Management of insomnia: current trends

Insomnia is one of the most commonly occurring sleep disorders worldwide.1 With increased prevalence of insomnia the demand of the people seeking pharmacological treatment for this disease is continuously increasing. Numerous options are currently available for its treatment and with our increased understanding of the neurophysiological factors involved in the insomnia continuous research is being conducted to seek newer pharmacological treatments. Recent advancement in treatment of insomnia is the introduction of non-benzodiazepine hypnotic medications such as zaleplon, zolpidem, and eszopiclone. Ramelteon, a melatonin agonist, is also helpful for sleep initiation difficulties. Tri-cyclic antidepressants have long been used for insomnia but use has been limited by unwanted anticholinergic side-effects. A hypocretin/orexin antagonist MK-4035 is presently in clinical trials. Serotonin antagonists and inverse agonists are being investigated for their usefulness in insomnia; newer research examining other mechanisms of action suggest that agents which modulate the histaminergic, serotonergic, melontonergic, and hypocretin/ orexin and perhaps gamma-aminobutyric acid B systems could play a promising role in management of insomnia

Effect of calcium channel blockers on the serum levels of thyroid hormone

Background: The effect of the calcium channel blockers on the cardiovascular system is implemented judiciously in different conditions related to cardiovascular system such as angina pectoris, hypertension, and in cardiac arrhythmias but the aspect that deals with the impact of blockade of calcium channels in other systems like endocrine system remains eclipsed. These effects generally go unnoticed and the present study was formulated to elucidate the serum T3, T4, TSH levels after administration of calcium channel blockers and to observe the resultant side effect on the endocrine glands, if any by this commonly used group of drugs.Methods: The study was conducted on male albino rabbits, they were divided in three groups of ten each and each group received one of the calcium channel blockers- Verapamil, Diltiazem and Nifedipine for three months. At the end of each month the serum T3, T4, TSH levels were evaluated by chemiluminisence.Results:It was found that on continuous daily administration of calcium channel blockers there was a gradual fall in levels of T3 and T4 with rise in TSH levels in comparison to the control value taken before initiating the drug therapy.Conclusion: These findings could have potential clinical implications and this study proposes the importance of blood thyroid hormone level follow up in the long-term calcium channel blocker therapy.

PHARMACOVIGILANCE IN THE ERA OF COVID-19: A CONCISE REVIEW OF THE CURRENT SCENARIO, IMPLICATIONS, AND CHALLENGES

The pandemic of Coronavirus Disease 2019 (COVID-19) has now affected the entire globe which was first surfaced in China in December 2019. In absence of effective therapy to manage COVID-19, repurposed therapies were being used to manage the condition. In view of an urgent need for definitive therapy, multiple repurposed drugs, and investigational drug candidates are being tried in clinical trials which may lead to the emergence of unknown short term and long term adverse drug reactions (ADRs), and hence it is crucial to assess the safety of the tried therapeutic interventions. The lag in the pharmacovigilance activities in the midst of this pandemic fosters under-reporting of ADRs. Difficulty in causality assessment due to factors like wide variations in clinical presentation, concomitant use of multiple drugs, associated comorbidities, drug-drug and drug-disease interaction which forestalls the appropriate causality assessment. Hydroxychloroquine, a repurposed antimalarial drug has been a part of hue and cry at present because of its in-question safety in patients with cardiac disorders. National and International Drug monitoring centers have stressed upon reporting of ADRs and to boost up the process and come up with various recommendations. We can overcome these issues by working cohesively, motivating HCPs and patients to report ADRs electronically, and by setting up dedicated pharmacovigilance rapid response team to tackle the issues at the earliest

Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits

The assigned work was aimed to examine the capability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regression of the atherosclerotic plaque. The chemical fingerprinting of the test extract was assessed by LC-MS/MS. Consequently, the analyses of in-vitro, in-vivo, and in-silico were executed by using the standard protocols. The in-vitro assessment of the test extract revealed 74.1% inhibition of HMG-CoA reductase. In-vivo assessments of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (P≤0.001) amelioration in the biomarker indices of the dyslipidaemia i.e., atherogenic index, Castelli risk index(I&II), atherogenic coefficient along with lipid profile. Subsequently, significant reductions were observed in the atherosclerotic plaque and antioxidant levels. The in-silico study of molecular docking shown interactions capabilities of the leading phytoconstituents of the test extract i.e., eicosanoic acid, linoleic acid, and flavan-3-ol with target protein of HMG-CoA reductase. The values of RSMF and potential energy of top docked complexes were show significant interactions. Accordingly, the free energy of solvation, interaction angle, radius of gyration and SASA were shown significant stabilities of top docked complex. The cumulative data of results indicate phytoconstituents of an aqueous seed extract of Acacia senegal have capabilities to inhibit the HMG-CoA reductase and improve the levels of antioxidants

Tocilizumab in COVID-19: a study of adverse drug events reported in the WHO database

leading to pneumonitis with a poor prognosis. Tocilizumab, a type of humanized monoclonal antibody antagonizing interleukin-6 receptors, is currently utilized to treat COVID-19. The present study reviews tocilizumab adverse drug events (ADEs) reported in the World Health Organization (WHO) pharmacovigilance database. Research design and methods: All suspected ADEs associated with tocilizumab between April to August 2020 were analyzed based on COVID-19 patients’ demographic and clinical variables, and severity of involvement of organ system. Results: A total of 1005 ADEs were reported among 513 recipients. The majority of the ADEs (46.26%) were reported from 18–64 years, were males and reported spontaneously. Around 80%, 20%, and 64% were serious, fatal, and administered intravenously, respectively. ‘Injury, Poisoning, and Procedural Complications’ remain as highest (35%) among categorized ADEs. Neutropenia, hypofibrinogenemia were common hematological ADEs. The above 64 years was found to have significantly lower odds than of below 45 years. In comparison, those in the European Region have substantially higher odds compared to the Region of Americas. Conclusion: Neutropenia, superinfections, reactivation of latent infections, hepatitis, and cardiac abnormalities were common ADEs observed that necessitate proper monitoring and reporting

Tocilizumab in COVID-19: a study of adverse drug events reported in the WHO database

leading to pneumonitis with a poor prognosis. Tocilizumab, a type of humanized monoclonal antibody antagonizing interleukin-6 receptors, is currently utilized to treat COVID-19. The present study reviews tocilizumab adverse drug events (ADEs) reported in the World Health Organization (WHO) pharmacovigilance database. Research design and methods: All suspected ADEs associated with tocilizumab between April to August 2020 were analyzed based on COVID-19 patients’ demographic and clinical variables, and severity of involvement of organ system. Results: A total of 1005 ADEs were reported among 513 recipients. The majority of the ADEs (46.26%) were reported from 18–64 years, were males and reported spontaneously. Around 80%, 20%, and 64% were serious, fatal, and administered intravenously, respectively. ‘Injury, Poisoning, and Procedural Complications’ remain as highest (35%) among categorized ADEs. Neutropenia, hypofibrinogenemia were common hematological ADEs. The above 64 years was found to have significantly lower odds than of below 45 years. In comparison, those in the European Region have substantially higher odds compared to the Region of Americas. Conclusion: Neutropenia, superinfections, reactivation of latent infections, hepatitis, and cardiac abnormalities were common ADEs observed that necessitate proper monitoring and reporting

Sample Size Calculation in Medical Research: A Primer

Quality of research is determined by many factors and one such climacteric factor is sample size. Inability to use correct sample size in study might lead to fallacious results in the form of rejection of true findings or approval of false results. Too large sample size is wastage of resources and use of too small sample size might fail to answer the research question or provide imprecise results and may question the validity of study. Despite being such a paramount aspect of research, the knowledge about sample size calculation is sparse among researchers. Why is it important to calculate sample size; when to calculate it; how to calculate it and what details about sample size calculation should be reported in research protocols or articles; are the lesser known basics to majority of researchers. The present review is directed to address these aforementioned fundamentals about sample size. Sample size should be calculated during the initial phase of planning of study. Several components are required for sample size calculation such as effect size, type-1 error, type-2 error, and variance. Researchers must be aware that there are different formulas for calculating sample size for different types of study designs. The researcher must include details about sample size calculation in the methodology section, so that it can be justified and it also adds to the transparency of the study. The literature about calculation of sample size for different study designs is scattered over many textbooks and journals. Scrupulous literature search was conducted to find the passable information for this review. This paper presents the sample size calculation formulas in a single review in a simplified manner with relevant examples, so that researchers may adequately use them in their research

Frequency of OXA-Type Carbapenemases among Carbapenem-Resistant <i>Acinetobacter baumannii</i> in Clinical Isolates from Adult Intensive Care Unit in India

Purpose Acinetobacter baumannii is a highly virulent bacteria in modern health care, with a high ability to acquire antimicrobial resistance. Carbapenemases production appears to be the most common mechanism involved in drug resistance to carbapenem. As the prevalence of carbapenem-resistant A. baumannii was high in intensive care unit (ICU) patients, this study was designed to find the frequency of oxacillinases (OXA) genes including OXA-23, OXA-24, OXA-51, and OXA-58