensitization to clusters. A more detailed description of the subjects' within-cluster c-sIgE responses in terms of the number of positive c-sIgEs and unique sensitization patterns added new information relevant to allergic diseases, both for diagnostic and prognostic purposes. For example, the increase in the number of within-cluster positive c-sIgEs at age 5 years was correlated with the increase in prevalence of asthma at ages 5 and 16 years, with the correlations being stronger in the prediction context (e.g. for the largest ‘Broad’ component cluster, contemporaneous: r = .28, p = .012; r = .22, p = .043; longitudinal: r = .36, p = .004; r = .27, p = .04).</span><p></p><p><b><span style="font-family: arial;">Conclusion</span></b></p><p><span style="font-family: arial;">Among sensitized individuals, a more detailed description of within-cluster c-sIgE responses in terms of the number of positive c-sIgE responses and distinct sensitization patterns, adds potentially important information relevant to allergic diseases.</span></p><p><b><span style="font-family: arial;">Key messages</span></b></p><p></p><ul style="text-align: left;"><li><span style="font-family: arial;">Clustering of c-sIgEs uncovers structure which reflects sources of allergenic proteins and/or their structural homogeneity;</span></li><li><span style="font-family: arial;">Number of positive c-sIgEs within each cluster adds information relevant to the diagnosis/prediction of asthma.</span></li><li><span style="font-family: arial;">Distinct within-cluster sensitization patterns differ in their association with health, asthma and rhinitis.</span></li></ul><div style="text-align: center;"><a href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/cea.14468" target="_blank"><span style="font-family: arial; font-size: medium;"><b>PDF</b></span></a></div><p></p><div><br /></div>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-44988266230723412982024-03-13T16:58:00.007-03:002024-03-13T16:59:09.761-03:00The Role of Extracellular Vesicles in Atopic Dermatitis.<p><span style="font-family: arial;"><span style="background-color: white; color: #222222;"></span></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://pub.mdpi-res.com/img/journals/ijms-logo.png?41930e44070e4940" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="140" data-original-width="650" height="43" src="https://pub.mdpi-res.com/img/journals/ijms-logo.png?41930e44070e4940" width="200" /></a></span></div><span style="font-family: arial;">Harvey-Seutcheu, C.; Hopkins, G.; Fairclough, L.C. <i><a href="https://www.mdpi.com/1422-0067/25/6/3255" target="_blank"><span style="background-color: white; box-sizing: border-box; color: #222222; line-height: inherit; max-height: 1e+06px;">Int. J. Mol. Sci.</span><span style="background-color: white; color: #222222;"> </span><span style="background-color: white; box-sizing: border-box; color: #222222; line-height: inherit; max-height: 1e+06px;">2024</span><span style="background-color: white; color: #222222;">, </span><span style="background-color: white; box-sizing: border-box; color: #222222; line-height: inherit; max-height: 1e+06px;">25</span><span style="background-color: white; color: #222222;">, 3255. https://doi.org/10.3390/ijms25063255</span></a></i></span><p></p><p><span style="font-family: arial;"><br /></span></p><p><span style="font-family: arial;"><b>Abstract</b></span></p><p><span style="font-family: arial;"></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://pub.mdpi-res.com/ijms/ijms-25-03255/article_deploy/html/images/ijms-25-03255-g002.png?1710326827" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="1752" data-original-width="2048" height="343" src="https://pub.mdpi-res.com/ijms/ijms-25-03255/article_deploy/html/images/ijms-25-03255-g002.png?1710326827" width="400" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span face="Arial, Arial, Helvetica, sans-serif" style="background-color: white; color: #222222; font-size: 13.2px; text-align: justify;">Summary of cells of origin, characteristics, and effects of </span><span class="html-italic" face="Arial, Arial, Helvetica, sans-serif" style="background-color: white; box-sizing: border-box; color: #222222; font-size: 13.2px; font-style: italic; max-height: 1e+06px; text-align: justify;">S. aureus</span><span face="Arial, Arial, Helvetica, sans-serif" style="background-color: white; color: #222222; font-size: 13.2px; text-align: justify;">-,<br /> </span><span class="html-italic" face="Arial, Arial, Helvetica, sans-serif" style="background-color: white; box-sizing: border-box; color: #222222; font-size: 13.2px; font-style: italic; max-height: 1e+06px; text-align: justify;">M. sympodialis</span><span face="Arial, Arial, Helvetica, sans-serif" style="background-color: white; color: #222222; font-size: 13.2px; text-align: justify;">-, and mast cell-derived EVs. </span></td></tr></tbody></table><span style="font-family: arial;">Atopic dermatitis, or eczema, is the most common chronic skin disorder, characterized by red and pruritic lesions. Its etiology is multifaceted, involving an interplay of factors, such as the allergic immune response, skin barrier dysfunction, and dysbiosis of the skin microbiota. Recent studies have explored the role of extracellular vesicles (EVs), which are lipid bilayer-delimitated particles released by all cells, in atopic dermatitis. Examination of the available literature identified that most studies investigated EVs released by Staphylococcus aureus, which were found to impact the skin barrier and promote the release of cytokines that contribute to atopic dermatitis development. <span></span></span><p></p><a name='more'></a><span style="font-family: arial;">In addition, EVs released by the skin fungus, Malassezia sympodialis, were found to contain allergens, suggesting a potential contribution to allergic sensitization via the skin. The final major finding was the role of EVs released by mast cells, which were capable of activating various immune cells and attenuating the allergic response. While research in this area is still in its infancy, the studies examined in this review provide encouraging insights into how EVs released from a variety of cells play a role in both contributing to and protecting against atopic dermatitis.</span><p></p><p style="text-align: center;"><span style="font-family: arial; font-size: medium;"><a href="https://www.mdpi.com/1422-0067/25/6/3255/pdf?version=1710326742" target="_blank"><b>PDF</b></a></span></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-50783190204199652112024-03-13T09:50:00.001-03:002024-03-13T09:50:42.296-03:00Allergic Rhinitis A Review<div><span style="font-family: arial;">Jonathan A. Bernstein, Joshua S. Bernstein, Richika Makol et al.</span></div><div><i><a href="Jonathan A. Bernstein, MD1; Joshua S. Bernstein, MD1; Richika Makol, MD2; et alStephanie Ward, MD2 Author Affiliations Article Information JAMA. 2024;331(10):866-877. doi:10.1001/jama.2024.0530" target="_blank"><span style="font-family: arial;">JAMA. 2024;331(10):866-877. doi:10.1001/jama.2024.0530</span></a></i></div><div><span style="font-family: arial;"><br /></span></div><div><div><b><span style="font-family: arial;">Abstract</span></b></div><div><b><span style="font-family: arial;"><br /></span></b></div><div><span style="font-family: arial;"><b>Importance </b> </span></div><div><span style="font-family: arial;">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.</span></div><div><span style="font-family: arial;"><br /></span></div><div><span style="font-family: arial;"><b><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://cdn.jamanetwork.com/ama/content_public/journal/jama/939336/m_jrv240003f1_1709580667.83601.png?Expires=1713356219&Signature=XBixZLYvagY72cPUPurK5GQ2KrDj8ZUPpZP4ok0vQO5TYeRuSjt9rCrXoaTsC4CBCwP8cEc0MEuKZZP3JEVknMXi~yVK50j88Hxg14zvcx8AHH1ZUBe1E0VMMnI-qgQR2JbnbUdAGpnkz3xs9mW5ffGfA~EceiP2YJ0II6ZTW6UdLZPoDwb5w5Joee2qH4aMHMVyroFcYPmXDjFKxRMul901-I1zJh~4WRbtMvq~PNEuupUTEkvh2PpY2Ay5HFMVKxPAoxRqNcBkohH5URbMtxXbPvpMrZUlem0q8R-RhPemsmL0Sue7retIAeVv325NT9M19jSOVVtLbHbR0vsG7w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="959" data-original-width="810" height="400" src="https://cdn.jamanetwork.com/ama/content_public/journal/jama/939336/m_jrv240003f1_1709580667.83601.png?Expires=1713356219&Signature=XBixZLYvagY72cPUPurK5GQ2KrDj8ZUPpZP4ok0vQO5TYeRuSjt9rCrXoaTsC4CBCwP8cEc0MEuKZZP3JEVknMXi~yVK50j88Hxg14zvcx8AHH1ZUBe1E0VMMnI-qgQR2JbnbUdAGpnkz3xs9mW5ffGfA~EceiP2YJ0II6ZTW6UdLZPoDwb5w5Joee2qH4aMHMVyroFcYPmXDjFKxRMul901-I1zJh~4WRbtMvq~PNEuupUTEkvh2PpY2Ay5HFMVKxPAoxRqNcBkohH5URbMtxXbPvpMrZUlem0q8R-RhPemsmL0Sue7retIAeVv325NT9M19jSOVVtLbHbR0vsG7w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" width="338" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-size: x-small;">The Pathogenesis of Allergic Rhinitis</span></td></tr></tbody></table>Observations</b> </span></div><div><span style="font-family: arial;">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.<span><a name='more'></a></span> 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.</span></div><div><span style="font-family: arial;"><br /></span></div><div><span style="font-family: arial;"><b>Conclusions and Relevance</b> </span></div><div><span style="font-family: arial;">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.</span></div></div><div><span style="font-family: arial;"><br /></span></div><div><div class="audio-player-wrap" style="box-sizing: inherit; color: #243647; display: flex; font-family: "LL Akkurat Web", Helvetica, Arial, sans-serif; font-size: 16px; margin-bottom: 16px;"><div class="mp--thumbnail" style="box-sizing: inherit;"><div class="clsFixer" style="box-sizing: inherit; width: 155.906px;"><img alt="<title>Diagnosis and Treatment of Allergic Rhinitis</title>" src="https://cdn.edhub.ama-assn.org/ama/content_public/multimedia/jsx240034audio1_thumb.jpeg?Expires=1713279741&Signature=zin1Gl7p7P94HWNUfixvGtJTH4tVCEWJGRBhJ5AZ3TWOllHIMHZrogxFv3iSmmbojaLITWjkLTTQeyYk-sPvU6~YusIjsmFELrR-Lf4aATXMERQ6HNA09PKeXS-TCdMSOQN9WsA70rcxDG-9HhZfwZEbwyUf-PdOLTd~FOnt9oGyRS0aZ8rHMahmeVUjW6wP5E0mwmzHATC0VX4us8On3iAk04tOMTlsJvlZpuMk9MLlQrQCgib9jJPn8CTDr03NBGQv7WB3FKbp0Y3d2WWbV~pz1zAAJm-8tuTh9OhzPvUkikOZWCjpDGFmpYmVAggsh1UMXIik7n1zHfMhzKJsOg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" style="box-sizing: inherit; 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line-height: 1.7;"></p><p class="para" style="box-sizing: inherit; line-height: 1.7; margin-top: 24px;">Allergic rhinitis affects an estimated 15% of the US population and is associated with impaired quality of life. JAMA Deputy Editor Mary McGrae McDermott, MD, discusses current evidence regarding the diagnosis and treatment of allergic rhinitis with author Jonathan A. Bernstein, MD, College of Medicine, University of Cincinnati.</p></div></div><div><span style="font-family: arial;"><br /></span></div><div style="text-align: center;"><a href="https://watermark.silverchair.com/jama_bernstein_2024_rv_240003_1709580667.65093.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAy0wggMpBgkqhkiG9w0BBwagggMaMIIDFgIBADCCAw8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMOJ_WQqrniW9yOuKLAgEQgIIC4OVta7mw-AkZQA0x2CPri2NLicke-wsuwH3nI-Q7no38d-rLH99SpoyBmCuKVX70G3iGpVlX5hoj_rygFUiDy278yuS8rPSyOj9D4LXUEBgME3HOaCFev3gIBTiiz19ccDbJg-O0cDnzZtZqlZtb17ruLnt2bStF6pTTvl8Xza5gFZiEQ8sxeCNiQW_cMbv56xqDvyKdlAlzCk0Eyq_VLRnbvCF8DZcinykD0gko8F5BAiL3H_yzcDUCfhQJdhYkXzQa18wiSxxjt75i2LmHge8hSW3HAurW2rM5mQNozifwcihqEJS80IRtmhFOC6X_bxHemoIw1OSgKJ82I1XpLHzFsNJgC35djl72fAfyQF9T2fEQA3FRZgRkUWCx4Oi_z13wRkq4oYimHkxyle1qOIBgLdq57x1A2pVOA6TyENRIGw0RVxIDyaWNBEfvIFCz1gcCDU28zJFFznW6i-J0U5hdZQMQ_5nEQhA8ZWd0EHJMDspE5rlgoxBGZGqz13I_tg8iRJ6c7HNhlUq3ANdMATrxbkF6J40uiRChjb09XlyT9id5hDhic4UiZ9ZAYjrLH5JtJD0n45PAnSYzbSxvrvLr8Rl9F9g8fFiRTp6BHYEj4Al0QaSK0Jqf9fW8Trud3NQvnk1uLl0CZvqT3z6gEyIt-sV9LrDGJiuPKUzxGZ7ynpXMy0p54dPvi5oWBo5Q3mHJRoGUafJ-OEdaDv4oaWi-91aOX8NnMkWrs2Ah_tNRCJ6bp3psczeFJc1UMoqcWmeUOEiarbwKSZ-Xo1L3Muwt4_-o4-Mk7XFoCG15VbtdH5e84CCC4Pr0OyckgOUQjfgAraWJVmseKkh9cyl5ZiF6K25WVbaSY2QmTbFumZVPc6NaW7-DuMMF2sNg3H6RtDrQsEBoTRE3v3JrKHdQyYziuaUoH3vvwcltbJRJQIU7AV9G7pW31epPFAD8ZI_6f2mGXZhBeyA2Gj9AVJOCEt4" target="_blank"><span style="font-family: arial; font-size: medium;"><b>PDF</b></span></a></div>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-24277371943798805542024-03-12T10:31:00.003-03:002024-03-12T10:31:37.560-03:00Introduction of a penicillin allergy de-labelling program with direct oral challenge and its effects on utilization of beta-lactam antimicrobials: a multicenter retrospective parallel cohort study<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://media.springernature.com/lw725/springer-cms/rest/v1/content/733132/data/v3" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="119" data-original-width="189" height="79" src="https://media.springernature.com/lw725/springer-cms/rest/v1/content/733132/data/v3" width="126" /></a></span></div><span style="font-family: arial;">Mir, A., Lanoue, D., Zanichelli, V. et al. <i><a href="https://aacijournal.biomedcentral.com/articles/10.1186/s13223-024-00877-9" target="_blank">Allergy Asthma Clin Immunol 20, 20 (2024). https://doi.org/10.1186/s13223-024-00877-9</a></i></span><p></p><p><span style="font-family: arial;"><b>Abstract</b></span></p><p><span style="font-family: arial;"><b>Background</b></span></p><p><span style="font-family: arial;">Self-reported penicillin allergy labels are common and often inaccurate after assessment. These labels can lead to reduced use of first-line beta-lactam antibiotics and worse outcomes. We measured the impact of a previously performed inpatient proactive systematic penicillin allergy de-labelling program on subsequent antibiotic use. This prior program included assessment, risk-stratification, and low risk direct oral amoxicillin challenge.</span></p><p><span style="font-family: arial;"><b>Methods</b></span></p><p><span style="font-family: arial;"></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13223-024-00877-9/MediaObjects/13223_2024_877_Fig1_HTML.png?as=webp" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="765" data-original-width="685" height="320" src="https://media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13223-024-00877-9/MediaObjects/13223_2024_877_Fig1_HTML.png?as=webp" width="287" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="background-color: white; color: #333333; text-align: start;"><span style="font-size: x-small;">Schematic representation of the de-labelling implementation program</span></span></td></tr></tbody></table><span style="font-family: arial;">We performed a retrospective comparison of parallel cohorts from two separate tertiary care hospital campuses in Ottawa, Canada across two penicillin de-labelling intervention periods across April 15th to April 30th, 2021, and February 15th to March 8th, 2022. Outcomes, including penicillin allergy labelling and antibiotic use, were collected for the index admission and the subsequent 6-month period. Descriptive statistics and multivariate regression analyses were performed.</span><p></p><p><span style="font-family: arial;"><b>Results</b></span></p><p><span style="font-family: arial;">A total of 368 patients with penicillin allergy label were included across two campuses and study periods. 24 (13.8%) patients in the intervention groups had sustained penicillin allergy label removal at 30 days from admission vs. 3 (1.5%) in the non-intervention group (p < 0.001). <span></span></span></p><a name='more'></a><span style="font-family: arial;">In the 6-months following admission, beta-lactams were prescribed more frequently in the intervention groups vs. the non-intervention groups for all patients (28 [16.1%] vs.15 [7.7%], p = 0.04) and were prescribed more frequently amongst those who received at least one antibiotic (28/46 [60.9%] vs.15/40 [37.5%], p = 0.097). In a multivariate regression analysis, the intervention groups were found to be associated with an increased odds of beta-lactam prescribing in all patients (OR 2.49, 95%CI 1.29–5.02) and in those prescribed at least one antibiotic (OR 2.44, 95%CI 1.00–6.15). No drug-related adverse events were reported.</span><p></p><p><span style="font-family: arial;"><b>Conclusions</b></span></p><p><span style="font-family: arial;">Proactive penicillin allergy de-labelling for inpatients was associated with a reduction in penicillin allergy labels and increased utilizatio<b>n of beta-lactams in the subsequent 6-months.</b></span></p><p style="text-align: center;"><a href="https://aacijournal.biomedcentral.com/counter/pdf/10.1186/s13223-024-00877-9.pdf" target="_blank"><span style="font-family: arial;"><b>PDF</b></span></a></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-45720558900993890272024-03-11T17:16:00.001-03:002024-03-11T17:16:41.839-03:00Documentation of comorbidities, lifestyle factors, and asthma management during primary care scheduled asthma contacts.<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh3y-h2IwpvtOiHdnW6lbMCRJ-uI4MyfPTDfbf12uUsehc16W62s6v9hDVM3XhnjtkIgVrwxrmXuN0WAsZOIvYiYDn11McAzlrak1R4zvzjDP7SN8B844tuxgw_O794nO5d6N2BS926v0IcslY_B_GZSMkkPd4evqKTgTD6mDyOovM1S-FT-XQ2NzbT87I/s497/NPJ.png" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="45" data-original-width="497" height="29" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh3y-h2IwpvtOiHdnW6lbMCRJ-uI4MyfPTDfbf12uUsehc16W62s6v9hDVM3XhnjtkIgVrwxrmXuN0WAsZOIvYiYDn11McAzlrak1R4zvzjDP7SN8B844tuxgw_O794nO5d6N2BS926v0IcslY_B_GZSMkkPd4evqKTgTD6mDyOovM1S-FT-XQ2NzbT87I/s320/NPJ.png" width="320" /></a></span></div><span style="font-family: arial;">Takala, J., Vähätalo, I., Tuomisto, L.E. et al. <i><a href="https://www.nature.com/articles/s41533-024-00360-3" target="_blank">npj Prim. Care Respir. Med. 34, 2 (2024). https://doi.org/10.1038/s41533-024-00360-3</a></i></span><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><span style="font-family: arial;"></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41533-024-00360-3/MediaObjects/41533_2024_360_Fig3_HTML.png?as=webp" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="478" data-original-width="685" height="223" src="https://media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41533-024-00360-3/MediaObjects/41533_2024_360_Fig3_HTML.png?as=webp" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span face="-apple-system, "system-ui", "Segoe UI", Roboto, Oxygen-Sans, Ubuntu, Cantarell, "Helvetica Neue", sans-serif" style="background-color: white; color: #222222; text-align: start;"><span style="font-size: x-small;">Green colour describes the performed assessment that were implemented <br />well, yellow colour describes moderate implementation, <br />and the orange describes the measures that are poorly implemented.</span><span style="font-size: xx-small;"> </span></span></td></tr></tbody></table><span style="font-family: arial;">Systematically assessing asthma during follow-up contacts is important to accomplish comprehensive treatment. No previous long-term studies exist on how comorbidities, lifestyle factors, and asthma management details are documented in scheduled asthma contacts in primary health care (PHC). We showed comorbidities and lifestyle factors were poorly documented in PHC in this real-life, 12-year, follow-up study. Documented information on rhinitis was found in 8.9% and BMI, overweight, or obesity in ≤1.5% of the 542 scheduled asthma contacts. <span></span></span><p></p><a name='more'></a><span style="font-family: arial;">Of the 145 patients with scheduled asthma contacts, 6.9% had undergone revision of their inhalation technique; 16.6% had documentation of their asthma action plan. Screening of respiratory symptoms was recorded in 79% but nasal symptoms in only 15.5% of contacts. Lifestyle guidance interventions were found in <1% of contacts. These results, based on documented patient data, indicate a need exists to further improve the assessment and guidance of asthma patients in PHC.</span><p></p><p style="text-align: center;"><a href="https://www.nature.com/articles/s41533-024-00360-3.pdf" target="_blank"><span style="font-family: arial;"><b>PDF</b></span></a></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-12104522161434874062024-03-09T12:39:00.007-03:002024-03-09T12:39:47.608-03:00Food-dependent exercise-induced allergic reactions in Lipid Transfer Protein (LTP) hypersensitive subjects: new data and a critical reappraisal<p><span style="background-color: white; color: #212121; font-size: 16px;"><span style="font-family: arial;"></span></span></p><div class="separator" style="clear: both; text-align: left;"><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiKa7GC_LeKWe2aWWbuAt7XqHFY3czlf8VGBaySqPFGBXne9YgGQhAfgdqOHOODxqCKOqPyg3Sxp14v1UeodZR0q0QQgaYi7Z0ok4GcwzpRkswuLxc4NSDY_0sHrcFQaSD_x7_kjUaCH_7XQRHkOXJb3v7KtPgjMU4bOyftVscdQnrUthEoRvBV16e_Xes/s468/volume--5722imhp1.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="468" data-original-width="364" height="110" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiKa7GC_LeKWe2aWWbuAt7XqHFY3czlf8VGBaySqPFGBXne9YgGQhAfgdqOHOODxqCKOqPyg3Sxp14v1UeodZR0q0QQgaYi7Z0ok4GcwzpRkswuLxc4NSDY_0sHrcFQaSD_x7_kjUaCH_7XQRHkOXJb3v7KtPgjMU4bOyftVscdQnrUthEoRvBV16e_Xes/w86-h110/volume--5722imhp1.jpg" width="86" /></a></span></div><span style="font-family: arial;">Scala E, Villella V, Asero R. <i><a href="http://www.eurannallergyimm.com/cont/online-first/1321/original-articlebrfooddependent-exerciseinduced-allergic-reactions-lipid-transfer.asp" target="_blank">Eur Ann Allergy Clin Immunol. 2024 Mar 6. doi: 10.23822/EurAnnACI.1764-1489.334. </a></i></span></div><p></p><span style="font-family: arial;"><b>Summary</b></span><div><span style="font-family: arial;"><b><br />Background</b> Lipid transfer protein is the main cause of both primary food allergy and food-dependent exercise-induced allergic reactions (FDEIAR) in Italy. What characterizes LTP-hypersensitive patients with FDEIAR is still unclear. We investigated the key characteristics of LTP-hypersensitive patients with or without FDEIAR in a large cohort of individuals sensitized to this allergen.</span></div><div><span style="font-family: arial;"><br /></span><div><span style="font-family: arial;"><b>Methods</b> 1,203 food-allergic patients, diagnosed on the basis of unequivocal clinical history and presence of circulating food allergen-specific IgE were studied. Serum IgE reactivity was assessed using the Allergen ExplorerALEX® system (Macroarray Diagnostics, Vienna, Austria).<span><a name='more'></a></span> Association of specific IgE reactivities with FDEIAR was investigated, and patients with and without FDEIAR sensitized to LTP were compared.</span></div><div><span style="font-family: arial;"> </span></div><div><span style="font-family: arial;"><b><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEggj503JPT4lJwTTtqPUpyBJOjzuXj_u_ixtkxr4dxSpmK_b3A3ztfpx8hLA2Odk-aOPxAG0BebnAem_763Ev8WByRyUMQe7FmleWwJE0hn7HvsNjGEdJwcpgtSY1fOQ5ny8JpT0X0DOaTvJiAjVNgIWSLqK5xOg-aboe41KPRekX-7f21-TlG82BcttRQ/s648/forest.png" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="336" data-original-width="648" height="166" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEggj503JPT4lJwTTtqPUpyBJOjzuXj_u_ixtkxr4dxSpmK_b3A3ztfpx8hLA2Odk-aOPxAG0BebnAem_763Ev8WByRyUMQe7FmleWwJE0hn7HvsNjGEdJwcpgtSY1fOQ5ny8JpT0X0DOaTvJiAjVNgIWSLqK5xOg-aboe41KPRekX-7f21-TlG82BcttRQ/s320/forest.png" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-size: xx-small;">Forest diagram depicting the correlation between sensitization to various<br /> food
allergens and Food-Dependent Exercise-Induced Allergic Reactions. </span></td></tr></tbody></table>Results </b>116 subjects (9.6%) had FDEIAR. Among these, 77 (66.3%) were LTP-reactors and 16 (13.8%) were sensitized to Tri a 19 (omega-5-gliadin). Different LTPs and omega-5-gliadin emerged as the sole allergens clearly associated with FDEIAR. Severity of allergic reactions was paralleled the level of specific IgE to LTPs. Patients with FDEIAR showed significantly lower IgE levels than their counterparts with food allergy at rest, and displayed nearly identical IgE levels regardless of the severity of allergic reactions induced by exercise.</span></div><div><span style="font-family: arial;"><br /></span></div><div><span style="font-family: arial;"><b>Conclusions </b>FDEIAR are associated with specific allergens. Specific IgE levels in LTP-hypersensitive patients with FDEIAR show an intermediate titer between those simply sensitized and those showing classic food allergy.</span></div><div><span style="font-family: arial;"><br /></span></div><div style="text-align: center;"><a href="http://www.eurannallergyimm.com/cont/online-first/1321/original-articlebrfooddependent-exerciseinduced-allergic-reactions-lipid-transfer-5765allasp1.pdf" target="_blank"><span style="font-family: arial; font-size: medium;"><b>PDF</b></span></a></div></div>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-79173200883922951342024-03-09T10:09:00.007-03:002024-03-09T10:09:53.606-03:00Computerized Clinical Decision Support To Prevent Medication Errors and Adverse Drug Events: Rapid Review.<span style="font-family: arial;"><div class="separator" style="clear: both; text-align: center;"><a href="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-ahrqsaferhealthcare4-lrg.png" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="200" data-original-width="160" height="200" src="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-ahrqsaferhealthcare4-lrg.png" width="160" /></a></div>Syrowatka A, Motala A, Lawson E, Shekelle P. 2024 Feb. In: Making Healthcare Safer IV: A Continuous Updating of Patient Safety Harms and Practices <a href="https://pubmed.ncbi.nlm.nih.gov/38381911/">Agency for Healthcare Research and Quality (US); 2023 Jul–.2024 Feb</a></span><div><span style="font-family: arial;"><a href="https://pubmed.ncbi.nlm.nih.gov/38381911/"></a><br /><b>Excerpt</b><br /><br /><b>Objectives:</b> To assess the evidence on the effects of computerized clinical decision support systems (CDSSs) on the prevention of medication errors and adverse drug events, related implementation outcomes such as rates of medication alert overrides, and unintended consequences of use. We also summarized the literature around the effective implementation of a CDSS.<br /><br /><b>Methods:</b> We followed the rapid review processes of the Agency for Healthcare Research and Quality Evidence-based Practice Center Program. We queried PubMed and the Cochrane Library to locate relevant systematic reviews and primary studies published from 2015 to April 2023, supplemented by a targeted review of the grey literature. We narratively synthesized the evidence and assessed the overall strength of evidence for the outcomes of interest. The protocol for the review has been registered in PROSPERO (CRD42023449710).<span><a name='more'></a></span><span></span><br /><b><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh52poU4G5CjGF_j4DpLYrWET9cpent_61NdpNDF-Ex_RiIFDkxOffbpFs6Bw63L4TYaXGhZuAxehyGKjO9qCibUbJ7_1Z9lfwoLgUyZeixjvYQiAlYg0cQ9p7D7Q6XHimhrUiCeDbiVWHe5fvBZomCBN-VMMA2hqywkl1xP4Gid9iJaoQpIhIawpobYtk/s558/DA.png" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="267" data-original-width="558" height="153" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh52poU4G5CjGF_j4DpLYrWET9cpent_61NdpNDF-Ex_RiIFDkxOffbpFs6Bw63L4TYaXGhZuAxehyGKjO9qCibUbJ7_1Z9lfwoLgUyZeixjvYQiAlYg0cQ9p7D7Q6XHimhrUiCeDbiVWHe5fvBZomCBN-VMMA2hqywkl1xP4Gid9iJaoQpIhIawpobYtk/s320/DA.png" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-size: x-small;">Overall assessments of the strength (certainty) of evidence</span></td></tr></tbody></table>Findings:</b> Our search yielded 1,335 unique abstracts, of which 33 articles met the target criteria and were included in the review (27 systematic reviews, one overview of reviews, and five primary studies). Twenty reviews (out of 22) reporting on effectiveness were rated “good” or “fair” quality. One primary study included in the narrative synthesis was rated as having a “low” risk of bias. The evidence covered the effects of CDSSs across various healthcare settings and specialties. The type of decision support provided by the CDSSs and outcomes were heterogeneous between studies. Overall, computerized provider order entry with medication-related CDSSs were associated with reduced medication errors (moderate strength of evidence) and prevention of adverse drug events (low strength of evidence). Improved or targeted medication-related CDSSs were associated with reductions of medication errors and adverse drug events (moderate strength of evidence). However, alert override rates were high and varied between studies, and the appropriateness of the overrides was largely influenced by the type of alert. Other unintended consequences included CDSS-related errors, overdependence on alerts, alert fatigue, inappropriate alert overrides, and provider burnout. An additional 48 articles focused on barriers and facilitators of CDSS implementation.<br /><br /><b>Conclusions:</b> Overall, CDSSs reduce medication errors and adverse drug events, with moderate- and low-certainty evidence, respectively. However, there were several unintended consequences of CDSS implementation and use. The evidence of benefits and harms was generally reported in different studies with varying contexts, making the net benefit difficult to estimate. Future research should focus on measuring these outcomes and unintended consequences in the same study to generate evidence on both the benefits and harms associated with using a CDSS in the same context.</span></div><div><span style="font-family: arial;"><br /></span></div><div style="text-align: center;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK600580/pdf/Bookshelf_NBK600580.pdf" target="_blank"><span style="font-family: arial;">PDF</span></a></div>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-19976959439171575042024-03-07T10:04:00.001-03:002024-03-07T10:04:57.791-03:00Intranasal corticosteroids reduced acute rhinosinusitis in children with allergic rhinitis: A nested case–control study<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://ars.els-cdn.com/content/image/1-s2.0-S1684118224X0002X-cov150h.gif" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="150" data-original-width="113" height="150" src="https://ars.els-cdn.com/content/image/1-s2.0-S1684118224X0002X-cov150h.gif" width="113" /></a></span></div><span style="font-family: arial;">Lin CL, Lee KH, Huang WT, Hsieh LC, Wang CM.<i style="font-weight: bold;"> </i><i><a href="https://www.sciencedirect.com/science/article/pii/S1684118223002116" target="_blank">J Microbiol Immunol Infect. 2024 Feb;57(1):175-183. doi: 10.1016/j.jmii.2023.11.005.</a></i></span><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><b><span style="font-family: arial;">Background</span></b></p><p><span style="font-family: arial;">Children with allergic rhinitis (AR) have substantially more acute rhinosinusitis than children without AR. We evaluated whether intranasal corticosteroids (INCS), second-generation antihistamines (SGH), and/or intranasal antihistamines (INH) for AR affect acute rhinosinusitis in children with AR aged 2–18 years.</span></p><p><b><span style="font-family: arial;">Methods</span></b></p><p><span style="font-family: arial;"></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://ars.els-cdn.com/content/image/1-s2.0-S1684118223002116-gr1.jpg" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="213" data-original-width="580" height="118" src="https://ars.els-cdn.com/content/image/1-s2.0-S1684118223002116-gr1.jpg" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="color: #1f1f1f; text-align: start;"><span style="font-size: x-small;">Flow chart of participant enrollment.</span></span></td></tr></tbody></table><span style="font-family: arial;">By using the National Health Research Institutes Database 2005 of Taiwan, a cohort of patients with AR aged 2–18 years treated with AR medications between 2002 and 2018 was made, within which a nested case–control study was performed. Risk settings for acute rhinosinusitis cases matched controls for age, sex, and comorbidities. Current users of INCS, INH, and/or SGH were compared with remote and recent users of any AR medications and current users of INCS with and without SGH were compared with current users of SGH.<span></span></span><p></p><a name='more'></a><p></p><p><b><span style="font-family: arial;">Results</span></b></p><p><span style="font-family: arial;">Current users of SGH and/or INCS had a higher risk of acute rhinosinusitis than remote users of AR drugs, and current users of SGH had a higher risk of acute rhinosinusitis than recent users; however, no difference in the risk of acute rhinosinusitis was found between current users of INCS and recent users of AR drugs. Current users of INCS with and without SGH had a lower risk of acute rhinosinusitis than current users of SGH alone.</span></p><p><b><span style="font-family: arial;">Conclusions</span></b></p><p><span style="font-family: arial;">Treatment of INCS with and without SGH diminished the risk of acute rhinosinusitis compared with treatment using SGH alone. Adequate INCS treatment for patients with AR is important to reduce the incidence of acute rhinosinusitis.</span></p><p style="text-align: center;"><span style="font-family: arial;"><a href="https://www.sciencedirect.com/science/article/pii/S1684118223002116/pdfft?md5=fb079bb30c5a09a030c5208b72cf1d23&pid=1-s2.0-S1684118223002116-main.pdf" target="_blank">PDF</a></span></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-15996679923007967492024-03-05T10:26:00.008-03:002024-03-05T10:26:55.955-03:00Advancing Treatment in Atopic Dermatitis: A Comprehensive Review of Clinical Efficacy, Safety, and Comparative Insights Into Corticosteroids, Calcineurin Inhibitors, and Phosphodiesterase-4 Inhibitors as Topical Therapies<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://public.cureus.com/new-nav-bar/cureus-logo-new-nav.png" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><span style="font-family: arial;"><img border="0" data-original-height="124" data-original-width="456" height="41" src="https://public.cureus.com/new-nav-bar/cureus-logo-new-nav.png" width="153" /></span></a></div><span style="font-family: arial;">Hernandez T D, Aleman S J, Bao-Loc-Trung M, et al. <a href="https://www.cureus.com/articles/228950-advancing-treatment-in-atopic-dermatitis-a-comprehensive-review-of-clinical-efficacy-safety-and-comparative-insights-into-corticosteroids-calcineurin-inhibitors-and-phosphodiesterase-4-inhibitors-as-topical-therapies#!/" target="_blank">Cureus 16(3): e55393. doi:10.7759/cureus.55393</a></span><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><span style="font-family: arial;">Atopic dermatitis (AD) is a pervasive and multifaceted dermatological disorder causing daily distress to afflicted individuals worldwide. This comprehensive review synthesizes the historical and contemporary advancements in therapeutic strategies, offering a critical analysis of their efficacy, safety profiles, and adaptability. The enduring role of topical corticosteroids in managing AD is examined, acknowledging their potent anti-inflammatory properties alongside their potential adverse side effects, particularly in extended usage. The article explores the utilization of topical calcineurin inhibitors like tacrolimus and pimecrolimus, highlighting their novel anti-inflammatory pathways while also scrutinizing concerns over potential malignancies that relegate them to second-line therapy. <table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiAZESiE8iTOLAJp-kJQKWxZ5dae9KEpdlbUblXZWrORMZQQY_jcLPaKOubnXXAyAcZ7Vua17uNXwkQqbp2aabq8W1VQj5xZGrcYieDo8kvhVX2XdORnaE_ZbwTkDurpiGzDwxhA9k9i4dHsWlu_70A4WCe9pFks7pEdiTbyP0pt-4EvSl3saTUIhHUS34/s997/ADT.png" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="482" data-original-width="997" height="194" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiAZESiE8iTOLAJp-kJQKWxZ5dae9KEpdlbUblXZWrORMZQQY_jcLPaKOubnXXAyAcZ7Vua17uNXwkQqbp2aabq8W1VQj5xZGrcYieDo8kvhVX2XdORnaE_ZbwTkDurpiGzDwxhA9k9i4dHsWlu_70A4WCe9pFks7pEdiTbyP0pt-4EvSl3saTUIhHUS34/w400-h194/ADT.png" width="400" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="background-color: white; color: #222222; text-align: start;"><span style="font-size: x-small;">Comparative studies of PDE4 inhibitors, calcineurin inhibitors, and topical <br />corticosteroids in the pharmacological management of atopic dermatitis</span></span></td></tr></tbody></table><span></span></span></p><a name='more'></a><span style="font-family: arial;">The present investigation features the emergence of crisaborole, a phosphodiesterase four inhibitor. Its innovative mode of action, benign safety profile, and applicability to mild and moderate AD are thoroughly evaluated. The review also includes challenges, particularly cost considerations, which constrain accessibility and necessitate nuanced implementation in therapeutic regimens. This study underscores the need for persistent investigation, teamwork, and innovations in managing AD. In this regard, AD requires a united approach between clinicians, researchers, affected individuals, and policymakers to refine patient-focused treatment and develop precise, economical strategies to address this chronic and frequently life-altering health condition.</span><p></p><p style="text-align: center;"><a href="https://www.cureus.com/articles/228950-advancing-treatment-in-atopic-dermatitis-a-comprehensive-review-of-clinical-efficacy-safety-and-comparative-insights-into-corticosteroids-calcineurin-inhibitors-and-phosphodiesterase-4-inhibitors-as-topical-therapies#" target="_blank"><span style="font-family: arial;">PDF</span></a></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-64889279456828707952024-03-05T09:44:00.000-03:002024-03-05T09:44:20.423-03:00Revised clinical practice guidelines for diagnosing, classifying, and treating allergic bronchopulmonary aspergillosis/mycoses: a Delphi statement from the ISHAM-ABPA working group<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://erj.ersjournals.com/sites/default/files/styles/medium/public/highwire/erj/63/2.cover-source.jpg?itok=wyj2PIf3" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="220" data-original-width="165" height="158" src="https://erj.ersjournals.com/sites/default/files/styles/medium/public/highwire/erj/63/2.cover-source.jpg?itok=wyj2PIf3" width="119" /></a></span></div><span style="font-family: arial;"><br />Agarwal R, Singh Sehgal I, Muthu Vet al. <i><a href="https://erj.ersjournals.com/content/early/2024/02/15/13993003.00061-2024.long" target="_blank">Eur Respir J. 2024 Feb 29:2400061. doi: 10.1183/13993003.00061-2024.</a></i></span><p></p><span style="font-family: arial;"><b>Abstract<br /><br />Background</b> The ISHAM working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) nearly a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics.<br /><br /><b>Methods</b> An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM, fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms “recommend” and “suggest” are used when the consensus was ≥70% and <70%.<br /><b><br /><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjyKj-JdXFHg_ndKZ2eXMGw6AnQRTf9rjwbRWneHFoWDYTaKuSKkFzbmEOk1Xpt7VdRQ9Ec6m0NDj2Fnpb1u0KVxnz1M2zG4LyWdV0SUgfr8xISqtmZIJlivhj51Lw5QZ2pNQnRekcHzvPPMvomxoUCMK10nlqsBephi7LwfxlcFjzex9a35iYWMqmY7Ko/s600/RABPA.png" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="533" data-original-width="600" height="284" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjyKj-JdXFHg_ndKZ2eXMGw6AnQRTf9rjwbRWneHFoWDYTaKuSKkFzbmEOk1Xpt7VdRQ9Ec6m0NDj2Fnpb1u0KVxnz1M2zG4LyWdV0SUgfr8xISqtmZIJlivhj51Lw5QZ2pNQnRekcHzvPPMvomxoUCMK10nlqsBephi7LwfxlcFjzex9a35iYWMqmY7Ko/s320/RABPA.png" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-size: xx-small;">Revised International Society for Human and Animal Mycology (ISHAM)-ABPA
<br />working group (AWG) consensus criteria for diagnosing allergic <br />bronchopulmonary
mycosis (ABPM)</span></td></tr></tbody></table>Results</b> We recommend screening for A. fumigatus sensitization using fungus-specific IgE in all newly diagnosed adult asthmatics at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitization and serum total IgE ≥500 IU·mL−1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia, or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum.<br />We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response.<br /><br /><b>Conclusion </b>We have framed consensus guidelines for diagnosing, classifying, and treating ABPA(M) for patient care and research.</span><div><span style="font-family: arial;"><br /></span></div><div style="text-align: center;"><a href="https://erj.ersjournals.com/content/erj/early/2024/02/15/13993003.00061-2024.full.pdf" target="_blank"><span style="font-family: arial;"><b>PDF</b></span></a></div>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-28032573435288266192024-03-04T12:10:00.005-03:002024-03-04T12:11:44.451-03:00Maternal dietary indexes are not linked to early childhood wheezing or atopic eczema<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://onlinelibrary.wiley.com/cms/asset/d2bf6d3e-4fc0-428f-af52-634216bf32a2/pai.v35.3.cover.jpg" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="778" data-original-width="594" height="134" src="https://onlinelibrary.wiley.com/cms/asset/d2bf6d3e-4fc0-428f-af52-634216bf32a2/pai.v35.3.cover.jpg" width="102" /></a></span></div><span style="font-family: arial;">Sivula E, Puharinen H, Hantunen S, Keski-Nisula L, Backman K. <i><a href="Sivula E, Puharinen H, Hantunen S, Keski-Nisula L, Backman K. Maternal dietary indexes are not linked to early childhood wheezing or atopic eczema. Pediatr Allergy Immunol. 2024; 35:e14099. doi:10.1111/pai.14099" target="_blank">Pediatr Allergy Immunol. 2024; 35:e14099. doi:10.1111/pai.14099</a></i></span><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><b><span style="font-family: arial;">Background</span></b></p><p><span style="font-family: arial;">Several recent studies have investigated the association between maternal diet during pregnancy and wheezing or asthma in children. However, whether a specific dietary pattern during pregnancy protects children from wheezing or atopic diseases remains unclear. This study investigated the association between The Alternative Healthy Eating Index for Pregnancy (AHEI-P), the Dietary Inflammatory Index (DII), and the risk for wheezing and atopic eczema in children during the first year of life.</span></p><p><b><span style="font-family: arial;">Methods</span></b></p><p><span style="font-family: arial;">This study included 1330 mother–child pairs who attended the Kuopio Birth Cohort (KuBiCo) study and had dietary information during the last trimester and information on children's health in the first year of life. <span></span></span></p><a name='more'></a><span style="font-family: arial;">AHEI-P and DII indicate a healthy diet and dietary inflammation potential during pregnancy. The AHEI-P and DII were compared with reported wheezing and doctor-diagnosed atopic eczema in children during the first year of life.</span><p></p><p><b><span style="font-family: arial;">Results</span></b></p><p><span style="font-family: arial;"></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjqeKU9jJqZy_3OJfRtYXde-ZvstHcJW6wTZbU6Kel8xdDeD0XujXs1eqtYsF3zhbcfuU9KL2GodI0Pn0No7xJ7KL3BvQxlZb_0qECTWl0uaHXvWDfyef0NnkuuNCPhgj0UFka5CEtsMHON7WM9RAHjR4WUJPlPwA6JTFX8m-vzposZA6FnzdsVuIkZFe8/s700/diet.png" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="174" data-original-width="700" height="100" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjqeKU9jJqZy_3OJfRtYXde-ZvstHcJW6wTZbU6Kel8xdDeD0XujXs1eqtYsF3zhbcfuU9KL2GodI0Pn0No7xJ7KL3BvQxlZb_0qECTWl0uaHXvWDfyef0NnkuuNCPhgj0UFka5CEtsMHON7WM9RAHjR4WUJPlPwA6JTFX8m-vzposZA6FnzdsVuIkZFe8/w400-h100/diet.png" width="400" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span face=""Open Sans", icomoon, sans-serif" style="background-color: white; text-align: start;"><span style="font-family: arial; font-size: x-small;">Maternal dietary patterns by continuous variables, in relation to <br />the wheezing and atopic eczema in children.</span></span></td></tr></tbody></table><span style="font-family: arial;">Neither AHEI-P nor DII is associated with wheezing or atopic eczema in children when analyzed by continuous variables and by tertiles. The odds ratio (95% CI) for AHEI-P and wheezing was 0.99 (0.98–1.01), for AHEI-P and atopic eczema1.01 (0.99–1.02), for DII and wheezing 1.02 (0.95–1.09), and for DII and atopic eczema 0.97 (0.91–1.04).</span><p></p><p><b><span style="font-family: arial;">Conclusion</span></b></p><p><span style="font-family: arial;">In this cohort study, AHEI-P and DII during pregnancy were not associated with wheezing or atopic eczema in the offspring during the first year of life.</span></p><p style="text-align: center;"><span style="font-family: arial;"><a href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/pai.14099" target="_blank">PDF</a></span></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-22952341925780733022024-03-04T12:04:00.002-03:002024-03-04T12:04:41.364-03:00House dust mite SCIT reduces asthma risk and significantly improves long-term rhinitis and asthma control—A RWE study<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://onlinelibrary.wiley.com/cms/asset/6b7aec81-c288-4c78-a1e3-e4378d6e4b5d/all.v79.3.cover.jpg" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><span style="font-family: arial;"><img border="0" data-original-height="782" data-original-width="595" height="124" src="https://onlinelibrary.wiley.com/cms/asset/6b7aec81-c288-4c78-a1e3-e4378d6e4b5d/all.v79.3.cover.jpg" width="94" /></span></a></div><span style="font-family: arial;">Jutel M, Klimek L, Richter H, Brüggenjürgen B, Vogelberg C. <i><a href="https://onlinelibrary.wiley.com/doi/10.1111/all.16052" target="_blank">Allergy. 2024; 00: 1-10. doi:10.1111/all.16052</a></i></span><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><b><span style="font-family: arial;">Background</span></b></p><p><span style="font-family: arial;">The German Therapy Allergen Ordinance (TAO) triggered an ongoing upheaval in the market for house dust mite (HDM) allergen immunotherapy (AIT) products. Three HDM subcutaneous AIT (SCIT) products hold approval in Germany and therefore will be available after the scheduled completion of the TAO procedure in 2026. In general, data from clinical trials on the long-term effectiveness of HDM AIT are rare. We evaluated real-world data (RWD) in a retrospective, observational cohort study based on a longitudinal claims database including 60% of all German statutory healthcare prescriptions to show the long-term effectiveness of one of these products in daily life. Aim of this analysis was to provide a per product analysis on effectiveness of mite AIT as it is demanded by international guidelines on AIT.</span></p><p><b><span style="font-family: arial;">Methods</span></b></p><p><span style="font-family: arial;">Subjects between 5 and 70 years receiving their first (index) prescription of SCIT with a native HDM product (SCIT group) between 2009 and 2013 were included. The exactly 3:1 matched control group received prescriptions for only symptomatic AR medication (non-AIT group); <span></span></span></p><a name='more'></a><span style="font-family: arial;">the evaluation period for up to 6 years of follow-up ended in February 2017. Study endpoints were the progression of allergic rhinitis (AR) and asthma, asthma occurrence and time to the onset of asthma after at least 2 treatment years.</span><p></p><p><b><span style="font-family: arial;">Results</span></b></p><p><span style="font-family: arial;"></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://onlinelibrary.wiley.com/cms/asset/a1429c3c-72d7-415a-aa49-60814c48d446/all16052-fig-0001-m.jpg" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="845" data-original-width="2048" height="165" src="https://onlinelibrary.wiley.com/cms/asset/a1429c3c-72d7-415a-aa49-60814c48d446/all16052-fig-0001-m.jpg" width="400" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-size: xx-small;">Changes (%) from index to up to 6 years of follow-up in the number <br />of prescriptions for (a) symptomatic treatment of allergic rhinitis/rhinoconjunctivitis<br /> in the SCIT (total population n = 892, children/adolescents n = 284, adults n</span></td></tr></tbody></table><span style="font-family: arial;">In total, 892 subjects (608 adults and 284 children/adolescents) were included in the SCIT group and 2676 subjects (1824 adults and 852 children/adolescents) in the non-AIT group. During the follow-up period after at least 2 years of SCIT, the number of prescriptions in the SCIT group was reduced by 62.8% (p < .0001) for AR medication and by 42.4% for asthma medication (p = .0003). New-onset asthma risk was significantly reduced in the SCIT vs non-AIT group by 27.0% (p = .0212). The asthma-preventive effect of SCIT occurred 15 months after start of the treatment. In the SCIT group, the time to onset of asthma was prolonged compared to the non-AIT group (p = .0010).</span><p></p><p><b><span style="font-family: arial;">Conclusion</span></b></p><p><span style="font-family: arial;">In this first product based RWD analysis on SCIT with a native HDM product, patients aged 5 to 70 years benefited from AIT in the long term in terms of reduced progression of AR and asthma after at least 2 years of treatment. The effects seemed to last for up to 6 years after treatment termination. A significantly reduced risk of asthma onset was observed, starting after 15 months of treatment.</span></p><p style="text-align: center;"><a href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16052" target="_blank"><span style="font-family: arial;">PDF</span></a></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-21290160872592517932024-03-03T08:02:00.002-03:002024-03-03T08:02:16.019-03:00Attenuation of allergen-specific immunotherapy for atopic dermatitis by ectopic colonization of Brevundimonas vesicularis in the intestine.<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://www.cell.com/cms/asset/atypon:cms:attachment:img:d159e6:rev:1709062029349-14946:pii:S2666379123X00032/cover.tif.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="768" data-original-width="591" height="126" src="https://www.cell.com/cms/asset/atypon:cms:attachment:img:d159e6:rev:1709062029349-14946:pii:S2666379123X00032/cover.tif.jpg" width="97" /></a></span></div><span style="font-family: arial;">Liu X, Xu B, Xu X, Wang Z, Luo Y, Gao Y, Ling S, Wang A, Zhou Y, Wang X, Leng SX, Li W, Yao X. <i><a href="https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(23)00557-8" target="_blank">Cell Rep Med. 2023 Dec 19;4(12):101340. doi: 10.1016/j.xcrm.2023.101340.</a></i></span><p></p><p><b><span style="font-family: arial;">Highlights</span></b></p><p><span style="font-family: arial;">• The oral and gut microbiota are changed in patients with AD undergoing AIT</span></p><p><span style="font-family: arial;">• B. vesicularis in the oral and gut microbiota is decreased following AIT</span></p><p><span style="font-family: arial;">• Oral B. vesicularis may ectopically colonizes the gut of patients with AD</span></p><p><span style="font-family: arial;">• B. vesicularis promotes Th17 polarization and attenuates the efficacy of AIT</span></p><p><b><span style="font-family: arial;">Summary</span></b></p><p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://www.cell.com/cms/attachment/6cd3a2c1-f0cc-496a-ba27-8bc0caa26b81/fx1.jpg" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><span style="font-family: arial;"><img border="0" data-original-height="375" data-original-width="375" height="375" src="https://www.cell.com/cms/attachment/6cd3a2c1-f0cc-496a-ba27-8bc0caa26b81/fx1.jpg" width="375" /></span></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-family: arial; font-size: x-small;">Graphical abstract</span></td></tr></tbody></table><span style="font-family: arial;">Allergen-specific immunotherapy (AIT) has shown beneficial effects against atopic dermatitis (AD); however, the mechanisms and parameters underlying the efficacy of AIT remain unclear. Here, we report that the community structure and function of the oral and gut microbiota are changed in patients with AD undergoing AIT. Transplantation of fecal microbiota from patients who respond well to AIT improves AD-like dermatitis in mice. The abundance of Brevundimonas vesicularis in the gut of AD patients has been found to be positively correlated with disease severity and is decreased following AIT. <span></span></span></p><a name='more'></a><span style="font-family: arial;">Furthermore, we find that B. vesicularis from the oral cavity might ectopically colonize the gut of AD patients. In AD model mice, meanwhile, B. vesicularis promotes the skewing of the Treg/Th17 balance toward Th17 polarization and attenuates the efficacy of ovalbumin-specific immunotherapy. Our findings provide potential strategies for the optimization of AIT for AD via the modulation of the gut microbiota.</span><p></p><p style="text-align: center;"><span style="font-family: arial;"><a href="https://www.cell.com/cell-reports-medicine/pdfExtended/S2666-3791(23)00557-8" target="_blank">PDF</a></span></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-78568901942836308232024-03-02T09:25:00.004-03:002024-03-02T09:26:02.934-03:00Short-Term Exposure to Fine Particulate Matter and Nitrogen Dioxide and Mortality in 4 Countries<p><span class="heading-text thm-col h3 cb section-type-keyPoints decorated-hed sb-sc" style="box-sizing: inherit; clear: both; display: inline-block; line-height: 1.3; margin-bottom: 0.5em; margin-top: 0.2em;"><span style="font-family: arial;"></span></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiRAYg6G2NOIwYRxJOAdZ-SW8xhu2zZiEyvGhGKmThK022ZqHrubm9Kbrvrn6PLRGbTM9gEKwSuixvJeUOFaOgroEAZiLJ5eC5m4XVaFu4sGaaT4pl4s6la24GM7s4GuEAI0ynHShlfC7rHNqMoJCX0P16IINWKZRcNTDeQgOQQfJgDhtKHA4-_-sua4rc/s178/JNO.png" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="59" data-original-width="178" height="59" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiRAYg6G2NOIwYRxJOAdZ-SW8xhu2zZiEyvGhGKmThK022ZqHrubm9Kbrvrn6PLRGbTM9gEKwSuixvJeUOFaOgroEAZiLJ5eC5m4XVaFu4sGaaT4pl4s6la24GM7s4GuEAI0ynHShlfC7rHNqMoJCX0P16IINWKZRcNTDeQgOQQfJgDhtKHA4-_-sua4rc/s1600/JNO.png" width="178" /></a></span></div><span style="font-family: arial;">Ma Y, Nobile F, Marb A, Dubrow R, Stafoggia M, Breitner S, Kinney PL, Chen K. <i><a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2815655" target="_blank">JAMA Netw Open. 2024 Mar 4;7(3):e2354607. doi: 10.1001/jamanetworkopen.2023.54607.</a></i> PMID: 38427355.</span><p></p><p><span class="heading-text thm-col h3 cb section-type-keyPoints decorated-hed sb-sc" style="box-sizing: inherit; clear: both; display: inline-block; line-height: 1.3; margin-bottom: 0.5em; margin-top: 0.2em;"><span style="color: #ed0973; font-family: arial;"><span style="font-size: 1.75em;">Key Points</span></span></span></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Question</strong> <span style="box-sizing: inherit;">What are the associations between short-term changes in fine particulate matter (PM<sub style="box-sizing: inherit;">2.5</sub>) and nitrogen dioxide (NO<sub style="box-sizing: inherit;">2</sub>) concentrations and changes in daily all-cause mortality rates?</span></span></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Findings</strong> <span style="box-sizing: inherit;">This cross-sectional study of more than 8.9 million deaths found that a 10-μg/m<sup style="box-sizing: inherit; line-height: 1;">3</sup> increase in daily PM<sub style="box-sizing: inherit;">2.5</sub> concentrations was associated with increases in daily all-cause deaths per 100 000 people of 0.01 in Jiangsu, China, 0.03 in California, 0.10 in central-southern Italy, and 0.04 in Germany; corresponding increases in mortality rates for the same increase in NO<sub style="box-sizing: inherit;">2</sub> concentrations were 0.04, 0.03, 0.10, and 0.05, respectively.<span></span></span></span></p><a name='more'></a><p></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Meaning</strong> <span style="box-sizing: inherit;">The findings of this study add to the growing evidence that increases in short-term exposures to PM<sub style="box-sizing: inherit;">2.5</sub> and NO<sub style="box-sizing: inherit;">2</sub> may be associated with increases in mortality rates.</span></span></p><div class="h3 cb section-type-abstract decorated-hed" style="box-sizing: inherit; clear: both; color: #333333; font-size: 1.75em; line-height: 1.3; margin-bottom: 0.5em; margin-top: 0.2em;"><div class="heading-text thm-col sb-sc" style="box-sizing: inherit; color: #ed0973;"><span style="font-family: arial;">Abstract</span></div></div><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Importance</strong> <span style="box-sizing: inherit;">The association between short-term exposure to air pollution and mortality has been widely documented worldwide; however, few studies have applied causal modeling approaches to account for unmeasured confounders that vary across time and space.</span></span></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Objective</strong> <span style="box-sizing: inherit;">To estimate the association between short-term changes in fine particulate matter (PM<sub style="box-sizing: inherit;">2.5</sub>) and nitrogen dioxide (NO<sub style="box-sizing: inherit;">2</sub>) concentrations and changes in daily all-cause mortality rates using a causal modeling approach.</span></span></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Design, Setting, and Participants</strong> <span style="box-sizing: inherit;">This cross-sectional study used air pollution and mortality data from Jiangsu, China; California; central-southern Italy; and Germany with interactive fixed-effects models to control for both measured and unmeasured spatiotemporal confounders. A total of 8 963 352 deaths in these 4 regions from January 1, 2015, to December 31, 2019, were included in the study. Data were analyzed from June 1, 2021, to October 30, 2023.</span></span></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Exposure</strong> <span style="box-sizing: inherit;">Day-to-day changes in county- or municipality-level mean PM<sub style="box-sizing: inherit;">2.5</sub> and NO<sub style="box-sizing: inherit;">2</sub> concentrations.</span></span></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Main Outcomes and Measures</strong> <span style="box-sizing: inherit;">Day-to-day changes in county- or municipality-level all-cause mortality rates.</span></span></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;"></strong></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://cdn.jamanetwork.com/ama/content_public/journal/jamanetworkopen/939327/m_zoi231600f1_1708540946.67816.png?Expires=1712405768&Signature=tm4crAxEAmctd0OwuwdUIrbAOpFIMWPk5clOGKGAbFu~AL5-2k1nxAvKQVud3lpIu6sEL3pgyM-8gNT2lYizVI9tvSp8pc8iX1~U2A53ZiMCR363vq0Z1Q0meMMlwhu6xNDRJI9s6Gz5Zjetp~O9MPaALseAlZZI21ANoUaqxMEOwIcQi1e3gdhNiSetGZC73S88nmLbLehQiR1x-hstOMVv-OTNf7T25ncPFxUUWQsRp9QVctZwSk4BAjFV9wvR4qPgSMMpcVm1LY3SzbT15tKYbJsCo~-sVSGHGEUOx-vBuVsuCwcb1wpNpDceZOhTS5kD3YTrwNHNMMgTr3pv8w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="587" data-original-width="810" height="232" src="https://cdn.jamanetwork.com/ama/content_public/journal/jamanetworkopen/939327/m_zoi231600f1_1708540946.67816.png?Expires=1712405768&Signature=tm4crAxEAmctd0OwuwdUIrbAOpFIMWPk5clOGKGAbFu~AL5-2k1nxAvKQVud3lpIu6sEL3pgyM-8gNT2lYizVI9tvSp8pc8iX1~U2A53ZiMCR363vq0Z1Q0meMMlwhu6xNDRJI9s6Gz5Zjetp~O9MPaALseAlZZI21ANoUaqxMEOwIcQi1e3gdhNiSetGZC73S88nmLbLehQiR1x-hstOMVv-OTNf7T25ncPFxUUWQsRp9QVctZwSk4BAjFV9wvR4qPgSMMpcVm1LY3SzbT15tKYbJsCo~-sVSGHGEUOx-vBuVsuCwcb1wpNpDceZOhTS5kD3YTrwNHNMMgTr3pv8w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-size: xx-small;"><span style="color: #333333; text-align: start;">Daily Mean Fine Particulate Matter (PM</span><sub style="box-sizing: inherit; color: #333333; text-align: start;">2.5</sub><span style="color: #333333; text-align: start;">) and Nitrogen Dioxide (NO</span><sub style="box-sizing: inherit; color: #333333; text-align: start;">2</sub><span style="color: #333333; text-align: start;">) <br />Concentrations in Each Spatial Unit in All Study Regions</span></span></td></tr></tbody></table><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Results</strong> <span style="box-sizing: inherit;">Among the 8 963 352 deaths in the 4 study regions, a 10-μg/m<sup style="box-sizing: inherit; line-height: 1;">3</sup> increase in daily PM<sub style="box-sizing: inherit;">2.5</sub> concentration was associated with an increase in daily all-cause deaths per 100 000 people of 0.01 (95% CI, 0.001-0.01) in Jiangsu, 0.03 (95% CI, 0.004-0.05) in California, 0.10 (95% CI, 0.07-0.14) in central-southern Italy, and 0.04 (95% CI, 0.02- 0.05) in Germany. The corresponding increases in mortality rates for a 10-μg/m<sup style="box-sizing: inherit; line-height: 1;">3</sup> increase in NO<sub style="box-sizing: inherit;">2</sub> concentration were 0.04 (95% CI, 0.03-0.05) in Jiangsu, 0.03 (95% CI, 0.01-0.04) in California, 0.10 (95% CI, 0.05-0.15) in central-southern Italy, and 0.05 (95% CI, 0.04-0.06) in Germany. Significant effect modifications by age were observed in all regions, by sex in Germany (eg, 0.05 [95% CI, 0.03-0.06] for females in the single-pollutant model of PM<sub style="box-sizing: inherit;">2.5</sub>), and by urbanicity in Jiangsu (0.07 [95% CI, 0.04-0.10] for rural counties in the 2-pollutant model of NO<sub style="box-sizing: inherit;">2</sub>).</span></span><p></p><p><span style="font-family: arial;"><a class="article-section-id-anchor" id="249514911" style="box-sizing: inherit; color: #9e1f63; font-size: 16px; transition: all 0.15s ease-in-out 0s;"></a><span style="color: #333333; font-size: 16px;"></span></span></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word;"><span style="font-family: arial;"><strong style="box-sizing: inherit; color: black;">Conclusions and Relevance</strong> <span style="box-sizing: inherit;">The findings of this cross-sectional study contribute to the growing body of evidence that increases in short-term exposures to PM<sub style="box-sizing: inherit;">2.5</sub> and NO<sub style="box-sizing: inherit;">2</sub> may be associated with increases in all-cause mortality rates. The interactive fixed-effects model, which controls for unmeasured spatial and temporal confounders, including unmeasured time-varying confounders in different spatial units, can be used to estimate associations between changes in short-term exposure to air pollution and changes in health outcomes.</span></span></p><p style="box-sizing: inherit; color: #333333; font-feature-settings: "liga", "dlig"; font-size: 16px; line-height: 1.7; margin: 0px 0px 1.25em; overflow-wrap: break-word; text-align: center;"><b><a href="https://watermark.silverchair.com/ma_2024_oi_231600_1708540946.50325.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAy4wggMqBgkqhkiG9w0BBwagggMbMIIDFwIBADCCAxAGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMrKjUSKTBoQtAvgyrAgEQgIIC4TkoRAsNDhwBnkuL5vgBKpfUhIHi8hXknfwEeGpH3oaRVVdlo-NTPjmvcBeMup5ePkATc64uSCHZqHvx28dg8ajJzdiPmbyO5wetY5Nb3ZySgdp5eio-lfFrMZomglbx5fvhwqD_6HsQ3D1hvghp6HvIt1Exi4wsNePkYuIFDRKI95AFFZCds62XrY9RrR3rMo72kjbTbRV78hGr82GNwJIwPp4lhEEIrLCU5qMzG61SrnelTPCeBhAUPJQmVaZwMGXZMRpSfiGUPVfe1FeONBSZgQZlC7BSkUST_U-hOe4JIxwMiba2UkT9xPmFBxI57Z_2xarjzM_ZZrhTsGh7vLm8cZLXq8mnpkIUEZc3UrJlWfekgpa2IwS68nvKQQ9xVIUWIa5ZA_-_h8qCRAhSacQ5sKq-BByN-D3n3nRwt6joZaWDO9RPBm6EmzsUJX6veJGTBS3bb5s88gA8ntcgmn4gHnyRBIwM7gmE-GerzKhcJOX_jOSSsLvv8Tx19Agy4i76Zw9oAsOF8Y013H3xcoucuaCKjjFvruQSG2WYm1eYss98CnJujblzAWJS7NNCLd_RA2wNk6InKO3iLuYpD2rzhUFmWHmTZd-RKfDx2LGcNd-BeRcVdGk2rudgREe7hFnKcsJU4TlgUIz_IDhRnKIG2Yp7DgLFNvsSZVM8J2-xSHIouHBBJLHAwaZIqatAfofrgHFqa5suaEpYKtkkt9L-t3WUSUZMLvjvmmMe40_uHmuQ5GlVuCnYQjjvtPkrXCf4OnKrwkYlsbD069jgzX6am7don31U1jqAKBuLR77ti2gey27c0kjCNEv2LrllgTNyIqWQbOcHCRLpG4xL59cRatI81oCzG0qzBucozG2j8oIU5-V-uJAm6R3ErigPa5_W8w_QG3rmyj6EgFMTVRSBe_nrO0oaIzTQFPAR01L_YgCfqR8rJSLrlJeSrGY846ujRjrtqDYrRkYbfbpwQ-T6" target="_blank"><span style="font-family: arial;">PDF</span></a></b></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-39046557210265786092024-03-01T17:44:00.002-03:002024-03-01T17:47:12.686-03:00Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in Children With Cow’s Milk Allergy A Randomized Clinical Trial<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://cdn.edhub.ama-assn.org/ama/content_public/multimedia/pmi200002audioa_thumb.jpeg?Expires=1710851470&Signature=S8BiwB46-mhUhJoVgAJGtbhEc1X7Ajx58fQ0FWHVBzQvoIgRsYSiAuh6bhXyqROH0fJv0yNS48U3gsHqq2I7yLGtXy0ItLlLCSJUh-MwN0r07gbX1EtFOa8eRQAr08pCC5A0jqKRIUlBbN6hpwO7UWLJeG6u6mGKUkz8QAWZXj2l8CZt4ZdHQ7FIFTOBJIEXsG4Th1WI5Fa9v4~dRNsEyKC1PADOQrv8Kg5ED~aZrLn809yhh0SDKA-zoxQYOC5O8YOeEIdSqYHys0KreQeKzK2B9~FL6w6ZfTawwojFYRhwep~~vIlEw1Z60qw9mvSudw4TCxFRTwc~zJye-TtmGA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><span style="font-family: arial;"><img border="0" data-original-height="450" data-original-width="450" height="200" src="https://cdn.edhub.ama-assn.org/ama/content_public/multimedia/pmi200002audioa_thumb.jpeg?Expires=1710851470&Signature=S8BiwB46-mhUhJoVgAJGtbhEc1X7Ajx58fQ0FWHVBzQvoIgRsYSiAuh6bhXyqROH0fJv0yNS48U3gsHqq2I7yLGtXy0ItLlLCSJUh-MwN0r07gbX1EtFOa8eRQAr08pCC5A0jqKRIUlBbN6hpwO7UWLJeG6u6mGKUkz8QAWZXj2l8CZt4ZdHQ7FIFTOBJIEXsG4Th1WI5Fa9v4~dRNsEyKC1PADOQrv8Kg5ED~aZrLn809yhh0SDKA-zoxQYOC5O8YOeEIdSqYHys0KreQeKzK2B9~FL6w6ZfTawwojFYRhwep~~vIlEw1Z60qw9mvSudw4TCxFRTwc~zJye-TtmGA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" width="200" /></span></a></div><span style="font-family: arial;">Petroni D, Bégin P, Bird JA, Brown-Whitehorn T, Chong HJ, Fleischer DM, Gagnon R, Jones SM, Leonard S, Makhija MM, Oriel RC, Shreffler WG, Sindher SB, Sussman GL, Yang WH, Bee KJ, Bois T, Campbell DE, Green TD, Rutault K, Sampson HA, Wood RA.<b> </b><i><a href="https://jamanetwork.com/journals/jamapediatrics/fullarticle/2815455" target="_blank">JAMA Pediatr. 2024 Feb 26:e236630. doi: 10.1001/jamapediatrics.2023.6630</a></i></span><div><span style="font-family: arial;"><i><br /></i></span><div><span style="font-family: arial;"><b>Key Points</b></span><p></p><p><span style="font-family: arial;"><b>Question</b> Was a safe and efficacious dose of Viaskin milk identified in this phase 1/2 clinical trial?</span></p><p><span style="font-family: arial;"><b>Findings</b> In this randomized clinical trial, a statistically significant treatment response was observed in children who received 12 months of daily epicutaneous immunotherapy (EPIT) with Viaskin milk at a dose of 300 μg compared with placebo, with no adverse safety signal observed.</span></p><p><span style="font-family: arial;"><b>Meaning </b> With no approved treatment for immunoglobulin E-mediated cow’s milk allergy, EPIT with Viaskin milk may be a viable therapeutic option, with potential to assess Viaskin milk in future clinical trials.</span></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><span style="font-family: arial;"><b>Importance</b> No approved treatment exists for allergen-specific immunoglobulin E (IgE)–mediated cow’s milk allergy (CMA), a common childhood food allergy.</span></p><p><span style="font-family: arial;"><b>Objective</b> To assess dose, efficacy, and safety of epicutaneous immunotherapy with Viaskin milk in children with IgE-mediated CMA.<span></span></span></p><a name='more'></a><p></p><p><span style="font-family: arial;"><b>Design, Setting, and Participants</b> A phase 1/2, 2-part, randomized, double-blind, placebo-controlled dose-ranging clinical trial in children aged 2 to 17 years with IgE-mediated CMA was conducted between November 2014 through December 2017. It took place at 17 trial sites in the US and Canada. Current CMA was confirmed by double-blind, placebo-controlled food challenge at study entry. Part A assessed the short-term safety of 150 μg, 300 μg, or 500 μg of Viaskin milk; part B evaluated the efficacy and safety of the 3 doses vs placebo over 12 months of treatment. Of the 308 screened participants with physician-diagnosed CMA, 198 met eligibility criteria (including an eliciting dose 300 mg or less) and were randomized.</span></p><p><span style="font-family: arial;"><b>Intervention</b> Safety of Viaskin milk (150-μg, 300-μg, or 500-μg doses) was evaluated over a 3-week period (part A). In part B, 180 additional participants were randomized to receive Viaskin milk at doses of 150 μg, 300 μg, or 500 μg or placebo (1:1:1:1) for 12 months.</span></p><p><span style="font-family: arial;"><b>Main Outcomes and Measures</b> The primary outcome was the proportion of treatment responders, defined as a 10-fold or more increase in the cumulative reactive dose of cow’s milk protein (reaching at least 144 mg) or a cumulative reactive dose of cow’s milk protein at 1444 mg or more at the month 12 double-blind, placebo-controlled food challenge.</span></p><p><span style="font-family: arial;"><b></b></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://cdn.jamanetwork.com/ama/content_public/journal/peds/0/m_poi230097f3_1708717685.81461.png?Expires=1712345500&Signature=HqbtPcx~Zds~lJ3BM3mVL45imgQHXvFvoLd153e2Y1UwBeMkG6RhXqui8hyhAcC2sDLVchIsit65l-1wl7E7C6EOW9HiBfK3--bYm~jCodUihlPjffpH6MfWTNKqcpPYuUxNGkyyweK307H9N2ru52mEgilqc9z1LQ3K~Tr5dyeAP1Qd-LgTY4iCzAi942XbWcuozpiVz66KkEZ03hP3zcWOUdWJtLRo2MY4l1hSzAkuXfoyOqpL4JFGHBmM5AgcqUyEhABvv~6rsdgxrZ1I0zj1Yj6CKarHcx6p8GKqwOeRJKEJYUsU8V9JdUywWcTdu6jvDfp~goxccWsiMvjEvA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="812" data-original-width="810" height="320" src="https://cdn.jamanetwork.com/ama/content_public/journal/peds/0/m_poi230097f3_1708717685.81461.png?Expires=1712345500&Signature=HqbtPcx~Zds~lJ3BM3mVL45imgQHXvFvoLd153e2Y1UwBeMkG6RhXqui8hyhAcC2sDLVchIsit65l-1wl7E7C6EOW9HiBfK3--bYm~jCodUihlPjffpH6MfWTNKqcpPYuUxNGkyyweK307H9N2ru52mEgilqc9z1LQ3K~Tr5dyeAP1Qd-LgTY4iCzAi942XbWcuozpiVz66KkEZ03hP3zcWOUdWJtLRo2MY4l1hSzAkuXfoyOqpL4JFGHBmM5AgcqUyEhABvv~6rsdgxrZ1I0zj1Yj6CKarHcx6p8GKqwOeRJKEJYUsU8V9JdUywWcTdu6jvDfp~goxccWsiMvjEvA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" width="319" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="color: #333333; text-align: start;"><span style="font-size: xx-small;">Median Changes From Month 0 to Month 12 of Specific Immunoglobulin E (IgE) <br />and IgG4to Caseins, Alpha-lactalbumin, and Beta-lactoglobulin by Treatment Group</span></span></td></tr></tbody></table><span style="font-family: arial;"><b>Results</b> A total of 95.5% of the randomized participants (mean [SD] age, 8 [4.17] years; 124 of 198 were male [62.6%]) completed treatment. The highest response rate was observed in participants who received Viaskin milk at the 300-μg dose with 24 of 49 responders (49.0%) overall vs 16 of 53 responders (30.2%) in the placebo group (odds ratio, 2.19; 95% CI, 0.91-5.41; P = .09), highest in the 2 to 11 years age group (22 of 38 [57.9%] vs 13 of 40 [32.5%]; P = .04). Most treatment-emergent adverse events were mild or moderate application-site reactions. One participant in the 500-μg Viaskin milk dose group experienced treatment-related anaphylaxis.</span><p></p><p><span style="font-family: arial;"><b>Conclusions and Relevance </b> In this randomized clinical trial, 12 months of daily epicutaneous immunotherapy with a dose of Viaskin milk at 300 μg was associated with a statistically significant treatment response in 2- to 11-year-old children with IgE-mediated CMA. Treatment-related anaphylaxis and treatment-related discontinuation rates were low. Further research is needed to explore Viaskin milk as a viable treatment option for children with IgE-mediated CMA.</span></p><p style="text-align: center;"><span style="font-family: arial;"><b><a href="https://watermark.silverchair.com/jamapediatrics_petroni_2024_oi_230097_1708717685.43462.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAzIwggMuBgkqhkiG9w0BBwagggMfMIIDGwIBADCCAxQGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMY_j7eMZ1ajZdg_K2AgEQgIIC5faFvpdMnYv7uzD7rc_OVIxcQlNND_K_HXDYQxvnmmoivBLa1QNaC5hwhfXf72ZBhlaU_BirLyWm7sVj7OYXScAqC3_a422yDLrfib5BJfql5Gp2mEGnzqjVROpR1VWORyTVD_O4D-ZLAch8G8fIqp_ihw0aSt-Me88ht1WuGmBG-3Ob30FUDhcLGQ0lrZeIQOI8moUUXqy_lvV8vDwaAkKFAJY88Ty1qMqca5g-jlJFxVYE4XR-1uNGS9KBD8IJ7swRzNbSm3nv2FyNtaDkYOKnvbTAK2emm4QslrETqr-Gq_t0MM_bUBCEURzpd-RUfNkDkhaHgzklk8Cu9hyfLVow8QnDri1h4FWx9eZ8S176tyRyefwVMtlVzhaQ4QxRLpkrM-OGtS2pMJad0U07DbsR4lJPPMl7rD50hLFaYvOJGoUyGmPSVJAAbJbQCtSA4AjQrHJAG99tx2Aznfp_CYfkCVWhIEq8HomledDAPrKj7GsseS53FHifRShon_mkwSHGEtXoUF0BrF18yeCznWYxtZItwIK75sA49awOtmNb2XbvIq-i3A4E78Ck1EwkixE4bBgFYcaGQI_Ry_oz1D4vk4dkxMP69HGt4uQgGb4j31o3IT7CWTwdNZGVDS1v8UCWTcwWaKivkHjXjhSo5Nn_vdTxVTvUKTRWpgfzDRSwbrjx8HTGQXHU1u4WdklKOo6kjvai5ockGv0bygGlDEn0rEdu3a6pEbKoP0ozpJx_BQ2kmITuRddIaxjd4uxRgk4JSigevm3SP6y7qkaz4zp217psDQ3FAtMuc7UeqBQl9eXPoH0x7GJbDJva4FrBHSbUxopOwOG0zjkbvZPTHASfm6FgIqXMxrOGqzrcX-czudhVyMfeOqH9kZvwFayZBBggfQUc7PKc-ox4q4LBsAHkXJRMb_LrpWo0csC4W-Fz3D9MPC8546_kHsC1VG6Eq2m_6aZ0NJP5MPJP1NNv6dmUMYpuZg">PDF</a></b></span></p></div></div>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-8555677630084672422024-02-29T09:31:00.004-03:002024-02-29T09:31:56.904-03:00Cost-effectiveness analysis of grass pollen specific immunotherapy in children with allergic rhinitis compared to the standard of care symptomatic treatment in Portugal<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgHa57kpfIU_BhTxTUzkLhqVby1KUevI_L_4ESosTxra64GUAOzuuZgyAnBtu3FaNcWi_W0KAfhqorBhmbnkEjg6ia4hXf55XXfK7fuHs1LXhITWDLWXR07v4HzjbQ9QAc-T7aYwKxu9YYK0ORaZ260DQP9e1EhQFGLKKngdmDlAf7nHh3RwuSXi6V649Y/s1595/volume--5617imhp1.jpg" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="1595" data-original-width="1241" height="107" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgHa57kpfIU_BhTxTUzkLhqVby1KUevI_L_4ESosTxra64GUAOzuuZgyAnBtu3FaNcWi_W0KAfhqorBhmbnkEjg6ia4hXf55XXfK7fuHs1LXhITWDLWXR07v4HzjbQ9QAc-T7aYwKxu9YYK0ORaZ260DQP9e1EhQFGLKKngdmDlAf7nHh3RwuSXi6V649Y/w83-h107/volume--5617imhp1.jpg" width="83" /></a></span></div><span style="font-family: arial;"><span>Farraia M, Paciência I, Castro Mendes F, Cavaleiro Rufo J, Delgado L, Moreira A. </span><i><a href="http://www.eurannallergyimm.com/cont/journals-articles/1251/volume-costeffectiveness-analysis-grass-pollen-specific.asp" target="_blank">Eur Ann Allergy Clin Immunol. 2023;55(5):212-228. doi: 10.23822/EurAnnACI.1764-1489.240.</a></i></span><p></p><p><span style="background-color: white;"><b><span style="font-family: arial;">Summary</span></b></span></p><p><span style="background-color: white;"><span style="font-family: arial;"><b>Background.</b> Cost-effectiveness studies evaluating allergen immunotherapy (AIT) in children are scarce. We aim to compare the cost-effectiveness of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) against standard-of-care (SOC) treatment in children with grass pollen allergic rhinitis. </span></span></p><p><span style="background-color: white;"><span style="font-family: arial;"><b>Methods.</b> We created a Markov model to compare the three strategies over a 10-year horizon. SOC was the reference to calculate the incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analysis were used to assess models' uncertainty. <span></span></span></span></p><a name='more'></a><p></p><p><span style="background-color: white;"><span style="font-family: arial;"><b></b></span></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgzOH6QxC4uAGph3J6Z6v0qagFS8ebUjOmB5iGy9H06uYNQFzL_RkuZnC150foQu9llJ_q4fHTl0xHXMJ_s1Y6lkl8QM8LMLQF6fBQtLd-tLIedUdMu4ENZIburVMZYdYbGEKMjTE1u8xOPRMncm5DVnTC0eap5ByKe0AUN8L8CBMWbH9C45tAbotpRs8Q/s664/IT.png" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><span style="font-family: arial;"><img border="0" data-original-height="369" data-original-width="664" height="178" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgzOH6QxC4uAGph3J6Z6v0qagFS8ebUjOmB5iGy9H06uYNQFzL_RkuZnC150foQu9llJ_q4fHTl0xHXMJ_s1Y6lkl8QM8LMLQF6fBQtLd-tLIedUdMu4ENZIburVMZYdYbGEKMjTE1u8xOPRMncm5DVnTC0eap5ByKe0AUN8L8CBMWbH9C45tAbotpRs8Q/s320/IT.png" width="320" /></span></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-family: arial; font-size: xx-small;">Results of the probabilistic sensitivity analysis graphically represented on a <br />cost-effectiveness plan. </span></td></tr></tbody></table><span style="background-color: white;"><span style="font-family: arial;"><b>Results.</b> We obtained an ICER of €12,605 and € 6,318 for SLIT and SCIT, respectively. In sensitivity analysis, SCIT was more cost-effective than SLIT. </span></span><p></p><p><span style="font-family: arial;"><span style="background-color: white;"><b>Conclusions.</b> AIT is cost-effective in children with grass pollen allergic rhinitis, especially for the subcutaneous route.</span><br style="background-color: #ececec;" /></span></p><p style="text-align: center;"><span style="font-family: arial;"><span style="background-color: white;"><a href="http://www.eurannallergyimm.com/cont/journals-articles/1251/volume-costeffectiveness-analysis-grass-pollen-specific-5471allasp1.pdf" target="_blank"><b>PDF</b></a></span></span></p><p><span style="background-color: white;"><span face="Arial, Helvetica, sans-serif" style="color: #666666; font-size: 14px;"><br /></span></span></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-83835756194706276712024-02-28T16:06:00.004-03:002024-02-28T16:06:58.189-03:00A Perception-Based Survey on Practice Patterns Pertaining to the Diagnosis and Management of Allergic Rhinitis in India<p><span style="font-family: arial;"></span></p><div class="separator" style="clear: both; text-align: center;"><span style="font-family: arial;"><a href="https://d13i5xhouzkrd.cloudfront.net/assets/publisher-colored-logos/logo-innovative-cureus.png" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="160" data-original-width="160" height="105" src="https://d13i5xhouzkrd.cloudfront.net/assets/publisher-colored-logos/logo-innovative-cureus.png" width="105" /></a></span></div><span style="font-family: arial;">Gupte V, Thakur G, Upadhyaya A, et al. (February 27, 2024) <a href="https://www.cureus.com/articles/218950-a-perception-based-survey-on-practice-patterns-pertaining-to-the-diagnosis-and-management-of-allergic-rhinitis-in-india#!/" target="_blank"><i>Cureus 16(2): e55032. doi:10.7759/cureus.55032</i></a></span><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><span style="font-family: arial;"><b>Introduction: </b>Allergic rhinitis (AR) is increasingly prevalent in India, affecting a significant portion of the population and adversely impacting their quality of life. This nationwide survey aimed to explore the perceptions and clinical preferences of Indian physicians regarding the perceived prevalence, common symptoms, and various available treatments for AR.</span></p><p><span style="font-family: arial;"><b>Methods:</b> This cross-sectional, observational, digital questionnaire-based survey was conducted from September 2022 to March 2023, involving physicians sharing insights on prevalence rates, diagnostic approaches, medication preferences, and immunotherapy practices in AR management.</span></p><p><span style="font-family: arial;"><b></b></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://assets.cureus.com/uploads/figure/file/861847/article_river_d638ee509fe011ee9a46355e33ee4b1e-Figure-1.png" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="521" data-original-width="800" height="208" src="https://assets.cureus.com/uploads/figure/file/861847/article_river_d638ee509fe011ee9a46355e33ee4b1e-Figure-1.png" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-size: xx-small;"><span style="background-color: white; color: #222222; text-align: start;">Recommended duration of therapy with different molecule</span><span style="background-color: white; color: #222222; text-align: start;">s</span></span></td></tr></tbody></table><span style="font-family: arial;"><b>Results:</b> A total of 1608 physicians participated in this survey. The majority of physicians (n=684, 42.5%) reported that the prevalence of AR in routine clinical practice is between 21 and 40%. Physicians also noted a substantial burden of AR with asthma (n=626, around 40%). Total IgE count was reported as a mandatory test for the diagnosis of AR by 47.5% of physicians (n=764). For the management of mild cases of seasonal or perennial AR, 980 (60.9%) physicians preferred fexofenadine as an oral antihistamine of choice. Fluticasone furoate was the preferred intranasal corticosteroid (INCS) option (67.1% of physicians (n=1079)), for the management of patients with moderate to severe AR, the most recommended duration of INCS therapy was two to four months (40.9% of physicians). <span></span></span><p></p><a name='more'></a><span style="font-family: arial;">Doctors recommended a montelukast and antihistamine combination in mild AR (n=152, 9.5%), mild AR not responding to antihistamine alone (n=291, 18.1%), moderate to severe AR along with INCS (n=252, 15.7%), and AR with mild asthma (n=74, 4.6%). The majority of physicians (n=1512, 75.6%) preferred using fexofenadine in combination with montelukast for the management of AR. The majority of physicians (n=839, 52.2%) opined that the efficacy rate of oral montelukast-fexofenadine was 60-90% in the management of mild-moderate AR. Around 55.3% of physicians (n=889) had not used immunotherapy in their clinical practice.</span><p></p><p><span style="font-family: arial;"><b>Conclusion: </b>These observations offer a holistic view of how Indian physicians perceive the management of AR, a condition highly prevalent in India and often associated with asthma. It also highlights the treatment strategies employed in their day-to-day clinical practice.</span></p><p style="text-align: center;"><a href="https://www.cureus.com/articles/218950-a-perception-based-survey-on-practice-patterns-pertaining-to-the-diagnosis-and-management-of-allergic-rhinitis-in-india#" target="_blank"><span style="font-family: arial;">PDF</span></a></p><p><br /></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-58474705034975141762024-02-25T10:04:00.008-03:002024-02-25T10:04:54.121-03:00United States expert panel consensus on uniform nomenclature and diagnosis for neuropathic pruritus<span style="font-family: arial;"><div class="separator" style="clear: both; text-align: center;"><a href="https://images.journals.lww.com/itch/SmallThumb.01893704-202310010-00000.CV.jpeg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" data-original-height="131" data-original-width="98" height="131" src="https://images.journals.lww.com/itch/SmallThumb.01893704-202310010-00000.CV.jpeg" width="98" /></a></div><span style="font-size: x-small;">Kwatra, Shawn G. MDa; Elmariah, Sarina MD, PhD, MPHb; Chisolm, Sarah MDc; Mollanazar, Nicholas MDd; Fassett, Marlys MD, PhDe; Cole, Emily F. MDc; Chen, Suephy MDf; Lerner, Ethan MD, PhDb; Berger, Timothy MDe; Yosipovitch, Gil MDg. <i><a href="https://journals.lww.com/itch/fulltext/2024/01010/united_states_expert_panel_consensus_on_uniform.1.aspx" target="_blank">Itch 9(1):e0073, January-March 2024. | DOI: 10.1097/itx.0000000000000073</a></i></span></span><div><span style="font-family: arial;"><br /></span></div><div><div><b><span style="font-family: arial;">Abstract</span></b></div><div><b><span style="font-family: arial;"><br /></span></b></div><div><b><span style="font-family: arial;">Importance: </span></b></div><div><span style="font-family: arial;">Neuropathic pruritus is a debilitating condition lacking a uniform approach to nomenclature and diagnosis.</span></div><div><span style="font-family: arial;"><br /></span></div><div><b><span style="font-family: arial;">Objective: </span></b></div><div><span style="font-family: arial;">A panel of dermatologist experts in pruritus was convened to develop definitions, diagnostic recommendations, and treatment guidelines for neuropathic pruritus.</span></div><div><span style="font-family: arial;"><br /></span></div><div><b><span style="font-family: arial;">Evidence review: </span></b></div><div><span style="font-family: arial;">A roundtable discussion of 10 experts was conducted on November 3, 2021, via the Zoom platform. This study follows the Standards for Reporting Qualitative Research reporting guidelines for qualitative studies. A systematic review of prior literature on the definition, scope, diagnostic, and treatment was performed, looking at sources of treatment from 1991 to 2021. Consensus was defined as >70% agreement for acceptance of a definition or recommendation. A draft of evidence was subjected to revision by all participants and was endorsed by all participants.<span><a name='more'></a></span></span></div><div><span style="font-family: arial;"><br /></span></div><div><b><span style="font-family: arial;">Findings: </span></b></div><div><span style="font-family: arial;"><table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left; margin-right: 1em; text-align: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgsvAfUH9AGg36sAazgB9LY0JhY5Eaigv-Pgl8tZv6aPalWl-rkT7Mo_n5bL_Fb_vL7T9YCFl2f8OfOqGEx-3g6c1uWNsaXNBBsgEXFC9xYfiRu25AQnjGXwkRy4821wcn9_9_eu5A2z1UAZM6hiA2we1urbhyUhnZwllQN42TH-5oMoprnkkRr0cbBDVc/s721/DWNP.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" data-original-height="290" data-original-width="721" height="129" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgsvAfUH9AGg36sAazgB9LY0JhY5Eaigv-Pgl8tZv6aPalWl-rkT7Mo_n5bL_Fb_vL7T9YCFl2f8OfOqGEx-3g6c1uWNsaXNBBsgEXFC9xYfiRu25AQnjGXwkRy4821wcn9_9_eu5A2z1UAZM6hiA2we1urbhyUhnZwllQN42TH-5oMoprnkkRr0cbBDVc/s320/DWNP.png" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span style="font-size: x-small;">Diagnostic workup of neuropathic pruritus.</span></td></tr></tbody></table>The roundtable identified definitions for neuropathic pruritus, which included different forms of the condition based on cause and presentation such as brachioradial pruritus, notalgia paresthetica, and scalp pruritus. Diagnostic and treatment guidelines were also established. Limitations of this process included lack of randomized controlled studies. These recommendations are also based on expert consensus and must be further supported by evidence-based outcomes research.</span></div><div><span style="font-family: arial;"><br /></span></div><div><b><span style="font-family: arial;">Conclusions: </span></b></div><div><span style="font-family: arial;">Neuropathic pruritus contains numerous subtypes, causes, diagnostic methods, and treatment modalities. The recommendations developed by this panel are meant to serve as shared nomenclature for future clinical studies.</span></div></div><div><span style="font-family: arial;"><br /></span></div><div style="text-align: center;"><b><a href="https://journals.lww.com/itch/_layouts/15/oaks.journals/downloadpdf.aspx?trckng_src_pg=ArticleViewer&an=01893704-202401010-00001" target="_blank"><span style="font-family: arial;">PDF</span></a></b></div><div style="text-align: center;"><br /></div>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0tag:blogger.com,1999:blog-2455692912615822431.post-91138601854179949912024-02-25T09:46:00.009-03:002024-02-25T09:48:04.821-03:00Risk prediction model construction for asthma after allergic rhinitis by blood immune T effector cells.<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://images.journals.lww.com/md-journal/XLargeThumb.00005792-202402230-00000.CV.jpeg" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><span style="font-family: arial;"><img border="0" data-original-height="222" data-original-width="160" height="121" src="https://images.journals.lww.com/md-journal/XLargeThumb.00005792-202402230-00000.CV.jpeg" width="87" /></span></a></div><span style="font-family: arial;">Wang J, Jiang T, Hu J-D. <a href="https://journals.lww.com/md-journal/fulltext/2024/02230/risk_prediction_model_construction_for_asthma.57.aspx" target="_blank"><i>Medicine 2024;103:8(e37287)</i></a>.</span><p></p><p><b><span style="font-family: arial;">Abstract</span></b></p><p><b><span style="font-family: arial;">Background: </span></b></p><p><span style="font-family: arial;">Allergic rhinitis (AR) and asthma (AS) are prevalent and frequently co-occurring respiratory diseases, with mutual influence on each other. They share similar etiology, pathogenesis, and pathological changes. Due to the anatomical continuity between the upper and lower respiratory tracts, allergic inflammation in the nasal cavity can readily propagate downwards, leading to bronchial inflammation and asthma. AR serves as a significant risk factor for AS by potentially inducing airway hyperresponsiveness in patients. Currently, there is a lack of reliable predictors for the progression from AR to AS.</span></p><p><b><span style="font-family: arial;">Methods: </span></b></p><p><span style="font-family: arial;">In this exhaustive investigation, we reexamined peripheral blood single cell RNA sequencing datasets from patients with AS following AR and healthy individuals. <span></span></span></p><a name='more'></a><span style="font-family: arial;">In addition, we used the bulk RNA sequencing dataset as a validation lineup, which included AS, AR, and healthy controls. Using marker genes of related cell subtype, signatures predicting the progression of AR to AS were generated.</span><p></p><p><b><span style="font-family: arial;">Results: </span></b></p><p><span style="font-family: arial;"></span></p><table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left;"><tbody><tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjg0XtdPdpqBGdXx1qL3Tq09FKKlxWcI7mHtwJc6VxFAfyEdTllGnfMZ04Pn5ga1vD1sL0QfiPC2ED5O7KsVCHDb_d40vOXzpGf0AE9thuHwKjbo9Tv5tFC_kHRl0lj7mLtWPja-O11LPpoiAmd7oGn91UZiRzTwPTA0lySBzXm0FagUL0A0sbPyB5YflU/s2400/Original.00005792-202402230-00057.F3.jpeg" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" data-original-height="1569" data-original-width="2400" height="209" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjg0XtdPdpqBGdXx1qL3Tq09FKKlxWcI7mHtwJc6VxFAfyEdTllGnfMZ04Pn5ga1vD1sL0QfiPC2ED5O7KsVCHDb_d40vOXzpGf0AE9thuHwKjbo9Tv5tFC_kHRl0lj7mLtWPja-O11LPpoiAmd7oGn91UZiRzTwPTA0lySBzXm0FagUL0A0sbPyB5YflU/s320/Original.00005792-202402230-00057.F3.jpeg" width="320" /></a></td></tr><tr><td class="tr-caption" style="text-align: center;"><span face=""Fira Sans", Arial, "Helvetica Neue", Helvetica, sans-serif" style="background-color: white; color: #353535; font-size: 13px; text-align: left;">Examination of Teff cells in the AS dataset</span></td></tr></tbody></table><span style="font-family: arial;">We identified a subtype of immune-activating effector T cells that can distinguish patients with AS after AR. By combining specific marker genes of effector T cell subtype, we established prediction models of 16 markers. The model holds great promise for assessing AS risk in individuals with AR, providing innovative avenues for clinical diagnosis and treatment strategies.</span><p></p><p><b><span style="font-family: arial;">Conclusion: </span></b></p><p><span style="font-family: arial;">Subcluster T effector cells may play a key role in post-AR AS. Notably, ACTR3 and HSPA8 genes were significantly upregulated in the blood of AS patients compared to healthy patients.</span></p><p style="text-align: center;"><span style="font-family: arial;"><b><a href="https://journals.lww.com/md-journal/_layouts/15/oaks.journals/downloadpdf.aspx?trckng_src_pg=ArticleViewer&an=00005792-202402230-00057" target="_blank">PDF</a></b></span></p>ivancev@gmail.comhttp://www.blogger.com/profile/17253138794829455807noreply@blogger.com0