Evidence-based dentistry skill acquisition by second-year dental students.

INTRODUCTION: Identification and assessment of Evidence-based dentistry (EBD) outcomes have been elusive. Our objective was to describe EBD skill acquisition during the second (D2) year of pre-doctoral dental education and student competency at the end of the year. METHODS: The first and fourth (final) curricular-required EBD Exercises (ie, application of the first 4 steps of the 5-Step evidence-based practice process applied to a real or hypothetical situation) completed by D2 students (n = 151) during 2014-2015 and 2015-2016 were evaluated to measure skill acquisition through use of a novel rubric with measures of performance from novice to expert. Exercises were evaluated on the performance for each step, identification of manuscript details and reflective commentary on manuscript components. Changes in performance were evaluated using the chi-square test for trend and the Wilcoxon signed-rank test. RESULTS: Seventy-eight per cent of students scored competent or higher on the Ask step at the beginning of the D2 year; scores improved with 58% scoring proficient or expert on the fourth Exercise (P < .001). Most students were advanced beginners or higher in the Acquire, Appraise and Apply steps at the beginning of the D2 year, with minimal growth observed during the year. Identification of manuscript details improved between the first and fourth Exercises (P = .015); however, depth of commentary skills did not change. DISCUSSION: Unlike previous investigations evaluating EBD knowledge or behaviour in a testing situation, we evaluated skill acquisition using applied Exercises. CONCLUSION: Consistent with their clinical and scientific maturity, D2 students minimally performed as advanced beginners at the end of their D2 year.

An approach on defining competency in evidence-based dentistry.

INTRODUCTION: Assessment of evidence-based dentistry (EBD) knowledge and behaviour is hampered by lack of explicit competency criteria. This void impedes instructional design and assessment of student growth during the educational process. METHODS: Knowledge and cognitive domains supporting educational objectives in a pre-doctoral dental programme were identified for each level of the EBD five-step process. We articulated educational objectives with behavioural expectations for each level of skill acquisition at each step of the EBD process. Outcome evaluation criteria identify students' progressive level of skill acquisition from novice to expert. RESULTS: The educational objectives, type of knowledge, and nature of the cognitive process supporting these objectives are presented for each step of the EBD process. For example, educational objectives of the "Ask" step include (i) to construct a question from the patient presentation and knowledge limitations that addresses the clinical problem and (ii) to articulate the Problem, Intervention/Exposure, Comparison, Outcome (PICO) components. Achievement of these objectives requires both factual information regarding the PICO format and the cognitive process of understanding. Educational outcome criteria consistent with a competent clinician include clear articulation of the PICO with identifiable pieces that relate to the clinical situation. DISCUSSION: Assessment strategies for progression towards EBD competency are limited due to the complexity associated with evaluating EBD knowledge and behaviours. To evaluate performance, the EBD academic community must define competency expectations for entry into unsupervised general dental practice. CONCLUSION: This framework offers measurable outcome evaluation criteria to initiate a conversation with academic peers regarding current gaps in EBD assessment.

Late effects of a brief psychological intervention in patients with intermittent claudication in a randomized clinical trial.

BACKGROUND: The authors previously reported the early results of a trial of a brief psychological intervention to increase physical activity in patients with intermittent claudication. After 4 months, participants in the intervention group walked a mean of 1576 more steps per day than control group participants. The present study followed the original participants to determine whether this behaviour change was maintained over 2 years. METHODS: This was a randomized single-centre parallel-group trial. Fifty-eight patients newly diagnosed with intermittent claudication were assigned randomly to one of two groups. The control group (30 patients) received usual care: lifestyle advice and consultation with a vascular surgeon to agree a treatment plan. The treatment group (28) received usual care plus a brief psychological intervention designed to modify illness and walking beliefs, and develop a personalized walking action plan. The primary outcome was daily steps measured by pedometer. Secondary outcomes included revascularization rate, quality of life and perceived pain-free walking distance. Follow-up was conducted at 1 and 2 years. Between-group differences were analysed by analysis of co-variance. RESULTS: Participants in the brief psychological intervention group walked significantly more than those in the control group. The mean difference at 1 year was 1374 (95 per cent confidence interval 528 to 2220) steps per day and the difference at 2 years was 1630 (495 to 2765) steps per day. CONCLUSION: Modifying illness and walking beliefs, and assisting patients to develop a personalized walking action plan led to increases in walking behaviour in patients with claudication that were maintained for 2 years. REGISTRATION NUMBER: ISRCTN28051878 (http://www.controlled-trials.com).

Student performance and course evaluations before and after use of the Classroom Performance System ™ in a third-year veterinary radiology course.

Effective teaching of veterinary radiology can be challenging in a traditional classroom environment. Audience response systems, colloquially known as "clickers," provide a means of encouraging student interaction. The purpose of this study was to compare student performance and course evaluations before and after using the Classroom Performance System™ in the third-year (fifth semester) didactic radiology course at the University of Tennessee College of Veterinary Medicine. Overall student performance was assessed by comparing median numeric final course grades (%) between years without and with use of the Classroom Performance System™. Grades of students were determined for individual instructors' sections. Student evaluations of the radiology course were compared for the years available (2007-2010). Student interactions were also evaluated subjectively by instructors who used the Classroom Performance System™. There was a significant difference (p = 0.009) between the median student grade before (2005 - 2008, median 82.2%; interquartile range 77.6-85.7%; range 61.9-95.5%) and after use of the classroom performance system (2009-2010, median 83.6%; interquartile range 79.9-87.9%; range 68.2-93.2%). There was no statistically significant difference in median student grades for individual instructors over the study period. The radiology course student evaluation scores were significantly higher in years where the Classroom Performance System™ was used in comparison to previous years (P = 0.019). Subjectively, students appeared more involved when using clickers. Findings indicated that the Classroom Performance System™ may be a useful tool for enhancing veterinary radiology education.

Randomized clinical trial of a brief psychological intervention to increase walking in patients with intermittent claudication.

BACKGROUND: Increased walking is often recommended for patients with intermittent claudication (IC). Current methods to increase walking in these patients increase capability but not daily behaviour. This trial assessed whether a brief psychological intervention could increase daily walking at 4 months. METHODS: This randomized, single-centre, parallel-group trial was conducted between April 2008 and July 2010. Patients newly diagnosed with IC were randomly assigned into two groups. All clinical staff involved in patient management were blinded to allocation. The control group received usual care plus researcher contact, and the treatment group received usual care and a brief psychological intervention to modify illness and walking beliefs and to develop a personalized walking action plan. The psychological intervention was delivered in two 1-h sessions in participants' homes. The primary outcome was daily steps measured by pedometer 4 months later. Analyses were by intention to treat. RESULTS: Of 109 patients screened, 72 were eligible for inclusion; 58 patients consented to participate and were randomly allocated to usual care (30) or brief psychological intervention (28). All 58 participants were included in the analysis of the primary outcome. Compared with controls at 4-month follow-up, participants who received the psychological intervention walked a mean of 1575·63 (95 per cent confidence interval 731·97 to 2419·29) more steps per day. There were no adverse events. CONCLUSION: A brief psychological intervention significantly increased daily walking in patients with IC at 4 months. This study provided support for a potentially new direction in the treatment of IC. REGISTRATION NUMBER: ISRCTN28051878 (http://www.controlled-trials.com).

Intrinsic stability and functional properties of disulfide bond-stabilized coagulation factor VIIIa variants.

BACKGROUND: The utility of purified coagulation factor (F)VIII for treatment of hemophilia A is limited in part by its instability following activation by thrombin, which is caused by spontaneous dissociation of the A2 domain from the activated FVIII (FVIIIa) heterotrimer. To prevent this A2 domain dissociation in FVIIIa, we previously engineered a cysteine pair (C664-C1826) in recombinant FVIII that formed a disulfide bond cross-linking the A2 domain in the heavy chain to the A3 domain in the light chain. This engineered disulfide bond resulted in a more stable FVIIIa. AIMS: Here, we characterize the functional parameters of C664-C1828 FVIII and of a new disulfide bond-stabilized FVIII (C662-C1828 FVIII). METHODS: In order to assess whether these FVIII variants might be good candidates for a new therapeutic agent to treat hemophilia A, we investigated a variety of functional parameters that might affect the in vivo properties of the variants, including half-life of disulfide bond-stabilized FVIII and FVIIIa and the potency of these FVIIIa molecules in the FXase complex. RESULTS: Both disulfide bond-stabilized variants had improved affinity for von Willebrand factor (VWF). In studies of FX activation by purified FIXa and FVIIIa, C662-C1828 FVIIIa had normal activity while C664-C1826 FVIIIa had reduced activity. Both C664-C1826 FVIIIa and C662-C1828 FVIIIa were inactivated by activated protein C (APC) but the rates of inactivation were different. CONCLUSION: Overall, the specific location of the disulfide bridge between the A2 and A3 domains appears to affect functional properties of FVIIIa. In summary, introduction of engineered interdomain disulfides results in FVIIIa variants that resist spontaneous loss of activity while retaining susceptibility to APC proteolytic inactivation and maintaining VWF binding.

LMAN1 is a molecular chaperone for the secretion of coagulation factor VIII.

Combined deficiency of both coagulation factors (F)V and VIII is a rare autosomal recessive bleeding disorder caused by null expression of LMAN1 (previously termed ERGIC-53) in a majority of affected individuals. Previously, a requirement for a functional LMAN1 cycling pathway between the ER and Golgi was demonstrated for efficient secretion of FV and FVIII (Moussalli et al. J Biol Chem 1999; 274: 32569), however, the molecular nature of the interaction between LMAN1 and its cargo was not characterized. Using coimmunoprecipitation of LMAN1 and FVIII from transfected HeLa and COS-1 cells, we demonstrate an interaction between LMAN1 and FVIII in vivo. The interaction was mediated via high mannose-containing asparagine-linked oligosaccharides that are densely situated within the B domain of FVIII, as well as protein-protein interactions. These results are interpreted based on the recent determination of the crystal structure of the carbohydrate recognition domain of LMAN1.

Routine evaluation of the cervical spine in head-injured patients with dynamic fluoroscopy: a reappraisal.

BACKGROUND: The mechanism for clearing the cervical spine in patients with altered mental status remains controversial. Recommendations have ranged from removal of the cervical collar after 24 hours in patients with normal radiographs, to indefinite immobilization in a cervical collar, and recently cervical flexion-extension examinations using dynamic fluoroscopy. The purpose of this study was to evaluate the efficacy and safety of dynamic fluoroscopy flexion-extension examinations in identifying ligamentous cervical spine injury and clearing the cervical spine in patients with altered mental status after trauma. METHODS: Patients with a Glasgow Coma Scale score < 13 for greater than 48 hours after admission and normal cervical spine radiographs were candidates for fluoroscopic evaluation. The protocol required visualization of the entire cervical spine, through T1, through full extension and flexion under the direct supervision of a radiologist. Oblique fluoroscopic views were obtained, as necessary, to visualize the cervicothoracic junction. Demographic data, fluoroscopy time, total time per study, true and false positives and negatives, and complications were recorded. RESULTS: From July 1992 through December 1999, fluoroscopic examinations were performed on 301 patients. There were 297 true-negative examinations, 2 true-positive examinations (stable injuries), 1 false-negative examination, and 1 false-positive examination. The incidence of ligamentous injury identified by fluoroscopy in this study was 2 of 301 (0.7%). Unstable cervical spine ligamentous injuries were identified in only 0.02% of all trauma patients. One patient developed quadriplegia when fluoroscopic evaluation was performed after two protocol violations. CONCLUSION: Unstable cervical spine ligamentous injury without fracture is a rare occurrence. The cervical spine may be cleared after a normal cervical spine series (plain radiograph and computed tomographic scan) as recommended in the 1998 Eastern Association for the Surgery of Trauma guidelines. If dynamic fluoroscopy is to be used, adherence to the protocol, including review of the cervical spine radiographs before fluoroscopy and visualization of the entire cervical spine, C1-T1, is mandatory to ensure patient safety.

Glucose monitoring in type 2 diabetes.

A major goal in the treatment of type 2 diabetes is to maintain blood glucose values in the normal or near normal range. A system of monitoring glycemic control, which includes self-monitoring of blood glucose (SMBG) by the patient, and frequent glycated protein assays, is an important tool for achieving this goal. Optimal use of SMBG by the patient is best accomplished through comprehensive glucose monitoring education, which includes appropriate monitor selection and use and strategies to use monitoring results to improve glycemic control.

Protease-activated receptor 1 mediates thrombin-dependent, cell-mediated renal inflammation in crescentic glomerulonephritis.

Protease-activated receptor (PAR)-1 is a cellular receptor for thrombin that is activated after proteolytic cleavage. The contribution of PAR-1 to inflammatory cell-mediated renal injury was assessed in murine crescentic glomerulonephritis (GN). A pivotal role for thrombin in this model was demonstrated by the capacity of hirudin, a selective thrombin antagonist, to attenuate renal injury. Compared with control treatment, hirudin significantly reduced glomerular crescent formation, T cell and macrophage infiltration, fibrin deposition, and elevated serum creatinine, which are prominent features of GN. PAR-1-deficient (PAR-1(-/-)) mice, which have normal coagulation, also showed significant protection from crescentic GN compared with wild-type mice. The reductions in crescent formation, inflammatory cell infiltration, and serum creatinine were similar in PAR-1(-/-) and hirudin-treated mice, but hirudin afforded significantly greater protection from fibrin deposition. Treatment of wild-type mice with a selective PAR-1-activating peptide (TRAP) augmented histological and functional indices of GN, but TRAP treatment did not alter the severity of GN in PAR(-/-) mice. These results indicate that activation of PAR-1 by thrombin or TRAP amplifies crescentic GN. Thus, in addition to its procoagulant role, thrombin has proinflammatory, PAR-1-dependent effects that augment inflammatory renal injury.

Tissue factor and factor VIIa receptor/ligand interactions induce proinflammatory effects in macrophages.

The potential for tissue factor (TF) to enhance inflammation by factor VIIa-dependent induction of proinflammatory changes in macrophages was explored. Purified recombinant human factor VIIa enhanced reactive oxygen species production by human monocyte-derived macrophages expressing TF in vitro. This effect was dose- and time-dependent, ligand- and receptor-specific, and independent of other coagulation proteins. This receptor/ligand binding induced phospholipase C-dependent intracellular calcium fluxes. Transfection studies using a human monocyte-derived cell line (U937) demonstrated that an intact intracytoplasmic domain of TF is required for factor VIIa-induced intracellular calcium fluxes. The capacity of TF to enhance proinflammatory functions of rabbit peritoneal-elicited macrophages (production of reactive oxygen species and expression of major histocompatibility complex class II and cell adhesion molecules) was demonstrated in vivo by treatment with an anti-TF antibody. These data demonstrate that, in addition to its role in activation of coagulation, TF can directly augment macrophage activation. These effects are initiated by binding factor VIIa and are independent of other coagulation proteins. These studies provide the first demonstration of a direct proinflammatory role for TF acting as a cell-signaling receptor.

Immunopathogenesis of crescentic glomerulonephritis.

Crescentic glomerulonephritis provides an important therapeutic challenge because of its rapidly progressive course and poor outcome. Studies in animal models have elucidated some of the pivotal pathogenetic mechanisms, and human studies increasingly support the clinical relevance of these animal data. Accumulating evidence suggests that crescentic glomerulonephritis results from a complex cell-mediated nephritogenic immune response. Interruption of a number of immune and inflammatory mediators can improve the outcome of this disease.

Using choice-based conjoint to determine the relative importance of dental benefit plan attributes.

The purpose of this study was to use conjoint analysis to determine the importance of specific dental benefit plan features for University of Iowa (UI) staff and to build a model to predict enrollment. From a random sample of 2000 UI staff, 40 percent responded (N = 773). The survey instrument was developed using seven attributes (five dental benefit plan features and two facility characteristics) each offered at three levels (e.g., premium = $20, $15, $10/month). Pilot testing was used to find a realistic range of plan options. Twenty-seven hypothetical dental benefit plans were developed using fractional factorial combinations of the three levels for each of the seven attributes. For all of the hypothetical plans, dental care was to be provided in the UI predoctoral dental clinic. Plan profiles were arranged four per page by combining the existing plan with three hypothetical plans, for a total of nine pages. Respondents' task was to select one plan from each set of four. A regression-like statistical model (Multinomial Logit) was used to estimate importance of each attribute and each attribute level. Relative importance (and coefficients) for each of the seven attributes are as follows: maximum annual benefit (.98), orthodontic coverage (.72), routine restorative (.70), major restorative (.67), time to complete treatment (.61), clinic hours of operation (.47), premium (.18). For each attribute, relative importance of each of three levels will also be presented. These coefficients for each level are used to predict enrollment for plans with specific combinations of the dental benefit plan features.

Tissue factor pathway inhibitor expression in human crescentic glomerulonephritis.

BACKGROUND: Tissue factor (TF) pathway inhibitor (TFPI), the major endogenous inhibitor of extrinsic coagulation pathway activation, protects renal function in experimental crescentic glomerulonephritis (GN). Its glomerular expression and relationship to TF expression and fibrin deposition in human crescentic GN have not been reported. METHODS: Glomerular TFPI, TF, and fibrin-related antigen (FRA) expression were correlated in renal biopsies from 11 patients with crescentic GN. Biopsies from 11 patients with thin basement membrane disease and two normal kidneys were used as controls. RESULTS: TFPI was undetectable in control glomeruli but was detectable in interstitial microvessels. In crescentic biopsies, TFPI was detected in cellular crescents and was more prominent in fibrous/fibrocellular crescents, indicating a correlation with the chronicity of crescentic lesions. TFPI appeared to be associated with macrophages but not endothelial or epithelial cells. TFPI was generally undetectable in regions of the glomerular tuft with minimal damage. In contrast, TF and FRA were strongly expressed in regions of minimal injury, as well as in more advanced proliferative and necrotizing lesions. Despite prominent TF expression, FRA was less prominent in fibrous/fibrocellular crescents in which TFPI expression was maximal. CONCLUSIONS: These data suggest that TFPI is strongly expressed in the later stages of crescent formation and is inversely correlated with the presence of FRA in human crescentic GN. This late induction of TFPI may inhibit TF activity and favor reduced fibrin deposition in the chronic stages of crescent formation.

Prominence of cell-mediated immunity effectors in "pauci-immune" glomerulonephritis.

The majority of patients with rapidly progressive crescentic glomerulonephritis show histologic features of extensive necrosis and focal and segmental proliferation with fibrin production, but little or absent Ig deposition in the glomerulus. This subcategory of the disease, labeled "pauci-immune" glomerulonephritis, has recently been shown to be associated with the presence of antineutrophil cytoplasmic antibody in the patient's circulation (but not within the glomerulus). The absence of the effectors of humoral immunity at the site of renal injury led to this investigation of the contribution of cell-mediated immunity to the glomerular injury in this form of glomerulonephritis. In 15 patients presenting acutely with pauci-immune glomerulonephritis, CD3-positive T cells (3.7+/-2.5 [mean +/- SD] cells per glomerular cross section, [c/gcs]), CD45RO-positive T cells (2.7+/-1.9 c/cgs), macrophages (7.3+/-6.1 c/gcs), fibrin (3+), and endothelial-associated tissue factor were demonstrated to be prominent in glomeruli. These mediators were absent in a group of 12 patients with thin basement membrane disease and only occasionally observed in a group of eight patients with "humorally mediated"(noncrescentic) glomerulonephritis. Thus, in pauci-immune glomerulonephritis, there is the development of significant cell-mediated immunity with activated T cells, macrophages, tissue factor, and fibrin at the site of glomerular injury, suggesting that this glomerular disease is most likely a manifestation of T cell-directed cognate immune injury.

Does free fluid on abdominal computed tomographic scan after blunt trauma require laparotomy?

BACKGROUND: Abdominal computed tomographic (CT) scans are used in the evaluation of blunt trauma. The purpose of this study was to determine if isolated intraperitoneal fluid seen on CT scan necessitates laparotomy. METHODS: Trauma registry records of patients who underwent abdominal computed tomography from January 1994 through January 1997 were studied. Data were reviewed for age, gender, CT scan interpretation, associated injuries, and operative findings. RESULTS: Abdominal injury was identified in 126 patients. Seventy-eight patients had evidence of solid-organ injury and 17 patients had extraperitoneal injury. Isolated intraperitoneal fluid was identified in 31 patients. All patients with isolated fluid underwent laparotomy; 29 of these procedures (94%) were therapeutic. Bowel injuries occurred in 18 patients and mesenteric injuries in 8 patients. Five patients had intraperitoneal bladder rupture, and undetected solid-organ injuries were found in two patients. Other organs injured included the stomach, pancreas, ovary, and uterus. CONCLUSION: Exploratory laparotomy was therapeutic in 94% of patients. Isolated intraperitoneal fluid on CT scan after blunt trauma mandates laparotomy.

Medical versus surgical management of diverticulitis in patients under age 40.

BACKGROUND: Diverticulitis in patients under age 40 is a distinct entity. We compared the medical versus surgical management of diverticulitis for complications and outcomes in these patients. METHODS: A retrospective review was performed for treatment, hospitalizations, complications, and outpatient visits. Complications included readmission, recurrent symptoms after antibiotic therapy, and postoperative problems. RESULTS: Twenty-nine patients had a radiographic or surgical diagnosis of diverticulitis (18 surgical, 11 medical). Medically managed patients had significantly more emergency department visits (4.7 +/- 6.6 versus 0.3 +/- 0.6, P < or =0.01), and readmissions (7 versus 4, P < or =0.02). Three surgical patients (17%) had a total of 6 complications as compared with 6 medical patients (55%) with 25 complications (chi square, P < or =0.05). All medically treated patients had recurrent symptoms, and 6 required surgery. CONCLUSION: Medically managed patients had significantly more emergency department visits and complications than those managed surgically. Surgery is the indicated treatment for the first episode of diverticulitis in patients under age 40.

Impact of mutations at the P4 and P5 positions on the reaction of antithrombin with thrombin and elastase.

Antithrombin (AT) is a serpin capable of trapping thrombin (IIa) in a stable and covalent complex. Complex formation is prevented by leukocyte elastase (LE) cleavage near the AT reactive centre. We mutated the known LE cleavage sites of AT to explore the possibility of producing an LE-resistant AT molecule. Initially, six rabbit AT variants differing only at residue 390 (P4) were generated in a cell-free system, and gel-based assays were used to assess IIa-mediated complex formation and LE-mediated cleavage of the variants. Substitution of charged residues (Glu or Arg) reduced complex formation by 50-60%, while the Ser variant was incapable of inhibiting thrombin; LE reactivity was less affected. The least (Trp) and most (Ser) affected variants were expressed in COS-1 cells. Again, the Ser variant was incapable of detectably reducing the rate of thrombin-mediated amidolysis while the Trp variant inhibited thrombin at a slightly reduced rate (-28%). LE inactivated the Trp variant and the wild-type AT to a similar extent. Recreation of the Trp mutation in COS-derived human AT showed similar results. Since retention of LE-sensitivity could have arisen due to cleavage at Val389 (P5), we produced and characterized a human AT substitution mutant with Trp at both P4 and P5. This variant showed a slight reduction in thrombin inhibitory activity (-22%), but remained susceptible to LE inactivation. These results suggest either that LE cleaves at secondary sites if its primary cleavage sites are blocked, or that the substrate specificity of LE differs in polypeptides as compared to peptide substrates.