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BackgroundLupus is a heterogenous diseases which results in significant premature mortality. Most studies have evaluated risk factors for lupus mortality using regression models which considers the phenotype in isolation. Identifying clusters of patients on the other hand may help overcome the limitations of such analyses.ObjectivesThe objectives of this study were to describe the causes of mortality and to analyze survival across clusters based on clinical phenotype and autoantibodies in patients of the Indian SLE Inception cohort for Research (INSPIRE)MethodsOut of all patients, enrolled in the INSPIRE database till March 3st 2022, those who had <10% missing variables in the clustering variables were included in the study. The cause of mortality and duration between the recruitment into the cohort and mortality was calculated. Agglomerative unsupervised hierarchical cluster analysis was performed using 25 variables that define SLE phenotype in clinical practice. The number of clusters were fixed using the elbow and silhouette methods. Survival rates were examined using Cox proportional hazards models: unadjusted, adjusted for age at disease onset, socio-economic status, steroid pulse, CYC, MMF usage and cluster of the patients.ResultsIndian patients with lupus have significant early mortality and the majority of deaths occurs outside the hospital setting.Out of 2211 patients in the cohort, 2072 were included into the analysis. The median (IQR) age of the patients was 26 (20-33) years and 91.7% were females. There were 288 (13.1%) patients with juvenile onset lupus. The median (range) duration of follow up of the patients was 37 (6-42) months. There were 170 deaths, with only 77 deaths occurring in a health care setting. Death within 6 months of enrollment occured in in 80 (47.1%) patients. Majority (n=87) succumbed to disease activity, 23 to infections, 24 to coexisting disease activity and infection and 21 to other causes. Pneumonia was the leading cause of death (n=24). Pneumococcal infection led to death in 11 patients and SARS-COV2 infection in 7 patients. The hierarchical clustering resulted in 4 clusters and the characteristics of these clusters are represented in a heatmap (Figure-1A,B). The mean (95% confidence interval [95% CI] survival was 39.17 (38.45-39.90), 39.52 (38.71-40.34), 37.73 (36.77-38.70) and 35.80 (34.10-37.49) months (p<0.001) in clusters 1, 2, 3 and 4, respectively with an HR (95% CI) of 2.34 (1.56, 3.49) for cluster 4 with cluster 1 as reference(Figure 1C). The adjusted model showed an HR (95%CI) for cluster 4 of 2.22 (1.48, 3.22) with an HR(95%CI) of 1.78 (1.29, 2.45) for low socioeconomic status as opposed to a high socioeconomic status (Table 1).ConclusionIndian patients with lupus have significant early mortality and the majority of deaths occurs outside the hospital setting. Disease activity as determined by the traditional activity measures may not be sufficient to understand the true magnitude of organ involvement resulting in mortality. Clinically relevant clusters can help clinicians identify those at high risk for mortality with greater accuracy.Table 1.Univariate and multivariate Cox regression models predicting mortalityUnivariateMultivariateVariablesHazard ratio (95% Confidence interval)P valueHazard ratio (95% Confidence interval)P valueCluster1Reference-Reference-20.87 (0.57, 1.34)0.5320.89 (0.57, 1.38)0.59831.22 (0.81, 1.84)0.3371.15 (0.76, 1.73)0.51342.34 (1.56, 3.49)<0.0012.22(1.48, 3.22)<0.001Socioeconomic statusLower1.78 (1.29, 2.45)<0.001Pulse steroidYes1.6 (0.99, 2.58)0.051MMFYes0.71 (0.48, 1.05)0.083CYCYes1.42 (0.99, 2.02)0.052Proliferative LNYes0.99 (0.62, 1.56)0.952Date of birth age0.99 (0.98, 1.01)0.657CYC- cyclophosphamide, MMF- Mycophenolate mofetilFigure 1.A. Agglomerative clustering dendrogram depicting the formation of four clusters. B.Heatmap depicting distribution of variables used in clustering C. Kaplan-Meier curve showing the survival function across the 4 clusters[Figure omitted. See PDF]REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone eclared.
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Background: Improving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). Material(s) and Method(s): This is a retrospective study done over 6 years (2016-2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. Result(s): Over all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n = 6951;30.1%) followed by Klebsiella pneumoniae (n = 5801;25.1%) and Pseudomonas aeroginosa (n = 3041;13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan-June 2016 to 12.2% in July-Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%-20.6%, CR Acinetobacter (66.6%-17.02%) and CR E. coli (21.6%-19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. Conclusion(s): This study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.Copyright © 2023 Indian Association of Medical Microbiologists
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"COVID-2019,” a recently emerged novel coronavirus disease, is causing serious health issues to the public and becoming more and more fatal every next day. On December 31, 2019, low respiratory infection cases were detected in Wuhan, China, which is in China's Hubei province. The cases were reported to the WHO Office of China and they could not identify the agents for the cause. The first cases were classified to be "pneumonia of unknown etiology.” The investigation program was initiated by the Chinese Center for Disease Control and Prevention (CDC). The etiology of the disease was attributed to a novel virus of the coronavirus (CoV) family. Dr. Tedros Adhanom Ghebreyesus, WHO Director-General, called the disease caused by this CoV the "COVID-19,” which is an acronym for "coronavirus disease 2019.” It is found that "COVID-19” is caused by bête-coronavirus named "severe acute coronavirus-2” (SARS-CoV-2). It belongs to those virus families that appear as pneumonia in the human body. It affects the lower respiratory tract badly. This virus has been identified as another version of the family of severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) [1, 2]. SARS-CoV-2, SARS-CoV, and MERS-CoV possess similarity with them. They have differences in genotypic and phenotypic structure that guide their pathogenesis. So far, as per the findings, this virus originated in bats. It reached humans through contact with unknown animals. The transmission of this virus among humans is via direct contacts, inhalation of infected droplets, and contaminated hands and surfaces. Some of the symptoms of this disease are cough, sore cough, fever, fatigue, and dyspnea/breathlessness. The remedy of this disease is to diagnose the infection at the initial stage, supportive treatment to survive, self-quarantines, mass-quarantines, etc. This paper presents a systematic review of the origin of coronavirus, its types, transmissions, symptoms, and the current developments in diagnosing testing and vaccine trials. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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Intro: While the pediatric population has largely remained free of severe COVID- 19, in some situations SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). Recently, cases of hepatitis in children have caused tremendous worry across the globe, we describe a unique presentation from 2021, subsequent to asymptomatic infection of SARS-CoV-2, a unique form of severe hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The clinical presentations, temporal association, and viral parameters of CAH-C cases, and contrast to that of MIS-C cases are presented here. Method(s): As a retrospective and follow-up case-control study we reviewed all children within 14 years presenting with "sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice. After performing all routine tests among them, those lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis (A-E) or previous underlying liver disease, and (b) multi-system involvement", being unique such cases were classified as CAH-C, and are described here. Finding(s): Among 475 children who tested positive, 37/47 cases had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers, 100% positivity for SARS-CoV-2 antibodies, and uneventful recovery. The remaining 10/47 having MIS-C had protracted illness, multiple system involvement, required admission to critical care, and a mortality rate of 30%. Among controls, only 26/50 (52%) had SARS-CoV-2 antibodies. Discussion(s): During the pandemic, various COVID-19 complications have been observed posing safety concerns, where our study identified a unique form of acute hepatitis in children designated as CAH-C. Conclusion(s): With the emergence of newer variants, including the Delta variant which predominated the second wave of infections in India and spread worldwide with changing presentations and complications, CAH-C is such new entity in children. It needs early identification and differentiation from other emerging syndromes during the ongoing pandemic for preventing adversities through timely intervention.Copyright © 2023
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COVID-19 is the transmittable disease that emerged as a recent epidemic and threatened the lives of various people. The emerged pandemic initiated a change in the people's routine and impacted a serious financial crisis. This initiated a necessity for developing a deeper insight of the COVID-19 disease and multiple researches are performed based on the COVID-19 epidemic, which possess the challenges of basic analysis of information about the disease, lack of data, lack of knowledge about the parameters that cause disease and to overcome this a deep COVID-19 analysis epidemic via the deep CNN classifier is accomplished in the research. The impact of the disease is examined based on the gender, age group, symptoms and outbreak of the disease. This analysis provides comprehensive information about the disease and helps in making the preventive measures, which will greatly reduce the impacts of the disease. The accomplishment of deep CNN instinctively analyzes the essential features needed for the classification that helps in reducing the effort and time of the individuals. The performance is analyzed with the metrics specificity, accuracy and sensitivity, which obtained values of 0.48 %, 0.27 %, 2.82 % corresponding to and 2.88 %, 1.5 %, 0.36% considering training percentage, which is more efficient. © 2023 IEEE.
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Background: The COVID-19 pandemic has had an unprecedented impact on the United States health system and its ability to deliver care. In particular, surgical and interventional procedures suffered a significant decline in the early stages of the pandemic for a multitude of reasons including, PPE and personnel shortages, the deference of elective procedures, and governmental bans on elective procedures. The impact of these factors on electrophysiology (EP) procedural rates in the United States is unknown. Objective(s): To study the impact of the COVID-19 pandemic on EP procedural volume in the United States (2019-2020). Method(s): We analyzed the National inpatient sample (2019-2020) to identify hospitalizations involving EP procedures using ICD-10-PCS codes. Weighted analysis was performed to determine the number of procedures performed on a monthly basis. The US census data was employed to ascertain procedure rates per million population, the trends of which are displayed in Figure 1. Result(s): A total of 236,991 EP procedures were performed in 2020 - a 9% decrease from 2019 (n= 260,615). This included an annualized 11.25% decrease in device implantations (ICD and PPM), a 7.7% drop in AF ablations, and a 5.4% decrease in VT ablations as compared to 2019. Interestingly rates of left atrial appendage occlusion (LAAO) procedures saw an annualized 3.7% increase in 2020. The maximal per-month decline in procedural volume was noted in April 2020. An overall decline of 48% in EP procedures was noted, with the most precipitous drop with LAAO (90%), followed by AF Ablation (65%), PPM (4.3%), ICD (3.8%), and least with VT ablation (2.5%). Conclusion(s): The COVID-19 pandemic has had a significant and heterogonous impact on EP procedural volume. Despite a precipitous 48% decline in April 2020, overall, 2020 procedure rates have recovered to a 9% drop from 2019. [Formula presented]Copyright © 2023
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A patient presented with COVID-19-induced enteritis and colitis associated with a high D-dimer. Serotonin released by activated platelets can lead to inflammation and multiorgan failure in COVID-19 infection. Cyproheptadine blocks serotonin receptors. In light of a prior report that showed that cyproheptadine successfully treated neurologic sequelae in COVID-19, we applied this treatment to this patient. Rapid clinical improvement and reduction of D-dimer occurred after 3 doses of cyproheptadine. This inexpensive, well-Tolerated, oral medication may be applicable to treat hyperinflammatory sequelae of COVID-19 infection.Copyright © 2023 American College of Gastroent. All rights reserved.
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Indian power system witnessed its largest very short-time demand ramping during light off event conducted to express solidarity with COVID-19 volunteers. 32 GW demand ramping was observed within 25 minutes and recorded as the highest ramping event across the globe. System operator has taken precautions and successfully handled the event with the help of hydro generation. However, system experienced severe frequency and voltage deviations due to unexpected consumer behaviour. A systematic study and an in-depth analysis of such a severe event would help system operators and planners to prepare for similar events. This paper presents a critical analysis of the activity and conducted a survey to understand consumer response during that event. It also proposes a modified Bottom-Up Approach to estimate Expected Demand Reduction (EDR) for such critical events. Proposed model is validated using data collected from the conducted survey. Proposed EDR estimation model offers better results than the Top Down and Bottom-up approach models used by system operator. © 2022 IEEE.
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PurposeThis study aims to investigate the role of consumption coping in managing collective tragedy stress and stress outcomes using the COVID-19 pandemic context. Design/methodology/approachA mixed-method study with a sample size of 931 was conducted to develop the questionnaire, followed by a quantitative study with 1,215 respondents to test the hypotheses. FindingsThe results of this study empirically validated the use of consumption coping and found it effective in managing collective tragedy stress and its outcomes (subjective well-being and continuance intention). Research limitations/implicationsThis study advances the literature on stress coping in a collective tragedy context, with a specific focus on consumption coping. Practical implicationsThe COVID-19 pandemic has affected all elements of the marketing mix. Understanding pandemic-induced stress and the role of consumption coping can help managers to proactively formulate strategic responses suitable for changing consumer habits. Social implicationsThe COVID-19 pandemic has affected all elements of the marketing mix. Understanding pandemic-induced stress and the role of consumption coping can help managers to proactively formulate strategic responses suitable for changing consumer habits. This should lead to better social outcomes. Originality/valueThis study developed a scale for pandemic-induced stress that integrates various well-established theories to identify the role of consumption coping in managing collective tragedy stress and the psychological mechanism behind the shift in consumer behavior after a collective tragedy.
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Bell's palsy is described as an acute, unilateral mononeuropathy of the facial nerve resulting in partial or complete paralysis of the face with no identifiable cause. Although facial palsy is often idiopathic, its development soon after the BB-152 Covid vaccine is exceedingly rare. We report a patient with transient acute-onset unilateral infranuclear facial palsy following vaccination, after an exhaustive work-up for other common causes was negative. With no detectable aetiology the likelihood of an association of the Covid-19 vaccine and Bell's palsy remains.
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Background: It has been previously reported during the first COVID outbreak that patients presenting with ST-Segment Elevation Myocardial Infarction (STEMI) and concurrent COVID-19 infection have increased thrombus burden and poorer outcomes [1]. Subsequently, there have been multiple further waves of the pandemic with the emergence of at least two new COVID-19 variants and the emergence of vaccinations. To-date, there have been no reports comparing the outcomes of COVID-19-positive STEMI patients across all waves of the pandemic. Purpose(s): The purpose of this study was to compare the baseline demographic, procedural and angiographic characteristics alongside the clinical outcomes of patients presenting with STEMI and concurrent COVID-19 infection across the COVID-19 pandemic in the UK. Method(s): This was a single-centre, observational study of 1250 consecutive patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention (PCI) at Barts Heart Centre between 01/03/2020 and 10/03/2022. COVID +ve patients were split into 3 groups based upon the time course of the pandemic (Wave 1: March 2020-June 2020, Wave 2: Sept 2020-March 2021, Wave 3: October 2021-March 2022). Comparison was made between waves and with a control group of COVID-ve patients treated during the same timeframe. Result(s): A total of 135 COVID +ive patients with STEMI (1st Wave: 39 patients, 2nd Wave: 60 patients, 3rd wave 35 pts) were included in the present analysis;and compared with 1115 COVID negative patients. Significant changes in the baseline characteristics, angiographic features and clinical outcomes of COVID +ive patients occurred over time. Early during the pandemic (Wave 1 2020), STEMI patients presenting with concurrent COVID-19 infection had high rates of cardiac arrest, evidence of increased thrombus burden (higher rates of multi-vessel thrombosis, stent thrombosis, higher modified thrombus grade higher use of GP IIb/IIIa inhibitors and thrombus aspiration, coagulability (more heparin for therapeutic ACT), bigger infarcts (lower myocardial blush grade and left ventricular function) and worse outcomes (mortality). However, by wave 3 (late 2021/2022), no differences existed in clinical characteristics, thrombus burden, infarct size or outcomes between COVID +ive patients and those without concurrent COVID-19 infection with significant differences compared to earlier COVID +ve patients. Poor outcomes later in the study period were predominantly in unvaccinated individuals. Conclusion(s): Significant changes have occurred in the clinical characteristics, angiographic features and outcomes of STEMI patients with COVID- 19 infection treated by primary PCI during the course of the pandemic. Importantly it appears that angiographic features and outcomes of recent waves are no different to a non-COVID-19 population.
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Objective: The objectives of the study were: (1) To assess life style changes among children of <=15 years of age during COVID-19 pandemic and (2) to find out the effect of the life style changes on health of children of <=15 years of age. Method(s): The cross-sectional comparative study conducted at department of pediatrics, Vivekananda Polyclinic and Institute of Medical Sciences, Lucknow for duration of 1 year and sample size found to be 276 on calculation by applying the formula. Result(s): Out of 278 children, about 39% (108) were female children. Most of children were studying in primary level classes (52.51%) and most of enrolled children had joint family (66.18%). Level of physical activity reduced significantly due to closure of school and restriction on outdoor activities. Weight of children increased significantly during COVID-19 pandemic seems to be due to decreased in physical activities and consumption of more fast food/fried food (high calorie intake) and sedentary life style. Conclusion(s): During COVID-19 pandemic due to closure of schools and restricted outdoor activities results in decrease level of physical activities, increased consumption of high calorie food and sedentary behavior lead to increase in weight of children and changes in sleeping pattern of children.Copyright © 2023 The Authors. Published by Innovare Academic Sciences Pvt Ltd.
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Objective: The objective of this study was to compare the screen time (ST) in pre-COVID and COVID era in children aged 5-15 years and to analyse the ST effect in pre-COVID and COVID era in the children. Method(s): The study was done at Vivekananda Polyclinic and Institute of Medical Sciences, Lucknow. Two hundred and seventy-six children aged between 5 and 15 years, attending outpatient department or inpatient department were enrolled in the study. Result(s): It was observed that the ST was significantly increased in post-COVID as compared to pre-COVID time and the difference was statistically significant (p<0.0001*). It was also observed that the screening time was significantly increased in post-COVID as compared to pre-COVID time and the difference was statistically significant (p<0.0001*). Conclusion(s): The present study found that when screening duration was analysed, the screening time during COVID-19 was significantly longer than the screening time before COVID-19 which may be associated with the various health problems reported among children during COVID-19 pandemic.Copyright © 2023 The Authors. Published by Innovare Academic Sciences Pvt Ltd.
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More than 6 million people have lost their lives due to COVID-19 across the world (Ghatkopar in Fake negative COVID-19 certificate scam unearthed, 2019, [2];WHO (World Health Organization) in https://covid19.who.int/table, [3]). Recently, fake COVID-19 test certificate scams have spiked up drastically and become one of the reasons for the spread of COVID-19. In light of the current scenario, this paper proposes a decentralized approach called, "D-Test” for COVID-19 testing which allows the hospital and the general public to register themselves at a common platform which follows the concept of CIA triad (Confidentiality, Integrity, and Availability) and allows users to register without any fear of data breach. This platform registers users based on smart contract and enables the user to do the following once registered successfully: (a) Book Testing Slot, (b) Find nearby registered testing laboratories, and c) Generate the COVID-19 reports which could be imported and exported as and when required by the user. This has a higher value of trust because the source of the report can be traced back since usage of Blockchain prevents the likelihood of data tampering by an entity. This framework could help the government(s) keep track of distributing authentic COVID-19 testing certificates, prevent the fake COVID-19 testing certificate scams, and will speed up the process of verifying the users' test reports, thereby saving lives of many citizens around the world. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
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The novel coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affected millions of people worldwide at an alarming rate. Moreover, the development of vaccines is still hope, but its camouflage mutations during transmission are still a challenge. In the dire condition of this pandemic, drug repurposing with the exploitation of computational modeling has become the cynosure to repurpose the already existing drugs such as remdesivir, Favipiravir, dexamethasone, and other drugs at clinical levels. Furthermore, their safety and efficacy against COVID-19 remain a challenge in different age groups and populations with preexisting conditions like heart disease, hepatic and renal impairment, pregnancy, and immunocompromised states. Moreover, computational modeling allows studying physiological and biochemical parameters on drug transport, delivery, and therapeutic efficacy of dosage forms. This review explicitly provides a comprehensive account of the challenges and opportunities for developing physiologically based pharmacokinetic models (PBPK) and pharmacodynamic(PD) models to establish a therapeutic dosage regimen based on dose selection, safety, and efficacy. We also highlight the pharmacologic targeting strategies for ACE receptors, toxicity concerns, combination therapy, and drug-drug interactions for different repurposed drugs against COVID-19. In dreadful scenarios, PBPK and PD models hold promise for human PK and dose prediction in COVID-19, along with paving new horizons to improve the therapeutic as well as immuno-therapeutic efficacy using nano-drug delivery approaches, computer-aided drug design (CADD), and speed up clinical trials with a better understanding of quantitative in vitro to in vivo extrapolation (QIVIE) and established PK data. © 2022 by the authors.
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Managing uncertainty is a critical leadership capability. Keeping the COVID-19 pandemic as the background, we conducted a panel discussion with senior corporate leaders to understand how they had approached challenging situations in the past, managed uncertainties, and how these learnings have contributed to their development as leaders. We draw upon the extant literature on leadership under uncertainty and leader development to frame our study. The rich narratives of the panellists provide theoretical insights and significant lessons for managers and emerging leaders. © 2023
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The coronavirus disease (COVID-19) pandemic has created a lot of healthcare concerns. Over the past two years, healthcare professionals worked hard to develop numerous vaccines to combat this virus which is truly remarkable. However, a large proportion of the global population is skeptical about the vaccines and the sudden emergence of the new strain of the virus is stirring up mixed emotions causing the use of opinion terms having varying polarities in different contexts which poses a challenge to predict the accurate sentiments from the user-generated data. In this work, a novel architecture namely a deep fusion model (DFM) with a meta-learning ensemble method is proposed for sentiment analysis of public opinions on COVID-19 vaccines and omicron variant on Twitter. The proposed model employed using natural language processing with deep learning models such as LSTM, GRU, CNN, and their various combinations. The purpose of this study is to understand the public opinion around COVID-19 vaccines and omicron variant through the proposed model. In addition, the experiment demonstrated effectiveness with an accuracy of up to 88% in comparison with state-of-the-art models. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
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Background: The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod in UC. This analysis evaluated the cumulative long-term safety of ozanimod in these studies, which included pts with up to ~3 years of treatment exposure. Method(s): In TN, pts were randomised to once-daily ozanimod 0.92 mg or placebo, or to open-label ozanimod for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo in the maintenance period through Week 52. TN pts were eligible to enrol in the OLE and receive ozanimod if they did not achieve clinical response at the end of induction (Week 10), lost response during maintenance, or completed maintenance at Week 52. This interim analysis of the TN OLE (data cutoff: 10 January 2022) included all pts who entered the OLE from TN (n=823). Safety was monitored from the first dose of ozanimod in TN and throughout the subsequent OLE. Exposureadjusted incidence rates per 100 patient-years (PY) were calculated. Result(s): The average age of TN OLE study participants was 41.7 years (+/-13.6), 41% were female, 62% had left-sided UC disease, and 35% had prior exposure to tumor necrosis factor inhibitors. Total PY exposure to ozanimod was 2219 years (mean [SD] exposure = 2.7 [1.6]). The most frequent treatment-emergent adverse events (TEAEs) reported through OLE Week 94 (up to 146 weeks of continuous treatment) are listed in the Table. Most TEAEs were nonserious;TEAEs leading to discontinuation were uncommon. Bradycardia was reported in 3 pts (0.4%;EAIR 0.1/100 PY;2 in TN and 1 in OLE;no pts were discontinued from treatment). Macular edema was reported in 2 (0.2%;EAIR 0.1/100 PY) pts. Reductions in ALC were common (470 [57.1%] had ALC < 500 cells/mm3), as previously described, but ALC reductions were not associated with the occurrence of TEAEs. Malignancies were uncommon (n=13 [1.6%];EAIR 0.6/100 PY), and included 6 basal cell carcinomas and 3 colorectal neoplasms. Two deaths were reported: 1 due to COVID-19 and 1 sudden death. Investigators deemed both to be unrelated to treatment. Ozanimod was not associated with an increased risk of ischemic heart disease or thromboembolic events. Conclusion(s): Long-term exposure to ozanimod for up to 3 years was well tolerated in pts with moderately to severely active UC. No new safety signals were observed with long-term ozanimod use in UC (2219 PY exposure). Safety findings are consistent with previous reports from the UC and multiple sclerosis development programs (>16,512 PY exposure). (Table Presented).
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Dental implants are a standard of care in contemporary dental practice and are widely employed for the restoration of missing teeth. The long-term utility of an implant is largely dependent on the successful implant osseointegration and maintenance of the same over time. Bone metabolism and inflammatory mechanism are interrelated phenomena and are usually collectively termed osteoimmunology, which may affect the predictability and success of implant osseointegration. Many biochemical mediators of inflammation, especially Interleukin (IL)1, IL-6, and Tumour necrosis factor (TNF)alpha, have been documented to increase the activity of bone-resorbing cells through the Receptor Activator of Nuclear Factor Kappa-B (RANK) and Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)systems. Some of the earlier studies with very limited data suggest that SARS-CoV2 infection may also directly affect bone resorption. Thus, it is imperative to understand the pathophysiology of osseointegration in COVID-19 patients, to enhance successful implant osseointegration and prevent peri-implant bone loss in these patients. Here, we present a summary of the connection between inflammatory pathways and bone metabolism on a molecular basis which may assume a significant bearing in situations of exaggerated host immune response as seen in COVID-19 infection.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.