The effects of laryngeal mask airway passage simulation training on the acquisition of undergraduate clinical skills: a randomised controlled trial

Background\ud Effective use of the laryngeal mask airway (LMA) requires learning proper insertion technique in normal patients undergoing routine surgical procedures. However, there is a move towards simulation training for learning practical clinical skills, such as LMA placement. The evidence linking different amounts of mannequin simulation training to the undergraduate clinical skill of LMA placement in real patients is limited. The purpose of this study was to compare the effectiveness in vivo of two LMA placement simulation courses of different durations. \ud \ud Methods\ud Medical students (n = 126) enrolled in a randomised controlled trial. Seventy-eight of these students completed the trial. The control group (n = 38) received brief mannequin training while the intervention group (n = 40) received additional more intensive mannequin training as part of which they repeated LMA insertion until they were proficient. The anaesthetists supervising LMA placements in real patients rated the participants' performance on assessment forms. Participants completed a self-assessment questionnaire. \ud \ud Results\ud Additional mannequin training was not associated with improved performance (37% of intervention participants received an overall placement rating of > 3/5 on their first patient compared to 48% of the control group, $X^2$ = 0.81, p = 0.37). The agreement between the participants and their instructors in terms of LMA placement success rates was poor to fair. Participants reported that mannequins were poor at mimicking reality. \ud \ud Conclusions\ud The results suggest that the value of extended mannequin simulation training in the case of LMA placement is limited. Educators considering simulation for the training of practical skills should reflect on the extent to which the in vitro simulation mimics the skill required and the degree of difficulty of the procedure. \ud \u

Asymptomatic bacteriuria in sickle cell disease: a cross-sectional study

BACKGROUND: It is known that there is significant morbidity associated with urinary tract infection and with renal dysfunction in sickle cell disease (SCD). However, it is not known if there are potential adverse outcomes associated with asymptomatic bacteriuria (ASB) infections in sickle cell disease if left untreated. This study was undertaken to determine the prevalence of ASB, in a cohort of patients with SCD. METHODS: This is a cross-sectional study of patients in the Jamaican Sickle Cell Cohort. Aseptically collected mid-stream urine (MSU) samples were obtained from 266 patients for urinalysis, culture and sensitivity analysis. Proteinuria was measured by urine dipsticks. Individuals with abnormal urine culture results had repeat urine culture. Serum creatinine was measured and steady state haematology and uric acid concentrations were obtained from clinical records. This was completed at a primary care health clinic dedicated to sickle cell diseases in Kingston, Jamaica. There were 133 males and 133 females in the sample studied. The mean age (mean ± sd) of participants was 26.6 ± 2.5 years. The main outcome measures were the culture of ≥ 10(5 )colony forming units of a urinary tract pathogen per milliliter of urine from a MSU specimen on a single occasion (probable ASB) or on consecutive occasions (confirmed ASB). RESULTS: Of the 266 urines collected, 234 were sterile and 29 had significant bacteriuria yielding a prevalence of probable ASB of 10.9% (29/266). Fourteen patients had confirmed ASB (prevalence 5.3%) of which 13 had pyuria. Controlling for genotype, females were 14.7 times more likely to have confirmed ASB compared to males (95%CI 1.8 to 121.0). The number of recorded visits for symptomatic UTI was increased by a factor of 2.5 (95% CI 1.4 to 4.5, p < 0.005) but serum creatinine, uric acid and haematology values were not different in patients with confirmed ASB compared with those with sterile urine. There was no association with history of gram negative sepsis. CONCLUSION: ASB is a significant problem in individuals with SCD and may be the source of pathogens in UTI. However, further research is needed to determine the clinical significance of ASB in SCD

Molecular response to aromatase inhibitor treatment in primary breast cancer

BackgroundAromatase inhibitors such as anastrozole and letrozole are highly effective suppressants of estrogen synthesis in postmenopausal women and are the most effective endocrine treatments for hormone receptor positive breast cancer in such women. Little is known of the molecular effects of these agents on human breast carcinomas in vivo.MethodsWe randomly assigned primary estrogen receptor positive breast cancer patients to treatment with anastrozole or letrozole for 2 weeks before surgery. Expression profiling using cDNA arrays was conducted on pretreatment and post-treatment biopsies. Sample pairs from 34 patients provided sufficient RNA for analysis.ResultsProfound changes in gene expression were seen with both aromatase inhibitors, including many classical estrogen-dependent genes such as TFF1, CCND1, PDZK1 and AGR2, but also many other genes that are likely to represent secondary responses; decrease in the expression of proliferation-related genes were particularly prominent. Many upregulated genes are involved in extracellular matrix remodelling, including collagens and members of the small leucine-rich proteoglycan family (LUM, DCN, and ASPN). No significant differences were seen between letrozole and anastrozole in terms of molecular effects. The gene changes were integrated into a Global Index of Dependence on Estrogen (GIDE), which enumerates the genes changing by at least twofold with therapy. The GIDE varied markedly between tumours and related significantly to pretreatment levels of HER2 and changes in immunohistochemically detected Ki67.ConclusionOur findings identify the transcriptional signatures associated with aromatase inhibitor treatment of primary breast tumours. Larger datasets using this approach should enable identification of estrogen-dependent molecular changes, which are the determinants of benefit or resistance to endocrine therapy

Defining the minimal important difference for the visual analogue scale assessing dyspnea in patients with malignant pleural effusions

BACKGROUND: The minimal important difference (MID) is essential for interpreting the results of randomised controlled trials (RCTs). Despite a number of RCTs in patients with malignant pleural effusions (MPEs) which use the visual analogue scale for dyspnea (VASD) as an outcome measure, the MID has not been established. METHODS: Patients with suspected MPE undergoing a pleural procedure recorded their baseline VASD and their post-procedure VASD (24 hours after the pleural drainage), and in parallel assessed their breathlessness on a 7 point Likert scale. FINDINGS: The mean decrease in VASD in patients with a MPE reporting a 'small but just worthwhile decrease' in their dyspnea (i.e. equivalent to the MID) was 19mm (95% CI 14-24mm). The mean drainage volume required to produce a change in VASD of 19mm was 760ml. INTERPRETATION: The mean MID for the VASD in patients with a MPE undergoing a pleural procedure is 19mm (95% CI 14-24mm). Thus choosing an improvement of 19mm in the VASD would be justifiable in the design and analysis of future MPE studies

Biological Convergence of Cancer Signatures

Gene expression profiling has identified cancer prognostic and predictive signatures with superior performance to conventional histopathological or clinical parameters. Consequently, signatures are being incorporated into clinical practice and will soon influence everyday decisions in oncology. However, the slight overlap in the gene identity between signatures for the same cancer type or condition raises questions about their biological and clinical implications. To clarify these issues, better understanding of the molecular properties and possible interactions underlying apparently dissimilar signatures is needed. Here, we evaluated whether the signatures of 24 independent studies are related at the genome, transcriptome or proteome levels. Significant associations were consistently observed across these molecular layers, which suggest the existence of a common cancer cell phenotype. Convergence on cell proliferation and death supports the pivotal involvement of these processes in prognosis, metastasis and treatment response. In addition, functional and molecular associations were identified with the immune response in different cancer types and conditions that complement the contribution of cell proliferation and death. Examination of additional, independent, cancer datasets corroborated our observations. This study proposes a comprehensive strategy for interpreting cancer signatures that reveals common design principles and systems-level properties

Source patterns of potentially toxic elements (PTEs) and mining activity contamination level in soils of Taltal city (northern Chile)

Mining activities are among the main sources of potentially toxic elements (PTEs) in the environment which constitute a real concern worldwide, especially in developing countries. These activities have been carried out for more than a century in Chile, South America, where, as evidence of incorrect waste disposal practices, several abandoned mining waste deposits were left behind. This study aimed to understand multi-elements geochemistry, source patterns and mobility of PTEs in soils of the Taltal urban area (northern Chile). Topsoil samples (n = 125) were collected in the urban area of Taltal city (6 km2) where physicochemical properties (redox potential, electric conductivity and pH) as well as chemical concentrations for 35 elements were determined by inductively coupled plasma optical emission spectrometer. Data were treated following a robust workflow, which included factor analysis (based on ilr-transformed data), a new robust compositional contamination index (RCCI), and fractal/multi-fractal interpolation in GIS environment. This approach allowed to generate significant elemental associations, identifying pool of elements related either to the geological background, pedogenic processes accompanying soil formation or to anthropogenic activities. In particular, the study eventually focused on a pool of 6 PTEs (As, Cd, Cr, Cu, Pb, and Zn), their spatial distribution in the Taltal city, and the potential sources and mechanisms controlling their concentrations. Results showed generally low baseline values of PTEs in most sites of the surveyed area. On a smaller number of sites, however, higher values concentrations of As, Cd, Cu, Zn and Pb were found. These corresponded to very high RCCI contamination level and were correlated to potential anthropogenic sources, such as the abandoned mining waste deposits in the north-eastern part of the Taltal city. This study highlighted new and significant insight on the contamination levels of Taltal city, and its links with anthropogenic activities. Further research is considered to be crucial to extend this assessment to the entire region. This would provide a comprehensive overview and vital information for the development of intervention limits and guide environmental legislation for these pollutants in Chilean soils