A retrospective study to evaluate the pattern of spontaneously reported antiretroviral induced adverse drug reactions in a tertiary care hospital

Background: To evaluate the adverse effect profile of spontaneously reported cases of adverse drug reactions due to antiretroviral (ART) drugs in a tertiary care teaching hospital.Methods: A descriptive retrospective study of pattern of ART induced adverse drug reactions (ADRs) spontaneously reported to the Pharmacology department at a tertiary care hospital from January 2011 to December 2016. The details of suspected ADRs including drugs involved, treatment given for ADRs, and the outcome were also documented. These ADRs were analyzed for causality (WHO scale), severity (Hartwig et al. scale), seriousness (ICH E 2A guidelines), preventability (Schumock and Thornton scale) and type based on Edwards and Aronson classification system.Results: Of the 75 cases of ART induced ADRs, reactions were slightly more common in males (52%) and had median age and duration of ART as 36 years and 109 days respectively. Drug induced anemia was the most common presentation followed by cutaneous ADR and zidovudine being the commonest offender. Severity was moderate in 85.3% and causality was probable in 16% and possible in 84% cases. The type reaction was augmented type in 41.3% and not preventable in 76%.Conclusions: Zidovudine is the commonest drug implicated in causing anemia amongst the antiretrovirals. Spontaneous reporting method for antiretroviral pharmacovigilance is insufficient. Targeted spontaneous reporting or cohort event monitoring need to be studied for antiretroviral pharmacovigilance

Evaluation of knowledge, attitude and practice of pharmacovigilance among interns and nursing students in a tertiary care teaching hospital

Background: Even though the role of spontaneous reporting of adverse drug reactions (ADRs) is well established in pharmacovigilance, it is not followed in the practice and a large number of ADRs goes unreported. In our institute, almost all of the ADR reported to the department of pharmacology are through either the faculty members or the residents and very few by the nurses and interns.Methods: The current survey was thus conducted to assess the knowledge, attitude and practice (KAP) of nursing students and interns. It is expected that the results should help us to designs specific activities to improve ADR reporting. The study was a questionnaire based survey to assess the knowledge, attitude and practices (KAP) of the interns (n=74) and nursing students (n=108) regarding ADR reporting and pharmacovigilance in this tertiary care centre.Results: More interns gave correct responses to knowledge based and attitude based questions of pharmacovigilance compared to the nursing students. On the other hand, more nursing students came across ADRs in the patients compared to interns. Even though 93.24% interns responded to have got training on “how to report ADRs”, only 6.76% ever reported ADR to pharmacovigilance centre.Conclusions: Proper training on pharmacovigilance, with easy way for reporting ADRs would be a useful step in improving pharmacovigilance status in nursing students and interns

Knowledge, attitude and practice of pharmacovigilance among medical professionals at a tertiary care hospital in Mumbai, Maharashtra, India

Background: Many adverse drug reactions (ADRs), interactions and specific toxicities are known once drug is exposed to a larger population. Spontaneous reporting adverse events (AEs) are fundamental to a robust pharmacovigilance (PhV). Increasing physician awareness about the pharmacovigilance and ADR reporting can significantly contribute the safety of medicines. Objective of the study was to assess the knowledge, attitude and practices related to PhV among medical professionals at a tertiary care teaching hospital.Methods: Postgraduate students (PGs) and medical teachers at a Medical College and tertiary care hospital were evaluated for their knowledge, attitude and practice of pharmacovigilance with the help of a structured questionnaire. Suggestions for improving the effectiveness of the pharmacovigilance practices were also sought.Results: One-hundred and fifty doctors [91 (60.7%) PGs and 59 (39.3%) medical teachers] participated. Overall, 48.7% were males. 96% believed that PhV is important in medical practice but only 79.3% knew the definition of pharmacovigilance. Only 24.7% were aware of the existing nationwide pharmacovigilance program whereas the international collaborating center was known to 26% of the participants. 96% believed that it is the duty of a treating physician to report an ADR while 36.7% felt that ADR reporting should be the responsibility of a separate team. Surprisingly, 54% felt that financial aid should be provided for ADR reporting. 42.7% have not reported any ADR whilst only 16% have reported more than 10 ADRs in their career. To create an ADR database (79.3%) was the common expectation from the PhV center. 98.7% suggested continued medical education (CME) and trainings to improve the effectiveness of PhV in Indian setting.Conclusions: Regardless of a fair attitude towards PhV, the practice of ADR reporting is poor probably because of lack of sufficient knowledge about PhV. Motivating the physicians through CMEs and trainings so as to improve and strengthen the pharmacovigilance practices is the current need in India

A retrospective study to evaluate the pattern of spontaneously reported antiretroviral induced adverse drug reactions in a tertiary care hospital

Background: To evaluate the adverse effect profile of spontaneously reported cases of adverse drug reactions due to antiretroviral (ART) drugs in a tertiary care teaching hospital.Methods: A descriptive retrospective study of pattern of ART induced adverse drug reactions (ADRs) spontaneously reported to the Pharmacology department at a tertiary care hospital from January 2011 to December 2016. The details of suspected ADRs including drugs involved, treatment given for ADRs, and the outcome were also documented. These ADRs were analyzed for causality (WHO scale), severity (Hartwig et al. scale), seriousness (ICH E 2A guidelines), preventability (Schumock and Thornton scale) and type based on Edwards and Aronson classification system.Results: Of the 75 cases of ART induced ADRs, reactions were slightly more common in males (52%) and had median age and duration of ART as 36 years and 109 days respectively. Drug induced anemia was the most common presentation followed by cutaneous ADR and zidovudine being the commonest offender. Severity was moderate in 85.3% and causality was probable in 16% and possible in 84% cases. The type reaction was augmented type in 41.3% and not preventable in 76%.Conclusions: Zidovudine is the commonest drug implicated in causing anemia amongst the antiretrovirals. Spontaneous reporting method for antiretroviral pharmacovigilance is insufficient. Targeted spontaneous reporting or cohort event monitoring need to be studied for antiretroviral pharmacovigilance

Effects of substrate binding site residue substitutions of xynA from Bacillus amyloliquefaciens on substrate specificity

Abstract Background The aromatic residues of xylanase enzyme, W187, Y124, W144, Y128 and W63 of substrate binding pocket from Bacillus amyloliquefaciens were investigated for their role in substrate binding by homology modelling and sequence analysis. These residues are highly conserved and play an important role in substrate binding through steric hindrance. The substitution of these residues with alanine allows the enzyme to accommodate nonspecific substrates. Results Wild type and mutated genes were cloned and overexpressed in BL21. Optimum pH and temperature of rBAxn exhibited pH 9.0 and 50 °C respectively and it was stable up to 215 h. Along with the physical properties of rBAxn, kinetic parameters (K m 19.34 ± 0.72 mg/ml; k cat 6449.12 ± 155.37 min− 1 and k cat /K m 333.83 ± 6.78 ml min− 1 mg− 1) were also compared with engineered enzymes. Out of five mutations, W63A, Y128A and W144A lost almost 90% activity and Y124A and W187A retained almost 40–45% xylanase activity. Conclusions The site-specific single mutation, led to alteration in substrate specificity from xylan to CMC while in case of double mutant the substrate specificity was altered from xylan to CMC, FP and avicel, indicating the role of aromatic residues on substrate binding, catalytic process and overall catalytic efficiency

Additional file 1: of Effects of substrate binding site residue substitutions of xynA from Bacillus amyloliquefaciens on substrate specificity

Table S1. Primer sequences used for the fragment generation. Figure S1. BLAST analysis and sequence alignment of xylanase with available online database using UniprotKb alignment tool. Red color shows reported active site residues and yellow color displays the location of active residues present in the XYNA of Bacillus amyloliquefaciens. Orange color indicates conserved aromatic residues across the family of xylanase enzymes. The black color boxes display the selected aromatic amino acid residues for single mutation in XYNA of Bacillus amyloliquefaciens. (DOCX 1540 kb