BHU Institutional Repository :: Browsing by Author "Kaur, Upinder"

Browsing by Author "Kaur, Upinder"

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A prospective observational safety study on ChAdOx1 nCoV-19 corona virus vaccine (recombinant) use in healthcare workers- first results from India
(Elsevier Ltd, 2021) Kaur, Upinder; Ojha, Bisweswar; Pathak, Bhairav Kumar; Singh, Anup; Giri, Kiran R.; Singh, Amit; Das, Agniva; Misra, Anamika; Yadav, Ashish Kumar; Kansal, Sangeeta; Chakrabarti, Sankha Shubhra
Background: We provide the first post-approval safety analysis of COVISHIELD in health care workers (HCWs) in northern India. Methods: This continuing prospective observational study (February 2021 to May 2022) enrolled participants ?18 years receiving COVISHIELD vaccination. Primary outcome was safety and reactogenicity. Categories (FDA toxicity grading) and outcomes of adverse events following immunization (AEFIs) were recorded, causality assessment performed, and risk factors analysed. Findings: We present the results of an interim analysis of 804 participants. AEFIs following first dose were reported in 321 (40%; systemic involvement in 248). Among 730 participants who completed a 7-day follow-up post second dose, AEFIs occurred in 115 (15.7%; systemic in 99). Majority of AEFIs were mild-moderate and resolved spontaneously. Serious AEFIs, leading to hospitalization was noticed in 1 (0.1%) participant with suspicion of immunization stress related response (ISRR). AEFIs of grade 3 severity (FDA) were recorded in 4 participants (0.5%). No deaths were recorded. Regression analysis showed increased risk of AEFIs in younger individuals, a two times higher odds in females, those with hypertension or with history of allergy; and three times higher odds in individuals with hypothyroidism. Interpretation: COVISHIELD carries an overall favourable safety profile with AEFI rates much less than reported for other adenoviral vaccines. Females, those with hypertension, individuals with history of allergy and hypothyroidism may need watchful vaccine administration. This being an interim analysis and based on healthcare workers who may not reflect the general population demographics, larger inclusive studies are warranted for confirming the findings. Funding: No funding support. � 2021 The Author(s)
A Prospective Observational Study on BBV152 Coronavirus Vaccine Use in Adolescents and Comparison with Adults: Interim Results of the First Real-World Safety Analysis
(Adis, 2022) Kaur, Upinder; K.L, Anju; Chauhan, Mayank; Joshi, Aditi; Das, Agniva; Kansal, Sangeeta; Jaisawal, Vaibhav; Patwardhan, Kishor; Chakrabarti, Sankha Shubhra
Introduction: The BBV152 coronavirus disease 2019 (COVID-19) vaccine (COVAXIN) has recently been approved for adolescents. Objective: We provide the first real-world safety data of COVAXIN use in adolescents and compare with adults. Methods: A prospective observational study was initiated in January 2022. Enrolled adolescents and adults were contacted by telephone after 14�days of receiving the BBV152 vaccine. The primary outcome was vaccine safety assessed as rate of adverse events following immunization (AEFIs). Severity grading of AEFIs was done using the Food and Drug Administration (FDA) scale. Interim results are presented. Results: A total of 698 adolescents and 326 adults were enrolled. AEFIs after the first dose developed in 243 out of 670 adolescents (36.3%), with 21% reporting only local AEFIs and 15.2% reporting systemic AEFIs. Among 340 adolescents who had received the second dose of vaccine, 129 (37.9%) developed AEFIs, with only local involvement in 20.3% and systemic involvement in 17.6%. Injection site pain and fever were the common AEFIs. The majority of AEFIs were mild-moderate. Nearly 0.9% of adolescents receiving the first dose reported severe AEFIs. Atypical AEFIs were observed in 0.6�0.9% of adolescents. The majority of the AEFIs resolved in 1�2�days. AEFIs were persistent in > 2% of adolescents at day 14 after the second dose, and also in 3.7% of adults overall at follow-up. No difference was observed in AEFI incidence and patterns between adolescents and adults. Regression analysis showed females and those with a history of allergy to be, respectively, at 1.6 times and 3 times increased risk of AEFIs among adolescents. Conclusions: COVAXIN carries an overall favorable short-term safety profile in adolescents. The observed AEFI rates in adolescents are much lower than that reported with mRNA vaccines, but head�head comparisons in the same population are required to generate relative vaccine safety data. Female adolescents and those with a history of allergy need watchfulness for severe and persistent AEFIs. With some AEFIs persisting at 14 days, a longer follow-up is recommended to strengthen the safety data of COVAXIN. � 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
A Real-world Pilot Observational Study of Neuropathic Pain Medications in Older Adult Patients in North India
(Bentham Science Publishers, 2022) Kaur, Upinder; Dwivedi, Vandana; Singh, Alok; Singh, Amit; Pandey, Arun Raj; Acharya, Kumudini; Chakrabarti, Sankha Shubhra
Aims: This pilot study aimed to make head-to-head comparisons of multiple classes of drugs used in the management of neuropathic pain in North Indian older adult patients pre-senting to the geriatric clinic of a tertiary medical institution. Background: Chronic neuropathic pain is a condition affecting nearly one third of older adults. There is paucity of data on head-to-head comparisons of drugs used in neuropathic pain in older adults. Real world studies may be a useful tool to study diverse neuropathic pain medications in this population. Objectives: The study objective was to measure NPRS (numeric pain rating scale), GDS (geri-atric depression scale), IADL (instrumental activities of daily living), HMSE (Hindi mental state examination) scores at baseline, and 4-and 12-week follow-ups in all older adult patients receiving neuropathic pain medications. Methods: A prospective observational study was conducted involving older adult patients ? 50 years of age with painful peripheral neuropathy of any etiology (n=60; mean age 63�8.4 years). The patients received either gabapentin, pregabalin, duloxetine, amitriptyline, or me-thyl-cobalamin complex. NPRS, GDS, IADL, and HMSE scores were measured at baseline and post-therapy. Results: All groups except amitriptyline showed statistically significant improvement in NPRS at 4 weeks and 12 weeks compared to baseline. 30% response rate at 4 weeks was maximum for pregabalin (72%) and 50% response rate at 12 weeks was maximum for gabapentin (58%). Numerically maximum improvement in depression was seen with duloxetine. There was no statistically significant difference in the measured parameters between the drug groups across time. Mean daily dose was 172 mg (gabapentin group), 75 mg (pregabalin group) and 20 mg (duloxetine group). The adverse drug reaction rate was 10.5%. Conclusion: All drug groups showed beneficial effects on neuropathic pain at much lower doses than those described in the literature. The effectiveness at these low doses and the lower rates of adverse effects sets the foundation for larger studies in the future in diverse ethnic and aged populations. � 2022 Bentham Science Publishers.
Acute Cardiac Events After ChAdOx1 nCoV-19 Corona Virus Vaccine: Report of Three Cases
(Lippincott Williams and Wilkins, 2022) Singh, Rohit; Chakrabarti, Sankha Shubhra; Gambhir, Indrajeet Singh; Verma, Ashish; Kumar, Ishan; Ghosh, Soumik; Tiwari, Ashutosh; Chandan, Gourav; Chakrabarti, Sasanka; Kaur, Upinder
[No abstract available]
Aripiprazole-induced Parkinsonism with pregabalin as a confounder
(Springer Science and Business Media Deutschland GmbH, 2021) Kaur, Upinder; Ojha, Bisweswar; Pathak, Bhairav Kumar; Singh, Amit; Gambhir, Indrajeet Singh; Chakrabarti, Sankha Shubhra
[No abstract available]
Case Report: Isoniazid-Associated Delirium in an Elderly Female with Spinal Tuberculosis
(American Society of Tropical Medicine and Hygiene, 2022) Kaur, Upinder; Singh, Rohit; Singh, Amit; Chakrabarti, Sankha Shubhra
Isoniazid is an important component of first-line antitubercular therapy. The drug at its therapeutic dose is known to cause hepatitis and peripheral neuropathy. The association of isoniazid with pure delirium is rare. Here, we present an interesting case of new-onset delirium associated with isoniazid in an elderly female with spinal tuberculosis. Remarkable improvement was noticed in the patient following drug discontinuation and pyridoxine augmentation. Copyright � 2022 by The American Society of Tropical Medicine and Hygiene.
Case Report: Nocardia amamiensis Infection Leading to Worsening of Chronic Obstructive Pulmonary Disease Symptoms in an Elderly Man
(American Society of Tropical Medicine and Hygiene, 2023) Kanakan, Ahalya; Kumar, Amit; Kaur, Upinder; Narwade, Prity; Rain, Zinnu; Yadav, Nidhi; Kumar, Ishan; Kumar, Deepak; Chakrabarti, Sankha Shubhra
Nocardiosis is a rare opportunistic infection mostly affecting the lungs, brain, or skin of immunocompromised individuals. Most pulmonary nocardiosis patients present with nonspecific clinical features such as productive cough, exertional dyspnea, and fever. The disease is uncommonly suspected, especially in tuberculosis-endemic regions, and clinical diagnosis is often delayed, resulting in high mortality. Pulmonary nocardiosis in apparently immunocompetent individuals is uncommon. Here, we present the case of an elderly gentleman with a background history of poorly controlled diabetes but no history of systemic steroid use who presented with worsening symptoms of chronic obstructive pulmonary disease in the form of productive cough and dyspnea. The patient had diffuse crepitations in bilateral lung fields and an arterial oxygen saturation of 86% at admission. Sputum microscopy revealed gram-positive filamentous bacteria that could be successfully cultured and identified as Nocardia amamiensis on 16S ribosomal RNA sequencing. Contrast-enhanced computed tomography of the lungs revealed cavitary nodules and consolidation. The patient responded well to treatment with specific antibiotics based on sensitivity patterns. Because of the nonspecific clinical and radiological findings in pulmonary nocardiosis, a high index of suspicion is required, especially in tuberculosis-endemic regions. � 2023 American Society of Tropical Medicine and Hygiene. All rights reserved.
Case Report: Rhino-orbital Mucormycosis Related to COVID-19: A Case Series Exploring Risk Factors
(American Society of Tropical Medicine and Hygiene, 2022) Aggarwal, Sushil Kumar; Kaur, Upinder; Talda, Dolly; Pandey, Akshat; Jaiswal, Sumit; Kanakan, Ahalya; Singh, Anshuman; Chakrabarti, Sankha Shubhra
There has been a surge of rhino-orbital mucormycosis cases in India in the wake of the second wave of the COVID-19 pandemic. It has been widely suggested that dysglycemia resulting from diabetes which is a common comorbidity in COVID-19 patients, and indiscriminate steroid use has resulted in this surge. We report a series of 13 cases of rhino-orbital mucormycosis in COVID-19 patients admitted to our center between mid-April and early June 2021. The cases showed a male preponderance, two patients had loss of vision, and four of them showed intracranial extension of disease. Twelve patients had received steroids and 12 had preexisting or newly diagnosed diabetes, both steroid use and diabetes being the most common identified risk factors. Considering other possible risk factors, immunosuppressed state, antiviral or ayurvedic (Indian traditional) medications, and oxygen therapy were not associated with a definite risk of mucormycosis, because they were not present uniformly in the patients. We propose that COVID-19 itself, through molecular mechanisms, predisposes to mucormycosis, with other factors such as dysglycemia or steroid use increasing the risk. � 2022 American Society of Tropical Medicine and Hygiene. All rights reserved.
Cross-immunity and trained immunity in explaining variable COVID-19 mortality�Guidance for future pandemics
(John Wiley and Sons Inc, 2021) Chakrabarti, Sasanka; Chakrabarti, Sankha S.; Kaur, Upinder; Agrawal, Bimal K.; Ganguly, Upasana; Jin, Kunlin
[No abstract available]
Determinants of COVID-19 Breakthrough Infections and Severity in ChAdOx1 nCoV-19�Vaccinated Priority Groups
(American Society of Tropical Medicine and Hygiene, 2022) Kaur, Upinder; Bala, Sapna; Ojha, Bisweswar; Pathak, Bhairav Kumar; Joshi, Aditi; Yadav, Ashish Kumar; Singh, Anup; Kansal, Sangeeta; Chakrabarti, Sankha Shubhra
The current analysis is a part of an ongoing observational study that began in February 2021 in the Sir Sunder Lal Hospital (Varanasi, Uttar Pradesh) in northern India and is expected to continue until June 2022. This analysis aimed to delineate the clinical presentation and risk factors of occurrence and severity of COVID-19 in vaccinated individuals. The study enrolled health-care workers and the elderly receiving the COVID-19 vaccine at one of three centers linked to the study hospital. The participants received the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine based on the chimpanzee adenovirus platform (manufactured in India by the Serum Institute of India). The adenovirus codes for the spike (S) protein of SARS-CoV-2. Participants were contacted by phone at pre-decided intervals and questioned about the occurrence of COVID-19, clinical presentation, severity, and persistence of symptoms. A logistic regression analysis was performed to predict the risk factors of occurrence and severity of COVID-19. Of the 1,500 participants included in the analysis, 418 developed COVID-19 (27.9%). Fever was the most common symptom (72%), followed by cough (34%) and rhinitis (26%). Cardiovascular involvement was seen in more than 2% of individuals, and 11% had post-COVID-19 complaints. Regression analysis showed 1.6 times greater odds of contracting the disease in females and in those younger than 40 years, 1.4 times greater odds in individuals who were overweight, and 2.9 times greater odds in those receiving only one dose, compared with respective comparators. Individuals receiving two doses at a gap of ? 30 days had 6.7 times greater odds of infection than those receiving at a > 60-day interval. There was no association between COVID-19 occurrence in the vaccinees and pre-vaccination history of SARS-CoV-2 infection. Males were at a 3.6 times greater risk, and persons with preexisting lung disease�mainly asthma�had a 5.9 times greater risk of experiencing moderate to severe COVID-19 than comparators. While an extended interval between the two vaccine doses seems to be a better strategy, gender differences and an association of asthma phenotypes with COVID-19 need to be explored. Copyright � 2022 The author(s)
Did COVID-19 or COVID-19 Vaccines Influence the Patterns of Dengue in 2021? An Exploratory Analysis of Two Observational Studies from North India
(American Society of Tropical Medicine and Hygiene, 2023) Kaur, Upinder; Jethwani, Parth; Mishra, Shraddha; Dehade, Amol; Yadav, Ashish Kumar; Chakrabarti, Sasanka; Chakrabarti, Sankha Shubhra
Dengue experienced a rise in disease burden in 2021 in specific regions of India. We aimed to explore the risk factors of dengue occurrence and severity in the post-COVID-19 and post-COVID-19 vaccination era and performed an exploratory analysis involving participants from two prior observational studies conducted from February 2021 to April 2022 in a tertiary hospital in North India. Health care workers constituted the majority of the study participants. Individuals were stratified into five groups based on COVID-19 infection and timing of vaccination: COVID-No Vaccine, Vaccine-No COVID (VNC), COVID After Vaccine (CAV), Vaccine After COVID (VAC), and No Vaccine-No COVID (NVNC) groups. The occurrence of laboratory-confirmed dengue and severe forms of dengue were the main outcomes of interest. A total of 1,701 participants (1,520 vaccinated, 181 unvaccinated) were included. Of these, symptomatic dengue occurred in 133 (7.8%) and was �severe� in 42 (31.6%) cases. Individuals with a history of COVID-19 in 2020 had a 2-times-higher odds of developing symptomatic dengue (P 5 0.002). The VAC group had 3.6 (P 5 0.019)-, 2 (P 5 0.002)-, and 1.9 (P 5 0.01)-times-higher odds of developing symptomatic dengue than the NVNC, VNC, and CAV groups, respectively. The severity of dengue was not affected by COVID-19 vaccination but with marginal statistical significance, a 2-times-higher risk of severe dengue was observed with any COVID-19 of the past (P 5 0.08). We conclude that COVID-19 may enhance the risk of developing symptomatic dengue. Future research should explore the predisposition of COVID-19-recovered patients toward other viral illnesses. Individuals receiving COVID-19 vaccines after recovering from COVID-19 particularly seem to be at greater risk of symptomatic dengue and need long-term watchfulness. Possible mechanisms, such as antibody-dependent enhancement or T-cell dysfunction, should be investigated in COVID-19-recovered and vaccinated individuals. Copyright � 2023 The author(s)
Drug Induced Ulceration of Extremities
(Springer Nature, 2023) Kaur, Upinder
Medications are a rare and often ignored cause of limb ulcers. It is presumed that around 1.1% of chronic leg ulcers can be caused by drugs. Limb ulcers can be related to the pharmacological action of drugs or can be the manifestation of drug induced vasculitis or immunological alterations. Early suspicion of drug involvement in the induction of ulcers can result in timely intervention and can prevent considerable morbidity and mortality. Cutaneous ulcers can be observed in complicated cases of drug related immunological conditions such as Stevens-Johnson syndrome (SJS). The aim of the present chapter is to provide a comprehensive review on common drugs implicated in limb ulcers, the possible mechanisms of ulcer development, the phenotypic patterns of drug induced extremity ulcers, their management, and outcomes. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.
Effectiveness of ChAdOx1 nCoV-19 vaccine during the delta (B.1.617.2) variant surge in India
(Elsevier Ltd, 2022) Chakrabarti, Sasanka; Chakrabarti, Sankha Shubhra; Chandan, Gourav; Kaur, Upinder; Agrawal, Bimal Kumar
[No abstract available]
Esketamine: a glimmer of hope in treatment-resistant depression
(Springer Science and Business Media Deutschland GmbH, 2021) Kaur, Upinder; Pathak, Bhairav Kumar; Singh, Amit; Chakrabarti, Sankha Shubhra
The motive of this article is to review the pharmacological and clinical aspects of esketamine (ESK), an NMDA-receptor antagonist approved recently by the FDA for treatment-resistant depression (TRD). PubMed/Medline database was searched using keywords �esketamine� and �depression�, �S-ketamine� and �depression�, and �NMDA antagonist� and �depression�. Individual trials were searched from ClinicalTrials.gov. We included English-language articles evaluating pharmacokinetics and pharmacodynamics of intranasal (IN) esketamine, along with clinical trial data related to its efficacy and safety in patients diagnosed with TRD. Compared to placebo, IN esketamine causes significant and rapid improvement in depression. Dizziness, vertigo, headache, increase in blood pressure are some of its common adverse effects. With the growing number of patients of TRD, additional effective and safe treatment is the need of the hour. Esketamine appears to be an effective therapy when combined with oral antidepressants in patients with TRD. It is of special value due to the rapid onset of its action. Long-term clinical studies are, however, needed to ascertain its safety profile. � 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
Fisetin 8-C-glucoside as entry inhibitor in SARS CoV-2 infection: molecular modelling study
(Taylor and Francis Ltd., 2022) Mishra, Abha; Kaur, Upinder; Singh, Amit
Coronaviruses are RNA viruses that infect varied species including humans. TMPRSS2 is gateway for SARS CoV-2 entry into the host cell. It causes proteolytic activation of spike protein and discharge of the peptide into host cell. The TMPRSS2 inhibition could be one of the approaches to stop the viral entry, therefore, interaction pattern and binding energies for Fisetin and TMPRSS2 have been explored in the present study. TMPRSS2 peptide was used for homology modelling and then for further study. Molecular docking score and MMGBSA Binding energy of Fisetin was better than Nafamostat, a known inhibitor of TMPRSS2. Post docking MM-GBSA free energy for Fisetin and Nafamostat was ?42.78 and ?21.11 kcal/mol, respectively. Fisetin forms H bond with Val 25, His 41, Lys 42, Lys 45, Glu 44, Ser186. Nafamostat formed H bonds with Lys 85, Asp 90, Asp 203. RMSD plots of TMPRSS2, TMPRSS2-Fisetin and TMPRSS2-Nafamostat complex showed stable profile with very small fluctuation during entire simulation of 150 ns. Significant decrease in TMPRSS2-Fisetin and TMPRSS2-Nafamostat complex fluctuation occurred around His 41, Glu 44, Gly 136, Ser 186 in RMSF study. During simulation Fisetin interaction was observed with residues Val 25, His 41, Glu 44, Lys 45, Lys 87, Gly 136, Gln 183, Ser 186 likewise interaction of Nafamostat with Lys 85, Asp 90, Asn 163, Asp 203 and Ser 205. Post simulation MM-GBSA free energy was found to be ?51.87 � 4.3 and ?48.23 � 4.39 kcal/mol for TMPRSS2 with Fisetin and Nafamostat, respectively. Communicated by Ramaswamy H. Sarma. � 2020 Informa UK Limited, trading as Taylor & Francis Group.
Hyper-Eosinophilic Syndrome with Myocarditis after Inactivated SARS-CoV-2 Vaccination-A Case Study
(Bentham Science Publishers, 2023) Tiwari, Ashutosh; Karna, Gaurav; Chakrabarti, Sankha Shubhra; Panda, Prasan Kumar; Kaur, Upinder
Introduction: COVID-19 vaccine-induced serious adverse reactions are rare. Hyper-eosinophilia syndrome with myocarditis has not been reported earlier following BBV152 vaccine administration. Case Presentation: A young man without any co-morbidities presented with persistent periorbital swelling along with itchy swelling over fingers, resting tachycardia, and exertional breathlessness following the first dose of an inactivated SARS-CoV-2 vaccine (BBV152, COVAXIN). On inves-tigation, the patient had elevated blood eosinophils (maximum 21.5% with an absolute eosinophil count of 2767/mm3) and myocarditis (Lake Louise Criteria). He was successfully treated with ster-oids and supportive treatment. Conclusion: This is the first reported case of hyper-eosinophilia syndrome after COVAXIN ad-ministration. Prior history of the allergic disease may be a predisposing factor in this case. Hyper-eosinophilia can present with variable symptoms. In the current case, myocarditis was present with persistent resting tachycardia and dyspnea. Steroid and antiallergic drugs may be successful for the treatment of vaccine-induced hyper-eosinophilia with myocarditis. Increased vigilance is needed for such adverse events. � 2023 Bentham Science Publishers.
Iron Isomaltoside-Induced Anaphylaxis
(Lippincott Williams and Wilkins, 2022) Kaur, Upinder; Singh, Amit; Gambhir, Indrajeet S.; Kashyap, Shubham; Singh, Anup; Chakrabarti, Sankha S.
[No abstract available]
Levosulpiride associated neuroleptic malignant syndrome in an elderly patient: a tale of confusing brand names
(Springer Science and Business Media Deutschland GmbH, 2022) Kaur, Upinder; Acharya, Kumudini; Singh, Amit; Gambhir, Indrajeet Singh; Chakrabarti, Sankha Shubhra
[No abstract available]
Long-Term Safety Analysis of the ChAdOx1-nCoV-19 Corona Virus Vaccine: Results from a Prospective Observational Study in Priority Vaccinated Groups in North India
(Adis, 2023) Kaur, Upinder; Fatima, Zeba; Maheshwari, Kalika; Sahni, Vikas; Dehade, Amol; Kl, Anju; Yadav, Ashish Kumar; Kansal, Sangeeta; Jaisawal, Vaibhav; Chakrabarti, Sankha Shubhra
Introduction: Various vaccines for protection against COVID-19 were provided emergency approval in late 2020 to early 2021. There is a scarcity of long-term safety data for many of these. Objective: The main aim of this study is to provide the one-year safety results of the ChAdOx1-nCoV-19/AZD1222 vaccine and determine the risk factors of adverse events of special interest (AESIs) and persistent AESIs. Methods: This was a prospective observational study conducted from February 2021 to April 2022 in a tertiary hospital in North India and its two associated centers. Health care workers, other frontline workers, and the elderly vaccinated with the ChAdOx1-nCoV-19 vaccine constituted the study population. Individuals were contacted telephonically at pre-decided intervals for one year and health issues of significant concern were recorded. Atypical adverse events developing after a booster dose of the COVID-19 vaccine were assessed. Regression analysis was conducted to determine risk factors of AESI occurrence and determinants of AESIs persisting for at least one month at the time of final telephonic contact. Results: Of 1650 individuals enrolled, 1520 could be assessed at one-year post-vaccination. COVID-19 occurred in 44.1% of participants. Dengue occurred in 8% of participants. The majority of the AESIs belonged to the MedDRA� SOC of musculoskeletal disorders (3.7% of 1520). Arthropathy (knee joint involvement) was the most common individual AESI (1.7%). Endocrinal disorders such as thyroid abnormalities and metabolic disorders such as newly diagnosed diabetes developed in 0.4% and 0.3% of individuals, respectively. Regression analysis showed females, individuals with a pre-vaccination history of COVID-19, diabetes, hypothyroidism, and arthropathy had 1.78-, 1.55-, 1.82-, 2.47- and 3.9-times higher odds of AESI development. Females and individuals with hypothyroidism were at 1.66- and 2.23-times higher risk of persistent AESIs. Individuals receiving the vaccine after COVID-19 were at 2.85- and 1.94 times higher risk of persistent AESIs compared, respectively, to individuals with no history of COVID-19 and individuals developing COVID-19 after the vaccine. Among participants receiving a booster dose of the COVID-19 vaccine (n = 185), 9.7% developed atypical adverse events of which urticaria and new-onset arthropathy were common. Conclusion: Nearly half of the ChAdOx1-nCoV-19 vaccine recipients developed COVID-19 over one year. Vigilance is warranted for AESIs such as musculoskeletal disorders. Females, individuals with hypothyroidism, diabetes, and pre-vaccination history of COVID-19 are at higher risk of adverse events. Vaccines received after natural SARS-CoV-2 infection may increase the risk of persistence of adverse events. Sex and endocrinal differences and timing of the COVID-19 vaccine with respect to natural infection should be explored as determinants of AESIs in the future. Pathogenetic mechanisms of vaccine-related adverse events should be investigated along with comparisons with an unvaccinated arm to delineate the overall safety profile of COVID-19 vaccines. � 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Multi-Target Directed Ligands (MTDLs): Promising Coumarin Hybrids for Alzheimer�s Disease
(Bentham Science Publishers, 2021) Bhatia, Rohit; Chakrabarti, Sankha S.; Kaur, Upinder; Parashar, Gaurav; Banerjee, Anindita; Rawal, Ravindra K.
Alzheimer�s disease (AZD) is an age-associated neurodegenerative disorder and is one of the common health issues around the globe. It is characterized by memory loss and a decline in other cognitive domains, including executive function. The progression of AZD is associated with complex events, and the exact pathogenesis is still unrevealed. Various mechanisms which are thought to be associated with the initiation of AZD include a decreased concentration of acetylcholine (ACh), deposition of amyloid-? (A?) peptide, dyshomeostasis of redox metal ions, and prolonged oxidative stress. Due to the simultaneous progression of diverse pathogenetic pathways, no ideal therapeutic agent has been developed to date. The drugs which are available against AZD provide only symptomatic benefits and do not have disease-modifying activity. Therefore, in search of ideal therapeutic candidates, the concept of molecular hybrids has been under keen investigation for the past few years. Hybrid molecules are able to inhibit or activate or modify the physiology of more than one target simultaneously. Coumarin scaffold have shown the excellent potential of ACh esterase inhibition, MAO-B inhibition, and anti-A? aggregation. In the present review, we have focused on different reported coumarin hybrids as multi-target-directed agents against AZD. These include hybrids of coumarin with carbazole, benzofuran, dithiocarbamate, quinoline, pargyline, tacrine, N-benzyl pyridinium, donepezil, purine, piperidine, morpholine, aminophenol, benzylamino, halophenylalkylamidic, thiazole, thiourea, hydroxypyridinone, triazole, piperazine, chalcone, etc. Along with the therapeutic potentials of these hybrids, important clinical investigations and the structure-activity relationship have also been discussed in this compilation. � 2021 Bentham Science Publishers.

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