A systematic review of resident‐as‐teacher programmes

Context Residents in all disciplines serve as clinical teachers for medical students. Since the 1970s, there has been increasing evidence to demonstrate that residents wish to teach and that they respond positively to formal teacher training. Effective resident‐as‐teacher (RaT) programmes have resulted in improved resident teaching skills. Current evidence, however, is not clear about the specific features of an effective RaT programme. Objectives This study was performed in order to investigate the effectiveness of RaT programmes on resident teaching abilities and to identify the features that ensure success. Methods of assessment used to ascertain the effectiveness of RaT programmes are also explored. Methods The literature search covered the period between 1971 and 2008. Articles focusing on improving resident teaching skills were included. Each study was reviewed by two reviewers and data were collected using a standard abstraction summary sheet. Study outcomes were graded according to a modified Kirkpatrick's model of educational outcomes. Results Twenty‐nine studies met review inclusion criteria. Interventions included workshops, seminars, lectures and teaching retreats. Twenty‐six studies used a pre‐ and post‐intervention outcome comparison method. Subjective outcome measures included resident self‐evaluation of teaching skills or evaluation by medical students, peers and faculty members. Objective outcome measures included written tests, evaluation of teaching performance by independent raters and utilisation of objective structured teaching examinations. One study objectively measured learning outcomes at the level of medical students, utilising the results of an objective structured clinical examination. Overall resident satisfaction with RaT programmes was high. Participants reported positive changes in attitudes towards teaching. Participant knowledge of educational principles improved. Study methodologies allowed for significant risks of bias. Conclusions More rigorous study designs and the use of objective outcome measures are needed to ascertain the true effectiveness of RaT programmes. Future research should focus on determining the impact of RaT programmes on learning achievement at the level of medical students.     

Norepinephrine transporter and α2c adrenoceptor allelic variants and personality factors

It has been suggested that reward dependence, as measured by the Tridimensional Personality Questionnaire (TPQ), is related to central noradrenergic activity, a proposition supported by two studies of urinary norepinephrine metabolite. In the current investigation, 190 normal young Han Chinese were examined, with genetic polymorphisms determined for the norepinephrine transporter (1287G/A) and the α_2c‐adrenoceptor (Del322–325) to test the association with TPQ personality traits. No significant association was demonstrated for these two polymorphisms and any of the TPQ personality‐factor scores, including reward dependence and its subscales. Our negative findings suggest that the investigated polymorphisms of the norepinephrine transporter and the α_2c adrenoceptor do not play a major role in the reward‐dependence personality trait as assessed by TPQ. © 2002 Wiley‐Liss, Inc.     

Re‐detection vs. new acquisition of high‐risk human papillomavirus in mid‐adult women

To understand high‐risk (hr) human papillomavirus (HPV) epidemiology in mid‐adulthood, we assessed whether associations between incident detection of hrHPV DNA and recent sexual behavior differed according to whether or not there was serologic evidence of prior infection. From 2011 to 2012, we enrolled 409 women aged 30–50 years into a 6‐month longitudinal study. We collected health and sexual behavior histories, enrollment sera for HPV antibody testing, and monthly self‐collected vaginal swabs for HPV DNA genotyping. Generalized estimating equations logistic regression identified risk factors for type‐specific incident hrHPV DNA, stratified by type‐specific hrHPV serostatus at enrollment. Population attributable risks of hrHPV due to prior and recent exposure were estimated. When type‐specific hrHPV serology was negative, recent sexual risk behavior was positively associated with incident hrHPV DNA (odds ratio in women reporting ≥3 recent sexual risk behaviors [e.g., new or multiple partners] vs. no recent sexual activity = 9.8, 95% CI: 2.4–40.6). No associations with recent sexual behavior were observed with positive type‐specific hrHPV serology. Thirty percent of incident hrHPV DNA detection was attributable to prior infection (with positive serology) and 40% was attributable to recent sexual risk behavior (with negative serology). The proportion of incident hrHPV DNA detection attributable to recent sexual risk behavior decreased with increasing age. Among women with serologic evidence of prior infection, re‐detection of the same hrHPV type is likely due to reactivation or intermittent detection of persistent infection. Without serologic evidence of prior infection, new detection is likely due to new acquisition or to intermittent detection of persisting infection.     

Characterization of the GNMT‐HectH9‐PREX2 tripartite relationship in the pathogenesis of hepatocellular carcinoma

The pathogenesis of hepatocellular carcinoma (HCC) involves many molecular pathways. Glycine N‐methyltransferase (GNMT) is downregulated in almost all HCC and its gene knockout mice developed HCC with high penetrance. We identified PREX2, a novel PTEN inhibitor, as a GNMT‐interacting protein. Such interaction enhanced degradation of PREX2 through an E3 ligase HectH9‐mediated proteasomal ubiquitination pathway. Depletion of GNMT or HectH9 resulted in AKT activation in a PREX2 dependent manner and enhanced cell proliferation. An elevated PREX2 protein expression accompanied by activation of AKT was observed in the liver of Gnmt knockout mice. PREX2 protein expression was upregulated in 54.9% of human HCC samples, while its mRNA level was comparable in tumor and tumor‐adjacent tissue, suggesting a post‐translational alteration of PREX2 expression. Higher level of PREX2 in the tumor tissues was associated with poorer survival. These results reveal a novel mechanism in which GNMT participates in AKT signaling and HCC tumorigenesis by promoting HectH9‐mediated PREX2 degradation.     

Who should be screened for primary aldosteronism? A comprehensive review of current evidence

Arterial hypertension is a major risk factor for cardiovascular disease. The prevalence of primary aldosteronism (PA) ranges from 5% to 10% in the general hypertensive population and is regarded as one of the most common causes of secondary hypertension. There are two major causes of PA: bilateral adrenal hyperplasia and aldosterone‐producing adenoma. The diagnosis of PA comprises screening, confirmatory testing, and subtype differentiation. The Endocrine Society Practice Guidelines for the diagnosis and treatment of PA recommends screening of patients at an increased risk of PA. These categories include patients with stage 2 and 3 hypertension, drug‐resistant hypertension, hypertensive with spontaneous or diuretic‐induced hypokalemia, hypertension with adrenal incidentaloma, hypertensive with a family history of early onset hypertension or cerebrovascular accident at a young age, and all hypertensive first‐degree relatives of patients with PA. Recently, several studies have linked PA with obstructive sleep apnea and atrial fibrillation unexplained by structural heart defects and/or other conditions known to cause the arrhythmia, which may be partly responsible for the higher rates of cardiovascular and cerebrovascular accidents in patients with PA. The aim of this review is to discuss which patients should be screened for PA, focusing not only on well‐established guidelines but also on additional groups of patients with a potentially higher prevalence of PA, as has been reported in recent research.     

Mitigating ipatasertib‐induced glucose increase through dose and meal timing modifications

Ipatasertib, an AKT inhibitor, in combination with prednisone and abiraterone, is under evaluation for the treatment of metastatic castration‐resistant prostate cancer (mCRPC). Hyperglycemia is an on‐target effect of ipatasertib. An open‐label, single‐arm, single‐sequence, signal‐seeking study (n = 25 mCRPC patients) was conducted to evaluate the glucose changes across four different treatment periods: ipatasertib alone, ipatasertib‐prednisone combination, ipatasertib‐prednisone‐abiraterone combination (morning dose), and ipatasertib‐prednisone‐abiraterone combination (evening dose). Continuous glucose monitoring (CGM) was used in this study to compare the dynamic glucose changes across the different treatment periods. Four key parameters: average glucose, peak glucose and % time in range (70–180 and >180 mg/dl) were evaluated for this comparison. Ipatasertib‐prednisone‐abiraterone combination when administered in the morning after an overnight fast significantly increased average glucose, peak glucose and % time in range >180 mg/dl compared to ipatasertib monotherapy. Ipatasertib, when co‐administered with abiraterone, increased ipatasertib and M1 (G‐037720) metabolite exposures by approximately 1.5‐ and 2.2‐fold, respectively. Exposure–response analysis results show that increased exposures of ipatasertib in combination with abiraterone are associated with increased glucose levels. When ipatasertib‐prednisone‐abiraterone combination was administered as an evening dose compared to a morning dose, lowered peak glucose and improved % time in range was observed. The results from this study suggest that dosing ipatasertib after an evening meal followed by overnight fasting can be an effective strategy for managing increased glucose levels.

Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Clinical development of PI3K/AKT inhibitors has been particularly challenging given their toxicity profiles, hyperglycemia being one of the on‐target effects. WHAT QUESTION DID THIS STUDY ADDRESS? This study evaluated the real‐time changes in glucose levels post‐ipatasertib administration using a continuous glucose‐monitoring wearable device. This study further evaluated morning versus evening dosing of ipatasertib in combination with prednisone and abiraterone. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? The results from this study suggest that offering ipatasertib, an AKT inhibitor, as an evening dose after evening meal may offer a better option at de‐risking hyperglycemia incidences. The study also provides preliminary information that a low dose of steroids does not lead to a marked increase in glucose levels when administered in combination with ipatasertib. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This is a novel clinical pharmacology study, wherein a safety finding was investigated using an innovative continuous glucose‐monitoring device and results were discussed in the context of pharmacokinetic results and drug–drug interactions. The conclusions and the methodology are supportive of further investigations to mitigate hyperglycemia risk for oncology drugs that inhibit the AKT/PI3K pathway, as this class of drugs are known to cause an increase in blood glucose.     

Renosplenic Shunting in the Nutcracker Phenomenon: A Discussion and Paradigm Shift in Options? A Novel Approach to Treating Nutcracker Syndrome

The nutcracker syndrome is a rare clinical manifestation of symptoms caused by the compression of the left renal vein by an overriding superior mesenteric artery, an anatomical variant otherwise known as the nutcracker phenomenon. Usually present in women and children, when symptomatic, it commonly presents with hematuria, proteinuria, and chronic pelvic pain. Effective modalities of treatment apart from conservative management, include both invasive surgical procedures such as renal vein transposition and autotransplantation of the kidney and more popular recently, the less invasive endovascular stenting. Both options, however, are not without complications, such as, retroperitoneal hematomas or stent migration, thrombosis and restenosis. We now present a case of spontaneous renosplenic shunting in a 68-year-old lady of Chinese descent with the nutcracker syndrome—the first of such cases to be ever reported in a patient with no preexisting predilection for chronic liver disease and portosystemic shunting. Despite having significant pelvic venous congestion as evident on computed tomography scans, she remained asymptomatic. This may present a novel paradigm shift for the treatment of the nutcracker syndrome —surgical creation of a renosplenic bypass instead of current modalities, an alternative solution which can be performed laparoscopically and is without problems related to stent use. The creation of laparoscopic splenorenal bypass has been reported once thus far in Cleveland Ohio by Chung and Gill with good symptomatic improvement but no further studies since to validate its long-term effectiveness.