Assessment of Transverse Isotropy in Clinical-Level CT Images of Trabecular Bone Using the Gradient Structure Tensor

The aim of this study was to develop a GST-based methodology for accurately measuring the degree of transverse isotropy in trabecular bone. Using femoral sub-regions scanned in high-resolution peripheral QCT (HR-pQCT) and clinical-level-resolution QCT, trabecular orientation was evaluated using the mean intercept length (MIL) and the gradient structure tensor (GST) on the HR-pQCT and QCT data, respectively. The influence of local degree of transverse isotropy (DTI) and bone mineral density (BMD) was incorporated into the investigation. In addition, a power based model was derived, rendering a 1:1 relationship between GST and MIL eigenvalues. A specific DTI threshold (DTI thres) was found for each investigated size of region of interest (ROI), above which the estimate of major trabecular direction of the GST deviated no more than 30° from the gold standard MIL in 95% of the remaining ROIs (mean error: 16°). An inverse relationship between ROI size and DTI thres was found for discrete ranges of BMD. A novel methodology has been developed, where transversal isotropic measures of trabecular bone can be obtained from clinical QCT images for a given ROI size, DTI thres and power coefficient. Including DTI may improve future clinical QCT finite-element predictions of bone strength and diagnoses of bone disease.

FAIR_OSCE – Feedback structure for assessment of interactive roleplay in Objective Structured Clinical Exams

Introduction Since the quality of patient portrayal of standardized patients (SPs) during an Objective Structured Clinical Exam (OSCE) has a major impact on the reliability and validity of the exam, quality control should be initiated. Literature about quality control of SPs’ performance focuses on feedback [1, 2] or completion of checklists [3, 4]. Since we did not find a published instrument meeting our needs for the assessment of patient portrayal, we developed such an instrument after being inspired by others [5] and used it in our high-stakes exam. Project description SP trainers from five medical faculties collected and prioritized quality criteria for patient portrayal. Items were revised twice, based on experiences during OSCEs. The final instrument contains 14 criteria for acting (i.e. adequate verbal and non-verbal expression) and standardization (i.e. verbatim delivery of the first sentence). All partners used the instrument during a high-stakes OSCE. SPs and trainers were introduced to the instrument. The tool was used in training (more than 100 observations) and during the exam (more than 250 observations). Outcome High quality of SPs’ patient portrayal during the exam was documented. More than 90% of SP performances were rated to be completely correct or sufficient. An increase in quality of performance between training and exam was noted. For example, the rate of completely correct reaction in medical tests increased from 88% to 95%. Together with 4% of sufficient performances these 95% add up to 99% of the reactions in medical tests meeting the standards of the exam. SP educators using the instrument reported an augmentation of SPs’ performance induced by the use of the instrument. Disadvantages mentioned were the high concentration needed to observe all criteria and the cumbersome handling of the paper-based forms. Discussion We were able to document a very high quality of SP performance in our exam. The data also indicates that our training is effective. We believe that the high concentration needed using the instrument is well invested, considering the observed enhancement of performance. The development of an iPad-based application for the form is planned to address the cumbersome handling of the paper.

CD62L (L-selectin) shedding for assessment of functional blockade of TNF alpha in anti-TNF treated IBD patients: clinical feasibility and perspectives (DOP060)

Background Tumor necrosis factor (TNF) inhibition is central to the therapy of inflammatory bowel diseases (IBD). However, loss of response (LOR) is frequent and additional tests to help decision making with costly anti-TNF Therapy are needed. Methods Consecutive IBD Patients receiving anti-TNF therapy (Infliximab (IFX) or Adalimumab (after IFX LOR) from Bern University Hospital were identified and followed prospectively. Patient whole blood was stimulated with a dose-titration of two triggers of TLR receptors human: TNF and LPS. Median fluorescence intensity of CD62L on the surface of granulocytes was quantified by surface staining with specific antibodies (CD33, CD62L) and flow cytometry and logistic curves to these data permits the calculation of EC50 or the half maximal effective concentration TNF concentration to induce shedding [1]. A shift in the concentration were CD62L shedding occurred was seen before and after the anti-TNF agent administraion which permits to predict the response to the drug. This predicted response was correlated to the clinical evolution of the patients in order to analyze the ability of this test to identify LOR to IFX. Results We collected prospective clinical data and blood samples, before and after anti-TNF agent administration, on 33 IBD patients, 25 Crohn's disease and 8 ulcerative colitis patients (45% females) between June 2012 and November 2013. The assay showed a functional blockade of IFX (PFR) for 22 patients (17 CD and 5 UC) whereas 11 (8 CD and 3 UC) had no functional response (NR) to IFX. Clinical characteristics (e.g. diagnosis, disease location, smoking status, BMI and number of infusions) were no significantly different between predicted PFR and NR. Among the 22 Patients with PRF, only 1 patient was a clinical non responder (LOR to IFX), based on clinical prospective evaluation by IBD gastroenterologists (PJ, AM), and among the 11 predicted NR, 3 had no clinical LOR. Sensitivity of this test was 95% and specificity 73% and AUC adjusted for age and gender was 0.81 (Figure 1). During follow up (median 10 mo, 3–15) 8 “hard” outcomes occured (3 medic. flares, 4 resections and 1 new fistula) 2 in the PFR and 6 in the NR group (25% vs. 75%; p < 0.01). Correlation with clinical response is presented in Figure 2. Figure 1. Figure 2. Correlation clinical response - log EC50 changes: 1 No, 2 partial, 3 complete clinical response. Conclusion CD62L (L-Selectin) shedding is the first validated test of functional blockade of TNF alpha in anti-TNF treated IBD patients and will be a useful tool to guide medical decision on the use of anti-TNF agents. Comparative studies with ATI and trough level of IFX are ongoing. 1. Nicola Patuto, Emma Slack, Frank Seibold and Andrew J. Macpherson, (2011), Quantitating Anti-TNF Functionality to Inform Dosing and Choice of Therapy, Gastroenterology, 140 (5, Suppl. I), S689.

Computer-based summative assessment of clinical reasoning in clerkships: A mixed-method comparison of key feature problems with case-based multiple choice questions

Background: It is yet unclear if there are differences between using electronic key feature problems (KFPs) or electronic case-based multiple choice questions (cbMCQ) for the assessment of clinical decision making. Summary of Work: Fifth year medical students were exposed to clerkships which ended with a summative exam. Assessment of knowledge per exam was done by 6-9 KFPs, 9-20 cbMCQ and 9-28 MC questions. Each KFP consisted of a case vignette and three key features (KF) using “long menu” as question format. We sought students’ perceptions of the KFPs and cbMCQs in focus groups (n of students=39). Furthermore statistical data of 11 exams (n of students=377) concerning the KFPs and (cb)MCQs were compared. Summary of Results: The analysis of the focus groups resulted in four themes reflecting students’ perceptions of KFPs and their comparison with (cb)MCQ: KFPs were perceived as (i) more realistic, (ii) more difficult, (iii) more motivating for the intense study of clinical reasoning than (cb)MCQ and (iv) showed an overall good acceptance when some preconditions are taken into account. The statistical analysis revealed that there was no difference in difficulty; however KFP showed a higher discrimination and reliability (G-coefficient) even when corrected for testing times. Correlation of the different exam parts was intermediate. Conclusions: Students perceived the KFPs as more motivating for the study of clinical reasoning. Statistically KFPs showed a higher discrimination and higher reliability than cbMCQs. Take-home messages: Including KFPs with long menu questions into summative clerkship exams seems to offer positive educational effects.

Assessment of foot health and animal welfare: clinical findings in 229 dairy Mediterranean Buffaloes (Bubalus bubalis) affected by foot disorders.

BACKGROUND Lameness represents the third most important health-related cause of economic loss in the dairy industry after fertility and mastitis. Although, dairy Mediterranean Buffaloes (MB) and dairy cows share similar breeding systems predisposing to similar herd problems, published studies exploring its relevance and role in these ruminants are still rare and incomplete. The aims of this study were to describe the clinical findings of foot disorders (FDs) in dairy MB and their influence on animal welfare, determined by assessment of locomotion score (LS), body condition score (BCS) and cleanliness score (CS). RESULTS Of 1297 multiparous MB submitted to routine trimming procedures, 229 buffaloes showed at least one FD. The prevalence of buffaloes affected by FDs was 17.7 %, while motility and lameness indexes were 84.1 % (1091/1297) and 15.9 % (206/1297), respectively. Overgrowth was present in 17.0 % (220/1297), corkscrew claw in 15.8 % (205/1297), interdigital phlegmon in 0.9 % (12/1297), white line abscess in 0.8 % (11/1297), digital dermatitis in 0.1 % (1/1297) and interdigital hyperplasia in 0.1 % (1/1297). Simultaneous presence of FDs was recorded in 17.0 % of MB (221/1297): overgrowth and corkscrew claw occurred together in 15.8 % of cases (205/1297), overgrowth and interdigital phlegmon in 0.3 % (4/1297), overgrowth and white line abscess in 0.8 % (11/1297), digital dermatitis and interdigital hyperplasia in 0.1 % (1/1297). The presence of FDs was always associated with lameness (LS > 2), except from 23 MB with simultaneous overgrowth and interdigital phlegmon occurrence. The majority of MB within the under-conditioned group (95.5 %, 43/45) and all those with CS > 2 (122/122) had a locomotion score above the threshold of normality (LS > 2). Furthermore, foot diseases such as interdigital hyperplasia, white line abscess and digital dermatitis or interdigital hyperplasia seemed to occur more frequently associated with decreased BCS and increased CS scores. CONCLUSIONS This study describes for the first time the involvement of white line disease, interdigital phlegmona, digital dermatitis and interdigital hyperplasia in foot disorders of dairy Mediterranean buffalo and shows their association with an impairment of animal welfare.

Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials

BACKGROUND: Neovascular age-related macular degeneration (AMD) has a poor prognosis if left untreated, frequently resulting in legal blindness. Ranibizumab is approved for treating neovascular AMD. However, further guidance is needed to assist ophthalmologists in clinical practice to optimise treatment outcomes. METHODS: An international retina expert panel assessed evidence available from prospective, multicentre studies evaluating different ranibizumab treatment schedules (ANCHOR, MARINA, PIER, SAILOR, SUSTAIN and EXCITE) and a literature search to generate evidence-based and consensus recommendations for treatment indication and assessment, retreatment and monitoring. RESULTS: Ranibizumab is indicated for choroidal neovascular lesions with active disease, the clinical parameters of which are outlined. Treatment initiation with three consecutive monthly injections, followed by continued monthly injections, has provided the best visual-acuity outcomes in pivotal clinical trials. If continued monthly injections are not feasible after initiation, a flexible strategy appears viable, with monthly monitoring of lesion activity recommended. Initiation regimens of fewer than three injections have not been assessed. Continuous careful monitoring with flexible retreatment may help avoid vision loss recurring. Standardised biomarkers need to be determined. CONCLUSION: Evidence-based guidelines will help to optimise treatment outcomes with ranibizumab in neovascular AMD.

Older Breast Cancer Survivors: Geriatric Assessment Domains Are Associated With Poor Tolerance of Treatment Adverse Effects and Predict Mortality Over 7 Years of Follow-Up

Purpose To evaluate geriatric assessment (GA) domains in relation to clinically important outcomes in older breast cancer survivors. Methods Six hundred sixty women diagnosed with primary breast cancer in four US geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island) were selected with disease stage I to IIIA, age ≥ 65 years at date of diagnosis, and permission from attending physician to contact. Data were collected over 7 years of follow-up from consenting patients' medical records, telephone interviews, physician questionnaires, and the National Death Index. Outcomes included self-reported treatment tolerance and all-cause mortality. Four GA domains were described by six individual measures, as follows: sociodemographic by adequate finances; clinical by Charlson comorbidity index (CCI) and body mass index; function by number of physical function limitations; and psychosocial by the five-item Mental Health Index (MHI5) and Medical Outcomes Study Social Support Survey (MOS-SSS). Associations were evaluated using t tests, χ2 tests, and regression analyses. Results In multivariable regression including age and stage, three measures from two domains (clinical and psychosocial) were associated with poor treatment tolerance; these were CCI ≥ 1 (odds ratio [OR] = 2.49; 95% CI, 1.18 to 5.25), MHI5 score less than 80 (OR = 2.36; 95% CI, 1.15 to 4.86), and MOS-SSS score less than 80 (OR = 3.32; 95% CI, 1.44 to 7.66). Four measures representing all four GA domains predicted mortality; these were inadequate finances (hazard ratio [HR] = 1.89; 95% CI, 1.24 to 2.88; CCI ≥ 1 (HR = 1.38; 95% CI, 1.01 to 1.88), functional limitation (HR = 1.40; 95% CI, 1.01 to 1.93), and MHI5 score less than 80 (HR = 1.34; 95% CI, 1.01 to 1.85). In addition, the proportion of women with these outcomes incrementally increased as the number of GA deficits increased. Conclusion This study provides longitudinal evidence that GA domains are associated with poor treatment tolerance and predict mortality at 7 years of follow-up, independent of age and stage of disease.

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months.

Comprehensive assessment of gesture production: a new test of upper limb apraxia (TULIA)

BACKGROUND: Only few standardized apraxia scales are available and they do not cover all domains and semantic features of gesture production. Therefore, the objective of the present study was to evaluate the reliability and validity of a newly developed test of upper limb apraxia (TULIA), which is comprehensive and still short to administer. METHODS: The TULIA consists of 48 items including imitation and pantomime domain of non-symbolic (meaningless), intransitive (communicative) and transitive (tool related) gestures corresponding to 6 subtests. A 6-point scoring method (0-5) was used (score range 0-240). Performance was assessed by blinded raters based on videos in 133 stroke patients, 84 with left hemisphere damage (LHD) and 49 with right hemisphere damage (RHD), as well as 50 healthy subjects (HS). RESULTS: The clinimetric findings demonstrated mostly good to excellent internal consistency, inter- and intra-rater (test-retest) reliability, both at the level of the six subtests and at individual item level. Criterion validity was evaluated by confirming hypotheses based on the literature. Construct validity was demonstrated by a high correlation (r = 0.82) with the De Renzi-test. CONCLUSION: These results show that the TULIA is both a reliable and valid test to systematically assess gesture production. The test can be easily applied and is therefore useful for both research purposes and clinical practice.

Assessment and management of dental erosion

Studies have shown a growing trend toward increasing prevalence of dental erosion, associated with the declining prevalence of caries disease in industrialized countries. Erosion is an irreversible chemical process that results in tooth substance loss and leaves teeth susceptible to damage as a result of wear over the course of an individual's lifetime. Therefore, early diagnosis and adequate prevention are essential to minimize the risk of tooth erosion. Clinical appearance is the most important sign to be used to diagnose erosion. The Basic Erosive Wear Examination (BEWE) is a simple method to fulfill this task. The determination of a variety of risk and protective factors (patient-dependent and nutrition-dependent factors) as well as their interplay are necessary to initiate preventive measures tailored to the individual. When tooth loss caused by erosive wear reaches a certain level, oral rehabilitation becomes necessary.

Significance of Periodontal Risk Assessment in the recurrence of periodontitis and tooth loss

Aim: To investigate the association of the Periodontal Risk Assessment (PRA) model categories with periodontitis recurrence and tooth loss during supportive periodontal therapy (SPT) and to explore the role of patient compliance. Material and Methods: In a retrospective cohort, PRA was performed for 160 patients after active periodontal therapy (APT) and after 9.5 ± 4.5 years of SPT. The recurrence of periodontitis and tooth loss were analysed according to the patient's risk profile (low, moderate or high) after APT and compliance with SPT. The association of risk factors with tooth loss and recurrence of periodontitis was investigated using logistic regression analysis. Results: In 18.2% of patients with a low-risk profile, in 42.2% of patients with a moderate-risk profile and in 49.2% of patients with a high-risk profile after APT, periodontitis recurred. During SPT, 1.61 ± 2.8 teeth/patient were lost. High-risk profile patients lost significantly more teeth (2.59 ± 3.9) than patients with moderate- (1.02 ± 1.8) or low-risk profiles (1.18 ± 1.9) (Kruskal–Wallis test, p=0.0229). Patients with erratic compliance lost significantly (Kruskal–Wallis test, p=0.0067) more teeth (3.11 ± 4.5) than patients compliant with SPT (1.07 ± 1.6). Conclusions: In multivariate logistic regression analysis, a high-risk patient profile according to the PRA model at the end of APT was associated with recurrence of periodontitis. Another significant factor for recurrence of periodontitis was an SPT duration of more than 10 years.

Assessment of publication bias in dental specialty journals

OBJECTIVE: The purpose of this study was to investigate the presence of publication bias (acceptance of articles indicating statistically significant results). METHODS: The journals possessing the highest impact factor (2008 data) in each dental specialty were included in the study. The content of the 6 most recent issues of each journal was hand searched and research articles were classified into 4 type categories: cross-sectional, case-control, cohort, and interventional (nonrandomized clinical trials and randomized controlled trials). In total, 396 articles were included in the analysis. Descriptive statistics and univariate and multivariate logistic regression was used to examine the association between article-reported statistical significance (dependent variable) and journal impact factor and article study type subject area (independent variables). RESULTS: A statistically significant acceptance rate of positive result was found, ranging from 75% to 90%, whereas the value of impact factor was not related to publication bias among leading dental journals. Compared with other research designs, clinical intervention studies (randomized or nonrandomized) presented the highest percentage of nonsignificant findings (20%); RCTs represented 6% of the examined investigations. CONCLUSIONS: Compared with the Journal of Clinical Periodontology, all other subspecialty journals, except the Journal of Oral and Maxillofacial Surgery, showed significantly decreased odds of publishing an RCT, which ranged from 60% to 93% (P < .05).