Attentional selectivity,automaticity, and self-efficacy predict simulator-acquired skill transfer to the clinical environment

Introduction

Several studies demonstrated that simulator-acquired skill transfer to the operating room is incomplete. Our objective was to identify trainee characteristics that predict the transfer of simulator-acquired skill to the operating room.

Frontotemporal dementia and parkinsonism linked to chromosome 17 with the N279K tau mutation

We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) harboring the N279K mutation in the MAPT gene from the family known as pallido‐ponto‐nigral degeneration (PPND). This 49‐year‐old man was followed for 17 years. He presented at age 41 years with left leg stiffness and en‐bloc turning. During the course of his illness he developed a constellation of symptoms including parkinsonism, pyramidal signs, vertical gaze palsy, dysphagia, dystonia, personality and cognitive dysfunction, weight loss and mutism. Gross neuropathological examination showed mild atrophy of the cerebral cortex, hippocampal formation, amygdala, thalamus, subthalamic nucleus and depigmentation of the substantia nigra. Microscopy revealed neuronal loss and gliosis in the same regions. Tau immunohistochemistry showed pretangles, numerous threads, grain‐like structures and oligodendroglial tau‐positive inclusions (“coiled bodies”). In the spinal cord the tau pathology was more abundant in gray than white matter. Pretangles and threads were present in the anterior and, to a lesser extent, in the posterior horns. FTDP‐17 should be suspected in patients with a history of familial parkinsonism combined with behavioral and cognitive changes, onset before age 65 years and an aggressive clinical course.     

Locally aggressive central odontogenic fibroma associated to an inflammatory cyst: a clinical, histological and immunohistochemical study

The case describes a 38-year-old woman presenting a multilocular radiolucency affecting the entire right half of the lower jaw, with an unerupted third molar displaced to the region of the coronoid process. The histological study showed the presence of fibroblasts, focally with pleomorphic nuclei, dense collagen and an odontogenic epithelium with dystrophic calcifications. A cyst with an important inflammatory infiltrate was, moreover, observed.     

Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans

The calcium channel blocker verapamil [2,8-bis-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] undergoes extensive biotransformation in man. We have previously demonstrated cytochrome P450 (CYP) 3A4 and 1A2 to be the enzymes responsible for verapamil N-dealkylation (formation of D-617 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile]), and verapamil N-demethylation (formation of norverapamil [2,8-bis(3,4-dimethoxyphenyl)-2-isopropyl-6-azaoctanitrile]), while there was no involvement of CYP3A4 and CYP1A2 in the third initial metabolic step of verapamil, which is verapamil O-demethylation. This pathway yields formation of D-703 [2-(4-hydroxy-3-methoxyphenyl)-8-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] and D-702 [2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)6-methyl-2-isopropyl-6-azaoctanitrile]. The enzymes catalyzing verapamil O-demethylation have not been characterized so far. We have therefore identified and characterized the enzymes involved in verapamil O-demethylation in humans by using the following in vitro approaches: (I) characterization of O-demethylation kinetics in the presence of the microsomal fraction of human liver, (II) inhibition of verapamil O-demethylation by specific antibodies and selective inhibitors and (111) investigation of metabolite formation in microsomes obtained from yeast strain Saccharomyces cerevisiae W(R), that was genetically engineered for stable expression of human CYP2C8, 2C9 and 2C18.In human liver microsomes (n=4), the intrinsic clearance (CL_int), as derived from the ratio of V _max/K_m, was significantly higher for O-demethylation to D-703 compared to formation of D-702 following incubation with racemic verapamil (13.9±1.0 vs 2.4±0.6 ml^*min^{-1 *}g^-1 mean±SD; p<0.05), S-Verapamil (16.8±3.3 vs 2.2±1.2 ml^* mini^*g^-1, p<0.05) and R-verapamil (12.1±2.9 vs 3.6 ±1.3 ml^*min^{-1 *} g^-1; p<0.05), thus indicating regioselectivity of verapamil O-demethylation process. The CL_int of D-703 formation in human liver microsomes showed a modest but significant degree of stereo selectivity (p<0.05) with a S/R-ratio of 1.41±0.17. Anti-LKM2 (anti-liver/kidney microsome) autoantibodies (which inhibit CYP2C9 and 2C19) and sulfaphenazole (a specific CYP2C9 inhibitor) reduced the maximum rate of formation of D-703 by 81.5±4.5% and 45%, that of D-702 by 52.7±7.5% and 72.5%, respectively. Both D-703 and D-702 were formed by stably expressed CYP2C9 and CYP2C18, whereas incubation with CYP2C8 selectively yielded D-703.In conclusion, our results show that enzymes of the CYP2C subfamily are mainly involved in verapamil O-demethylation. Verapamil therefore has the potential to interact with other drugs which inhibit or induce these enzymes.     

THE MEASUREMENT OF SOCIOECONOMIC INEQUALITY AND SOCIAL CLASS IN AUSTRALIA: A REVIEW OF PAST PRACTICES AND RECENT DEVELOPMENTS

Recent findings have pointed to an association between socioeconomic status and health in Australia but have, in the process, raised important questions about the validity of various methods of determining a respondent's location within the hierarchy. While some of the problems associated with the use of the Australian Bureau of Statistics classification were known, the full extent of these deficiencies was not. This paper reviews past and present methods of measuring socioeconomic inequality in Australia. After pointing to the criteria which should be applied to determine the adequacy of any method of socioeconomic classification, the paper reviews the main strengths and weaknesses of the methods of classification used in health-related research in Australia.     

Limitations of a convolution method for modeling geometric uncertainties in radiation therapy: the radiobiological dose-per-fraction effect

The convolution method can be used to model the effect of random geometric uncertainties into planned dose distributions used in radiation treatment planning. This is effectively done by linearly adding infinitesimally small doses, each with a particular geometric offset, over an assumed infinite number of fractions. However, this process inherently ignores the radiobiological dose-per-fraction effect since only the summed physical dose distribution is generated. The resultant potential error on predicted radiobiological outcome [quantified in this work with tumor control probability (TCP), equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and generalized equivalent uniform dose (gEUD)] has yet to be thoroughly quantified. In this work, the results of a Monte Carlo simulation of geometric displacements are compared to those of the convolution method for random geometric uncertainties of 0, 1, 2, 3, 4, and 5 mm (standard deviation). The alpha/betaCTV ratios of 0.8, 1.5, 3, 5, and 10 Gy are used to represent the range of radiation responses for different tumors, whereas a single alpha/betaOAR ratio of 3 Gy is used to represent all the organs at risk (OAR). The analysis is performed on a four-field prostate treatment plan of 18 MV x rays. The fraction numbers are varied from 1-50, with isoeffective adjustments of the corresponding dose-per-fractions to maintain a constant tumor control, using the linear-quadratic cell survival model. The average differences in TCP and EUD of the target, and in NTCP and gEUD of the OAR calculated from the convolution and Monte Carlo methods reduced asymptotically as the total fraction number increased, with the differences reaching negligible levels beyond the treatment fraction number of > or =20. The convolution method generally overestimates the radiobiological indices, as compared to the Monte Carlo method, for the target volume, and underestimates those for the OAR. These effects are interconnected and attributed to assuming an infinite number of fractions inherent in the implementation of the convolution technique, irrespective of the uniqueness of each treatment schedule. Based on the fraction numbers analyzed (1-50), and the range of fraction numbers normally used clinically (> or =20), the convolution method can be used safely to estimate the effects of random geometric uncertainties on prostate treatment radiobiological outcomes, for both the target and the OAR. Although the results of this study is likely to apply to other clinical sites and treatment techniques other than the four-field, further validation similar to those done in this study may be necessary prior to clinical implementation.     

Complication Rates Following Total Ankle Arthroplasty in Inpatient versus Outpatient Populations: A Systematic Review & Meta-Analysis

Total ankle arthroplasty (TAA) is used as an alternative to ankle arthrodesis for adults with severe ankle arthritis. Numerous orthopedic centers have entered the healthcare market offering fast-tracked joint replacement protocols, meanwhile, TAA has been excluded from these joint centers, and is primarily performed in the inpatient setting. The purpose of this study is to examine short-term complications in the inpatient and outpatient settings following TAA using a systematic review and quantitative analysis. We considered all studies examining short-term complications following TAA performed in the inpatient versus outpatient setting occuring within 1 year of the index operation. We summarized data using a pooled relative risk and random effects model. A pooled sensitivity analysis was performed for studies with data on complication rates for inpatient or outpatient populations, which did not have a control group. The quality of included studies was assessed using the Cochrane risk of bias tool. Nine studies were included in the quantitative analysis, with 4 studies in the final meta-analysis. Subjects undergoing inpatient surgery experienced a 5-times higher risk of short-term complications compared to the outpatient group (risk ratio 5.27, 95% confidence interval 3.31, 8.42). Results did not change after sensitivity analysis (inpatient weighted mean complication rate: 9.62% vs outpatient weighted mean 5.02%, p value <.001). The overall level of evidence of included studies was level III, with a moderate to high risk of bias. Outpatient TAAs do not appear to pose excess complication risks compared to inpatient procedures, and may therefore be a reasonable addition to experienced centers that have established a fast-track outpatient total joint protocol.