Unexpected Return for Follow-up During the First Year of Multidisciplinary Care May Be Predictive of Rapid Deterioration of Renal Function

Multidisciplinary predialysis education and team care (MDC) may slow the decline in renal function in patients with chronic kidney disease (CKD). However, associations between unexpected return during MDC and progression of renal dysfunction have not been characterized in patients with CKD. Our study aimed to determine the association between exacerbation of renal dysfunction and the frequency of unexpected return during follow-up.A total of 437 patients with CKD receiving multidisciplinary care between January 2009 and June 2013 at the Shin-Kong Wu Ho-Su Memorial Hospital were included in this retrospective observational cohort study, and multiple imputations were performed for missing data. The predictor was the frequency of unexpected return for follow-up during the first year after entering MDC. Main outcome was monthly declines in estimated glomerular filtration rates (eGFR). Moreover, the demographic data, comorbidities, history of medication, and routine laboratory data for patients with CKD were collected.Among all patients, 59.7% were male, the mean age at initiation of MDC was 69.4 ± 13.2 years, and the duration of follow-up was 21.4 ± 3.3 months. The subjects were divided into 2 groups according to frequencies of follow-up (≤4 and > 4 visits) during the 1st year of MDC. The patients with CKD were regularly followed up every 3 months as a part of MDC in our hospital, and patients who returned for more than 4 follow-up visits were included in the unexpected return group. In crude regression analyses, unexpected return was significantly associated with higher monthly declines of eGFR (β = 0.092, 95% confidence interval, 0.014–0.170). This association remained after adjustments for multiple variables, and subgroup analyses of unexpected return showed that male gender, older age, CKD stage 1 to 3, hypertension, history of coronary artery disease, and use of renin–angiotensin system blockade were significantly associated with declines in renal function.In conclusion, unexpected return for follow-up during the 1st year of MDC was significantly associated with the deterioration of renal function.     

Introducing dental students to clinical patient care: The complete denture prosthodontics transition clinic

Using complete denture treatment as an introduction to clinical patient care for dental students, the purposes of the Complete Denture Prosthodontics Transition Clinic at the University of Colorado School of Dentistry are to reduce the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience, and to encourage development of student self-confidence and skills. In the 2002 spring semester, faculty at the University of Colorado School of Dentistry initiated the Complete Denture Prosthodontics Transition Clinic for DS-II (second-year) dental students, as an introduction to clinical patient care. Each patient was assigned to a team of two dental students. Three Division of Prosthodontics faculty members staffed each clinic session, providing a student-to-faculty ratio of approximately 6.6:1 and a patient-to-faculty ratio of approximately 3.3:1. All DS-II students in the Class of 2004 delivered their first complete dentures no later than 8 months (average, 184 days) after the last day of the preclinical complete denture prosthodontics course. The time from the diagnostic appointment through the denture placement appointment averaged 39 days for patients treated in this program, compared with an average of 98 days or more for previous classes. The program was successful in achieving the goal of reducing the time lapse between the preclinical complete denture prosthodontics course and the first denture patient experience.     

采用泌尿道前列腺切除器经肛门内镜切除直肠肿瘤：131例患者应用的经验

目的：直肠腺瘤和其他疑似为良性的病变应用经肛门内镜切除术并未普及。该项研究旨在评估经肛门内镜切除术的效能和安全性。方法：回顾性研究分析在1993-2004年之间3所斯德哥尔摩医院中经肛门内镜切除术的患，内容包括患自身及病变特性、并发症、随访时间和复发率。结果：180例中共131例行经肛门内镜切除术。160例经组织学诊断为腺瘤，12例为癌瘤，其余8例分别为增生、纤维化或正常黏膜。直肠腺瘤患中，77例仅行单次经肛门内镜切除术，16例因巨大腺瘤而多次行该手术，27例因复发而需另行经肛门内镜切除术或其他手术。中位复发时间为7个月，但未出现直肠癌。16例手术患出现并发症。2例患必须行Hartman手术，1例因肠穿孔，另1例因出血。手术期间无死亡。未复发的中位随访期为32个月（极差0—67）。[编按]     

A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung disease.

Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR. All eight genes are involved in the early development of the enteric nervous system, and most act through two distinct biochemical pathways mediated by RET and EDNRB. Mutations in RET and EDNRB account for up to 50% and 5% of HSCR cases in the general population, respectively. Interaction between these two signaling pathways could modify RET expression and, therefore, HSCR phenotype. Here, we report the case of a 1-year-old Taiwanese boy who presented with abdominal distension since birth and bilious vomiting after feeding. HSCR (short-segment type) was diagnosed based on X-ray, lower gastrointestinal series and biopsy findings. Mutation analysis revealed a heterozygous T>C missense mutation in exon 1 of the EDNRB gene, that substitutes the highly conserved cysteine-90 residue in the extracellular domain of the G protein-coupled receptor with an arginine residue (C90R). No RET gene mutation was detected in this patient.     

Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases.

Serine hydroxymethyltransferase (SHMT) provides activated one-carbon units required for the biosynthesis of nucleotides, protein, and methyl group by converting serine and tetrahydrofolate to glycine and N(5),N(10)-methylenetetrahydrofolate. It is postulated that SHMT activity is associated with the development of methotrexate resistance and the in vivo activity of SHMT is regulated by the binding of N(5)-CHO-THF, the rescue agent in high-dose methotrexate chemotherapy. The aim of this study is to advance our understanding of the folate-mediated one-carbon metabolism in zebrafish by characterizing zebrafish mitochondrial SHMT. The cDNA encoding zebrafish mitochondrial SHMT was cloned, overexpressed in Escherichia coli, and purified with a three-step purification protocol. Similarities in structural, physical, and kinetic properties were revealed between the recombinant zebrafish mitochondrial SHMT and its mammalian orthologs. Surprisingly, leucovorin significantly inhibits the aldol cleavage of serine catalyzed by zebrafish cytosolic SHMT but inhibits to a lesser extent the reaction catalyzed by the mitochondrial isozyme. This is, to our knowledge, the first report on zebrafish mitochondrial folate enzyme as well as the differential inhibition of leucovorin on these two SHMT isoforms. Western blot analysis revealed tissue-specific distribution with the highest enrichment present in liver for both cytosolic and mitochondrial SHMTs. Intracellular localization was confirmed by confocal microscopy for both mitochondrial and cytosolic SHMTs. Unexpectedly, the cytosolic isoform was observed in both nucleus and cytosol. Together with the previous report on zebrafish cytosolic SHMT, we suggest that zSHMTs can be used in in vitro assays for folate-related investigation and antifolate drug discovery.     

Interobserver Agreement for the Diagnosis of Venous Thromboembolism on Computed Tomography Chest Angiography and Indirect Venography of the Lower Extremities in Emergency Department Patients

Objectives: To determine interobserver agreement between radiologists for computed tomography (CT) angiography and venography. CT venography of the lower extremities combined with standard CT angiography of the chest may result in an increased overall diagnosis rate of venous thromboembolism (pulmonary embolism or deep venous thrombosis).
Methods: The study had a retrospective cohort design. The population consisted of emergency department patients who were evaluated for suspected pulmonary embolism. A random sample of 50 patients diagnosed and treated for venous thromboembolism and 50 age- and gender-matched patients whose CT angiograms and venograms were read as negative were enrolled. The original reading (R1) was compared with readings of two study radiologists: R2, a general radiologist, and R3, a radiologist with fellowship training in cross-sectional imaging. All readers were blinded to each other.
Results: Both R2 and R3 found both CT angiogram and venogram components technically adequate in 95% (95% CI = 89% to 98%) and 86% (95% CI = 78% to 92%) of studies, respectively. The agreement was very good for CT angiography (lowest agreement = 92%; lowest κ = 0.83) and was good for CT venography (85%, κ = 0.65). In nine cases, R1 read the CT angiogram as negative but the venogram as positive for DVT, whereas both R2 and R3 read both components as negative in four of these nine, suggesting a false-positive isolated DVT rate of 44% (95% CI = 19% to 73%). In no case did R1 read both scan components as negative when R2 and R3 agreed on presence of pulmonary embolism or DVT.
Conclusions: Diagnosis of pulmonary embolism on CT angiography is more reliable than diagnosis of isolated DVT on CT venography.     

Assessing ethical problem solving by reasoning rather than decision making

Context The assessment of ethical problem solving in medicine has been controversial and challenging. The purposes of this study were: (i) to create a new instrument to measure doctors’ decisions on and reasoning approach towards resolving ethical problems; (ii) to evaluate the scores generated by the new instrument for their reliability and validity, and (iii) to compare doctors’ ethical reasoning abilities between countries and among medical students, residents and experts. Methods This study used 15 clinical vignettes and the think‐aloud method to identify the processes and components involved in ethical problem solving. Subjects included volunteer ethics experts, postgraduate Year 2 residents and pre‐clerkship medical students. The interview data were coded using the instruments of the decision score and Ethical Reasoning Inventory (ERI). The ERI assessed the quality of ethical reasoning for a particular case (Part I) and for an individual globally across all the vignettes (Part II). Results There were 17 Canadian and 32 Taiwanese subjects. Based on the Canadian standard, the decision scores between Taiwanese and Canadian subjects differed significantly, but made no discrimination among the three levels of expertise. Scores on the ERI Parts I and II, which reflect doctors’ reasoning quality, differed between countries and among different levels of expertise in Taiwan, providing evidence of construct validity. In addition, experts had a greater organised knowledge structure and considered more relevant variables in the process of arriving at ethical decisions than did residents or students. The reliability of ERI scores was 0.70–0.99 on Part I and 0.75–0.80 on Part II. Conclusions Expertise in solving ethical problems could not be differentiated by the decisions made, but could be differentiated according to the reasoning used to make those decisions. The difference between Taiwanese and Canadian experts suggests that cultural considerations come into play in the decisions that are made in the course of providing humane care to patients.