A STUDY OF MEDICATION ERRORS IN GENERAL MEDICINE WARDS OF THE SOUTH INDIAN TERTIARY CARE HOSPITAL

ABSTRACTObjective: To identify and evaluate medication errors, opportunities like medication documentation errors and possible drug-drug interactions by aclinical pharmacist, in general, medicine wards of the South-Indian tertiary care hospital.Methods: A study was conducted for a period of 6-month. The data were collected by chart review method from the inpatient records from the dayof admission to the day of discharge. If medication error or any opportunity to cause error was observed, it was documented and clinical pharmacistinterventions were done. The parameters, such as medication error rate, types of errors, opportunities of errors, and outcome of errors, wereevaluated.Results: A total of 32 medication errors were reported in 497 patients and the medication error rate was 6.4%. Administration errors (28; 87.5%)were found to be higher than prescription errors (4; 12.5%). Omission error was the most common (12; 42.9%) administration error. Factors whichincrease the risk of medication errors such as medication documentation errors were found in 316 (63.6%) medication orders and 203 (40.8%) had574 possible drug-drug interactions of which the majority (65.2%) of the interactions were of moderate severity. The outcome of error was found tobe error, no harm category for the majority (90.6%) of errors. 32 pharmacist interventions were done and 29 (90.6%) were accepted by health-careprofessionals.Conclusion: A medication error reporting is a new and evolving concept in Indian hospitals. This study highlights the role of a clinical pharmacist indetection, evaluation, and prevention of medication errors in an Indian hospital.Keywords: Medication error, Hospital, Medication error outcome, Clinical pharmacists' intervention, Documentation errors

Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in familial pancreatic cancer.

We sequenced 11 germline exomes from five families with familial pancreatic cancer (FPC). One proband had a germline nonsense variant in ATM with somatic loss of the variant allele. Another proband had a nonsense variant in PALB2 with somatic loss of the variant allele. Both variants were absent in a relative with FPC. These findings question the causal mechanisms of ATM and PALB2 in these families and highlight challenges in identifying the causes of familial cancer syndromes using exome sequencing

GAD1 Upregulation Programs Aggressive Features of Cancer Cell Metabolism in the Brain Metastatic Microenvironment

The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here, we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway. In cell-based culture and brain metastasis models, we found that downregulation of the DNA methyltransferase DNMT1 induced by the brain microenvironment-derived clusterin resulted in decreased GAD1 promoter methylation and subsequent upregulation of GAD1 expression in brain metastatic tumor cells. In a system to dynamically visualize cellular metabolic responses mediated by GAD1, we monitored the cytosolic NADH:NAD+ equilibrium in tumor cells. Reducing GAD1 in metastatic cells by primary glia cell coculture abolished the capacity of metastatic cells to utilize extracellular glutamine, leading to cytosolic accumulation of NADH and increased oxidative status. Similarly, genetic or pharmacologic disruption of the GABA metabolic pathway decreased the incidence of brain metastasis in vivo Taken together, our results show how epigenetic changes in GAD1 expression alter local glutamate metabolism in the brain metastatic microenvironment, contributing to a metabolic adaption that facilitates metastasis outgrowth in that setting

Paricle identification at VAMOS++ with machine learning techniques

Multi-nucleon transfer reaction between 136Xe beam and 198Pt target was performed using the VAMOS++ spectrometer at GANIL to study the structure of n-rich nuclei around N=126. Unambiguous charge state identification was obtained by combining two supervised machine learning methods, deep neural network (DNN) and positional correction using a gradient-boosting decision tree (GBDT). The new method reduced the complexity of the kinetic energy calibration and outperformed the conventional method improving the charge state resolution by 8%

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Effectiveness and Safety of Heparinized Saline versus Normal Saline in Maintaining Patency of Peripheral Intravenous Locks in Neonates at a Tertiary Care Hospital

Introduction: Heparinized saline is usually used as a regular flush solution to prevent occlusion of peripheral intravenous locks in neonates but the risks associated with the use of heparin cannot be ignored in these patients. Aim: To assess and compare the efficacy and safety of Heparinized Saline (HS) and Normal Saline (NS) flush solution in neonates. Materials and Methods: A prospective study was conducted for a period of 12 months using 1 unit/ml HS and NS 0.9% solution. The mean number of catheters removed due to nonelective reasons was calculated to evaluate the effectiveness of flushing solutions. To evaluate the safety, the reason for catheter removal was noted and platelet nadir was used to assess the thrombocytopenia. Poisson regression, Pearson Chi-square test and stratified analysis were conducted. Results: Data were analysed from 100 neonates. We found no significant difference between HS and NS flushes in neonates in maintaining the patency of 24 gauge peripheral intravenous locks {rate ratio= 1.12, p-value =0.584}. Gestational age, body weight and site of insertion did not significantly affect the patency. The reasons for removal of catheter were similar in both the groups and majority were due to non-elective reasons. HS group reported more cases of thrombocytopenia that was attributed to sepsis. Conclusion: Standard NS can be considered as an alternative flush in neonates as both the solutions were found to be equally efficacious and safe in our patient group. Factors like gestational age, body weight and site of insertion did not significantly affect the patency

Exome sequencing identifies nonsegregating nonsense ATM and PALB2variants in familial pancreatic cancer

Abstract We sequenced 11 germline exomes from five families with familial pancreatic cancer (FPC). One proband had a germline nonsense variant in ATM with somatic loss of the variant allele. Another proband had a nonsense variant in PALB2 with somatic loss of the variant allele. Both variants were absent in a relative with FPC. These findings question the causal mechanisms of ATM and PALB2 in these families and highlight challenges in identifying the causes of familial cancer syndromes using exome sequencing

GAD1 Upregulation Programs Aggressive Features of Cancer Cell Metabolism in the Brain Metastatic Microenvironment

The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here, we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway. In cell-based culture and brain metastasis models, we found that downregulation of the DNA methyltransferase DNMT1 induced by the brain microenvironment-derived clusterin resulted in decreased GAD1 promoter methylation and subsequent upregulation of GAD1 expression in brain metastatic tumor cells. In a system to dynamically visualize cellular metabolic responses mediated by GAD1, we monitored the cytosolic NADH:NAD+ equilibrium in tumor cells. Reducing GAD1 in metastatic cells by primary glia cell coculture abolished the capacity of metastatic cells to utilize extracellular glutamine, leading to cytosolic accumulation of NADH and increased oxidative status. Similarly, genetic or pharmacologic disruption of the GABA metabolic pathway decreased the incidence of brain metastasis in vivo Taken together, our results show how epigenetic changes in GAD1 expression alter local glutamate metabolism in the brain metastatic microenvironment, contributing to a metabolic adaption that facilitates metastasis outgrowth in that setting

Half-life determination of 215^{215}At and 221^{221}Ra with high-purity radioactive ion beams

International audienceAt CERN-ISOLDE, high-purity radioactive ion beams of $^{219}$Fr and $^{221}$RaF were investigated with $\alpha$-decay spectroscopy at the CRIS and ASET experiments in the course of three different experimental campaigns. The half-life of $^{215}$At, $\alpha$-decay daughter of $^{219}$Fr, is measured to be 36.3(3)[9]μs, and that of $^{221}$Ra was determined to be 26.2(1)[6]s, both of which are well in line with the trends in this region of the nuclear landscape but at odds with some of the reported literature