Beyond the Medical Record

Studies before and since the 1999 Institute of Medicine report have noted the limitations of using medical record reporting for reliably quantifying and understanding medical error. Quantitative macro analyses of large datasets should be supplemented by small-scale qualitative studies to provide insight into micro-level daily events in clinical and hospital practice that contribute to errors and adverse events and how they are reported. Design : The study design involved semistructured face-to-face interviews with residents about the medical errors in which they recently had been involved and included questions regarding how those errors were acknowledged. Objective : This paper reports the ways in which medical error is or is not reported and residents' responses to a perceived medical error. Participants : Twenty-six residents were randomly sampled from a total population of 85 residents working in a 600-bed teaching hospital. Measurements : Outcome measures were based on analysis of cases residents described. Using Ethnograph and traditional methods of content analysis, cases were categorized as Documented, Discussed, and Uncertain. Results : Of 73 cases, 30 (41.1%) were formally acknowledged and Documented in the medical record; 24 (32.9%) were addressed through Discussions but not documented; 19 cases (26%) cases were classified as Uncertain. Twelve cases involved medication errors, which were acknowledged in different categories. Conclusions : The supervisory discussion, the informal discussion, and near-miss contain important information for improving clinical care. Our study also shows the need to improve residents' education to prepare them to recognize and address medical errors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72013/1/j.1525-1497.2005.0098.x.pd

A rapid intrinsic heart rate resetting response with thermal acclimation in rainbow trout, Oncorhynchus mykiss.

We examined cardiac pacemaker rate resetting in rainbow trout following a reciprocal temperature transfer. In the original experiment, performed in winter, 4°C-acclimated fish transferred to 12°C reset intrinsic heart rate after just 1 h (from 56.8±1.2 to 50.8±1.5 beats min-1); 12°C-acclimated fish transferred to 4°C reset intrinsic heart rate after 8 h (from 33.4±0.7 to 37.7±1.2 beats min-1). However, in a replicate experiment, performed in the summer using a different brood year, intrinsic heart rate was not reset, even after 10 weeks at a new temperature. Using this serendipitous opportunity, we compared mRNA expression changes of a suite of proteins in sinoatrial node (SAN), atrial and ventricular tissues after both 1 h and longer than 3 weeks for both experimental acclimation groups to identify those changes only associated with pacemaker rate resetting. Of the changes in mRNA expression occurring after more than 3 weeks of warm acclimation and associated with pacemaker rate resetting, we observed downregulation of NKA α1c in the atrium and ventricle, and upregulation of HCN1 in the ventricle. However, in the SAN there were no mRNA expression changes unique to the fish with pacemaker rate resetting after either 1 h or 3 weeks of warm acclimation. Thus, despite identifying changes in mRNA expression of contractile cardiac tissues, there was an absence of changes in mRNA expression directly involved with the initial, rapid pacemaker rate resetting with warm acclimation. Importantly, pacemaker rate resetting with thermal acclimation does not always occur in rainbow trout.This work is supported by the Natural Science and Engineering Research Council (NSERC) Discovery Grant 2015-05059 to A.P.F. who holds a Canada Research Chair (Tier I)

Investigation of the effects of new potential drugs on leukaemia cells in vitro.

Leukaemia is a deadly clonal blood cancer originated from a single mutant progenitor blood cell, with wide prognosis and multifactorial aetiology. Mutations are needed to induce uncontrolled cell proliferation and avoid apoptosis. The tumour-suppressor gene p53 has been linked to inhibition of abnormal cell growth; while the chaperone molecule Heat Shock Protein-90 (HSP90) to cell proliferation. This project aimed to investigate the responses regarding cell viability and apoptosis of human Leukemic T-lymphoblasts cells (Jurkat E6.1) when exposed in vitro to new potential drugs. Method Jurkat E6.1 cells were incubated with different synthesized compounds (C1 to C4, C6 to C8, at concentrations of 50µM, 500µM and 1000µM) for 24 and 48 hours. Phosphate buffered saline was the negative control and hydroxyurea 500µM the positive. Cell viability and proliferation were determined using Trypan Blue exclusion assay and confirmed using FITC Annexin-V assay through flow cytometry. Gene expression of p53 and HSP90 was assessed by real time reverse transcriptase polymerase chain reaction. Results C2 at 500µM and C6 at 1000µM produced a significant reduction of cell viability (20% and 58% at 24 hours; 35% and 64% at 48 hours respectively; p<0.05). There is a significant increase of cells undergoing early and late apoptosis post-treatment with C2 and C6 (p-value<0.001). HSP90 gene was downregulated (24 hours) and p53 upregulated after treatment with C6. C2 induced downregulation of p53 and upregulation of HSP90. Conclusion C2 and C6 induced apoptosis in Jurkat E6.1 cells in vitro, also, C6 modified the gene expression of p53 and HSP90, thus suppressing cell proliferation and displaying promising anti-cancer activity. However, further investigation is required to verify results, assess cytotoxicity and evaluated other gene targets

Surgery for rheumatic heart disease in the Northern Territory, Australia, 1997-2016: what have we gained?

Background: Between 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival. Methods: A retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016. Survival was examined using Kaplan-Meier and Cox regression analysis. Findings: The cohort included 281 adults and 61 children. The median (IQR) age at first surgery was 31 (18-42) years; 173/342 (51%) had a valve replacement, 113/342 (33%) had a valve repair and 56/342 (16%) had a commissurotomy. There were 93/342 (27%) deaths during a median (IQR) follow-up of 8 (4-12) years. The overall 10-year survival was 70% (95% CI: 64% to 76%). It was 62% (95% CI: 53% to 70%) in those having valve replacement. There were 204/281 (73%) adults with at least 1 preoperative comorbidity. Preoperative comorbidity was associated with earlier death, the risk of death increasing with each comorbidity (HR: 1.3 (95% CI: 1.2 to 1.5), p50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death. Interpretation: Survival after valve replacement for RHD in this region of Australia has not improved. Although the patients were young, many had multiple comorbidities, which influenced long-term outcomes. The increasing prevalence of complex comorbidity in the region is a barrier to achieving optimal health outcomes

CO I Barcoding Reveals New Clades and Radiation Patterns of Indo-Pacific Sponges of the Family Irciniidae (Demospongiae: Dictyoceratida)

DNA barcoding is a promising tool to facilitate a rapid and unambiguous identification of sponge species. Demosponges of the order Dictyoceratida are particularly challenging to identify, but are of ecological as well as biochemical importance.Here we apply DNA barcoding with the standard CO1-barcoding marker on selected Indo-Pacific specimens of two genera, Ircinia and Psammocinia of the family Irciniidae. We show that the CO1 marker identifies several species new to science, reveals separate radiation patterns of deep-sea Ircinia sponges and indicates dispersal patterns of Psammocinia species. However, some species cannot be unambiguously barcoded by solely this marker due to low evolutionary rates.We support previous suggestions for a combination of the standard CO1 fragment with an additional fragment for sponge DNA barcoding

Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism

SummaryWe have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1

Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.

International audienceRare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation