PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

COVID-19 OUTCOME IN AN ITALIAN RHEUMATOID ARTHRITIS COHORT

BackgroundIt is known that rheumatologic patients often present a course of COVID-19 similar to that of the general population. Some factors are linked to a worse COVID-19 outcome, such as moderate glucocorticoid (GC) dose, high body mass index (BMI), and comorbidities.ObjectivesTo describe the outcome of COVID-19 in patients with rheumatoid arthritis (RA) in terms of symptoms, therapy and need for hospitalization compared to a control group. Also, to evaluate the variation in disease activity before and after COVID-19.MethodsIn this monocentric prospective study, we recruited consecutive adult patients with RA classified according to ACR-EULAR 2010 criteria who received a diagnosis of COVID-19 through molecular or rapid antigen swab tests between September 2020 and December 2022. Demographic and clinical data, including age, BMI, smoking habit, comorbidities, treatment at the diagnosis of COVID-19, duration of COVID-19, symptoms related to the infection and therapy required, together with the vaccination status were collected through a self-administered questionnaire. We compared DAS28-CRP before the infection and at the first visit after the resolution. As controls (Cs), individuals with COVID-19 but with no referred diagnosis of rheumatic/autoimmune disease were recruited.ResultsWe enrolled 111 patients affected by RA (males 15%, median age 56 years, IQR 25) and 89 Cs (males 44%, median age 47 years, IQR 43), whose demographic and clinical characteristics are reported in Table 1. The median RA disease duration was 108 months (IQR 201). At the COVID-19 diagnosis, 62 patients (56%) were assuming csDMARDs, 67 (60%) bDMARDs, and 18 (16%) GC with a median prednisone equivalent dose of 4 mg/day (IQR 1). DAS28-CRP was available for 62 patients, with a median value of 1.67 (IQR 2.71);42 patients (60%) were in remission (Figure 1). Before developing COVID-19, only 35 (32%) RA patients and 42 (47%) Cs had completed the vaccinal cycle, which was performed by mRNA vaccine in all the patients and 87% of Cs. The median COVID-19 duration was 18 days (IQR 18) for RA patients and 14 days (IQR 13.5) for Cs (p>0.7). Cs reported a significantly higher frequency of constitutional symptoms (headache and asthenia) compared to RA patients (p<0.00001). When hospitalization was required, RA patients received heparin more frequently than Cs (p<0.039). Once COVID-19 was resolved, RA patients were evaluated after a median of 2 months (IQR 2). DAS28-CRP was available for 68 patients, with a median value of 1.61 (IQR 1.77);42 patients (68%) were in remission (Figure 1).No differences in terms of COVID-19 duration, clinical manifestations, and therapy emerged comparing RA patients in remission (40;58%) with patients with the active disease before COVID-19 (29;42%). Also, in vaccinated subjects, the outcome of COVID-19 was similar in RA patients and Cs, irrespective of RA activity.ConclusionCOVID-19's impact on patients with RA was not significantly different from the general population, even for patients with active RA. Patients did not suffer from reactivation of RA because of COVID-19. In our opinion, these positive results could be ascribed to the massive vaccination campaign.References[1]Conway R et al, Ir J Med Sci. 2023[2]Andersen KM et al, Lancet Rheumatol. 2022Table 1.Clinical characteristics, COVID-19 symptoms, and therapy of the two groups. Values in brackets are expressed as percentages unless specified. Musculoskeletal diseases: osteoarthritis and osteoporosis.Rheumatoid arthritis N=111Controls N=89P value*ACTIVE SMOKERS13 (12)20 (22)BMI (IQR)24 (7)23(6)COMORBIDITIES64 (58)44 (49)Cardiovascular26 (23)18 (20)Endocrine24 (22)14 (16)Musculoskeletal11 (10)6 (7)Neoplastic12 (11)3 (3)CLINICAL MANIFESTATIONS96 (86)74 (83)Fever50 (45)47 (53)Constitutional symptoms52 (47)75 (84)p <0.00001Respiratory symptoms100 (90)86 (97)Gastrointestinal symptoms12 (11)13 (15)THERAPY88 (79)74 (67)NSAIDs41 (37)31 (35)Glucocorticoids24 (22)21 (30)Antibiotics33 (30)27 (24)Oxygen6 (5)5 (6)Heparin8 (7)0 (0)p <0.039HOSPITALIZATION10 (9)6 (9)*Where not indi ated, p value >0.5Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Non-steroidal anti-inflammatory drugs amid COVID-19 pandemic: An ally or an enemy?

As the current global pandemic of the novel coronavirus diseases 2019 (COVID-19) continues to rage, the scientific and medical worlds are working to establish an effective therapy against the illness. Recently questions regarding non-steroidal anti-inflammatory drugs (NSAIDs) as a potential therapeutic option for COVID-19 have surfaced. While some studies hint towards the possible benefit of NSAIDs against SARS-CoV-2 infection, the current body of evidence also sheds light on the potential risk of using NSAIDs in COVID-19 patients. Thus, the available literature does not provide conclusive evidence for or against the use of NSAIDs for treating COVID-19 patients. Given the limited data available, we suggest cautionary approaches for the public to avoid possible harm until further evidence emerges. NSAIDs should not be used as the first-line agents for COVID-19 unlessunder medical supervision. Moreover, patients with chronic inflammatory conditions should continue the NSAIDs as per their regular prescriptions.

FREQUENCY OF VACCINE-RELATED ADVERSE EVENTS IN PATIENTS WITH RHEUMATIC DISEASE

BackgroundPatients with rheumatic diseases are at greater risk of developing serious infections due to dysregulation of the immune system and the use of immunosuppressants1. Therefore, preventing infection is crucial, with vaccination being the most important primary prevention intervention, leading to a lower rate of hospital admissions due to infections. However, vaccine hesitancy among persons with rheumatic diseases is widespread due to concerns regarding the safety of vaccines2.ObjectivesDescribe the frequency of adverse events associated with vaccination in patients with rheumatic diseases.MethodsObservational, descriptive, cross-sectional and retrospective study was carried out in patients with rheumatic diseases from the Rheumatology Department of the Hospital Regional 1° de Octubre ISSSTE, from February to May 2022;it included patients over 18 years of age with an established diagnosis of rheumatic disease who had received a vaccine;the researcher applied the vaccine-associated adverse events survey to those patients who agreed to participate by signing the informed consent. The sample size was of 95 patients. Descriptive statistics and summary measures were employed for analysis. We used the chi-square test or Fisher's exact test (when <5) for the comparative analysis of the frequencies of nominal qualitative variables. P<0.05 was considered significant.ResultsThe survey was applied to 115 patients. 85.2% were women;mean age 57.9 years;61.7% had rheumatoid arthritis (RA), followed by systemic lupus erythematosus (SLE) in 13.9%. 55.6% of the patients were treated with steroids, 52.2% received bDMARDs and 48.7% csDMARDs. Patients received various vaccines, of which the most frequent was the one for COVID-19, with 99.1% of included patients having received at least one dose, followed by influenza in 30.4%. 78% of the patients who received at least one dose of a vaccine against COVID-19 presented ≥1 adverse events. The disease in which the highest frequency of adverse events occurred was RA, without this difference being statistically significant (Table 1). The adverse events according to the type of COVID-19 vaccine were the following: Sputnik-V 80%, Pfizer 76.6% and AstraZeneca 76.1%, without statistically significant difference between vaccine types. The most frequently occurring adverse events were injection site pain (80.1%), headache (30.7%), and fatigue (30.7%);In addition, the main vaccine-associated musculoskeletal symptoms were joint pain, myalgia, and morning joint stiffness (Figure 1), which on most cases improved after a NSAID use. Joint pain was more frequent after the second dose of certain vaccine types.Table 1.Frequency of AE after COVID-19 vaccination in patients according to disease.AE (%)pRA560.790SLE140.326Spondyloarthritis40.068Osteoarthritis60.614ConclusionVaccination-associated AE occurred more frequently than reported in international studies;however, they were not more serious. Providing this information to patients is important to improve vaccine acceptance. In addition, the administration of NSAID after the application of the vaccine could be proposed to reduce the presence of side effects.References[1]Rotondo, Cinzia, et. al. Preliminary Data on Post Market Safety Profiles of COVID 19 Vaccines in Rheumatic Diseases: Assessments on Various Vaccines in Use, Different Rheumatic Disease Subtypes, and Immunosuppressive Therapies: A Two-Centers Study. Vaccines, 2021;9(7):730-440.[2]Furer, Victoria, et. al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2020;79:39–52.AcknowledgementsTo the residents and staff at HR 1 Octubre for their help in compilating data.Disclosure of InterestsDaniel Xavier Xibille Friedmann Speakers bureau: GSK, Lilly, UCB, Paid instructor for: GSK, Lilly, UCB, Consultant of: GSK, Lilly, UCB, Vanessa Balderas Reyes: None declared, María Olvera: None declared, María Alcocer León: None declared, ALFREDO ALEXANDRI REYES SALINAS Paid instructor for: Abbvie, Janssen, ovartis, Minerva Rodríguez Falcón: None declared, Sandra Miriam Carrillo Vazquez Speakers bureau: Abbvie, Janssen, UCB, Paid instructor for: Abbvie, Janssen, UCB, Consultant of: Abbvie, Janssen, UCB.

PERICARDITIS AFTER COVID-19 VACCINATION: A CASE SERIES

BackgroundCOVID-19 vaccination campaigns successfully impacted on viral spreading and in particular on clinical course of the disease. However, secondary to a highly extended vaccination program, several local and systemic adverse events associated with mRNA COVID-19 vaccines have been reported. Pericarditis and myocarditis are examples of cardiac complications related to these vaccines. In particular, cases of pericarditis have occurred after mRNA COVID-19 vaccination (mostly secondary to vaccination with Moderna than Pfizer-BioNTech), especially in male adolescents and young adults, more often after the second dose. The incidence is approximately of 1-2 cases/100.000.ObjectivesAim of our study was to study the clinical profile of pericarditis occurred within 30 days after COVID-19 vaccines in our clinic.MethodsWe present a case series of patients who developed pericarditis after COVID-19 vaccination in the Department of Internal Medicine at Fatebenefratelli Hospital in Milan, followed from December 1, 2021 to April 15, 2022.ResultsTwenty-five individuals, of which 18 (72%) were women and 7 (28%) were males, had vaccine related pericarditis. Two patients were vaccinated with AstraZeneca, 2 with Moderna, the remaining with Pfizer-BioNTech. Median age was of 42 years. Of all patients, one subject was affected by constrictive effusive pericarditis, while another required treatment of pericarditis with Anakinra, switched to Canakinumab after severe skin reactions, because of failure of therapeutic response to first-line treatments.Two patients required hospital admission, in one case for a transient constrictive pericarditis. In the remaining cases clinical symptoms associated with post-vaccines pericarditis were mild and didn't require hospitalization.Chest pain was reported in 100% of cases, whereas pericardial effusion (in one case larger than 10 mm) was evidenced in 30% of subjects. Eighty percent of patients experienced tachycardia, whereas 90% reported asthenia.An increase in indices of inflammation (CRP) was documented in 50% of patients, usually mild.With regard to therapy, 90% of patients were treated with NSAIDs, 95% with colchicine, while 50% of cases required treatment with low-dose steroids.ConclusionCOVID-19 vaccination induces a particular form of pericarditis, often insidious and very troublesome, but with good prognosis. The clinical phenotype showed less typical chest pain, often normal indices of inflammation and little or no instrumental changes, but patients often experimented tachycardia and functional limitation. With regard to therapy, we used NSAIDs at adequate dosages to control the clinical condition, or low-dose colchicine. Low doses of cortisone (e.g., prednisone 5-10 mg a day) were useful in the presence of marked asthenia or systemic symptoms. Beta-blockers or ivabradine were used in the presence of tachycardia.References[1]Barda N, Children 2021, 8(7), 607;Safety of the BNT162b2 mRNA Covid-19 in a Nationwide setting. N Engl J med 2021;385:1078-1090.[2]Diaz GA, Myocarditis and Pericarditis After Vaccination for COVID-19. JAMA 2021;326 (12): 1210-1212.[3]Bibhuti D, Myocarditis and Pericarditis Following mRNA COVID-19 Vaccination: What Do We Know So Far?. Children 2021, 8(7), 607.[4]Giacomo Maria Viani, Patrizia Pedrotti, Romano Seregni, and Brucato Antonio;Effusive–constrictive pericarditis after the second dose of BNT162b2 vaccine (Comirnaty): a case report;European Heart Journal - Case Reports (2022) 6(2), 1–6.[5]Francesco Perna, Elena Verecchia, Gaetano Pinnacchio, Laura Gerardino, Antonio Brucato, and Raffaele Manna;Rapid resolution of severe pericardial effusion using anakinra in a patient with COVID-19 vaccine-related acute pericarditis relapse:a case report;European Heart Journal - Case Reports (2022) 6, 1–6.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

STUDY OF ADVERSE REACTIONS TO COVID-19 VACCINATION IN PATIENTS WITH RHEUMATIC DISEASES

BackgroundVaccination has been recommended in the midst of the COVID-19 pandemic, but some patients are not vaccinated due to concerns about adverse reactions.ObjectivesThe purpose of this study is to investigate the adverse reactions in rheumatic diseases and to guide the decision-making of patients and physicians.MethodsA questionnaire was sent to patients with rheumatic diseases, and patients who could be counted as of September 2021, when they consented to this study, were surveyed.ResultsThe subjects were 123 (male:female=10:113), 84 with rheumatoid arthritis and 39 with other immune diseases. The therapeutic agents used were PSL 31(25.2%), MTX 65(52.8%), NSAID/COX inhibitors 28(22.8%), bDMARDs 42(34.1%). adverse reactions after the first and second vaccination were fever 17(13.8%)/50(40.7%), joint symptoms 7(5.7%)/22(17.9%), local injection reactions (pain/irritation) 22(17.9%), local injection reactions (pain/erythema) 93(75.6)/98(79.7), systemic skin symptoms 0(0%)/2(1.6%), other symptoms (malaise, myalgia, etc.) 59(48.0%)/85(69.1%), and treatment intensification 5(4.1%)/12(9.7%). These responses differed in occurrence only for fever with and without PSL medication (22.5%: 47.3% (p=0.02)).The odds ratio for disease worsening after the first dose of vaccine and again after the second dose was 33.5 (p<0.01).ConclusionNo specific adverse reactions other than the commonly known ones were observed, but some patients experienced worsening of symptoms after vaccination, requiring intensified treatment. Based on the results of this study, we believe that adverse reactions to vaccination are acceptable. We plan to accumulate more cases and analyze them in the future.The exacerbation of disease after the first vaccination would predict the exacerbation after the second vaccination.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Repurposing Anti-inflammatory Agents in the Potential Treatment of SARS-COV-2 Infection

SARS-Cov-2 is the novel coronavirus with predominantly inflammatory pathogenesis. The inflammation can be initiated and finally aggravated through a number of interconnected inflammatory pathways such as NF-κB, JAK-STAT, MAPK TLRs, iNOS, COX, etc. In the current chapter, these signaling pathways which instigate inflammation in SARS-Cov-2 are discussed. Moreover, drugs inhibiting these pathways in other inflammatory conditions or diseases are either in clinical use as COVID-19 therapy, or have been proposed as potential future therapeutic interventions in this chapter. These repurposing strategies can halt the COVID-19 symptoms as well as disease progression. This was demonstrated by establishing a link between the regulatory actions of these molecules or drugs in the inflammatory pathway like cytokine release against the COVID-19-related inflammatory havoc. Hence, the chapter will provide profound insights in the inflammatory control pertaining to COVID-19 severity and complications. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

NSAID-induced gastropathies associated with the treatment of SARS-CoV-2 infection: how to improve therapy safety? Focus on esomeprazole

Objective — Using mFSSG questionnaire, to define the presences of gastrointestinal disturbances, associated with the intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with moderate course of SARS-CoV-2 infection and to investigate ability of esomeprazole (Ezonexa, Farmak) to preventing the development of dyspeptic and reflux symptoms in these patients. Materials and methods. All patients with the established diagnosis of coronaviral disease (n = 85), hospitalized for treatment in the Centre of Therapy of Clinical Emergency Hospital in Lviv, who signed the informed consent, became the participants of an open controlled trial of Ezonexa efficacy at this pathology. The medication was administered in a dose of 20 mg/day in the morning, 30 mins before meals, used to prevent NSAID-induces gas-tropathies for 28 days. Simple blinded method was used to randomize patients into two groups. Subjects of the first group (n = 45) took esomeprazole, second group included controls (n = 40) without active prophylaxis of NSAID-induces gastropathies. The mean patients' age was 69.4 ± 2.6 years. The men age of male subjects was 66.4 ± 2.4 years, of females 72.3 ± 2.7 years. The follow up period lasted 4 weeks. All patients underwent standard examinations and survey to assess the dynamics of clinical manifestations of the disease against the background of the treatment of coronaviral infection. Besides, patients used mFSSG questionnaire to evaluate the intensity of dyspeptic and reflux symptoms. Examinations and survey were performed on the 1st, 10 — 14th and 28th days of follow up. The quality of life indices were assessed with the use of SF-36 questionnaire in all patients at baseline and 4 weeks after the study start. Results. No significant difference in mFSSG scores was reveled in the patients of both groups on the 1st day in terms of clinical manifestations of dyspepsia and reflux. At the second testing on 10 — 14th days, the assessment of dyspeptic and reflux symptoms didn't change in patients of the 1st group, whereas in 49.6 % subjects of the control group presence of the signs of NSAID-induced gastropathy with a pronounced dyspeptic and moderate reflux syndrome was registered. At 28th day, symptoms of both dyspepsia and reflux developed in 11.3 % of patients in the first group, and 78.6 % in the second group. No differences in age and gender ratio were reveled after comparative analysis. However, comorbid pathology, for which patients constantly took low doses of ace-tylsalicylic acid, was an additional aggravating risk factor of the development of NSAID-induced gastropathy. Analysis of the baseline indices of quality of life in both groups showed the significant (р < 0.05) decrease in the majority of scores, except for the scales of physical functions and pain. Positive dynamics against the background of esomeprazole treatment was defined in all indices of the quality of life, in the most extent in the scores of pain, vitality, social and role emotional functions. Conclusions. Esomeprazole in a dose of 20 mg demonstrated excellent protective effects in regard to the gastrointestinal mucosa in elderly patients from the high-risk group, who are particularly sensitive to the gastroduo-denal NSAID-induced toxicity even at short therapeutic course for coronaviral infection. Ezonexa may be considered as a drug of choice to treat NSAID-induced gastropathy;due to its prolonged and stable acid-inhibiting ability, Ezonexa promotes prompt symptoms' relief. Owing to the phenomenon of stereoselectivity, the drug has pharmacokinetic properties that ensure its high clinical efficacy in acid-dependent diseases. © 2021, Publishing Company VIT-A-POL. All rights reserved.

MULTIFOCAL OSTEONECROSIS AS A CONSEQUENCE OF A NEW CORONAVIRUS INFECTION.

The impact of the transferred coronavirus infection on the musculoskeletal system still remains an urgent problem. Arthralgia, myalgia, arthritis, autoimmune disorders and also osteonecrosis are may be development of the post-COVID period. This article discusses the case of the debut of multifocal osteonecrosis after a coronavirus infection.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

Combating the opioid epidemic: The examination of dental prescribing practices in treating post-operative pain after third molar extractions

The abuse and misuse of opioids continues to be a major problem in the United States, making opioids the leading cause of overdose-induced deaths. During the COVID-19 pandemic, approximately 30% more Americans died from drug overdoses in comparison to any other recent 12-month period. Three quarters of overdose-induced deaths were caused by opioids. When misused, opioids can be dangerous. Opioid addiction can begin with just one legitimate prescription administered by a trusted certified healthcare professional. An understanding of the decision-making practices used by dentists can lead to ways to curb abuse. This dissertation examines decision-making surrounding the prescribing practices of dentists in the treatment of post-operative pain following third molar extractions. Using a qualitative study method, the researcher gained understanding of the "how" and "why" of the decision-making process. The research included 55 licensed dentists (participants) currently practicing throughout the United States and its territories. Four themes that emerged from the survey data were: (1) Personal belief;(2) Prescribing practices have changed over time in the field of dentistry;(3) Non-steroidal Anti-inflammatory Drugs (NSAIDS) are the preferred drug for post-operative pain management after third molar extractions but may be combined with opioids;and (4) dentists perceive the opioid epidemic as a serious issue that influence their prescribing practices. Overall, the dentists who participated in the research appeared knowledgeable and well-informed on the efficacy of NSAIDs alone, and the efficacy of the NSAID + Acetaminophen combination. Nonetheless, they still routinely prescribed opioids to ensure their patients' pain management outcomes were met. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Modulation of the immune response to SARS-CoV-2 vaccination by NSAIDs.

Evidence is scarce to guide the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to mitigate SARS-CoV-2 vaccine related adverse effects, given the possibility of blunting the desired immune response. In this pilot study, we deeply phenotyped a small number of volunteers who did or did not take NSAIDs concomitant with SARS-CoV-2 immunizations to seek initial information on the immune response. A SARS-CoV-2 vaccine specific RBD-IgG antibody response and efficacy in the evoked neutralization titers were evident irrespective of concomitant NSAID consumption. Given the sample size, only a large and consistent signal of immunomodulation would have been detectable, and this was not apparent. However, the information gathered may inform the design of a definitive clinical trial. Here, we report a series of divergent omics signals that invite additional hypotheses testing. Significance Statement A SARS-CoV-2 vaccine specific immune response was evident irrespective of concomitant NSAID consumption in a clinical pilot study of small sample size.

Early Multi-Target Treatment of Mild-to-Moderate COVID-19, Particularly in Terms of Non-Steroidal Anti-Inflammatory Drugs and Indomethacin

Recently, in Italy, a flowchart to be used by General Practitioners for the at-home treatment of patients with COVID-19, has been released. It states that early at-home treatment for SARS-CoV-2 infection is possible due to the availability of specific antiviral drugs to be used in at-risk patients, and that non-steroidal anti-inflammatory drugs (NSAIDs) have an important function in combating the virus. Therefore, the use of NSAIDs is not only rational but also effective in cases that cannot be treated using antivirals. These seemingly simple concepts have been applied in Italy since the beginning of the pandemic by doctors that belong to Italian groups created in order to help COVID-19 patients early at home, at a time of organizational difficulties within Italian health institutions and government. However, this approach was largely boycotted by both the Italian Ministry of Health and medical institutions, which mainly suggested the use of paracetamol as symptomatic, and a wait-and-watch approach for the first three days from the onset of symptoms. In this article, we analyze the rationale for the use of NSAIDs and, in particular, the multi-targeted approach including indomethacin in synergism with flavonoids and low-dose aspirin, as early at-home treatment of patients with COVID-19. Applying these simple concepts from the beginning could have reduced the high lethality of the disease during the first two years of the pandemic and prevented hospital overload. In perspective, it is still necessary to systematically address the comparison between different therapeutic approaches to this viral disease on an experimental basis. [ FROM AUTHOR] Copyright of BioMed is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Heterotopic ossification post COVID-19: Report of two cases.

Heterotopic ossification is often associated with trauma and surgery, and infrequently reported with immobilization due to critical illness. We present 2 patients who developed heterotopic ossification following severe COVID-19 infection. Both patients were middle-aged females who were hospitalized for one month or greater due to COVID-19 requiring mechanical ventilation. Both developed shoulder pain and/or stiffness a few months after discharge, with imaging studies clearly illustrating development of heterotopic ossification around the shoulders. The etiology is unclear, with immobilization and hypoxia being the primary considerations. Physical examination and radiography are essential to diagnosis. Awareness of this complication and early diagnosis may help minimize functional impairment.

The occurrence of emerging compounds in real urban wastewater before and after the COVID-19 pandemic in Cali, Colombia.

The COVID-19 pandemic is considered one of the most significant global disasters in the last years. The rapid increase in infections, deaths, treatment, and the vaccination process has resulted in the excessive use of pharmaceuticals that have entered the environment as micropollutants. Considering the prior information about the presence of pharmaceuticals found in the wastewater of Cali, Colombia, which was collected from 2015 to 2022. The data monitored after the COVID-19 pandemic showed an increase in the concentration of analgesics and anti-inflammatory drugs of up to 91%. This increase was associated with the consumption of pharmaceuticals for mild symptoms, such as fever and pain. Moreover, the increase in concentration of pharmaceuticals poses a highly ecological threat, which was up to 14 times higher than that reported before of COVID-19 pandemic. These results showed that the COVID-19 had not only impacted human health but also had an effect on environmental health.

Adverse drugs reactions to paracetamol and ibuprofen in children: a 5-year report from a pediatric poison control center in Italy.

BACKGROUND: This study aimed to analyze all the patients who contacted the hospital's pediatric poison control center (PPCC) for exposure to ibuprofen and acetaminophen, in order to assess the incidence of any adverse reactions. METHODS: We retrospectively reported the clinical data of children who accessed the PPCC of the Bambino Gesù Children's Hospital, IRCCS, Rome, from January 1, 2018 to September 30, 2022 due to wrong, accidental or intentional intake of inappropriate doses of acetaminophen and/or ibuprofen. In addition, we compared patients according to the intake of one of the two drugs and reported the trimestral distribution of cases during the study period. RESULTS: A total of 351 patients accessed the PPCC during the study period. The median age was 3.0 years. Most patients were females (57.8%). The most common reason for inappropriate oral intake of paracetamol or ibuprofen was a wrong use or an accidental intake (78.6%), with a fifth of patients taking the drug with suicidal intent (21.1%). According to the PPCC evaluation, most patients were not intoxicated (70.4%). Hospitalization was required for 30.5% of patients. Adverse reactions were reported in 10.5% of cases, with a similar incidence in patients who took paracetamol or ibuprofen. Nausea and vomiting were the most commonly reported adverse reactions. A higher frequency of moderate intoxication was found in patients who took paracetamol compared to ibuprofen (p = 0.001). The likelihood of intoxication was also higher in the paracetamol cohort. A spike of cases was registered at the end of 2021. CONCLUSIONS: We analyze exposures to the two most commonly used pediatric molecules, paracetamol and ibuprofen, to assess the frequency of adverse reactions. We demonstrated that these relatively "safe" drugs may be associated with intoxications and adverse reactions when inappropriately administered.

Nonsteroidal Anti-Inflammatory Drugs in Viral Infections Disease, Specially COVID-19.

During the current SARS-CoV-2 (COVID-19) pandemic, some reports were presented based on those nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. According to this, we aimed to collate information available in published articles to identify any evidence behind these statements with the aim of helping clinicians on how best to treat patients. We could not find published conclusive evidence for or against the use of NSAIDs in COVID-19 patients. Meanwhile, there appeared to be some evidence that corticosteroids may be beneficial if utilized in the early acute phase of infection, however, conflicting WHO (World Health Organization) evidence surrounding corticosteroid use in certain viral infections means this evidence is not conclusive. Given the current availability of literature, caution should be exercised until further evidence emerges surrounding the use of NSAIDs and corticosteroids in COVID-19 patients. However, the availability of reliable information for clinicians and patients is paramount.

Hypothesis: Efficacy of early treatments with some NSAIDs in COVID-19: Might it also depend on their direct and/or indirect zinc chelating ability?

The present work argues for the involvement of the zinc chelating ability of some non-steroidal anti-inflammatory drugs as an additive mechanism able to increase their efficacy against COVID-19.

Reactive arthritis occurring after COVID-19 infection: a narrative review.

PURPOSE: Reactive arthritis is acute aseptic arthritis occurring 1 to 4 weeks after a distant infection in a genetically predisposed individual. It may occur after COVID-19 infection. We summarize, in this article, the current findings of reactive arthritis following COVID-19 infection. METHODS: A literature search has been performed from December 2019 to December 2021. We included case reports of reactive arthritis occurring after COVID-19 infection. We collected demographic, clinical, and paraclinical data. RESULTS: A total of 22 articles were reviewed. There were 14 men and 11 women with a mean age of 44.96 + 17.47 years. Oligoarticular involvement of the lower limbs was the most frequent clinical presentation. The time between arthritis and COVID infection ranged from 6 to 48 days. The diagnosis was based on clinical and laboratory findings. The pharmacological management was based on non-steroidal anti-inflammatory drugs in 20 cases. Systemic or local steroid therapy was indicated in 13 patients. Sulfasalazine was indicated in two cases. Alleviation of symptoms and recovery were noted in 22 cases. The mean duration of the clinical resolution was 16 + 57 days. CONCLUSION: The diagnosis of reactive arthritis should be considered in patients with a new onset of arthritis following COVID-19 infection. Its mechanism is still unclear.

Hypothesis: Efficacy of early treatments with some NSAIDs in COVID-19: Might it also depend on their direct and/or indirect zinc chelating ability?

The present work argues for the involvement of the zinc chelating ability of some non-steroidal anti-inflammatory drugs as an additive mechanism able to increase their efficacy against COVID-19.