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1.
  • Munch, Marie W., et al. (author)
  • Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
  • 2021
  • In: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
  • Journal article (peer-reviewed)abstract
    • Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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  • Feldman, V.I., et al. (author)
  • Effect of matrix and substituent on the electronic structure of trapped benzene radical cations
  • 2000
  • In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 2:1, s. 29-35
  • Journal article (peer-reviewed)abstract
    • The structure and dynamics of the radical cations produced from benzene, monodeuterated benzene and toluene in various low-temperature matrices were characterized by EPR and ENDOR spectroscopy. It was found that the nature of the matrix had a dramatic effect on the EPR spectra of benzene cation. Rigid structures corresponding to the 2B(1g) and 2B(2g) states are revealed in solid argon and halocarbon (CFCl3) matrices, respectively, whereas only dynamically averaged patterns are observed in other hosts used (krypton, xenon, sulfur hexafluoride). Deuterium monosubstitution has no appreciable effect on the cation structure observed in argon and halocarbon matrices, which implies matrix control of the preferred electronic state. In contrast, the toluene radical cation exhibits only a 2B(2g)-like structure both in argon and in CFCl3 matrices, that is, the internal structural effect strongly predominates over environment effects in this case. The results are discussed in qualitative terms taking into consideration the matrix and substituent effects on the charge distribution in benzene cation.
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4.
  • Jayakumar, O. D., et al. (author)
  • Surfactant-induced enhanced room temperature ferromagnetism in Zn0.96Mn0.03Li0.01O nanoparticles : Prepared by solid-state pyrolitic reaction
  • 2007
  • In: Journal of Crystal Growth. - : Elsevier BV. - 0022-0248 .- 1873-5002. ; 307:2, s. 315-320
  • Journal article (peer-reviewed)abstract
    • We report the synthesis of nanoparticles of Zn0.96Mn0.03Li0.01O by a low-temperature solid-state pyrolitic reaction, followed by a surfactant-assisted calcination at 400 degrees C. The X-ray diffraction and transmission electron microscopy analyses showed the formation of impurity free nanocrystals of Mn doped Li co-cloped ZnO with wurtzite structure. XPS data revealed that Mn exists in + 2 oxidation state. DC magnetization measurements as a function of field and temperature showed enhanced room temperature ferromagnetism for the surfactant-treated Zn0:96Mn0.03Li0.01O. FMR signal observed in the EPR spectrum further confirmed its ferromagnetic nature.
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5.
  • Joshi, Mrudula, et al. (author)
  • Listening to patients, for the patients : The COVAD Study-Vision, organizational structure, and challenges
  • 2024
  • In: International Journal of Rheumatic Diseases. - : John Wiley & Sons. - 1756-1841 .- 1756-185X. ; 27:5
  • Journal article (peer-reviewed)abstract
    • Background: The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy.Objectives: The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown.Methods: Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs).Discussion: We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them.Conclusion: Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them.
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6.
  • Kadam, Esha, et al. (author)
  • Collating the voice of people with autoimmune diseases : Methodology for the Third Phase of the COVAD Studies
  • 2024
  • In: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 44:7, s. 1233-1244
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail.METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors.CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.
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7.
  • Shinde, S. P., et al. (author)
  • Characterization of basaltic rock aquifer parameters using hydraulic parameters, Theis’s method and aquifer test software in the hard rock area of Buchakewadi watershed Maharashtra, India
  • 2022
  • In: Applied water science. - : Springer Nature. - 2190-5487 .- 2190-5495. ; 12:9
  • Journal article (peer-reviewed)abstract
    • The twelve wells were selected to carry out the various test, duration of pumping (min), maximum draw drown (m), duration of recovery (min), residual drawdown, and aquifer type in the basaltic rock aquifer parameters of Buchakewadi watershed. The source and flow of groundwater are essential concerns in hydrological systems that concern both spatially and temporally components of groundwater discharge and water supply problems. The content and temperature of groundwater flowing through an aquifer might change depending on the aquifer environment. As a result, hydrodynamic analyses can provide valuable information about a region’s subsurface geology. The present research attempts of aquifer variables such as transmissivity (T) and storativity (S) estimation are significant for groundwater resource development and evaluation. There are numerous approaches for calculating precise aquifer characteristics (i.e., hydrograph analysis, pumping test, etc.). A most frequent in situ analysis is a well-pumping test, which accurately measures the decline and rise of groundwater levels. During an aquifer pumping test, to characterize aquifer properties in an undiscovered location to forecast the rate of depletion of the groundwater table/potentiometric surface. The shallow, weathering subsurface water accessible above the Deccan traps in an unconfined state is insufficient to satisfy the ever-increasing pressure on water supplies. Maharashtra is similarly dominated by hard rocks, whose rainfall susceptibility is limited by weathering and primary porosity, as is their volume to store and convey water. Based on the hydraulic parameters and Theis method, results are optimized. Aquifer mapping and pumping test results can be more important for solving problems such as water scarcity, nonpolluting water, health issues, and source of fresh water on the earth surface. However, the characterization of aquifer parameters should be significant role in the scientific planning and engineering practices. © 2022, The Author(s).
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  • Shumnalieva, Russka, et al. (author)
  • Characteristics of emerging new autoimmune diseases after COVID-19 vaccination : A sub-study by the COVAD group
  • 2024
  • In: International journal of rheumatic diseases. - : John Wiley & Sons. - 1756-1841 .- 1756-185X. ; 27:5
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Despite the overall safety and efficacy of COVID-19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post-vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post-vaccination.METHODS: A cross-sectional study was conducted among participants with self-reported new-onset SAIDs using the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset-a validated, patient-reported e-survey-to analyze the long-term safety of COVID-19 vaccines. Baseline characteristics of patients with new-onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio.RESULTS: Of 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new-onset SAID post-vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new-onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9-9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3-5.3; p = .004). New-onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1-1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3-1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2-4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4-0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs.CONCLUSION: This study reports a low occurrence of new-onset SAIDs following COVID-19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre-existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID-19 vaccination in the general population. However, long-term studies are needed to understand the autoimmune phenomena arising post-vaccination.
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  • Upadhayaya, Ram Shankar, et al. (author)
  • Synthesis and antimycobacterial activity of prodrugs of indeno[2,1-c]quinoline derivatives
  • 2011
  • In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 46:4, s. 1306-1324
  • Journal article (peer-reviewed)abstract
    • Recently we have reported anti-TB properties of a new class of conformationally-constrained indeno[2,1-c]quinolines, which are although considerably active (MIC 0.39-0.78 mu g/mL) suffered from intense solubility problems. We thought of improving their bioavailability by prodrugs approach. Accordingly esters of the "Lead" indeno[2,1-c]quinolines 1,15 and 27 derivatives were synthesized and their prodrug nature at the physiological pH were confirmed. Prodrugs were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv by MABA assay to show that they have 2- to 4-fold improved anti-TB activities, increased aqueous solubility and superior selectivity index over their respective parent compounds. MIC of these prodrugs was in the range of <0.20-6.0 mu g/mL and in general, no cytotoxicity was observed in VERO cells.
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