An observational study on dapagliflozin as an add-on therapy in type-2 diabetes mellitus patients in a tertiary care teaching hospital

Background: Diabetes mellitus is one of the prevalent morbid conditions all over the world and no exception for India. Day by day, increase in its prevalence is attributed to lifestyle derangements. To treat this condition many drugs and treatment modalities are developed. Dapagliflozin is an oral antidiabetic drug which acts by sodium-glucose cotransport-2 (SGLT-2) inhibition. Its effectiveness seen in type-2 diabetes mellitus makes it an option for Add-On therapy. Methods: This study is a retrospective observational study conducted at tertiary care hospital, GGH, Kurnool. The study proposal has been reviewed and approved by institutional ethics committee. All adult diabetic patients who were prescribed Dapagliflozin during the period of January 2021 to February 2022, total 45 were included in the study. FBG, HbA1c collected through hospital records from General Medicine and Endocrinology. Patients who stopped drug before 3 months period were excluded. Results: Administration of dapagliflozin as an add-on therapy was found 26.63% decrease in base line mean FBG 184 mg/dl to 135 mg/dl after 3mnoths which is significant (p=0.001). Mean HbA1c significantly reduced by 0.96 percentage point after 3 months (p=0.001). Dapagliflozin effectively reduced the FBG and HbA1c when used in combination with other OHAs or insulin within 3 months. Conclusions: Dapagliflozin as an add-on therapy significantly reduced the HbA1c level and fasting blood glucose of Type-2DM patients, in a 3-month treatment period. Due to the frequency of Genitourinary tract infections, caution is indicated while treating the patients

Taxanes induced hypersensitivity reactions in cancer chemotherapy patients reported at adverse drug reaction monitoring centre at a tertiary care hospital

Background: Cancer chemotherapy involves highly complex regimens using antineoplastic agents like taxanes (paclitaxel, docetaxel) etc. Taxanes cause hypersensitivity reactions (HSRs) like redness, rashes, dyspnoea, severe anaphylaxis and death. In this study, adverse drug reactions (ADRs) associated with taxanes are described & analysed on their severity and preventability. The present study aims to analyse and determine the prevalence of ADRs, especially HSRs in patients treated with taxanes.Methods: After getting IEC approval, the present study is done retrospectively by assessing the HSRs in suspected ADR reporting forms from December 2019 to February 2022 in ADR monitoring centre (AMC) in the Department of Pharmacology at Kurnool Medical College, Kurnool. Descriptive statistics used to analyse patient demography, frequency, various carcinomas under treatment & organ involved, causality assessment using WHO-UMC Scale and Naranjo's Algorithm, severity assessment using modified Hartwig & Siegel’s scale and preventability by modified Schumock & Thornton scale.Results: A total of 258 ADRs were recorded, of which 30 cases reported HSRs with taxanes-paclitaxel (22) and docetaxel (8). The most commonly occurred HSR is shortness of breath. Naranjo’s algorithm showed 52.5% possible (score 1-4) HSRs. WHO-UMC causality assessment scale showed 56.4% as probable HSRs. Modified Hartwig & Siegel severity scale showed 46.6% moderate (level 3). Modified Schumock and Thornton scale showed 76.9% as not preventable.Conclusions: Chemotherapy-related ADRs among cancer patients urges the oncologists to be actively involved in ADR reporting, in the need of the hour in order to mitigate, avoid their occurrence and reducing morbidity and mortality, when practiced with diligence

Evaluation of knowledge, attitude and practice towards drug-drug interactions among postgraduates in tertiary care hospital, Kurnool

Background: Drug-drug interactions (DDIs) are changes in a drug’s effects due to concurrent use of another drug. Clinically significant interactions lead to undesired adverse effects, therapeutic failure, toxicity or may even cause death of the patients. The Aim is to evaluate the Knowledge, Attitude and Practice of Postgraduates regarding DDIs and implementation of educational program may enhance patient’s safety.Methods: A cross-sectional study was conducted among postgraduates in all clinical departments of Government general hospital, Kurnool in the month of October 2021. Pre-validated questionnaire was used to assess the KAP. It contains demographic data, knowledge and practice questions related to DDIs and attitude towards the preferable sources of drug interaction information. Data analysis was done by using SPSS version 26.Results: Out of 220 questionnaires distributed, 126 postgraduates submitted with complete answers(n=126). Overall response rate is 57%. By using the Bloom’s cut-off points, most of the respondents (43.5%) had low level of knowledge towards DDIs. Even respondents with high knowledge level (19%) are not practicing the drug interaction screening during the admission of patients. Majority of PGs with low level knowledge agreed to ask doctors than pharmacist about DDIs and prefer to search for DDIs using reference book than online mode as the source of drug information.Conclusions: In my study, most of the respondents had insufficient knowledge to prevent life threatening DDI’s. So, there is a need to increase medical educational program regarding the importance of screening and assessing of DDI’s before prescribing medicines

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

PTC&amp;B Construction of Genetic Map of Jute (Corchorus olitorius L.) Based on RAPD Markers

The first and preliminary genetic linkage map of the jute genome was constructed with RAPD markers using two parents (Variety O-9897 and Accession No. 1805) and their F2 populations. Linkage analysis at a LOD (Log of odds base 10) score of 3.0 and a maximum distance 50 cM revealed 18 linkage groups. Among the 18 linkage groups, 15 contained single locus and the remaining three groups 16, 17 and 18 contained 2, 11 and 12 loci, respectively. The three multi locus linkage groups varying in length from 15.9- 241.7 cM, snapped a total length of 463.7 cM with an average marker density of 19.6 cM between adjacent markers. The basic chromosome number of Corchorus spp. is seven (2n = 14), so in saturated map, seven linkage groups should have been obtained to represent the genome. But for linkage group analysis, the effort was very limited and the total number of loci (40) was also low

Mutagenicity and Acute Oral Toxicity Test for Herbal Poultry Feed Supplements

Herbal products are being used and trusted globally for thousands of years for their health benefits and limited side effects. Globally, a general belief amongst the consumers is that herbal supplements are always safe because they are “natural.” But later, research reveals that they may not be safe. This raises concern on their safety and implications for their use as feed supplement or medicine. Toxicity testing can reveal some of the risks that may be associated with use of herbs, therefore avoiding potential harmful effects. The present study was designed to investigate five poultry feed supplements (PFS), EGMAX® (to revitalize ovarian activity), FEED-X™ (feed efficiency enhancer), KOLIN PLUS™ (natural replacer of synthetic choline chloride), PHYTOCEE® (natural defence enhancer), and STODI® (to prevent and control loose droppings), for their possible mutagenicity and toxicity. Bacterial reverse mutation (BRMT) and acute oral toxicity tests were employed to assess the PFS for their possible mutagenicity and toxicity. Results indicated that the PFS were devoid of mutagenic effects in BRMT and showed higher safety profile in rodent acute oral toxicity test