A pattern of serious adverse drug reactions reported in a tertiary care hospital, Rangaraya Medical College, Kakinada, Andhra Pradesh

Background: Serious adverse drug reactions (ADRs) constitute a major limitation in clinical development of a drug thus necessitating close monitoring. Studies regarding the pattern of serious ADRs are limited in southern India. The present study was conducted in tertiary care hospital in Andhra Pradesh with an objective to evaluate the pattern of severe cutaneous and non-cutaneous ADRs in our hospital and to assess the causality, severity, and preventability of these reactions.Methods: A retrospective observational study was conducted over two years, from January 2016 till January 2018 in our ADR monitoring center. The pattern of serious adverse drug reactions, the nature of ADR, suspected drug, the outcome and preventability were analyzed using Modified Hartwig and Siegel scale, and modified Schumock and Thorton scale.Results: Out of 734 ADRs reported, 42 were serious, while 692 were non-serious. Out of 42, 22 were dermatological in origin while the others were acute kidney injury, acute psychosis, febrile neutropenia, gynecomastia, and lipodystrophy. According to WHO causality assessment scale, 27 were probable while 15 were possible. The majority were reported in the age group of 16 to 65 years with female (34) preponderance. The most common drug category responsible was antimicrobials, followed by antiretrovirals, anti-epileptics, and analgesics.Conclusions: Antimicrobial, anti-epileptics, and analgesics contributed to serious ADRs. Although non-cutaneous ADRs did not result in hospitalization, they caused social inhibition and mental stress in the patient

Evaluation of safety and efficacy of intravenous iron sucrose therapy for moderate anaemia in antenatal women

Background: Prevalence of iron deficiency anaemia is high in developing countries like India. Treatment of iron deficiency anaemia in pregnancy is very important to bring down maternal mortality rate as blood loss during delivery can lead to death of the patient. The aim and objective of our study is to evaluate the efficacy and safety of intravenous iron sucrose infusions in antenatal women admitted in hospital suffering from moderate iron deficiency anaemia. Special emphasis was given to observe adverse drug effects.Methods: This was a prospective observational study conducted in Obstetrics and Gynaecology department, Government General Hospital, Rangaraya Medical College, Kakinada, Andhra Pradesh. Study period was two months and study population included antenatal women with gestational age less than 37 weeks with moderate iron deficiency anaemia. Peripheral smear was examined for microcytic hypochromic anaemia and they were treated with intravenous infusion of iron sucrose. Haemoglobin levels were checked before and 5 weeks after iron infusions. Monitoring was done for adverse reactions.Results: Out of 322 admissions, 95% were found to be anaemic. 72 patients were suffering from moderate anaemia from which 25 have been included and treated with intravenous iron sucrose infusions. They were observed for efficacy and safety parameters. Two minor adverse events were reported (fever with chills and angioedema of lips) and they were excluded from study. Mean haemoglobin concentration was found to be raised from 7.08±0.73 (SD) to 11.33±0.48 (SD) within 5 weeks for 23 patients.Conclusions: Iron sucrose infusion is safe and effective for anaemia in pregnancy

Quercetin activates vitamin D receptor and ameliorates breast cancer induced hepatic inflammation and fibrosis

AimsTo explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).Main methodsWe used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR.Key findingsIn EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin.SignificanceDietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR

Antixenosis and antibiosis mechanisms of resistance to pod borer, Helicoverpa armigera in wild relatives of chickpea, Cicer arietinum

The noctuid pod borer, Helicoverpa armigera is one of the most damaging pests of chickpea, Cicer arietinum. The levels of resistance to H. armigera in the cultivated chickpea are low to moderate, but the wild relatives of chickpea have exhibited high levels of resistance to this pest. To develop insect-resistant cultivars with durable resistance, it is important to understand the contribution of different components of resistance, and therefore, we studied antixenosis and antibiosis mechanisms of resistance to H. armigera in a diverse array of wild relatives of chickpea. The genotypes IG 70012, PI 599046, IG 70022, PI 599066, IG 70006, IG 70018 (C. bijugum), ICC 506EB, ICCL 86111 (cultivated chickpea), IG 72933, IG 72953 (C. reticulatum), IG 69979 (C. cuneatum) and IG 599076 (C. chrossanicum) exhibited non preference for oviposition by the females of H. armigera under multi-choice, dual-choice and no-choice cage conditions. Based on detached leaf assay, the genotypes IG 70012, IG 70022, IG 70018, IG 70006, PI 599046, PI 599066 (C. bijugum), IG 69979 (C. cuneatum), PI 568217, PI 599077 (C. judaicum) and ICCW 17148 (C. microphyllum) suffered significantly lower leaf damage, and lower larval weights indicating high levels of antibiosis than on the cultivated chickpea. Glandular and non-glandular trichomes showed negative correlation with oviposition, while the glandular trichomes showed a significant and negative correlation with leaf damage rating. Density of non-glandular trichomes was negatively correlated with larval survival. High performance liquid chromatography (HPLC) fingerprints of leaf surface exudates showed a negative correlation of oxalic acid with oviposition, but positive correlation with malic acid. Both oxalic acid and malic acid showed a significant negative correlation with larval survival. The wild relatives exhibiting low preference for oviposition and high levels of antibiosis can be used as sources of resistance to increase the levels and diversify the basis of resistance to H. armigera in cultivated chickpea

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Peer reviewe