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Describes an exchange teacher program intended to develop more active learning communities with students and existing faculty. Observes that dialogue between teachers in the lounge and after school began to change. Notes that students engaged in more active learning and began to view themselves in a different light, taking ownership of their learning. (SG)

Learning outcomes for continuing medical education should be derived from learner perspectives. Concise, clear objectives assist learners in selecting appropriate learning activities, structuring learning experiences, and determining what has been learned. (SK)

The enzyme 5.1O-methenyltetrahydrofolate synthetase catalyzes the key enzymatic reaction in the pathway by which 5-formyl tetrahydrofolate (leucovorin) enters the folate coenzyme pool. The distribution of this enzyme in different organs and tumor cell lines was studied. This enzyme has a wide distribution among organs and tumor cell lines with highest levels of activity in liver and kidney. Tumor cell lines also contain significant levels of this enzyme activity. Thus, leucovorin can be converted to active folate coenzyme forms in organs and tumor cells, and does not require conversion in liver alone. The implications of these findings for leucovorin usage as "rescue" after methotrexate treatment or to augment fluoropyrimidine cytotoxicity are discussed.

Background: During pregnancy, the demand for folic acid increases since the fetus requires this nutrient for its rapid growth and cell proliferation. The placenta concentrates folic acid into the fetal circulation; as a result the fetal levels are 2 to 4 times higher than the maternal level. Animal and in vitro studies have suggested that alcohol may impair transport of folic acid across the placenta by decreasing expression of transport proteins. We aim to determine if folate transfer to the fetus is altered in human pregnancies with chronic alcohol consumption. Methodology/Principal Findings: Serum folate was measured in maternal blood and umbilical cord blood at the time of delivery in pregnancies with chronic and heavy alcohol exposure (n = 23) and in non-drinking controls (n = 24). In the alcohol-exposed pairs, the fetal:maternal serum folate ratio was >1.0 in over half (n = 14), whereas all but one of the controls were >1.0. Mean folate in cord samples was lower in the alcohol-exposed group than in the controls (33.15±19.89 vs 45.91±20.73, p = 0.04). Conclusions/Significance: Our results demonstrate that chronic and heavy alcohol use in pregnancy impairs folate transport to the fetus. Altered folate concentrations within the placenta and in the fetus may in part contribute to the deficits observed in the fetal alcohol spectrum disorders. [ABSTRACT FROM AUTHOR]

We previously showed that severe inspiratory resistive loads cause acute (<1 h) cardiorespiratory failure characterized by arterial hypotension, multifocal myocardial infarcts, and diaphragmatic fatigue. The mechanisms responsible for cardiovascular failure are unknown, but one factor may be the increased ventricular afterload caused by the large negative intrathoracic pressures generated when breathing against an inspiratory load. Because expiratory threshold loads increase intrathoracic pressure and decrease left ventricular afterload, we hypothesized that anesthetized rats forced to breathe against such a load would experience only diaphragmatic failure. Loading approximately doubled end-expiratory lung volume, halved respiratory frequency, and caused arterial hypoxemia and hypercapnia, respiratory acidosis, and increased inspiratory drive. Although hyperinflation immediately reduced the diaphragm's mechanical advantage, fatigue did not occur until near load termination. Mean arterial pressure progressively fell, becoming significant (cardiovascular failure) midway through loading despite tachycardia. Loading was terminated (endurance 125 ± 43 mm; range 82-206 mm) when mean arterial pressure dropped below 50 mmHg. Blood samples taken immediately after load termination revealed hypoglycemia, hyperkalemia, and cardiac troponin T, the last indicating myocardial injury that was, according to histology, mainly in the right ventricle. This damage probably reflects a combination of decreased 02 delivery (decreased venous return and arterial hypoxemia) and greater afterload due to hyperinflation-induced increase in pulmonary vascular resistance. Thus, in rats breathing at an increased end-expiratory lung volume, cardiorespiratory, not just respiratory, failure still occurred. Right heart injury and dysfunction may contribute to the increased morbidity and mortality associated with acute exacerbations of obstructive airway disease. [ABSTRACT FROM AUTHOR]

Background: Drug abuse is a frequent factor in emergency department (ED) visits. Although commonly performed, qualitative testing of urine for drugs of abuse (u-DOA) is inherently limited in its ability to establish the identity, timing or dose of substances used. Previous studies have demonstrated these limitations, but their designs cannot be used to determine whether the results of u-DOA tests affect physicians' patient care decisions. Our objective was to determine the impact of u-DOA testing on the care of patients who present to the ED. Methods: All adults 18 years of age or older who had u-DOA testing in 2 urban teaching EDs were eligible. Victims of vehicular trauma or sexual assault were excluded. Just prior to communicating the results of u-DOA testing for a patient, an investigator interviewed the ordering physician or consultant physician about the patient care plans for that patient. Test results were then revealed, and the questions immediately repeated. This design isolated the impact of knowledge of u-DOA test results on physicians' patient care decisions. Any intended changes in patient care plans reported by the interviewed physician were compared to a priori criteria for substantive change and then subsequently reviewed by an independent expert to determine whether that change was justified. Results: Of the 110 u-DOA test results studied and the resultant 133 opportunities to influence physician management plans, there were 4 reported changes in management. One management change was judged to be substantive, but none of the 4 reported changes were considered by the independent expert reviewer to be justified. Urine-DOA testing thus led to a justified change in management in 0/133 instances (95% confidence interval 0%-2.3%). Conclusions: Urine-DOA is rarely helpful in guiding patient care decisions in the ED. The results of this study call into question the need for this test in the ED setting. [ABSTRACT FROM AUTHOR]

: ObjectivesSalivary analysis is a noninvasive alternative that may be more acceptable to patients, especially children. As such, it has the potential for incorporation into comprehensive, dynamic investigations of metabolic dysfunctions - a significant advancement over a single time point serum analysis. In this study, we wanted to determine if the serum cortisol assay on our routine immunoassay analyzer could reliably measure salivary cortisol concentrations. Because of potential fluctuations in salivary concentrations, we included a biologic variation study as a main facet of our preliminary method evaluation.: Design and methodsTwenty-eight healthy individuals (12 males, 16 females) volunteered to provide 5 nonconsecutive first morning saliva samples over a two-week period. Samples were stored frozen at home until the completion of the study. Following thawing and centrifugation, cortisol was measured in batch mode for each set of participant samples on the ROCHE Elecsys. Biologic variation was determined following removal of outliers. A method comparison was performed with the DPC Coat-A-Count Cortisol assay following the recommended modifications for salivary analysis, and with the Salimetrics HS-Cortisol two-site monoclonal assay optimized for salivary cortisol.: ResultsMean salivary cortisol concentration was 20.4 nmol/L. Analytical variation (CVA = 3.8%), within-subject variation (CVI = 6.3%), between-subject variation (CVG = 20.5%), index of individuality (II = 0.36) and reference change value (RCV = 20.4%) were determined. A negative 40% proportional bias was observed on the Elecsys compared to the two methods that have already been optimized for salivary analysis.: ConclusionsThis study demonstrated that salivary cortisol can be reliably measured on a routine automated immunoassay analyzer such as the ROCHE Elecsys. This particular assay needs to be optimized at the low end of the standard curve for routine use with salivary samples. Based on the relatively small intra-individual variation and low index of individuality, reference change values are preferable to the use of population reference intervals for this assay. [Copyright &y& Elsevier]

Objectives: Previous literature has approached proficiency testing (PT) performance by defining the minimum levels, and combinations of imprecision and bias, necessary to meet PT requirements. In this case report, current PT performance was assessed and modeling performed to prioritize our quality improvement efforts.Methods: A total of 1006 chemistry challenge results from Ontario’s Laboratory Proficiency Testing Program (LPTP, now QMPLS) performed on 69 tests during 1999 and 2000 were used for this retrospective analysis. Peer group means, all method means and results from reference labs were used for comparison. QMPLS flagging and recommended performance criteria were compiled, and modeling performed to predict different levels of performance.Results: Our internal imprecision is <5% for 72% of our 69 tests; however, only 20% of our tests had a CV/PT <25%. Of the 1006 challenges performed, 136 (13.5%) results were outside PT limits, 55 (5.5%) results were flagged, and 12 requests were received from QMPLS seeking clarification on 24 (2.4%) results. Follow-up identified 9 (38%) nonanalytical errors, 8 (33%) method bias errors, 4 (17%) random errors, 2 poor methods, and one with no error identified. Modeling predicted flagging rates of 2.4% using QMPLS recommended precision performance, 1.6% using our current internal imprecision, 2.2% or 7.0% if we included an overall 20% or 50% relative bias rate with our current imprecision levels, or 15.0% when an estimate of our actual bias for each analyte was considered along with our current imprecision levels.Conclusions: If imprecision were the only cause of PT errors, our flagging rate for this study period would be 1.6%, and we would need to formally investigate 8 results a year. In practice, strict application of the QMPLS PT criteria would result in 68 investigations annually; however, judicial review of the results before request for clarification significantly reduced this number to 12 investigations (of which 38% were nonanalytical errors). At the present time bias is a significant cause of poor PT performance in a variety of assays. Individual laboratories need to address the problem of bias, and ultimately so do manufacturers. It would be helpful if PT programs also acknowledged this necessary evolution in both their criteria and processes. [Copyright &y& Elsevier]

Highlights ways to derive learning outcome objectives that address a variety of traditional and nontraditional continuing medical education (CME) outcomes. Ways to write concise, clear objectives; Role of objectives in enhancing learning; Practical tips on using learning outcome objectives effectively.

Recent years have seen a steady decline in the number of new physician-investigation (Association of American Medical Colleges, 2000). To encourage medical students to select research careers, the Queen's University Faculty of Health Sciences curriculum includes a mandatory Critical Enquiry elective in the 2nd year. An anonymous written survey was administered to medical students before and after the elective to determine their perceptions of the value of the elective and its impact on their decision to pursue a career in medical research. There was a significant increase in the number of students expressing an interest in pursuing a research career following the elective (35-42%, p = 0.029). Students recognized other benefits including the development of critical appraisal, information literacy, and critical thinking skills; and the opportunity to select an area of and form contacts for postgraduate training. Even students who choose not to pursue careers in medical research perceive benefits to a mandatory undergraduate research elective. [ABSTRACT FROM AUTHOR]

Respiratory loads can cause respiratory pump failure but the underlying causes, often assumed to be asphyxia and inspiratory muscle fatigue, remain unresolved. In rat, we hypothesized that breathing at an increased end-expiratory lung volume would cause not just respiratory but cardiovascular failure. Rats breathed at an increased lung volume until inspiratory pressure generation decreased to half the loaded values (respiratory pump failure) or mean arterial pressure dropped below 60 mmHg (cardiovascular failure). Loading resulted in immediate arterial hypoxemia and hypercapnia, as well as a decrease in diaphragmatic contractility (ratio of transdiaphragmatic pressure to integrated phrenic activity). Contractility remained at this level during loading, despite arterial hypoxemia and hypercapnia/acidosis, until decreasing again at the time of respiratory pump failure. Respiratory drive was maintained and heart rate increased but blood pressure declined steadily. At termination of loading, cardiac troponin T was detected in the blood, indicating myocardial injury; moreover, the rats were hyperkalemic and hypoglycemic. Thus, in rats forced to breathe at an increased lung volume, cardiorespiratory, not just respiratory, failure occurs and factors other than fatigue, hypoxia and hypercapnia/ acidosis, such as hypoglycemia and hyperkalemia, may contribute. [ABSTRACT FROM AUTHOR]

Abstract Background Diagnosis, prognostication and treatment in chronic kidney disease is often informed by an estimate of the glomerular filtration rate (GFR). Commonly used GFR estimation (eGFR) equations are based on serum creatinine (Cr) concentrations and display suboptimal precision and accuracy. Newer equations incorporating additional endogenous markers such as β-Trace Protein (BTP), β 2 -Microglobulin (B2M) and cystatin C (cysC) have been developed but require validation. Methods This prospective cohort study evaluated the performance of 6 eGFR equations developed by the chronic kidney disease - epidemiology collaboration group (CKD-EPI) against urinary inulin clearance GFR in patients recruited from outpatient nephrology clinics. Results Mean biases were negligible and similar between equations. The eGFR-EPI Cr/cysC had the best precision and accuracy of all the equations and the best agreement with inulin mGFR when classifying participants into GFR categories. The BTP and B2M equations displayed the worst precisions and accuracies and showed the least consistent performance across levels of GFR. Thus, the eGFR-EPI Cr/cysC is the least biased, most precise and has the highest accuracy as compared to other eGFR-EPI equations. Conclusions The BTP and B2M equations are the worst performing of the eGFR-EPI equations, and no benefit is observed with the addition of BTP or B2M to Cr/cysC. [ABSTRACT FROM AUTHOR]

Background: The international initiative to standardize creatinine (Cr) assays by tracing reference materials to Isotope Dilution Mass Spectrometry (IDMS) assigned values was implemented to reduce interlaboratory variability and improve assay accuracy., Objective: The aims of this study were to examine whether IDMS standardization has improved Cr assay accuracy (bias), interlaboratory variability (precision), total error (TE), and attainment of recommended analytical performance goals., Methods: External Quality Assessment (EQA) data (n = 66 challenge vials) from Ontario, Canada, were analyzed. The bias, precision, TE, and the number of EQA challenge vials meeting performance goals were determined by assay manufacturer before (n = 32) and after (n = 34) IDMS implementation., Results: The challenge vials with the worst bias and precision were spiked with known common interfering substances (glucose and bilirubin). IDMS standardization improved assay bias (10.4%-1.6%, P < .001), but precision remained unchanged (5.0%-4.7%, P = .5) with performance goals not consistently being met. Precision and TE goals based on biologic variation were attained by only 29% to 69% and 32% to 62% of challenge vials., Conclusions: While IDMS standardization has improved Cr assay accuracy and thus reduced TE, significant interlaboratory variability remains. Contemporary Cr assays do not currently meet the standards required to allow for accurate and consistent estimated glomerular filtration rate assessment and chronic kidney disease diagnosis across laboratories. Further improvements in Cr assay performance are needed., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: The tracing of creatinine (Cr) reference materials to isotope dilution mass spectrometry-assigned values was implemented worldwide to reduce interlaboratory variability and improve assay accuracy. The aims of this study were to examine the current extent of interlaboratory variability and its effect on eGFR., Design, Setting, Participants, & Measurements: Leftover plasma from 2-3 consecutive days was obtained from 53 intensive care unit patients with a range of kidney functions. Individual patient samples were pooled and split and sent to 12 different laboratories for Cr measurement. For each patient, the mean Cr and Chronic Kidney Disease Epidemiology Collaboration eGFR (eGFR-EPI), assuming a 65-year-old nonblack woman, were determined. Interlaboratory variability was assessed by the range and SD of Cr and eGFR-EPI. This was repeated after stratifying by assay type and by the median Cr of 1.36 mg/dl. For patients whose eGFR-EPI range included 60 ml/min per 1.73 m 2 , the percentage of laboratories with eGFR-EPI<60 ml/min per 1.73 m 2 was determined., Results: The mean±SD of the Cr and eGFR-EPI ranges were 0.20±0.09 mg/dl and 14±9 ml/min per 1.73 m 2 for Cr<1.36 mg/dl. Jaffe Cr results were an average 0.1 mg/dl (Cr≥1.36 mg/dl) and 0.05 mg/dl (Cr<1.36 mg/dl) higher than enzymatic results (P<0.001 for both). Ten patients had an eGFR-EPI range that included 60 ml/min per 1.73 m 2 . Their median eGFR-EPI range was 15 ml/min per 1.73 m 2 . There was significant discordance in the diagnosis of CKD (eGFR-EPI<60 ml/min per 1.73 m 2 ), with laboratories using Jaffe Cr methods making the diagnosis more frequently than those using enzymatic Cr methods (60% versus 39%)., Conclusions: Significant interlaboratory variability in Cr measurement still exists. Jaffe assays yield higher Cr values than enzymatic assays, leading to lower eGFR-EPIs and more frequent CKD diagnoses. Further improvements in assay performance are required to standardize patient CKD diagnosis and to facilitate longitudinal Cr monitoring across laboratories., (Copyright © 2016 by the American Society of Nephrology.)

The biochemical diagnosis of male hypogonadism remains a controversial issue. The problem is compounded by the variety of laboratory assays available to measure serum testosterone (T) and the limited understanding, among clinicians, of their relative diagnostic validity. It is widely accepted that only the testosterone not bound to sex hormone-bounding globulin is metabolically active. Therefore, for diagnostic purposes it is frequent practice to order the measurement of free T (FT) or bioavailable T (BAT). Our objective is to describe the methods available for measuring FT and to review the literature to determine the relevance of ordering FT as a diagnostic laboratory tool in cases of suspected hypogonadism. We also provide our biochemical approach in evaluating men with T deficiency. The limited information available in this regard is frequently confined to the biochemistry literature. The few reliable studies indicate that analog-based measurement of FT offers no diagnostic or financial advantage over automated assay for total T. The manuscript also describes "How we do it." For optimal diagnostic accuracy and financial responsibility, total T and calculated FT (cFT) should be the tests employed for initial and confirmatory diagnosis respectively. Measurement of bioavailable T is an alternative option but not germane to the points to which we are calling attention in this paper. While clinicians should be discouraged from ordering FT assays, laboratories performing it should indicate what method was used and warned about possible reliability concerns. FT assays should no longer be a reimbursable test.

Background and Objectives: Cystatin C (CysC) is a promising marker of GFR. Several equations have been derived to estimate GFR from its serum concentration. Heterogeneity in the performance of these equations exists in validation studies even when the same CysC assay from the same manufacturer is utilized. This study was designed to examine the differences in CysC and GFR estimation (eGFR) using Siemens' nephelometric immunoassay and the Mayo Clinic equation. The ability of the eGFRs to predict measured GFR was also examined., Design, Setting, Participants, & Measurements: Ninety-seven split samples were sent to laboratories at Children's Hospital of Eastern Ontario (CHEO) in Ottawa, Canada, and at the Mayo Clinic in Rochester, Minnesota., Results: The mean CHEO CysC was 0.17 mg/L (10%) lower than the mean Mayo Clinic CysC. Using the Mayo Clinic equation, the mean eGFR difference was 7.2 ml/min per 1.73 m(2) (15%). Approximately 36% of the results agreed within 10%, while 13% were discordant by greater than 30%. Larger absolute differences in mean eGFR between the two laboratories were found in the subgroup with CysC less than 1.41 mg/L as compared with the subgroup greater than 1.41 mg/L (9.5 versus 5.0 ml/min per 1.73 m(2)). Correction of CHEO values to the Mayo Clinic did not improve GFR estimation., Conclusions: Significant differences in CysC measurement exist between laboratories using the same assay by the same manufacturer and these lead to clinically relevant differences in GFR estimation. This interlaboratory variability needs to be recognized when interpreting and comparing CysC and eGFR results.

Objectives: Salivary analysis is a noninvasive alternative that may be more acceptable to patients, especially children. As such, it has the potential for incorporation into comprehensive, dynamic investigations of metabolic dysfunctions - a significant advancement over a single time point serum analysis. In this study, we wanted to determine if the serum cortisol assay on our routine immunoassay analyzer could reliably measure salivary cortisol concentrations. Because of potential fluctuations in salivary concentrations, we included a biologic variation study as a main facet of our preliminary method evaluation., Design and Methods: Twenty-eight healthy individuals (12 males, 16 females) volunteered to provide 5 nonconsecutive first morning saliva samples over a two-week period. Samples were stored frozen at home until the completion of the study. Following thawing and centrifugation, cortisol was measured in batch mode for each set of participant samples on the ROCHE Elecsys. Biologic variation was determined following removal of outliers. A method comparison was performed with the DPC Coat-A-Count Cortisol assay following the recommended modifications for salivary analysis, and with the Salimetrics HS-Cortisol two-site monoclonal assay optimized for salivary cortisol., Results: Mean salivary cortisol concentration was 20.4 nmol/L. Analytical variation (CV(A) = 3.8%), within-subject variation (CV(I) = 6.3%), between-subject variation (CV(G) = 20.5%), index of individuality (II = 0.36) and reference change value (RCV = 20.4%) were determined. A negative 40% proportional bias was observed on the Elecsys compared to the two methods that have already been optimized for salivary analysis., Conclusions: This study demonstrated that salivary cortisol can be reliably measured on a routine automated immunoassay analyzer such as the ROCHE Elecsys. This particular assay needs to be optimized at the low end of the standard curve for routine use with salivary samples. Based on the relatively small intra-individual variation and low index of individuality, reference change values are preferable to the use of population reference intervals for this assay.