Impact of the Foundations of Clinical Medicine Course on USMLE Scores

BACKGROUND  The synthesis of basic and clinical science knowledge during the clerkship years has failed to meet educational expectations. OBJECTIVES  We hypothesized that a small-group course emphasizing the basic science underpinnings of disease, Foundations of Clinical Medicine (FCM), could be integrated into third year clerkships and would not negatively impact the United States Medical Licensure Examination (USMLE) step 2 scores. DESIGN  In 2001–2002, all third year students met weekly in groups of 8–12 clustered within clerkships to discuss the clinical and basic science aspects of prescribed, discipline-specific cases. PARTICIPANTS  Students completing USMLE step 2 between 1999 and 2004 (n = 743). MEASUREMENTS  Course evaluations were compared with the overall institutional average. Bivariate analyses compared the mean USMLE steps 1 and 2 scores across pre- and post-FCM student cohorts. We used multiple linear regression to assess the association between USMLE step 2 scores and FCM cohort controlling for potential confounders. RESULTS  Students’ average course evaluation score rose from 66 to 77 (2001–2004) compared to an institutional average of 73. The unadjusted mean USMLE step 1 score was higher for the post-FCM cohort (212.9 vs 207.5, respectively, p < .001) and associated with step 2 scores (estimated coefficient = 0.70, p < .001). Post-FCM cohort (2002–2004; n = 361) mean step 2 scores topped pre-FCM (1999–2001; n = 382) scores (215.9 vs 207.7, respectively, p < .001). FCM cohort remained a significant predictor of higher step 2 scores after adjustment for USMLE step 1 and demographic characteristics (estimated coefficient = 4.3, p = .002). CONCLUSIONS  A curriculum integrating clinical and basic sciences during third year clerkships is feasible and associated with improvement in standardized testing. Electronic supplementary material  The online version of this article (doi: ) contains supplementary material, which is available to authorized users.     

Neuropsychological characteristics of Italian children with fetal alcohol spectrum disorders

Background: Children with fetal alcohol spectrum disorders (FASD) display many problems ranging from deficits in intelligence to behavioral difficulties. Thus, many studies have aimed at defining the neuropsychological characteristics of children with FASD. The current article describes the neuropsychological characteristics of Italian children with severe diagnosis within FASD and compares them with controls. It was expected that intellectual functioning, language comprehension, academic skills, and inattention/hyperactivity would discriminate children with FASD from randomly selected peers without FASD. Methods: This article presents data from a second cohort of children examined in 2005 as part of an in‐school epidemiological study of FASD in Italy. Of 80 children, 23 diagnosed with a FASD, and 57 randomly selected control children from the same first‐grade classes, participated. After screening for FASD via growth and dysmorphology, the children were administered a test of general intelligence (WISC‐R) as well as tests of nonverbal reasoning (Raven Colored Progressive Matrices), language comprehension (Rustioni), academic achievement (IPDA), and problem behavior (Disruptive Behavior Disorder Rating Scale). Results: Children diagnosed with a FASD achieved lower scores than control children on Verbal, Performance, and Full Scale IQ. Profile analysis of the WISC‐R indicates overall differences between the groups. However, some intact functioning within the FASD group was found, as the Similarities and Vocabulary subtests were similar to the controls. After an alpha adjustment to 0.004, the Block Design, Object Assembly, and Mazes subtests were significantly different from controls. On tests of nonverbal reasoning, language comprehension, and academic achievement, the children with a FASD scored significantly lower. Moreover, teachers rated children with a severe diagnosis within FASD as showing more inattentive symptoms than controls, while hyperactive/impulsive characteristics among children with a FASD were comparable with the control children. Significant correlations between head circumference, child dysmorphology, WISC‐R, and Raven CPM scores are also reported. Conclusions: This study indicates that a sample of Italian children with a FASD, when compared with control children, display poorer functioning on measures of general intelligence, nonverbal reasoning, academic achievement, and teacher‐rated problem behaviors. The findings also contribute to the formulation of a neuropsychological profile of children diagnosed with a FASD.     

Effect of vitamin A supplementation on measles-specific antibody levels in Guinea-Bissau

We have previously reported that vitamin A supplementation with measles vaccine at age 9 months increases measles-specific antibody concentrations in children at age 18 months compared with placebo. We examined these children when they reached age 6-8 years. Fewer vitamin A-supplemented children had non-protective antibody concentrations (p=0.0095); among children with protective antibody levels, vitamin A-supplemented children tended to have higher geometric mean antibody titres (p=0.09). Thus, simultaneous administration of vitamin A and measles vaccine at age 9 months had a long-term effect on measles-specific antibody levels and may contribute to improved measles control in less-developed countries.     

Dimensions and anatomic variations of left main coronary artery in normal population: multidetector computed tomography assessment

OBJECTIVES: The aim of our study was to determine the dimensions, morphology and anatomic variations of the left main coronary artery (LMCA) in normal participants, on multidetector computed tomography. BACKGROUND: Accurate imaging of LMCA dimensions and configuration is crucial to avoid misdiagnosis of LMCA disease. MATERIALS AND METHODS: Seventy morphologically normal LMCAs of 70 participants were carefully selected from among 600 consecutive coronary computed tomography angiography studies performed in our institute. LMCA cross-sectional diameters and areas were obtained at three points of each vessel: ostium, midvessel and distal. The length, cross-sectional shape, three-dimensional (3D) morphology and position of origin were studied. Influences of age, body weight, height and body surface area (BSA) on LMCA dimensions were evaluated. RESULTS: Different dimensions in each measured point of the LMCA were detected. Cross-sectional elliptic shape at ostium, mid-LMCA and distal LMCA was found in 66/70 (94%), 51/70 (73%) and 54/70 (77%) of the participants, respectively. On the basis of the 3D presentation, four types of LMCA were identified: biconcave-shape appearance (type 1), tapering morphology (type 2), combined morphology (type 3) and funnel-shape appearance (type 4). Fifty-two of the 70 participants had an LMCA orifice originating in the middle third of the aortic sinus, 15/70 in the posterior third and 3/70 in the anterior third. In men, significant correlation was found between LMCA cross-sectional area and body weight, height and BSA. In women, no correlation was found regarding body weight, height and BSA. CONCLUSION: LMCA is not a simple straight tube but usually has various anatomical configurations, variable dimensions and cross-sectional shapes. Ostial angulation is a normal variant usually associated with the posterior position of the LMCA orifice of origin in the aortic sinus.     

TEG® and RapidTEG® are unreliable for detecting warfarin-coagulopathy: a prospective cohort study

Background

Thromboelastography^® (TEG) utilizes kaolin, an intrinsic pathway activator, to assess clotting function. Recent published studies suggest that TEG results are commonly normal in patients receiving warfarin, despite an increased International Normalized Ratio (INR). Because RapidTEG? includes tissue factor, an extrinsic pathway activator, as well as kaolin, we hypothesized that RapidTEG would be more sensitive in detecting a warfarin-effect.

Methods

Included in this prospective study were 22 consecutive patients undergoing elective cardioversion and receiving warfarin. Prior to cardioversion, blood was collected to assess INR, Prothrombin Time, TEG, and RapidTEG.

Results

INR Results: 2.8?±?0.5 (1.6 to 4.2). Prothrombin Time Results: 19.1?±?2.2 (13.9. to 24.3). TEG Results (Reference Range): R-Time: 8.3?±?2.7 (2–8); K-Time: 2.1?±?1.4 (1–3); Angle: 62.5?±?10.3 (55–78); MA: 63.2?±?10.3 (51–69); G: 9.4?±?3.5 (4.6-10.9); R-Time within normal range: 10 (45.5%) with INR 2.9?±?0.3; Correlation coefficients for INR and each of the 5 TEG variables were insignificant (P?>?0.05). RapidTEG Results (Reference Range): ACT: 132?±?58 (86–118); K-Time: 1.2?±?0.5 (1–2); Angle: 75.4?±?5.2 (64–80); MA: 63.4?±?5.1 (52–71); G: 8.9?±?2.0 (5.0-11.6); ACT within normal range: 9 (40.9%) with INR 2.7?±?0.5; Correlation coefficients for INR and each of the 5 RapidTEG variables were insignificant (P?>?0.05).

Conclusions

TEG, using kaolin activation, and RapidTEG, with kaolin and tissue factor activation, were normal in a substantial percent of warfarin patients, despite an increased INR. The false-negative rate for detecting warfarin coagulopathy with either test is unacceptable. The lack of correlation between INR and all TEG and RapidTEG components further indicates that these methodologies are insensitive to warfarin effects. Findings suggest that intrinsic pathway activation may mitigate detection of an extrinsic pathway coagulopathy.     

Coronary artery disease among asymptomatic diabetic and nondiabetic patients undergoing coronary computed tomography angiography

OBJECTIVES: The aim of this study was to determine the prevalence and severity of coronary artery disease (CAD) and the plaque composition in asymptomatic diabetic and nondiabetic patients undergoing coronary computed tomography angiography (CCTA). BACKGROUND: CAD is the major cause of death among patients with diabetes. The true prevalence of CAD in asymptomatic diabetic patients, however, remains unknown. MATERIALS AND METHODS: A total of 328 consecutive patients (each with at least one risk factor or abnormal stress-test results) were referred for cardiac evaluation, 42 with diabetes and 286 without diabetes, all asymptomatic for cardiac-related symptoms. Groups were matched for age, sex, and CAD risk factors. CAD was defined as coronary atherosclerosis, with obstructive or nonobstructive lesions. CCTA was performed and findings compared between patients with diabetes and those without. RESULTS: CAD was present in 39 (93%) diabetic patients and in 211 (73%) nondiabetic patients (P=0.006). Obstructive CAD was more common in diabetic patients than in nondiabetic patients (29 vs. 6.6%, respectively; P<0.0001). In diabetic patients, more coronary segments with atherosclerosis per patient were detected (5.5 segments/patient vs. 2.8 segments/patient in nondiabetics; P<0.0001). The total Agatston score was significantly higher in diabetic patients vs. nondiabetic patients (370+/-96 and 79.9+/-16, respectively; P<0.0001). CONCLUSION: Our results indicate a high prevalence (93%) of CAD in asymptomatic diabetic patients with either nonobstructive or obstructive lesions. CCTA may be a useful imaging modality for selecting patients at high risk who would benefit most from further evaluation for subclinical ischemia.     

A Toolbox for Herpesvirus miRNA Research: Construction of a Complete Set of KSHV miRNA Deletion Mutants

Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes 12 viral microRNAs (miRNAs) that are expressed during latency. Research into KSHV miRNA function has suffered from a lack of genetic systems to study viral miRNA mutations in the context of the viral genome. We used the Escherichia coli Red recombination system together with a new bacmid background, BAC16, to create mutants for all known KSHV miRNAs. The specific miRNA deletions or mutations and the integrity of the bacmids have been strictly quality controlled using PCR, restriction digestion, and sequencing. In addition, stable viral producer cell lines based on iSLK cells have been created for wildtype KSHV, for 12 individual miRNA knock-out mutants (ΔmiR-K12-1 through -12), and for mutants deleted for 10 of 12 (ΔmiR-cluster) or all 12 miRNAs (ΔmiR-all). NGS, in combination with SureSelect technology, was employed to sequence the entire latent genome within all producer cell lines. qPCR assays were used to verify the expression of the remaining viral miRNAs in a subset of mutants. Induction of the lytic cycle leads to efficient production of progeny viruses that have been used to infect endothelial cells. Wt BAC16 and miR mutant iSLK producer cell lines are now available to the research community.