Drug related critical incidents

Drug related incidents are a common form of reported medical errors. This paper reviews the critical incidents related to drug errors reported from the main operating theatre suite in a teaching hospital in a developing country from January 1997 to December 2002. Each report was evaluated individually by two reviewers using a structured process. During this period, 44 874 anaesthetics were administered; 768 critical incidents were reported, 165 (21%) of which were related to drug errors. Underdosage, side-effect/drug reaction and syringe swap were the most common. A total of 76% were classified as preventable; 56% due to human error and 19% due to system error. High risk incidents accounted for 10% of all drug errors and most of these were related to the use of neuromuscular blocking drugs. This analysis has been found useful in addressing some issues about priorities

Anaesthesia for surgical correction of scoliosis with spinal cord monitoring--a case series

Objective: To share our experience of anaesthetic management of scoliosis with intra-operative somatosensory evoked potential monitoring and wake up test.Methods: All the cases of scoliosis surgery scheduled during a period of two years in which SSEP and intra-operative wake-up test was planned were included in the study. The patient in which intra-operative wake-up test was not planned were excluded from this case series.Results: We managed a series of sixteen cases of scoliosis in our hospital. Eleven patients were female and five were male with the age ranging from six to twenty two years. SSEPs were monitored throughout the procedure and wake up test was done intra-operatively after surgical manipulation of spinal cord. Intra-operative wake-up test was completed successfully in all the patients. None of the patients had any neurological damage and were also successfully extubated at the end of procedure.CONCLUSION: Intra-operative wake up test and SSEP monitoring are reliable methods for detection of intra-operative spinal cord ischemia during scoliosis surgery

Anesthetic management of a patient with hypertrophic obstructive cardiomyopathy undergoing modified radical mastectomy.

Hypertrophic obstructive cardiomyopathy (HOCM) is a rare genetic disorder characterized by left ventricular outflow tract (LVOT) obstruction. Clinical presentation ranges from absence of symptoms to sudden death. Our 60 year old Patient scheduled for left modified radical mastectomy had HOCM since seventeen years with severe LVOT obstruction and mitral regurgitation. An implantable cardioverter defibrillator (ICD) and permanent pacemaker (PPM) was inserted 15 months earlier for ventricular tachycardia. Anesthetic management of these Patients presents considerable challenges and requires maintenance of desired hemodynamic parameters and management of specific complications. Factors like tachycardia, hypovolemia, vasodilation and increased cardiac contractility leads to exacerbation of the obstruction. In our Patient there was the additional consideration of the ICD which required to be turned off during surgery with full provision for external defibrillation. We managed to successfully maintain the desired hemodynamics throughout the surgery and the Patient was discharged home on the seventh postoperative day

Peer review audit of trauma deaths in a developing country

OBJECTIVES: Peer review of trauma deaths can be used to evaluate the efficacy of trauma systems. The objective of this study was to estimate teh proportion of preventable trauma deaths and the factors contributing to poor outcome using peer review in a tertiary care hospital in a developing country. METHODS: All trauma deaths during a 2-year period (1 January 1998 to 30 December 1998) were identified and registered in a computerized trauma registry, and the probability of survival was calculated for all patients. Summary data, including registry information and details of prehospital, emergency room, and definitive care, were provided to all members of the peer review committee 1 week before the committee meeting. The committee then reviewed all cases and classified each death as preventable, potentially preventable, or non-preventable.RESULTS AND CONCLUSION: A total fo 279 patients were registered in the trauma registry during the study period, including 18 trauma deaths. Peer review judged that six were preventable, seven were potentially preventable, and four were non-preventable. One patient was excluded because the record was not available for review. The proportion of preventable and potentially preventable deaths was significantly higher in our study than from developed countries. Of the multiple contributing factors identified, the most important were inadequate prehospital transfer, limited hospital resources, and an absence of integrated and organized trauma care. This study summarizes the challenges faced in trauma care in a developing country

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Efficacy and Safety of Artemether in the Treatment of Chronic Fascioliasis in Egypt: Exploratory Phase-2 Trials

Fasciola hepatica and F. gigantica are two liver flukes that parasitize herbivorous large size mammals (e.g., sheep and cattle), as well as humans. A single drug is available to treat infections with Fasciola flukes, namely, triclabendazole. Recently, laboratory studies and clinical trials in sheep and humans suffering from acute fascioliasis have shown that artesunate and artemether (drugs that are widely used against malaria) also show activity against fascioliasis. Hence, we were motivated to assess the efficacy and safety of oral artemether in patients with chronic Fasciola infections. The study was carried out in Egypt and artemether administered according to two different malaria treatment regimens. Cure rates observed with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. In addition, high efficacy was observed when triclabendazole, the current drug of choice against human fascioliasis, was administered to patients remaining Fasciola positive following artemether treatment. Concluding, monotherapy with artemether does not represent an alternative to triclabendazole against fascioliasis, but its role in combination chemotherapy regimen remains to be investigated

Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs

Identification and Molecular Characterization of a New Ovarian Cancer Susceptibility Locus at 17q21.31

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3 ′ untranslated region at putative microRNA (miRNA) binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA binding site single nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (OR=1.12, P =10−8 ) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion ( P =10−10 ). Variation at 17q21.31 associates with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes

Complete Genome Sequence of the N2-Fixing Broad Host Range Endophyte Klebsiella pneumoniae 342 and Virulence Predictions Verified in Mice

We report here the sequencing and analysis of the genome of the nitrogen-fixing endophyte, Klebsiella pneumoniae 342. Although K. pneumoniae 342 is a member of the enteric bacteria, it serves as a model for studies of endophytic, plant-bacterial associations due to its efficient colonization of plant tissues (including maize and wheat, two of the most important crops in the world), while maintaining a mutualistic relationship that encompasses supplying organic nitrogen to the host plant. Genomic analysis examined K. pneumoniae 342 for the presence of previously identified genes from other bacteria involved in colonization of, or growth in, plants. From this set, approximately one-third were identified in K. pneumoniae 342, suggesting additional factors most likely contribute to its endophytic lifestyle. Comparative genome analyses were used to provide new insights into this question. Results included the identification of metabolic pathways and other features devoted to processing plant-derived cellulosic and aromatic compounds, and a robust complement of transport genes (15.4%), one of the highest percentages in bacterial genomes sequenced. Although virulence and antibiotic resistance genes were predicted, experiments conducted using mouse models showed pathogenicity to be attenuated in this strain. Comparative genomic analyses with the presumed human pathogen K. pneumoniae MGH78578 revealed that MGH78578 apparently cannot fix nitrogen, and the distribution of genes essential to surface attachment, secretion, transport, and regulation and signaling varied between each genome, which may indicate critical divergences between the strains that influence their preferred host ranges and lifestyles (endophytic plant associations for K. pneumoniae 342 and presumably human pathogenesis for MGH78578). Little genome information is available concerning endophytic bacteria. The K. pneumoniae 342 genome will drive new research into this less-understood, but important category of bacterial-plant host relationships, which could ultimately enhance growth and nutrition of important agricultural crops and development of plant-derived products and biofuels