Adverse drug reaction reporting in a tertiary care teaching hospital in eastern India: a retrospective study

Background: Adverse drug reactions (ADRs) are one of the prime causes of morbidity and mortality, increase in hospital stay and socioeconomic burden on the patients. Periodic monitoring aids in formulating methods for safe usage of medicines in hospitals. This study was undertaken to study the patterns, assessment of causality, severity, preventability, body systems affected from ADRs received by the Pharmacovigilance cell, Department of Pharmacology between April 2018 to June 2019.Methods: The present study is an observational, retrospective, non-interventional analysis of voluntarily reported ADRs. Demography of patients, causative drugs, reactions, outcome, and severity are recorded. Data were analysed and expressed in numbers, percentages.Results: A total of 180 ADRs were spontaneously reported. Dermatology (42.8%), psychiatry (23.9%) and general medicine (18.3%) are the major departments reporting ADRs in our hospital. 60.6% reports were in males. The body system with maximum reactions is dermatological (51.1%). Drug class most commonly affected is anti-microbials (36.1%). Paracetamol (8.9%) is the most common drug with reactions. Causality assessment stated that 41.7% ADRs are probable and 58.3% were possible. Severity assessment showed 86.7% as mild and 13.3% as moderate. Preventability assessment stated that 93.3% ADRs not preventable, 5.6% probably preventable and 1.1% definitely preventable.Conclusions: The study provides a valuable insight with regards to the pattern of ADRs in our hospital. This will be useful in initiating a reporting culture, increase awareness, reducing under-reporting of ADR in our set up

Adverse cutaneous drug reactions reporting in a tertiary care teaching hospital in Eastern India: a retrospective study

Background: Any unwanted changes to mucous membrane, skin, its appendages and drug eruptions related adverse events are known as adverse cutaneous drug reaction (ACDR). It has 2-5% incidence in developing countries. The current study was undertaken to analyse adverse cutaneous drug reactions spectrum clinically, drugs responsible, assessment of causality, severity, and preventability in our setup.Methods: Current study was an observational, retrospective, non-interventional analysis of voluntarily reported ADRs forms, between April 2018 and January 2020.  All cutaneous ADRs reported within this period were identified. Data obtained were expressed in numbers, percentages.Results: 130 cutaneous ADRs was reported during the period of study. Fixed drug eruptions (30%) was the most common cutaneous reaction. The most common causal drug groups were antimicrobials (58.5%). Amongst antimicrobials, ornidazole (8.5%) was the most common drug. The most common drug in NSAID group was paracetamol (14.6%). The major drug causing ACDRs in our study was Paracetamol (14.6%). Assessment of causality revealed 37.7% were probable and 62.3% were possible reactions. Assessment of severity showed 78.5% as mild and 21.5% as moderate. Assessment of preventability showed that 6.1% probably preventable and 93.9% not preventable.Conclusions: Knowledge of the pattern of cutaneous reactions and the causative drugs guides us in early diagnosis of the condition, better management and associated decrease in morbidity, mortality. In the current study, the most common causal drug group were antimicrobials. The most common morphological pattern and drug causing ACDRs were fixed drug eruptions and paracetamol, respectively

Knowledge, attitude and practice of pharmacovigilance towards adverse drug reactions reporting among health care professionals (nurses) in a tertiary care teaching hospital in Eastern India: an observational study

Background: Nursing staffs spend most time in patient care and are bedside caregivers. To expect voluntary reporting of adverse reactions, it is essential that they possess proper knowledge, right attitude and practice reporting. Therefore, the present study was aimed to assess the Knowledge, Attitude and Practice of Pharmacovigilance towards ADRs reporting.Methods: A prospective, cross sectional, observational, questionnaire-based survey was conducted among nurses in a tertiary care teaching hospital in Eastern India. Questionnaire containing 15 questions was used to assess knowledge, attitude and practice. The questionnaire was administered to 150 nurses. Analysis of data was done using statistical software..Results: The response rate in our study was 86.67%. Nurses have good knowledge of pharmacovigilance and adverse reaction. However, only 10% have reported an adverse reaction in our study. This shows that in spite of having a good knowledge of reporting, nurses have poor attitude, which is reflected by a low reporting rate. Nurses opined that taking patient care is of prime importance than report an adverse reaction. This corroborates the low reporting rate in our set up.Conclusions: Majority of nurses have good knowledge on pharmacovigilance and adverse drug reaction. The concern remains on the low reporting rate. Continuous training programmes, and reminders likely to enhance the voluntary reporting from the nursing staffs

Cell cycle-dependent regulation of the bi-directional overlapping promoter of human BRCA2/ZAR2 genes in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>BRCA2 gene expression is tightly regulated during the cell cycle in human breast cells. The expression of BRCA2 gene is silenced at the G0/G1 phase of cell growth and is de-silenced at the S/G2 phase. While studying the activity of BRCA2 gene promoter in breast cancer cells, we discovered that this promoter has bi-directional activity and the product of the reverse activity (a ZAR1-like protein, we named ZAR2) silences the forward promoter at the G0/G1 phase of the cell. Standard techniques like cell synchronization by serum starvation, flow cytometry, N-terminal or C-terminal FLAG epitope-tagged protein expression, immunofluorescence confocal microscopy, dual luciferase assay for promoter evaluation, and chromatin immunoprecipitation assay were employed during this study.</p> <p>Results</p> <p>Human <it>BRCA2 </it>gene promoter is active in both the forward and the reverse orientations. This promoter is 8-20 fold more active in the reverse orientation than in the forward orientation when the cells are in the non-dividing stage (G0/G1). When the cells are in the dividing state (S/G₂), the forward activity of the promoter is 5-8 folds higher than the reverse activity. The reverse activity transcribes the ZAR2 mRNA with 966 nt coding sequence which codes for a 321 amino acid protein. ZAR2 has two C4 type zinc fingers at the carboxyl terminus. In the G0/G1 growth phase ZAR2 is predominantly located inside the nucleus of the breast cells, binds to the BRCA2 promoter and inhibits the expression of BRCA2. In the dividing cells, ZAR2 is trapped in the cytoplasm.</p> <p>Conclusions</p> <p><it>BRCA2 </it>gene promoter has bi-directional activity, expressing BRCA2 and a novel C4-type zinc finger containing transcription factor ZAR2. Subcellular location of ZAR2 and its expression from the reverse promoter of the BRCA2 gene are stringently regulated in a cell cycle dependent manner. ZAR2 binds to BRCA2/ZAR2 bi-directional promoter <it>in vivo </it>and is responsible, at least in part, for the silencing of BRCA2 gene expression in the G0/G1 phase in human breast cells.</p

piRNAs as Modulators of Disease Pathogenesis

Advances in understanding disease pathogenesis correlates to modifications in gene expression within different tissues and organ systems. In depth knowledge about the dysregulation of gene expression profiles is fundamental to fully uncover mechanisms in disease development and changes in host homeostasis. The body of knowledge surrounding mammalian regulatory elements, specifically regulators of chromatin structure, transcriptional and translational activation, has considerably surged within the past decade. A set of key regulators whose function still needs to be fully elucidated are small non-coding RNAs (sncRNAs). Due to their broad range of unfolding functions in the regulation of gene expression during transcription and translation, sncRNAs are becoming vital to many cellular processes. Within the past decade, a novel class of sncRNAs called PIWI-interacting RNAs (piRNAs) have been implicated in various diseases, and understanding their complete function is of vital importance. Historically, piRNAs have been shown to be indispensable in germline integrity and stem cell development. Accumulating research evidence continue to reveal the many arms of piRNA function. Although piRNA function and biogenesis has been extensively studied in Drosophila, it is thought that they play similar roles in vertebrate species, including humans. Compounding evidence suggests that piRNAs encompass a wider functional range than small interfering RNAs (siRNAs) and microRNAs (miRNAs), which have been studied more in terms of cellular homeostasis and disease. This review aims to summarize contemporary knowledge regarding biogenesis, and homeostatic function of piRNAs and their emerging roles in the development of pathologies related to cardiomyopathies, cancer, and infectious diseases

Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress

<p>Abstract</p> <p>Background</p> <p>Widespread use of chromium (Cr) contaminated fields due to careless and inappropriate management practices of effluent discharge, mostly from industries related to metallurgy, electroplating, production of paints and pigments, tanning, and wood preservation elevates its concentration in surface soil and eventually into rice plants and grains. In spite of many previous studies having been conducted on the effects of chromium stress, the precise molecular mechanisms related to both the effects of chromium phytotoxicity, the defense reactions of plants against chromium exposure as well as translocation and accumulation in rice remain poorly understood.</p> <p>Results</p> <p>Detailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice. To check whether the Cr-specific motifs were indeed significantly over represented in the promoter regions of Cr-responsive genes, occurrence of these motifs in whole genome sequence was carried out. In the background of whole genome, the lift value for these 14 and 13 motifs was significantly high in the test dataset. Though no functional role has been assigned to any of the motifs, but all of these are present as promoter motifs in the Database of orthologus promoters.</p> <p>Conclusion</p> <p>These findings clearly suggest that a complex network of regulatory pathways modulates Cr-response of rice. The integrated matrix of both transcriptome and metabolome data after suitable normalization and initial calculations provided us a visual picture of the correlations between components. Predominance of different motifs in the subsets of genes suggests the involvement of motif-specific transcription modulating proteins in Cr stress response of rice.</p

Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Background Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally. Methods We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available. Findings Globally in 2019, 1.14 billion (95% uncertainty interval 1.13-1.16) individuals were current smokers, who consumed 7.41 trillion (7.11-7.74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27.5% [26. 5-28.5] reduction) and females (37.7% [35.4-39.9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0.99 billion (0.98-1.00) in 1990. Globally in 2019, smoking tobacco use accounted for 7.69 million (7.16-8.20) deaths and 200 million (185-214) disability-adjusted life-years, and was the leading risk factor for death among males (20.2% [19.3-21.1] of male deaths). 6.68 million [86.9%] of 7.69 million deaths attributable to smoking tobacco use were among current smokers. Interpretation In the absence of intervention, the annual toll of 7.69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a dear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Seeking entitlement: a performance ethnography exploring the paradoxes of trauma and testimonial in refugee performance

This dissertation responds to some significant publications on refugee theatre and performance that have been released in the last fifteen years. Consolidating some of the major concerns and debates, the problems confronted have been conceptualized as paradoxes: (1) the paradox of trauma and neo-colonial benevolence in applied theatre and (2) the paradox of testimonial authenticity in the portrayal of refugees in staged performances. The research is an ethnographic case study of three young asylum seekers partaking in a theatre production in Canterbury. The devising process of the theatre project is set alongside the daily activities of the migrants’ lives and unfolding action of their asylum claim. The theatre monologues were featured in a community project on migration to Kent in April 2014. With an overarching objective to bear witness to the project participants, the research questions are as follows (1) how does the language of trauma come to bear on the biographies of individual asylum seekers? (2) how can refugee performance illuminate and respond to the paradox of language, narrative and representation? Using a self-reflexive ethnographic methodology, the researcher writes about her own becoming as a devised theatre practitioner and community volunteer (befriender). The collected data includes the researcher’s journal entries, the participant’s performance pieces and creative pseudo-fictions inspired by the relationships between the researcher and her participants. The study concludes that (1) refugee theatre has a tendency to presume the biases of audiences, thereby perpetuating the paradoxes of trauma and testimonial, (2) the language of trauma can be powerful in the asylum seeking procedure and that (3) migrants rely on performance in everyday life to subvert the forces of control that dictate their situations. The dissertation then provides suggestions for applied theatre interventions scripts involving refugees and witnessing studies

Vacuolar ATPase (V-ATPase) Proton Pump and Its Significance in Human Health

Vacuolar H + -ATPases (V-ATPase), is an ATP-dependent proton transporter that transports protons across intracellular and cellular plasma membranes. V-ATPase is a multi-protein complex, which functions as an ATP-driven proton pump and is involved in maintaining pH homeostasis. The V-ATPase is a housekeeping proton pump and is highly conserved during evolution. The proton-pumping activity of V-ATPases allows acidification of intracellular compartments and influences a diverse range of cellular and biological processes. Thus, V-ATPase aberrant overexpression, mis-localization, and mutations in the genes for subunits are associated with several human diseases. This chapter focuses on a detailed view of V-type ATPase, and how V-ATPase contributes to human health and disease