Background: Psychotropic medications extend corrected QT (QTc) period in the electrocardiogram (ECG). Psychiatric patients exposed to ⩾1 psychotropic medication(s) represent a group with marked probability of drug-activated QTc-prolongation. Prolonged QTc interval in elderly patients (age > 60 years) is connected to greater risk of all-cause and coronary heart disease deaths. This study aimed at investigating pattern of utilization of QTc-interval protracting medications, QT-extending drug interactions, and prevalence of QTc-interval extending hazard factors in elderly patients. Methods: This was a cross-sectional, prospective study at the Psychiatry OPD at All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand, India from 1 October 2017 to 30 August 2019 employing the pertinent prescriptions. Results: A total of 832 elderly patients (age 60 years or more) visiting the Psychiatry OPD during the aforementioned study duration were investigated. About 420 (50.5%) patients were males while 412 (49.5%) were females. Of the 832 patients, 588 (70.7%) were using interacting agents with capacity to produce TdP. Almost 1152 interacting torsadogenic medication pairs were unraveled. As per AzCERT/CredibleMeds Classification, 1016 (48.8%), 724 (34.8%), and 248 (12%) agents with potential to interact were identified with ‘known’, ‘possible’, and ‘conditional risk of TdP’, respectively. The common interacting medications belonged to antidepressant (288), proton pump inhibitor (364), antipsychotic (340), antinausea (184), antimicrobial (156), and H2 receptor antagonist (60) therapeutic categories. The all-inclusive frequency of potentially inappropriate psychotropic (PIP) agents administered was 62% (1343/2166) with Beers Criteria 2019, and 46% (997/2166) with STOPP Criteria 2015. Conclusion: Many geriatric patients were administered drugs and drug combinations with heightened proclivity toward QT-interval prolongation. Furthermore, reliable evidence-based online drug knowledge resources, such as AzCERT/CredibleMeds Drug Lists, Medscape Drug Interactions Checker, Epocrates Online Interaction Check, and Drugs.com Drug Interactions Checker, can facilitate clinical professionals in selecting drugs for psychiatric patients. A wise choice of medications is imperative to preclude serious adverse sequelae. Therefore, we need to exigently embrace precautionary safety means, be vigilant, and forestall QT-extension and TdP in clinical environments.
Nucleotide-binding oligomerization domain NOD-like receptors (NLRs) are conserved cytosolic pattern recognition receptors (PRRs) that track the intracellular milieu for the existence of infection, disease-causing microbes, as well as metabolic distresses. The NLRP3 inflammasome agglomerates are consequent to sensing a wide spectrum of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Certain members of the NLR family have been documented to lump into multimolecular conglomerates called inflammasomes, which are inherently linked to stimulation of the cysteine protease caspase-1. Following activation, caspase-1 severs the proinflammatory cytokines interleukin (IL)-1β and IL-18 to their biologically active forms, with consequent commencement of caspase-1-associated pyroptosis. This type of cell death by pyroptosis epitomizes a leading pathway of inflammation. Accumulating scientific documentation has recorded overstimulation of NLRP3 (NOD-like receptor protein 3) inflammasome involvement in a wide array of inflammatory conditions. IL-1β is an archetypic inflammatory cytokine implicated in multiple types of inflammatory maladies. Approaches to impede IL-1β’s actions are possible, and their therapeutic effects have been clinically demonstrated; nevertheless, such strategies are associated with certain constraints. For instance, treatments that focus on systemically negating IL-1β (i.e., anakinra, rilonacept, and canakinumab) have been reported to result in an escalated peril of infections. Therefore, given the therapeutic promise of an NLRP3 inhibitor, the concerted escalated venture of the scientific sorority in the advancement of small molecules focusing on direct NLRP3 inflammasome inhibition is quite predictable.
COVID-19 has emerged as a global pandemic. There is currently a spurt of clinical research to generate evidence to treat this novel disease. The aim of the current study is to characterise the pharmacotherapeutic intervention-related clinical trials registered in India. COVID-19 clinical trials registered in India were analysed from data retrieved from Clinical Trial Registry-India, ClinicalTrials.gov and International Clinical Trial Registry Platform. Parameters such as study design, sample size, pharmacotherapeutic interventions and primary outcomes were evaluated. A total of 267 studies were screened among which 103 clinical trials were assessed for descriptive analysis. Majority of registered trials (55.3%) were in Indian System of Medicine followed by antimalarials such as hydroxychloroquine/chloroquine (10.5%) and plasma therapy (7.1%). Most commonly used study design was randomised parallel group in 63%. Open-label study was seen in 47.5%. Primary outcome was improvement of clinical symptoms in 46.6% followed by rate and time of viral load reduction in 18.2%. Maharashtra (n = 35) followed by Delhi (n = 29) had the maximum number of registered trial sites. The study gives broad perspective on the current trend of clinical trials on COVID-19 being conducted in India. The outcomes of these trials will lead to generation of valuable data for evidence-based treatment of COVID-19.
In 2021, the US Food and Drug Administration approved 50 novel drugs. Twenty three of the 50 (46%) drugs were categorized as orphan drug, and 9 of the 50 (18%) were approved under accelerated approval. This review includes a summary of the novel drugs approved by the US Food and Drug Administration in 2021
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