Qualitative Scoring System Research Articles

Are semi-automated software program designed for adults accurate for the identification of vertebral fractures in children?

ObjectivesTo assess whether diagnostic accuracy of morphometric vertebral fracture (VF) diagnosis in children can be improved using AVERT™ (a 33-point semi-automated program developed for VF diagnosis in adults) compared with SpineAnalyzer™ (a 6-point program), which has previously been shown to be of insufficient accuracy.Materials and methodsLateral spine radiographs (XR) and dual-energy X-ray absorptiometry (DXA) scans of 50 children and young people were analysed by two observers using two different programs (AVERT™ and SpineAnalyzer™). Diagnostic accuracy (sensitivity, specificity, false-negative (FN) and false-positive rates (FP)) was calculated by comparing with a previously established consensus arrived at by three experienced paediatric musculoskeletal radiologists, using a simplified algorithm-based qualitative scoring system. Observer agreement was calculated using Cohen’s kappa.ResultsFor XR, overall sensitivity, specificity, FP and FN rates using AVERT™ were 36%, 95%, 5% and 64% respectively and 26%, 98%, 2% and 75% respectively, using SpineAnalyzer™. For DXA, overall sensitivity, specificity, FP and FN rates using AVERT™ were 41%, 91%, 9% and 59% respectively and 31%, 96%, 4% and 69% respectively, using SpineAnalyzer. Reliability (kappa) ranged from 0.34 to 0.37 (95%CI, 0.26–0.46) for AVERT™ and from 0.26 to 0.31 (95%CI, 0.16–0.44) for SpineAnalyzer™. Inter- and intra-observer agreement ranged from 0.41 to 0.47 for AVERT™ and from 0.50 to 0.79 for SpineAnalyzer™.ConclusionAVERT™ has slightly higher accuracy but lower observer reliability for the representation of vertebral morphometry in children when compared with SpineAnalyzer™. However, neither software program is satisfactorily reliable for VF diagnosis in children.Key Points• SpineAnalyzer™ and AVERT™ have low diagnostic accuracy and observer agreement when compared to three paediatric radiologists’ readings for the diagnosis of vertebral fractures (VF) in children.• Neither AVERT™ nor SpineAnalyzer™ is satisfactorily reliable for VF diagnosis in children.• Development of specific paediatric software and normative values (incorporating age-related physiological variation in children) is required.

The Flipped Classroom: A Critical Appraisal.

IntroductionThe objective of this study was to review and critically appraise the medical education literature pertaining to a flipped-classroom (FC) education model, and to highlight influential papers that inform our current understanding of the role of the FC in medical education.MethodsA search of the English-language literature querying Education Resources Information Center (ERIC), PsychINFO, PubMed, and Scopus identified 296 papers related to the FC using either quantitative, qualitative, or review methods. Two reviewers independently screened each category of publications using previously established exclusion criteria. Eight reviewers then independently scored the remaining 54 publications using either a qualitative, quantitative, or review-paper scoring system. Each scoring system consisted of nine criteria and used parallel metrics that have been previously used in critical appraisals of education research.ResultsA total of 54 papers (33 quantitative, four qualitative, and 17 review) on FC met a priori criteria for inclusion and were critically appraised and reviewed. The top 10 highest scoring articles (five quantitative studies, two qualitative studies, and three review papers) are summarized in this article.ConclusionThis installment of the Council of Emergency Medicine Residency Directors (CORD) Academy Critical Appraisal series highlights 10 papers that describe the current state of literature on the flipped classroom, including an analysis of the benefits and drawbacks of an FC approach, practical implications for emergency medicine educators, and next steps for future research.

The Diagnostic Yield of Dental Radiography and Cone-Beam Computed Tomography for the Identification of Dentoalveolar Lesions in Cats.

The objective of this study was to evaluate the diagnostic yield of dental radiography (DR) and 3 cone-beam computed tomography (CBCT) software modules for the identification of 32 pre-defined dentoalveolar lesions in cats. For 5 feline cadaver heads and 22 client-owned cats admitted for evaluation and treatment of dental disease, 32 predefined dentoalveolar lesions were evaluated separately and scored by use of dental radiography and 3 CBCT software modules [multiplanar reconstructions (MPR), tridimensional (3-D) rendering, and reconstructed panoramic views]. A qualitative scoring system was used. Dentoalveolar lesions were grouped into 14 categories for statistical analysis. Point of reference for presence or absence of a dentoalveolar lesion was determined as the method that could be used to clearly identify the disorder as being present. Accuracy, sensitivity, specificity, and positive and negative predictive values were calculated with the McNemar χ2 test of marginal homogeneity of paired data. When all 3 CBCT software modules were used in combination, the diagnostic yield of CBCT was significantly higher than that of dental radiography for 4 of 14 categories (missing teeth, horizontal bone loss, loss of tooth integrity, feline resorptive lesions), and higher, although not significantly so, for 9 categories (supernumerary teeth, supernumerary roots, abnormally shaped roots, vertical bone loss, buccal bone expansion, periapical disease, inflammatory root resorption, and external replacement root resorption). In conclusion, we found that CBCT provided more clinically relevant detailed information as compared to dental radiography. Therefore, CBCT should be considered better suited for use in diagnosing dentoalveolar lesions in cats.

The Rey-Osterrieth Complex Figure: a Useful Measure of Organizational Skills for Adolescents with ADHD?

Deficits in organization, time management, and planning (OTMP) abilities are common in adolescents with attention-deficit/hyperactivity disorder (ADHD) and contribute to impairment. Assessment of these skills is vital, but few measures have been validated for youth with ADHD. The Rey-Osterrieth Complex Figure (ROCF) task is frequently used in research and clinical settings despite limited validity evidence. The present study evaluated whether ROCF performance, as scored via the Boston Qualitative Scoring System, exhibited validity as a measure of OTMP skills in a large (N = 285) sample of adolescents comprehensively diagnosed with ADHD. ROCF performance exhibited minimal associations with measures of OTMP, executive functioning, or aspects of academic impairment affected by OTMP abilities; all correlations were nonsignificant after accounting for the influence of intelligence. Further, ROCF task performance did not differ by ADHD presentation or medication status. Correlations with other variables that may be confounded with ROCF performance (anxiety symptoms, depressive symptoms, parent education) also demonstrated nonsignificant correlations with all BQSS scores. The ROCF may not adequately capture OTMP abilities of adolescents with ADHD; future directions for the assessment of OTMP skills are discussed.

Noninvasive prediction of portal pressure with MR elastography and DCE‐MRI of the liver and spleen: Preliminary results

Portal hypertension (PH), defined by hepatic venous pressure gradient (HVPG) ≥5 mmHg and clinically significant PH, defined by HVPG ≥10 mmHg, are complications of chronic liver disease. To assess the diagnostic performance of MR elastography (MRE) and dynamic contrast-enhanced MRI (DCE-MRI) of the liver and spleen for the prediction of PH and clinically significant PH, in comparison with a qualitative PH imaging scoring system. IRB-approved prospective study. In all, 34 patients with chronic liver disease who underwent HVPG measurement. 1.5/3T examination including 2D-GRE MRE (n = 33) and DCE-MRI of the liver/spleen (n = 28). Liver and spleen stiffness were calculated from elastogram maps. DCE-MRI was analyzed using model-free parameters and pharmacokinetic modeling. Two observers calculated qualitative PH imaging scores based on routine images. Imaging parameters were correlated with HVPG. Receiver operating characteristic (ROC) analysis was performed for prediction of PH and clinically significant PH. There were significant correlations between DCE-MRI parameters (liver time-to-peak, r = 0.517 / P = 0.006, liver distribution volume, r = 0.494 / P = 0.009, liver upslope, r = -0.567 / P = 0.002), liver stiffness (r = 0.478 / P = 0.016), PH imaging score (r = 0.441 / P = 0.009), and HVPG. ROC analysis provided significant area under the ROC (AUROCs) for PH (liver upslope 0.765, liver stiffness 0.809, spleen volume/diameter 0.746-0.731, PH imaging score 0.756) and for clinically significant PH (liver and spleen perfusion parameters 0.733-0.776, liver stiffness 0.742, PH imaging score 0.742). The ratio of liver stiffness to liver upslope had the highest AUROC for diagnosing PH (0.903) and clinically significant PH (0.785). These preliminary results suggest that the combination of liver stiffness and perfusion metrics provide excellent accuracy for diagnosing PH, and fair accuracy for clinically significant PH. Combined MRE and DCE-MRI outperformed qualitative imaging scores for prediction of PH. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1091-1103.

Development and reliability of the rating of compensatory movements in upper limb prosthesis wearers during work-related tasks

Study DesignReliability study. IntroductionQuantifying compensatory movements during work-related tasks may help to prevent musculoskeletal complaints in individuals with upper limb absence. Purpose of the Study(1) To develop a qualitative scoring system for rating compensatory shoulder and trunk movements in upper limb prosthesis wearers during the performance of functional capacity evaluation tests adjusted for use by 1-handed individuals (functional capacity evaluation-one handed [FCE-OH]); (2) to examine the interrater and intrarater reliability of the scoring system; and (3) to assess its feasibility. MethodsMovement patterns of 12 videotaped upper limb prosthesis wearers and 20 controls were analyzed. Compensatory movements were defined for each FCE-OH test, and a scoring system was developed, pilot tested, and adjusted. During reliability testing, 18 raters (12 FCE experts and 6 physiotherapists/gait analysts) scored videotapes of upper limb prosthesis wearers performing 4 FCE-OH tests 2 times (2 weeks apart). Agreement was expressed in % and kappa value. Feasibility (focus area's “acceptability”, “demand,” and “implementation”) was determined by using a questionnaire. ResultsAfter 2 rounds of pilot testing and adjusting, reliability of a third version was tested. The interrater reliability for the first and second rating sessions were к = 0.54 (confidence interval [CI]: 0.52-0.57) and к = 0.64 (CI: 0.61-0.66), respectively. The intrarater reliability was к = 0.77 (CI: 0.72-0.82). The feasibility was good but could be improved by a training program. DiscussionIt seems possible to identify compensatory movements in upper limb prosthesis wearers during the performance of FCE-OH tests reliably by observation using the developed observational scoring system. ConclusionsInterrater reliability was satisfactory in most instances; intrarater reliability was good. Feasibility was established.

Qualitative Evaluation of the Immediate Copy of the Rey-Osterrieth Complex Figure: Comparison Between Vascular and Degenerative MCI Patients.

The immediate copy of the Rey-Osterrieth Complex Figure (ROCF) is considered a visuo-spatial test. However, reproducing this complex structure possibly involves also executive functions, such as planning and organizational strategies. In a previous study, we found a high rate of impaired performances in this test in a sample of subcortical vascular mild cognitive impairment patients. Executive functions contribution in the immediate copy of the ROCF can be assessed with the Boston Qualitative Scoring System (BQSS). We aimed at examining whether BQSS executive scores of ROCF immediate copy: (1) differ between vascular (v-MCI) and degenerative MCI (d-MCI) patients; (2) can at least partly explain the high rate of abnormal ROCF immediate copy performances in v-MCI patients. Thirty d-MCI patients (age 75.2 ± 4.4) and 27 v-MCI (age 73.2 ± 6.9) were enrolled. The performances of patients were scored using the BQSS executive scores (Fragmentation, Planning, Organization, Perseveration) during the accomplishment of ROCF immediate copy. Comparing d-MCI and v-MCI performances, d-MCI patients scored worse on ROCF delayed recall (9.9 ± 4.7 vs. 13.4 ± 5.9, p = .020) and MMSE (23.9 ± 2.6 vs. 27.8 ± 2.3, p = .001) while v-MCI patients had more frequently impaired performances in ROCF immediate copy (40% vs. 81%, p = .001) and showed worse scores on Fragmentation (2.4 ± 0.9 vs. 1.8 ± 1.3, p = .035), Planning (2.4 ± 0.8 vs. 1.8 ± 1, p = .039), Organization (4.8 ± 1.3 vs. 3.6 ± 2.1, p = .017), and Perseveration (3.5 ± 0.8 vs. 2.9 ± 1.2, p = .048). The performance of v-MCI patients in ROCF immediate copy seemed to be more affected by executive dysfunction than the performance obtained by d-MCI. When analyzing ROCF performances, a qualitative approach allows to evaluate patients' strategies during the reproduction, and thus to discriminate between executive and visuo-constructional abilities.

Clinical Scoring of Disease Activity in Animal Models.

Disease severity in murine arthritis models, such as collagen-induced arthritis (CIA), is commonly assessed by clinical scoring of paw swelling and histological examination of joints. Clinical scoring using a qualitative scoring system of paw inflammation (paw thickness, width, or volume) over time is the standard method used for subjective quantification of arthritis activity. To evaluate paw swelling status, a quantitative method using three-dimensional T2-weighted flash sequence magnetic resonance imaging (MRI) is introduced. The efficacy of a therapeutic approach can be semiologically quantified using a clinical scoring system and an index of paw inflammation in CIA mice.

Efficiency of polymerization of bulk-fill composite resins: a systematic review.

This systematic review assessed the literature to evaluate the efficiency of polymerization of bulk-fill composite resins at 4 mm restoration depth. PubMed, Cochrane, Scopus and Web of Science databases were searched with no restrictions on year, publication status, or article's language. Selection criteria included studies that evaluated bulk-fill composite resin when inserted in a minimum thickness of 4 mm, followed by curing according to the manufacturers' instructions; presented sound statistical data; and comparison with a control group and/or a reference measurement of quality of polymerization. The evidence level was evaluated by qualitative scoring system and classified as high-, moderate- and low- evidence level. A total of 534 articles were retrieved in the initial search. After the review process, only 10 full-text articles met the inclusion criteria. Most articles included (80%) were classified as high evidence level. Among several techniques, microhardness was the most frequently method performed by the studies included in this systematic review. Irrespective to the "in vitro" method performed, bulk fill RBCs were partially likely to fulfill the important requirement regarding properly curing in 4 mm of cavity depth measured by depth of cure and / or degree of conversion. In general, low viscosities BFCs performed better regarding polymerization efficiency compared to the high viscosities BFCs.

STRATEGY CLASSIFICATION OF CLOCK-DRAWING TEST CONSTRUCTION

The Clock Drawing Test (CDT) has been widely used as an executive function and visuoconstructive measure. However, scoring systems that describe planning and organization strategies in clock drawing does not exist. The objective of the present article is to map, describe and classify the different planning and organizing strategies of clock drawing. 77 older volunteers without cognitive complain. CDT execution's process and time were registered. Drawings were scored with semi-quantitative (Sunderland et al., 1989) and qualitative (Parsey and Edgecombe et al., 2011) systems. The strategies of clock drawing test drawing were classified and associated to sociodemographic data, scores of the qualitative scoring system and executive function tests (Rey Complex Figure Test; Cubes – WAIS-III). The results showed diversity in the patterns of strategies of drawing. The most frequent strategies were a general sequence (circle-number-center-hand) and a numerical sequence which followed a sequential pattern of increasing numerical order. On the other hand, better results in executive function measures were more associated with circle-number-center-hand (general sequence) and quadrant (numerical sequence) strategies. This new method of classification complements the previous existing semi-quantitative and qualitative scoring criteria.

A validated clinical MRI injury scoring system in neonatal hypoxic-ischemic encephalopathy.

Deep nuclear gray matter injury in neonatal hypoxic-ischemic encephalopathy (HIE) is associated with worse neurodevelopmental outcomes. We previously published a qualitative MRI injury scoring system utilizing serial T1-weighted, T2-weighted and diffusion-weighted imaging (DWI), weighted for deep nuclear gray matter injury. To establish the validity of the MRI scoring system with neurodevelopmental outcome at 18-24months. MRI scans from neonates with moderate to severe HIE treated with therapeutic hypothermia were evaluated. Signal abnormality was scored on T1-weighted, T2-weighted and DWI sequences and assessed using an established system in five regions: (a) subcortical: caudate nucleus, globus pallidus and putamen, thalamus and the posterior limb of the internal capsule; (b) white matter; (c) cortex, (d) cerebellum and (e) brainstem. MRI injury was graded as none, mild, moderate or severe. Inter-rater reliability was tested on a subset of scans by two independent and blinded neuroradiologists. Surviving infants underwent the Bayley Scales of Infant and Toddler Development-III (Bayley-III) at 18-24months. Data were analyzed using univariate and multivariate linear and logistic regression. Fifty-seven eligible neonates underwent at least one MRI scan in the first 2weeks of life. Mean postnatal age at scan 1 was 4±2days in 50/57 (88%) neonates and 48/54 (89%) surviving infants underwent scan 2 at 10±2days. In 54/57 (95%) survivors, higher MRI injury grades were significantly associated with worse outcomes in the cognitive, motor and language domains of the Bayley-III. A qualitative MRI injury scoring system weighted for deep nuclear gray matter injury is a significant predictor of neurodevelopmental outcome at 18-24months in neonates with HIE.

Reliability of MR Quantification of Rotator Cuff Muscle Fatty Degeneration Using a 2-point Dixon Technique in Comparison with the Goutallier Classification: Validation Study by Multiple Readers

Presurgical assessment of fatty degeneration is important in the management of patients with rotator cuff tears. The Goutallier classification is widely accepted as a qualitative scoring system, although it is highly observer-dependent and has poor reproducibility. The objective of this study was to quantify fatty degeneration of the supraspinatus muscle using a 2-point Dixon technique in patients with rotator cuff tears by multiple readers, and to evaluate the reproducibility compared to Goutallier classification. Two hundred patients with rotator cuff tears who underwent magnetic resonance imaging (MRI), including 2-point Dixon sequence at 3.0-T, were selected retrospectively. Qualitative and quantitative analyses of fatty degeneration were performed by two radiologists and three orthopedic surgeons independently. The fat quantification was performed by measuring signal intensity values of in phase (S(In)) and fat image (S(Fat)), and calculating fat fraction as S(Fat)/S(In). The reproducibility of MR quantification was analyzed by the intra- and interclass correlation coefficients and Bland-Altman plots. The interobserver agreement of the Goutallier classification among five readers was moderate (k = 0.51), whereas the interclass correlation coefficient regarding fat fraction value quantified in 2-point Dixon sequence was excellent (0.893). The mean differences in fat fraction values from the individual segmentation results were from -0.072 to 0.081. Proposed fat fraction grading and Goutallier grading showed similar frequency and distribution in severity of rotator cuff tears. Fat quantification in the rotator cuff muscles using a 2-point Dixon technique at 3.0-T MRI is highly reproducible and clinically feasible in comparison to the qualitative evaluation using Goutallier classification.

Feedback in Medical Education: A Critical Appraisal.

The objective was to review and critically appraise the medical education literature pertaining to feedback and highlight influential papers that inform our current understanding of the role of feedback in medical education. A search of the English language literature in querying Education Resources Information Center (ERIC), PsychINFO, PubMed, and Scopus identified 327 feedback-related papers using either quantitative (hypothesis-testing or observational investigations of educational interventions), qualitative methods (exploring important phenomena in emergency medicine [EM] education), or review methods.Two reviewers independently screened each category of publications using previously established exclusion criteria. Six reviewers then independently scored the remaining 54 publications using a qualitative, quantitative, or review paper scoring system. Each scoring system consisted of nine criteria and used parallel scoring metrics that have been previously used in critical appraisals of education research. Fifty-four feedback papers (25 quantitative studies, 24 qualitative studies, five review papers) met the a priori criteria for inclusion and were reviewed. Eight quantitative studies, nine qualitative studies, and three review papers were ranked highly by the reviewers and are summarized in this article. This inaugural Council of Emergency Medicine Residency Directors Academy critical appraisal highlights 20 feedback in medical education papers that describe the current state of the feedback literature. A summary of current factors that influence feedback effectiveness is discussed, along with practical implications for EM educators and the next steps for research.

Use of the parallel beam task for skilled walking in a rat model of cerebral ischemia: A qualitative approach

The parallel beam task (PBT), in which animals walk across two elevated parallel beams, is commonly used to assess motor deficits in laboratory rodents. Performance of the PBT challenges postural balance, inter-limb coordination and skilled walking abilities, and is typically assessed by quantitative measures such as number of foot slips and/or successful traversals. We proposed that including qualitative movement analysis of skilled walking would increase resolution and sensitivity of PBT assessments in rats with cortical ischemic lesion. Pre-trained rats with a unilateral devascularization of the primary motor cortex and controls were recorded from lateral and ventral views as they traversed a PBT made of two parallel metal beams. The new qualitative skilled walking scoring system analyzed four elements of posture, limb placement, and targeting (limb rotation and position, number of placing attempts and foot slips) based on frame-by-frame video analysis. The analysis revealed that motor cortex lesions produced significant deficits in contralateral limb rotation and limb placement in both fore- and hind limbs, compared to ipsilateral limbs and control animals. Fore- and hind limbs showed different patterns in limb placement impairments. The results indicate that forelimb foot slips are a more sensitive measure of lesion-induced deficits than hind limb foot slips. Thus, the PTB is an effective task for the assessment of skilled walking and motor learning strategies especially when combined with qualitative movement analysis in rodent models of stroke.

Efficacy of qualitative response assessment interpretation criteria at 18F-FDG PET-CT for predicting outcome in locally advanced cervical carcinoma treated with chemoradiotherapy

ObjectivesTo evaluate the utility of a standardized qualitative scoring system for treatment response assessment at 18F-FDG PET-CT in patients undergoing chemoradiotherapy for locally advanced cervical carcinoma and correlate this with subsequent patient outcome.MethodsNinety-six consecutive patients with locally advanced cervical carcinoma treated with radical chemoradiotherapy (CRT) in a single centre between 2011 and 2014 underwent 18F-FDG PET-CT approximately 3 months post-treatment. Tumour metabolic response was assessed qualitatively using a 5-point scale ranging from background level activity only through to progressive metabolic disease. Clinical and radiological (MRI pelvis) follow-up was performed in all patients. Progression-free (PFS) and overall survival (OS) was calculated using the Kaplan-Meier method (Mantel-Cox log-rank) and correlated with qualitative score using Chi-squared test.ResultsForty patients (41.7 %) demonstrated complete metabolic response (CMR) on post-treatment PET-CT (Score 1/2) with 38 patients (95.0 %) remaining disease free after a minimum follow-up period of 18 months. Twenty-four patients (25.0 %) had indeterminate residual uptake (ID, Score 3) at primary or nodal sites after treatment, of these eight patients (33.3 %) relapsed on follow-up, including all patients with residual nodal uptake (n = 4Eleven11 of 17 patients (64.7 %) with significant residual uptake (partial metabolic response, PMR, Score 4) subsequently relapsed. In 15 patients (15.6 %) PET-CT demonstrated progressive disease (PD, Score 5) following treatment. Kaplan-Meier analysis showed a highly statistically significant difference in PFS and OS between patients with CMR, indeterminate uptake, PMR and PD (Log-rank, P < 0.0001). Chi-squared test demonstrated a highly statistically significant association between increasing qualitative score and risk of recurrence or death (P < 0.001).ConclusionUse of a 5-point qualitative scoring system to assess metabolic response to CRT in locally advanced cervical carcinoma predicts survival outcome and this prognostic information may help guide further patient management.

Utility of Boston Qualitative Scoring System for Rey-Osterrieth Complex Figure: evidence from a Parkinson's Diseases sample.

This study examined the ability of the Boston Qualitative Scoring System (BQSS) in comparison to the Osterrieth scoring method to separate Parkinson's Disease patients without dementia from healthy controls at the Rey-Osterrieth Complex Figure (ROCF) copy. 30 PD participants and 30 healthy participants completed ROCF copy. The performance was scored according to both methods. The results indicated thatPD patients performed significantly worse on ROCF. According to ROC analyses, BQSS Copy Total score represented the most suitable index to distinguish between the two groups: a score below or equal to 16 indicates an impaired performance. Moreover, PD participants reported lower performance in the BQSS scores of Planning and Neatness. PD patients' poor performance in ROCF copy was related to executive difficulties, specifically in terms of planning and impulsivity, instead of global visuo-constructional impairments. An extensive evaluation of copy drawings allowing to disentangle between different involved cognitive domains would be suitable, specifically in those clinical conditions like PD, in which motor impairments affect drawing performance.

TH-AB-207A-10: Sub-MSv Cerebral CT Perfusion Imaging Using Prior Image Constrained Compressed Sensing: A Prospective Clinical Trial

Purpose: A prospective clinical study was conducted to assess whether sub-mSv cerebral CT perfusion (CTP) imaging can be achieved using the Prior Image Constrained Compressed Sensing (PICSS) reconstruction algorithm. Methods: Following a standard dose (SD) CTP acquisition, 31 patients (median age, 62 years; 15 M/16 F; median BMI, 27) underwent an additional reduced dose (RD) CTP acquisition at 20% of the standard dose level. Several algorithms (PICCS, ASIR, and FBP) were used to reconstruct CTP source images of the RD series. SD-FBP served as the reference standard. Two clinical observers (one neuroradiologist and one neurosurgeon) scored CTP maps using qualitative scoring system and quantitative noise measurements were performed. Statistical analyses were performed to interpret the qualitative and quantitative assessments. Results: The CTDIvol and effective dose for the RD series was 44.5 mGy and 0.75 mSv respectively, compared with 222.6 mGy and 3.74 mSv respectively for the SD series. The average image quality scores of the RD-PICCS series were 3.8±0.7 for CBF, 3.5±0.9 for CBV, 3.9±0.9 for MTT. In comparison, subjective image quality scores of SD-FBP were 3.5±0.8 for CBF, 3.5±0.9 for CBV, 3.3±0.8 for MTT. The average noise of RD-PICCS (CBF, 5.8±1.9 mL/100 g/min; CBV, 0.74±0.26 mL/100 g; MTT, 5.5±1.2 s) were lower than those of SD-FBP (CBF, 8.1±2.5 mL/100 g/min; CBV, 0.86±0.28 mL/100 g; MTT, 6.4±1.2 s) with statistical significance (p < 0.001). Both subjective scores and objective noise of RD-ASIR and RD-FBP were significantly inferior to those of SD-FBP (p < 0.001). Conclusions: PICCS enables sub-mSv cerebral CTP imaging without compromising diagnostic image quality. Funding Support: 2015 AAPM Research Seed Grant. Disclosures: J. Tang: Employee, GE Healthcare; H. Rowley: Research Consultant, Bracco Group, Guerbet SA, GE Healthcare, F. Hoffmann-La Roche Ltd, W.L. Gore & Associates, Lundbeck Group; C. Strother: Research Consultant, Siemens AX; G.-H. Chen: Research funded, GE Healthcare, Siemens AX.

Amorphous solid dispersions of BCS class II drugs: A rational approach to solvent and polymer selection

Miniaturised solvent casting (MSC) has been developed as a method for screening the stability of amorphous solid dispersions (ASD) of BCS class II drugs. The aim of the work was to further develop a rapid screening technique for drug–polymer amorphous dispersions made by solvent removal techniques. A second aim was to assess the impact of varying dissolution solvent on the resultant ASD stability. The technique was rapid, repeatable and practically straightforward. Storage stability of resultant ASD films was monitored over 4 weeks. The method is suited to pre-formulation as a risk-reduction tool during the formulation of drug product. Four drugs, seven polymers and five solvents have been examined. The resultant ASD films were monitored for stability and homogeneity over a four week period using polarised light microscopy (PLM), X-ray powder diffraction (XRD) and photography. A qualitative scoring system indicating the approximate proportion of amorphous and crystalline content of the films was developed. Results were rationalised against the physiochemical properties of the drugs, the functionality of the polymeric excipients and the physical properties of the solvents.

Local Administration of Simvastatin Stimulates Healing of an Avascular Meniscus in a Rabbit Model of a Meniscal Defect

Background: Repair of an avascular meniscus is challenging because of its low capacity for healing. Several reports have shown that simvastatin stimulates the anabolic activity of intervertebral fibrochondrocytes, suggesting that simvastatin may be used for the treatment of meniscal defects. Purpose: To test whether the local administration of simvastatin stimulates healing of an avascular meniscus in rabbits. Study Design: Controlled laboratory study. Methods: In 30 Japanese White rabbits, a cylindrical defect (1.5-mm diameter) was introduced into the avascular zone of the anterior part of the medial meniscus in bilateral knees. Either a gelatin hydrogel (control group) or simvastatin-conjugated gelatin hydrogel (simvastatin group) was implanted into the defect. Histological assessments were performed using qualitative scoring systems, and immunohistochemical analysis was performed at 12 weeks after surgery. The occupation ratio (OR) and safranin O staining occupation ratio (SOR) were evaluated quantitatively at each time point. Stiffness of the regenerated tissue was analyzed biomechanically at 12 weeks after surgery. Rabbit meniscal cells were cultured in the presence or absence of 0.5 μM simvastatin, and then real-time polymerase chain reaction was performed to evaluate gene expression. Results: The qualitative score was significantly higher in the simvastatin group after 8 and 12 weeks (P = .031 and .035, respectively). The mean OR and SOR were also significantly higher in the simvastatin group (OR at 8 weeks: 0.396 ± 0.019 [control] vs 0.564 ± 0.123 [simvastatin], P = .008; OR at 12 weeks: 0.451 ± 0.864 [control] vs 0.864 ± 0.035 [simvastatin], P = .001; SOR at 8 weeks: 0.071 ± 0.211 [control] vs 0.487 ± 0.430 [simvastatin], P = .009; SOR at 12 weeks: 0.093 ± 0.088 [control] vs 0.821 ± 0.051 [simvastatin], P = .006). Immunohistochemical analysis showed that at 12 weeks, the reparative tissue was more strongly positive for type I collagen (COL1), type II collagen (COL2), bone morphogenetic protein 2 (BMP-2), and BMP-7 in the simvastatin group than in the control group. Biomechanical analysis showed significantly higher stiffness in the simvastatin group (2.417 ± 1.593 N/ms [control] vs 5.172 ± 1.078 N/ms [simvastatin]; P = .005). In rabbit meniscal cells, BMP-2 and BMP-7 were upregulated after 4 and 8 hours and after 7 and 14 days, whereas COL1A1 and COL2A1 were significantly upregulated by simvastatin after 7 and 14 days. Conclusion: The local administration of simvastatin promotes the regeneration of an avascular meniscus in the rabbit model of a meniscal defect. The mechanism may involve the upregulation of BMPs and the subsequent upregulation of COL1 and COL2. Clinical Relevance: This study suggests that simvastatin stimulated intrinsic healing of an avascular meniscus. The local administration of simvastatin is safe and inexpensive and seems to be a promising treatment of meniscal injuries.

Quantification of 18FDG in the Normal Colon-A First Step in Investigating Whether Its Presence Is a Marker of a Physiological Process.

The visibility of the colon in positron emission tomography (PET) scans of patients without gastrointestinal disease indicating the presence of 18F Fluorodeoxyglucose (18FDG) is well recognised, but unquantified and unexplained. In this paper a qualitative scoring system was applied to PET scans from 30 randomly selected patients without gastrointestinal disease to detect the presence of 18FDG in 4 different sections of the colon and then both the total pixel value and the pixel value per unit length of each section of the colon were determined to quantify the amount of 18FDG from a randomly selected subset of 10 of these patients. Analysis of the qualitative scores using a non-parametric ANOVA showed that all sections of the colon contained 18FDG but there were differences in the amount of 18FDG present between sections (p<0.05). Wilcoxon matched-pair signed-rank tests between pairs of segments showed statistically significant differences between all pairs (p<0.05) with the exception of the caecum and ascending colon and the descending colon. The same non-parametric statistical analysis of the quantitative measures showed no difference in the total amount of 18FDG between sections (p>0.05), but a difference in the amount/unit length between sections (p<0.01) with only the caecum and ascending colon and the descending colon having a statistically significant difference (p<0.05). These results are consistent since the eye is drawn to focal localisation of the 18FDG when qualitatively scoring the scans. The presence of 18FDG in the colon is counterintuitive since it must be passing from the blood to the lumen through the colonic wall. There is no active mechanism to achieve this and therefore we hypothesise that the transport is a passive process driven by the concentration gradient of 18FDG across the colonic wall. This hypothesis is consistent with the results obtained from the qualitative and quantitative measures analysed.