Known by the company we keep: Stigma by association effects the workplace

C1 - Refereed Journal Articl

Beyond standard checklist assessment: Question sequence may impact student performance

Contains fulltext : 172025.pdf (publisher's version ) (Open Access)INTRODUCTION: Clinical encounters are often assessed using a checklist. However, without direct faculty observation, the timing and sequence of questions are not captured. We theorized that the sequence of questions can be captured and measured using coherence scores that may distinguish between low and high performing candidates. METHODS: A logical sequence of key features was determined using the standard case checklist for an observed structured clinical exam (OSCE). An independent clinician educator reviewed each encounter to provide a global rating. Coherence scores were calculated based on question sequence. These scores were compared with global ratings and checklist scores. Results : Coherence scores were positively correlated to checklist scores and to global ratings, and these correlations increased as global ratings improved. Coherence scores explained more of the variance in student performance as global ratings improved. DISCUSSION: Logically structured question sequences may indicate a higher performing student, and this information is often lost when using only overall checklist scores. CONCLUSIONS: The sequence test takers ask questions can be accurately recorded, and is correlated to checklist scores and to global ratings. The sequence of questions during a clinical encounter is not captured by traditional checklist scoring, and may represent an important dimension of performance

Neoadjuvant targeted therapy and advanced kidney cancer: observations and implications for a new treatment paradigm.

International audienceOBJECTIVE To evaluate our early experience with neoadjuvant therapy (sunitinib or sorafenib) in advanced renal cell carcinoma (RCC), to explore the effect on both tumour biology and potential for downstaging advanced tumours, as systemic therapy for RCC has historically resulted in little if any primary tumour response, but recent experience with targeted therapy suggests otherwise. PATIENTS AND METHODS The preliminary experience with neoadjuvant therapy for the surgical management of RCC was reviewed at two large referral centres. Several unique patients were identified who had a novel response to systemic therapy that altered the surgical strategy. RESULTS Four patients who had targeted therapy before surgery are described and in whom there were effects on tumour biology not seen previously with chemotherapy and cytokine therapy. The selected patients who had neoadjuvant targeted therapy had shrinkage of a tumour thrombus in the inferior vena cava, nodal involvement, renal fossa recurrence and tumour within a solitary kidney. CONCLUSIONS The introduction of new molecular agents has revolutionized the treatment of patients with metastatic RCC. Responses to targeted therapy within the primary tumour, tumour thrombus, renal fossa recurrence, and lymph node metastases are novel findings not seen during treatment with immunotherapeutic-based strategies. This might be a signal for urological surgeons to re-evaluate the paradigm for the surgical management of advanced RCC. Potential applications are presented to encourage further investigations with targeted therapy in the neoadjuvant setting

Cardiopulmonary bypass and renal cell carcinoma with level IV tumour thrombus: can deep hypothermic circulatory arrest limit perioperative mortality?

International audienceStudy Type - Therapy (case series) Level of Evidence 4 OBJECTIVE To review experience with nephrectomy/thrombectomy for a renal cell carcimoma (RCC) with a level IV tumour thrombus and to evaluate the benefit of deep hypothermic circulatory arrest (DHCA) with cardiopulmonary bypass (CPBP). PATIENTS AND METHODS A multi-institutional retrospective database was created to assess the outcomes of surgery for RCC and associated level IV tumour thrombus from 1983 to 2007. Patients were identified based on radiographic records/operative findings. Only cases using CPBP were analysed. Clinicopathological and operative characteristics including use of DHCA were recorded. Overall survival (OS) for all patients and by use of DHCA was assessed. Comparisons of clinical and operative characteristics by use of DHCA were performed. A Cox regression model determined predictors of perioperative/in-hospital mortality. RESULTS In all, 63 patients underwent resection with CPBP; overall perioperative mortality was 22.2%. There were no significant differences in clinicopathological characteristics, operative duration, estimated blood loss, transfusions, and hospital stay by use of DHCA. Perioperative mortality rate was lower in patients undergoing DHCA (8.3% vs 37.5%, P= 0.006). The median OS was longer for the patients undergoing DHCA (15.8 vs 7.7 months); however, this failed to reach statistical significance (P= 0.357). On multivariate analysis, age of >60 years (hazard ratio [HR] 6.7, 95% confidence interval [CI] 1.5-31.1, P= 0.015) and the use of DHCA (HR 0.13, 95% CI 0.036-0.51, P= 0.003) were independent predictors of perioperative mortality. CONCLUSIONS Radical nephrectomy and level IV tumour thrombectomy is associated with significant mortality. The use of DHCA does not appear to adversely affect operative characteristics and may limit perioperative mortality. Further prospective studies should be performed to confirm the benefit of DHCA

Architecture of the Human and Yeast General Transcription and DNA Repair Factor TFIIH

TFIIH is essential for both RNA polymerase II transcription and DNA repair, and mutations in TFIIH can result in human disease. Here, we determine the molecular architecture of human and yeast TFIIH by an integrative approach using chemical crosslinking/mass spectrometry (CXMS) data, biochemical analyses, and previously published electron microscopy maps. We identified four new conserved “topological regions” that function as hubs for TFIIH assembly and more than 35 conserved topological features within TFIIH, illuminating a network of interactions involved in TFIIH assembly and regulation of its activities. We show that one of these conserved regions, the p62/Tfb1 Anchor region, directly interacts with the DNA helicase subunit XPD/Rad3 in native TFIIH and is required for the integrity and function of TFIIH. We also reveal the structural basis for defects in patients with Xeroderma pigmentosum and Trichothiodystrophy, with mutations found at the interface between the p62 Anchor region and the XPD subunit

The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy

OBJECTIVE: To update the evidence-based recommendations for the prevention and management of hypertension in adults for 2009. OPTIONS AND OUTCOMES: For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease. EVIDENCE: A Cochrane collaboration librarian conducted an independent MEDLINE search from 2007 to August 2008 to update the 2008 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS: For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to less than 2300 mg (100 mmol)/day (and 1500 mg to 2300 mg [65 mmol to 100 mmol]/day in hypertensive patients); perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m(2) to 24.9 kg/m(2)) and waist circumference (smaller than 102 cm for men and smaller than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a diet that is reduced in saturated fat and cholesterol, and that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on by the patient\u27s global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin- converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as the initial treatment of hypertension if the systolic blood pressure is 20 mmHg above the target or if the diastolic blood pressure is 10 mmHg above the target. The combination of ACE inhibitors and ARBs should not be used. Other agents appropriate for first-line therapy for isolated systolic hypertension include long- acting dihydropyridine CCBs or ARBs. In patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually