10-Minute Delayed Recall from the Modified Mini-Mental State Test Predicts Alzheimer’s Disease Pathology

PubMed Central

Lyness, Scott A.; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L.; Chui, Helena C.

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer’s disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0–9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation. PMID:24240637

10-minute delayed recall from the modified mini-mental state test predicts Alzheimer's disease pathology.

PubMed

Lyness, Scott A; Lee, Ae Young; Zarow, Chris; Teng, Evelyn L; Chui, Helena C

2014-01-01

We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer's disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. 10-min delayed recall scores ≤4 (score range = 0-9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation.

HCG administration after endogenous LH rise negatively influences pregnancy rate in modified natural cycle for frozen-thawed euploid blastocyst transfer: a pilot study.

PubMed

Litwicka, Katarzyna; Mencacci, Cecilia; Arrivi, Cristiana; Varricchio, Maria Teresa; Caragia, Alina; Minasi, Maria Giulia; Greco, Ermanno

2018-03-01

The aim of the present study was to evaluate whether in a modified natural cycle (modified-NC) for a frozen-thawed single euploid blastocyst transfer, a critical LH value, above which human chorionic gonadotropin (hCG) administration should be avoided, may be defined. One hundred and sixty-seven patients underwent modified natural cycle in order to transfer a single frozen-thawed euploid blastocyst. All embryos were obtained by intracytoplasmic sperm injection and were biopsied at the blastocyst stage and analyzed by means of array comparative genomic hybridization (aCGH). Ovulation was induced using 10.000 IU hCG when the mean follicle diameter was at least of 17 mm, independently from LH values. The primary end points were the hCG-positive test and clinical pregnancy. The interim analysis showed that LH value ≥ 13 mIU/ml on the day of hCG injection may negatively influence the clinical results, suggesting that in this condition, it should be advisable waiting for spontaneous ovulation. Among patients who received hCG for ovulation induction, the hCG-positive test and clinical pregnancy rates in modified-NC were significantly lower in cycles with LH ≥ 13 mIU/ml in respect to those with LH < 13 mIU/ml (45.4 vs 73.3 and 36.4 vs 65.9%, in LH ≥ 13 and LH < 13 groups, respectively). In patients with LH value ≥ 13 mIU/ml, hCG administration led to significantly lower rates of hCG-positive test (45.4 vs 74.5% in hCG administration and spontaneous ovulation groups, respectively) and clinical pregnancy (36.4 vs 64.7% in hCG administration and spontaneous ovulation groups, respectively). The baseline patient characteristics were comparable in all groups. The findings of this study highlight that LH elevation ≥ 13 mIU/ml prior to hCG administration may negatively affect clinical pregnancy rates in modified-NC for single euploid blastocyst transfer. The LH determination should be routinely performed during follicular monitoring. In the presence of LH level ≥ 13 mIU/ml, hCG administration should be avoided, and the embryo transfer should be planned only after spontaneous follicular rupture.

Modified Test Protocol Improves Sensitivity of the Stereo Fly Test.

PubMed

De La Cruz, Angie; Morale, Sarah E; Jost, Reed M; Kelly, Krista R; Birch, Eileen E

2016-01-01

Stereoacuity measurement is a common element of pediatric ophthalmic examinations. Although the Stereo Fly Test is routinely used to establish the presence of coarse stereopsis (3000 arcsecs), it often yields a false negative "pass" due to learned responses and non-stereoscopic cues. We developed and evaluated a modified Stereo Fly Test protocol aimed at increasing sensitivity, thus reducing false negatives. The Stereo Fly Test was administered according to manufacturer instructions to 321 children aged 3-12 years. Children with a "pass" outcome (n = 147) were re-tested wearing glasses fitted with polarizers of matching orientation for both eyes to verify that they were responding to stereoscopic cues (modified protocol). The response to the standard Stereo Fly Test was considered a false negative (pass) if the child still pinched above the plate after disparity cues were eliminated. Randot ® Preschool Stereoacuity and Butterfly Tests were used as gold standards. Sensitivity was 81% (95% CI: 0.75 - 0.86) for standard administration of the Stereo Fly Test (19% false negative "pass"). The modified protocol increased sensitivity to 90% (95% CI: 0.85 - 0.94). The modified two-step protocol is a simple and convenient way to administer the Stereo Fly Test with increased sensitivity in a clinical setting. © 2016 Board of regents of the University of Wisconsin System, American Orthoptic Journal, Volume 66, 2016, ISSN 0065-955X, E-ISSN 1553-4448.

The relationship between clinical and standardized tests for hand-arm vibration syndrome.

PubMed

Poole, C J M; Mason, H; Harding, A-H

2016-06-01

Standardized laboratory tests are undertaken to assist the diagnosis and staging of hand-arm vibration syndrome (HAVS), but the strength of the relationship between the tests and clinical stages of HAVS is unknown. To assess the relationship between the results of thermal aesthesiometry (TA), vibrotactile (VT) thresholds and cold provocation (CP) tests with the modified Stockholm scales for HAVS and to determine whether the relationship is affected by finger skin temperature. Consecutive records of workers referred to a Tier 5 HAVS assessment centre from 2006 to 2015 were identified. The diagnosis and staging of cases was undertaken from the clinical information contained in the records. Cases with alternative or mixed diagnoses were excluded and staging performed according to the modified Stockholm scale without knowledge of the results of the standardized laboratory tests. A total of 279 cases of HAVS were analysed. Although there was a significant trend for sensorineural (SN) and vascular scores to increase with clinical stage (P < 0.01), there was no significant difference in scores between 2SN early and 2SN late or between 2SN late and 3SN. There was moderate correlation between the TA and VT scores and the clinical SN stages (r = 0.6). This correlation did not change when subjects were divided into those with a finger skin temperature <30 and >30°C. CP scores distributed bimodally and correlated poorly with clinical staging (r = 0.2). Standardized SN tests distinguish between the lower Stockholm stages, but not above 2SN early. This has implications for health surveillance and UK policy. © Crown copyright 2016.

26 CFR 1.28-1 - Credit for clinical testing expenses for certain drugs for rare diseases or conditions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... section 41(b) (relating to the credit for increasing research activities) as modified by section 28(b)(1... benefits to the taxpayer from the conduct of the clinical testing (for example, increased experience in the...), before the date on which a license for such drug is issued under section 351 of the Public Health...

26 CFR 1.28-1 - Credit for clinical testing expenses for certain drugs for rare diseases or conditions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... section 41(b) (relating to the credit for increasing research activities) as modified by section 28(b)(1... benefits to the taxpayer from the conduct of the clinical testing (for example, increased experience in the...), before the date on which a license for such drug is issued under section 351 of the Public Health...

26 CFR 1.28-1 - Credit for clinical testing expenses for certain drugs for rare diseases or conditions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... section 41(b) (relating to the credit for increasing research activities) as modified by section 28(b)(1... benefits to the taxpayer from the conduct of the clinical testing (for example, increased experience in the...), before the date on which a license for such drug is issued under section 351 of the Public Health...

26 CFR 1.28-1 - Credit for clinical testing expenses for certain drugs for rare diseases or conditions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... section 41(b) (relating to the credit for increasing research activities) as modified by section 28(b)(1... benefits to the taxpayer from the conduct of the clinical testing (for example, increased experience in the...), before the date on which a license for such drug is issued under section 351 of the Public Health...

The passive hamstring stretch test: clinical evaluation.

PubMed

Fisk, J W

1979-03-28

The passive hamstring stretch test is described. Using a modified goniometer it is shown that independent measurements taken by trained examiners approximate very closely to each other. This establishes the test as a valid objective measurement. The possible value of this test as a research tool in low back pain problems is discussed.

Sensitivity and specificity of modified 100-g oral glucose tolerance tests for diagnosis of gestational diabetes mellitus.

PubMed

Hansarikit, Jarunee; Manotaya, Saknan

2011-05-01

To study the sensitivity and specificity of the modified 100-g oral glucose tolerance test for diagnosis of gestational diabetes mellitus (GDM). Medical records of pregnant women attending the antenatal clinic of King Chulalongkorn Memorial Hospital, Thailand, who underwent a 100-g oral glucose tolerance test (OGTT) during March 2004 to September 2009, were retrospectively reviewed. Three modified criteria were proposed for diagnosis of GDM. The screening efficacy of the modified criteria were assessed, using the National Diabetes Data Group (NDDG) criterion as gold standard. A total of 729 records were reviewed, 511 were included for analysis. Using the NDDG criterion as the gold standard, the modified II criterion has the highest sensitivity of 96.8%, and the highest accuracy of 90.8%. The modified II criterion can detect the same proportion of maternal and neonatal complications, compared to the NDDG criterion. The modified II criterion, using the fasting plasma glucose and 2-hour plasma glucose measurements, showed high sensitivity and accuracy, with moderate specificity for diagnosis of GDM. Its potential use as an alternative to standard 100-g OGTT should be evaluated in the prospective study.

Vestibular Assessments in Children With Global Developmental Delay: An Exploratory Study.

PubMed

Dannenbaum, Elizabeth; Horne, Victoria; Malik, Farwa; Villeneuve, Myriam; Salvo, Lora; Chilingaryan, Gevorg; Lamontagne, Anouk

2016-01-01

To compare results of 3 clinical vestibular tests between children with global developmental delay (GDD) and children with typical development (TD) and investigate the test-retest reliability. Twenty children with GDD (aged 4.1-12.1 years) and 11 age-matched controls with TD participated. Participants with GDD underwent 2 sessions of testing. Each session consisted of the Clinical Test of Sensory Interaction and Balance (CTSIB), Dynamic Visual Acuity (DVA) test, and the modified Emory Clinical Vestibular Chair Test (m-ECVCT). Up to 33% of the children with GDD had abnormal DVA scores. m-ECVCT results of children with GDD demonstrated larger variance than children with TD. The CTSIB score was significantly reduced in the group with GDD. The test-retest reliability varied, with good reliability for the m-ECVCT and CTSIB, and fair reliability for the DVA. Findings suggest vestibular involvement in children in GDD. The clinical tests demonstrated moderate test-retest reliability.

Proposal of quality indicators for cardiac rehabilitation after acute coronary syndrome in Japan: a modified Delphi method and practice test.

PubMed

Ohtera, Shosuke; Kanazawa, Natsuko; Ozasa, Neiko; Ueshima, Kenji; Nakayama, Takeo

2017-01-27

Cardiac rehabilitation is underused and its quality in practice is unclear. A quality indicator is a measurable element of clinical practice performance. This study aimed to propose a set of quality indicators for cardiac rehabilitation following an acute coronary event in the Japanese population and conduct a small-size practice test to confirm feasibility and applicability of the indicators in real-world clinical practice. This study used a modified Delphi technique (the RAND/UCLA appropriateness method), a consensus method which involves an evidence review, a face-to-face multidisciplinary panel meeting and repeated anonymous rating. Evidence to be reviewed included clinical practice guidelines available in English or Japanese and existing quality indicators. Performance of each indicator was assessed retrospectively using medical records at a university hospital in Japan. 10 professionals in cardiac rehabilitation for the consensus panel. In the literature review, 23 clinical practice guidelines and 16 existing indicators were identified to generate potential indicators. Through the consensus-building process, a total of 30 indicators were assessed and finally 13 indicators were accepted. The practice test (n=39) revealed that 74% of patients underwent cardiac rehabilitation. Median performance of process measures was 93% (IQR 46-100%). 'Communication with the doctor who referred the patient to cardiac rehabilitation' and 'continuous participation in cardiac rehabilitation' had low performance (32% and 38%, respectively). A modified Delphi technique identified a comprehensive set of quality indicators for cardiac rehabilitation. The single-site, small-size practice test confirmed that most of the proposed indicators were measurable in real-world clinical practice. However, some clinical processes which are not covered by national health insurance in Japan had low performance. Further studies will be needed to clarify and improve the quality of care in cardiac rehabilitation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Best practices for clinical pathology testing in carcinogenicity studies.

PubMed

Young, Jamie K; Hall, Robert L; O'Brien, Peter; Strauss, Volker; Vahle, John L

2011-02-01

The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) convened a Clinical Pathology in Carcinogenicity Studies Working Group to recommend best practices for inclusion of clinical pathology testing in carcinogenicity studies. Regulatory guidance documents and literature were reviewed, and veterinary pathologists from North America, Japan, and Europe were surveyed regarding current practices, perceived value, and recommendations for clinical pathology testing in carcinogenicity studies. For two-year rodent carcinogenicity studies, the Working Group recommends that clinical pathology testing be limited to collection of blood smears at scheduled and unscheduled sacrifices to be examined only if indicated to aid in the diagnosis of possible hematopoietic neoplasia following histopathologic evaluation. Additional clinical pathology testing is most appropriately used to address specific issues from prior toxicity studies or known test article-related class effects. Inadequate data were available to make a recommendation concerning clinical pathology testing for alternative six-month carcinogenicity assays using genetically modified mice, although the Working Group suggests that it may be appropriate to use the same approach as for two-year carcinogenicity studies since the study goal is the same.

HIV Vaccines

MedlinePlus

... an NIH-supported clinical trial was launched to test a modified HIV vaccine. This current vaccine trial, called HVTN 702, is testing whether an experimental vaccine regimen safely prevents HIV infection among South African adults. Learn more in this blog post and in the video below. /* // ** // */ Why Do We ...

Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function.

PubMed

Severgnini, Paolo; Selmo, Gabriele; Lanza, Christian; Chiesa, Alessandro; Frigerio, Alice; Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Novario, Raffaele; Gregoretti, Cesare; de Abreu, Marcelo Gama; Schultz, Marcus J; Jaber, Samir; Futier, Emmanuel; Chiaranda, Maurizio; Pelosi, Paolo

2013-06-01

The impact of intraoperative ventilation on postoperative pulmonary complications is not defined. The authors aimed at determining the effectiveness of protective mechanical ventilation during open abdominal surgery on a modified Clinical Pulmonary Infection Score as primary outcome and postoperative pulmonary function. Prospective randomized, open-label, clinical trial performed in 56 patients scheduled to undergo elective open abdominal surgery lasting more than 2 h. Patients were assigned by envelopes to mechanical ventilation with tidal volume of 9 ml/kg ideal body weight and zero-positive end-expiratory pressure (standard ventilation strategy) or tidal volumes of 7 ml/kg ideal body weight, 10 cm H2O positive end-expiratory pressure, and recruitment maneuvers (protective ventilation strategy). Modified Clinical Pulmonary Infection Score, gas exchange, and pulmonary functional tests were measured preoperatively, as well as at days 1, 3, and 5 after surgery. Patients ventilated protectively showed better pulmonary functional tests up to day 5, fewer alterations on chest x-ray up to day 3 and higher arterial oxygenation in air at days 1, 3, and 5 (mmHg; mean ± SD): 77.1 ± 13.0 versus 64.9 ± 11.3 (P = 0.0006), 80.5 ± 10.1 versus 69.7 ± 9.3 (P = 0.0002), and 82.1 ± 10.7 versus 78.5 ± 21.7 (P = 0.44) respectively. The modified Clinical Pulmonary Infection Score was lower in the protective ventilation strategy at days 1 and 3. The percentage of patients in hospital at day 28 after surgery was not different between groups (7 vs. 15% respectively, P = 0.42). A protective ventilation strategy during abdominal surgery lasting more than 2 h improved respiratory function and reduced the modified Clinical Pulmonary Infection Score without affecting length of hospital stay.

One year comparative clinical evaluation of EQUIA with resin-modified glass ionomer and a nanohybrid composite in noncarious cervical lesions

PubMed Central

Vaid, Deepa Sunil; Shah, Nimisha Chinmay; Bilgi, Priyanka Shripad

2015-01-01

Aims: Comparative evaluation of EQUIA with a resin-modified glass ionomer cement (RMGIC; GC Gold Label glass ionomer light cured universal restorative cement) and a nanohybrid composite (Tetric N-Ceram) in noncarious cervical lesions (NCCLs). Background: To establish the most suitable material for the restoration of NCCLs. Settings and Design: In vivo study. Materials and Methods: Eighty-seven NCCLs were randomly restored with EQUIA, a RMGIC, and a nanohybrid composite. Clinical evaluation of the restorations was done following the Unites States Public Health criteria by a single-blinded investigator. Data were formulated, and statistical analysis was done by Chi-square test. Statistical Analysis Used: Chi-square test. Results: No significant difference was found between EQUIA, RMGIC, and nanohybrid composite at 1-month, at 6 months, and at 1-year (P > 0.05). Conclusions: EQUIA, resin-modified glass ionomer, and nanohybrid composite performed equally at 1-month, 6 months, and 1-year follow-up periods. PMID:26752837

Clinical assessment of scapular positioning in musicians: an intertester reliability study.

PubMed

Struyf, Filip; Nijs, Jo; De Coninck, Kris; Giunta, Marco; Mottram, Sarah; Meeusen, Romain

2009-01-01

The reliability of the measurement of the distance between the posterior border of the acromion and the wall and the reliability of the modified lateral scapular slide test have not been studied. Overall, the reliability of the clinical tools used to assess scapular positioning has not been studied in musicians. To examine the intertester reliability of scapular observation and 2 clinical tests for the assessment of scapular positioning in musicians. Intertester reliability study. University research laboratory. Thirty healthy student musicians at a single university. Two assessors performed a standardized observation protocol, the measurement of the distance between the posterior border of the acromion and the wall, and the modified lateral scapular slide test. Each assessor was blinded to the other's findings. The intertester reliability coefficients (kappa) for the observation in relaxed position, during unloaded movement, and during loaded movement were 0.41, 0.63, and 0.36, respectively. The kappa values for the observation of tilting and winging at rest were 0.48 and 0.42, respectively; during unloaded movement, the kappa values were 0.52 and 0.78, respectively; and with a 1-kg load, the kappa values were 0.24 and 0.50, respectively. The intraclass correlation coefficient (ICC) of the measurement of the acromial distance was 0.72 in relaxed position and 0.75 with the participant actively retracting both shoulders. The ICCs for the modified lateral scapular slide test varied between 0.63 and 0.58. Our results demonstrated that the modified lateral scapular slide test was not a reliable tool to assess scapular positioning in these participants. Our data indicated that scapular observation in the relaxed position and during unloaded abduction in the frontal plane was a reliable assessment tool. The reliability of the measurement of the distance between the posterior border of the acromion and the wall in healthy musicians was moderate.

Clinical Assessment of Scapular Positioning in Musicians: An Intertester Reliability Study

PubMed Central

Struyf, Filip; Nijs, Jo; De Coninck, Kris; Giunta, Marco; Mottram, Sarah; Meeusen, Romain

2009-01-01

Abstract Context: The reliability of the measurement of the distance between the posterior border of the acromion and the wall and the reliability of the modified lateral scapular slide test have not been studied. Overall, the reliability of the clinical tools used to assess scapular positioning has not been studied in musicians. Objective: To examine the intertester reliability of scapular observation and 2 clinical tests for the assessment of scapular positioning in musicians. Design: Intertester reliability study. Setting: University research laboratory. Patients or Other Participants: Thirty healthy student musicians at a single university. Main Outcome Measure(s): Two assessors performed a standardized observation protocol, the measurement of the distance between the posterior border of the acromion and the wall, and the modified lateral scapular slide test. Each assessor was blinded to the other's findings. Results: The intertester reliability coefficients (κ) for the observation in relaxed position, during unloaded movement, and during loaded movement were 0.41, 0.63, and 0.36, respectively. The κ values for the observation of tilting and winging at rest were 0.48 and 0.42, respectively; during unloaded movement, the κ values were 0.52 and 0.78, respectively; and with a 1-kg load, the κ values were 0.24 and 0.50, respectively. The intraclass correlation coefficient (ICC) of the measurement of the acromial distance was 0.72 in relaxed position and 0.75 with the participant actively retracting both shoulders. The ICCs for the modified lateral scapular slide test varied between 0.63 and 0.58. Conclusions: Our results demonstrated that the modified lateral scapular slide test was not a reliable tool to assess scapular positioning in these participants. Our data indicated that scapular observation in the relaxed position and during unloaded abduction in the frontal plane was a reliable assessment tool. The reliability of the measurement of the distance between the posterior border of the acromion and the wall in healthy musicians was moderate. PMID:19771291

Evaluation of esthetic parameters of resin-modified glass-ionomer materials and a polyacid-modified resin composite in Class V cervical lesions.

PubMed

Gladys, S; Van Meerbeek, B; Lambrechts, P; Vanherle, G

1999-09-01

The purpose of this study was to compare the esthetics of 3 resin-modified glass-ionomer materials and 1 polyacid-modified resin composite to the esthetics of a conventional glass-ionomer control material. One hundred eighty-seven Class V cervical restorations were observed clinically over 18 months. The esthetic index system that was used evaluated color match, translucency or opacity, and surface roughness. The tested materials behaved very dissimilarly and inconsistently. In general, the esthetic results of the resin-modified glass-ionomer materials and the polyacid-modified resin composite were far from optimal. The esthetic appearance of restorations seriously deteriorated during clinical service, mainly because of discoloration of margins, changes in translucency and opacity, and rapidly appearing roughness or dullness on the surface. Both the resin-modified glass-ionomer materials and the polyacid-modified resin composite evaluated in this study performed better esthetically than did the conventional glass-ionomer material. Indications for these combination materials are limited to areas where esthetics is not a primary concern but where their ease of application may guarantee a more durable functional result.

Environmental contact factors in eczema and the results of patch testing Chinese patients with a modified European standard series of allergens.

PubMed

Li, Lin-Feng; Guo, Jing; Wang, Jing

2004-07-01

Environmental contact factors in eczema were investigated in China by clinical questionnaire and patch testing patients with a modified European standard series of allergens. 217 consecutive eczema patients were studied. Contact dermatitis (CD) was clinically diagnosed in 30% of the patients. Among the patients patch tested, 46 patients had clinically diagnosed allergic CD (ACD), 20 patients clinically had non-ACD (NACD) (including 16 cases of irritant contact dermatitis, 1 case of phototoxic contact reaction and 3 cases of asteatotic eczema) and 115 patients had clinically suspected ACD. 45 patients (98%) in the ACD group went on to have relevant patch test results. The most common ACD was from metals, fragrance materials, cosmetics and rubber materials. The most common contact allergens identified were nickel, fragrance mix, para-phenylenediamine (PPD), carba mix and thimerosal. No adverse reactions were observed to patch testing, except for pruritus in patch-test-positive patients. The positive rate of patch testing in ACD was much higher than that in NACD (98% versus 15%, P < 0.05, chi(2)-test). 60 (28%) patients had facial dermatitis (FD). Among these, 20 (33%) were confirmed as having ACD. 48 (22%) patients had hand dermatitis (HD). Among these, 7 (15%) were confirmed as having ACD. Fewer patients were confirmed as having ACD in the HD group than in the FD (15% versus 33%, P < 0.05, chi(2)-test). Although the difference was not significant, the total positivity rate in the HD group (55%) was lower than in the other groups. 65 (30%) patients had unclassified endogenous eczema (UEE). The total positive rate of patch testing in the UEE group (56%) was no different from that in the FD or HD groups. However, the relevance of positive patch tests was hard to determine in UEE. These results indicate that CD is common in eczema; relatively more patients with FD have ACD, while other factors, such as irritation, may play more of a role in HD. The total positive rate of patch testing in the UEE group was no different from that in the FD or HD groups, suggesting that patch testing should be stressed in UEE and the relevance of positive patch test results in UEE should be studied further. It is effective and safe to patch eczema patients with a modified European standard series of allergens in China.

Is This the Carbapenemase Test We've Been Waiting for? A Multicenter Evaluation of the Modified Carbapenem Inactivation Method.

PubMed

Butler-Wu, Susan M; Abbott, April N

2017-08-01

A plethora of phenotypic methods exist for the detection of carbapenemases; however, clinical laboratories have struggled for years with accurate, objective phenotypic detection of carbapenemase activity in Enterobacteriaceae In this issue of the Journal of Clinical Microbiology , V. M. Pierce et al. (J Clin Microbiol 55:2321-2333, 2017, https://doi.org/10.1128/JCM.00193-17) report on a multicenter evaluation of the modified carbapenem inactivation method (mCIM). The high sensitivity, specificity, reproducibility, and ease of interpretation associated with the mCIM for Enterobacteriaceae will likely lead to its adoption by clinical laboratories. Copyright © 2017 American Society for Microbiology.

Evaluating the Impact of EBP Education: Development of a Modified Fresno Test for Acute Care Nursing.

PubMed

Halm, Margo A

2018-05-14

Proficiency in evidence-based practice (EBP) is essential for relevant research findings to be integrated into clinical care when congruent with patient preferences. Few valid and reliable tools are available to evaluate the effectiveness of educational programs in advancing EBP attitudes, knowledge, skills, or behaviors, and ongoing competency. The Fresno test is one objective method to evaluate EBP knowledge and skills; however, the original and modified versions were validated with family physicians, physical therapists, and speech and language therapists. To adapt the Modified Fresno-Acute Care Nursing test and develop a psychometrically sound tool for use in academic and practice settings. In Phase 1, modified Fresno (Tilson, 2010) items were adapted for acute care nursing. In Phase 2, content validity was established with an expert panel. Content validity indices (I-CVI) ranged from .75 to 1.0. Scale CVI was .95%. A cross-sectional convenience sample of acute care nurses (n = 90) in novice, master, and expert cohorts completed the Modified Fresno-Acute Care Nursing test administered electronically via SurveyMonkey. Total scores were significantly different between training levels (p < .0001). Novice nurses scored significantly lower than master or expert nurses, but differences were not found between the latter cohorts. Total score reliability was acceptable: (interrater [ICC (2, 1)]) = .88. Cronbach's alpha was 0.70. Psychometric properties of most modified items were satisfactory; however, six require further revision and testing to meet acceptable standards. The Modified Fresno-Acute Care Nursing test is a 14-item test for objectively assessing EBP knowledge and skills of acute care nurses. While preliminary psychometric properties for this new EBP knowledge measure for acute care nursing are promising, further validation of some of the items and scoring rubric is needed. © 2018 Sigma Theta Tau International.

Multi-level assessment protocol (MAP) for adoption in multi-site clinical trials

PubMed Central

Guydish, J.; Manser, S.T.; Jessup, M.; Tajima, B.; Sears, C.; Montini, T.

2010-01-01

The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is intended to test promising drug abuse treatment models in multi-site clinical trials, and to support adoption of new interventions into clinical practice. Using qualitative research methods we asked: How might the technology of multi-site clinical trials be modified to better support adoption of tested interventions? A total of 42 participants, representing 8 organizational levels ranging from clinic staff to clinical trial leaders, were interviewed about their role in the clinical trial, its interactions with clinics, and intervention adoption. Among eight clinics participating in the clinical trial, we found adoption of the tested intervention in one clinic only. In analysis of interview data we identified four conceptual themes which are likely to affect adoption and may be informative in future multi-site clinical trials. We offer the conclusion that planning for adoption in the early stages of protocol development will better serve the aim of integrating new interventions into practice. PMID:20890376

Comparison of the Carba NP, Modified Carba NP, and Updated Rosco Neo-Rapid Carb Kit Tests for Carbapenemase Detection

PubMed Central

AbdelGhani, Sameh; Thomson, Gina K.; Snyder, James W.

2015-01-01

The accurate detection of carbapenemase-producing organisms is a major challenge for clinical laboratories. The Carba NP test is highly accurate but inconvenient, as it requires frequent preparation of fresh imipenem solution. The current study was designed to compare the Carba NP test to two alternative tests for accuracy and convenience. These were a modified Carba NP test that utilized intravenous (i.v.) imipenem-cilastatin, which is less expensive than reference standard imipenem powder, and an updated version of the Rosco Neo-Rapid Carb kit, which does not require the preparation of imipenem solution and has a shelf life of 2 years. The comparison included 87 isolates that produced class A carbapenemases (including KPC-2, -3, -4, -5, -6, and -8, NMC-A, and SME type), 40 isolates that produced metallo-β-lactamases (including NDM-1, GIM-1, SPM-1, IMP-1, -2, -7, -8, -18, and -27, and VIM-1, -2, and -7), 11 isolates that produced OXA-48, and one isolate that produced OXA-181. Negative controls consisted of 50 isolates that produced extended-spectrum β-lactamases (ESBLs), AmpCs (including hyperproducers), K1, other limited-spectrum β-lactamases, and porin and efflux mutants. Each test exhibited 100% specificity and high sensitivity (Carba NP, 100%; Rosco, 99% using modified interpretation guidelines; and modified Carba NP, 96%). A modified approach to interpretation of the Rosco test was necessary to achieve the sensitivity of 99%. If the accuracy of the modified interpretation is confirmed, the Rosco test is an accurate and more convenient alternative to the Carba NP test. PMID:26311862

A new modification of the individually designed polymer implant visible in X-ray for orbital reconstruction.

PubMed

Jazwiecka-Koscielniak, Ewa; Kozakiewicz, Marcin

2014-10-01

Orbital reconstruction makes higher demands on symmetry and axial precision than other parts of the skull, because the position of the eye globe determines proper vision. The aim of this study is to evaluate titanium surface marking of polymers (UHMW-PE and PA6) to check implants position in CT examination and clinical application of such modified individual implant. One hundred and twenty-four polymer blocks were prepared. New method of ultrasounds welding to connect the titanium markers to the polymer surface was developed and tested. Titanium marked polymer blocks were examined by CT to evaluate the quality of the cover. Then, two modified UHMW-PE individual implants were applied clinically and implant position was checked by CT. The biggest titanium cover was in PA6 [25 ± 18% of processed surface] and for UHMW-PE [19 ± 12%] without significance [p = 0.14]. Both covers were visible in CT. Clinical application revealed proper reconstruction, uneventful post-operational outcome and well visible surface of the implants in CT. The conducted tests make it possible to determine the suitability of ultrasonic technology for the deposition of titanium markers in polymer. The clinical use of modified individual implants allows to confirm the correct position of the implants because they are accurate visible in CT. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

ASSOCIATIONS BETWEEN THREE CLINICAL ASSESSMENT TOOLS FOR POSTURAL STABILITY

PubMed Central

Saxion, Casie E.; Cameron, Kenneth L.; Gerber, J. Parry

2010-01-01

Study Design: Clinical Measurement, Correlation, Reliability Objectives: To assess the relationship between the Single Leg Balance (SLB), modified Balance Error Scoring System (mBESS), and modified Star Excursion Balance (mSEBT) tests and secondarily to assess inter-rater and test-retest reliability of these tests. Background: Ankle sprains often result in chronic instability and dysfunction. Several clinical tests assess postural deficits as a potential cause of this dysfunction; however, limited information exists pertaining to the relationship that these tests have with one another. Methods: Two independent examiners measured the performance of 34 healthy participants completing the SLB Test, mBESS test, and mSEBT at two different time periods. The relationship between tests was assessed using the Pearson Correlation and Fisher's Exact Tests. Inter-rater and test-retest reliability were assessed using the intraclass correlation coefficient (ICC) and Kappa statistics. Results: A significant correlation (r = -0.35) was observed between the mSEBT and the mBESS. Fisher's Exact Test showed a significant association between the SLB Test and mBESS (P = .048), but no association between the SLB and mSEBT (P = 1.000). Inter-rater reliability was excellent for the mSEBT and fair for the mBESS (ICCs of .91 and .61 respectively). Excellent agreement was observed between raters for the SLB test (k = 1.00). Test-retest reliability was excellent for the mSEBT (ICC = 0.98) and fair for the mBESS (ICC = 0.74). There was poor test-retest agreement for the SLB test (k = .211). Conclusion: There was a significant relationship observed between the SLB Test, mBESS test, and mSEBT: however; strength of association measures showed limited overlap between these tests. This suggests that these tests are interrelated but may not assess equal components of postural stability. PMID:21589668

Hip Strength Testing of Soccer Players With Long-Standing Hip and Groin Pain: What are the Clinical Implications of Pain During Testing?

PubMed

Rafn, Bolette S; Tang, Lars; Nielsen, Martin P; Branci, Sonia; Hölmich, Per; Thorborg, Kristian

2016-05-01

To investigate whether self-reported pain during hip strength testing correlates to a large degree with hip muscle strength in soccer players with long-standing unilateral hip and groin pain. Cross-sectional study. Clinical assessments at Sports Orthopaedic Research Center-Copenhagen (SORC-C), Arthroscopic Centre Amager, Copenhagen University Hospital, Denmark. Twenty-four male soccer players with unilateral long-standing hip and groin pain. The soccer players performed 5 reliable hip muscle strength tests (isometric hip flexion, adduction, abduction, isometric hip flexion-modified Thomas test, and eccentric hip adduction). Muscle strength was measured with a hand-held dynamometer, and the players rated the pain during testing on a numerical rating scale (0-10). In 4 tests (isometric hip adduction, abduction, flexion, and eccentric adduction), no significant correlations were found between pain during testing and hip muscle strength (Spearman rho = -0.28 to 0.06, P = 0.09-0.39). Isometric hip flexion (modified Thomas test position) showed a moderate negative correlation between pain and hip muscle strength (Spearman rho = -0.44, P = 0.016). Self-reported pain during testing does not seem to correlate with the majority of hip muscle strength tests used in soccer players with long-standing hip and groin pain.

Photoplethysmography using a smartphone application for assessment of ulnar artery patency: a randomized clinical trial

PubMed Central

Di Santo, Pietro; Harnett, David T.; Simard, Trevor; Ramirez, F. Daniel; Pourdjabbar, Ali; Yousef, Altayyeb; Moreland, Robert; Bernick, Jordan; Wells, George; Dick, Alexander; Le May, Michel; Labinaz, Marino; So, Derek; Motazedian, Pouya; Jung, Richard G.; Chandrasekhar, Jaya; Mehran, Roxana; Chong, Aun-Yeong

2018-01-01

BACKGROUND: Radial artery access is commonly performed for coronary angiography and invasive hemodynamic monitoring. Despite limitations in diagnostic accuracy, the modified Allen test (manual occlusion of radial and ulnar arteries followed by release of the latter and assessment of palmar blush) is used routinely to evaluate the collateral circulation to the hand and, therefore, to determine patient eligibility for radial artery access. We sought to evaluate whether a smartphone application may provide a superior alternative to the modified Allen test. METHODS: We compared the modified Allen test with a smartphone heart rate–monitoring application (photoplethysmography readings detected using a smartphone camera lens placed on the patient’s index finger) in patients undergoing a planned cardiac catheterization. Test order was randomly assigned in a 1:1 fashion. All patients then underwent conventional plethysmography of the index finger, followed by Doppler ultrasonography of the radial and ulnar arteries (the diagnostic standard). The primary outcome was diagnostic accuracy of the heart rate–monitoring application. RESULTS: Among 438 patients who were included in the study, we found that the heart rate–monitoring application had a superior diagnostic accuracy compared with the modified Allen test (91.8% v. 81.7%, p = 0.002), attributable to its greater specificity (93.0% v. 82.8%, p = 0.001). We also found that this application had greater diagnostic accuracy for assessment of radial or ulnar artery patency in the ipsilateral and contralateral wrist (94.0% v. 84.0%, p < 0.001). INTERPRETATION: A smartphone application used at the bedside was diagnostically superior to traditional physical examination for confirming ulnar patency before radial artery access. This study highlights the potential for smartphone-based diagnostics to aid in clinical decision-making at the patient’s bedside. Trial registration: Clinicaltrials.gov, no. NCT02519491. PMID:29615421

Assessment of higher order cognitive skills in undergraduate education: modified essay or multiple choice questions? Research paper

PubMed Central

Palmer, Edward J; Devitt, Peter G

2007-01-01

Background Reliable and valid written tests of higher cognitive function are difficult to produce, particularly for the assessment of clinical problem solving. Modified Essay Questions (MEQs) are often used to assess these higher order abilities in preference to other forms of assessment, including multiple-choice questions (MCQs). MEQs often form a vital component of end-of-course assessments in higher education. It is not clear how effectively these questions assess higher order cognitive skills. This study was designed to assess the effectiveness of the MEQ to measure higher-order cognitive skills in an undergraduate institution. Methods An analysis of multiple-choice questions and modified essay questions (MEQs) used for summative assessment in a clinical undergraduate curriculum was undertaken. A total of 50 MCQs and 139 stages of MEQs were examined, which came from three exams run over two years. The effectiveness of the questions was determined by two assessors and was defined by the questions ability to measure higher cognitive skills, as determined by a modification of Bloom's taxonomy, and its quality as determined by the presence of item writing flaws. Results Over 50% of all of the MEQs tested factual recall. This was similar to the percentage of MCQs testing factual recall. The modified essay question failed in its role of consistently assessing higher cognitive skills whereas the MCQ frequently tested more than mere recall of knowledge. Conclusion Construction of MEQs, which will assess higher order cognitive skills cannot be assumed to be a simple task. Well-constructed MCQs should be considered a satisfactory replacement for MEQs if the MEQs cannot be designed to adequately test higher order skills. Such MCQs are capable of withstanding the intellectual and statistical scrutiny imposed by a high stakes exit examination. PMID:18045500

Photoplethysmography using a smartphone application for assessment of ulnar artery patency: a randomized clinical trial.

PubMed

Di Santo, Pietro; Harnett, David T; Simard, Trevor; Ramirez, F Daniel; Pourdjabbar, Ali; Yousef, Altayyeb; Moreland, Robert; Bernick, Jordan; Wells, George; Dick, Alexander; Le May, Michel; Labinaz, Marino; So, Derek; Motazedian, Pouya; Jung, Richard G; Chandrasekhar, Jaya; Mehran, Roxana; Chong, Aun-Yeong; Hibbert, Benjamin

2018-04-03

Radial artery access is commonly performed for coronary angiography and invasive hemodynamic monitoring. Despite limitations in diagnostic accuracy, the modified Allen test (manual occlusion of radial and ulnar arteries followed by release of the latter and assessment of palmar blush) is used routinely to evaluate the collateral circulation to the hand and, therefore, to determine patient eligibility for radial artery access. We sought to evaluate whether a smartphone application may provide a superior alternative to the modified Allen test. We compared the modified Allen test with a smartphone heart rate-monitoring application (photoplethysmography readings detected using a smartphone camera lens placed on the patient's index finger) in patients undergoing a planned cardiac catheterization. Test order was randomly assigned in a 1:1 fashion. All patients then underwent conventional plethysmography of the index finger, followed by Doppler ultrasonography of the radial and ulnar arteries (the diagnostic standard). The primary outcome was diagnostic accuracy of the heart rate-monitoring application. Among 438 patients who were included in the study, we found that the heart rate-monitoring application had a superior diagnostic accuracy compared with the modified Allen test (91.8% v. 81.7%, p = 0.002), attributable to its greater specificity (93.0% v. 82.8%, p = 0.001). We also found that this application had greater diagnostic accuracy for assessment of radial or ulnar artery patency in the ipsilateral and contralateral wrist (94.0% v. 84.0%, p < 0.001). A smartphone application used at the bedside was diagnostically superior to traditional physical examination for confirming ulnar patency before radial artery access. This study highlights the potential for smartphone-based diagnostics to aid in clinical decision-making at the patient's bedside. Trial registration: Clinicaltrials.gov, no. NCT02519491. © 2018 Joule Inc. or its licensors.

Expanding syphilis testing: a scoping review of syphilis testing interventions among key populations.

PubMed

Ong, Jason J; Fu, Hongyun; Smith, M Kumi; Tucker, Joseph D

2018-05-01

Syphilis is an important sexually transmitted infection (STI). Despite inexpensive and effective treatment, few key populations receive syphilis testing. Innovative strategies are needed to increase syphilis testing among key populations. Areas covered: This scoping review focused on strategies to increase syphilis testing in key populations (men who have sex with men (MSM), sex workers, people who use drugs, transgender people, and incarcerated individuals). Expert commentary: We identified many promising syphilis testing strategies, particularly among MSM. These innovations are separated into diagnostic, clinic-based, and non-clinic based strategies. In terms of diagnostics, self-testing, dried blood spots, and point-of-care testing can decentralize syphilis testing. Effective syphilis self-testing pilots suggest the need for further attention and research. In terms of clinic-based strategies, modifying default clinical procedures can nudge physicians to more frequently recommend syphilis testing. In terms of non-clinic based strategies, venue-based screening (e.g. in correctional facilities, drug rehabilitation centres) and mobile testing units have been successfully implemented in a variety of settings. Integration of syphilis with HIV testing may facilitate implementation in settings where individuals have increased sexual risk. There is a strong need for further syphilis testing research and programs.

Pilot Testing Behavior Therapy for Chronic Tic Disorders in Neurology and Developmental Pediatrics Clinics.

PubMed

Ricketts, Emily J; Gilbert, Donald L; Zinner, Samuel H; Mink, Jonathan W; Lipps, Tara D; Wiegand, Geoffrey A; Vierhile, Amy E; Ely, Laura J; Piacentini, John; Walkup, John T; Woods, Douglas W

2016-03-01

Comprehensive Behavioral Intervention for Tics (CBIT) is an efficacious treatment with limited regional availability. As neurology and pediatric clinics are often the first point of therapeutic contact for individuals with tics, the present study assessed preliminary treatment response, acceptability, and feasibility of an abbreviated version, modified for child neurology and developmental pediatrics clinics. Fourteen youth (9-17) with Tourette disorder across 2 child neurology clinics and one developmental pediatrics clinic participated in a small case series. Clinician-rated tic severity (Yale Global Tic Severity Scale) decreased from pre- to posttreatment, z = -2.0, P < .05, r = -.48, as did tic-related impairment, z = -2.4, P < .05, r = -.57. Five of the 9 completers (56%) were classified as treatment responders. Satisfaction ratings were high, and therapeutic alliance ratings were moderately high. Results provide guidance for refinement of this modified CBIT protocol. © The Author(s) 2015.

Validation of a modified FRAX® tool for improving outpatient efficiency--part of the "Catch Before a Fall" initiative.

PubMed

Parker, Simon; Ciaccio, Maria; Cook, Erica; Davenport, Graham; Cooper, Alun; Grange, Simon; Smitham, Peter

2015-01-01

We have validated our touch-screen-modified FRAX® tool against the traditional healthcare professional-led questionnaire, demonstrating strong concordance between doctor- and patient-derived results. We will use this in outpatient clinics and general practice to increase our capture rate of at-risk patients, making valuable use of otherwise wasted patient waiting times. Outpatient clinics offer an opportunity to collect valuable health information from a captive population. We have previously developed a modified fracture risk assessment (FRAX®) tool, enabling patients to self-assess their osteoporotic fracture risk in a touch-screen computer format and demonstrated its acceptability with patients. We aim to validate the accuracy of our tool against the traditional questionnaire. Fifty patients over 50 years of age within the fracture clinic independently completed a paper equivalent of our touch-screen-modified FRAX® questionnaire. Responses were analysed against the traditional healthcare professional (HCP)-led questionnaire which was carried out afterwards. Correlation was assessed by sensitivity, specificity, Cohen's kappa statistic and Fisher's exact test for each potential FRAX® outcome of "treat", "measure BMD" and "lifestyle advice". Age range was 51-98 years. The FRAX® tool was completed by 88 % of patients; six patients lacked confidence in estimating either their height or weight. Following question adjustment according to patient response and feedback, our tool achieved >95 % sensitivity and specificity for the "treat" and "lifestyle advice" groups, and 79 % sensitivity and 100 % specificity in the "measure BMD" group. Cohen's kappa value ranged from 0.823 to 0.995 across all groups, demonstrating "very good" agreement for all. Fisher's exact test demonstrated significant concordance between doctor and patient decisions. Our modified tool provides a simple, accurate and reliable method for patients to self-report their own FRAX® score outside the clinical contact period, thus releasing the HCP from the time required to complete the questionnaire and potentially increasing our capture rate of at-risk patients.

An investigation into the use of two polyacid-modified composite resins (compomers) and a resin-modified glass poly(alkenoate) cement used to retain orthodontic bands.

PubMed

Williams, P H; Sherriff, M; Ireland, A J

2005-06-01

The aim of this investigation was to determine the effectiveness of a conventional glass poly(alkenoate) cement (Intact) and newer polyacid-modified composite resin cements (Transbond Plus and Ultra Band-Lok) to retain orthodontic bands. In the in vitro part of this study, stainless steel bands were cemented to 240 extracted third molar teeth in three test groups comprising Intact, Transbond Plus and Ultra Band-Lok. The force to deband (N) for all three cements was recorded using an Instron universal testing machine after the following observation periods: 20 minutes and 3, 6 and 12 months. The results indicated that all three cements increased their median force to deband after 12 months. Of the two compomers, Transbondtrade mark Plus demonstrated the highest median force to deband at all four time intervals. In the in vivo part of the study, 30 patients participated in a randomized cross-mouth clinical trial where the molar bands were cemented in place using either Intact or Transbond Plus. Ultra Band-Lok was not used in the clinical part of the study. The results showed there to be no clinically significant difference in band failure rates between the two cements. When patients were asked to score each for taste, there was a significant difference, with the glass poly(alkenoate) cement (Intact) being more acceptable than the polyacid-modified composite Transbond Plus (P < 0.001). No significant differences were observed in the in vitro median force to deband or in vivo band failure rates between the glass poly(alkenoate) cement and the polyacid-modified composite resins. The choice of cementing agent can therefore be made on patient factors, e.g. taste, or operator factors, e.g. ease of handling, cost and shelf life.

Balance Training with Wii Fit Plus for Community-Dwelling Persons 60 Years and Older.

PubMed

Roopchand-Martin, Sharmella; McLean, Roshé; Gordon, Carron; Nelson, Gail

2015-06-01

This study sought to determine the effect of 6 weeks of training, using activities from the Nintendo(®) (Kyoto, Japan) "Wii™ Fit Plus" disc, on balance in community-dwelling Jamaicans 60 years and older. A single group pretest/posttest design was used. Thirty-three subjects enrolled and 28 completed the study. Participants completed 30-minute training sessions on the Nintendo "Wii Fit" twice per week for 6 weeks. Activities used included "Obstacle Course," "Penguin Slide," "Soccer Heading," "River Bubble," "Snow Board," "Tilt Table," "Skate Board," and "Yoga Single Tree Pose." Balance was assessed with the Berg Balance Scale, the Multi Directional Reach Test, the Star Excursion Balance Test and the Modified Clinical Test for Sensory Integration in Balance. There was significant improvement in the mean Berg Balance Scale score (P=0.004), Star Excursion Balance Test score (SEBT) (P<0.001 both legs), and Multi Directional Reach Test score (P=0.002). There was no significant change on the Modified Clinical Test for Sensory Integration in Balance. Balance games on the Nintendo "Wii Fit Plus" disc can be used as a tool for balance training in community-dwelling persons 60 years of age and older.

Difficulties in clinical diagnosis of measles: proposal for modified clinical case definition.

PubMed

Ferson, M J; Young, L C; Robertson, P W; Whybin, L R

1995-10-02

To examine the accuracy of clinical diagnosis of measles and to develop an improved measles clinical case definition. Case survey. Eastern Sydney, December 1990 to August 1993. All cases of measles notified to the Eastern Sydney Public Health Unit without or before serological confirmation. Demographic and clinical details, measles- and rubella-specific IgM and measles complement fixation titres in acute and convalescent (when available) sera and epidemiological links with confirmed measles cases. Of 49 subjects reported and with complete follow-up, 24 were confirmed with measles, four with rubella and 21 had no definite diagnosis. Clinical diagnosis of measles had a false positive rate of 51%. Subjects with confirmed measles were significantly more likely to have a cough (23/24) than those with no definite diagnosis (15/21; P = 0.03) and to be febrile on the day of rash onset (23/24 versus 10/21; P = 0.001). The Centers for Disease Control definition had a sensitivity of 92% but specificity of only 24%. A modified case definition of rash, cough and fever present at onset of rash had equal sensitivity but greater specificity (57%). As measles is no longer common in Australia, clinical diagnosis is unreliable. When a public health response is needed, cases should be confirmed by serological tests or, if not available, we propose use of our modified clinical case definition.

The progress test as a diagnostic tool for a new PBL curriculum.

PubMed

Al Alwan, I; Al-Moamary, M; Al-Attas, N; Al Kushi, A; AlBanyan, E; Zamakhshary, M; Al Kadri, H M F; Tamim, H; Magzoub, M; Hajeer, A; Schmidt, H

2011-12-01

The College of Medicine at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) is running a PBL-based curriculum. A progress test was used to evaluate components of the basic medical and clinical sciences curriculum. To evaluate the performance of students at different levels of the college of medicine curriculum through USMLE-based test that focused on basic medical and clinical sciences topics. The USMLE-based basic medical and clinical sciences progress test has been conducted since 2007. It covers nine topics, including: anatomy; physiology; histology; epidemiology; biochemistry; behavioral sciences, pathology, pharmacology and immunology/microbiology. Here we analyzed results of three consecutive years of all students in years 1-4. There was a good correlation between progress test results and students' GPA. Progress test results in the clinical topics were better than basic medical sciences. In basic medical sciences, results of pharmacology, biochemistry, behavioral sciences and histology gave lower results than the other disciplines. Results of our progress test proved to be a useful indicator for both basic medical sciences and clinical sciences curriculum. Results are being utilized to help in modifying our curriculum.

Reliable scar scoring system to assess photographs of burn patients.

PubMed

Mecott, Gabriel A; Finnerty, Celeste C; Herndon, David N; Al-Mousawi, Ahmed M; Branski, Ludwik K; Hegde, Sachin; Kraft, Robert; Williams, Felicia N; Maldonado, Susana A; Rivero, Haidy G; Rodriguez-Escobar, Noe; Jeschke, Marc G

2015-12-01

Several scar-scoring scales exist to clinically monitor burn scar development and maturation. Although scoring scars through direct clinical examination is ideal, scars must sometimes be scored from photographs. No scar scale currently exists for the latter purpose. We modified a previously described scar scale (Yeong et al., J Burn Care Rehabil 1997) and tested the reliability of this new scale in assessing burn scars from photographs. The new scale consisted of three parameters as follows: scar height, surface appearance, and color mismatch. Each parameter was assigned a score of 1 (best) to 4 (worst), generating a total score of 3-12. Five physicians with burns training scored 120 representative photographs using the original and modified scales. Reliability was analyzed using coefficient of agreement, Cronbach alpha, intraclass correlation coefficient, variance, and coefficient of variance. Analysis of variance was performed using the Kruskal-Wallis test. Color mismatch and scar height scores were validated by analyzing actual height and color differences. The intraclass correlation coefficient, the coefficient of agreement, and Cronbach alpha were higher for the modified scale than those of the original scale. The original scale produced more variance than that in the modified scale. Subanalysis demonstrated that, for all categories, the modified scale had greater correlation and reliability than the original scale. The correlation between color mismatch scores and actual color differences was 0.84 and between scar height scores and actual height was 0.81. The modified scar scale is a simple, reliable, and useful scale for evaluating photographs of burn patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Mallampati test as a predictor of laryngoscopic view.

PubMed

Adamus, Milan; Fritscherova, Sarka; Hrabalek, Lumir; Gabrhelik, Tomas; Zapletalova, Jana; Janout, Vladimir

2010-12-01

To determine the accuracy of the modified Mallampati test for predicting difficult tracheal intubation. A cross-sectional, clinical, observational, non-blinded study. A quality analysis of anesthetic care. Operating theatres and department of anesthesiology in a university hospital. Following the local ethics committee approval and patients' informed consent to anesthesia, all adult patients (> 18 yrs) presenting for any type of non-emergency surgical procedures under general anesthesia requiring endotracheal intubation were enrolled. Prior to anesthesia, Samsoon and Young's modification of the Mallampati test (modified Mallampati test) was performed. Following induction, the anesthesiologist described the laryngoscopic view using the Cormack-Lehane scale. Classes 3 or 4 of the modified Mallampati test were considered a predictor of difficult intubation. Grades 3 or 4 of the Cormack-Lehane classification of the laryngoscopic view were defined as impaired glottic exposure. The sensitivity, specificity, positive and negative predictive value, relative risk, likelihood ratio and accuracy of the modified Mallampati test were calculated on 2x2 contingency tables. Of the total 1,518 patients enrolled, 48 had difficult intubation (3.2%). We failed to detect as many as 35.4% patients in whom glottis exposure during direct laryngoscopy was inadequate (sensitivity 0.646). Compared to the original article by Mallampati, we found lower specificity (0.824 vs. 0.995), lower positive predictive value (0.107 vs. 0.933), higher negative predictive value (0.986 vs. 0.928), lower likelihood ratio (3.68 vs. 91.0) and accuracy (0.819 vs. 0.929). When used as a single examination, the modified Mallampati test is of limited value in predicting difficult intubation.

The Six-Minute Walk Test for Adults with Intellectual Disability: A Study of Validity and Reliability

ERIC Educational Resources Information Center

Nasuti, Gabriella; Stuart-Hill, Lynneth; Temple, Viviene A.

2013-01-01

Background: The Six-Minute Walk Test (6MWT) has been used with clinical and healthy populations to assess functional capacity and cardiovascular fitness. The aim of this study was to determine the test-retest reliability of a modified-6MWT as well as concurrent validity of walk distance with peak oxygen uptake (VO[subscript 2] peak). Method:…

A Reactive Balance Rating Method that Correlates with Kinematics after Trip-Like Perturbations on a Treadmill and Fall Risk Among Residents of Older Adult Congregate Housing.

PubMed

Madigan, Michael L; Aviles, Jessica; Allin, Leigh J; Nussbaum, Maury A; Alexander, Neil B

2018-04-16

A growing number of studies are using modified treadmills to train reactive balance after trip-like perturbations that require multiple steps to recover balance. The goal of this study was thus to develop and validate a low-tech reactive balance rating method in the context of trip-like treadmill perturbations to facilitate the implementation of this training outside the research setting. Thirty-five residents of five senior congregate housing facilities participated in the study. Subjects completed a series of reactive balance tests on a modified treadmill from which the reactive balance rating was determined, along with a battery of standard clinical balance and mobility tests that predict fall risk. We investigated the strength of correlation between the reactive balance rating and reactive balance kinematics. We compared the strength of correlation between the reactive balance rating and clinical tests predictive of fall risk, with the strength of correlation between reactive balance kinematics and the same clinical tests. We also compared the reactive balance rating between subjects predicted to be at a high or low risk of falling. The reactive balance rating was correlated with reactive balance kinematics (Spearman's rho squared = .04 - .30), exhibited stronger correlations with clinical tests than most kinematic measures (Spearman's rho squared = .00 - .23), and was 42-60% lower among subjects predicted to be at a high risk for falling. The reactive balance rating method may provide a low-tech, valid measure of reactive balance kinematics, and an indicator of fall risk, after trip-like postural perturbations.

Cross-Cultural Adaptation of the Urticaria Control Test From German to Castilian Spanish.

PubMed

García-Díez, I; Curto-Barredo, L; Weller, K; Pujol, R M; Maurer, M; Giménez-Arnau, A M

2015-11-01

The clinical concept of urticaria embraces a heterogeneous group of conditions classified according to their clinical course as acute (lasting less than 6 weeks) or chronic (lasting 6 weeks or more). Chronic urticaria may be either spontaneous or induced. Few tools are available for monitoring the various clinical forms of this disease or for evaluating its impact on quality of life. The recently developed Urticaria Control Test to evaluate disease control is available in German, the original language, and American English. To culturally adapt the long and short versions of the Urticaria Control Test to Castilian Spanish to ensure equivalence between the translated items and those of the original version. To translate the Urticaria Control Test we followed the International Society for Pharmacoeconomics and Outcomes Research good practice guidelines, starting with forward translation and moving through back translation and cognitive debriefing steps. Three items were modified when the first Spanish version, translated from German, was discussed (cognitive debriefing). The revised translation was then translated back to German and sent to the Urticaria Control Test authors, who modified one item they considered had acquired a different focus through translation. A third Spanish version was then prepared and after minor proofreading changes was considered definitive. This study was the first step in making it possible to use the Urticaria Control Test questionnaire in Castilian Spanish. The next step will be to validate the translated questionnaire. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Cytologic diagnosis: expression of probability by clinical pathologists.

PubMed

Christopher, Mary M; Hotz, Christine S

2004-01-01

Clinical pathologists use descriptive terms or modifiers to express the probability or likelihood of a cytologic diagnosis. Words are imprecise in meaning, however, and may be used and interpreted differently by pathologists and clinicians. The goals of this study were to 1) assess the frequency of use of 18 modifiers, 2) determine the probability of a positive diagnosis implied by the modifiers, 3) identify preferred modifiers for different levels of probability, 4) ascertain the importance of factors that affect expression of diagnostic certainty, and 5) evaluate differences based on gender, employment, and experience. We surveyed 202 clinical pathologists who were board-certified by the American College of Veterinary Pathologists (Clinical Pathology). Surveys were distributed in October 2001 and returned by e-mail, fax, or surface mail over a 2-month period. Results were analyzed by parametric and nonparametric tests. Survey response rate was 47.5% (n = 96) and primarily included clinical pathologists at veterinary schools (n = 58) and diagnostic laboratories (n = 31). Eleven of 18 terms were used "often" or "sometimes" by >/= 50% of respondents. Broad variability was found in the probability assigned to each term, especially those with median values of 75 to 90%. Preferred modifiers for 7 numerical probabilities ranging from 0 to 100% included 68 unique terms; however, a set of 10 terms was used by >/= 50% of respondents. Cellularity and quality of the sample, experience of the pathologist, and implications of the diagnosis were the most important factors affecting the expression of probability. Because of wide discrepancy in the implied likelihood of a diagnosis using words, defined terminology and controlled vocabulary may be useful in improving communication and the quality of data in cytology reporting.

The Society for Translational Medicine: clinical practice guidelines for sperm DNA fragmentation testing in male infertility

PubMed Central

Cho, Chak-Lam; Majzoub, Ahmad; Esteves, Sandro C.

2017-01-01

Sperm DNA fragmentation (SDF) testing has been emerging as a valuable tool for male fertility evaluation. While the essential role of sperm DNA integrity in human reproduction was extensively studied, the clinical indication of SDF testing is less clear. This clinical practice guideline provides recommendations of clinical utility of the test supported by evidence. It is intended to serve as a reference for fertility specialists in identifying the circumstances in which SDF testing should be of greatest clinical value. SDF testing is recommended in patients with clinical varicocele and borderline to normal semen parameters as it can better select varicocelectomy candidates. Outcomes of natural pregnancy and assisted reproductive techniques (ART) can be predicted by result of SDF tests. High SDF is also linked with recurrent pregnancy loss (RPL) and failure of ART. Result of SDF testing may change the management decision by selecting the most appropriate ART with the highest success rate for infertile couples. Several studies have demonstrated the benefit in using testicular instead of ejaculated sperm in men with high SDF, oligozoospermia or recurrent in vitro fertilization (IVF) failure. Infertile men with modifiable lifestyle factor may benefit from SDF testing by reinforcing risk factor modification and monitoring patient’s progress to intervention. PMID:29082206

Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges

PubMed Central

Kim, Dana; Kim, Young-Sam; Shin, Dong Wun; Park, Chang-Shin

2016-01-01

No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era. PMID:27819412

Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges.

PubMed

Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee

2016-10-01

No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

A Case-Controlled Investigation of Tactile Reactivity in Young Children with and without Global Developmental Delay

ERIC Educational Resources Information Center

Barney, Chantel C.; Tervo, Raymond; Wilcox, George L.; Symons, Frank J.

2017-01-01

Assessing tactile function among children with intellectual, motor, and communication impairments remains a clinical challenge. A case control design was used to test whether children with global developmental delays (GDD; n = 20) would be more/less reactive to a modified quantitative sensory test (mQST) compared to controls (n = 20). Reactivity…

A Twofold Comparison between Dual Cure Resin Modified Cement and Glass Ionomer Cement for Orthodontic Band Cementation.

PubMed

Attar, Hanaa El; Elhiny, Omnia; Salem, Ghada; Abdelrahman, Ahmed; Attia, Mazen

2016-12-15

To test the solubility of dual cure resin modified resin cement in a food simulating solution and the shear bond strength compared to conventional Glass ionomer cement. The materials tested were self-adhesive dual cure resin modified cement and Glass Ionomer (GIC). Twenty Teflon moulds were divided into two groups of tens. The first group was injected and packed with the modified resin cement, the second group was packed with GIC. To test the solubility, each mould was weighed before and after being placed in an analytical reagent for 30 days. The solubility was measured as the difference between the initial and final drying mass. To measure the Shear bond strength, 20 freshly extracted wisdom teeth were equally divided into two groups and embedded in self-cure acrylic resin. Four mm sections of stainless steel bands were cemented to the exposed buccal surfaces of teeth under a constant load of 500 g. Shear bond strength was measured using a computer controlled materials testing machine and the load required to deband the samples was recorded in Newtons. GIC showed significantly higher mean weight loss and an insignificant lower Shear bond strength, compared to dual cure resin Cement. It was found that dual cure resin modified cement was less soluble than glass ionomer cement and of comparable bond strength rendering it more useful clinically for orthodontic band cementation.

Therapeutic management of botulism in dairy cattle.

PubMed

Pandian, S Jegaveera; Subramanian, M; Vijayakumar, G; Balasubramaniam, G A; Sukumar, K

2015-11-01

To report the successful recovery of few dairy cattle from botulism in response to a modified therapeutic strategy. Seventy four naturally-occurring clinical cases of bovine botulism encountered during the period of 2012-2014 which were confirmed by mouse lethality test became material for this study. Affected animals were made into three groups based on the treatment modifications made during the course of study. With the modified therapeutic regimen, 17 animals recovered after 7-10 days of treatment. Clinical recovery took 2-30 days. Animals which were not given intravenous fluid and calcium recovered uneventfully. Cattle which were already treated with intravenous fluids, calcium borogluconate, and antibiotics did not recover. They were either died or slaughtered for salvage. In cattle with botulism, administration of Vitamin AD3E and activated charcoal aid the clinical recovery. Besides, strictly avoiding anti-clostridial antibiotics, fluid therapy, and calcium therapy may facilitate the clinical recovery. Upon fluid administration, the pulmonary congestion existed in the ailing cattle might have worsened the anoxia. Administration of antibiotics like penicillin, aminoglycosides, and tetracyclines further worsen the neuronal paralysis by increasing the availability of botulinum neurotoxin. Cattle in early botulism have fair chances of recovery with the modified therapy.

Aminopenicillin-associated exanthem: lymphocyte transformation testing revisited.

PubMed

Trautmann, A; Seitz, C S; Stoevesandt, J; Kerstan, A

2014-12-01

The lymphocyte transformation test (LTT) has been promoted as in-vitro test for diagnosis of drug hypersensitivity. For determination of statistical LTT sensitivity, series of patients with clinically uniform reactions followed by complete drug hypersensitivity work-up are mandatory. Assessment of LTT specificity requires control patients who tolerated exposure to the drug studied. To prospectively determine the diagnostic value of the LTT in a clinically and diagnostically well-defined series of patients. Patients with exanthematous skin eruptions after ampicillin (AMP) intake were included in this study. After exclusion or confirmation of delayed-onset allergic AMP hypersensitivity by skin and provocation testing, two independent LTTs were performed: one standard LTT and a modified LTT with additional anti-CD3/anti-CD28 monoclonal antibody stimulation. By testing, delayed-onset allergic AMP hypersensitivity was diagnosed in 11 patients and definitely ruled out in 26. The standard LTT reached a diagnostic sensitivity of 54.5% while the modified LTT yielded 72.7%. However, the methodical test modification resulted in a decline of specificity from 92.3% (standard LTT) to 76.9%. In cases of AMP-associated exanthems, the diagnostic value of the LTT compared with routine allergy testing is limited. When evaluating such exanthems, provocation testing remains the gold standard. Delayed reading of intradermal skin tests remains most useful to avoid positive provocation reactions. © 2014 John Wiley & Sons Ltd.

Modified endoscopic medial maxillectomy for zygomatic implant salvage.

PubMed

Schwartz, Joseph S; Tajudeen, Bobby A; Adappa, Nithin D; Palmer, James N

2016-01-01

Odontogenic chronic rhinosinusitis (CRS) is an epidemiologically important disease process due, in part, to the increasingly commonplace use of dental restorative procedures such as zygomatic implantation. Traditional management of this clinical entity typically entails extraction of the infected hardware via an open or endoscopic approach. We describe a novel management strategy of odontogenic CRS following bilateral zygomatic implantation for oral rehabilitation that we surgically salvaged via a modified endoscopic medial maxillectomy. We describe the presentation and management of a case of metachronous development of bilateral CRS subsequent to zygomatic implantation. The patient's postoperative course was characterized by marked endoscopic, radiologic, and symptomatic improvement as measured by the 22-item Sino-Nasal Outcome Test. We describe a novel treatment strategy for the management of odontogenic sinusitis resulting from erroneous zygomatic implant placement. Modified endoscopic medial maxillectomy in this clinical context facilitates mucosal normalization of the affected sinus, while permitting preservation of oral function through salvage of the displaced implant.

Comprehensive Hand Repetitive Intensive Strengthening Training (CHRIST)-induced morphological changes in muscle size and associated motor improvement in a child with cerebral palsy: an experimenter-blind study.

PubMed

Lee, Dong Ryul; You, Joshua H; Lee, Nam Gi; Oh, Jin Hwan; Cha, You Jin

2009-01-01

This case study was conducted to determine Comprehensive Hand Repetitive Intensive Strengthening Training (CHRIST)-induced morphological changes in the commonly affected extensor carpi radialis (ECR) and triceps brachii (TRI) muscle and associated muscle strength and motor performance in a child with hemiparetic cerebral palsy (CP) using standardized clinical tests and ultrasound imaging. A single case study with pre-/post-test. A 4.9-year-old female, diagnosed with hemiparetic CP. The child received a 5-week course of CHRIST course, comprising of 60-minute periods a day, five times a week. A real-time ultrasound imaging was performed to determine the CHRIST-induced changes in cross-sectional area (CSA) of the ECR and TRI. Clinical tests including the modified Wolf Motor function test (WMFT), the modified Jebsen-taylor hand function test (Jebsen hand) and the modified Pediatric Motor Activity Log (PMAL) questionnaire were used to compare the intervention-related changes in motor performance in upper extremity. Ultrasound imaging data showed that the CSAs of both ECR and TRI muscles of the affected upper limb at relaxation and contraction states were enhanced and these therapy-induced morphological changes were associated with enhanced muscle strength and gross motor performance in reaching and grasping skills. Our results suggest that the CHRIST is effective in treating muscle weakness and motor function in a child with hemiparetic CP. This is the first evidence in literature that might shed light on the therapeutic efficacy of our novel intervention on muscle size, associated muscle strength and motor improvement.

Effect of Surgical Curve Correction on Exercise Tolerance and Physical Capacities in Patients of Severe Spinal Deformity.

PubMed

Patil, Prateek C; Rathod, Ashok K; Borde, Mandar; Singh, Vishwajeet; Singh, Hemant U

2016-12-01

Traditionally, surgical intervention for patients with a spinal deformity has been considered for cosmetic benefits, but surgical intervention can alter the lung physiology or volumes and in turn leads to increase in physical capacity and exercise tolerance. Therefore, we conducted this to determine whether a surgical correction would restore the lung physiology, physical capacity and exercise tolerance in patients with kyphoscoliosis. To evaluate the usage of six-minute walk test scores and modified Borg scores as tools/measures for exercise tolerance in patients with spinal deformity and to study the effects of surgical correction of spinal deformity on exercise tolerance with above parameters as the measures. Thirty patients with spinal deformity, who had undergone surgery for deformity correction, were evaluated. All patients were investigated pre-operatively with x-rays of the spine (anteroposterior and lateral views). Clinical tests like breath holding time (after full inspiration) in number of seconds, modified Borg scores, six-minute walk test scores (heart rate, respiratory rate, maximum distance walked); were recorded as measures of exercise tolerance. The patients were followed up on the first, third, sixth and twelfth month post-operatively and tested clinically for breath holding time, modified Borg scores, six-minute walk test scores (heart rate, respiratory rate, maximum distance walked) and x-rays of the spine (anteroposterior and lateral views). In our study, breath holding time (p-value = 0.001) and modified Borg scores (p-value = 0.012) showed a significant improvement at 12 months post-operatively. We noted similar findings with heart rate, respiratory rate and maximum distance walked after a six-minute walk test. Improvements were noted in all the parameters, especially in the group of patients with greater than 60 degrees of cobb angle. However, the differences between the two groups (pre-operative cobb angle less than 60 degrees and pre-operative cobb angle more than 60 degrees) were not significant. The results were analysed and tested for significance using Student's t-test (paired and unpaired as appropriate) and Wilcoxon signed rank test. Surgical correction in cases of spinal deformity improves the cosmetic appearance and balance in the patients. Favourable results of surgical intervention were found in exercise tolerance with improvements in modified Borg scores, six-minute walk test results and breath holding time. The above parameters appear to be good tools for the assessment of physical capacity and exercise tolerance in patients with spinal deformity.

The effect of subcrestal placement of the polished surface of ITI implants on marginal soft and hard tissues.

PubMed

Hämmerle, C H; Brägger, U; Bürgin, W; Lang, N P

1996-06-01

In order to achieve esthetically more satisfying results, it has been proposed to place ITI implants with their border between the rough and smooth surfaces below the level of the alveolar crest, thereby obtaining a submucosally located implant shoulder following healing. The aim of the present experimental study was to clinically and radiographically evaluate the tissue response to the placement of one-stage transmucosal implants with the border between the rough and the smooth surfaces sunk by 1 mm into a subcrestal location. 11 patients underwent comprehensive dental care including the placement of 2 implants of the ITI Dental Implant System in the same quadrant (test and control). Randomly assigned control implants were placed according to the manufacturer's instructions, i.e. the border between the rough titanium plasma-sprayed and the smooth polished surfaces precisely at the alveolar crest. At the test implant the apical border of the polished surface was placed approximately 1 mm below the alveolar crest. Probing bone levels were assessed at implant placement (baseline), 4 and 12 months later. Modified plaque and modified gingival indices were recorded at 1, 2, 3, 4 and 12 months. Clinical probing depth and "attachment" levels were measured at 4 and 12 months. All parameters were assessed at 6 sites around each implant. The mean for each implant was calculated and used for analysis. The Wilcoxon matched pairs signed rank test and the Student t-test were applied to detect differences over time and between the test and control implants. At baseline, a mean difference in probing bone level of -0.86 mm (SD 0.43 mm, p < 0.05) was found between test and control implants with the test implants being placed more deeply. Both test and control implants lost a significant amount of clinical bone height during the first 4 months (test 1.16 mm, p < 0.05; control 0.58 mm, p < 0.05). However, only the test implants significantly lost clinical bone height from 4-12 months (test 1.04 mm, p < 0.05; control 0.45 mm, p = 0.08). Overall, the test implants lost 2.26 mm and the control implants 1.02 mm of bone height during the first year of service. On the average, the test implants demonstrated a bone level of 0.38 mm lower than the controls at 12 months. Except for the modified gingival index at 4 months (mean difference 0.21, SD 0.19, p < 0.05), no clinical parameters yielded significant differences between test and control implants at any time. It is concluded that in addition to the crestal bone resorption occurring at implants placed under standard conditions, the bone adjacent to the polished surface of more deeply placed ITI implants is also lost over time. From a biological point of view, the placement of the border between the rough and the smooth surfaces into a subcrestal location should not be recommended.

Current and experimental treatments of Parkinson disease: A guide for neuroscientists.

PubMed

Oertel, Wolfgang; Schulz, Jörg B

2016-10-01

Over a period of more than 50 years, the symptomatic treatment of the motor symptoms of Parkinson disease (PD) has been optimized using pharmacotherapy, deep brain stimulation, and physiotherapy. The arsenal of pharmacotherapies includes L-Dopa, several dopamine agonists, inhibitors of monoamine oxidase (MAO)-B and catechol-o-methyltransferase (COMT), and amantadine. In the later course of the disease, motor complications occur, at which stage different oral formulations of L-Dopa or dopamine agonists with long half-life, a transdermal application or parenteral pumps for continuous drug supply can be subscribed. Alternatively, the patient is offered deep brain stimulation of the subthalamic nucleus (STN) or the internal part of the globus pallidus (GPi). For a more efficacious treatment of motor complications, new formulations of L-Dopa, dopamine agonists, and amantadine as well as new MAO-B and COMT inhibitors are currently tested in clinical trials, and some of them already yielding positive results in phase 3 trials. In addition, non-dopaminergic agents have been tested in the early clinical phase for the treatment of motor fluctuations and dyskinesia, including adenosine A2A antagonists (istradefylline, preladenant, and tozadenant) and modulators of the metabolic glutamate receptor 5 (mGluR5 - mavoglurant) and serotonin (eltoprazine) receptors. Recent clinical trials testing coenzyme Q10, the dopamine agonist pramipexole, creatine monohydrate, pioglitazone, or AAV-mediated gene therapy aimed at increasing expression of neurturin, did not prove efficacious. Treatment with nicotine, caffeine, inosine (a precursor of urate), and isradipine (a dihydropyridine calcium channel blocker), as well as active and passive immunization against α-synuclein and inhibitors or modulators of α-synuclein-aggregation are currently studied in clinical trials. However, to date, no disease-modifying treatment is available. We here review the current status of treatment options for motor and non-motor symptoms, and discuss current investigative strategies for disease modification. This review provides basic insights, mainly addressing basic scientists and non-specialists. It stresses the need to intensify therapeutic PD research and points out reasons why the translation of basic research to disease-modifying therapies has been unsuccessful so far. The symptomatic treatment of the motor symptoms of Parkinson disease (PD) has been constantly optimized using pharmacotherapy (L-Dopa, several dopamine agonists, inhibitors of monoamine oxidase (MAO)-B and catechol-o-methyltransferase (COMT), and amantadine), deep brain stimulation, and physiotherapy. For a more efficacious treatment of motor complications, new formulations of L-Dopa, dopamine agonists, and amantadine as well as new MAO-B and COMT inhibitors are currently tested in clinical trials. Non-dopaminergic agents have been tested in the early clinical phase for the treatment of motor fluctuations and dyskinesia. Recent clinical trials testing coenzyme Q10, the dopamine agonist pramipexole, creatine monohydrate, pioglitazone, or AAV-mediated gene therapy aimed at increasing expression of neurturin, did not prove efficacious. Treatment with nicotine, caffeine, and isradipine - a dihydropyridine calcium channel blocker - as well as active and passive immunization against α-synuclein and inhibitors of α-synuclein-aggregation are currently studied in clinical trials. However, to date, no disease-modifying treatment is available for PD. We here review the current status of treatment options and investigative strategies for both motor and non-motor symptoms. This review stresses the need to intensify therapeutic PD research and points out reasons why the translation of basic research to disease-modifying therapies has been unsuccessful so far. This article is part of a special issue on Parkinson disease. © 2016 International Society for Neurochemistry.

Characterization of the modified Hodge test-positive isolates of Enterobacteriaceae in Taiwan.

PubMed

Hung, Kuei-Hsiang; Yan, Jing-Jou; Lu, Jang-Jih; Chen, Hung-Mo; Wu, Jiunn-Jong

2013-02-01

The modified Hodge test is a phenotypic test to detect KPC-type carbapenemase producers among Enterobacteriaceae, as recommended by the Clinical Laboratory Standards Institute. However, false positive results were reported. In this study, we aimed to large-scale investigate the characterization of the modified Hodge test-positive isolates of Enterobacteriaceae collected between 2006 and 2010 in Taiwan. Fifty-six isolates, including 24 Enterobacter cloacae, 17 Escherichia coli, 10 Klebsiella pneumoniae, and 5 Citrobacter freundii, tested positive with the modified Hodge test. The in vitro activities of 10 antimicrobial agents were determined by the agar dilution method. Boronic acid combined-disk test was used to further confirm the KPC producers. Phenotype of ESBL, AmpC, class B carbapenemases, and profile of outer membrane proteins were investigated by the confirmatory test, boronic acid disk method, 2-mercaptopropionic acid double-disk method, and urea/sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), respectively. β-lactamase genes were examined by PCR and sequencing. These isolates were resistant to ceftazidime (100%), aztreonam (82.1%), ertapenem (64.3%), gentamicin (53.6%), ciprofloxacin (50%), levofloxacin (48.2%), cefepime (19.6%), imipenem (16.1%), meropenem (12.5%), and amikacin (8.9%). Phenotypic testing among isolates revealed the production of ESBLs, metallo-β-lactamases (MBLs), and AmpC in 10 (17.9%), 16 (28.6%), and 12 (44.4%) isolates, respectively. Carbapenemase and non-carbapenemase β-lactamase genes bla(TEM-1), bla(SHV), bla(CTX-M), bla(IMP-8), bla(CMY-2), and bla(DHA-1) were found in 32 (57.1%), 19 (33.9%), 4 (7.1%), 16 (28.6%), 14 (25%), and 5 (8.9%) of the strains, respectively. No class A and D carbapenemase genes were detected. Outer membrane protein profile showed obviously decreased expression in 49 (87.5%) isolates with positive result of modified Hodge test. Our data show that ESBLs, AmpC, and imipenemase-8 (IMP-8) carbapenemase coupled with decreased expression of outer membrane protein were prevalent in Enterobacteriaceae isolates testing positive for the modified Hodge test in Taiwan. Copyright © 2012. Published by Elsevier B.V.

Are medical students being taught anatomy in a way that best prepares them to be a physician?

PubMed

Meral Savran, Mona; Tranum-Jensen, Jørgen; Frost Clementsen, Paul; Hastrup Svendsen, Jesper; Holst Pedersen, Jesper; Seier Poulsen, Steen; Arendrup, Henrik; Konge, Lars

2015-07-01

Reasoning in a clinical context is an attribute of medical expertise. Clinical reasoning in medical school can be encouraged by teaching basic science with a clinical emphasis. The aim of this study was to investigate whether anatomy is being taught in a way that facilitates the development of clinical reasoning. Two multiple-choice tests on thoracic anatomy were developed using a modified Delphi approach with groups of four clinical consultants and four teachers, respectively, expressing their opinions about knowledge relevant to thoracic anatomy. Validity was assessed by administering the tests to clinical consultants, anatomy teachers, and pre-course medical students. Post-course medical students took both tests to explore the focus of the course, i.e., whether it facilitated clinical reasoning. The pre-course students scored significantly lower than the teachers and post-course students on both tests and lower than the consultants on the consultants' test (P < 0.001 for all comparisons). The teachers significantly outperformed the consultants (P = 0.03 on the consultants' test, P < 0.001 on the teachers' test) and the medical students (P < 0.001 on both tests). The post-course students scored significantly lower on the consultants' test (P = 0.001) and significantly higher on the teachers' test (P = 0.02) than the consultants. This study demonstrates poor performances by medical students on a test containing clinically relevant anatomy, implying that the teaching they have received has not encouraged clinical reasoning. © 2015 Wiley Periodicals, Inc.

An immunohistochemical and fluorescence in situ hybridization-based comparison between the Oracle HER2 Bond Immunohistochemical System, Dako HercepTest, and Vysis PathVysion HER2 FISH using both commercially validated and modified ASCO/CAP and United Kingdom HER2 IHC scoring guidelines.

PubMed

O'Grady, Anthony; Allen, David; Happerfield, Lisa; Johnson, Nicola; Provenzano, Elena; Pinder, Sarah E; Tee, Lilian; Gu, Mai; Kay, Elaine W

2010-12-01

Immunohistochemistry (IHC) is used as the frontline assay to determine HER2 status in invasive breast cancer patients. The aim of the study was to compare the performance of the Leica Oracle HER2 Bond IHC System (Oracle) with the current most readily accepted Dako HercepTest (HercepTest), using both commercially validated and modified ASCO/CAP and UK HER2 IHC scoring guidelines. A total of 445 breast cancer samples from 3 international clinical HER2 referral centers were stained with the 2 test systems and scored in a blinded fashion by experienced pathologists. The overall agreement between the 2 tests in a 3×3 (negative, equivocal and positive) analysis shows a concordance of 86.7% and 86.3%, respectively when analyzed using commercially validated and modified ASCO/CAP and UK HER2 IHC scoring guidelines. There is a good concordance between the Oracle and the HercepTest. The advantages of a complete fully automated test such as the Oracle include standardization of key analytical factors and improved turn around time. The implementation of the modified ASCO/CAP and UK HER2 IHC scoring guidelines has minimal effect on either assay interpretation, showing that Oracle can be used as a methodology for accurately determining HER2 IHC status in formalin fixed, paraffin-embedded breast cancer tissue.

Computer simulation to aid the risk assessment of wheelchair and special seating systems used in transport.

PubMed

Rogers, P D; Gibson, C; Wilcox, S J; Chong, A

2009-01-01

The crashworthiness of occupied proprietary wheelchairs, which are transported in motor vehicles, is currently assessed by physical crash testing in accordance with ISO 7176-19. If such wheelchairs are modified to meet the needs of the occupant, e.g. the addition of special seating, environmental control systems or life support equipment, then those making the modifications take on the manufacturer's responsibilities, one of these being the assessment of the modified wheelchair's ability to withstand vehicle crash forces. Destructively testing bespoke wheelchair designs is not practical so, currently, the transport-related risk is assessed using best engineering judgement. To improve this process virtual crash testing of the wheelchair and occupant was used. A modified crash criteria from ISO 7176-19 is proposed to enable assessment of the wheelchair's crashworthiness and provide the clinical engineer with an informed judgement of how both wheelchair alone and occupant and wheelchair together will behave in a crash.

Optimization and evaluation of Flexicult® Vet for detection, identification and antimicrobial susceptibility testing of bacterial uropathogens in small animal veterinary practice.

PubMed

Guardabassi, Luca; Hedberg, Sandra; Jessen, Lisbeth Rem; Damborg, Peter

2015-10-26

Urinary tract infection (UTI) is a common reason for antimicrobial prescription in dogs and cats. The objective of this study was to optimize and evaluate a culture-based point-of-care test for detection, identification and antimicrobial susceptibility testing of bacterial uro-pathogens in veterinary practice. Seventy-two urine samples from dogs and cats with suspected UTI presenting to seven veterinary facilities were used by clinical staff and an investigator to estimate sensitivity and specificity of Flexicult Vet A compared to laboratory reference standards for culture and susceptibility testing. Subsequently, the test was modified by inclusion of an oxacillin-containing compartment for detection of methicillin-resistant staphylococci. The performance of the modified product (Flexicult Vet B) for susceptibility testing was evaluated in vitro using a collection of 110 clinical isolates. Bacteriuria was reported by the laboratory in 25 (35 %) samples from the field study. The sensitivity and specificity of Flexicult Vet A for detection of bacteriuria were 83 and 100 %, respectively. Bacterial species were correctly identified in 53 and 100 % of the positive samples by clinical staff and the investigator, respectively. The susceptibility results were interpreted correctly by clinical staff for 70 % of the 94 drug-strain combinations. Higher percentages of correct interpretation were observed when the results were interpreted by the investigator in both the field (76 %) and the in vitro study (94 %). The most frequent errors were false resistance to β-lactams (ampicillin, amoxicillin-clavulanate and cephalotin) in Escherichia coli for Flexicult Vet A, and false amoxicillin-clavulanate resistance in E. coli and false ampicillin susceptibility in Staphylococcus pseudintermedius for Flexicult Vet B. The latter error can be prevented by categorizing staphylococcal strains growing in the oxacillin compartment as resistant to all β-lactams. Despite the shortcomings regarding species identification by clinical staff and β-lactam susceptibility testing of E. coli, Flexicult Vet B (commercial name Flexicult(®) Vet) is a time- and cost-effective point-of-care test to guide antimicrobial choice and facilitate implementation of antimicrobial use guidelines for treatment of UTIs in small animals, provided that clinical staff is adequately trained to interpret the results and that clinics meet minimum standards to operate in-house culture.

Potential reliability and validity of a modified version of the Unified Parkinson’s Disease Rating Scale that could be administered remotely

PubMed Central

Abdolahi, Amir; Scoglio, Nicholas; Killoran, Annie; Dorsey, Ray; Biglan, Kevin M.

2013-01-01

Background By permitting remote assessments of patients and research participants, telemedicine has the potential to reshape clinical care and clinical trials for Parkinson disease. While the majority of the motor Unified Parkinson’s Disease Rating Scale (UPDRS) items can be conducted visually, rigidity and retropulsion pull testing require hands-on assessment by the rater and are less feasible to perform remotely in patients' homes. Methods In a secondary data analysis of the Comparison of the Agonist pramipexole vs. Levodopa on Motor complications in Parkinson’s Disease (CALM-PD) study, a randomized clinical trial, we assessed the cross-sectional (baseline and 2 years) and longitudinal (change from baseline to 2 years) reliability of a modified motor UPDRS (removing rigidity and retropulsion items) compared to the standard motor UPDRS (all items) using intraclass correlation coefficients (ICC), stratified by treatment group. Internal consistency of the modified UPDRS (mUPDRS) was measured using Cronbach’s alpha, and concurrent validity was assessed using Pearson’s correlation coefficient (r) between the standard motor UPDRS and mUPDRS. Results The mUPDRS versus standard motor UPDRS is cross-sectionally (ICC ≥ 0.92) and longitudinally (ICC ≥ 0.92) reliable for both treatment groups. High internal consistencies were also observed (α ≥ 0.96). The mUPDRS had high concurrent validity with the standard UPDRS at both time points and longitudinally (r ≥ 0.93, p < 0.0001). Conclusions A modified version of the motor UPDRS without rigidity and retropulsion pull testing is reliable and valid and may lay the foundation for its use in remote assessments of patients and research participants. PMID:23102808

Potential reliability and validity of a modified version of the Unified Parkinson's Disease Rating Scale that could be administered remotely.

PubMed

Abdolahi, Amir; Scoglio, Nicholas; Killoran, Annie; Dorsey, E Ray; Biglan, Kevin M

2013-02-01

By permitting remote assessments of patients and research participants, telemedicine has the potential to reshape clinical care and clinical trials for Parkinson disease. While the majority of the motor Unified Parkinson's Disease Rating Scale (UPDRS) items can be conducted visually, rigidity and retropulsion pull testing require hands-on assessment by the rater and are less feasible to perform remotely in patients' homes. In a secondary data analysis of the Comparison of the Agonist pramipexole vs. Levodopa on Motor complications in Parkinson's Disease (CALM-PD) study, a randomized clinical trial, we assessed the cross-sectional (baseline and 2 years) and longitudinal (change from baseline to 2 years) reliability of a modified motor UPDRS (removing rigidity and retropulsion items) compared to the standard motor UPDRS (all items) using intraclass correlation coefficients (ICC), stratified by treatment group. Internal consistency of the modified UPDRS (mUPDRS) was measured using Cronbach's alpha, and concurrent validity was assessed using Pearson's correlation coefficient (r) between the standard motor UPDRS and mUPDRS. The mUPDRS versus standard motor UPDRS is cross-sectionally (ICC ≥ 0.92) and longitudinally (ICC ≥ 0.92) reliable for both treatment groups. High internal consistencies were also observed (α ≥ 0.96). The mUPDRS had high concurrent validity with the standard UPDRS at both time points and longitudinally (r ≥ 0.93, p < 0.0001). A modified version of the motor UPDRS without rigidity and retropulsion pull testing is reliable and valid and may lay the foundation for its use in remote assessments of patients and research participants. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of Genetics on the Clinical Management of Channelopathies

PubMed Central

Schwartz, Peter J.; Ackerman, Michael J.; George, Alfred L.; Wilde, Arthur A.M.

2013-01-01

There are few areas in cardiology where the impact of genetics and of genetic testing on clinical management has been as great as in cardiac channelopathies, arrhythmic disorders of genetic origin related to the ionic control of the cardiac action potential. Among the growing number of diseases identified as channelopathies, three are sufficiently prevalent to represent significant clinical and societal problems and to warrant adequate understanding by practicing cardiologists: long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome. This review will focus selectively on the impact of genetic discoveries on clinical management of these three diseases. For each disorder, we will discuss to what extent genetic knowledge and clinical genetic test results modify the way cardiologists should approach and manage affected patients. We will also address the optimal use of genetic testing including its potential limitations and the potential medico-legal implications when such testing is not performed. We will highlight how important can be to understand the ways by which genotype can impact clinical manifestations, risk stratification, and responses to the therapy. We will also illustrate the close bridge between molecular biology and clinical medicine, and will emphasize that consideration of the genetic basis for these hereditable arrhythmia syndromes, as well as the proper use and interpretation of clinical genetic testing, should remain the standard-of-care. PMID:23684683

Planning Future Clinical Trials for Machado-Joseph Disease.

PubMed

Saute, Jonas Alex Morales; Jardim, Laura Bannach

2018-01-01

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is an autosomal dominant multiple neurological systems degenerative disorder caused by a CAG repeat expansion at ATXN3 gene. Only a few treatments were evaluated in randomized clinical trials (RCT) in SCA3/MJD patients, with a lack of evidence for both disease-modifying and symptomatic therapies. The present chapter discuss in detail major methodological issues for planning future RCT for SCA3/MJD. There are several potential therapies for SCA3/MJD with encouraging preclinical results. Route of treatment, dosage titration and potential therapy biomarkers might differ among candidate drugs; however, the core study design and protocol will be mostly the same. RCT against placebo group is the best study design to test a disease-modifying therapy; the same cannot be stated for some symptomatic treatments. Main outcomes for future RCT are clinical scales: the Scale for the Assessment and Rating of ataxia (SARA) is currently the instrument of choice to prove efficacy of disease-modifying or symptomatic treatments against ataxia, the most important disease feature. Ataxia quantitative scales or its composite scores can be used as primary outcomes to provide preliminary evidence of efficacy in phase 2 RCT, due to a greater sensitivity to change. Details regarding eligibility criteria, randomization, sample size estimation, duration and type of analysis for both disease modifying and symptomatic treatment trials, were also discussed. Finally, a section anticipates the methodological issues for testing novel drugs when an effective treatment is already available. We conclude emphasizing four points, the first being the need of RCT for a number of different aims in the care of SCA3/MJD. Due to large sample sizes needed to warrant power, RCT for disease-modifying therapies should be multicenter enterprises. There is an urge need for surrogate markers validated for several drug classes. Finally, engagement of at risk or presymptomatic individuals in future trials will enable major advances on treatment research for SCA3/MJD.

Replication of a Modified Factor Structure for the Eating Disorder Examination-Questionnaire: Extension to Clinical Eating Disorder and Non-clinical Samples in Portugal.

PubMed

Machado, Paulo P P; Grilo, Carlos M; Crosby, Ross D

2018-01-01

Psychometric investigations of the Eating Disorder Examination-Questionnaire (EDE-Q) have generally not supported the original scale structure. The present study tested an alternative brief factor structure in two large Portuguese samples: (1) a non-clinical sample of N = 4117 female students and (2) a treatment-seeking sample of N = 609 patients diagnosed with eating disorders. Confirmatory factor analysis revealed a poor fit for the original EDE-Q structure in both the non-clinical and the clinical samples but revealed a good fit for the alternative 7-item 3-factor structure (dietary restraint, shape/weight overvaluation and body dissatisfaction). Factor loadings were invariant across samples and across the different specific eating disorder diagnoses in the clinical sample. These confirmatory factor analysis findings, which replicate findings from studies with diverse predominately overweight/obese samples, supported a modified 7-item, 3-factor structure for the EDE-Q. The reliable findings across different non-clinical and clinical eating disorder groups provide confidence regarding the potential utility of this brief version. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

A retrospective clinical study of cervical restorations: longevity and failure-prognostic variables.

PubMed

Namgung, C; Rho, Y J; Jin, B H; Lim, B S; Cho, B H

2013-01-01

The aim of this retrospective clinical study was to compare the longevity of cervical restorations between resin composite (RC) and glass ionomer (GI) and to investigate variables predictive of their outcome. The clinical performance of the two restorative materials in function was compared using the ratings of the modified United States Public Health Service (USPHS) criteria. A total of 479 cervical restorations were included in the study. Ninety-one already-replaced restorations were reviewed from dental records. The other 388 restorations still in function were evaluated according to the modified USPHS criteria by two investigators. Longevity and prognostic variables were analyzed with the Kaplan-Meier survival analysis and multivariate Cox proportional hazard model. The clinical performances of the two materials were evaluated according to the ratings of the USPHS criteria and compared using the Pearson chi-square test and Fisher exact test. The longevity was not significantly different between RC and GI (median survival time, 10.4 ± 0.7 and 11.5 ± 1.1 years, respectively). The main reasons for failure were loss of retention (82.2%) and secondary caries (17.8%). The longevity of cervical restoration was significantly influenced by tooth group and operator group (Wald test, p<0.05), while material, gender, presence or absence of systemic diseases, arch, and reason for treatment did not affect the longevity. Contrary to the longevity, the clinical performance of RC was superior to GI in the criteria of retention, marginal discoloration, and marginal adaptation, but similar in secondary caries, wear, and postoperative sensitivity.

A Twofold Comparison between Dual Cure Resin Modified Cement and Glass Ionomer Cement for Orthodontic Band Cementation

PubMed Central

Attar, Hanaa El; Elhiny, Omnia; Salem, Ghada; Abdelrahman, Ahmed; Attia, Mazen

2016-01-01

AIM: To test the solubility of dual cure resin modified resin cement in a food simulating solution and the shear bond strength compared to conventional Glass ionomer cement. MATERIALS AND METHOD: The materials tested were self-adhesive dual cure resin modified cement and Glass Ionomer (GIC). Twenty Teflon moulds were divided into two groups of tens. The first group was injected and packed with the modified resin cement, the second group was packed with GIC. To test the solubility, each mould was weighed before and after being placed in an analytical reagent for 30 days. The solubility was measured as the difference between the initial and final drying mass. To measure the Shear bond strength, 20 freshly extracted wisdom teeth were equally divided into two groups and embedded in self-cure acrylic resin. Four mm sections of stainless steel bands were cemented to the exposed buccal surfaces of teeth under a constant load of 500 g. Shear bond strength was measured using a computer controlled materials testing machine and the load required to deband the samples was recorded in Newtons. RESULTS: GIC showed significantly higher mean weight loss and an insignificant lower Shear bond strength, compared to dual cure resin Cement. CONCLUSION: It was found that dual cure resin modified cement was less soluble than glass ionomer cement and of comparable bond strength rendering it more useful clinically for orthodontic band cementation. PMID:28028417

Triton Hodge Test: Improved Protocol for Modified Hodge Test for Enhanced Detection of NDM and Other Carbapenemase Producers

PubMed Central

Pasteran, Fernando; Gonzalez, Lisandro J.; Albornoz, Ezequiel; Bahr, Guillermo; Vila, Alejandro J.

2015-01-01

Accurate detection of carbapenemase-producing Gram-negative bacilli is of utmost importance for the control of nosocomial spread and the initiation of appropriate antimicrobial therapy. The modified Hodge test (MHT), a carbapenem inactivation assay, has shown poor sensitivity in detecting the worldwide spread of New Delhi metallo-β-lactamase (NDM). Recent studies demonstrated that NDM is a lipoprotein anchored to the outer membrane in Gram-negative bacteria, unlike all other known carbapenemases. Here we report that membrane anchoring of β-lactamases precludes detection of carbapenemase activity by the MHT. We also show that this limitation can be overcome by the addition of Triton X-100 during the test, which allows detection of NDM. We propose an improved version of the assay, called the Triton Hodge test (THT), which allows detection of membrane-bound carbapenemases with the addition of this nonionic surfactant. This test was challenged with a panel of 185 clinical isolates (145 carrying known carbapenemase-encoding genes and 40 carbapenemase nonproducers). The THT displayed test sensitivity of >90% against NDM-producing clinical isolates, while improving performance against other carbapenemases. Ertapenem provided the highest sensitivity (97 to 100%, depending on the type of carbapenemase), followed by meropenem (92.5 to 100%). Test specificity was not affected by the addition of Triton (87.5% and 92.5% with ertapenem and meropenem, respectively). This simple inexpensive test confers a large improvement to the sensitivity of the MHT for the detection of NDM and other carbapenemases. PMID:26719442

ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging. A report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group.

PubMed

2006-10-01

Under the auspices of the American College of Cardiology Foundation (ACCF) together with key specialty and subspecialty societies, appropriateness reviews were conducted for 2 relatively new clinical cardiac imaging modalities, cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) imaging. The reviews assessed the risks and benefits of the imaging tests for several indications or clinical scenarios and scored them based on a scale of 1 to 9, where the upper range (7 to 9) implies that the test is generally acceptable and is a reasonable approach, and the lower range (1 to 3) implies that the test is generally not acceptable and is not a reasonable approach. The mid-range (4 to 6) indicates an uncertain clinical scenario. The indications for these reviews were drawn from common applications or anticipated uses, as few clinical practice guidelines currently exist for these techniques. These indications were reviewed by an independent group of clinicians and modified by the Working Group, and then panelists rated the indications based on the ACCF Methodology for Evaluating the Appropriateness of Cardiovascular Imaging, which blends scientific evidence and practice experience. A modified Delphi technique was used to obtain first and second round ratings of clinical indications after the panelists were provided with a set of literature reviews, evidence tables, and seminal references. The final ratings were evenly distributed among the 3 categories of appropriateness for both CCT and CMR. Use of tests for structure and function and for diagnosis in symptomatic, intermediate coronary artery disease (CAD) risk patients was deemed appropriate, while repeat testing and general screening uses were viewed less favorably. It is anticipated that these results will have a significant impact on physician decision making and performance, reimbursement policy, and future research directions.

Therapeutic management of botulism in dairy cattle

PubMed Central

Pandian, S. Jegaveera; Subramanian, M.; Vijayakumar, G.; Balasubramaniam, G. A.; Sukumar, K.

2015-01-01

Aim: To report the successful recovery of few dairy cattle from botulism in response to a modified therapeutic strategy. Materials and Methods: Seventy four naturally-occurring clinical cases of bovine botulism encountered during the period of 2012-2014 which were confirmed by mouse lethality test became material for this study. Affected animals were made into three groups based on the treatment modifications made during the course of study. Results and Discussion: With the modified therapeutic regimen, 17 animals recovered after 7-10 days of treatment. Clinical recovery took 2-30 days. Animals which were not given intravenous fluid and calcium recovered uneventfully. Cattle which were already treated with intravenous fluids, calcium borogluconate, and antibiotics did not recover. They were either died or slaughtered for salvage. Conclusion: In cattle with botulism, administration of Vitamin AD3E and activated charcoal aid the clinical recovery. Besides, strictly avoiding anti-clostridial antibiotics, fluid therapy, and calcium therapy may facilitate the clinical recovery. Upon fluid administration, the pulmonary congestion existed in the ailing cattle might have worsened the anoxia. Administration of antibiotics like penicillin, aminoglycosides, and tetracyclines further worsen the neuronal paralysis by increasing the availability of botulinum neurotoxin. Cattle in early botulism have fair chances of recovery with the modified therapy. PMID:27047034

Assessment of a Learning Strategy among Spine Surgeons.

PubMed

Gotfryd, Alberto Ofenhejm; Corredor, Jose Alfredo; Teixeira, William Jacobsen; Martins, Delio Eulálio; Milano, Jeronimo; Iutaka, Alexandre Sadao

2017-02-01

Pilot test, observational study. To evaluate objectively the knowledge transfer provided by theoretical and practical activities during AOSpine courses for spine surgeons. During two AOSpine principles courses, 62 participants underwent precourse assessment, which consisted of questions about their professional experience, preferences regarding adolescent idiopathic scoliosis (AIS) classification, and classifying the curves by means of the Lenke classification of two AIS clinical cases. Two learning strategies were used during the course. A postcourse questionnaire was applied to reclassify the same deformity cases. Differences in the correct answers of clinical cases between pre- and postcourse were analyzed, revealing the number of participants whose accuracy in classification improved after the course. Analysis showed a decrease in the number of participants with wrong answers in both cases after the course. In the first case, statistically significant differences were observed in both curve pattern (83.3%, p   =  0.005) and lumbar spine modifier (46.6%, p   =  0.049). No statistically significant improvement was seen in the sagittal thoracic modifier (33.3%, p   =  0.309). In the second case, statistical improvement was obtained in curve pattern (27.4%, p   =  0.018). No statistically significant improvement was seen regarding lumbar spine modifier (9.8%, p   =  0.121) and sagittal thoracic modifier (12.9%, p   =  0.081). This pilot test showed objectively that learning strategies used during AOSpine courses improved the participants' knowledge. Teaching strategies must be continually improved to ensure an optimal level of knowledge transfer.

Assessment of a Learning Strategy among Spine Surgeons

PubMed Central

Gotfryd, Alberto Ofenhejm; Teixeira, William Jacobsen; Martins, Delio Eulálio; Milano, Jeronimo; Iutaka, Alexandre Sadao

2017-01-01

Study Design Pilot test, observational study. Objective To evaluate objectively the knowledge transfer provided by theoretical and practical activities during AOSpine courses for spine surgeons. Methods During two AOSpine principles courses, 62 participants underwent precourse assessment, which consisted of questions about their professional experience, preferences regarding adolescent idiopathic scoliosis (AIS) classification, and classifying the curves by means of the Lenke classification of two AIS clinical cases. Two learning strategies were used during the course. A postcourse questionnaire was applied to reclassify the same deformity cases. Differences in the correct answers of clinical cases between pre- and postcourse were analyzed, revealing the number of participants whose accuracy in classification improved after the course. Results Analysis showed a decrease in the number of participants with wrong answers in both cases after the course. In the first case, statistically significant differences were observed in both curve pattern (83.3%, p  =  0.005) and lumbar spine modifier (46.6%, p  =  0.049). No statistically significant improvement was seen in the sagittal thoracic modifier (33.3%, p  =  0.309). In the second case, statistical improvement was obtained in curve pattern (27.4%, p  =  0.018). No statistically significant improvement was seen regarding lumbar spine modifier (9.8%, p  =  0.121) and sagittal thoracic modifier (12.9%, p  =  0.081). Conclusion This pilot test showed objectively that learning strategies used during AOSpine courses improved the participants' knowledge. Teaching strategies must be continually improved to ensure an optimal level of knowledge transfer. PMID:28451507

Osteoblastic differentiating potential of dental pulp stem cells in vitro cultured on a chemically modified microrough titanium surface.

PubMed

DE Colli, Marianna; Radunovic, Milena; Zizzari, Vincenzo L; DI Giacomo, Viviana; DI Nisio, Chiara; Piattelli, Adriano; Calvo Guirado, José L; Zavan, Barbara; Cataldi, Amelia; Zara, Susi

2018-03-30

Titanium surface modification is critical for dental implant success. Our aim was to determine surfaces influence on dental pulp stem cells (DPSCs) viability and differentiation. Implants were divided into sandblasted/acid-etched (control) and sandblasted/acid-etched coated with calcium and magnesium ions (CaMg), supplied as composite (test). Proliferation was evaluated by MTT, differentiation checking osteoblastic gene expression, PGE2 secretion and matrix formation, inflammation by Interleukin 6 (IL-6) detection. MTT and IL-6 do not modify on test. A PGE2 increase on test is recorded. BMP2 is higher on test at early experimental points, Osterix and RUNX2 augment later. Alizarin-red S reveals higher matrix production on test. These results suggest that test surface is more osteoinductive, representing a start point for in vivo studies aiming at the construction of more biocompatible dental implants, whose integration and clinical performance are improved and some undesired effects, such as implant stability loss and further surgical procedures, are reduced.

The Complexity of Clinical Huntington's Disease: Developments in Molecular Genetics, Neuropathology and Neuroimaging Biomarkers.

PubMed

Tippett, Lynette J; Waldvogel, Henry J; Snell, Russell G; Vonsattel, Jean-Paul; Young, Anne B; Faull, Richard L M

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by extensive neuronal loss in the striatum and cerebral cortex, and a triad of clinical symptoms affecting motor, cognitive/behavioural and mood functioning. The mutation causing HD is an expansion of a CAG tract in exon 1 of the HTT gene. This chapter provides a multifaceted overview of the clinical complexity of HD. We explore recent directions in molecular genetics including the identification of loci that are genetic modifiers of HD that could potentially reveal therapeutic targets beyond the HTT gene transcript and protein. The variability of clinical symptomatology in HD is considered alongside recent findings of variability in cellular and neurochemical changes in the striatum and cerebral cortex in human brain. We review evidence from structural neuroimaging methods of progressive changes of striatum, cerebral cortex and white matter in pre-symptomatic and symptomatic HD, with a particular focus on the potential identification of neuroimaging biomarkers that could be used to test promising disease-specific and modifying treatments. Finally we provide an overview of completed clinical trials in HD and future therapeutic developments.

Modified endoscopic medial maxillectomy for zygomatic implant salvage

PubMed Central

Tajudeen, Bobby A.; Adappa, Nithin D.; Palmer, James N.

2016-01-01

Objectives: Odontogenic chronic rhinosinusitis (CRS) is an epidemiologically important disease process due, in part, to the increasingly commonplace use of dental restorative procedures such as zygomatic implantation. Traditional management of this clinical entity typically entails extraction of the infected hardware via an open or endoscopic approach. We describe a novel management strategy of odontogenic CRS following bilateral zygomatic implantation for oral rehabilitation that we surgically salvaged via a modified endoscopic medial maxillectomy. Methods: We describe the presentation and management of a case of metachronous development of bilateral CRS subsequent to zygomatic implantation. Results: The patient's postoperative course was characterized by marked endoscopic, radiologic, and symptomatic improvement as measured by the 22-item Sino-Nasal Outcome Test. Conclusion: We describe a novel treatment strategy for the management of odontogenic sinusitis resulting from erroneous zygomatic implant placement. Modified endoscopic medial maxillectomy in this clinical context facilitates mucosal normalization of the affected sinus, while permitting preservation of oral function through salvage of the displaced implant. PMID:28107147

Global measurement of coagulation in plasma from normal and haemophilia dogs using a novel modified thrombin generation test – Demonstrated in vitro and ex vivo

PubMed Central

Madsen, Daniel Elenius; Nichols, Timothy C.; Merricks, Elizabeth P.; Waters, Emily K.; Wiinberg, Bo

2017-01-01

Introduction Canine models of severe haemophilia resemble their human equivalents both regarding clinical bleeding phenotype and response to treatment. Therefore pre-clinical studies in haemophilia dogs have allowed researchers to make valuable translational predictions regarding the potency and efficacy of new anti-haemophilia drugs (AHDs) in humans. To refine in vivo experiments and reduce number of animals, such translational studies are ideally preceded by in vitro prediction of compound efficacy using a plasma based global coagulation method. One such widely used method is the thrombin generation test (TGT). Unfortunately, commercially available TGTs are incapable of distinguishing between normal and haemophilia canine plasma, and therefore in vitro prediction using TGT has so far not been possible in canine plasma material. Aim Establish a modified TGT capable of: 1) distinguishing between normal and haemophilia canine plasma, 2) monitoring correlation between canine plasma levels of coagulation factor VIII (FVIII) and IX (FIX) and thrombin generation, 3) assessing for agreement between compound activity and thrombin generation in ex vivo samples. Methods A modified TGT assay was established where coagulation was triggered using a commercially available activated partial thromboplastin time reagent. Results With the modified TGT a significant difference was observed in thrombin generation between normal and haemophilia canine plasma. A dose dependent thrombin generation was observed when assessing haemophilia A and B plasma spiked with dilution series of FVIII and FIX, respectively. Correlation between FVIII activity and thrombin generation was observed when analyzing samples from haemophilia A dogs dosed with canine FVIII. Limit of detection was 0.1% (v/v) FVIII or FIX. Conclusion A novel modified TGT suitable for monitoring and prediction of replacement therapy efficacy in plasma from haemophilia A and B dogs was established. PMID:28384182

An improved genetic algorithm for designing optimal temporal patterns of neural stimulation

NASA Astrophysics Data System (ADS)

Cassar, Isaac R.; Titus, Nathan D.; Grill, Warren M.

2017-12-01

Objective. Electrical neuromodulation therapies typically apply constant frequency stimulation, but non-regular temporal patterns of stimulation may be more effective and more efficient. However, the design space for temporal patterns is exceedingly large, and model-based optimization is required for pattern design. We designed and implemented a modified genetic algorithm (GA) intended for design optimal temporal patterns of electrical neuromodulation. Approach. We tested and modified standard GA methods for application to designing temporal patterns of neural stimulation. We evaluated each modification individually and all modifications collectively by comparing performance to the standard GA across three test functions and two biophysically-based models of neural stimulation. Main results. The proposed modifications of the GA significantly improved performance across the test functions and performed best when all were used collectively. The standard GA found patterns that outperformed fixed-frequency, clinically-standard patterns in biophysically-based models of neural stimulation, but the modified GA, in many fewer iterations, consistently converged to higher-scoring, non-regular patterns of stimulation. Significance. The proposed improvements to standard GA methodology reduced the number of iterations required for convergence and identified superior solutions.

Developing standards for the development of glaucoma virtual clinics using a modified Delphi approach.

PubMed

Kotecha, Aachal; Longstaff, Simon; Azuara-Blanco, Augusto; Kirwan, James F; Morgan, James Edwards; Spencer, Anne Fiona; Foster, Paul J

2018-04-01

To obtain consensus opinion for the development of a standards framework for the development and implementation of virtual clinics for glaucoma monitoring in the UK using a modified Delphi methodology. A modified Delphi technique was used that involved sampling members of the UK Glaucoma and Eire Society (UKEGS). The first round scored the strength of agreement to a series of standards statements using a 9-point Likert scale. The revised standards were subjected to a second round of scoring and free-text comment. The final standards were discussed and agreed by an expert panel consisting of seven glaucoma subspecialists from across the UK. A version of the standards was submitted to external stakeholders for a 3-month consultation. There was a 44% response rate of UKEGS members to rounds 1 and 2, consisting largely of consultant ophthalmologists with a specialist interest in glaucoma. The final version of the standards document was validated by stakeholder consultation and contains four sections pertaining to the patient groups, testing methods, staffing requirements and governance structure of NHS secondary care glaucoma virtual clinic models. Use of a modified Delphi approach has provided consensus agreement for the standards required for the development of virtual clinics to monitor glaucoma in the UK. It is anticipated that this document will be useful as a guide for those implementing this model of service delivery. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Developing a Decision Support System for Tobacco Use Counseling Using Primary Care Physicians

PubMed Central

Marcy, Theodore W.; Kaplan, Bonnie; Connolly, Scott W.; Michel, George; Shiffman, Richard N.; Flynn, Brian S.

2009-01-01

Background Clinical decision support systems (CDSS) have the potential to improve adherence to guidelines, but only if they are designed to work in the complex environment of ambulatory clinics as otherwise physicians may not use them. Objective To gain input from primary care physicians in designing a CDSS for smoking cessation to ensure that the design is appropriate to a clinical environment before attempts to test this CDSS in a clinical trial. This approach is of general interest to those designing similar systems. Design and Approach We employed an iterative ethnographic process that used multiple evaluation methods to understand physician preferences and workflow integration. Using results from our prior survey of physicians and clinic managers, we developed a prototype CDSS, validated content and design with an expert panel, and then subjected it to usability testing by physicians, followed by iterative design changes based on their feedback. We then performed clinical testing with individual patients, and conducted field tests of the CDSS in two primary care clinics during which four physicians used it for routine patient visits. Results The CDSS prototype was substantially modified through these cycles of usability and clinical testing, including removing a potentially fatal design flaw. During field tests in primary care clinics, physicians incorporated the final CDSS prototype into their workflow, and used it to assist in smoking cessation interventions up to eight times daily. Conclusions A multi-method evaluation process utilizing primary care physicians proved useful for developing a CDSS that was acceptable to physicians and patients, and feasible to use in their clinical environment. PMID:18713526

A Diagnostic Model for Dementia in Clinical Practice-Case Methodology Assisting Dementia Diagnosis.

PubMed

Londos, Elisabet

2015-04-02

Dementia diagnosis is important for many different reasons. Firstly, to separate dementia, or major neurocognitive disorder, from MCI (mild cognitive impairment), mild neurocognitive disorder. Secondly, to define the specific underlying brain disorder to aid treatment, prognosis and decisions regarding care needs and assistance. The diagnostic method of dementias is a puzzle of different data pieces to be fitted together in the best possible way to reach a clinical diagnosis. Using a modified case methodology concept, risk factors affecting cognitive reserve and symptoms constituting the basis of the brain damage hypothesis, can be visualized, balanced and reflected against test results as well as structural and biochemical markers. The model's origin is the case method initially described in Harvard business school, here modified to serve dementia diagnostics.

A Diagnostic Model for Dementia in Clinical Practice—Case Methodology Assisting Dementia Diagnosis

PubMed Central

Londos, Elisabet

2015-01-01

Dementia diagnosis is important for many different reasons. Firstly, to separate dementia, or major neurocognitive disorder, from MCI (mild cognitive impairment), mild neurocognitive disorder. Secondly, to define the specific underlying brain disorder to aid treatment, prognosis and decisions regarding care needs and assistance. The diagnostic method of dementias is a puzzle of different data pieces to be fitted together in the best possible way to reach a clinical diagnosis. Using a modified case methodology concept, risk factors affecting cognitive reserve and symptoms constituting the basis of the brain damage hypothesis, can be visualized, balanced and reflected against test results as well as structural and biochemical markers. The model’s origin is the case method initially described in Harvard business school, here modified to serve dementia diagnostics. PMID:26854146

Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial

PubMed Central

Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

2016-01-01

[Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists. PMID:27134355

Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.

PubMed

Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

2016-03-01

[Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists.

Triton Hodge Test: Improved Protocol for Modified Hodge Test for Enhanced Detection of NDM and Other Carbapenemase Producers.

PubMed

Pasteran, Fernando; Gonzalez, Lisandro J; Albornoz, Ezequiel; Bahr, Guillermo; Vila, Alejandro J; Corso, Alejandra

2016-03-01

Accurate detection of carbapenemase-producing Gram-negative bacilli is of utmost importance for the control of nosocomial spread and the initiation of appropriate antimicrobial therapy. The modified Hodge test (MHT), a carbapenem inactivation assay, has shown poor sensitivity in detecting the worldwide spread of New Delhi metallo-β-lactamase (NDM). Recent studies demonstrated that NDM is a lipoprotein anchored to the outer membrane in Gram-negative bacteria, unlike all other known carbapenemases. Here we report that membrane anchoring of β-lactamases precludes detection of carbapenemase activity by the MHT. We also show that this limitation can be overcome by the addition of Triton X-100 during the test, which allows detection of NDM. We propose an improved version of the assay, called the Triton Hodge test (THT), which allows detection of membrane-bound carbapenemases with the addition of this nonionic surfactant. This test was challenged with a panel of 185 clinical isolates (145 carrying known carbapenemase-encoding genes and 40 carbapenemase nonproducers). The THT displayed test sensitivity of >90% against NDM-producing clinical isolates, while improving performance against other carbapenemases. Ertapenem provided the highest sensitivity (97 to 100%, depending on the type of carbapenemase), followed by meropenem (92.5 to 100%). Test specificity was not affected by the addition of Triton (87.5% and 92.5% with ertapenem and meropenem, respectively). This simple inexpensive test confers a large improvement to the sensitivity of the MHT for the detection of NDM and other carbapenemases. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

PubMed

Rybicki, B A; Kryvenko, O N; Wang, Y; Jankowski, M; Trudeau, S; Chitale, D A; Gupta, N S; Rundle, A; Tang, D

2016-06-01

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing-suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection.

Lifting the veil: how to use clinical neuropsychology to assess dementia.

PubMed

Burrell, James R; Piguet, Olivier

2015-11-01

Neurologists often struggle to interpret the results of neuropsychological testing, even though cognitive assessments are an integral component of the diagnostic process in dementia syndromes. This article reviews the principles underlying clinical neuropsychology, background on common neuropsychological tests, and tips on how to interpret the results when assessing patients with dementia. General cognitive screening tools, appropriate for use by general neurologists and psychiatrists, as well as specific cognitive tests examining the main cognitive domains (attention and orientation, memory, visuospatial function, language and executive function) in patients with dementia are considered. Finally, the pattern of deficits, helpful in defining clinical dementia phenotypes and sometimes in predicting the underlying molecular pathology, are outlined. Such clinicopathological associations will become invaluable as disease-modifying treatments for dementia are developed and implemented. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Effect of surface modification using laser on wear resistance of titanium].

PubMed

Sato, Yohei

2005-02-01

Severe wear of cast commercial pure (CP) titanium teeth was observed in a clinical survey. This study evaluated the wear resistance of cast CP titanium and titanium alloy teeth after the surface was modified using laser technology. Teeth patterns were duplicated from artificial first molars (Livdent FB30, GC, Japan). All teeth specimens were cast with CP Ti grade 3 (T-Alloy H, GC) and Ti-6Al-7Nb (T-Alloy Tough, GC). After the occlusal surface was blasted with Al(2)O(3), the occlusal contact points were modified using a laser (Neo laser L, Girrbach, Germany) at the following irradiation conditions (voltage: 260 V; pulse: 7 ms; focus: 1.5 mm). These parameters were determined by preliminary study. As a control, Type IV gold alloy (PGA-3, Ishifuku, Japan) was also cast conventionally. Both maxillary and mandibular teeth were worn using an in vitro two-body wear testing apparatus that simulated chewing function (60 strokes/min; grinding distance: 2 mm under flowing water). Wear resistance was assessed as volume loss (mm(3)) at 5 kgf (grinding force) after 50,000 strokes. The results (n=5) were analyzed by ANOVA/Scheffé's test (alpha=0.05). The gold alloy showed the best wear resistance of all the metals tested. Of all the titanium specimens tested, the modified surface indicated significantly greater wear resistance than did conventional titanium teeth without surface modification (p<0.05). Wear resistance was increased by modification of the surface using a laser. If severe wear of titanium teeth was observed clinically, little wear occurred when the occlusal facets were irradiated using a laser.

Urine Toxicology in Adults Evaluated for a Central Hypersomnia and How the Results Modify the Physician's Diagnosis

PubMed Central

Kosky, Christopher A.; Bonakis, Anastasios; Yogendran, Arthee; Hettiarachchi, Gihan; Dargan, Paul I.; Williams, Adrian J.

2016-01-01

Study Objectives: Drugs and psychoactive substances can cause sleepiness and when undetected, may lead to over diagnosis of central hypersomnias. We performed urine drug testing using gas chromatography-mass spectrometry in adults undergoing multiple sleep latency testing (MSLT) for a suspected central hypersomnia. We examined how the drug test results modified the treating physician's diagnosis. Methods: One hundred eighty-six consecutive patients with a suspected central hypersomnia who underwent clinical assessment, MSLT and urine drug testing by gas chromatography-mass spectrometry were retrospectively studied. Physicians made a diagnosis after clinical assessment and MSLT and were initially blinded to the urine drug test results. Results: A third of patients assessed for subjective hypersomnia had a positive urine drug test for a substance affecting sleep. Opioids, cannabis, and amphetamines were the commonest drugs detected. Using MSLT, 35 (18.8%) of 186 patients had objective hypersomnia that may have been due to a drug or substance. Drugs or substances may have confounded the MSLT in 11 (20.1%) of 53 patients who fulfilled diagnostic criteria for idiopathic hypersomnia, and 12 (52%) of 23 of those who fulfilled diagnostic criteria for narcolepsy without cataplexy. Of the 75 positive urine drug samples, 61 (81%) were substances or medications not revealed in the physician interview. The treating physician had not suspected drugs or substances as a possible cause of objective hypersomnia in 34 (97%) of the 35 patients. Conclusions: Drugs and psychoactive substances can confound the results of the MSLT and when undetected could lead to over diagnosis of central hypersomnias. Citation: Kosky CA, Bonakis A, Yogendran A, Hettiarachchi G, Dargan PI, Williams AJ. Urine toxicology in adults evaluated for a central hypersomnia and how the results modify the physician's diagnosis. J Clin Sleep Med 2016;12(11):1499–1505. PMID:27568897

Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus.

PubMed

Sacks, David B; Arnold, Mark; Bakris, George L; Bruns, David E; Horvath, Andrea Rita; Kirkman, M Sue; Lernmark, Ake; Metzger, Boyd E; Nathan, David M

2011-06-01

Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association. In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A(1c) (HbA(1c)) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of HbA(1c). The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended.

International definition of a point-of-care test in family practice: a modified e-Delphi procedure.

PubMed

Schols, Angel M R; Dinant, Geert-Jan; Hopstaken, Rogier; Price, Christopher P; Kusters, Ron; Cals, Jochen W L

2018-01-29

The use of point-of-care tests (POCTs) in family practice is increasing, and the term POCT is often used in medical literature and clinical practice. Yet, no widely supported definition by several professional fields exists. To reach consensus on an international definition of a POCT in family practice. We performed a modified international e-Delphi procedure of four rounds among expert panel members from different professional backgrounds-family practitioners, laboratory specialists, policymakers, researchers and manufacturers. Of 27 panel members from seven different countries, 26 participated in all rounds. Most panel members were active in POCT research or policymaking and 70% worked in family medicine. After choosing important components, structuring of answers and feedback, the following definition was chosen as the best or second best definition by 81% of panel members: a point-of-care test in family practice is a test to support clinical decision making, which is performed by a qualified member of the practice staff nearby the patient and on any part of the patient's body or its derivatives, during or very close to the time of consultation, to help the patient and physician to decide upon the best suited approach, and of which the results should be known at the time of the clinical decision making. The definition emerging from this study can inform family practitioners, laboratory specialists, policymakers and manufacturers on the most widely supported and recognized definition and could act as a clear starting point for the organization and execution of professional point-of-care testing in family practice worldwide. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Factor Analysis of the Modified Sexual Adjustment Questionnaire-Male

PubMed Central

Wilmoth, Margaret C.; Hanlon, Alexandra L.; Ng, Lit Soo; Bruner, Debra W.

2015-01-01

Background and Purpose The Sexual Adjustment Questionnaire (SAQ) is used in National Cancer Institute–sponsored clinical trials as an outcome measure for sexual functioning. The tool was revised to meet the needs for a clinically useful, theory-based outcome measure for use in both research and clinical settings. This report describes the modifications and validity testing of the modified Sexual Adjustment Questionnaire-Male (mSAQ-Male). Methods This secondary analysis of data from a large Radiation Therapy Oncology Group trial employed principal axis factor analytic techniques in estimating validity of the revised tool. The sample size was 686; most subjects were White, older than the age 60 years, and with a high school education and a Karnofsky performance scale (KPS) score of greater than 90. Results A 16-item, 3-factor solution resulted from the factor analysis. The mSAQ-Male was also found to be sensitive to changes in physical sexual functioning as measured by the KPS. Conclusion The mSAQ-Male is a valid self-report measure of sexuality that can be used clinically to detect changes in male sexual functioning. PMID:25255676

Does intuition have a role in psychiatric diagnosis?

PubMed

Srivastava, Anil; Grube, Michael

2009-06-01

Psychiatric diagnosis is invariably guided by self-report. When such self-report is questioned, reliance on formalized testing predominates. The situation is less certain, however, when such methods and clinical "feel", or intuition, conflict. While many argue for the supremacy of actuarial methods, fields such as Management have increasingly emphasized the importance of intuition; Psychiatry, although with few objective tests and reliance on the clinical encounter, offers surprisingly few answers. We explore here the use of intuition in decision-making through a case example and suggest that it is not inferior to other diagnostic methods: intuition should be used to suggest, guide, and modify psychiatric diagnosis. Mostly, there is a need for greater discussion among Psychiatrists including consideration to the clinical, legal, and ethical implications of the use of intuition in psychiatric decision-making.

In vivo Selection of Autologous MGMT Gene-Modified Cells Following Reduced Intensity Conditioning with BCNU and Temozolomide in the Dog Model

PubMed Central

Gori, Jennifer L.; Beard, Brian C.; Ironside, Christina; Karponi, Garyfalia; Kiem, Hans-Peter

2012-01-01

Chemotherapy with BCNU and temozolomide (TMZ) is commonly used for the treatment of glioblastoma multiforme (GBM) and other cancers. In preparation for a clinical gene therapy study in patients with glioblastoma, we wished to study whether these reagents could be used as a reduced-intensity conditioning regimen for autologous transplantation of gene-modified cells. We used an MGMT(P140K)-expressing lentivirus vector to modify dog CD34+ cells and tested in 4 dogs whether these autologous cells engraft and provide chemoprotection after transplantation. Treatment with O6-benzylguanine (O6BG)/TMZ after transplantation resulted in gene marking levels up to 75%, without significant hematopoietic cytopenia, which is consistent with hematopoietic chemoprotection. Retrovirus integration analysis showed that multiple clones contribute to hematopoiesis. These studies demonstrate the ability to achieve stable engraftment of MGMT(P140K)-modified autologous HSCs after a novel reduced-intensity conditioning protocol using a combination of BCNU and TMZ. Furthermore, we show that MGMT(P140K)-HSC engraftment provides chemoprotection during TMZ dose escalation. Clinically, chemoconditioning with BCNU and TMZ should facilitate engraftment of MGMT(P140K)-modified cells while providing anti-tumor activity for patients with poor prognosis glioblastoma or alkylating agent sensitive tumors, thereby supporting dose-intensified chemotherapy regimens. PMID:22627392

The Formative Method for Adapting Psychotherapy (FMAP): A community-based developmental approach to culturally adapting therapy

PubMed Central

Hwang, Wei-Chin

2010-01-01

How do we culturally adapt psychotherapy for ethnic minorities? Although there has been growing interest in doing so, few therapy adaptation frameworks have been developed. The majority of these frameworks take a top-down theoretical approach to adapting psychotherapy. The purpose of this paper is to introduce a community-based developmental approach to modifying psychotherapy for ethnic minorities. The Formative Method for Adapting Psychotherapy (FMAP) is a bottom-up approach that involves collaborating with consumers to generate and support ideas for therapy adaptation. It involves 5-phases that target developing, testing, and reformulating therapy modifications. These phases include: (a) generating knowledge and collaborating with stakeholders (b) integrating generated information with theory and empirical and clinical knowledge, (c) reviewing the initial culturally adapted clinical intervention with stakeholders and revising the culturally adapted intervention, (d) testing the culturally adapted intervention, and (e) finalizing the culturally adapted intervention. Application of the FMAP is illustrated using examples from a study adapting psychotherapy for Chinese Americans, but can also be readily applied to modify therapy for other ethnic groups. PMID:20625458

Short term clinical effectiveness of a 0.07% cetylpyridinium chloride mouth rinse in patients undergoing fixed orthodontic appliance treatment.

PubMed

Pahwa, Narinder; Kumar, Atul; Gupta, Siddharth

2011-07-01

To test the short term clinical effectiveness of commercially available 0.07%.cetylpyridinium chloride mouth rinse in patients undergoing fixed orthodontic treatment as compared to a placebo mouth rinse and patients using toothbrush and toothpaste. Forty-five subjects for this double blind study were assigned randomly into three groups of 15 each. Gingival inflammation, plaque accumulation, and bleeding on probing, were recorded at baseline (10 days after prophylaxis), and at the end of one month in all the three groups and compared. Paired t test showed significant differences in bleeding index for pre and post treatment recordings for cetylpyridinium group. Modified gingival index showed no significant difference in the cetylpyridinium group. For plaque index significant difference was found for cetylpyridinium and control groups. Cetylpyridinium mouth rinse 0.7% was found to be effective in reducing the bleeding and plaque index scores. It was not effective in reducing the modified gingival index scores. Cetylpyridinium mouth rinse 0.07% improves the oral hygiene of orthodontic patients when used as an adjunct to normal oral hygiene measures.

High sensitivity and label-free detection of Enterovirus 71 by nanogold modified electrochemical impedance spectroscopy

NASA Astrophysics Data System (ADS)

Wang, Fang-Yu; Li, Hsing-Yuan; Tseng, Shing-Hua; Cheng, Tsai-Mu; Chu, Hsueh-Liang; Yang, Jyh-Yuan; Chang, Chia-Ching

2013-03-01

Enterovirus 71 (EV71), which is the most fulminant and invasive species of enterovirus, can cause children neurologic complications and death within 2-3 days after fever and rash developed. Besides, EV71 has high sequence similarity with Coxsackie A 16 (CA16) that makes differential diagnosis difficult in clinic and laboratory. Since conventional viral diagnostic method cannot diagnose EV71 quickly and EV71 can transmit at low viral titer, the patients might delay in treatment. A quick, high sensitive, and high specific test for EV71 detection is pivotal. Electrochemical impedance spectroscopy (EIS) has been applied for detecting bio-molecules as biosensors recently. In this study, we try to build a detection platform for EV71 detection by nanogold modified EIS probe. The result shows that our probe can detect 3.6 VP1/50 μl (one EV71 particle has 60 VP1) in 3 minutes. The test can also distinguish EV71 from CA16 and lysozyme. Diagnosis of enterovirus 71 by electrochemical impedance spectroscopy has the potential to apply in clinic.

Public health and clinical impact of increasing emergency department-based HIV testing: perspectives from the 2007 conference of the National Emergency Department HIV Testing Consortium.

PubMed

Kecojevic, Aleksandar; Lindsell, Christopher J; Lyons, Michael S; Holtgrave, David; Torres, Gretchen; Heffelfinger, James; Brown, Jeremy; Couture, Eileen; Jung, Julianna; Connell, Samantha; Rothman, Richard E

2011-07-01

Understanding perceived benefits and disadvantages of HIV testing in emergency departments (EDs) is imperative to overcoming barriers to implementation. We codify those domains of public health and clinical care most affected by implementing HIV testing in EDs, as determined by expert opinion. Opinions were systematically collected from attendees of the 2007 National ED HIV Testing Consortium meeting. Structured evaluation of strengths, weaknesses, opportunities, and threats analysis was conducted to assess the impact of ED-based HIV testing on public health. A modified Delphi method was used to assess the impact of ED-based HIV testing on clinical care from both individual patient and individual provider perspectives. Opinions were provided by 98 experts representing 42 academic and nonacademic institutions. Factors most frequently perceived to affect public health were (strengths) high volume of ED visits and high prevalence of HIV, (weaknesses) undue burden on EDs, (opportunities) reduction of HIV stigma, and (threats) lack of resources in EDs. Diagnostic testing and screening for HIV were considered to have a favorable impact on ED clinical care from both individual patient and individual provider perspectives; however, negative test results were not perceived to have any benefit from the provider's perspective. The need for HIV counseling in the ED was considered to have a negative impact on clinical care from the provider's perspective. Experts in ED-based HIV testing perceived expanded ED HIV testing to have beneficial impacts for both the public health and individual clinical care; however, limited resources were frequently cited as a possible impediment. Many issues must be resolved through further study, education, and policy changes if the full potential of HIV testing in EDs is to be realized. Copyright © 2011. Published by Mosby, Inc.

Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy

PubMed Central

Hogarth, Marshall W.; Houweling, Peter J.; Thomas, Kristen C.; Gordish-Dressman, Heather; Bello, Luca; Vishwanathan, V.; Chidambaranathan, S.; Douglas Biggar, W.; McAdam, Laura C.; Mah, Jean K.; Tulinius, Mar; Cnaan, Avital; Morgenroth, Lauren P.; Leshner, Robert; Tesi-Rocha, Carolina; Thangarajh, Mathula; Duong, Tina; Kornberg, Andrew; Ryan, Monique; Nevo, Yoram; Dubrovsky, Alberto; Clemens, Paula R.; Abdel-Hamid, Hoda; Connolly, Anne M.; Pestronk, Alan; Teasley, Jean; Bertorini, Tulio E.; Webster, Richard; Kolski, Hanna; Kuntz, Nancy; Driscoll, Sherilyn; Bodensteiner, John B.; Carlo, Jose; Gorni, Ksenija; Lotze, Timothy; Day, John W.; Karachunski, Peter; Henricson, Erik K.; Abresch, Richard T.; McDonald, Craig M.; Pegoraro, Elena; Hoffman, Eric P.; Head, Stewart I.; North, Kathryn N.

2017-01-01

Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and progressive weakness. There is considerable inter-patient variability in disease onset and progression, which can confound the results of clinical trials. Here we show that a common null polymorphism (R577X) in ACTN3 results in significantly reduced muscle strength and a longer 10 m walk test time in young, ambulant patients with DMD; both of which are primary outcome measures in clinical trials. We have developed a double knockout mouse model, which also shows reduced muscle strength, but is protected from stretch-induced eccentric damage with age. This suggests that α-actinin-3 deficiency reduces muscle performance at baseline, but ameliorates the progression of dystrophic pathology. Mechanistically, we show that α-actinin-3 deficiency triggers an increase in oxidative muscle metabolism through activation of calcineurin, which likely confers the protective effect. Our studies suggest that ACTN3 R577X genotype is a modifier of clinical phenotype in DMD patients. PMID:28139640

Indirect zirconia-reinforced lithium silicate ceramic CAD/CAM restorations: Preliminary clinical results after 12 months.

PubMed

Zimmermann, Moritz; Koller, Christina; Mehl, Albert; Hickel, Reinhard

2017-01-01

No clinical data are available for the new computer-aided design/computer-assisted manufacture (CAD/CAM) material zirconia-reinforced lithium silicate (ZLS) ceramic. This study describes preliminary clinical results for indirect ZLS CAD/CAM restorations after 12 months. Indirect restorations were fabricated, using the CEREC method and intraoral scanning (CEREC Omnicam, CEREC MCXL). Sixty-seven restorations were seated adhesively (baseline). Sixty restorations were evaluated after 12 months (follow-up), using modified FDI criteria. Two groups were established, according to ZLS restorations' post-processing procedure prior to adhesive seating: group I (three-step polishing, n = 32) and group II (fire glazing, n = 28). Statistical analysis was performed with Mann-Whitney U test and Wilcoxon test (P < .05). The success rate of indirect ZLS CAD/CAM restorations after 12 months was 96.7%. Two restorations clinically failed as a result of bulk fracture (failure rate 3.3%). No statistically significant differences were found for baseline and follow-up criteria (Wilcoxon test, P > .05). Statistically significant differences were found for criteria surface gloss for group I and group II (Mann-Whitney U test, P < .05). This study demonstrates ZLS CAD/CAM restorations have a high clinical success rate after 12 months. A longer clinical evaluation period is necessary to draw further conclusions.

Genetic advances in sarcomeric cardiomyopathies: state of the art

PubMed Central

Ho, Carolyn Y.; Charron, Philippe; Richard, Pascale; Girolami, Francesca; Van Spaendonck-Zwarts, Karin Y.; Pinto, Yigal

2015-01-01

Genetic studies in the 1980s and 1990s led to landmark discoveries that sarcomere mutations cause both hypertrophic and dilated cardiomyopathies. Sarcomere mutations also likely play a role in more complex phenotypes and overlap cardiomyopathies with features of hypertrophy, dilation, diastolic abnormalities, and non-compaction. Identification of the genetic cause of these important conditions provides unique opportunities to interrogate and characterize disease pathogenesis and pathophysiology, starting from the molecular level and expanding from there. With such insights, there is potential for clinical translation that may transform management of patients and families with inherited cardiomyopathies. If key pathways for disease development can be identified, they could potentially serve as targets for novel disease-modifying or disease-preventing therapies. By utilizing gene-based diagnostic testing, we can identify at-risk individuals prior to the onset of clinical disease, allowing for disease-modifying therapy to be initiated early in life, at a time that such treatment may be most successful. In this section, we review the current application of genetics in clinical management, focusing on hypertrophic cardiomyopathy as a paradigm; discuss state-of-the-art genetic testing technology; review emerging knowledge of gene expression in sarcomeric cardiomyopathies; and discuss both the prospects, as well as the challenges, of bringing genetics to medicine. PMID:25634555

A study of the age attribute in a query tool for a clinical data warehouse.

PubMed

Scheufele, Elisabeth L; Scheufele, Elisabeth Lee; Dubey, Anil; Dubey, Anil Kumar; Murphy, Shawn N

2008-11-06

The RPDR, a clinical data warehouse with a user-friendly Querytool, allows researchers to perform studies on patient data. Currently, the RPDR represents age as the patient's age at the present time, which is problematic in situations where age at the time of the event is more appropriate. We will modify the Querytool to consider this by assessing the perception of age via survey, testing backend query solutions, and developing modifications based on these results.

Potential Use of γ-Secretase Modulators in the Treatment of Alzheimer Disease

PubMed Central

Wagner, Steven L.; Tanzi, Rudolph E.; Mobley, William C.; Galasko, Douglas

2013-01-01

Although significant progress has occurred in the past 20 years regarding our understanding of Alzheimer disease pathogenesis, we have yet to identify disease-modifying therapeutics capable of substantially altering the clinical course of this prevalent neurodegenerative disease. In this short review, we discuss 2 approaches that are currently being tested clinically (γ-secretase inhibition and γ-secretase modulation) and emphasize the significant differences between these 2 therapeutic approaches. We also discuss certain genetic- and biomarker-based translational and clinical trial paradigms that may assist in developing a useful therapeutic agent. PMID:22801784

Engaging Patients and Caregivers Managing Rare Diseases to Improve the Methods of Clinical Guideline Development: A Research Protocol

PubMed Central

Kinnett, Kathi; Grant, Sean; Lucas, Ann; Martin, Ann; Denger, Brian; Peay, Holly; Coulter, Ian; Fink, Arlene

2017-01-01

Background Clinical guidelines provide systematically developed recommendations for deciding on appropriate health care options for specific conditions and clinical circumstances. Up until recently, patients and caregivers have rarely been included in the process of developing care guidelines. Objective This project will develop and test a new online method for including patients and their caregivers in this process using Duchenne muscular dystrophy (DMD) care guidelines as an example. The new method will mirror and complement the RAND/UCLA Appropriateness Method (RAM)—the gold standard approach for conducting clinical expert panels that uses a modified Delphi format. RAM is often used in clinical guideline development to determine care appropriateness and necessity in situations where existing clinical evidence is uncertain, weak, or unavailable. Methods To develop the new method for engaging patients and their caregivers in guideline development, we will first conduct interviews with experts on RAM, guideline development, patient engagement, and patient-centeredness and engage with Duchenne patients and caregivers to identify how RAM should be modified for the purposes of patient engagement and what rating criteria should patients and caregivers use to provide their input during the process of guideline development. Once the new method is piloted, we will test it by conducting two concurrently run patient/caregiver panels that will rate patient-centeredness of a subset of DMD care management recommendations already deemed clinically appropriate and necessary. The ExpertLens™ system—a previously evaluated online modified Delphi system that combines two rounds of rating with a round of feedback and moderated online discussions—will be used to conduct these panels. In addition to developing and testing the new engagement method, we will work with the members of our project’s Advisory Board to generate a list of best practices for enhancing the level of patient and caregiver involvement in the guideline development process. We will solicit input on these best practice from Duchenne patients, caregivers, and clinicians by conducting a series of round-table discussions and making a presentation at an annual conference on Duchenne. Results The study protocol was reviewed by RAND’s Human Subjects Protection Committee, which determined it to be exempt from review. Interviews with RAM experts have been completed. The projected study completion date is May 2020. Conclusions We expect that the new method will make it easier to engage large numbers of patients and caregivers in the process of guideline development in a rigorous and culturally appropriate manner that is consistent with the way clinicians participate in guideline development. Moreover, this project will develop best practices that could help involve patients and caregivers in the clinical guideline development process in other clinical areas, thereby facilitating the work of guideline developers. PMID:28455279

A modified oral sugar test for evaluation of insulin and glucose dynamics in horses.

PubMed

Lindåse, Sanna; Nostell, Katarina; Bröjer, Johan

2016-10-20

An oral sugar test (OST) using Karo ® Light Corn Syrup has been developed in the USA as a field test for the assessment of insulin dysregulation in horses but the syrup is not available in Scandinavian grocery stores. The aim of the study was to compare the results of a modified OST between horses with equine metabolic syndrome (EMS) and healthy horses using a Scandinavian commercially available glucose syrup (Dansukker glykossirap). In addition, the effect of breed and the repeatability of the test were evaluated. In the present study, clinically healthy horses (7 Shetland ponies, 8 Icelandic horses, 8 Standardbred horses) and 20 horses of various breeds with EMS underwent the modified OST test. The Icelandic horses and Shetland ponies underwent the OST twice. Insulin and glucose data from the OST were used to calculate peak insulin concentration (Peak INS ), time to peak insulin concentration (T-peak INS ), area under the curve for insulin (AUC INS ) and glucose (AUC GLU ) as well as whole body insulin sensitivity index (ISI COMP ). Compared to the healthy group, the EMS group had 6-7 times higher geometric mean for Peak INS and AUC INS and 8 times lower geometric mean for ISI COMP . The EMS group had a delayed T-peak INS compared to the healthy group. There was no effect of breed in the group of healthy horses on Peak INS , T-peak INS , AUC INS , AUC GLU and ISI COMP . Coefficient of variation for repeated tests was 19.8, 19.0 and 17.6 % for Peak INS , AUC INS and ISI COMP respectively. The results of the present study demonstrate that the modified OST appears to be a practical and useful diagnostic tool for assessment of insulin dysregulation in the horse. However, to make it possible to establish the most appropriate sampling interval and to evaluate the accuracy of the modified OST, further studies in horses with a variable degree of insulin resistance are needed, where results from the modified OST are compared with quantitative measurements for IS.

Comparison of Sleep Latency and Number of SOREMPs in the Home and Hospital With a Modified Multiple Sleep Latency Test: A Randomized Crossover Study.

PubMed

Beiske, Kornelia K; Sand, Trond; Rugland, Eyvind; Stavem, Knut

2017-05-01

Comparison of mean sleep latencies and number of sleep-onset rapid eye movement periods (SOREMPs) between modified multiple sleep latency test (MSLT) performed in the unattended home and in-hospital laboratory setting. A randomized crossover single-blinded design. Thirty-four subjects referred to MSLT for suspected hypersomnia or narcolepsy were included. Participants were randomized to perform modified MSLT in the unattended home or in the hospital first. Scores in the two settings were compared using Wilcoxon signed-rank test or exact McNemar test. Agreement between home and hospital categorized mean sleep latency and number of SOREMPs was assessed using simple kappa (κ) and proportion agreement. Agreement between home and hospital mean sleep latency was assessed using a Bland-Altman plot and an intraclass correlation coefficient. There was no difference between home and hospital assessment of mean sleep latency (P = 0.86). Two or more SOREMPs were found more frequently on modified MSLTs performed at home compared with those at the hospital (7 and 2, respectively; P = 0.025). Agreement was moderate for categorized sleep latency (κ = 0.53) and fair for categorized SOREMPs (κ = 0.39) in the 2 settings. Analysis of mean sleep latency using intraclass correlation coefficient showed a very good agreement between the two settings. Group mean sleep latency for home modified MSLTs seems to be reliable compared with that for the attended sleep-laboratory setting. Higher rate of SOREMP in the unattended home suggests that napping in a familiar environment facilitates the transition into REM sleep. Further studies are needed to assess the normal limit, sensitivity, and specificity for SOREMP at home before the clinical utility of home-based napping can be determined.

Evaluation of fit of cement-retained implant-supported 3-unit structures fabricated with direct metal laser sintering and vacuum casting techniques.

PubMed

Oyagüe, Raquel Castillo; Sánchez-Turrión, Andrés; López-Lozano, José Francisco; Montero, Javier; Albaladejo, Alberto; Suárez-García, María Jesús

2012-07-01

This study evaluated the vertical discrepancy of implant-fixed 3-unit structures. Frameworks were constructed with laser-sintered Co-Cr, and vacuum-cast Co-Cr, Ni-Cr-Ti, and Pd-Au. Samples of each alloy group were randomly luted in standard fashion using resin-modified glass-ionomer, self-adhesive, and acrylic/urethane-based cements (n = 12 each). Discrepancies were SEM analyzed. Three-way ANOVA and Student-Newman-Keuls tests were run (P < 0.05). Laser-sintered structures achieved the best fit per cement tested. Within each alloy group, resin-modified glass-ionomer and acrylic/urethane-based cements produced comparably lower discrepancies than the self-adhesive agent. The abutment position did not yield significant differences. All misfit values could be considered clinically acceptable.

Standardization and performance evaluation of "modified" and "ultrasensitive" versions of the Abbott RealTime HIV-1 assay, adapted to quantify minimal residual viremia.

PubMed

Amendola, Alessandra; Bloisi, Maria; Marsella, Patrizia; Sabatini, Rosella; Bibbò, Angela; Angeletti, Claudio; Capobianchi, Maria Rosaria

2011-09-01

Numerous studies investigating clinical significance of HIV-1 minimal residual viremia (MRV) suggest potential utility of assays more sensitive than those routinely used to monitor viral suppression. However currently available methods, based on different technologies, show great variation in detection limit and input plasma volume, and generally suffer from lack of standardization. In order to establish new tools suitable for routine quantification of minimal residual viremia in patients under virological suppression, some modifications were introduced into standard procedure of the Abbott RealTime HIV-1 assay leading to a "modified" and an "ultrasensitive" protocols. The following modifications were introduced: calibration curve extended towards low HIV-1 RNA concentration; 4 fold increased sample volume by concentrating starting material; reduced volume of internal control; adoption of "open-mode" software for quantification. Analytical performances were evaluated using the HIV-1 RNA Working Reagent 1 for NAT assays (NIBSC). Both tests were applied to clinical samples from virologically suppressed patients. The "modified" and the "ultrasensitive" configurations of the assay reached a limit of detection of 18.8 (95% CI: 11.1-51.0 cp/mL) and 4.8 cp/mL (95% CI: 2.6-9.1 cp/mL), respectively, with high precision and accuracy. In clinical samples from virologically suppressed patients, "modified" and "ultrasensitive" protocols allowed to detect and quantify HIV RNA in 12.7% and 46.6%, respectively, of samples resulted "not-detectable", and in 70.0% and 69.5%, respectively, of samples "detected <40 cp/mL" in the standard assay. The "modified" and "ultrasensitive" assays are precise and accurate, and easily adoptable in routine diagnostic laboratories for measuring MRV. Copyright © 2011 Elsevier B.V. All rights reserved.

Improving physical fitness of individuals with intellectual and developmental disability through a Virtual Reality Intervention Program.

PubMed

Lotan, Meir; Yalon-Chamovitz, Shira; Weiss, Patrice L Tamar

2009-01-01

Individuals with intellectual and developmental disabilities (IDD) are in need of effective physical fitness training programs. The aim was to test the effectiveness of a Virtual Reality (VR)-based exercise program in improving the physical fitness of adults with IDD. A research group (N=30; mean age=52.3+/-5.8 years; moderate IDD level) was matched for age, IDD level and functional abilities with a control group (N=30, mean age=54.3+/-5.4 years). A 5-6 week fitness program consisting of two 30 min sessions per week included game-like exercises provided by the Sony PlayStation II EyeToy VR system. Changes in physical fitness were monitored by the Energy Expenditure Index (EEI), the modified 12 min walk/run and the Total Heart Beat Index (THBI). Significant (p<0.05) improvements in physical fitness were demonstrated for the research group in comparison to the control group for the Modified Cooper test and the THBI but not for the EEI test. The EEI, Modified Cooper and THBI tests were found feasible to evaluate physical fitness levels and change of individuals with IDD under clinical conditions. VR technology intervention was suitable for adults with IDD and resulted in significant improvements in the physical fitness levels of the participants.

One-year clinical evaluation of two resin composites, two polymerization methods, and a resin-modified glass ionomer in non-carious cervical lesions.

PubMed

Koubi, Stephen; Raskin, Anne; Bukiet, Frédéric; Pignoly, Christian; Toca, Edwige; Tassery, Hervé

2006-11-01

The aim of this study was to examine clinically relevant data on four restorative procedures for non-carious cervical lesions using United States Public Health Service (USPHS)-compatible clinical and photographic criteria and to compare different methods of analyzing clinical data. Fourteen patients with at least one or two pairs of non-carious lesions under occlusion and a mean age of 50 were enrolled in this study. A total of 56 restorations (14 with each material) were placed by three experienced, calibrated dental practitioners. Two other experienced and calibrated practitioners, under single-blind conditions, followed up on all restorations for a period of one year. Three materials were randomly placed: a micro-hybrid composite with two polymerization methods (G1 and G2), a flowable micro-hydrid composite (G3), and a resin-modified glass ionomer (G4). Statistical analysis was performed using the Kruskall-Wallis test (p<0.05) and a Mann-Whitney U modified test with a corrected significance level. At the one year evaluation time, there were no restorations with secondary caries and the retention rates in G1 (IntenS with a hard polymerization), G2 (IntenS with a soft polymerization), G3 (Filtek flow), and G4 (Fuji II LC) were 85.7% (two losses), 92.8% (one loss), 100%, and 100%, respectively. The total visual comparison of the results at baseline (15 days later) showed significant differences only with the clinical acceptance criterion: G1 was different from G2, with a soft polymerization device (p<0.05). In terms of surface quality at one year, G1, G2, and G3 exhibited a statistically significant difference from G4, p<0.05. The digital analysis at baseline showed significant differences only with the clinical acceptance criterion: G1=G2 was different from G3=G4, p<0.05. At one year, only the microporosity criterion showed any statistical differences: G1=G2=G3 was different from G4, p<0.05. The resin-modified glass ionomer was easier to use and had a high retention rate, but it failed in terms of surface quality (visual mode) and porosity (digital mode) criteria compared to the others groups. Overall results showed no difference between groups G1 (hard-polymerized) and G2 (soft-polymerized), and only G1 was affected by the marginal edge (p<0.03) and integrity criteria (p<0.02) at one year.

Physical and composition characteristics of clinical secretions compared with test soils used for validation of flexible endoscope cleaning.

PubMed

Alfa, M J; Olson, N

2016-05-01

To determine which simulated-use test soils met the worst-case organic levels and viscosity of clinical secretions, and had the best adhesive characteristics. Levels of protein, carbohydrate and haemoglobin, and vibrational viscosity of clinical endoscope secretions were compared with test soils including ATS, ATS2015, Edinburgh, Edinburgh-M (modified), Miles, 10% serum and coagulated whole blood. ASTM D3359 was used for adhesion testing. Cleaning of a single-channel flexible intubation endoscope was tested after simulated use. The worst-case levels of protein, carbohydrate and haemoglobin, and viscosity of clinical material were 219,828μg/mL, 9296μg/mL, 9562μg/mL and 6cP, respectively. Whole blood, ATS2015 and Edinburgh-M were pipettable with viscosities of 3.4cP, 9.0cP and 11.9cP, respectively. ATS2015 and Edinburgh-M best matched the worst-case clinical parameters, but ATS had the best adhesion with 7% removal (36.7% for Edinburgh-M). Edinburgh-M and ATS2015 showed similar soiling and removal characteristics from the surface and lumen of a flexible intubation endoscope. Of the test soils evaluated, ATS2015 and Edinburgh-M were found to be good choices for the simulated use of endoscopes, as their composition and viscosity most closely matched worst-case clinical material. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Enhancing the Detection of Dysmorphic Red Blood Cells and Renal Tubular Epithelial Cells with a Modified Urinalysis Protocol.

PubMed

Chu-Su, Yu; Shukuya, Kenichi; Yokoyama, Takashi; Lin, Wei-Chou; Chiang, Chih-Kang; Lin, Chii-Wann

2017-01-11

Urinary sediment is used to evaluate patients with possible urinary tract diseases. Currently, numerous protocols are applied to detect dysmorphic red blood cells (RBCs) and renal tubular epithelial cells (RTECs) in urinary sediment. However, distinct protocols are used by nephrologists and medical technologists for specimen concentration and observation, which leads to major discrepancies in the differential counts of formed elements such as dysmorphic RBCs and RTECs and might interfere with an accurate clinical diagnosis. To resolve these problems, we first tested a modified urinalysis protocol with an increased relative centrifuge force and concentration factor in 20 biopsy-confirmed glomerulonephritis patients with haematuria. We successfully improved the recovery ratio of dysmorphic RBCs in clinical specimens from 34.7% to 42.0% (P < 0.001). Furthermore, we confirmed the correlation between counts by the modified urinary protocol and Sysmex UF-1000i urinary flow cytometer (r ≥ 0.898, P < 0.001). A total of 28 types of isomorphic and dysmorphic RBCs were detected using a bright field microscope, with results comparable to those using a standard phase contrast microscope. Finally, we applied Sternheimer stain to enhance the contrast of RTECs in the urinary sediments. We concluded that this modified urinalysis protocol significantly enhanced the quality of urinalysis.

Enhancing the Detection of Dysmorphic Red Blood Cells and Renal Tubular Epithelial Cells with a Modified Urinalysis Protocol

PubMed Central

Chu-Su, Yu; Shukuya, Kenichi; Yokoyama, Takashi; Lin, Wei-Chou; Chiang, Chih-Kang; Lin, Chii-Wann

2017-01-01

Urinary sediment is used to evaluate patients with possible urinary tract diseases. Currently, numerous protocols are applied to detect dysmorphic red blood cells (RBCs) and renal tubular epithelial cells (RTECs) in urinary sediment. However, distinct protocols are used by nephrologists and medical technologists for specimen concentration and observation, which leads to major discrepancies in the differential counts of formed elements such as dysmorphic RBCs and RTECs and might interfere with an accurate clinical diagnosis. To resolve these problems, we first tested a modified urinalysis protocol with an increased relative centrifuge force and concentration factor in 20 biopsy-confirmed glomerulonephritis patients with haematuria. We successfully improved the recovery ratio of dysmorphic RBCs in clinical specimens from 34.7% to 42.0% (P < 0.001). Furthermore, we confirmed the correlation between counts by the modified urinary protocol and Sysmex UF-1000i urinary flow cytometer (r ≥ 0.898, P < 0.001). A total of 28 types of isomorphic and dysmorphic RBCs were detected using a bright field microscope, with results comparable to those using a standard phase contrast microscope. Finally, we applied Sternheimer stain to enhance the contrast of RTECs in the urinary sediments. We concluded that this modified urinalysis protocol significantly enhanced the quality of urinalysis. PMID:28074941

Fatigue Behavior of Computer-Aided Design/Computer-Assisted Manufacture Ceramic Abutments as a Function of Design and Ceramics Processing.

PubMed

Kelly, J Robert; Rungruanganunt, Patchnee

2016-01-01

Zirconia is being widely used, at times apparently by simply copying a metal design into ceramic. Structurally, ceramics are sensitive to both design and processing (fabrication) details. The aim of this work was to examine four computer-aided design/computer-assisted manufacture (CAD/CAM) abutments using a modified International Standards Organization (ISO) implant fatigue protocol to determine performance as a function of design and processing. Two full zirconia and two hybrid (Ti-based) abutments (n = 12 each) were tested wet at 15 Hz at a variety of loads to failure. Failure probability distributions were examined at each load, and when found to be the same, data from all loads were combined for lifetime analysis from accelerated to clinical conditions. Two distinctly different failure modes were found for both full zirconia and Ti-based abutments. One of these for zirconia has been reported clinically in the literature, and one for the Ti-based abutments has been reported anecdotally. The ISO protocol modification in this study forced failures in the abutments; no implant bodies failed. Extrapolated cycles for 10% failure at 70 N were: full zirconia, Atlantis 2 × 10(7) and Straumann 3 × 10(7); and Ti-based, Glidewell 1 × 10(6) and Nobel 1 × 10(21). Under accelerated conditions (200 N), performance differed significantly: Straumann clearly outperformed Astra (t test, P = .013), and the Glidewell Ti-base abutment also outperformed Atlantis zirconia at 200 N (Nobel ran-out; t test, P = .035). The modified ISO protocol in this study produced failures that were seen clinically. The manufacture matters; differences in design and fabrication that influence performance cannot be discerned clinically.

[Evaluation of sensitization to Der p 1 and Der p 2 in a pediatric population of the North of Portugal].

PubMed

Peixoto, Sara; Soares, Joana; Monteiro, Tânia; Carvalho, Marisa; Santos, Marinela; Simões, Carla; Quaresma, Márcia

2017-12-28

In Portugal, data on the role of Der p 1 and Der p 2 in patients with house dust mite (HDM) allergy are scarce. Allergen-specific immunotherapy (sIT) is the only treatment that improves symptoms, reduces the need for pharmacological therapy and modifies the natural history of the disease. With this study, the authors aim to understand the local epidemiology and to clarify if the molecular assay of major allergens is advantageous in deciding and/or modifying the decision to initiate sIT in children with clinical indication which are sensitized to Dermatophagoides pteronyssinus. Retrospective study with analysis of patients with asthma and/or rhinitis. January/2013-December/2016. 1) positive prick-test to Dermatophagoides pteronyssinus; and 2) clinically relevant disease under treatment. Assay Der p 1 and Der p 2 values ≥0.35 kUA/L were considered positive. Statistical significance was set at P<.05. The clinical files of 279 patients. Mean ages 9.55 years (min.4-max.17). Asthma was present in 199 children (71.3%) and rhinitis in 245 (87.8%). Der p 1 and Der p 2 was <0.35kUA/L in 29 (10,4%) patients. The value of Der p 1/Der p 2 correlated with the size of the prick-test papule, the value of the eosinophils and the total IgE. Der p 1 and Der p 2 are dominant allergens in our population and there may be benefits in determining these molecular allergen levels in patients with a positive prick-test and a clinical indication for sIT prior to a decision of initiating sIT or not. Copyright © 2017. Publicado por Elsevier España, S.L.U.

Assessment of sedation level for endoscopic retrograde cholangiopancreatography - a prospective validation study.

PubMed

Jokelainen, Jarno; Mustonen, Harri; Kylänpää, Leena; Udd, Marianne; Lindström, Outi; Pöyhiä, Reino

2018-03-01

There is no consensus on how to assess the depth of sedation for endoscopic retrograde cholangiopancreatography (ERCP). This study was carried out in order to evaluate different methods of assessment of depth of sedation: bispectral index (BiS), modified Richmond Agitation/Sedation Scale (mRASS), modified Ramsay Sedation Scale (mRSS) and modified Observer Assessment of Alertness and Sedation (mOAAS) and their applicability to clinical practice. Two hundred patients were recruited. Sedation was given by standard clinical practice using propofol sedation or patient controlled sedation. Sedation was assessed on all patients using the above-mentioned methods. BiS was considered the reference point for sedation scales. Cronbach's alpha was calculated to determine the consistency of different scales in respect to each other and prediction probability and Spearman's correlation coefficients of sedation scales were calculated to show the relationship between sedation scales and BiS. All scales showed high reliability with overall Cronbach's alpha 0.943. Dropping scales suggested better consistency between mOAAS, mRSS and mRASS than with BiS. Spearman's correlation and prediction probability showed similar results with all tested scales: mOAAS (0.695, 0.739), mRSS (0.673, 0.735), mRASS (0.683, 0.738), p < .01 for all scales. All tested methods were found to be reliable in the assessment of the depth of sedation when compared with each other. However, mRASS, mRSS and mOAAS require the patient to respond to verbal or tactile stimulus, which may impair execution of ERCP, whereas BiS information is collected directly from electroencephalogram and thus may be preferable in clinical setting.

Evaluating a mobile application for improving clinical laboratory test ordering and diagnosis.

PubMed

Meyer, Ashley N D; Thompson, Pamela J; Khanna, Arushi; Desai, Samir; Mathews, Benji K; Yousef, Elham; Kusnoor, Anita V; Singh, Hardeep

2018-04-20

Mobile applications for improving diagnostic decision making often lack clinical evaluation. We evaluated if a mobile application improves generalist physicians' appropriate laboratory test ordering and diagnosis decisions and assessed if physicians perceive it as useful for learning. In an experimental, vignette study, physicians diagnosed 8 patient vignettes with normal prothrombin times (PT) and abnormal partial thromboplastin times (PTT). Physicians made test ordering and diagnosis decisions for 4 vignettes using each resource: a mobile app, PTT Advisor, developed by the Centers for Disease Control and Prevention (CDC)'s Clinical Laboratory Integration into Healthcare Collaborative (CLIHC); and usual clinical decision support. Then, physicians answered questions regarding their perceptions of the app's usefulness for diagnostic decision making and learning using a modified Kirkpatrick Training Evaluation Framework. Data from 368 vignettes solved by 46 physicians at 7 US health care institutions show advantages for using PTT Advisor over usual clinical decision support on test ordering and diagnostic decision accuracy (82.6 vs 70.2% correct; P < .001), confidence in decisions (7.5 vs 6.3 out of 10; P < .001), and vignette completion time (3:02 vs 3:53 min.; P = .06). Physicians reported positive perceptions of the app's potential for improved clinical decision making, and recommended it be used to address broader diagnostic challenges. A mobile app, PTT Advisor, may contribute to better test ordering and diagnosis, serve as a learning tool for diagnostic evaluation of certain clinical disorders, and improve patient outcomes. Similar methods could be useful for evaluating apps aimed at improving testing and diagnosis for other conditions.

Management of Chronic Periodontitis Using Subgingival Irrigation of Ozonized Water: A Clinical and Microbiological Study.

PubMed

Issac, Annie V; Mathew, Jayan Jacob; Ambooken, Majo; Kachappilly, Arun Jose; Pk, Ajithkumar; Johny, Thomas; Vk, Linith; Samuel, Anju

2015-08-01

Adjunctive use of professional subgingival irrigation with scaling and root planing (SRP) has been found to be beneficial in eradicating the residual microorganisms in the pocket. To evaluate the effect of ozonized water subgingival irrigation on microbiologic parameters and clinical parameters namely Gingival index, probing pocket depth, and clinical attachment level. Thirty chronic periodontitis patients with probing pocket depth ≥6mm on at least one tooth on contra lateral sides of opposite arches were included in the study. The test sites were subjected to ozonized water subgingival irrigation with subgingival irrigation device fitted with a modified subgingival tip. Control sites were subjected to scaling and root planing only. The following clinical parameters were recorded initially and after 4 weeks at the test sites and control sites. Plaque Index, Gingival Index, probing pocket depth, clinical attachment level. Microbiologic sampling was done for the test at the baseline, after scaling, immediately after ozonized water subgingival irrigation and after 4 weeks. In control sites microbiologic sampling was done at the baseline, after scaling and after 4 weeks. The following observations were made after 4 weeks. The results were statistically analysed using independent t-test and paired t-test. Test sites showed a greater reduction in pocket depth and gain in clinical attachment compared to control sites. The total anaerobic counts were significantly reduced by ozonized water subgingival irrigation along with SRP compared to SRP alone. Ozonized water subgingival irrigation can improve the clinical and microbiological parameters in patients with chronic periodontitis when used as an adjunct to scaling and root planing.

The use of health status questionnaires in the management of chronic obstructive pulmonary disease patients in clinical practice.

PubMed

van der Molen, Thys; Diamant, Zuzana; Kocks, Jan Willem H; Tsiligianni, Ioanna G

2014-08-01

Current guidelines recommend chronic obstructive pulmonary disease (COPD) management based on symptoms or health status assessment and lung function parameters. However, COPD is a complex and heterogeneous disease that needs an individualized approach for proper disease management. A structured consultation including health status assessment tools, such as the Clinical COPD Questionnaire and the COPD Assessment Test should improve the quality of the consultation, providing more information than symptoms alone. Both questionnaires are designed to provide the clinician information enabling a more personalized disease approach and subsequent management. Although both Clinical COPD Questionnaire and COPD Assessment Test have good discriminate properties, their use as prognostic markers of severity and their ability to modify disease management has not yet been fully established. New studies are needed to further determine their value on several disease outcomes.

Effect of one-year water storage on the surface microhardness of resin-modified versus conventional glass-ionomer cements.

PubMed

Ellakuria, J; Triana, R; Mínguez, N; Soler, I; Ibaseta, G; Maza, J; García-Godoy, F

2003-06-01

Conventional and resin-modified glass-ionomer cements (GIC, RM-GIC) are available for clinical use as restorative materials or as liners and bases. This study was conducted to compare the effect of a 12-month storage period in water on the surface microhardness, measured in Vickers units (VH), between a GIC and a RM-GIC group and to determine if the addition of resins improved the GIC microhardness. VH microhardness was assessed in three GIC: Ketac-Fil, Ketac-Molar and Ketac-Silver (KF, KM, KS) and three RM-GIC: Photac-Fil, Fuji II LC and Vitremer (PF, FU, VI) stored in distilled water at 37 degrees C for 12 months. Measurements were taken at 1, 7, 15, 30, 90, 180 and 365 days. The statistical evaluation was done by means of one-way analysis of variance (ANOVA) and Tukey's multiple comparison tests. There are significant VH differences among the materials studied and within each material over storage time. GICs, except for KS, showed a higher VH throughout the study period. Among the RM-GIC, VI showed a significantly higher VH at 12 months than at 1 day. The VH of PF diminished in the final stage of the study, whereas that of FU stabilized. The results suggest that the addition of resins to the GIC did not appear to improve the surface microhardness of these materials. Furthermore, the surface microhardness of both the conventional and resin-modified glass-ionomers suffered variations over time. However, these materials should not be deemed inadequate for use in clinical applications. Probably, conventional and resin-modified GICs placed in the oral environment would not be affected to the same extent as in in vitro tests.

[The maximum heart rate in the exercise test: the 220-age formula or Sheffield's table?].

PubMed

Mesquita, A; Trabulo, M; Mendes, M; Viana, J F; Seabra-Gomes, R

1996-02-01

To determine in the maximum cardiac rate in exercise test of apparently healthy individuals may be more properly estimated through 220-age formula (Astrand) or the Sheffield table. Retrospective analysis of clinical history and exercises test of apparently healthy individuals submitted to cardiac check-up. Sequential sampling of 170 healthy individuals submitted to cardiac check-up between April 1988 and September 1992. Comparison of maximum cardiac rate of individuals studied by the protocols of Bruce and modified Bruce, in interrupted exercise test by fatigue, and with the estimated values by the formulae: 220-age versus Sheffield table. The maximum cardiac heart rate is similar with both protocols. This parameter in normal individuals is better predicted by the 220-age formula. The theoretic maximum cardiac heart rate determined by 220-age formula should be recommended for a healthy, and for this reason the Sheffield table has been excluded from our clinical practice.

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

PubMed Central

Arnold, Mark; Bakris, George L.; Bruns, David E.; Horvath, Andrea Rita; Kirkman, M. Sue; Lernmark, Ake; Metzger, Boyd E.; Nathan, David M.

2011-01-01

BACKGROUND Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. APPROACH An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association. CONTENT In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A1c (HbA1c) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of HbA1c. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. SUMMARY The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended. PMID:21617108

ACCF/ASNC appropriateness criteria for single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI): a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group and the American Society of Nuclear Cardiology endorsed by the American Heart Association.

PubMed

Brindis, Ralph G; Douglas, Pamela S; Hendel, Robert C; Peterson, Eric D; Wolk, Michael J; Allen, Joseph M; Patel, Manesh R; Raskin, Ira E; Hendel, Robert C; Bateman, Timothy M; Cerqueira, Manuel D; Gibbons, Raymond J; Gillam, Linda D; Gillespie, John A; Hendel, Robert C; Iskandrian, Ami E; Jerome, Scott D; Krumholz, Harlan M; Messer, Joseph V; Spertus, John A; Stowers, Stephen A

2005-10-18

Under the auspices of the American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC), an appropriateness review was conducted for radionuclide cardiovascular imaging (RNI), specifically gated single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI). The review assessed the risks and benefits of the imaging test for several indications or clinical scenarios and scored them based on a scale of 1 to 9, where the upper range (7 to 9) implies that the test is generally acceptable and is a reasonable approach, and the lower range (1 to 3) implies that the test is generally not acceptable and is not a reasonable approach. The mid range (4 to 6) implies that the test may be generally acceptable and may be a reasonable approach for the indication. The indications for this review were primarily drawn from existing clinical practice guidelines and modified based on discussion by the ACCF Appropriateness Criteria Working Group and the Technical Panel members who rated the indications. The method for this review was based on the RAND/UCLA approach for evaluating appropriateness, which blends scientific evidence and practice experience. A modified Delphi technique was used to obtain first- and second-round ratings of 52 clinical indications. The ratings were done by a Technical Panel with diverse membership, including nuclear cardiologists, referring physicians (including an echocardiographer), health services researchers, and a payer (chief medical officer). These results are expected to have a significant impact on physician decision making and performance, reimbursement policy, and future research directions. Periodic assessment and updating of criteria will be undertaken as needed.

Urine Toxicology in Adults Evaluated for a Central Hypersomnia and How the Results Modify the Physician's Diagnosis.

PubMed

Kosky, Christopher A; Bonakis, Anastasios; Yogendran, Arthee; Hettiarachchi, Gihan; Dargan, Paul I; Williams, Adrian J

2016-11-15

Drugs and psychoactive substances can cause sleepiness and when undetected, may lead to over diagnosis of central hypersomnias. We performed urine drug testing using gas chromatography-mass spectrometry in adults undergoing multiple sleep latency testing (MSLT) for a suspected central hypersomnia. We examined how the drug test results modified the treating physician's diagnosis. One hundred eighty-six consecutive patients with a suspected central hypersomnia who underwent clinical assessment, MSLT and urine drug testing by gas chromatography-mass spectrometry were retrospectively studied. Physicians made a diagnosis after clinical assessment and MSLT and were initially blinded to the urine drug test results. A third of patients assessed for subjective hypersomnia had a positive urine drug test for a substance affecting sleep. Opioids, cannabis, and amphetamines were the commonest drugs detected. Using MSLT, 35 (18.8%) of 186 patients had objective hypersomnia that may have been due to a drug or substance. Drugs or substances may have confounded the MSLT in 11 (20.1%) of 53 patients who fulfilled diagnostic criteria for idiopathic hypersomnia, and 12 (52%) of 23 of those who fulfilled diagnostic criteria for narcolepsy without cataplexy. Of the 75 positive urine drug samples, 61 (81%) were substances or medications not revealed in the physician interview. The treating physician had not suspected drugs or substances as a possible cause of objective hypersomnia in 34 (97%) of the 35 patients. Drugs and psychoactive substances can confound the results of the MSLT and when undetected could lead to over diagnosis of central hypersomnias. © 2016 American Academy of Sleep Medicine

[Effect of a surgical mask on six minute walking distance].

PubMed

Person, E; Lemercier, C; Royer, A; Reychler, G

2018-03-01

Six minutes walking test (6MWT) is regularly used in pulmonology. To minimize the risk of cross-infection, some patients must wear surgical mask at rest and sometimes during exercise. To evaluate the effect of wearing a surgical mask during 6MWT in healthy subjects. It is a prospective study on 44 healthy subjects. After a first 6MWT for training, they performed randomly two 6MWT: with or without a surgical mask. Distance and dyspnea, heart rate and saturation variations were recorded. Distance was not modified by the mask (P=0.99). Dyspnea variation was significantly higher with surgical mask (+5.6 vs. +4.6; P<0.001) and the difference was clinically relevant. No difference was found for the variation of other parameters. Wearing a surgical mask modifies significantly and clinically dyspnea without influencing walked distance. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Direct pulp capping in primary molars using a resin-modified Portland cement-based material (TheraCal) compared to MTA with 12-month follow-up: a randomised clinical trial.

PubMed

Erfanparast, L; Iranparvar, P; Vafaei, A

2018-05-16

This study was to compare the success of resin-modified Portland cement-based material (TheraCal) with MTA in direct pulp capping (DPC) of primary molars. Symmetrical bilateral primary molars (92) from 46 healthy subjects aged 5-7 years were included in this split-mouth randomised clinical trial. DPC for small non-contaminated pulp exposures using either TheraCal or MTA were randomly performed in symmetrical molars. Thereafter, teeth were restored with amalgam. Clinical and radiographic evaluations were performed at 6 and 12 month follow-ups. Data were analysed using Chi square test at a significance level of 0.05. At the final follow-up session 74 teeth were available. After 12 months, the overall success rates for MTA and TheraCal were 94.5 and 91.8%, respectively. The difference between outcomes of the two groups was not statistically significant (P > 0.05). Within the limitations of the current study, radiographic and clinical findings revealed that TheraCal exhibited a comparable outcome to MTA in DPC of primary molars after 12 months.

How to apply clinical cases and medical literature in the framework of a modified "failure mode and effects analysis" as a clinical reasoning tool--an illustration using the human biliary system.

PubMed

Wong, Kam Cheong

2016-04-06

Clinicians use various clinical reasoning tools such as Ishikawa diagram to enhance their clinical experience and reasoning skills. Failure mode and effects analysis, which is an engineering methodology in origin, can be modified and applied to provide inputs into an Ishikawa diagram. The human biliary system is used to illustrate a modified failure mode and effects analysis. The anatomical and physiological processes of the biliary system are reviewed. Failure is defined as an abnormality caused by infective, inflammatory, obstructive, malignancy, autoimmune and other pathological processes. The potential failures, their effect(s), main clinical features, and investigation that can help a clinician to diagnose at each anatomical part and physiological process are reviewed and documented in a modified failure mode and effects analysis table. Relevant medical and surgical cases are retrieved from the medical literature and weaved into the table. A total of 80 clinical cases which are relevant to the modified failure mode and effects analysis for the human biliary system have been reviewed and weaved into a designated table. The table is the backbone and framework for further expansion. Reviewing and updating the table is an iterative and continual process. The relevant clinical features in the modified failure mode and effects analysis are then extracted and included in the relevant Ishikawa diagram. This article illustrates an application of engineering methodology in medicine, and it sows the seeds of potential cross-pollination between engineering and medicine. Establishing a modified failure mode and effects analysis can be a teamwork project or self-directed learning process, or a mix of both. Modified failure mode and effects analysis can be deployed to obtain inputs for an Ishikawa diagram which in turn can be used to enhance clinical experiences and clinical reasoning skills for clinicians, medical educators, and students.

Three-year rabies duration of immunity in dogs following vaccination with a core combination vaccine against canine distemper virus, canine adenovirus type-1, canine parvovirus, and rabies virus.

PubMed

Lakshmanan, Nallakannu; Gore, Thomas C; Duncan, Karen L; Coyne, Michael J; Lum, Melissa A; Sterner, Frank J

2006-01-01

Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV, and killed rabies virus vaccine. An additional 31 seronegative pups served as age-matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years after receiving the second vaccination and then were challenged with virulent rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32 vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies infection. These study results indicated that no immunogenic interference occurred between the modified-live vaccine components and the killed rabies virus component. Furthermore, these results indicated that the rabies component in the test vaccine provided protection against virulent rabies challenge in dogs 12 weeks of age or older for a minimum of 3 years following vaccination.

Genetic advances in sarcomeric cardiomyopathies: state of the art.

PubMed

Ho, Carolyn Y; Charron, Philippe; Richard, Pascale; Girolami, Francesca; Van Spaendonck-Zwarts, Karin Y; Pinto, Yigal

2015-04-01

Genetic studies in the 1980s and 1990s led to landmark discoveries that sarcomere mutations cause both hypertrophic and dilated cardiomyopathies. Sarcomere mutations also likely play a role in more complex phenotypes and overlap cardiomyopathies with features of hypertrophy, dilation, diastolic abnormalities, and non-compaction. Identification of the genetic cause of these important conditions provides unique opportunities to interrogate and characterize disease pathogenesis and pathophysiology, starting from the molecular level and expanding from there. With such insights, there is potential for clinical translation that may transform management of patients and families with inherited cardiomyopathies. If key pathways for disease development can be identified, they could potentially serve as targets for novel disease-modifying or disease-preventing therapies. By utilizing gene-based diagnostic testing, we can identify at-risk individuals prior to the onset of clinical disease, allowing for disease-modifying therapy to be initiated early in life, at a time that such treatment may be most successful. In this section, we review the current application of genetics in clinical management, focusing on hypertrophic cardiomyopathy as a paradigm; discuss state-of-the-art genetic testing technology; review emerging knowledge of gene expression in sarcomeric cardiomyopathies; and discuss both the prospects, as well as the challenges, of bringing genetics to medicine. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.

PubMed

Volz, A; Sutter, G

2017-01-01

Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.

Reliability of Performance-Based Clinical Measurements to Assess Shoulder Girdle Kinematics and Positioning: Systematic Review.

PubMed

D'hondt, Norman E; Kiers, Henri; Pool, Jan J M; Hacquebord, Sijmen T; Terwee, Caroline B; Veeger, Dirkjan H E J

2017-01-01

Deviant shoulder girdle movement is suggested as an eminent factor in the etiology of shoulder pain. Reliable measurements of shoulder girdle kinematics are a prerequisite for optimizing clinical management strategies. The purpose of this study was to evaluate the reliability, measurement error, and internal consistency of measurements with performance-based clinical tests for shoulder girdle kinematics and positioning in patients with shoulder pain. The MEDLINE, Embase, CINAHL, and SPORTDiscus databases were systematically searched from inception to August 2015. Articles published in Dutch, English, or German were included if they involved the evaluation of at least one of the measurement properties of interest. Two reviewers independently evaluated the methodological quality per studied measurement property with the 4-point-rating scale of the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) checklist, extracted data, and assessed the adequacy of the measurement properties. Forty studies comprising more than 30 clinical tests were included. Actual reported measurements of the tests were categorized into: (1) positional measurement methods, (2) measurement methods to determine dynamic characteristics, and (3) tests to diagnose impairments of shoulder girdle function. Best evidence synthesis of the tests was performed per measurement for each measurement property. All studies had significant limitations, including incongruence between test description and actual reported measurements and a lack of reporting on minimal important change. In general, the methodological quality of the selected studies was fair to poor. High-quality evidence indicates that measurements obtained with the Modified Scapular Assistance Test are not reliable for clinical use. Sound recommendations for the use of other tests could not be made due to inadequate evidence. Across studies, diversity in description, performance, and interpretation of similar tests was present, and different criteria were used to establish similar diagnoses, mostly without taking into account a clinically meaningful context. Consequently, these tests lack face validity, which hampers their clinical use. Further research on validity and how to integrate a clinically meaningful context of movement into clinical tests is warranted. © 2017 American Physical Therapy Association

Development and validation of an instrument to measure nurse educator perceived confidence in clinical teaching.

PubMed

Nguyen, Van N B; Forbes, Helen; Mohebbi, Mohammadreza; Duke, Maxine

2017-12-01

Teaching nursing in clinical environments is considered complex and multi-faceted. Little is known about the role of the clinical nurse educator, specifically the challenges related to transition from clinician, or in some cases, from newly-graduated nurse to that of clinical nurse educator, as occurs in developing countries. Confidence in the clinical educator role has been associated with successful transition and the development of role competence. There is currently no valid and reliable instrument to measure clinical nurse educator confidence. This study was conducted to develop and psychometrically test an instrument to measure perceived confidence among clinical nurse educators. A multi-phase, multi-setting survey design was used. A total of 468 surveys were distributed, and 363 were returned. Data were analyzed using exploratory and confirmatory factor analyses. The instrument was successfully tested and modified in phase 1, and factorial validity was subsequently confirmed in phase 2. There was strong evidence of internal consistency, reliability, content, and convergent validity of the Clinical Nurse Educator Skill Acquisition Assessment instrument. The resulting instrument is applicable in similar contexts due to its rigorous development and validation process. © 2017 The Authors. Nursing & Health Sciences published by John Wiley & Sons Australia, Ltd.

Windows of Opportunity for Lifestyle Interventions to Prevent Gestational Diabetes Mellitus

PubMed Central

Phelan, Suzanne

2017-01-01

Gestational diabetes mellitus (GDM) is linked with several acute maternal health risks and long-term development of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM similarly increases offspring risk of early life health complications and later disease. GDM recurrence is common, affecting 40–73% of women, and augments associated maternal/fetal/child health risks. Modifiable and independent risk factors for GDM include maternal excessive gestational weight gain and pre-pregnancy overweight and obesity. Lifestyle interventions that target diet, activity, and behavioral strategies can effectively modify adiposity. Randomized clinical trials testing the effects of lifestyle interventions during pregnancy to reduce excessive gestational weight gain have generally shown mixed effects on reducing GDM incidence. Trials testing the effects of postpartum lifestyle interventions among women with a history of GDM have shown reduced incidence of diabetes and improved cardiovascular disease risk factors. However, the long-term effects of inter-pregnancy or pre-pregnancy lifestyle interventions on subsequent GDM remain unknown. Future adequately powered and well-controlled clinical trials are needed to determine the effects of lifestyle interventions to prevent GDM and identify pathways to effectively reach reproductive-aged women across all levels of society, before, during, and after pregnancy. PMID:27487229

Short term clinical effectiveness of a 0.07% cetylpyridinium chloride mouth rinse in patients undergoing fixed orthodontic appliance treatment

PubMed Central

Pahwa, Narinder; Kumar, Atul; Gupta, Siddharth

2011-01-01

Objectives To test the short term clinical effectiveness of commercially available 0.07%.cetylpyridinium chloride mouth rinse in patients undergoing fixed orthodontic treatment as compared to a placebo mouth rinse and patients using toothbrush and toothpaste. Method Forty-five subjects for this double blind study were assigned randomly into three groups of 15 each. Gingival inflammation, plaque accumulation, and bleeding on probing, were recorded at baseline (10 days after prophylaxis), and at the end of one month in all the three groups and compared. Results Paired t test showed significant differences in bleeding index for pre and post treatment recordings for cetylpyridinium group. Modified gingival index showed no significant difference in the cetylpyridinium group. For plaque index significant difference was found for cetylpyridinium and control groups. Conclusion Cetylpyridinium mouth rinse 0.7% was found to be effective in reducing the bleeding and plaque index scores. It was not effective in reducing the modified gingival index scores. Cetylpyridinium mouth rinse 0.07% improves the oral hygiene of orthodontic patients when used as an adjunct to normal oral hygiene measures. PMID:23960507

Composition of a Vision Screen for Servicemembers With Traumatic Brain Injury: Consensus Using a Modified Nominal Group Technique

PubMed Central

Finkelstein, Marsha; Llanos, Imelda; Scheiman, Mitchell; Wagener, Sharon Gowdy

2014-01-01

Vision impairment is common in the first year after traumatic brain injury (TBI), including among service members whose brain injuries occurred during deployment in Iraq and Afghanistan. Occupational therapy practitioners provide routine vision screening to inform treatment planning and referral to vision specialists, but existing methods are lacking because many tests were developed for children and do not screen for vision dysfunction typical of TBI. An expert panel was charged with specifying the composition of a vision screening protocol for servicemembers with TBI. A modified nominal group technique fostered discussion and objective determinations of consensus. After considering 29 vision tests, the panel recommended a nine-test vision screening that examines functional performance, self-reported problems, far–near acuity, reading, accommodation, convergence, eye alignment and binocular vision, saccades, pursuits, and visual fields. Research is needed to develop reliable, valid, and clinically feasible vision screening protocols to identify TBI-related vision disorders in adults. PMID:25005505

Gelatin modified lipid nanoparticles for anti- viral drug delivery.

PubMed

K S, Joshy; S, Snigdha; Kalarikkal, Nandakumar; Pothen, Laly A; Thomas, Sabu

2017-10-01

The major challenges to clinical application of zidovudine are its moderate aqueous solubility and relative short half-life and serious side effects due to frequent administrations. We investigated the preparation of zidovudine-loaded nanoparticles based on lipids which were further modified with the polymer gelatin. Formulation and stability of the modified nanoparticles were analysed from the physico-chemical characterizations. The interactions of nanoparticles with blood components were tested by haemolysis and aggregation studies. The drug content and entrapment efficiencies were assessed by UV analysis. The effect of nanoparticles on protein adsorption was assessed by native polyacrylamide gel electrophoresis (PAGE). In vitro release studies showed a sustained release profile of zidovudine. In vitro cytotoxicity and cellular uptake of the zidovudine-loaded nanoparticles were performed in MCF-7 and neuro 2a brain cells. The enhanced cellular internalization of drug loaded modified nanoparticles in both the cell lines were revealed by fluorescence microscopy. Hence the present study focuses on the feasibility of zidovudine-loaded polymer modified lipid nanoparticles as carriers for safe and efficient HIV/AIDS therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of Chronic Periodontitis Using Subgingival Irrigation of Ozonized Water: A Clinical and Microbiological Study

PubMed Central

Mathew, Jayan Jacob; Ambooken, Majo; Kachappilly, Arun Jose; PK, Ajithkumar; Johny, Thomas; VK, Linith; Samuel, Anju

2015-01-01

Introduction Adjunctive use of professional subgingival irrigation with scaling and root planing (SRP) has been found to be beneficial in eradicating the residual microorganisms in the pocket. Objective To evaluate the effect of ozonized water subgingival irrigation on microbiologic parameters and clinical parameters namely Gingival index, probing pocket depth, and clinical attachment level. Materials and Methods Thirty chronic periodontitis patients with probing pocket depth ≥6mm on at least one tooth on contra lateral sides of opposite arches were included in the study. The test sites were subjected to ozonized water subgingival irrigation with subgingival irrigation device fitted with a modified subgingival tip. Control sites were subjected to scaling and root planing only. The following clinical parameters were recorded initially and after 4 weeks at the test sites and control sites. Plaque Index, Gingival Index, probing pocket depth, clinical attachment level. Microbiologic sampling was done for the test at the baseline, after scaling, immediately after ozonized water subgingival irrigation and after 4 weeks. In control sites microbiologic sampling was done at the baseline, after scaling and after 4 weeks. The following observations were made after 4 weeks. The results were statistically analysed using independent t-test and paired t-test. Result Test sites showed a greater reduction in pocket depth and gain in clinical attachment compared to control sites. The total anaerobic counts were significantly reduced by ozonized water subgingival irrigation along with SRP compared to SRP alone. Conclusion Ozonized water subgingival irrigation can improve the clinical and microbiological parameters in patients with chronic periodontitis when used as an adjunct to scaling and root planing. PMID:26436042

Evaluation of a novel supplement to reduce blood glucose through the use of a modified oral glucose tolerance test

PubMed Central

Smith, Adam J; Giunta, Brian; Shytle, R Douglas; Blum, James M

2011-01-01

Elevated blood glucose is a major component in metabolic syndrome and pre-diabetes, sometimes leading to type 2 diabetes mellitus (DM II). Additionally, it may lead to adipose deposits when left elevated for long periods. The epidemiology of DM II clearly shows that uncontrolled blood glucose levels leads to many adverse conditions including heart disease, retinal damage, renal failure, erectile dysfunction, and other significant medical conditions. Here we conducted a single-center, prospective, randomized, double-blinded, placebo-controlled, parallel-group- clinical trial of a nutraceutical supplement vs. placebo to measure its glucose lowering effect in generally healthy adults before and after a simple sugars meal. Subjects reported to the test clinic on multiple days to receive placebo or treatment, a simple sugars meal, as well as pre-and postprandial blood glucose measurement (modified oral glucose tolerance test). Each subject served as his or her own control and thirty-one subjects completed the trial with at least one oral glucose tolerance test (OGTT) with the nutraceutical supplement and placebo. Statistical analysis revealed the nutraceutical supplement significantly lowered postprandial glucose levels by 36% and 59% at 45 and 60 minutes, respectively (***P<.001). The study was limited by its composition of primarily overweight females. Future studies will be required over longer periods in more heterogeneous and larger groups to determine the long-term effect of this supplement on blood glucose levels in terms of prophylaxis or treatment for DM II. PMID:21416063

Modification of two capripoxvirus quantitative real-time PCR assays to improve diagnostic sensitivity and include beta-actin as an internal positive control.

PubMed

Das, Amaresh; Deng, Ming Y; Babiuk, Shawn; McIntosh, Michael T

2017-05-01

Capripoxviruses (CaPVs), consisting of Sheeppox virus (SPV), Goatpox virus (GPV), and Lumpy skin disease virus (LSDV) species, cause economically significant diseases in sheep, goats, and cattle, respectively. Quantitative real-time polymerase chain reaction (qPCR) assays are routinely used for rapid detection of CaPVs in surveillance and outbreak management programs. We further modified and optimized 2 previously published CaPV qPCR assays, referred to as the Balinsky and Bowden assays, by changing commercial PCR reagents used in the tests. The modified assays displayed 100% analytical specificity and showed no apparent changes in analytical sensitivities for detection of CaPVs compared with the original assays. Diagnostic sensitivities, assessed using 50 clinical reference samples from experimentally infected sheep, goats, and cattle, improved from 82% to 92% for the modified Balinsky assay and from 58% to 82% for the modified Bowden assay. The modified qPCR assays were multiplexed for detection of beta-actin as an indicator for potential false-negative results. The multiplex modified qPCR assays exhibited the same diagnostic sensitivities as the singleplex assays suggesting their utility in the detection of CaPVs.

Correlating In Vitro Splice Switching Activity With Systemic In Vivo Delivery Using Novel ZEN-modified Oligonucleotides.

PubMed

Hammond, Suzan M; McClorey, Graham; Nordin, Joel Z; Godfrey, Caroline; Stenler, Sofia; Lennox, Kim A; Smith, C I Edvard; Jacobi, Ashley M; Varela, Miguel A; Lee, Yi; Behlke, Mark A; Wood, Matthew J A; Andaloussi, Samir E L

2014-11-25

Splice switching oligonucleotides (SSOs) induce alternative splicing of pre-mRNA and typically employ chemical modifications to increase nuclease resistance and binding affinity to target pre-mRNA. Here we describe a new SSO non-base modifier (a naphthyl-azo group, "ZEN™") to direct exon exclusion in mutant dystrophin pre-mRNA to generate functional dystrophin protein. The ZEN modifier is placed near the ends of a 2'-O-methyl (2'OMe) oligonucleotide, increasing melting temperature and potency over unmodified 2'OMe oligonucleotides. In cultured H2K cells, a ZEN-modified 2'OMe phosphorothioate (PS) oligonucleotide delivered by lipid transfection greatly enhanced dystrophin exon skipping over the same 2'OMePS SSO lacking ZEN. However, when tested using free gymnotic uptake in vitro and following systemic delivery in vivo in dystrophin deficient mdx mice, the same ZEN-modified SSO failed to enhance potency. Importantly, we show for the first time that in vivo activity of anionic SSOs is modelled in vitro only when using gymnotic delivery. ZEN is thus a novel modifier that enhances activity of SSOs in vitro but will require improved delivery methods before its in vivo clinical potential can be realized.

Chemically modified tetracyclines an emerging host modulator in chronic periodontitis patients: A randomized, double-blind, placebo-controlled, clinical trial.

PubMed

Alyousef, Abdullah A; Divakar, Darshan Devang; Muzaheed

2017-09-01

Although periodontal diseases are caused by some of the specific pathogens, most of the tissue damage is caused by the host reaction to disease and not actually by the infections. Therefore, host modulatory therapy (HMT) has advanced benefit for the treatment of periodontitis, which works basically by reducing tissue destruction and regeneration in periodontium by altering the critical aspects of host response regulation and up regulating defensive regenerative responses. The present study was conducted with the goal to test an innovative therapeutic option using chemically modified tetracycline in patients affected with generalized, moderate and severe chronic periodontitis. We assumed that CMT might have the potential to provoke an assessable clinical result and pharmacologically impede the level inflammatory flow. CMT (incyclinide) treated group had significantly higher CAL (clinical attachment) values than Placebo Control suggesting an improved CAL in CMT treatment. Host modulation therapy width incyclinide can be as an adjunct to conventional nonsurgical therapies without antimicrobial resistance. Progress was noticed in the clinical parameters but not the serum CRP level in our study establishing the role of CMTs in controlling chronic periodontitis. Also CMT treatment indicates its role in anti-inflammatory process as it inhibited IL-12 and TNF alpha but IL-10 level was not affected. However, more randomized placebo-controlled clinical trials with large sample size are required in order to authenticate the usage of CMTs in chronic periodontitis treatment. Based on this understanding, exploration of the novel, low-cost synthetic inhibitors that can be used as potential therapeutic agents, has been tested. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical Scenarios for Discordant Anti-Xa

PubMed Central

Vera-Aguilera, Jesus; Yousef, Hindi; Beltran-Melgarejo, Diego; Teng, Teng Hugh; Jan, Ramos; Mok, Mary; Vera-Aguilera, Carlos; Moreno-Aguilera, Eduardo

2016-01-01

Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice. PMID:27293440

CAR T-cell therapy for glioblastoma: ready for the next round of clinical testing?

PubMed

Prinzing, Brooke L; Gottschalk, Stephen M; Krenciute, Giedre

2018-05-01

The outcome for patients with glioblastoma (GBM) remains poor, and there is an urgent need to develop novel therapeutic approaches. T cells genetically modified with chimeric antigen receptors (CARs) hold the promise to improve outcomes since they recognize and kill cells through different mechanisms than conventional therapeutics. Areas covered: This article reviews CAR design, tumor associated antigens expressed by GBMs that can be targeted with CAR T cells, preclinical and clinical studies conducted with CAR T cells, and genetic approaches to enhance their effector function. Expert commentary: While preclinical studies have highlighted the potent anti-GBM activity of CAR T cells, the initial foray of CAR T-cell therapies into the clinic resulted only in limited benefits for GBM patients. Additional genetic modification of CAR T cells has resulted in a significant increase in their anti-GBM activity in preclinical models. We are optimistic that clinical testing of these enhanced CAR T cells will be safe and result in improved anti-glioma activity in GBM patients.

The LIFE Cognition Study: design and baseline characteristics

PubMed Central

Sink, Kaycee M; Espeland, Mark A; Rushing, Julia; Castro, Cynthia M; Church, Timothy S; Cohen, Ronald; Gill, Thomas M; Henkin, Leora; Jennings, Janine M; Kerwin, Diana R; Manini, Todd M; Myers, Valerie; Pahor, Marco; Reid, Kieran F; Woolard, Nancy; Rapp, Stephen R; Williamson, Jeff D

2014-01-01

Observational studies have shown beneficial relationships between exercise and cognitive function. Some clinical trials have also demonstrated improvements in cognitive function in response to moderate–high intensity aerobic exercise; however, these have been limited by relatively small sample sizes and short durations. The Lifestyle Interventions and Independence for Elders (LIFE) Study is the largest and longest randomized controlled clinical trial of physical activity with cognitive outcomes, in older sedentary adults at increased risk for incident mobility disability. One LIFE Study objective is to evaluate the effects of a structured physical activity program on changes in cognitive function and incident all-cause mild cognitive impairment or dementia. Here, we present the design and baseline cognitive data. At baseline, participants completed the modified Mini Mental Status Examination, Hopkins Verbal Learning Test, Digit Symbol Coding, Modified Rey–Osterrieth Complex Figure, and a computerized battery, selected to be sensitive to changes in speed of processing and executive functioning. During follow up, participants completed the same battery, along with the Category Fluency for Animals, Boston Naming, and Trail Making tests. The description of the mild cognitive impairment/dementia adjudication process is presented here. Participants with worse baseline Short Physical Performance Battery scores (prespecified at ≤7) had significantly lower median cognitive test scores compared with those having scores of 8 or 9 with modified Mini Mental Status Examination score of 91 versus (vs) 93, Hopkins Verbal Learning Test delayed recall score of 7.4 vs 7.9, and Digit Symbol Coding score of 45 vs 48, respectively (all P<0.001). The LIFE Study will contribute important information on the effects of a structured physical activity program on cognitive outcomes in sedentary older adults at particular risk for mobility impairment. In addition to its importance in the area of prevention of cognitive decline, the LIFE Study will also likely serve as a model for exercise and other behavioral intervention trials in older adults. PMID:25210447

Novel end points for clinical trials in young children with cystic fibrosis.

PubMed

Simpson, Shannon J; Mott, Lauren S; Esther, Charles R; Stick, Stephen M; Hall, Graham L

2013-06-01

Cystic fibrosis (CF) lung disease commences early in the disease progression and is the most common cause of mortality. While new CF disease-modifying agents are currently undergoing clinical trial evaluation, the implementation of such trials in young children is limited by the lack of age-appropriate clinical trial end points. Advances in infant and preschool lung function testing, imaging of the chest and the development of biochemical biomarkers have led to increased possibility of quantifying mild lung disease in young children with CF and objectively monitoring disease progression over the course of an intervention. Despite this, further standardization and development of these techniques is required to provide robust objective measures for clinical trials in this age group.

Phase 1 clinical study of cyclophilin B peptide vaccine for patients with lung cancer.

PubMed

Gohara, Rumi; Imai, Nobue; Rikimaru, Toru; Yamada, Akira; Hida, Naoya; Ichiki, Masao; Kawamoto, Mayumi; Matsunaga, Kazuko; Ashihara, Junko; Yano, Sayoko; Tamura, Mayumi; Ohkouchi, Shinya; Yamana, Hideaki; Oizumi, Kotaro; Itoh, Kyogo

2002-01-01

Cyclophilin B (CypB) possesses two antigenic epitopes (CypB(84-92) and CypB(91-99) ) recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). To determine the safety of CypB-derived peptides and its ability to generate antitumor immune responses, patients with advanced lung cancer received subcutaneous vaccinations of these peptides or their modified peptides. All 16 patients were vaccinated with CypB(91-99) or its modified peptide, whereas only two patients were vaccinated with the modified CypB(84-92), as immediate-type hypersensitivity to CypB(84-92) or its modified peptide was observed in the remaining patients. No severe adverse events were associated with the vaccination. No significant increase in cellular responses to either peptides or tumor cells was observed in the postvaccination PBMCs by the conventional CTL assays in any patients tested. These results suggest that the vaccination of CypB(91-99) peptide was safe, but failed to induce objective immune responses at this regimen.

A modified Lowry protein test for dilute protein solutions

Treesearch

Garold F. Gregory; Keith F. Jensen

1971-01-01

A modified Lowry protein test for dilute protein solutions modified Lowry protein test was compared with the standard Lowry protein test. The modified test was found to give estimates of protein concentration that were as good as the standard test and has the advange that proteins can be measured in very dilute solutions.

What is needed to incorporate clinical pharmacogenetic tests into the practice of psychopharmacotherapy?

PubMed

de Leon, Jose; Spina, Edoardo

2016-01-01

This editorial considers two questions in psychopharmacotherapy: 1) What is needed to market pharmacogenetic tests in the US, since the US appears to lead other countries? and 2) What is needed for US-marketed pharmacogenetic tests to be incorporated by prescribers into long-term practice? US marketing of pharmacogenetic tests requires 1) understanding the pharmacological complexity of drug response, 2) modifying the oversight of non-FDA regulatory agencies, 3) clarifying the FDA's role and 4) promoting innovative marketing. The incorporation of pharmacogenetic tests into long-term practice requires 1) not jeopardizing pharmacogenetic testing by short-sighted marketing of non-validated tests, 2) educating prescribers about benefits, 3) educating patients about limitations and 4) considering the differences between isolated testing and generalized testing incorporating big data.

Developing Disease-Modifying Treatments in Alzheimer's Disease - A Perspective from Roche and Genentech.

PubMed

Doody, R

2017-01-01

Alzheimer's disease (AD) is a chronic neurodegenerative disease for which no preventative or disease-modifying treatments currently exist. Pathological hallmarks include amyloid plaques and neurofibrillary tangles composed of hyper-phosphorylated tau protein. Evidence suggests that both pathologies are self-propagating once established. However, the lag time between neuropathological changes in the brain and the onset of even subtle clinical symptomatology means that patients are often diagnosed late when pathology, and neurodegeneration secondary to these changes, may have been established for several years. Complex pathological pathways associated with susceptibility to AD and changes that occur downstream of the neuropathologic process further contribute to the challenging endeavour of developing novel disease-modifying therapy. Recognising this complexity, effective management of AD must include reliable screening and early diagnosis in combination with effective therapeutic management of the pathological processes. Roche and Genentech are committed to addressing these unmet needs through developing a comprehensive portfolio of diagnostics and novel therapies. Beginning with the most scientifically supported targets, this approach includes two targeted amyloid-β monoclonal antibody therapies, crenezumab and gantenerumab, and an anti-tau monoclonal antibody, RO7105705, as well as a robust biomarker platform to aid in the early identification of people at risk or in the early stages of AD. Identification and implementation of diagnostic tools will support the enrolment of patients into clinical trials; furthermore, these tools should also support evaluation of the clinical efficacy and safety profile of the novel therapeutic agents tested in these trials. This review discusses the therapeutic agents currently under clinical development.

Direct-to-consumer testing: more risks than opportunities.

PubMed

Lippi, G; Favaloro, E J; Plebani, M

2011-12-01

As a result of incessant genetic discoveries and remarkable technological advancements, the availability and the consequent consumer's request for genetic testing are growing exponentially, leading to the development of a 'parallel' market, i.e. the direct-to-consumer (DTC) testing, also known as 'direct access testing' (DAT). Analogous to the traditional laboratory diagnostics, drawbacks of DTC testing might arise from any step characterising the total testing process, and include poor control of both appropriateness and preanalytical requirements, potential operation outside national or international regulation for in vitro diagnostic testing, little evidence of quality as well as the risk of transfer of genetic materials from the companies to other entities. Another important issue is the test panels offered to consumers, which are often based on preliminary, speculative or unsupported scientific information. Finally, the potential of this type of testing to generate anxiety or false reassurance should also be carefully considered. Although DTC testing carries some theoretical advantages (e.g. greater consumer autonomy and empowerment), solid clinical studies and costs vs. benefit analyses are needed to definitely establish whether DTC testing might be effective for decreasing the burden of diseases, delay their onset or modify their progression and therefore the clinical outcome. © 2011 Blackwell Publishing Ltd.

Gram stain method shows better sensitivity than clinical criteria for detection of bacterial vaginosis in surveillance of pregnant, low-income women in a clinical setting.

PubMed Central

Tam, M T; Yungbluth, M; Myles, T

1998-01-01

OBJECTIVE: The purpose of the study is to determine whether the Gram stain method is superior to the clinical criteria for the diagnosis of bacterial vaginosis in low-income pregnant women seen in a resident clinic setting. The clinical criteria is the current diagnostic method employed to diagnose bacterial vaginosis. STUDY DESIGN: In this study, 51 pregnant women with vaginal discharge were prospectively evaluated. All were screened using the clinical criteria, Gram stain method, and culture of the discharge. The modified scoring system instituted by Nugent et al. (J Clin Microbiol 29:297-301, 1991) was employed in reading the Gram stain smears. The clinical criteria were then compared with the Gram stain method. Isolation of moderate to many Gardnerella vaginalis growth by culture was used as the confirmatory finding. RESULTS: Sensitivity of the Gram stain method (91%) was significantly higher than that of the clinical criteria (46%), (sign test P = 0.0023, < 0.01). The Gram stain method also has both a low false-negative (4%) and high negative predictive value (96%), making it an ideal diagnostic test. CONCLUSION: The Gram stain method is a rapid and cost-effective test that is also highly reproducible and readily available in many laboratories. These features make the Gram stain method a more desirable screening procedure for bacterial vaginosis in a clinic population. PMID:9894174

Design of clinical trials for therapeutic cancer vaccines development.

PubMed

Mackiewicz, Jacek; Mackiewicz, Andrzej

2009-12-25

Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

A comparison between modified Alvarado score and RIPASA score in the diagnosis of acute appendicitis.

PubMed

Singla, Anand; Singla, Satpaul; Singh, Mohinder; Singla, Deeksha

2016-12-01

Acute appendicitis is a common but elusive surgical condition and remains a diagnostic dilemma. It has many clinical mimickers and diagnosis is primarily made on clinical grounds, leading to the evolution of clinical scoring systems for pin pointing the right diagnosis. The modified Alvarado and RIPASA scoring systems are two important scoring systems, for diagnosis of acute appendicitis. We prospectively compared the two scoring systems for diagnosing acute appendicitis in 50 patients presenting with right iliac fossa pain. The RIPASA score correctly classified 88 % of patients with histologically confirmed acute appendicitis compared with 48.0 % with modified Alvarado score, indicating that RIPASA score is more superior to Modified Alvarado score in our clinical settings.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer

PubMed Central

Rybicki, BA; Kryvenko, ON; Wang, Y; Jankowski, M; Trudeau, S; Chitale, DA; Gupta, NS; Rundle, A; Tang, D

2016-01-01

BACKGROUND Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. METHODS Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I–III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). RESULTS Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR) = 0.47; 95% confidence interval (CI) = 0.27–0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR = 3.56; 95% CI = 1.15–10.99). Moreover, PSA velocity (P = 0.008) and frequency of PSA testing (P = 0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR = 2.97; 95% CI = 1.40–6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR = 1.91; 95% CI = 1.09–3.35). CONCLUSIONS In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing—suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection. PMID:26620738

Doxycycline-encapsulated nanotube-modified dentin adhesives.

PubMed

Feitosa, S A; Palasuk, J; Kamocki, K; Geraldeli, S; Gregory, R L; Platt, J A; Windsor, L J; Bottino, M C

2014-12-01

This article presents details of fabrication, biological activity (i.e., anti-matrix metalloproteinase [anti-MMP] inhibition), cytocompatibility, and bonding characteristics to dentin of a unique doxycycline (DOX)-encapsulated halloysite nanotube (HNT)-modified adhesive. We tested the hypothesis that the release of DOX from the DOX-encapsulated nanotube-modified adhesive can effectively inhibit MMP activity. We incorporated nanotubes, encapsulated or not with DOX, into the adhesive resin of a commercially available bonding system (Scotchbond Multi-Purpose [SBMP]). The following groups were tested: unmodified SBMP (control), SBMP with nanotubes (HNT), and DOX-encapsulated nanotube-modified adhesive (HNT+DOX). Changes in degree of conversion (DC) and microtensile bond strength were evaluated. Cytotoxicity was examined on human dental pulp stem cells (hDPSCs). To prove the successful encapsulation of DOX within the adhesives-but, more important, to support the hypothesis that the HNT+DOX adhesive would release DOX at subantimicrobial levels-we tested the antimicrobial activity of synthesized adhesives and the DOX-containing eluates against Streptococcus mutans through agar diffusion assays. Anti-MMP properties were assessed via β-casein cleavage assays. Increasing curing times (10, 20, 40 sec) led to increased DC values. There were no statistically significant differences (p > .05) in DC within each increasing curing time between the modified adhesives compared to SBMP. No statistically significant differences in microtensile bond strength were noted. None of the adhesives eluates were cytotoxic to the human dental pulp stem cells. A significant growth inhibition of S. mutans by direct contact illustrates successful encapsulation of DOX into the experimental adhesive. More important, DOX-containing eluates promoted inhibition of MMP-1 activity when compared to the control. Collectively, our findings provide a solid background for further testing of encapsulated MMP inhibitors into the synthesis of therapeutic adhesives that may enhance the longevity of hybrid layers and the overall clinical performance of adhesively bonded resin composite restorations. © International & American Associations for Dental Research.

Doxycycline-Encapsulated Nanotube-Modified Dentin Adhesives

PubMed Central

Feitosa, S.A.; Palasuk, J.; Kamocki, K.; Geraldeli, S.; Gregory, R.L.; Platt, J.A.; Windsor, L.J.; Bottino, M.C.

2014-01-01

This article presents details of fabrication, biological activity (i.e., anti–matrix metalloproteinase [anti-MMP] inhibition), cytocompatibility, and bonding characteristics to dentin of a unique doxycycline (DOX)–encapsulated halloysite nanotube (HNT)–modified adhesive. We tested the hypothesis that the release of DOX from the DOX-encapsulated nanotube-modified adhesive can effectively inhibit MMP activity. We incorporated nanotubes, encapsulated or not with DOX, into the adhesive resin of a commercially available bonding system (Scotchbond Multi-Purpose [SBMP]). The following groups were tested: unmodified SBMP (control), SBMP with nanotubes (HNT), and DOX-encapsulated nanotube-modified adhesive (HNT+DOX). Changes in degree of conversion (DC) and microtensile bond strength were evaluated. Cytotoxicity was examined on human dental pulp stem cells (hDPSCs). To prove the successful encapsulation of DOX within the adhesives—but, more important, to support the hypothesis that the HNT+DOX adhesive would release DOX at subantimicrobial levels—we tested the antimicrobial activity of synthesized adhesives and the DOX-containing eluates against Streptococcus mutans through agar diffusion assays. Anti-MMP properties were assessed via β-casein cleavage assays. Increasing curing times (10, 20, 40 sec) led to increased DC values. There were no statistically significant differences (p > .05) in DC within each increasing curing time between the modified adhesives compared to SBMP. No statistically significant differences in microtensile bond strength were noted. None of the adhesives eluates were cytotoxic to the human dental pulp stem cells. A significant growth inhibition of S. mutans by direct contact illustrates successful encapsulation of DOX into the experimental adhesive. More important, DOX-containing eluates promoted inhibition of MMP-1 activity when compared to the control. Collectively, our findings provide a solid background for further testing of encapsulated MMP inhibitors into the synthesis of therapeutic adhesives that may enhance the longevity of hybrid layers and the overall clinical performance of adhesively bonded resin composite restorations. PMID:25201918

Detection of anti-neutrophil antibodies in autoimmune neutropenia of infancy: a multicenter study.

PubMed

Sella, Ruti; Flomenblit, Lena; Goldstein, Itamar; Kaplinsky, Chaim

2010-02-01

Autoimmune neutropenia of infancy is caused by neutrophil-specific autoantibodies. Primary AIN is characterized by neutrophil count < 500 ml and a benign self-limiting course. Detecting specific antibodies against the polymorphic human neutrophil antigen usually confirms the diagnosis. Current available tests, however, are expensive and inapplicable in many laboratories as they require the use of isolated and fixed granulocytes obtained from donors pretyped for their distinct HNA alloform. To assess the performance of a modified test to identify by FACS-analysis granulocyte-specific antibodies in the sera of neutropenic children. We evaluated 120 children with a clinical suspicion of AIN, whose sera were analyzed by flow cytometry for the presence of autoantibodies using the indirect granulocyte immunofluorescence test. In contrast to the traditional tests, the sera were tested against randomly selected untyped neutrophils derived from a batch of 10 anonymous healthy subjects, presumably including the common HNA alloforms. Control sera samples were from patients with chemotherapy-induced, familial or congenital neutropenias. To further assure the quality of the new test, we retested six samples previously tested by the gold standard method. All medical files were screened and clinical outcomes were recorded. Our method showed specificity of 85%, sensitivity of 62.5%, and a positive predictive value of 91.8%, values quite similar to those obtained by more traditional methods. The new method showed high specificity for detection of anti-neutrophil antibodies in the appropriate clinical setting and could be an effective tool for clinical decision making.

Assessing emotional status following acquired brain injury: the clinical potential of the depression, anxiety and stress scales.

PubMed

Ownsworth, Tamara; Little, Trudi; Turner, Ben; Hawkes, Anna; Shum, David

2008-10-01

To investigate the clinical potential of the Depression, Anxiety and Stress Scales (DASS 42) and its shorter version (DASS 21) for assessing emotional status following acquired brain injury. Participants included 23 individuals with traumatic brain injury (TBI), 25 individuals with brain tumour and 29 non-clinical controls. Investigations of internal consistency, test-re-test reliability, theory-consistent differences, sensitivity to change and concurrent validity were conducted. Internal consistency of the DASS was generally acceptable (r > 0.70), with the exception of the anxiety scale for the TBI sample. Test-re-test reliability (1-3 weeks) was sound for the depression scale (r > 0.75) and significant but comparatively lower for other scales (r = 0.60-0.73, p < 0.01). Theory-consistent differences were only evident between the brain tumour sample and non-clinical control sample on the anxiety scale (p < 0.01). Sensitivity to change of the DASS in the context of hospital discharge was demonstrated for depression and stress (p < 0.01), but not for anxiety (p > 0.05). Concurrent validity with the Hospital Anxiety and Depression Scale was significant for all scales of the DASS (p < 0.05). While the results generally support the clinical application of the DASS following ABI, further research examining the factor structure of existing and modified versions of the DASS is recommended.

Modifiable Risk Factors for Attempted Suicide in Australian Clinical and Community Samples

ERIC Educational Resources Information Center

Carter, Gregory L.; Page, Andrew; Clover, Kerrie; Taylor, Richard

2007-01-01

Modifiable risk factors for suicide attempt require identification in clinical and community samples. The aim of this study was to determine if similar social and psychiatric factors are associated with suicide attempts in community and clinical settings and whether the magnitude of effect is greater in clinical populations. Two case-control…

Modifying the Curriculum: Teaching Clinical Students about Caring for Patients with Disabilities.

ERIC Educational Resources Information Center

Ettinger, Ellen Richter

2002-01-01

Examines how the curricula of optometry programs can be modified to prepare graduates to meet the needs of patients from special populations. Addresses student attitudes and the clinical encounter, including the case history, clinical examination, clinical decision making and determination of patient management plans, and case discussion of the…

One year duration of immunity of the modified live bovine viral diarrhea virus type 1 and type 2 and bovine herpesvirus-1 fractions of Vista® Once SQ vaccine.

PubMed

Purtle, Lisa; Mattick, Debra; Schneider, Corey; Smith, Linda; Xue, Wenzhi; Trigo, Emilio

2016-03-18

Three studies were performed to determine the duration of immunity of the bovine viral diarrhea virus type 1 and type 2 (BVDV-1 and BVDV-2) and bovine herpesvirus-1 (BHV-1) fractions of a commercially prepared modified-live vaccine. Vista® Once SQ (Vista®) vaccine contains five modified-live viruses, BVDV-1, BVDV-2, BHV-1, bovine respiratory syncytial virus, and bovine parainfluenza 3 virus, and two modified-live bacteria, Pasteurella multocida and Mannheimia haemolytica. For all three studies, calves were administered a single dose of vaccine or placebo vaccine subcutaneously, and were challenged with one of the three virulent viruses at least one year following vaccination. Calves were evaluated daily following challenge for clinical signs of disease associated with viral infection, nasal swab samples were evaluated for virus shedding, and serum was tested for neutralizing antibodies. Following the BVDV-1 and BVDV-2 challenges, whole blood was evaluated for white blood cell counts, and for the BVDV-2 study, whole blood was also evaluated for platelet counts. Calves vaccinated with BVDV type 1a, were protected from challenge with BVDV type 1b, and had significant reductions in clinical disease, fever, leukopenia, and virus shedding compared to control calves. Vaccinated calves in the BVDV-2 study were protected from clinical disease, mortality, fever, leukopenia, thrombocytopenia, and virus shedding compared to controls. Vaccinated calves in the BHV-1 study were protected from clinical disease and fever, and had significantly reduced duration of nasal virus shedding. These three studies demonstrated that a single administration of the Vista® vaccine to healthy calves induces protective immunity against BVDV-1, BVDV-2 and BHV-1 that lasts at least one year following vaccination. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development and psychometric properties of a measure of catheter burden with bladder drainage after pelvic reconstructive surgery.

PubMed

Carpenter, Janet S; Heit, Michael; Rand, Kevin L

2017-04-01

Catheter burden after pelvic reconstructive surgery is an important patient-reported quality of life outcome in research and clinical practice. However, existing tools focus on long-term catheter users rather than short-term postoperative patients. The study aim was to evaluate the psychometric properties of a modified version of the intermittent self-catheterization questionnaire (ISC-Q) in postoperative pelvic reconstructive patients. After experts convened to discuss and modify the ISC-Q items based on their knowledge of women's experiences and clinical practices, 178 women (108 with transurethral and 70 with suprapubic catheters) completed the modified scale and other measures as part of a larger parent study designed to assess health-related quality of life (HRQoL) following pelvic reconstructive surgery requiring bladder drainage. During psychometric testing, the modified ISC-Q was reduced to six items encompassing two factors: a three-item difficulty of use factor and a 3-item embarrassment factor. The new scale was named the short-term catheter burden questionnaire (STCBQ). The two-factor model was robust in both subsamples. Only scores within and not between subsamples can be meaningfully compared due to a lack of scalar invariance. Correlations among STCBQ total scores, subscores, and a single satisfaction item indicated good construct validity. Correlations with patient demographics provided further information about the scale. The STCBQ is a short, efficient assessment of short-term catheter burden following pelvic reconstructive surgery. The scale can be used as an important patient reported outcome measure in clinical practice and research. Neurourol. Urodynam. 36:1140-1146, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Clinical tests performed in acute stroke identify the risk of falling during the first year: postural stroke study in Gothenburg (POSTGOT).

PubMed

Persson, Carina U; Hansson, Per-Olof; Sunnerhagen, Katharina S

2011-03-01

To assess the likelihood of clinical tests for postural balance, walking and motor skills, performed during the first week after stroke, identifying the risk of falling. Prospective study. Patients with first stroke. Assessments were carried out during the first week, and the occurrence of falls was recorded 3, 6 and 12 months after stroke onset. The tests used were: 10-Metre Walking Test (10MWT), Timed Up & Go, Swedish Postural Assessment Scale for Stroke Patients, Berg Balance Scale and Modified Motor Assessment Scale. Cut-off levels were obtained by receiver operation characteristic curves, and odds ratios were used to assess cut-off levels for falling. The analyses were based on 96 patients. Forty-eight percent had at least one fall during the first year. All tests were associated with the risk of falling. The highest predictive values were found for the 10MWT (positive predictive value 64%, negative predictive value 76%). Those subjects who were unable to perform the 10MWT had the highest odds ratio, 6.06 (95% confidence interval 2.66-13.84, p<0.001) of falling. Clinical tests used during the first week after stroke onset can, to some extent, identify those patients at risk of falling during the first year after stroke.

"People like numbers": a descriptive study of cognitive assessment methods in clinical practice for Aboriginal Australians in the Northern Territory.

PubMed

Dingwall, Kylie M; Pinkerton, Jennifer; Lindeman, Melissa A

2013-01-31

Achieving culturally fair assessments of cognitive functioning for Aboriginal people is difficult due to a scarcity of appropriately validated tools for use with this group. As a result, some Aboriginal people with cognitive impairments may lack fair and equitable access to services. The objective of this study was to examine current clinical practice in the Northern Territory regarding cognitive assessment for Aboriginal people thereby providing some guidance for clinicians new to this practice setting. Qualitative enquiry was used to describe practice context, reasons for assessment, and current practices in assessing cognition for Aboriginal Australians. Semi-structured interviews were conducted with 22 clinicians working with Aboriginal clients in central and northern Australia. Results pertaining to assessment methods are reported. A range of standardised tests were utilised with little consistency across clinical practice. Nevertheless, it was recognised that such tests bear severe limitations, requiring some modification and significant caution in their interpretation. Clinicians relied heavily on informal assessment or observations, contextual information and clinical judgement. Cognitive tests developed specifically for Aboriginal people are urgently needed. In the absence of appropriate, validated tests, clinicians have relied on and modified a range of standardised and informal assessments, whilst recognising the severe limitations of these. Past clinical training has not prepared clinicians adequately for assessing Aboriginal clients, and experience and clinical judgment were considered crucial for fair interpretation of test scores. Interpretation guidelines may assist inexperienced clinicians to consider whether they are achieving fair assessments of cognition for Aboriginal clients.

Test-retest reliability of the assessment of postural stability in typically developing children and in hearing impaired children.

PubMed

De Kegel, A; Dhooge, I; Cambier, D; Baetens, T; Palmans, T; Van Waelvelde, H

2011-04-01

The purpose of this study was to establish test-retest reliability of centre of pressure (COP) measurements obtained by an AccuGait portable forceplate (ACG), mean COG sway velocity measured by a Basic Balance Master (BBM) and clinical balance tests in children with and without balance difficulties. 49 typically developing children and 23 hearing impaired children, with a higher risk for stability problems, between 6 and 12 years of age participated. Each child performed the modified Clinical Test of Sensory Interaction on Balance (mCTSIB), Unilateral Stance (US) and Tandem Stance on ACG, mCTSIB and US on BBM and clinical balance tests: one-leg standing, balance beam walking and one-leg hopping. All subjects completed 2 test sessions on 2 different days in the same week assessed by the same examiner. Among COP measurements obtained by the ACG, mean sway velocity was the most reliable parameter with all ICCs higher than 0.72. The standard deviation (SD) of sway velocity, sway area, SD of anterior-posterior and SD of medio-lateral COP data showed moderate to excellent reliability with ICCs between 0.55 and 0.96 but some caution must be taken into account in some conditions. BBM is less reliable but clinical balance tests are as reliable as ACG. Hearing impaired children exhibited better relative reliability (ICC) and comparable absolute reliability (SEM) for most balance parameters compared to typically developing children. Reliable information regarding postural stability of typically developing children and hearing impaired children may be obtained utilizing COP measurements generated by an AccuGait system and clinical balance tests. Copyright © 2011 Elsevier B.V. All rights reserved.

Developing Methodologies to Find Abbreviated Laboratory Test Names in Narrative Clinical Documents by Generating High Quality Q-Grams.

PubMed

Kim, Kyungmo; Choi, Jinwook

2017-01-01

Laboratory test names are used as basic information to diagnose diseases. However, this kind of medical information is usually written in a natural language. To find this information, lexicon based methods have been good solutions but they cannot find terms that do not have abbreviated expressions, such as "neuts" that means "neutrophils". To address this issue, similar word matching can be used; however, it can be disadvantageous because of significant false positives. Moreover, processing time is longer as the size of terms is bigger. Therefore, we suggest a novel q-gram based algorithm, named modified triangular area filtering, to find abbreviated laboratory test terms in clinical documents, minimizing the possibility to impair the lexicons' precision. In addition, we found the terms using the methodology with reasonable processing time. The results show that this method can achieve 92.54 precision, 87.72 recall, 90.06 f1-score in test sets when edit distance threshold(τ) = 3.

A phase II flexible screening design allowing for interim analysis and comparison with historical control.

PubMed

Wu, Wenting; Bot, Brian; Hu, Yan; Geyer, Susan M; Sargent, Daniel J

2013-07-01

Sargent and Goldberg [1] proposed a randomized phase II flexible screening design (SG design) which took multiple characteristics of candidate regimens into consideration in selecting a regimen for further phase III testing. In this paper, we extend the SG design by including provisions for an interim analysis and/or a comparison to a historical control. By including a comparison with a historical control, a modified SG design not only identifies a more promising treatment but also assures that the regimen has a clinically meaningful level of efficacy as compared to a historical control. By including an interim analysis, a modified SG design could reduce the number of patients exposed to inferior treatment regimens. When compared to the original SG design, the modified designs increase the sample size moderately, but expand the utility of the flexible screening design substantially. Copyright © 2013 Elsevier Inc. All rights reserved.

Differential Effect of Modified Medical Research Council Dyspnea, COPD Assessment Test, and Clinical COPD Questionnaire for Symptoms Evaluation Within the New GOLD Staging and Mortality in COPD.

PubMed

Casanova, Ciro; Marin, Jose M; Martinez-Gonzalez, Cristina; de Lucas-Ramos, Pilar; Mir-Viladrich, Isabel; Cosio, Borja; Peces-Barba, German; Solanes-García, Ingrid; Agüero, Ramón; Feu-Collado, Nuria; Calle-Rubio, Miryam; Alfageme, Inmaculada; de Diego-Damia, Alfredo; Irigaray, Rosa; Marín, Margarita; Balcells, Eva; Llunell, Antonia; Galdiz, Juan Bautista; Golpe, Rafael; Lacarcel, Celia; Cabrera, Carlos; Marin, Alicia; Soriano, Joan B; Lopez-Campos, Jose Luis; Soler-Cataluña, Juan José; de-Torres, Juan P

2015-07-01

The modified Medical Research Council (mMRC) dyspnea, the COPD Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been interchangeably proposed by GOLD (Global Initiative for Chronic Obstructive Lung Disease) for assessing symptoms in patients with COPD. However, there are no data on the prognostic value of these tools in terms of mortality. We endeavored to evaluate the prognostic value of the CAT and CCQ scores and compare them with mMRC dyspnea. We analyzed the ability of these tests to predict mortality in an observational cohort of 768 patients with COPD (82% men; FEV1, 60%) from the COPD History Assessment in Spain (CHAIN) study, a multicenter observational Spanish cohort, who were monitored annually for a mean follow-up time of 38 months. Subjects who died (n = 73; 9.5%) had higher CAT (14 vs 11, P = .022), CCQ (1.6 vs 1.3, P = .033), and mMRC dyspnea scores (2 vs 1, P < .001) than survivors. Receiver operating characteristic analysis showed that higher CAT, CCQ, and mMRC dyspnea scores were associated with higher mortality (area under the curve: 0.589, 0.588, and 0.649, respectively). CAT scores ≥ 17 and CCQ scores > 2.5 provided a similar sensitivity than mMRC dyspnea scores ≥ 2 to predict all-cause mortality. The CAT and the CCQ have similar ability for predicting all-cause mortality in patients with COPD, but were inferior to mMRC dyspnea scores. We suggest new thresholds for CAT and CCQ scores based on mortality risk that could be useful for the new GOLD grading classification. ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Clinical measures, smoking, radon exposure, and risk of lung cancer in uranium miners.

PubMed Central

Finkelstein, M M

1996-01-01

OBJECTIVES: Exposure to the radioactive daughters of radon is associated with increased risk of lung cancer in mining populations. An investigation of incidence of lung cancer following a clinical survey of Ontario uranium miners was undertaken to explore whether risk associated with radon is modified by factors including smoking, radiographic silicosis, clinical symptoms, the results of lung function testing, and the temporal pattern of radon exposure. METHODS: Miners were examined in 1974 by a respiratory questionnaire, tests of lung function, and chest radiography. A random selection of 733 (75%) of the original 973 participants was followed up by linkage to the Ontario Mortality and Cancer Registries. RESULTS: Incidence of lung cancer was increased threefold. Risk of lung cancer among miners who had stopped smoking was half that of men who continued to smoke. There was no interaction between smoking and radon exposure. Men with lung function test results consistent with airways obstruction had an increased risk of lung cancer, even after adjustment for cigarette smoking. There was no association between radiographic silicosis and risk of lung cancer. Lung cancer was associated with exposures to radon daughters accumulated in a time window four to 14 years before diagnosis, but there was little association with exposures incurred earlier than 14 years before diagnosis. Among the men diagnosed with lung cancer, the mean and median dose rates were 2.6 working level months (WLM) a year and 1.8 WLM/year in the four to 14 year exposure window. CONCLUSIONS: Risk of lung cancer associated with radon is modified by dose and time from exposure. Risk can be substantially decreased by stopping smoking. PMID:8943835

A Comprehensive Analysis of the SRS-Schwab Adult Spinal Deformity Classification and Confounding Variables: A Prospective, Non-US Cross-sectional Study in 292 Patients.

PubMed

Hallager, Dennis Winge; Hansen, Lars Valentin; Dragsted, Casper Rokkjær; Peytz, Nina; Gehrchen, Martin; Dahl, Benny

2016-05-01

Cross-sectional analyses on a consecutive, prospective cohort. To evaluate the ability of the Scoliosis Research Society (SRS)-Schwab Adult Spinal Deformity Classification to group patients by widely used health-related quality-of-life (HRQOL) scores and examine possible confounding variables. The SRS-Schwab Adult Spinal Deformity Classification includes sagittal modifiers considered important for HRQOL and the clinical impact of the classification has been validated in patients from the International Spine Study Group database; however, equivocal results were reported for the Pelvic Tilt modifier and potential confounding variables were not evaluated. Between March 2013 and May 2014, all adult spinal deformity patients from our outpatient clinic with sufficient radiographs were prospectively enrolled. Analyses of HRQOL variance and post hoc analyses were performed for each SRS-Schwab modifier. Age, history of spine surgery, and aetiology of spinal deformity were considered potential confounders and their influence on the association between SRS-Schwab modifiers and aggregated Oswestry Disability Index (ODI) scores was evaluated with multivariate proportional odds regressions. P values were adjusted for multiple testing. Two hundred ninety-two of 460 eligible patients were included for analyses. The SRS-Schwab Classification significantly discriminated HRQOL scores between normal and abnormal sagittal modifier classifications. Individual grade comparisons showed equivocal results; however, Pelvic Tilt grade + versus +  + did not discriminate patients according to any HRQOL score. All modifiers showed significant proportional odds for worse aggregated ODI scores with increasing grade levels and the effects were robust to confounding. However, age group and aetiology had individual significant effects. The SRS-Schwab sagittal modifiers reliably grouped patients graded 0 versus + / +  + according to the most widely used HRQOL scores and the effects of increasing grade level on odds for worse ODI scores remained significant after adjusting for potential confounders. However, effects of age group and aetiology should not be neglected. 3.

An inexpensive modification of the laboratory computer display changes emergency physicians' work habits and perceptions.

PubMed

Marinakis, Harry A; Zwemer, Frank L

2003-02-01

Little is known about how the availability of laboratory data affects emergency physicians' practice habits and satisfaction. We modified our clinical information system to display laboratory test status with continuous updates, similar to an airport arrival display. The objective of this study was to determine whether the laboratory test status display altered emergency physicians' work habits and increased satisfaction compared with the time period before implementation of laboratory test status. A retrospective analysis was performed of emergency physicians' actual use of the clinical information system before and after implementation of the laboratory test status display. Emergency physicians were retrospectively surveyed regarding the effect of laboratory test status display on their practice habits and clinical information system use. Survey responses were matched with actual use of the clinical information system. Data were analyzed by using dependent t tests and Pearson correlation coefficients. The study was conducted at a university hospital. Clinical information system use by 46 emergency physicians was analyzed. Twenty-five surveys were returned (71.4% of available emergency physicians). All emergency physicians perceived fewer clinical information system log ons per day after laboratory test status display. The actual average decrease was 19%. Emergency physicians who reported the greatest decrease in log ons per day tended to have the greatest actual decrease (r =-0.36). There was no significant correlation between actual and perceived total time logged on (r =0.08). In regard to effect on emergency physicians' practice habits, 95% reported increased efficiency, 80% reported improved satisfaction with data access, and 65% reported improved communication with patients. An inexpensive computer modification, laboratory test status display, significantly increased subjective efficiency, changed work habits, and improved satisfaction regarding data access and patient communication among emergency physicians. Knowledge of the test queue changed emergency physician behavior and improved satisfaction.

Clinical manifestation, serology marker & microscopic agglutination test (MAT) to mortality in human leptospirosis

NASA Astrophysics Data System (ADS)

Perdhana, S. A. P.; Susilo, R. S. B.; Arifin; Redhono, D.; Sumandjar, T.

2018-03-01

Leptospirosis is a potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding. Severe disease is estimated 5–15% of all human infections. Its mortality rate is 5-40%. MAT, isolation of the organism, or leptospiral DNA in PCR are used to confirm Leptospirosis. This cross-sectional analytic study recruited 26 hospitalized leptospirosis patients admitted to Dr. Moewardi Hospital Surakarta. The diagnosis was based on clinical, laboratory and epidemiological findings. The onset of the disease was the date when the first symptom started, and the end of the analysis was the date when the patient died or discharged. Modified Faine’s score ≥ 25 tend to die (45.5%) while modified Faine’s score 20 – 24 tend to heal (60%) (OR 1.250; CI 0.259-6.029; p=1.0). Seropositive IgM predicts mortality 7.8 times higher than seronegative IgM (OR 7.800; CI 1.162-52.353; p=0.038). MAT positive predict mortality 10.667 times higher than MAT negative (OR 10.667; CI 1.705-66.720; p=0.015). Clinical manifestation, MAT, and serologic marker are all correlated with mortality in Leptospirosis. However, statistically, clinical manifestation has an insignificant correlation.

Postoperative Swallowing Assessment After Lung Transplantation.

PubMed

Baumann, Brooke; Byers, Sara; Wasserman-Wincko, Tamara; Smith, Libby; Hathaway, Bridget; Bhama, Jay; Shigemura, Norihisa; Hayanga, J W Awori; D'Cunha, Jonathan; Johnson, Jonas T

2017-07-01

Dysphagia, aspiration, and potential pneumonia represent a major source of morbidity in patients undergoing lung transplantation. Conditions that potentiate dysphagia and aspiration include frailty and prolonged intubation. Our group of speech-language pathologists has been actively involved in performance of a bedside evaluation of swallowing, and instrumental evaluation of swallowing with modified barium swallow, and postoperative management in patients undergoing lung transplantation. All lung transplant patients from April 2009 to September 2012 were evaluated retrospectively. A clinical bedside examination was performed by the speech-language pathology team, followed by a modified barium swallow or fiberoptic endoscopic evaluation of swallowing. A total of 321 patients were referred for evaluation. Twenty-four patients were unable to complete the evaluation. Clinical signs of aspiration were apparent in 160 patients (54%). Deep laryngeal penetration or aspiration were identified in 198 (67%) patients during instrumental testing. A group of 81 patients (27%) had an entirely normal clinical examination, but were found to have either deep penetration or aspiration. The majority of patients aspirate after lung transplantation. Clinical bedside examination is not sensitive enough and will fail to identify patients with silent aspiration. A standard of practice following lung transplantation has been established that helps avoid postoperative aspiration associated with complications. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Empirical validation of guidelines for the management of pharyngitis in children and adults.

PubMed

McIsaac, Warren J; Kellner, James D; Aufricht, Peggy; Vanjaka, Anita; Low, Donald E

2004-04-07

Recent guidelines for management of pharyngitis vary in their recommendations concerning empirical antibiotic treatment and the need for laboratory confirmation of group A streptococcus (GAS). To assess the impact of guideline recommendations and alternative approaches on identification and treatment of GAS pharyngitis in children and adults. Throat cultures and rapid antigen tests were performed on 787 children and adults aged 3 to 69 years with acute sore throat attending a family medicine clinic in Calgary, Alberta, from September 1999 to August 2002. Recommendations from 2 guidelines (those of the Infectious Diseases Society of America and of the American College of Physicians-American Society of Internal Medicine/American Academy of Family Physicians/US Centers for Disease Control and Prevention) were compared with rapid testing alone, a clinical prediction rule (ie, the modified Centor score), and a criterion standard of treatment for positive throat culture results only. Sensitivity and specificity of each strategy for identifying GAS pharyngitis, total antibiotics recommended, and unnecessary antibiotic prescriptions. In children, sensitivity for streptococcal infection ranged from 85.8% (133/155; 95% confidence interval [CI], 79.3%-90.0%) for rapid testing to 100% for culturing all. In adults, sensitivity ranged from 76.7% (56/73; 95% CI, 65.4%-85.8%) for rapid testing without culture confirmation of negative results to 100% for culturing all. In children, specificity ranged from 90.3% (270/299; 95% CI, 86.4%-93.4%) for use of modified Centor score and throat culture to 100% for culturing all. In adults, specificity ranged from 43.8% (114/260; 95% CI, 37.7%-50.1%) for empirical treatment based on a modified Centor score of 3 or 4 to 100% for culturing all. Total antibiotic prescriptions were lowest with rapid testing (24.7% [194/787]; 95% CI, 21.7%-27.8%) and highest with empirical treatment of high-risk adults (45.7% [360/787]; 95% CI, 42.2%-49.3%), due to a high rate of unnecessary prescriptions in adults (43.8% [146/333]; 95% CI, 38.4%-49.4%). Guideline recommendations for the selective use of throat cultures but antibiotic treatment based only on positive rapid test or throat culture results can reduce unnecessary use of antibiotics for treatment of pharyngitis. However, empirical treatment of adults having a Centor score of 3 or 4 is associated with a high rate of unnecessary antibiotic use. In children, strategies incorporating throat culture or throat culture confirmation of negative rapid antigen test results are highly sensitive and specific. Throat culture of all adults or those selected on the basis of a clinical prediction rule had the highest sensitivity and specificity.

Development and psychometric testing of the Clinical Learning Organisational Culture Survey (CLOCS).

PubMed

Henderson, Amanda; Creedy, Debra; Boorman, Rhonda; Cooke, Marie; Walker, Rachel

2010-10-01

This paper describes the development and psychometric testing of the Clinical Learning Organisational Culture Survey (CLOCS) that measures prevailing beliefs and assumptions important for learning to occur in the workplace. Items from a tool that measured motivation in workplace learning were adapted to the nursing practice context. The tool was tested in the clinical setting, and then further modified to enhance face and content validity. Registered nurses (329) across three major Australian health facilities were surveyed between June 2007 and September 2007. An exploratory factor analysis identified five concepts--recognition, dissatisfaction, affiliation, accomplishment, and influence. VALIDITY AND RELIABILITY: Internal consistency measures of reliability revealed that four concepts had good internal consistency: recognition (alpha=.914), dissatisfaction (alpha=.771), affiliation (alpha=.801), accomplishment (alpha=.664), but less so for influence (alpha=.529). This tool effectively measures recognition, affiliation and accomplishment--three concepts important for learning in practice situations, as well as dissatisfied staff across all these domains. Testing of additional influence items identify that this concept is difficult to delineate. The CLOCS can effectively inform leaders about concepts inherent in the culture important for maximising learning by staff. Crown Copyright © 2009. Published by Elsevier Ltd. All rights reserved.

Assessing the risk of pH-dependent absorption for new molecular entities: a novel in vitro dissolution test, physicochemical analysis, and risk assessment strategy.

PubMed

Mathias, Neil R; Xu, Yan; Patel, Dhaval; Grass, Michael; Caldwell, Brett; Jager, Casey; Mullin, Jim; Hansen, Luke; Crison, John; Saari, Amy; Gesenberg, Christoph; Morrison, John; Vig, Balvinder; Raghavan, Krishnaswamy

2013-11-04

Weak base therapeutic agents can show reduced absorption or large pharmacokinetic variability when coadministered with pH-modifying agents, or in achlorhydria disease states, due to reduced dissolution rate and/or solubility at high gastric pH. This is often referred to as pH-effect. The goal of this study was to understand why some drugs exhibit a stronger pH-effect than others. To study this, an API-sparing, two-stage, in vitro microdissolution test was developed to generate drug dissolution, supersaturation, and precipitation kinetic data under conditions that mimic the dynamic pH changes in the gastrointestinal tract. In vitro dissolution was assessed for a chemically diverse set of compounds under high pH and low pH, analogous to elevated and normal gastric pH conditions observed in pH-modifier cotreated and untreated subjects, respectively. Represented as a ratio between the conditions, the in vitro pH-effect correlated linearly with clinical pH-effect based on the Cmax ratio and in a non-linear relationship based on AUC ratio. Additionally, several in silico approaches that use the in vitro dissolution data were found to be reasonably predictive of the clinical pH-effect. To explore the hypothesis that physicochemical properties are predictors of clinical pH-effect, statistical correlation analyses were conducted using linear sequential feature selection and partial least-squares regression. Physicochemical parameters did not show statistically significant linear correlations to clinical pH-effect for this data set, which highlights the complexity and poorly understood nature of the interplay between parameters. Finally, a strategy is proposed for implementation early in clinical development, to systematically assess the risk of clinical pH-effect for new molecular entities that integrates physicochemical analysis and in vitro, in vivo and in silico methods.

Validation of quality indicators for the organization of palliative care: a modified RAND Delphi study in seven European countries (the Europall project).

PubMed

Woitha, Kathrin; Van Beek, Karen; Ahmed, Nisar; Jaspers, Birgit; Mollard, Jean M; Ahmedzai, Sam H; Hasselaar, Jeroen; Menten, Johan; Vissers, Kris; Engels, Yvonne

2014-02-01

Validated quality indicators can help health-care professionals to evaluate their medical practices in a comparative manner to deliver optimal clinical care. No international set of quality indicators to measure the organizational aspects of palliative care settings exists. To develop and validate a set of structure and process indicators for palliative care settings in Europe. A two-round modified RAND Delphi process was conducted to rate clarity and usefulness of a previously developed set of 110 quality indicators. In total, 20 multi-professional palliative care teams of centers of excellence from seven European countries. In total, 56 quality indicators were rated as useful. These valid quality indicators concerned the following domains: the definition of a palliative care service (2 quality indicators), accessibility to palliative care (16 quality indicators), specific infrastructure to deliver palliative care (8 quality indicators), symptom assessment tools (1 quality indicator), specific personnel in palliative care services (9 quality indicators), documentation methodology of clinical data (14 quality indicators), evaluation of quality and safety procedures (1 quality indicator), reporting of clinical activities (1 quality indicator), and education in palliative care (4 quality indicator). The modified RAND Delphi process resulted in 56 international face-validated quality indicators to measure and compare organizational aspects of palliative care. These quality indicators, aimed to assess and improve the organization of palliative care, will be pilot tested in palliative care settings all over Europe and be used in the EU FP7 funded IMPACT project.

The impact of loss to follow-up on hypothesis tests of the treatment effect for several statistical methods in substance abuse clinical trials.

PubMed

Hedden, Sarra L; Woolson, Robert F; Carter, Rickey E; Palesch, Yuko; Upadhyaya, Himanshu P; Malcolm, Robert J

2009-07-01

"Loss to follow-up" can be substantial in substance abuse clinical trials. When extensive losses to follow-up occur, one must cautiously analyze and interpret the findings of a research study. Aims of this project were to introduce the types of missing data mechanisms and describe several methods for analyzing data with loss to follow-up. Furthermore, a simulation study compared Type I error and power of several methods when missing data amount and mechanism varies. Methods compared were the following: Last observation carried forward (LOCF), multiple imputation (MI), modified stratified summary statistics (SSS), and mixed effects models. Results demonstrated nominal Type I error for all methods; power was high for all methods except LOCF. Mixed effect model, modified SSS, and MI are generally recommended for use; however, many methods require that the data are missing at random or missing completely at random (i.e., "ignorable"). If the missing data are presumed to be nonignorable, a sensitivity analysis is recommended.

Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo.

PubMed

Altenburg, Arwen F; van de Sandt, Carolien E; Li, Bobby W S; MacLoughlin, Ronan J; Fouchier, Ron A M; van Amerongen, Geert; Volz, Asisa; Hendriks, Rudi W; de Swart, Rik L; Sutter, Gerd; Rimmelzwaan, Guus F; de Vries, Rory D

2017-08-17

Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies.

Effects of the sliding rehabilitation machine on balance and gait in chronic stroke patients - a controlled clinical trial.

PubMed

Byun, Seung-Deuk; Jung, Tae-Du; Kim, Chul-Hyun; Lee, Yang-Soo

2011-05-01

To investigate the effects of a sliding rehabilitation machine on balance and gait in chronic stroke patients. A non-randomized crossover design. Inpatient rehabilitation in a general hospital. Thirty patients with chronic stroke who had medium or high falling risk as determined by the Berg Balance Scale. Participants were divided into two groups and underwent four weeks of training. Group A (n = 15) underwent training with the sliding rehabilitation machine for two weeks with concurrent conventional training, followed by conventional training only for another two weeks. Group B (n = 15) underwent the same training in reverse order. The effect of the experimental period was defined as the sum of changes during training with sliding rehabilitation machine in each group, and the effect of the control period was defined as those during the conventional training only in each group. Functional Ambulation Category, Berg Balance Scale, Six-Minute Walk Test, Timed Up and Go Test, Korean Modified Barthel Index, Modified Ashworth Scale and Manual Muscle Test. Statistically significant improvements were observed in all parameters except Modified Ashworth Scale in the experimental period, but only in Six-Minute Walk Test (P < 0.01) in the control period. There were also statistically significant differences in the degree of change in all parameters in the experimental period as compared to the control period. The sliding rehabilitation machine may be a useful tool for the improvement of balance and gait abilities in chronic stroke patients.

The Trunk Impairment Scale - modified to ordinal scales in the Norwegian version.

PubMed

Gjelsvik, Bente; Breivik, Kyrre; Verheyden, Geert; Smedal, Tori; Hofstad, Håkon; Strand, Liv Inger

2012-01-01

To translate the Trunk Impairment Scale (TIS), a measure of trunk control in patients after stroke, into Norwegian (TIS-NV), and to explore its construct validity, internal consistency, intertester and test-retest reliability. TIS was translated according to international guidelines. The validity study was performed on data from 201 patients with acute stroke. Fifty patients with stroke and acquired brain injury were recruited to examine intertester and test-retest reliability. Construct validity was analyzed with exploratory and confirmatory factor analysis and item response theory, internal consistency with Cronbach's alpha test, and intertester and test-retest reliability with kappa and intraclass correlation coefficient tests. The back-translated version of TIS-NV was validated by the original developer. The subscale Static sitting balance was removed. By combining items from the subscales Dynamic sitting balance and Coordination, six ordinal superitems (testlets) were constructed. The TIS-NV was renamed the modified TIS-NV (TIS-modNV). After modifications the TIS-modNV fitted well to a locally dependent unidimensional item response theory model. It demonstrated good construct validity, excellent internal consistency, and high intertester and test-retest reliability for the total score. This study supports that the TIS-modNV is a valid and reliable scale for use in clinical practice and research.

Simple, rapid, and cost-effective modified Carba NP test for carbapenemase detection among Gram-negative bacteria

PubMed Central

Rudresh, Shoorashetty Manohara; Ravi, Giriyapur Siddappa; Sunitha, Lakshminarayanappa; Hajira, Sadiya Noor; Kalaiarasan, Ellappan; Harish, Belgode Narasimha

2017-01-01

PURPOSE: Detection of carbapenemases among Gram-negative bacteria (GNB) is important for both clinicians and infection control practitioners. The Clinical and Laboratory Standards Institute recommends Carba NP (CNP) as confirmatory test for carbapenemase production. The reagents required for CNP test are costly and hence the test cannot be performed on a routine basis. The present study evaluates modifications of CNP test for rapid detection of carbapenemases among GNB. MATERIALS AND METHODS: The GNB were screened for carbapenemase production using CNP, CarbAcineto NP (CANP), and modified CNP (mCNP) test. A multiplex polymerase chain reaction (PCR) was performed on all the carbapenem-resistant bacteria for carbapenemase genes. The results of three phenotypic tests were compared with PCR. RESULTS: A total of 765 gram negative bacteria were screened for carbapenem resistance. Carbapenem resistance was found in 144 GNB. The metallo-β-lactamases were most common carbapenemases followed by OXA-48-like enzymes. The CANP test was most sensitive (80.6%) for carbapenemases detection. The mCNP test was 62.1% sensitive for detection of carbapenemases. The mCNP, CNP, and CANP tests were equally sensitive (95%) for detection of NDM enzymes among Enterobacteriaceae. The mCNP test had poor sensitivity for detection of OXA-48-like enzymes. CONCLUSION: The mCNP test was rapid, cost-effective, and easily adoptable on routine basis. The early detection of carbapenemases using mCNP test will help in preventing the spread of multidrug-resistant organisms in the hospital settings. PMID:28966495

Simple, rapid, and cost-effective modified Carba NP test for carbapenemase detection among Gram-negative bacteria.

PubMed

Rudresh, Shoorashetty Manohara; Ravi, Giriyapur Siddappa; Sunitha, Lakshminarayanappa; Hajira, Sadiya Noor; Kalaiarasan, Ellappan; Harish, Belgode Narasimha

2017-01-01

Detection of carbapenemases among Gram-negative bacteria (GNB) is important for both clinicians and infection control practitioners. The Clinical and Laboratory Standards Institute recommends Carba NP (CNP) as confirmatory test for carbapenemase production. The reagents required for CNP test are costly and hence the test cannot be performed on a routine basis. The present study evaluates modifications of CNP test for rapid detection of carbapenemases among GNB. The GNB were screened for carbapenemase production using CNP, CarbAcineto NP (CANP), and modified CNP (mCNP) test. A multiplex polymerase chain reaction (PCR) was performed on all the carbapenem-resistant bacteria for carbapenemase genes. The results of three phenotypic tests were compared with PCR. A total of 765 gram negative bacteria were screened for carbapenem resistance. Carbapenem resistance was found in 144 GNB. The metallo-β-lactamases were most common carbapenemases followed by OXA-48-like enzymes. The CANP test was most sensitive (80.6%) for carbapenemases detection. The mCNP test was 62.1% sensitive for detection of carbapenemases. The mCNP, CNP, and CANP tests were equally sensitive (95%) for detection of NDM enzymes among Enterobacteriaceae. The mCNP test had poor sensitivity for detection of OXA-48-like enzymes. The mCNP test was rapid, cost-effective, and easily adoptable on routine basis. The early detection of carbapenemases using mCNP test will help in preventing the spread of multidrug-resistant organisms in the hospital settings.

Clinical relevance of the modified physical performance test versus the short physical performance battery for detecting mobility impairments in older men with peripheral arterial disease.

PubMed

Addison, Odessa; Kundi, Rishi; Ryan, Alice S; Goldberg, Andrew P; Patel, Richa; Lal, Brajesh K; Prior, Steven J

2017-08-23

The study is to compare the Modified Physical Performance Test (MPPT) and Short Physical Performance Battery (SPPB) as metrics of mobility and function in older men with peripheral arterial disease (PAD). A total of 51 men (55-87 years) with PAD underwent functional testing including the SPPB, MPPT, Walking Impairment Questionnaire (WIQ), stair ascent, and 6-min walk distance. Individuals were grouped according to SPPB and MPPT scores as not limited on either, limited only on the MPPT, or limited on both. The MPPT identified a higher proportion of patients as being functionally limited than the SPPB (p < 0.001). Men identified as limited only by the MPPT, and not the SPPB, were subsequently confirmed to have lower function on all measures compared to those not identified as limited by either the SPPB or the MPPT (p < 0.02). These findings suggest the MPPT is an appropriate measure to identify early declines in men with PAD and may identify global disability better than SPPB. Implications for rehabilitation Individuals with peripheral arterial disease have low activity levels and are at risk for a loss of independence and global disability. Early detection of decline in mobility and global function would allow for interventions before large changes in ambulatory ability or a loss of functional independence occur. This study shows the Modified Physical Performance Test may be an appropriate test to identify early decline in function in men with peripheral arterial disease.

Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus.

PubMed

Sacks, David B; Arnold, Mark; Bakris, George L; Bruns, David E; Horvath, Andrea Rita; Kirkman, M Sue; Lernmark, Ake; Metzger, Boyd E; Nathan, David M

2011-06-01

Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence Based Laboratory Medicine Committee of the AACC jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association. In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A(1c) (Hb A(1c)) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of Hb A(1c). The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended.

Verification of an Automated, Digital Dispensing Platform for At-Will Broth Microdilution-Based Antimicrobial Susceptibility Testing.

PubMed

Smith, Kenneth P; Kirby, James E

2016-09-01

With rapid emergence of multidrug-resistant bacteria, there is often a need to perform susceptibility testing for less commonly used or newer antimicrobial agents. Such testing can often be performed only by using labor-intensive, manual dilution methods and lies outside the capacity of most clinical labs, necessitating reference laboratory testing and thereby delaying the availability of susceptibility data. To address the compelling clinical need for microbiology laboratories to perform such testing in-house, we explored a novel, automated, at-will broth microdilution-based susceptibility testing platform. Specifically, we used the modified inkjet printer technology in the HP D300 digital dispensing system to dispense, directly from stock solutions into a 384-well plate, the 2-fold serial dilution series required for broth microdilution testing. This technology was combined with automated absorbance readings and data analysis to determine MICs. Performance was verified by testing members of the Enterobacteriaceae for susceptibility to ampicillin, cefazolin, ciprofloxacin, colistin, gentamicin, meropenem, and tetracycline in comparison to the results obtained with a broth microdilution reference standard. In precision studies, essential and categorical agreement levels were 96.8% and 98.3%, respectively. Furthermore, significantly fewer D300-based measurements were outside ±1 dilution from the modal MIC, suggesting enhanced reproducibility. In accuracy studies performed using a panel of 80 curated clinical isolates, rates of essential and categorical agreement and very major, major, and minor errors were 94%, 96.6%, 0%, 0%, and 3.4%, respectively. Based on these promising initial results, it is anticipated that the D300-based methodology will enable hospital-based clinical microbiology laboratories to perform at-will broth microdilution testing of antimicrobials and to address a critical testing gap. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Toxoplasmosis in Caribbean islands: Seroprevalence in pregnant women in ten countries, and isolation and report of new genetic types of Toxoplasma gondii from dogs from St. Kitts, West Indies

USDA-ARS?s Scientific Manuscript database

Little is known of clinical toxoplasmosis in humans and animals in the Caribbean countries. We investigated the prevalence of IgG and IgMantibodies in 437 pregnant women from 10 English speaking Caribbean countries. Antibodies (IgG) to T. gondii (modified agglutination test, MAT, cut-off 1:6) were f...

Search Algorithms as a Framework for the Optimization of Drug Combinations

PubMed Central

Coquin, Laurence; Schofield, Jennifer; Feala, Jacob D.; Reed, John C.; McCulloch, Andrew D.; Paternostro, Giovanni

2008-01-01

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms—originally developed for digital communication—modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs using only one-third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6–9 interventions in 80–90% of tests, compared with 15–30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution. PMID:19112483

Homemade thermometry instruments in the field.

PubMed

Pasquier, Mathieu; Rousson, Valentin; Zen Ruffinen, Grégoire; Hugli, Olivier

2012-03-01

Esophageal temperature is the gold standard for in-the-field temperature monitoring in hypothermic victims with cardiac arrest. For practical reasons, some mountain rescue teams use homemade esophageal thermometers to measure esophageal temperature; these consist of nonmedical inside/outside temperature monitoring instruments that have been modified to allow for esophageal insertion. We planned a study to determine the accuracy of such thermometers. Two of the same model of digital cabled indoor/outdoor thermometer were modified and tested in comparison with a reference thermometer. The thermometers were tested in a water bath at different temperatures between 10°C and 35.2°C. Three hundred measurements were taken with each thermometer. Our experimental study showed that both homemade thermometers provided a good correlation and a clinically acceptable agreement in comparison with the reference thermometer. Measurements were within 0.5°C in comparison with the reference thermometer 97.5% of the time. The homemade thermometers performed well in vitro, in comparison with a reference thermometer. However, because these devices in their original form are not designed for clinical use, their use should be restricted to situations when the use of a conventional esophageal thermometer is impossible. Copyright © 2012 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

A single group, pretest-posttest clinical trial for the effects of dry needling on wrist flexors spasticity after stroke.

PubMed

Fakhari, Zahra; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Mansouri, Korosh; Radinmehr, Hojjat

2017-01-01

Spasticity is a common complication after stroke. Dry needling (DN) is suggested as a novel method for treatment of muscle spasticity. To explore the effects of DN on wrist flexors spasticity poststroke. A single group, pretest-posttest clinical trial was used. Twenty nine patients with stroke (16 male; mean age 54.3 years) were tested at baseline (T0), immediately after DN (T1), and one hour after DN (T2). DN was applied for flexor carpi radialis (FCR) and flexor carpi ulnaris on the affected arm for single session, one minute per muscle. The Modified Modified Ashworth Scale (MMAS), passive resistance force, wrist active and passive range of motion, Box and Block Test, and FCR H-reflex were outcome measures. Significant reductions in MMAS scores were seen both immediately after DN and at 1-hour follow-up (median 2 at T0 to 1 at T1 and T2). There were significant improvements in other measures between the baseline values at T0 and those recorded immediately after the DN at T1 or one hour later at T2. This study suggests that DN reduced wrist flexors spasticity and alpha motor neuron excitability in patients with stroke, and improvements persisted for one hour after DN.

Classification of parotidectomy: a proposed modification to the European Salivary Gland Society classification system.

PubMed

Wong, Wai Keat; Shetty, Subhaschandra

2017-08-01

Parotidectomy remains the mainstay of treatment for both benign and malignant lesions of the parotid gland. There exists a wide range of possible surgical options in parotidectomy in terms of extent of parotid tissue removed. There is increasing need for uniformity of terminology resulting from growing interest in modifications of the conventional parotidectomy. It is, therefore, of paramount importance for a standardized classification system in describing extent of parotidectomy. Recently, the European Salivary Gland Society (ESGS) proposed a novel classification system for parotidectomy. The aim of this study is to evaluate this system. A classification system proposed by the ESGS was critically re-evaluated and modified to increase its accuracy and its acceptability. Modifications mainly focused on subdividing Levels I and II into IA, IB, IIA, and IIB. From June 2006 to June 2016, 126 patients underwent 130 parotidectomies at our hospital. The classification system was tested in that cohort of patient. While the ESGS classification system is comprehensive, it does not cover all possibilities. The addition of Sublevels IA, IB, IIA, and IIB may help to address some of the clinical situations seen and is clinically relevant. We aim to test the modified classification system for partial parotidectomy to address some of the challenges mentioned.

Windows of Opportunity for Lifestyle Interventions to Prevent Gestational Diabetes Mellitus.

PubMed

Phelan, Suzanne

2016-11-01

Gestational diabetes mellitus (GDM) is linked with several acute maternal health risks and long-term development of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM similarly increases offspring risk of early-life health complications and later disease. GDM recurrence is common, affecting 40 to 73% of women, and augments associated maternal/fetal/child health risks. Modifiable and independent risk factors for GDM include maternal excessive gestational weight gain and prepregnancy overweight and obesity. Lifestyle interventions that target diet, activity, and behavioral strategies can effectively modify body weight. Randomized clinical trials testing the effects of lifestyle interventions during pregnancy to reduce excessive gestational weight gain have generally shown mixed effects on reducing GDM incidence. Trials testing the effects of postpartum lifestyle interventions among women with a history of GDM have shown reduced incidence of diabetes and improved cardiovascular disease risk factors. However, the long-term effects of interpregnancy or prepregnancy lifestyle interventions on subsequent GDM remain unknown. Future adequately powered and well-controlled clinical trials are needed to determine the effects of lifestyle interventions to prevent GDM and identify pathways to effectively reach reproductive-aged women across all levels of society, before, during, and after pregnancy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Plaque, caries level and oral hygiene habits in young patients receiving orthodontic treatment.

PubMed

Martignon, S; Ekstrand, K R; Lemos, M I; Lozano, M P; Higuera, C

2010-09-01

To assess plaque, caries, and oral hygiene habits amongst patients receiving fixed-orthodontic treatment at the Dental-Clinic, Universidad-El-Bosque, Bogotá, Colombia. Test-group: 74 12-29-year-olds receiving fixed-orthodontic treatment; reference-group: 63 12-29-year-olds before they started the orthodontic treatment. Visual examinations (one examiner) recorded the following: Ortho-plaque-Index (OPI) expressed per patient as good, fair and poor-oral-hygiene. Caries was scored with the modified-ICDAS-II criteria as: 0-sound; 1B/1W-brown/white-opacity-after-air-drying; 2B/2W-brown/white-opacity-without-air-drying; 3-microcavity; 4-underlying-shadow; 5/6-distinct/extensive-cavity. Filled/missing surfaces due-to-caries and caries-lesions on buccal surfaces at three sites around the brackets were recorded. A 7-item self-administered oral-hygiene habits' questionnaire was used. Chi-square test revealed that the oral-hygiene level was significantly better in the reference group compared to the test group (p < 0.05). The traditional mean DMF-S was 6.7 +/- 6.3 in the test- and 6.2 +/- 5.9 in the reference-group (p > 0.05). When adding modified-ICDAS-II lesions scores 1-4, the figure increased to 23.6 +/- 9.4 in the test- and to 13.6 +/- 10.3 in the reference-group (p < 0.001). A total of 96% had > or = 1 white-opacity in the test group versus 56% in the reference group (P < 0.001). In the test-group the buccal-surfaces accounted for most white-opacities and close to 1/3 of these lesions on the upper-anterior teeth were located around the brackets. The questionnaire disclosed that 58% in the test- vs. 44% in the reference-group did not accept having dental caries lesions during the orthodontic treatment. The results showed a high prevalence of white-opacities related to orthodontic appliances and indicate the need to implement preventive programmes at the dental clinic.

Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis

PubMed Central

Schneider, Torben; Solanky, Bhavana S.; Yiannakas, Marios C.; Altmann, Dan R.; Wheeler-Kingshott, Claudia A. M.; Peters, Amy L.; Day, Brian L.; Thompson, Alan J.; Ciccarelli, Olga

2015-01-01

Spinal neurodegeneration is an important determinant of disability progression in patients with primary progressive multiple sclerosis. Advanced imaging techniques, such as single-voxel 1H-magnetic resonance spectroscopy and q-space imaging, have increased pathological specificity for neurodegeneration, but are challenging to implement in the spinal cord and have yet to be applied in early primary progressive multiple sclerosis. By combining these imaging techniques with new clinical measures, which reflect spinal cord pathology more closely than conventional clinical tests, we explored the potential for spinal magnetic resonance spectroscopy and q-space imaging to detect early spinal neurodegeneration that may be responsible for clinical disability. Data from 21 patients with primary progressive multiple sclerosis within 6 years of disease onset, and 24 control subjects were analysed. Patients were clinically assessed on grip strength, vibration perception thresholds and postural stability, in addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25-Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale. All subjects underwent magnetic resonance spectroscopy and q-space imaging of the cervical cord and conventional brain and spinal magnetic resonance imaging at 3 T. Multivariate analyses and multiple regression models were used to assess the differences in imaging measures between groups and the relationship between magnetic resonance imaging measures and clinical scores, correcting for age, gender, spinal cord cross-sectional area, brain T2 lesion volume, and brain white matter and grey matter volume fractions. Although patients did not show significant cord atrophy when compared with healthy controls, they had significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P = 0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than controls. Patients showed an increase in q-space imaging-derived indices of perpendicular diffusivity in both the whole cord and major columns compared with controls (P < 0.05 for all indices). Lower total N-acetyl-aspartate was associated with higher disability, as assessed by the Expanded Disability Status Scale (coefficient = −0.41, 0.01 < P < 0.05), Modified Ashworth Scale (coefficient = −3.78, 0.01 < P < 0.05), vibration perception thresholds (coefficient = −4.37, P = 0.021) and postural sway (P < 0.001). Lower glutamate-glutamine predicted increased postural sway (P = 0.017). Increased perpendicular diffusivity in the whole cord and columns was associated with increased scores on the Modified Ashworth Scale, vibration perception thresholds and postural sway (P < 0.05 in all cases). These imaging findings indicate reduced structural integrity of neurons, demyelination, and abnormalities in the glutamatergic pathways in the cervical cord of early primary progressive multiple sclerosis, in the absence of extensive spinal cord atrophy. The observed relationship between imaging measures and disability suggests that early spinal neurodegeneration may underlie clinical impairment, and should be targeted in future clinical trials with neuroprotective agents to prevent the development of progressive disability. PMID:25863355

Comparison between clinical and audiological results of tympanoplasty with modified sandwich technique and underlay technique.

PubMed

Nemade, Sanjana Vijay; Shinde, Kiran Jaywant; Naik, Chetana Shivadas; Qadri, Haris

Surgical repair of the tympanic membrane, termed a type one tympanoplasty is a tried and tested treatment modality. Overlay or underlay technique of tympanoplasty is common. Sandwich tympanoplasty is the combined overlay and underlay grafting of tympanic membrane. To describe and evaluate the modified sandwich graft (mediolateral graft) tympanoplasty using temporalis fascia and areolar fascia. To compare the clinical and audiological outcome of modified sandwich tympanoplasty with underlay tympanoplasty. A total of 88 patients of chronic otitis media were studied. 48 patients (Group A) underwent type one tympanoplasty with modified sandwich graft. Temporalis fascia was underlaid and the areolar fascia was overlaid. 48 patients (Group B) underwent type one tympanoplasty with underlay technique. We assessed the healing and hearing results. Successful graft take up was accomplished in 47 patients (97.9%) in Group A and in 40 patients (83.3%) Group B. The average Air-Bone gap closure achieved in Group A was 24.4±1.7dB while in Group B; it was 22.5±3.5dB. Statistically significant difference was found in graft healing rate. Difference in hearing improvement was not statistically significant. Double layered graft with drum-malleus as a 'meat' of sandwich maintains a perfect balance between sufficient stability and adequate acoustic sensitivity. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Translation of an Evidence-Based Tailored Childhood Injury Prevention Program

PubMed Central

Weaver, Nancy L.; Williams, Janice; Jacobsen, Heather A.; Botello-Harbaum, Maria; Glasheen, Cristie; Noelcke, Elizabeth; Nansel, Tonja R.

2008-01-01

This article describes the process of translating Safe n’ Sound, a computer-based program for parents of young children, for a general clinic environment. Safe n’ Sound is designed to reduce the risk of unintentional childhood injuries, the leading cause of death among children older than 1 year in the United States. The evidence-based program produces tailored information for parents and their healthcare provider about burns, falls, poisoning, drowning, suffocations, choking prevention, and car safety. To offer Safe n’ Sound to a broader audience, we translated the program from the form used for efficacy testing to a stand-alone application. Notable steps in this translation included (1) conducting an organizational assessment to determine the needs of the clinic staff and feasibility of implementation, (2) modifying the program to reduce length, prioritize risk areas, and update content, (3) repackaging the program to minimize cost and space requirements, and (4) developing promotional and instructional materials. Factors contributing to the success of this effort include strong collaborative partnerships, the relative advantage of Safe n’ Sound over traditional materials, the modifiable design of the program, and the support of the clinic staff and providers. Challenges and areas for future work are discussed. PMID:18287925

Clinical usefulness of the faecal calprotectin test in suspected paediatric inflammatory bowel disease.

PubMed

Akobeng, Anthony K

2018-04-29

The faecal calprotectin (FC) test is increasingly being used in clinical practice to help select children with gastrointestinal symptoms who might have inflammatory bowel disease (IBD) and benefit from endoscopies. We provide an overview of the advantages and limitations of the FC test. PubMed was searched for meta-analyses that had investigated the diagnostic accuracy of the FC test and the pooled sensitivity and specificity for distinguishing IBD from non-IBD patients were used to calculate likelihood ratios (LR). These were applied to practical examples to explain how easily clinicians can use the results to modify pre-test probabilities of IBD and generate post-test probabilities for IBD. The positive LR and negative LR of the FC test were 2.8 and 0.015, respectively. The usefulness of the FC test depended on the pre-test probability of IBD. When the pre-test probability of IBD was low, a positive FC test did not necessarily indicate IBD. However, because of the very small negative LR, a negative FC result virtually ruled out IBD in most cases. The FC test should not be used indiscriminately in children with gastrointestinal symptoms but should be targeted at those who are likely to have IBD. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Linking medical faculty stress/burnout to willingness to implement medical school curriculum change: a preliminary investigation.

PubMed

Arvandi, Zeinab; Emami, Amirhossein; Zarghi, Nazila; Alavinia, Seyed Mohammad; Shirazi, Mandana; Parikh, Sagar V

2016-02-01

Balancing administrative demands from the medical school while providing patient support and seeking academic advancement can cause personal hardship that ranges from high stress to clinically recognizable conditions such as burnout. Regarding the importance of clinical faculties' burnout and its effects on different aspects of their professional career, this study was conducted and aimed to evaluate the relationship between willingness to change teaching approaches as characterized by a modified stage-of-change model and measures of stress and burnout. This descriptive analytic study was conducted on 143 clinical faculty members of Tehran University of Medical Sciences in Iran. Participants were asked to complete three questionnaires: a modified stages of change questionnaire the Maslach Burnout Inventory and the General Health Questionnaire. Data were analysed by SPSS: 16 using non-parametric statistical tests such as multiple regression and ICC (intra-class coefficient) and Spearman correlation coefficient test. A significant relationship was found between faculty members' readiness to change teaching approaches and the subscales of occupational burnout. Specifically, participants with low occupational burnout were more likely to be in the action stage, while those with high burnout were in the attitude or intention stage, which could be understood as not being ready to implement change. There was no significant correlation between general health scores and stage of change. We found it feasible to measure stages of change as well as stress/burnout in academic doctors. Occupational burnout directly reduces the readiness to change. To have successful academic reform in medical schools, it therefore would be beneficial to assess and manage occupational burnout among clinical faculty members. © 2015 John Wiley & Sons, Ltd.

The effects of Lactobacillus reuteri probiotics combined with azithromycin on peri-implantitis: A randomized placebo-controlled study.

PubMed

Tada, Hiroaki; Masaki, Chihiro; Tsuka, Shintaro; Mukaibo, Taro; Kondo, Yusuke; Hosokawa, Ryuji

2018-01-01

The aim of this randomized placebo-controlled clinical study was to investigate the effects of a probiotic tablet containing Lactobacillus reuteri in peri-implantitis patients. Subjects comprised 30 patients with mild to moderate peri-implantitis. A baseline clinical examination and microbiological assessment were conducted, followed by an antibiotics treatment (azithromycin, 500mg, once a day for 3 days). Subjects were divided into probiotic and placebo groups. The clinical examination and bacterial sampling were performed 0, 4, 12 and 24 weeks after the intake of probiotics. The clinical examination included probing pocket depth (PPD), bleeding on probing (BOP), the modified plaque index (mPI), and modified bleeding index (mBI). The number of bacteria was assessed using the PCR-invader method. The Wilcoxon rank-sum test and Wilcoxon signed-rank test with Bonferroni corrections were used for data analyses. Although the number of bacteria decreased after the administration of azithromycin in both groups, they increased again thereafter. No significant difference was observed in bacterial numbers between the two groups. Although PPD in the probiotics group was significantly lower at 4 and 24 weeks than at 0 weeks (p<0.05), a significant decrease did not occur in the placebo group. The mBI score at 24 weeks was significantly lower in the probiotics group than in the placebo group (p<0.05). No significant difference was observed in BOP or mPI between the two groups. These results suggested that probiotics prevent inflammation by affecting host responses rather than improving microbial flora in peri-implant sulci in peri-implantitis patients. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Recruitment of subjects into clinical trials for Alzheimer disease.

PubMed

Knebl, Janice A; Patki, Deepti

2010-09-01

Alzheimer disease is a devastating neurodegenerative disorder affecting millions of Americans. It reduces the ability of the individual to remain independent, places a burden on caregivers, and substantially increases healthcare costs. New treatments are being tested in numerous clinical trials with the goal of preventing or delaying the onset of Alzheimer disease, slowing or modifying the disease's course, or finding a cure for patients with the disease. Alzheimer disease research can successfully proceed only if individuals who have this illness are willing to participate in clinical trials. However, recruitment and retention of subjects in clinical trials for Alzheimer disease is a challenging task. Furthermore, because of reductions in decision-making capacities of individuals with Alzheimer disease, clinical trials also need to involve caregivers. The present article delineates unique hurdles encountered in the recruitment process for Alzheimer disease clinical trials. The article also identifies strategies for effective recruitment of subjects in Alzheimer disease clinical trials, including guidelines to help principal investigators and clinical research coordinators reach recruitment goals.

Effectiveness of glucose monitoring systems modified for the visually impaired.

PubMed

Bernbaum, M; Albert, S G; Brusca, S; McGinnis, J; Miller, D; Hoffmann, J W; Mooradian, A D

1993-10-01

To compare three glucose meters modified for use by individuals with diabetes and visual impairment regarding accuracy, precision, and clinical reliability. Ten subjects with diabetes and visual impairment performed self-monitoring of blood glucose using each of the three commercially available blood glucose meters modified for visually impaired users (the AccuChek Freedom [Boehringer Mannheim, Indianapolis, IN], the Diascan SVM [Home Diagnostics, Eatontown, NJ], and the One Touch [Lifescan, Milpitas, CA]). The meters were independently evaluated by a laboratory technologist for precision and accuracy determinations. Only two meters were acceptable with regard to laboratory precision (coefficient of variation < 10%)--the Accuchek and the One Touch. The Accuchek and the One Touch did not differ significantly with regard to laboratory estimates of accuracy. A great discrepancy of the clinical reliability results was observed between these two meters. The Accuchek maintained a high degree of reliability (y = 0.99X + 0.44, r = 0.97, P = 0.001). The visually impaired subjects were unable to perform reliable testing using the One Touch system because of a lack of appropriate tactile landmarks and auditory signals. In addition to laboratory assessments of glucose meters, monitoring systems designed for the visually impaired must include adequate tactile and audible feedback features to allow for the acquisition and placement of appropriate blood samples.

Reporting Guidelines for Clinical Pharmacokinetic Studies: The ClinPK Statement.

PubMed

Kanji, Salmaan; Hayes, Meghan; Ling, Adam; Shamseer, Larissa; Chant, Clarence; Edwards, David J; Edwards, Scott; Ensom, Mary H H; Foster, David R; Hardy, Brian; Kiser, Tyree H; la Porte, Charles; Roberts, Jason A; Shulman, Rob; Walker, Scott; Zelenitsky, Sheryl; Moher, David

2015-07-01

Transparent reporting of all research is essential for assessing the validity of any study. Reporting guidelines are available and endorsed for many types of research but are lacking for clinical pharmacokinetic studies. Such tools promote the consistent reporting of a minimal set of information for end users, and facilitate knowledge translation of research. The objective of this study was to create a guideline to assist in the transparent and complete reporting of clinical pharmacokinetic studies. Preliminary content to be considered was identified from a systematic search of the literature and regulatory documents. Stakeholders were identified to participate in a modified Delphi exercise and a virtual meeting to generate consensus for items considered essential in the reporting of clinical pharmacokinetic studies. The proposed checklist was pilot tested on 100 recently published clinical pharmacokinetic studies. Overall and itemized compliance with the proposed guidance was determined for each study. Sixty-eight stakeholders from nine countries consented to participate. Four rounds of a modified Delphi survey and a series of small virtual meetings were required to generate consensus for a 24-item checklist considered to be essential to the reporting of clinical pharmacokinetic studies. When applied to the 100 most recently published clinical pharmacokinetic studies, 45 were determined to be compliant with at least 80 % of the checklist items. Explanatory text was prepared using examples of compliant reporting from these and other relevant studies. The reader's ability to judge the validity of pharmacokinetic research can be greatly compromised by the incomplete reporting of study information. Using consensus methods, we have developed a tool to guide transparent and accurate reporting of clinical pharmacokinetic studies. Endorsement and implementation of these guidelines by researchers, clinicians and journals would promote more consistent reporting of these studies and allow for better assessment of utility for clinical applications.

Modified bathroom scale and balance assessment: a comparison with clinical tests.

PubMed

Duchêne, Jacques; Hewson, David; Rumeau, Pierre

2016-01-01

Frailty and detection of fall risk are major issues in preventive gerontology. A simple tool frequently used in daily life, a bathroom scale (balance quality tester: BQT), was modified to obtain information on the balance of 84 outpatients consulting at a geriatric clinic. The results computed from the BQT were compared to the values of three geriatric tests that are widely used either to detect a fall risk or frailty (timed get up and go: TUG; 10 m walking speed: WS; walking time: WT; one-leg stand: OS). The BQT calculates four parameters that are then scored and weighted, thus creating an overall indicator of balance quality. Raw data, partial scores and the global score were compared with the results of the three geriatric tests. The WT values had the highest correlation with BQT raw data (r = 0.55), while TUG (r = 0.53) and WS (r = 0.56) had the highest correlation with BQT partial scores. ROC curves for OS cut-off values (4 and 5 s) were produced, with the best results obtained for a 5 s cut-off, both with the partial scores combined using Fisher's combination (specificity 85 %: <0.11, sensitivity 85 %: >0.48), and with the empirical score (specificity 85 %: <7, sensitivity 85 %: >8). A BQT empirical score of less than seven can detect fall risk in a community dwelling population.

Multiplex PCR for the detection of genes encoding aminoglycoside modifying enzymes and methicillin resistance among Staphylococcus species.

PubMed Central

Choi, Su Mi; Kim, Seung-Han; Kim, Hee-Jung; Lee, Dong-Gun; Choi, Jung-Hyun; Yoo, Jin-Hong; Kang, Jin-Han; Shin, Wan-Shik; Kang, Moon-Won

2003-01-01

We developed multiplex polymerase chain reaction (PCR) to detect aac(6 ')/aph(2 "), aph(3 ')-IIIa, and ant(4 ')-Ia, the genes encoding the most clinically relevant amino-glycoside modifying enzymes (AME), and simultaneously, the methicillin resistant gene, mecA, in Staphylococcus species. Clinical isolates of 45 S. aureus and 47 coagulase negative staphylococci (CNS) from tertiary university hospitals were tested by conventional susceptibility testing, using the agar dilution method and by multiplex PCR. Of a total of 92 isolates, 61 isolates were found to be methicillin-resistant. Of these, 54 isolates (89%) were found to be harboring mecA. Seventy-five percent of the 92 isolates demonstrated resistance to at least one of the aminoglycosides tested. Moreover, resistance to aminoglycosides was closely associated with methicillin-resistance (p<0.05). The most prevalent AME gene was aac(6 ')/aph(2 ") which was found in 65% of the isolates, and ant(4 ')-Ia and aph(3 ')-IIIa were present in 41% and 9% of the isolates, respectively. The concordance between methicillin-resistance and the presence of mecA gene was 98% in S. aureus and 81% in CNS. The concordance between gentamicin resistance and the presence of aac(6 ')/aph(2 ") gene was 100% in S. aureus and 85% in CNS. The multiplex PCR method that we developed appears to be both a more rapid and reliable than conventional method. PMID:14555812

[Current pharmacotherapies and immunotherapy in cocaine addiction].

PubMed

Karila, Laurent; Weinstein, Aviv; Benyamina, Amine; Coscas, Sarah; Leroy, Claire; Noble, Florence; Lowenstein, William; Aubin, Henri-Jean; Lépine, Jean-Pierre; Reynaud, Michel

2008-04-01

Cocaine is more and more used and abused in France. Cocaine dependence is quite serious and is associated with numerous adverse health consequences. No effective pharmacotherapy for cocaine dependence is yet available. Recent advances in neurobiology, brain imaging and some clinical trials suggest that certain medications that modulate GABAergic, dopaminergic, and glutamatergic systems, as well as immunotherapy, show promise in the treatment of cocaine addiction. Recent controlled clinical studies have tested some of these drugs, which act on the various neurobiological circuits modified by cocaine exposure and clinically improve patients' symptoms. Pharmacological agents such as modafinil, GABAergic agents (baclofen, topiramate, tiagabin, and vigabatrin), disulfiram, aripiprazole, N-acetylcysteine and cocaine vaccine seem very promising in the treatment of cocaine dependence. However, this must be confirmed in larger patient populations.

Brisk deep-tendon reflexes as a distinctive phenotype in an Argentinean spinocerebellar ataxia type 2 pedigree.

PubMed

Rosa, Alberto L; Molina, Irma; Kowaljow, Valeria; Conde, Cecilia B

2006-01-01

Slow saccades, postural/intention tremor, peripheral neuropathy, and decreased deep-tendon reflexes are valuable neurological signs for clinical suspicion of spinocerebellar ataxia type 2 (SCA2). We report the presence of abnormally brisk deep-tendon reflexes in nonsymptomatic carriers and mildly and severely affected subjects of a large Argentinean SCA2 pedigree. The identification of this distinctive SCA2 phenotype in an entire pedigree reinforces the current concept that clinical algorithms are of limited value as indicators for genetic testing in SCA. Combined with published pedigrees of SCA2 manifesting as levodopa-responsive parkinsonism, this finding suggests that modifier genes could influence the clinical phenotype of SCA2. Copyright (c) 2005 Movement Disorder Society.

[First Argentine consensus guidelines for in vitro antimicrobial susceptibility testing of clinically relevant anaerobic bacteria in humans/ Anaerobic Subcommittee of the Asociación Argentina de Microbiología].

PubMed

Legaria, María C; Bianchini, Hebe M; Castello, Liliana; Carloni, Graciela; Di Martino, Ana; Fernández Canigia, Liliana; Litterio, Mirta; Rollet, Raquel; Rossetti, Adelaida; Predari, Silvia C

2011-01-01

Through time, anaerobic bacteria have shown good susceptibility to clinically useful antianaerobic agents. Nevertheless, the antimicrobial resistance profile of most of the anaerobic species related to severe infections in humans has been modified in the last years and different kinds of resistance to the most active agents have emerged, making their effectiveness less predictable. With the aim of finding an answer and for the purpose of facilitating the detection of anaerobic antimicrobial resistance, the Anaerobic Subcommittee of the Asociación Argentina de Microbiología developed the First Argentine consensus guidelines for in vitro antimicrobial susceptibility testing of clinically relevant anaerobic bacteria in humans. This document resulted from the compatibilization of the Clinical and Laboratory Standards Institute recommendations, the international literature and the work and experience of the Subcommittee. The Consensus document provides a brief taxonomy review, and exposes why and when anaerobic antimicrobial susceptibility tests should be conducted, and which antimicrobial agents can be used according to the species involved. The recommendations on how to perform, read and interpret in vitro anaerobic antimicrobial susceptibility tests with each method are exposed. Finally, the antibiotic susceptibility profile, the classification of antibiotics according to their in vitro activities, the natural and acquired mechanisms of resistance, the emerging resistance and the regional antibiotic resistance profile of clinically relevant anaerobic species are shown.

Controversies in Alzheimer's disease drug development.

PubMed

Cummings, Jeffrey L

2008-08-01

Understanding of the pathophysiological basis of Alzheimer's disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer's disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described.

Role of preliminary registry data in development of a clinical trial for an innovative device: a small but integral piece of a health policy initiative

PubMed Central

Ricci, Donald R.; de Vries, Joost; Blanc, Raphael

2017-01-01

ABSTRACT Establishing a national health policy at a macro level involves the integration of a series of health initiatives across a spectrum of activities, including clinical care. Evaluation of the safety and efficacy of a new medical device ultimately evolves to testing in humans. The pathway to a formal prospective clinical trial includes a stepwise appreciation of pre-clinical data and detailed analysis of data obtained from preliminary registries, where information about appropriate patient selection and use of the device is obtained. Evaluation of procedural and follow-up efficacy and safety data in a preliminary series of cases, chosen to simulate published data, allows the design and conduct of clinical trials that are required to verify preliminary observations, closing the loop on one aspect of modifying health policy decisions. PMID:28321285

The Translational Science Benefits Model: A New Framework for Assessing the Health and Societal Benefits of Clinical and Translational Sciences

PubMed Central

Sarli, Cathy C.; Suiter, Amy M.; Carothers, Bobbi J.; Combs, Todd B.; Allen, Jae L.; Beers, Courtney E.; Evanoff, Bradley A.

2017-01-01

Abstract We report the development of the Translational Science Benefits Model (TSBM), a framework designed to support institutional assessment of clinical and translational research outcomes to measure clinical and community health impacts beyond bibliometric measures. The TSBM includes 30 specific and potentially measurable indicators that reflect benefits that accrue from clinical and translational science research such as products, system characteristics, or activities. Development of the TSBM was based on literature review, a modified Delphi method, and in‐house expert panel feedback. Three case studies illustrate the feasibility and face validity of the TSBM for identification of clinical and community health impacts that result from translational science activities. Future plans for the TSBM include further pilot testing and a resource library that will be freely available for evaluators, translational scientists, and academic institutions who wish to implement the TSBM framework in their own evaluation efforts. PMID:28887873

A modified haemagglutination inhibition test for rubella antibodies, using standardized, freeze-dried reagents. Report of a comparative multi-centre trial.

PubMed Central

van Weemen, B.; Kacaki, J.

1976-01-01

A modified haemagglutination inhibition test for rubella antibodies, using standardized freeze-dried reagents, was developed and compared with haemagglutination inhibition tests using fresh erythrocytes. This comparison was made in collaboration with six European laboratories. A total of 4205 serum samples were tested. The results show that: (1) Sensitivity and reliability of the modified test are good; (2) the modified test can be performed in polystyrene microtitration plates. PMID:789763

Prediction of Lateral Ankle Sprains in Football Players Based on Clinical Tests and Body Mass Index.

PubMed

Gribble, Phillip A; Terada, Masafumi; Beard, Megan Q; Kosik, Kyle B; Lepley, Adam S; McCann, Ryan S; Pietrosimone, Brian G; Thomas, Abbey C

2016-02-01

The lateral ankle sprain (LAS) is the most common injury suffered in sports, especially in football. While suggested in some studies, a predictive role of clinical tests for LAS has not been established. To determine which clinical tests, focused on potentially modifiable factors of movement patterns and body mass index (BMI), could best demonstrate risk of LAS among high school and collegiate football players. Case-control study; Level of evidence, 3. A total of 539 high school and collegiate football players were evaluated during the preseason with the Star Excursion Balance Test (SEBT) and Functional Movement Screen as well as BMI. Results were compared between players who did and did not suffer an LAS during the season. Logistic regression analyses and calculated odds ratios were used to determine which measures predicted risk of LAS. The LAS group performed worse on the SEBT-anterior reaching direction (SEBT-ANT) and had higher BMI as compared with the noninjured group (P < .001). The strongest prediction models corresponded with the SEBT-ANT. Low performance on the SEBT-ANT predicted a risk of LAS in football players. BMI was also significantly higher in football players who sustained an LAS. Identifying clinical tools for successful LAS injury risk prediction will be a critical step toward the creation of effective prevention programs to reduce risk of sustaining an LAS during participation in football. © 2015 The Author(s).

Effectiveness of problem based learning as an instructional tool for acquisition of content knowledge and promotion of critical thinking among medical students.

PubMed

Tayyeb, Rakhshanda

2013-01-01

To assess effectiveness of PBL as an instructional tool in clinical years to improve learning of undergraduate students in terms of acquisition of content knowledge, critical thinking and problem solving skills through problem based learning and traditional way of teaching. Quasi-experimental study. Fatima Jinnah Medical College for Women, Lahore, from October 2009 to April 2010. Final year medical students attending Obstetrics and Gynaecology and Surgery rotations were inducted as participants in this study. Two batches of 50 students each attended Gynaecology rotation and two batches attended Surgery rotation, i.e. 100 students in each. Each batch was divided into two groups i.e. A and B of 25 students each. Group-A learnt through traditional teaching, involving bedside teaching and lectures in wards and Group-B learnt relevant clinical knowledge through a modified PBL process. Content knowledge was tested by MCQs testing recall while clinical reasoning and problem were assessed by MCQs testing analysis and critical thinking. Intra-group comparison of mean scores of pre and post-test scores was done using paired sample t-tests while for intergroup comparison of mean scores was done through independent sample t-test. Teaching through traditional method significantly improved content knowledge, (p = 0.001) but did not considerably improve clinical reasoning and problem solving skills (p = 0.093) whereas, content knowledge of students who studied through PBL remained the same (p = 0.202) but there was marked improvement in their clinical reasoning and problem solving skills (p = < 0.001). PBL is an effective instructional tool to foster critical thinking and problem solving skills among medical students.

AmpC β-lactamases in nosocomial isolates of Klebsiella pneumoniae from India

PubMed Central

Gupta, Varsha; Kumarasamy, Karthikeyan; Gulati, Neelam; Garg, Ritu; Krishnan, Padma; Chander, Jagdish

2012-01-01

Background & objectives: AmpC β-lactamases are clinically significant since these confer resistance to cephalosporins in the oxyimino group, 7-α methoxycephalosporins and are not affected by available β-lactamase inhibitors. In this study we looked for both extended spectrum β-lactamases (ESBL) and AmpC β-lactamases in Klebsiella pneumoniae clinical isolates. Methods: One hundred consecutive, non-duplicate clinical isolates of K. pneumoniae collected over a period of one year (June 2008 - June 2009) were included in the study. An antibiotic susceptibility method was used with 10 antibiotics for Gram-negative infections which helped in screening for ESBL and AmpC β-lactamases and also in confirmation of ESBL production. The detection of AmpC β-lactamases was done based on screening and confirmatory tests. For screening, disc diffusion zones of cefoxitin <18 mm was taken as cefoxitin resistant. All cefoxitin resistant isolates were tested further by AmpC disk test and modified three dimensional test. Multiplex-PCR was performed for screening the presence of plasmid-mediated AmpC genes. Results: Of the 100 isolates of K. pneumoniae studied, 48 were resistant to cefoxitin on screening. AmpC disk test was positive in 32 (32%) isolates. This was also confirmed with modified three dimensional test. Indentation indicating strong AmpC producer was observed in 25 isolates whereas little distortion (weak AmpC) was observed in 7 isolates. ESBL detection was confirmed by a modification of double disk synergy test in 56 isolates. Cefepime was the best cephalosporin in synergy with tazobactam for detecting ESBL production in isolates co-producing AmpC β-lactamases. The subsets of isolates phenotypically AmpC β-lactamase positive were subjected to amplification of six different families of AmpC gene using multiplex PCR. The sequence analysis revealed 12 CMY-2 and eight DHA-1 types. Interpretation & conclusions: Tazobactam was the best β-lactamase inhibitor for detecting ESBL in presence of AmpC β-lactamase as this is a very poor inducer of AmpC gene. Amongst cephalosporins, cefepime was the best cephalosporin in detecting ESBL in presence of AmpC β-lactamase as it is least hydrolyzed by AmpC enzymes. Cefepime-tazobactam combination disk test would be a simple and best method in detection of ESBLs in Enterobacteriaceae co-producing AmpC β-lactamase in the routine diagnostic microbiology laboratories. PMID:22960890

Assessing working memory in children with ADHD: Minor administration and scoring changes may improve digit span backward's construct validity.

PubMed

Wells, Erica L; Kofler, Michael J; Soto, Elia F; Schaefer, Hillary S; Sarver, Dustin E

2018-01-01

Pediatric ADHD is associated with impairments in working memory, but these deficits often go undetected when using clinic-based tests such as digit span backward. The current study pilot-tested minor administration/scoring modifications to improve digit span backward's construct and predictive validities in a well-characterized sample of children with ADHD. WISC-IV digit span was modified to administer all trials (i.e., ignore discontinue rule) and count digits rather than trials correct. Traditional and modified scores were compared to a battery of criterion working memory (construct validity) and academic achievement tests (predictive validity) for 34 children with ADHD ages 8-13 (M=10.41; 11 girls). Traditional digit span backward scores failed to predict working memory or KTEA-2 achievement (allns). Alternate administration/scoring of digit span backward significantly improved its associations with working memory reordering (r=.58), working memory dual-processing (r=.53), working memory updating (r=.28), and KTEA-2 achievement (r=.49). Consistent with prior work, these findings urge caution when interpreting digit span performance. Minor test modifications may address test validity concerns, and should be considered in future test revisions. Digit span backward becomes a valid measure of working memory at exactly the point that testing is traditionally discontinued. Copyright © 2017 Elsevier Ltd. All rights reserved.

Empirical testing of criteria for dissociative schizophrenia.

PubMed

Laferrière-Simard, Marie-Christine; Lecomte, Tania; Ahoundova, Lola

2014-01-01

This study examined the validity of dissociative schizophrenia diagnostic criteria. In the first phase, 50 participants with a psychotic disorder were administered the Dissociative Experiences Scale and the Childhood Trauma Questionnaire to identify those with dissociative characteristics. In the second phase, we selected those who had a score of 15 or above on the Dissociative Experiences Scale. Fifteen of these participants were evaluated thoroughly with the Structured Clinical Interview for DSM-IV Axis I, Structured Clinical Interview for DSM-IV Axis II, and Structured Clinical Interview for DSM-IV Dissociative Disorders to determine whether they met the criteria for dissociative schizophrenia and to generate a clinical description. Our results indicated that 24% of the individuals we tested met these criteria. We propose making mandatory 1 of the 3 dissociative symptoms of the criteria to eliminate people with only nonspecific symptoms (e.g., extensive comorbidity). According to this modified criterion, 14% of our sample would receive a diagnosis of dissociative schizophrenia. However, a more comprehensive look at the clinical picture begs the question of whether dissociative schizophrenia is truly present in every person meeting the criteria. We discuss the relevance of creating a new schizophrenia subtype and offer recommendations for clinicians.

Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB)

PubMed Central

Sinai, Amanda; Hassiotis, Angela; Rantell, Khadija; Strydom, Andre

2016-01-01

Background Down syndrome is associated with specific cognitive deficits. Alongside this, older adults with Down syndrome are a high risk group for dementia. The Arizona Cognitive Test Battery (ACTB), a cognitive assessment battery specifically developed for use with individuals with Down syndrome, has been proposed for use as outcome measures for clinical trials in this population. It has not been validated in older adults with Down syndrome. This study aims to assess the use and validity of the ACTB in older adults with Down syndrome. Methods Participants with Down syndrome aged 45 and over were assessed using the ACTB, standard tabletop tests and informant ratings. Results Assessment outcomes of 49 participants were analysed. Of these, 19 (39%) had a diagnosis of dementia or possible dementia. Most participants were able to attempt most of the tasks, although some tasks had high floor effects (including CANTAB Intra-Extra Dimensional shift stages completed and Modified Dots Task). Of the ACTB tasks, statistically significant differences were observed between the dementia and no dementia groups on CANTAB Simple Reaction Time median latency, NEPSY Visuomotor Precision—Car and Motorbike and CANTAB Paired Associates Learning stages completed. No significant differences were observed for CANTAB Intra-Extra Dimensional Shift, Modified Dots Task, Finger Sequencing, NEPSY Visuomotor precision—Train and Car and CANTAB Paired Associates Learning first trial memory score. Several of the tasks in the ACTB can be used in older adults with Down syndrome and have mild to moderate concurrent validity when compared to tabletop tests and informant ratings, although this varies on a test by test basis. Conclusions Overall, scores for a number of tests in the ACTB were similar when comparing dementia and no dementia groups of older adults with Down syndrome, suggesting that it would not be an appropriate outcome measure of cognitive function for clinical trials of dementia treatments without further modification and validation. PMID:27171413

Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB).

PubMed

Sinai, Amanda; Hassiotis, Angela; Rantell, Khadija; Strydom, Andre

2016-01-01

Down syndrome is associated with specific cognitive deficits. Alongside this, older adults with Down syndrome are a high risk group for dementia. The Arizona Cognitive Test Battery (ACTB), a cognitive assessment battery specifically developed for use with individuals with Down syndrome, has been proposed for use as outcome measures for clinical trials in this population. It has not been validated in older adults with Down syndrome. This study aims to assess the use and validity of the ACTB in older adults with Down syndrome. Participants with Down syndrome aged 45 and over were assessed using the ACTB, standard tabletop tests and informant ratings. Assessment outcomes of 49 participants were analysed. Of these, 19 (39%) had a diagnosis of dementia or possible dementia. Most participants were able to attempt most of the tasks, although some tasks had high floor effects (including CANTAB Intra-Extra Dimensional shift stages completed and Modified Dots Task). Of the ACTB tasks, statistically significant differences were observed between the dementia and no dementia groups on CANTAB Simple Reaction Time median latency, NEPSY Visuomotor Precision-Car and Motorbike and CANTAB Paired Associates Learning stages completed. No significant differences were observed for CANTAB Intra-Extra Dimensional Shift, Modified Dots Task, Finger Sequencing, NEPSY Visuomotor precision-Train and Car and CANTAB Paired Associates Learning first trial memory score. Several of the tasks in the ACTB can be used in older adults with Down syndrome and have mild to moderate concurrent validity when compared to tabletop tests and informant ratings, although this varies on a test by test basis. Overall, scores for a number of tests in the ACTB were similar when comparing dementia and no dementia groups of older adults with Down syndrome, suggesting that it would not be an appropriate outcome measure of cognitive function for clinical trials of dementia treatments without further modification and validation.

The instrumented Timed Up and Go test: Potential outcome measure for disease modifying therapies in Parkinson's disease

PubMed Central

Zampieri, Cris; Salarian, Arash; Carlson-Kuhta, Patricia; Aminian, Kamiar; Nutt, John G.; Horak, Fay B.

2011-01-01

The Timed Up and Go (TUG) test has been used to assess balance and mobility in Parkinson’s Disease (PD). However, it is not known if this test is sensitive to subtle abnormalities present in early stages of the disease, when balance and gait problems are not clinically evident but may be detected with instrumented analysis of movement. We hypothesize that postural transitions and arm swing during gait will be the most sensitive characteristics of the TUG for early PD. In the present study, we instrumented the TUG test (iTUG) using portable inertial sensors, and extended the walking distance from 3 meters (traditional TUG) to 7 meters. Twelve subjects with early-to-moderate, untreated PD and 12 healthy individuals participated. Our findings show that although the stopwatch measure of TUG duration did not detect abnormalities in early-to-mid stage PD, the peak arm swing velocity on the more affected side, average turning velocity, cadence and peak trunk rotation velocity were significantly slower. These iTUG parameters were also correlated with the UPDRS Motor Scale. Thus, the iTUG test is sensitive to untreated PD and could potentially detect progression of PD and response to symptomatic and disease-modifying treatments. PMID:19726406

Implicit cognitive processes in psychopathology: an introduction.

PubMed

Wiers, Reinout W; Teachman, Bethany A; De Houwer, Jan

2007-06-01

Implicit or automatic processes are important in understanding the etiology and maintenance of psychopathological problems. In order to study implicit processes in psychopathology, measures are needed that are valid and reliable when applied to clinical problems. One of the main topics in this special issue concerns the development and validation of new or modified implicit tests in different domains of psychopathology. The other main topic concerns the prediction of clinical outcomes and new ways to directly influence implicit processes in psychopathology. We summarize the contributions to this special issue and discuss how they further our knowledge of implicit processes in psychopathology and how to measure them.

The Wundt-Jastrow illusion in the study of spatial hemi-inattention.

PubMed

Massironi, M; Antonucci, G; Pizzamiglio, L; Vitale, M V; Zoccolotti, P

1988-01-01

A new test to detect unilateral neglect was devised using a modified version of the Wundt-Jastrow area illusion. The test was given to three groups of subjects: left brain damaged (LBD), right brain damaged (RBD) patients and controls. Of RBD patients, 40.4% but no LBD patient or control, showed responses inconsistent with the visual illusion when the determinant features of the illusion pointed to the left visual field. These unexpected responses were highly related to a clinical evaluation of the severity of the hemi-inattention disorder. The sensitivity of this test and of other standard measures of hemi-neglect were compared. The possibility of identifying qualitatively different forms of hemi-neglect was also discussed.

Affected sib pair tests in inbred populations.

PubMed

Liu, W; Weir, B S

2004-11-01

The affected-sib-pair (ASP) method for detecting linkage between a disease locus and marker loci was first established 50 years ago, and since then numerous modifications have been made. We modify two identity-by-state (IBS) test statistics of Lange (Lange, 1986a, 1986b) to allow for inbreeding in the population. We evaluate the power and false positive rates of the modified tests under three disease models, using simulated data. Before estimating false positive rates, we demonstrate that IBS tests are tests of both linkage and linkage disequilibrium between marker and disease loci. Therefore, the null hypothesis of IBS tests should be no linkage and no LD. When the population inbreeding coefficient is large, the false positive rates of Lange's tests become much larger than the nominal value, while those of our modified tests remain close to the nominal value. To estimate power with a controlled false positive rate, we choose the cutoff values based on simulated datasets under the null hypothesis, so that both Lange's tests and the modified tests generate same false positive rate. The powers of Lange's z-test and our modified z-test are very close and do not change much with increasing inbreeding. The power of the modified chi-square test also stays stable when the inbreeding coefficient increases. However, the power of Lange's chi-square test increases with increasing inbreeding, and is larger than that of our modified chi-square test for large inbreeding coefficients. The power is high under a recessive disease model for both Lange's tests and the modified tests, though the power is low for additive and dominant disease models. Allowing for inbreeding is therefore appropriate, at least for diseases known to be recessive.

Gene therapy for Parkinson's disease: Disease modification by GDNF family of ligands.

PubMed

Kirik, Deniz; Cederfjäll, Erik; Halliday, Glenda; Petersén, Åsa

2017-01-01

Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor l-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of glial-cell line derived neurotrophic factor and neurturin to rescue degenerating dopaminergic neurons in the substantia nigra and their axon terminals in the striatum by delivery of these neurotrophic factors either as purified protein or by means of viral vector mediated gene delivery to the brain. Although gene therapy approaches tested so far have been shown to be safe, none met their primary endpoints in phase II clinical trials designed and powered to test the efficacy of the intervention. Within the scope of this review we aim to describe the state-of-the-art in the field, how different technical parameters were translated from pre-clinical studies in non-human primates to clinical trials, and what these trials taught us regarding important factors that may pave the way to the success of gene therapy for the treatment of Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Application description and policy model in collaborative environment for sharing of information on epidemiological and clinical research data sets.

PubMed

de Carvalho, Elias César Araujo; Batilana, Adelia Portero; Simkins, Julie; Martins, Henrique; Shah, Jatin; Rajgor, Dimple; Shah, Anand; Rockart, Scott; Pietrobon, Ricardo

2010-02-19

Sharing of epidemiological and clinical data sets among researchers is poor at best, in detriment of science and community at large. The purpose of this paper is therefore to (1) describe a novel Web application designed to share information on study data sets focusing on epidemiological clinical research in a collaborative environment and (2) create a policy model placing this collaborative environment into the current scientific social context. The Database of Databases application was developed based on feedback from epidemiologists and clinical researchers requiring a Web-based platform that would allow for sharing of information about epidemiological and clinical study data sets in a collaborative environment. This platform should ensure that researchers can modify the information. A Model-based predictions of number of publications and funding resulting from combinations of different policy implementation strategies (for metadata and data sharing) were generated using System Dynamics modeling. The application allows researchers to easily upload information about clinical study data sets, which is searchable and modifiable by other users in a wiki environment. All modifications are filtered by the database principal investigator in order to maintain quality control. The application has been extensively tested and currently contains 130 clinical study data sets from the United States, Australia, China and Singapore. Model results indicated that any policy implementation would be better than the current strategy, that metadata sharing is better than data-sharing, and that combined policies achieve the best results in terms of publications. Based on our empirical observations and resulting model, the social network environment surrounding the application can assist epidemiologists and clinical researchers contribute and search for metadata in a collaborative environment, thus potentially facilitating collaboration efforts among research communities distributed around the globe.

Predicting Recovery Potential for Individual Stroke Patients Increases Rehabilitation Efficiency.

PubMed

Stinear, Cathy M; Byblow, Winston D; Ackerley, Suzanne J; Barber, P Alan; Smith, Marie-Claire

2017-04-01

Several clinical measures and biomarkers are associated with motor recovery after stroke, but none are used to guide rehabilitation for individual patients. The objective of this study was to evaluate the implementation of upper limb predictions in stroke rehabilitation, by combining clinical measures and biomarkers using the Predict Recovery Potential (PREP) algorithm. Predictions were provided for patients in the implementation group (n=110) and withheld from the comparison group (n=82). Predictions guided rehabilitation therapy focus for patients in the implementation group. The effects of predictive information on clinical practice (length of stay, therapist confidence, therapy content, and dose) were evaluated. Clinical outcomes (upper limb function, impairment and use, independence, and quality of life) were measured 3 and 6 months poststroke. The primary clinical practice outcome was inpatient length of stay. The primary clinical outcome was Action Research Arm Test score 3 months poststroke. Length of stay was 1 week shorter for the implementation group (11 days; 95% confidence interval, 9-13 days) than the comparison group (17 days; 95% confidence interval, 14-21 days; P =0.001), controlling for upper limb impairment, age, sex, and comorbidities. Therapists were more confident ( P =0.004) and modified therapy content according to predictions for the implementation group ( P <0.05). The algorithm correctly predicted the primary clinical outcome for 80% of patients in both groups. There were no adverse effects of algorithm implementation on patient outcomes at 3 or 6 months poststroke. PREP algorithm predictions modify therapy content and increase rehabilitation efficiency after stroke without compromising clinical outcome. URL: http://anzctr.org.au. Unique identifier: ACTRN12611000755932. © 2017 American Heart Association, Inc.

Testing the Right Target and the Right Drug at the Right Stage

PubMed Central

Sperling, Reisa A.; Jack, Clifford R.; Aisen, Paul S.

2013-01-01

Alzheimer’s disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Recent disappointing trial results at the dementia stage of AD have raised multiple questions about our current approaches to the development of disease-modifying agents. Converging evidence suggests that the pathophysiological process of AD begins many years before the onset of dementia. So why do we keep testing drugs aimed at the initial stages of the disease process in patients at the end-stage of the illness? Alzheimer’s disease (AD) remains one of the most feared consequences of aging, affecting more than one out of every ten individuals over the age of 65. With more than 10,000 baby boomers turning 65 every day in the United States alone, we are truly facing an AD epidemic. Over the past decade, a string of disappointing clinical trial results have raised concerns about our current strategy for development of AD-modifying therapies. Three hypotheses can explain these recent AD trial failures: (i) We are targeting the wrong pathophysiological mechanisms; (ii) The drugs do not engage the intended targets in patients; and (iii) The drugs are hitting the right targets, but are doing so at the wrong stage of the disease. Here, we address the third supposition and suggest that specific amyloid-based therapies be directed at much earlier stages of ADperhaps even prior to the emergence of clinical symptoms. Furthermore, we argue that the field has sufficient tools to begin “secondary prevention” trials in asymptomatic individuals whoare at high risk for progression to cognitive impairment and AD dementia. PMID:22133718

Faecal shedding of canine parvovirus after modified-live vaccination in healthy adult dogs.

PubMed

Freisl, M; Speck, S; Truyen, U; Reese, S; Proksch, A-L; Hartmann, K

2017-01-01

Since little is known about the persistence and faecal shedding of canine parvovirus (CPV) in dogs after modified-live vaccination, diagnostic tests for CPV can be difficult to interpret in the post-vaccination period. The primary aim of this study was to determine the incidence, duration and extent of CPV vaccine virus shedding in adult dogs and to investigate related factors, including the presence of protective antibodies, increase in anti-CPV antibody titres and development of any gastrointestinal side-effects. A secondary objective was to assess prevalence of CPV field virus shedding in clinically healthy dogs due to subclinical infections. One hundred adult, healthy privately owned dogs were vaccinated with a commercial CPV-2 modified-live vaccine (MLV). Faeces were tested for the presence of CPV DNA on days 0 (prior to vaccination), 3, 7, 14, 21 and 28 by quantitative real-time PCR. Pre- and post-vaccination serum titres were determined by haemagglutination inhibition on days 0, 7 and 28. Transient excretion of CPV DNA was detected in 2.0% of dogs before vaccination. About one quarter of dogs (23.0%) shed CPV DNA during the post-vaccination period, but field and vaccine virus differentiation by VP2 gene sequencing was only successful in few samples. Faecal CPV excretion occurred despite protective serum antibody titres. Post-vaccination CPV shedding was not related to adequate antibody response after vaccination or to the occurrence of gastrointestinal side-effects. Despite individual differences, CPV DNA was detectable for up to 28 days after vaccination, although the faecal CPV DNA load in these clinically healthy dogs was very low. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T-cells

PubMed Central

Scholler, John; Brady, Troy L.; Binder-Scholl, Gwendolyn; Hwang, Wei-Ting; Plesa, Gabriela; Hege, Kristen M.; Vogel, Ashley N.; Kalos, Michael; Riley, James L.; Deeks, Steven G.; Mitsuyasu, Ronald T.; Bernstein, Wendy B.; Aronson, Naomi E.; Levine, Bruce L.; Bushman, Frederic D.; June, Carl H.

2015-01-01

The success of adoptive T cell gene transfer for treatment of cancer and HIV is predicated on generating a response that is both durable and safe. Here we report long term results from three clinical trials to evaluate gammaretroviral vector engineered T-cells for HIV. The vector encoded a chimeric antigen receptor (CAR) comprised of CD4 linked to the CD3-ζ signaling chain (CD4ζ). CAR T-cells were detected in 98% of samples tested for at least 11 years post-infusion at frequencies that exceed average T cell levels after most vaccine approaches. The CD4ζ transgene retained expression and function. There was no evidence of vector-induced immortalization of cells as integration site distributions showed no evidence of persistent clonal expansion or enrichment for integration sites near genes implicated in growth control or transformation. The CD4ζ T cells have stable levels of engraftment, with decay half-lives that exceed 16 years, in marked contrast to previous trials testing engineered T cells. These findings indicate that host immunosuppression prior to T cell transfer is not required in order to achieve long term persistence of gene-modified T cells. Further, our results emphasize the safety of T cells modified by retroviral gene transfer in clinical application, as measured in >500 patient years of follow up. Thus, previous safety issues with integrating viral vectors are hematopoietic stem cell or transgene intrinsic, and not a general feature of retroviral vectors. Engineered T cells are a promising form of synthetic biology for long term delivery of protein based therapeutics. These results provide a framework to guide the therapy of a wide spectrum of human diseases. PMID:22553251

Effects of Using Modified Items to Test Students with Persistent Academic Difficulties

ERIC Educational Resources Information Center

Elliott, Stephen N.; Kettler, Ryan J.; Beddow, Peter A.; Kurz, Alexander; Compton, Elizabeth; McGrath, Dawn; Bruen, Charles; Hinton, Kent; Palmer, Porter; Rodriguez, Michael C.; Bolt, Daniel; Roach, Andrew T.

2010-01-01

This study investigated the effects of using modified items in achievement tests to enhance accessibility. An experiment determined whether tests composed of modified items would reduce the performance gap between students eligible for an alternate assessment based on modified achievement standards (AA-MAS) and students not eligible, and the…

A modified shark-fin test simulating the single-step/double-mix technique: A comparison of three groups of elastomers.

PubMed

Huettig, Fabian; Chekhani, Usama; Klink, Andrea; Said, Fadi; Rupp, Frank

2018-06-08

The shark-fin test was modified to convey the clinical application of a single-step/double-mix technique assessing the behavior of two viscosities applied at one point in time. A medium and light body polyether (PE), a medium and light body polyvinylsiloxane (PVS), and a medium as well as heavy and light body vinyl polyether silicone (PVXE) impression material were analyzed solely, and in a layered mixture of 1:1 and 3:1 at working times of 50, 80, and 120 s. The fin heights were measured with a digital ruler. The wettability was measured 50 and 80 s after mixing by drop shape analysis. The results showed a synergistic effect of the medium and light body PE. This was not observed in PVXE and PVS. Interestingly, PVXE showed an antagonistic flow behavior in 3:1 mixture with medium body. PVXE was more hydrophilic than PE and PVS. Future rheological studies should clarify the detected flow effects.

Graded aerobic treadmill testing in pediatric sports-related concussion: safety, clinical use, and patient outcomes.

PubMed

Cordingley, Dean; Girardin, Richard; Reimer, Karen; Ritchie, Lesley; Leiter, Jeff; Russell, Kelly; Ellis, Michael J

2016-12-01

OBJECTIVE The objectives of this study were 2-fold: 1) to evaluate the safety, tolerability, and clinical use of graded aerobic treadmill testing in pediatric patients with sports-related concussion (SRC), and 2) to evaluate the clinical outcomes of treatment with a submaximal aerobic exercise program in patients with physiological post-concussion disorder (PCD). METHODS The authors conducted a retrospective chart review of pediatric patients (age < 20 years) with SRC who were referred to a multidisciplinary pediatric concussion program and underwent graded aerobic treadmill testing between October 9, 2014, and February 11, 2016. Clinical assessments were carried out by a single neurosurgeon and included clinical history taking, physical examination, and recording specific patient-reported concussion-related symptoms using the Post-Concussion Symptom Scale (PCSS). Graded aerobic treadmill testing using a modified Balke protocol for incremental increases in intensity was used as a diagnostic tool to assess physiological recovery, classify post-concussion syndrome (PCS) subtype, and reassess patients following treatment. Patients with a symptom-limited threshold on treadmill testing (physiological PCD) were treated with an individually tailored submaximal exercise prescription and multidisciplinary targeted therapies. RESULTS One hundred six patients (mean age 15.1 years, range 11-19 years) with SRC underwent a total of 141 treadmill tests. There were no serious complications related to treadmill testing in this study. Overall, 138 (97.9%) of 141 tests were well tolerated and contributed valuable clinical information. Treadmill testing confirmed physiological recovery in 63 (96.9%) of 65 patients tested, allowing successful return to play in 61 (93.8%). Treadmill testing was used to diagnose physiological PCD in 58 patients and cervicogenic PCD in 1 patient. Of the 41 patients with physiological PCD who had complete follow-up and were treated with tailored submaximal exercise prescription, 37 (90.2%) were classified as clinically improved and 33 (80.5%) successfully returned to sporting activities. Patients who did not respond or experienced an incomplete response to submaximal aerobic exercise treatment included 7 patients with migraine headaches and 1 patient with a postinjury psychiatric disorder. CONCLUSIONS Graded aerobic treadmill testing is a safe, tolerable, and clinically valuable tool that can assist in the evaluation and management of pediatric SRC. Future research is needed to confirm the clinical value of this tool in return-to-play decision making. Studies are also needed to understand the pathophysiology of physiological PCD and the effects of targeted treatment.

Do not fear the Framingham: Practical application to properly evaluate and modify cardiovascular risk in commercial divers.

PubMed

Suresh, Rahul; Pavela, James; Kus, Marcus S; Alleman, Tony; Sanders, Robert

2018-01-01

In April 2016 the Association of Diving Contractors International (ADCI) consensus guidelines began recommending annual cardiovascular risk stratification of commercial divers using the Framingham Risk Score (FRS). For those at elevated risk, further testing is recommended. This approach has raised concerns about potential operational and financial impacts. However, the prevalence of elevated cardiovascular risk and need for additional testing among commercial divers is not known. Clinical data required to calculate the FRS was abstracted for 190 commercial divers in two cohorts. Population demographics, FRS distribution, contributions of risk factors and effect of interventions on reducing risk-factor burden were assessed. Mean FRS score was 1.68 ± 6.35 points, with 13 divers (6.8%) at intermediate risk and none at high 10-year risk. In these 13 divers, the mean contributions to the FRS were from age (6.5 points), cholesterol (3.1 pts.), smoking (1.3 pts.), highdensity lipoprotein (1 pt.), and systolic blood pressure (0.8 pts). The youngest age group had a significantly higher modifiable risk core than the oldest age group (5.87 vs. 1.2 points, P ⟨ 0.001). All 13 intermediate risk divers could have been reclassified as low-risk with successful treatment of modifiable risk factors. The prevalence of elevated cardiovascular risk among commercial divers is low, and treatment of modifiable risk factors could reclassify those at intermediate risk to low risk. Therefore, FRS implementation coupled with intensive risk-reduction strategies for at risk-divers may help improve diver health and prolong the careers of divers while limiting the need for additional testing and adverse operational impact. Copyright© Undersea and Hyperbaric Medical Society.

Increasing chlamydia screening tests in general practice: a modified Zelen prospective Cluster Randomised Controlled Trial evaluating a complex intervention based on the Theory of Planned Behaviour.

PubMed

McNulty, Cliodna A M; Hogan, Angela H; Ricketts, Ellie J; Wallace, Louise; Oliver, Isabel; Campbell, Rona; Kalwij, Sebastian; O'Connell, Elaine; Charlett, Andre

2014-05-01

To determine if a structured complex intervention increases opportunistic chlamydia screening testing of patients aged 15-24 years attending English general practitioner (GP) practices. A prospective, Cluster Randomised Controlled Trial with a modified Zelen design involving 160 practices in South West England in 2010. The intervention was based on the Theory of Planned Behaviour (TPB). It comprised of practice-based education with up to two additional contacts to increase the importance of screening to GP staff and their confidence to offer tests through skill development (including videos). Practical resources (targets, posters, invitation cards, computer reminders, newsletters including feedback) aimed to actively influence social cognitions of staff, increasing their testing intention. Data from 76 intervention and 81 control practices were analysed. In intervention practices, chlamydia screening test rates were 2.43/100 15-24-year-olds registered preintervention, 4.34 during intervention and 3.46 postintervention; controls testing rates were 2.61/100 registered patients prior intervention, 3.0 during intervention and 2.82 postintervention. During the intervention period, testing in intervention practices was 1.76 times as great (CI 1.24 to 2.48) as controls; this persisted for 9 months postintervention (1.57 times as great, CI 1.27 to 2.30). Chlamydia infections detected increased in intervention practices from 2.1/1000 registered 15-24-year-olds prior intervention to 2.5 during the intervention compared with 2.0 and 2.3/1000 in controls (Estimated Rate Ratio intervention versus controls 1.4 (CI 1.01 to 1.93). This complex intervention doubled chlamydia screening tests in fully engaged practices. The modified Zelen design gave realistic measures of practice full engagement (63%) and efficacy of this educational intervention in general practice; it should be used more often. The trial was registered on the UK Clinical Research Network Study Portfolio database. UKCRN number 9722.

Establishing benchmarks and metrics for disruptive technologies, inappropriate and obsolete tests in the clinical laboratory.

PubMed

Kiechle, Frederick L; Arcenas, Rodney C; Rogers, Linda C

2014-01-01

Benchmarks and metrics related to laboratory test utilization are based on evidence-based medical literature that may suffer from a positive publication bias. Guidelines are only as good as the data reviewed to create them. Disruptive technologies require time for appropriate use to be established before utilization review will be meaningful. Metrics include monitoring the use of obsolete tests and the inappropriate use of lab tests. Test utilization by clients in a hospital outreach program can be used to monitor the impact of new clients on lab workload. A multi-disciplinary laboratory utilization committee is the most effective tool for modifying bad habits, and reviewing and approving new tests for the lab formulary or by sending them out to a reference lab. Copyright © 2013 Elsevier B.V. All rights reserved.

A distinct pattern of memory and attention deficiency in patients with depression.

PubMed

Luo, Lan-Lan; Chen, Xin; Chai, Yan; Li, Jin-Hong; Zhang, Mian; Zhang, Jian-Ning

2013-03-01

Depression related cognitive deficits are frequently considered as simple epiphenomena of the disorder. However, whether or not the depression might directly bring about cognitive deficits is still under investigation. This study was to investigate the distinct pattern of cognitive deficits in patients with depression by comparing the cognitive function before and after anti-depressive drug therapy. Sixty cases of patients, first-time diagnosed with depression, were assessed by 17-item Hamilton Rating Scale for Depression (HAMD17scale). The memory ability was tested by quantitatively clinical memory scale, while the attention ability by modified Ruff 2&7 Selective Attention Test. Forty-two healthy volunteers were recruited as controls. The depressive patients were treated with Venlafaxine (75 - 300 mg/d), Fluoxetine (20 - 40 mg/d), Paroxetine (20 - 40 mg/d), and Sertraline (50 - 150 mg/d). After 12 weeks treatment, patients were tested again by HAMD17scale, quantitatively clinical memory scale, and modified Ruff 2&7 selective attention test to assess the effect of anti-depressive drugs on cognitive deficits. The memory quotient (MQ) was significantly lowered in depressive patients. The selection speed was also significantly decreased and the number of missing and error hits increased in the depression group as compared to control. However, there was no significant difference in clinical memory scale and Ruff 2&7 selective attention test between mild-to-moderate and severe depression group. Importantly, after anti-depressive drug therapy, the HAMD17 scale scores in depressive patients were significantly decreased, but the MQ, directional memory (DM), free recall (FR), associative learning (AL), and face recognition were comparable with those before the treatment. Furthermore, the selection speed and the number of missing and error hits were also not significantly different after anti-depressive drugs treatment. Depressive patients suffer from short-term memory deficits, and attention extent, stability and rearrangement deficiency. Even though anti-depressive drugs sufficiently relieve the cardinal presentation of depression, they could not successfully alleviate the accompanying cognitive deficits. This might indicate a distinct pattern of cognitive deficits in patients with depression.

Social Cognition Psychometric Evaluation: Results of the Final Validation Study.

PubMed

Pinkham, Amy E; Harvey, Philip D; Penn, David L

2018-06-06

Social cognition is increasingly recognized as an important treatment target in schizophrenia; however, the dearth of well-validated measures that are suitable for use in clinical trials remains a significant limitation. The Social Cognition Psychometric Evaluation (SCOPE) study addresses this need by systematically evaluating the psychometric properties of promising measures. In this final phase of SCOPE, eight new or modified tasks were evaluated. Stable outpatients with schizophrenia (n = 218) and healthy controls (n = 154) completed the battery at baseline and 2-4 weeks later across three sites. Tasks included the Bell Lysaker Emotion Recognition Task (BLERT), Penn Emotion Recognition Task (ER-40), Reading the Mind in the Eyes Task (Eyes), The Awareness of Social Inferences Test (TASIT), Hinting Task, Mini Profile of Nonverbal Sensitivity (MiniPONS), Social Attribution Task-Multiple Choice (SAT-MC), and Intentionality Bias Task (IBT). BLERT and ER-40 modifications included response time and confidence ratings. The Eyes task was modified to include definitions of terms and TASIT to include response time. Hinting was scored with more stringent criteria. MiniPONS, SAT-MC, and IBT were new to this phase. Tasks were evaluated on (1) test-retest reliability, (2) utility as a repeated measure, (3) relationship to functional outcome, (4) practicality and tolerability, (5) sensitivity to group differences, and (6) internal consistency. Hinting, BLERT, and ER-40 showed the strongest psychometric properties and are recommended for use in clinical trials. Eyes, TASIT, and IBT showed somewhat weaker psychometric properties and require further study. MiniPONS and SAT-MC showed poorer psychometric properties that suggest caution for their use in clinical trials.

Automated encoding of clinical documents based on natural language processing.

PubMed

Friedman, Carol; Shagina, Lyudmila; Lussier, Yves; Hripcsak, George

2004-01-01

The aim of this study was to develop a method based on natural language processing (NLP) that automatically maps an entire clinical document to codes with modifiers and to quantitatively evaluate the method. An existing NLP system, MedLEE, was adapted to automatically generate codes. The method involves matching of structured output generated by MedLEE consisting of findings and modifiers to obtain the most specific code. Recall and precision applied to Unified Medical Language System (UMLS) coding were evaluated in two separate studies. Recall was measured using a test set of 150 randomly selected sentences, which were processed using MedLEE. Results were compared with a reference standard determined manually by seven experts. Precision was measured using a second test set of 150 randomly selected sentences from which UMLS codes were automatically generated by the method and then validated by experts. Recall of the system for UMLS coding of all terms was .77 (95% CI.72-.81), and for coding terms that had corresponding UMLS codes recall was .83 (.79-.87). Recall of the system for extracting all terms was .84 (.81-.88). Recall of the experts ranged from .69 to .91 for extracting terms. The precision of the system was .89 (.87-.91), and precision of the experts ranged from .61 to .91. Extraction of relevant clinical information and UMLS coding were accomplished using a method based on NLP. The method appeared to be comparable to or better than six experts. The advantage of the method is that it maps text to codes along with other related information, rendering the coded output suitable for effective retrieval.

Diagnosis of diabetes insipidus observed in Swiss Duroc boars.

PubMed

Grahofer, Alexander; Wiedemar, Natalie; Gurtner, Corinne; Drögemüller, Cord; Nathues, Heiko

2016-01-29

Diabetes insipidus (DI) is a rare disease in humans and animals, which is caused by the lack of production, malfunction or dysfunction of the distal nephron to the antidiuretic effect of the antidiuretic hormone (ADH). Diagnosis requires a thorough medical history, clinical examination and further laboratory confirmation. This case report describes the appearance of DI in five Duroc boars in Switzerland. Two purebred intact Duroc boars at the age of 8 months and 1.5 years, respectively, with a history of polyuric and polydipsic symptoms had been referred to the Swine Clinic in Berne. Based on the case history, the results of clinical examination and the analysis of blood and urine, a tentative diagnosis of DI was concluded. Finally, the diagnosis was confirmed by findings from a modified water deprivation test, macroscopic examinations and histopathology. Following the diagnosis, three genes known to be involved in inherited DI in humans were analyzed in order to explore a possible genetic background of the affected boars. The etiology of DI in pigs is supposed to be the same as in humans, although this disease has never been described in pigs before. Thus, although occurring only on rare occasions, DI should be considered as a differential diagnosis in pigs with polyuria and polydipsia. It seems that a modified water deprivation test may be a helpful tool for confirming a diagnosis in pigs. Since hereditary forms of DI have been described in humans, the occurrence of DI in pigs should be considered in breeding programs although we were not able to identify a disease associated mutation.

Predicting BRCA1 and BRCA2 gene mutation carriers: comparison of LAMBDA, BRCAPRO, Myriad II, and modified Couch models.

PubMed

Lindor, Noralane M; Lindor, Rachel A; Apicella, Carmel; Dowty, James G; Ashley, Amanda; Hunt, Katherine; Mincey, Betty A; Wilson, Marcia; Smith, M Cathie; Hopper, John L

2007-01-01

Models have been developed to predict the probability that a person carries a detectable germline mutation in the BRCA1 or BRCA2 genes. Their relative performance in a clinical setting is unclear. To compare the performance characteristics of four BRCA1/BRCA2 gene mutation prediction models: LAMBDA, based on a checklist and scores developed from data on Ashkenazi Jewish (AJ) women; BRCAPRO, a Bayesian computer program; modified Couch tables based on regression analyses; and Myriad II tables collated by Myriad Genetics Laboratories. Family cancer history data were analyzed from 200 probands from the Mayo Clinic Familial Cancer Program, in a multispecialty tertiary care group practice. All probands had clinical testing for BRCA1 and BRCA2 mutations conducted in a single laboratory. For each model, performance was assessed by the area under the receiver operator characteristic curve (ROC) and by tests of accuracy and dispersion. Cases "missed" by one or more models (model predicted less than 10% probability of mutation when a mutation was actually found) were compared across models. All models gave similar areas under the ROC curve of 0.71 to 0.76. All models except LAMBDA substantially under-predicted the numbers of carriers. All models were too dispersed. In terms of ranking, all prediction models performed reasonably well with similar performance characteristics. Model predictions were widely discrepant for some families. Review of cancer family histories by an experienced clinician continues to be vital to ensure that critical elements are not missed and that the most appropriate risk prediction figures are provided.

Test-Retest Reliability of Measures Commonly Used to Measure Striatal Dysfunction across Multiple Testing Sessions: A Longitudinal Study.

PubMed

Palmer, Clare E; Langbehn, Douglas; Tabrizi, Sarah J; Papoutsi, Marina

2017-01-01

Cognitive impairment is common amongst many neurodegenerative movement disorders such as Huntington's disease (HD) and Parkinson's disease (PD) across multiple domains. There are many tasks available to assess different aspects of this dysfunction, however, it is imperative that these show high test-retest reliability if they are to be used to track disease progression or response to treatment in patient populations. Moreover, in order to ensure effects of practice across testing sessions are not misconstrued as clinical improvement in clinical trials, tasks which are particularly vulnerable to practice effects need to be highlighted. In this study we evaluated test-retest reliability in mean performance across three testing sessions of four tasks that are commonly used to measure cognitive dysfunction associated with striatal impairment: a combined Simon Stop-Signal Task; a modified emotion recognition task; a circle tracing task; and the trail making task. Practice effects were seen between sessions 1 and 2 across all tasks for the majority of dependent variables, particularly reaction time variables; some, but not all, diminished in the third session. Good test-retest reliability across all sessions was seen for the emotion recognition, circle tracing, and trail making test. The Simon interference effect and stop-signal reaction time (SSRT) from the combined-Simon-Stop-Signal task showed moderate test-retest reliability, however, the combined SSRT interference effect showed poor test-retest reliability. Our results emphasize the need to use control groups when tracking clinical progression or use pre-baseline training on tasks susceptible to practice effects.

A simple screening test for the detection of metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter in a tertiary care hospital.

PubMed

Wan Nor Amilah, W A W; Noor Izani, N J; Ng, W K; Ashraful Haq, J

2012-12-01

Clinical utilization of carbapenems remains under threat with the emergence of acquired carbapenemase-producing bacteria, particularly metallo-β-lactamases (MBL). Rapid detection of MBL-producing Gram-negative bacilli is essential to prevent their widespread dissemination. However, no standardized detection method is available for routine laboratory use. The purpose of the study was to evaluate a chelating-agent based double disk synergic test and disk potentiation test for MBL-producing strain detection and to determine the isolation rate of MBL-producing Pseudomonas aeruginosa and Acinetobacter from clinical samples in our tertiary teaching hospital. A total of 22 and 66 imipenem-resistant P. aeruginosa and Acinetobacter isolates respectively were tested with ceftazidime (CAZ) disk by modified double disk synergic test and disk potentiation test using ethylenediaminetetraacetic acid (EDTA) and 2-mercaptopropionic acid (as chelating agents) to detect MBL production. The tests were compared with EDTA-phenanthroline-imipenem (EPI) microdilution MIC test as gold standard. MBL positive strains were detected in 17 (77.3%) P. aeruginosa and 2 (3.5%) Acinetobacter isolates. The disk potentiation test with 2-mercaptopropionic acid (2-MPA) dilution of 1:12 provided the most acceptable sensitivities and specificities (88.2% sensitivity and 100% specificity in P. aeruginosa; 100% sensitivity and specificity in Acinetobacter) compared to other screening methods used in this study. This study provided useful information on the local prevalence of MBL-producing P. aeruginosa and Acinetobacter in our hospital. Disc potentiation test with CAZ/2-MPA disc appears to be reliable and convenient MBL detection method in the routine clinical laboratory.

Can brief measures effectively screen for pain and somatic malingering? Examination of the Modified Somatic Perception Questionnaire and Pain Disability Index.

PubMed

Crighton, Adam H; Wygant, Dustin B; Applegate, Kathryn C; Umlauf, Robert L; Granacher, Robert P

2014-09-01

Recent rise in fraudulent disability claims in the United States has resulted in psychologists being increasingly called upon to use psychological tests to determine whether disability claims based on psychological or somatic/pain complaints are legitimate. To examine two brief measures, Modified Somatic Perception Questionnaire (MSPQ) and the Pain Disability Index (PDI), and their ability to screen for malingering in relation to the Bianchini et al. criteria for malingered pain-related disability published in The Spine Journal (2005). Examined brief self-report measures between litigating and nonlitigating pain samples. We compared 144 disability litigants, predominantly presenting a history of musculoskeletal injuries with psychiatric overlay, with 167 nonlitigating pain patients who were predominantly in treatment for chronic back pain issues and other musculoskeletal conditions. Modified Somatic Perception Questionnaire, Pain Disability Index, Minnesota Multiphasic Personality Inventory-2 Restructured Form, Test of Memory Malingering, Letter Memory Test, Victoria Symptom Validity Test, Structured Interview of Reported Symptoms-second edition, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders somatoform disorders module. We examined a sample of 144 individuals undergoing compensation-seeking evaluations in relation to 167 nonlitigating pain patients. Group differences on both the MSPQ and PDI were calculated, as well as sensitivities, specificities, and positive and negative predictive powers for both measures at selected cutoffs. The results suggest that both the MSPQ and PDI are useful to screen for pain malingering in forensic evaluations, especially the MSPQ, which performed the best in differentiating between the groups. Copyright © 2014 Elsevier Inc. All rights reserved.

Modifying Tests for Students with Disabilities.

ERIC Educational Resources Information Center

Smith, Douglas K.

Modifying standardized tests for students with disabilities is a complex issue. Tests should be modified only when alternative measures do not exist. Testing professionals should always be cognizant of the fact that whenever modifications are made, normative interpretations must be made very cautiously. In addition, the accommodations that were…

Reliability and equivalence of alternate forms for the Symbol Digit Modalities Test: implications for multiple sclerosis clinical trials.

PubMed

Benedict, Ralph H B; Smerbeck, Audrey; Parikh, Rajavi; Rodgers, Jonathan; Cadavid, Diego; Erlanger, David

2012-09-01

Cognitive impairment is common in multiple sclerosis (MS), but is seldom assessed in clinical trials investigating the effects of disease-modifying therapies. The Symbol Digit Modalities Test (SDMT) is a particularly promising tool due to its sensitivity and robust correlation with brain magnetic resonance imaging (MRI) and vocational disability. Unfortunately, there are no validated alternate SDMT forms, which are needed to mitigate practice effects. The aim of the study was to assess the reliability and equivalence of SDMT alternate forms. Twenty-five healthy participants completed each of five alternate versions of the SDMT - the standard form, two versions from the Rao Brief Repeatable Battery, and two forms specifically designed for this study. Order effects were controlled using a Latin-square research design. All five versions of the SDMT produced mean values within 3 raw score points of one another. Three forms were very consistent, and not different by conservative statistical tests. The SDMT test-retest reliability using these forms was good to excellent, with all r values exceeding 0.80. For the first time, we find good evidence that at least three alternate versions of the SDMT are of equivalent difficulty in healthy adults. The forms are reliable, and can be implemented in clinical trials emphasizing cognitive outcomes.

A Modified Collagen Gel Dressing Promotes Angiogenesis in a Pre-Clinical Swine Model of Chronic Ischemic Wounds

PubMed Central

Elgharably, Haytham; Ganesh, Kasturi; Dickerson, Jennifer; Khanna, Savita; Abas, Motaz; Ghatak, Piya Das; Dixit, Sriteja; Bergdall, Valerie; Roy, Sashwati; Sen, Chandan K.

2015-01-01

We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full thickness excisional wounds were established in the center of bi- pedicle ischemic skin flaps on the backs of animals. Ischemia was verified by Laser Doppler imaging and MCG was applied to the test group of wounds. Seven days post- wounding, macrophage recruitment to the wound was significantly higher in MCG- treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine IL-10 and of β-FGF. An increased expression of CCR2, a M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of TGF-β, VEGF, vWF, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post-wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I:III deposition. Taken together, MCG helped mount a more robust inflammatory response which resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome and post-wound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds. PMID:25224310

Clinical value of the VMI supplemental tests: a modified replication study.

PubMed

Avi-Itzhak, Tamara; Obler, Doris Richard

2008-10-01

To carry out a modified replication of the study performed by Kulp and Sortor evaluating the clinical value of the information provided by Beery's visual-motor supplemental tests of Visual Perception (VP) and Motor Coordination (MC) in normally developed children. The objectives were to (a) estimate the correlations among the three tests scores; (b) assess the predictive power of the VP and MC scores in explaining the variance in Visual-Motor Integration (VMI) scores; and (c) examine whether poor performance on the VMI is related to poor performance on VP or MC. METHODS.: A convenience sample of 71 children ages 4 and 5 years (M = 4.62 +/- 0.43) participated in the study. The supplemental tests significantly (F = 9.59; dF = 2; p < or = 0. 001) explained 22% of the variance in VMI performance. Only VP was significantly related to VMI (beta = 0.39; T = 3.49) accounting for the total amount of explained variance. Using the study population norms, 11 children (16% of total sample) did poorly on the VMI; of those 11, 73% did poorly on the VP, and none did poorly on the MC. None of these 11 did poorly on both the VP and MC. Nine percent of total sample who did poorly on the VP performed within the norm on the VMI. Thirteen percent who performed poorly on the MC performed within the norm on the VMI. Using the VMI published norms, 14 children (20% of total sample) who did poorly on the VP performed within the norm on the VMI. Forty-eight percent who did poorly on MC performed within the norm on the VMI. Findings supported Kulp and Sortor's conclusions that each area should be individually evaluated during visual-perceptual assessment of children regardless of performance on the VMI.

Associations between Diet Behaviors and Measures of Glycemia, in Clinical Setting, in Obese Adolescents.

PubMed

Wagner, Kelly A; Armah, Seth M; Smith, Lisa G; Pike, Julie; Tu, Wanzhu; Campbell, Wayne W; Boushey, Carol J; Hannon, Tamara S; Gletsu-Miller, Nana

2016-10-01

To determine the influence of dietary behaviors, assessed in a clinical setting, on measures of glycemia in overweight and obese adolescents. The study is a retrospective, cross-sectional chart review. Eligible participants were overweight youth (N = 146, age 9-21 years) who attended the Youth Diabetes Prevention Clinic in Indianapolis, IN. Glycemic status was assessed during a 2-hour oral glucose tolerance test (OGTT). In the Bright Futures Questionnaire, a recommended clinical tool for assessing unhealthy behaviors in youth, nutrition-specific questions were modified to quantify dietary habits. Associations between dietary habits and measures of glycemia were determined using multiple linear regression models. Skewed data are presented as geometric means and 95% confidence intervals. Of the 146 adolescents who were assessed [60% girls, age 13.7 years (13.3, 14.0), BMI 33.9 kg/m(2) (33.3, 34.5)], 40% were diagnosed with prediabetes. Higher intake of dessert foods was associated with increased glucose levels at 2 hours following the OGTT (β = 0.23, p = 0.004), and higher intake of packaged snack foods was associated with elevated levels of hemoglobin A1c (β = 0.04, p = 0.04), independent of adiposity. In obese youth, high intakes of dessert and packaged snack items were associated with elevated concentrations of glucose at 2 hours following the OGTT and hemoglobin A1c. Findings demonstrate the usefulness of a modified Bright Futures Questionnaire, used in a clinical setting, for identifying dietary behaviors associated with hyperglycemia in obese adolescents. ClinicalTrials.gov registration number: NCT02535169.

Sporadic Inclusion Body Myositis: MRI Findings and Correlation With Clinical and Functional Parameters.

PubMed

Guimaraes, Julio Brandao; Zanoteli, Edmar; Link, Thomas M; de Camargo, Leonardo V; Facchetti, Luca; Nardo, Lorenzo; Fernandes, Artur da Rocha Correa

2017-12-01

The purpose of this prospective study is to assess MRI findings in patients with sporadic inclusion body myositis (IBM) and correlate them with clinical and functional parameters. This study included 12 patients with biopsy-proven sporadic IBM. All patients underwent MRI of the bilateral upper and lower extremities. The images were scored for muscle atrophy, fatty infiltration, and edema pattern. Clinical data included onset and duration of disease. Muscle strength was measured using the Medical Research Council (MRC) scale, and functional status was assessed using the Modified Rankin Scale. Correlation between MRI and different clinical and functional parameters was calculated using the Spearman rank test and Pearson correlation. All patients showed MRI abnormalities, which were more severe within the lower limbs and the distal segments. The most prevalent MRI finding was fat infiltration. There was a statistically significant correlation between disease duration and number of muscles infiltrated by fat (r = 0.65; p = 0.04). The number of muscles with fat infiltration correlated with the sum of the scores of MRC (r = -0.60; p = 0.04) and with the Modified Rankin Scale (r = 0.48; p = 0.03). Our findings suggest that most patients with biopsy-proven sporadic IBM present with a typical pattern of muscle involvement at MRI, more extensively in the lower extremities. Moreover, MRI findings strongly correlated with clinical and functional parameters, because both the extent and severity of muscle involvement assessed by MRI and clinical and functional parameters are associated with the early onset of the disease and its duration.

Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease

PubMed Central

Varsani, Hemlata; Charman, Susan C; Li, Charles K; Marie, Suely K N; Amato, Anthony A; Banwell, Brenda; Bove, Kevin E; Corse, Andrea M; Emslie-Smith, Alison M; Jacques, Thomas S; Lundberg, Ingrid E; Minetti, Carlo; Nennesmo, Inger; Rushing, Elisabeth J; Sallum, Adriana M E; Sewry, Caroline; Pilkington, Clarissa A; Holton, Janice L; Wedderburn, Lucy R

2015-01-01

Objectives To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. Methods 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers’ ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. Results Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. Conclusions The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM. PMID:24064003

Reliable critical sized defect rodent model for cleft palate research.

PubMed

Mostafa, Nesrine Z; Doschak, Michael R; Major, Paul W; Talwar, Reena

2014-12-01

Suitable animal models are necessary to test the efficacy of new bone grafting therapies in cleft palate surgery. Rodent models of cleft palate are available but have limitations. This study compared and modified mid-palate cleft (MPC) and alveolar cleft (AC) models to determine the most reliable and reproducible model for bone grafting studies. Published MPC model (9 × 5 × 3 mm(3)) lacked sufficient information for tested rats. Our initial studies utilizing AC model (7 × 4 × 3 mm(3)) in 8 and 16 weeks old Sprague Dawley (SD) rats revealed injury to adjacent structures. After comparing anteroposterior and transverse maxillary dimensions in 16 weeks old SD and Wistar rats, virtual planning was performed to modify MPC and AC defects dimensions, taking the adjacent structures into consideration. Modified MPC (7 × 2.5 × 1 mm(3)) and AC (5 × 2.5 × 1 mm(3)) defects were employed in 16 weeks old Wistar rats and healing was monitored by micro-computed tomography and histology. Maxillary dimensions in SD and Wistar rats were not significantly different. Preoperative virtual planning enhanced postoperative surgical outcomes. Bone healing occurred at defect margin leaving central bone void confirming the critical size nature of the modified MPC and AC defects. Presented modifications for MPC and AC models created clinically relevant and reproducible defects. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Clinical pharmacology of novel anti-Alzheimer disease modifying medications.

PubMed

Caraci, Filippo; Bosco, Paolo; Leggio, Gian Marco; Malaguarnera, Michele; Drago, Filippo; Bucolo, Claudio; Salomone, Salvatore

2013-01-01

In recent years, efforts have been directed to develop "disease-modifying" medications to treat Alzheimer's disease (AD), able to halt or slow the pathological process. Because the earlier the treatment starts, the greater is the possibility of efficacy, it is important to set up biomarkers for early diagnosis of functional brain abnormalities, before the clinical manifestation of the overt disease. Up to now, strategies to develop disease-modifying drugs have mainly targeted β amyloid (Aβ, accumulation, aggregation, clearance) and/or tau protein (phosphorylation and aggregation). Active and passive immunotherapy is the main strategy aimed at increasing Aβ clearance. Unfortunately several candidate diseasemodifying drugs have failed in phase III clinical trials conducted in mild to moderate AD. More recently, in phase III studies, bapineuzumab has been discontinued because it did not prove clinically effective (despite its significant effect on biomarkers), while solaneuzumab has been found effective in slowing AD progression. Several methological problems have been recently pointed out to explain the lack of clinical efficacy of novel disease-modifying drug-treatments; moreover, new insights in pathophysiology of AD give the premise to develop novel drug targeting. Clinical trials recently completed and/or still ongoing are discussed in the present review.

A NEW APPROACH TO THE STUDY OF MUCOADHESIVENESS OF POLYMERIC MEMBRANES USING SILICONE DISCS.

PubMed

Nowak, Karolina Maria; Szterk, Arkadiusz; Fiedor, Piotr; Bodek, Kazimiera Henryka

2016-01-01

The introduction of new test methods and the modification of existing ones are crucial for obtaining reliable results, which contributes to the development of innovative materials that may have clinical applications. Today, silicone is commonly used in medicine and the diversity of its applications are continually growing. The aim of this study is to evaluate the mucoadhesiveness of polymeric membranes by a method that modifies the existing test methods through the introduction of silicone discs. The matrices were designed for clinical application in the management of diseases within the oral cavity. The use of silicone discs allows reliable and reproducible results to be obtained, which allows us to make various tensometric measurements. In this study, different types of polymeric matrices were examined, as well as their crosslinking and the presence for the active pharmaceutical ingredient were compared to the pure dosage form. The lidocaine hydrochloride (Lid(HCl)) was used as a model active substance, due to its use in dentistry and clinical safety. The results were characterized by a high repeatability (RSD < 10.6%). The advantage of silicone material due to its mechanical strength, chemical and physical resistance, allowed a new test method using a texture analyzer to be proposed.

Controversies in Alzheimer’s disease drug development

PubMed Central

Cummings, Jeffrey L.

2010-01-01

Understanding of the pathophysiological basis of Alzheimer’s disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer’s disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described. PMID:18925488

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short-Acting β-Agonist Formulations.

PubMed

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai; Ahrens, Richard C

2018-04-01

Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration-recommended 3-by-1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3-by-1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90-μg test dose and a 720-μg reference dose (42% cost reduction). Combining a 180-μg test dose and a 720-μg reference dose produced an estimated 36% cost reduction. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials

PubMed Central

Foong, Rachel E.; Harper, Alana J.; King, Louise; Turkovic, Lidija; Davis, Miriam; Clem, Charles C.; Davis, Stephanie D.; Ranganathan, Sarath; Hall, Graham L.

2018-01-01

The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed. Healthy children and children with CF aged 3–6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan. MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials. This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible. PMID:29707562

Development and use of active clinical decision support for preemptive pharmacogenomics

PubMed Central

Bell, Gillian C; Crews, Kristine R; Wilkinson, Mark R; Haidar, Cyrine E; Hicks, J Kevin; Baker, Donald K; Kornegay, Nancy M; Yang, Wenjian; Cross, Shane J; Howard, Scott C; Freimuth, Robert R; Evans, William E; Broeckel, Ulrich; Relling, Mary V; Hoffman, James M

2014-01-01

Background Active clinical decision support (CDS) delivered through an electronic health record (EHR) facilitates gene-based drug prescribing and other applications of genomics to patient care. Objective We describe the development, implementation, and evaluation of active CDS for multiple pharmacogenetic test results reported preemptively. Materials and methods Clinical pharmacogenetic test results accompanied by clinical interpretations are placed into the patient's EHR, typically before a relevant drug is prescribed. Problem list entries created for high-risk phenotypes provide an unambiguous trigger for delivery of post-test alerts to clinicians when high-risk drugs are prescribed. In addition, pre-test alerts are issued if a very-high risk medication is prescribed (eg, a thiopurine), prior to the appropriate pharmacogenetic test result being entered into the EHR. Our CDS can be readily modified to incorporate new genes or high-risk drugs as they emerge. Results Through November 2012, 35 customized pharmacogenetic rules have been implemented, including rules for TPMT with azathioprine, thioguanine, and mercaptopurine, and for CYP2D6 with codeine, tramadol, amitriptyline, fluoxetine, and paroxetine. Between May 2011 and November 2012, the pre-test alerts were electronically issued 1106 times (76 for thiopurines and 1030 for drugs metabolized by CYP2D6), and the post-test alerts were issued 1552 times (1521 for TPMT and 31 for CYP2D6). Analysis of alert outcomes revealed that the interruptive CDS appropriately guided prescribing in 95% of patients for whom they were issued. Conclusions Our experience illustrates the feasibility of developing computational systems that provide clinicians with actionable alerts for gene-based drug prescribing at the point of care. PMID:23978487

The Efficacy of Fast ForWord-Language Intervention in School-Age Children with Language Impairment: A Randomized Controlled Trial

PubMed Central

Gillam, Ronald B.; Loeb, Diane Frome; Hoffman, LaVae M.; Bohman, Thomas; Champlin, Craig A.; Thibodeau, Linda; Widen, Judith; Brandel, Jayne; Friel-Patti, Sandy

2008-01-01

Purpose A randomized controlled trial (RCT) was conducted to compare the language and auditory processing outcomes of children assigned to Fast ForWord-Language (FFW-L) to the outcomes of children assigned to nonspecific or specific language intervention comparison treatments that did not contain modified speech. Method Two hundred and sixteen children between the ages of 6 and 9 years with language impairments were randomly assigned to one of four arms: Fast ForWord-Language (FFW-L), academic enrichment (AE), computer-assisted language intervention (CALI), or individualized language intervention (ILI) provided by a speech-language pathologist. All children received 1 hour and 40 minutes of treatment, 5 days per week, for 6 weeks. Language and auditory processing measures were administered to the children by blinded examiners before treatment, immediately after treatment, 3 months after treatment, and 6 months after treatment. Results The children in all four arms improved significantly on a global language test and a test of backward masking. Children with poor backward masking scores who were randomized to the FFW-L arm did not present greater improvement on the language measures than children with poor backward masking scores who were randomized to the other three arms. Effect sizes, analyses of standard error of measurement, and normalization percentages supported the clinical significance of the improvements on the CASL. There was a treatment effect for the Blending Words subtest on the Comprehensive Test of Phonological Processing (Wagner, Torgesen, & Rashotte, 1999). Participants in the FFW-L and CALI arms earned higher phonological awareness scores than children in the ILI and AE arms at the six-month follow-up testing. Conclusion Fast ForWord-Language, the language intervention that provided modified speech to address a hypothesized underlying auditory processing deficit, was not more effective at improving general language skills or temporal processing skills than a nonspecific comparison treatment (AE) or specific language intervention comparison treatments (CALI and ILI) that did not contain modified speech stimuli. These findings call into question the temporal processing hypothesis of language impairment and the hypothesized benefits of using acoustically modified speech to improve language skills. The finding that children in the three treatment arms and the active comparison arm made clinically relevant gains on measures of language and temporal auditory processing informs our understanding of the variety of intervention activities that can facilitate development. PMID:18230858

A Pilot Study of an Adaptive, Idiographic, and Multi-Component Attention Bias Modification Program for Social Anxiety Disorder

PubMed Central

Amir, Nader; Kuckertz, Jennie M.; Strege, Marlene V.

2016-01-01

An attentional bias toward threat may be one mechanism underlying clinical anxiety. Attention bias modification (ABM) aims to reduce symptoms of anxiety disorders by directly modifying this deficit. However, existing ABM training programs have not consistently modified attentional bias and may not reflect optimal learning needs of participants (i.e., lack of explicit instruction, training goal unclear to participants, lack of feedback, non-adaptive, inability to differentiate or target different components of attentional bias). In the current study, we introduce a new adaptive ABM program (AABM) and test its feasibility in individuals with social anxiety disorder. We report task characteristics and preliminary evidence that this task consistently modifies attentional bias and that changes in attentional bias (but not number of trials) correlate with the level of symptom reduction. These results suggest that AABM may be a targeted method for the next generation of studies examining the utility of attention training. PMID:27795598

Disease-modifying and symptomatic treatment of amyotrophic lateral sclerosis

PubMed Central

Dorst, Johannes; Ludolph, Albert C.; Huebers, Annemarie

2017-01-01

In this review, we summarize the most important recent developments in the treatment of amyotrophic lateral sclerosis (ALS). In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results. Therefore, riluzole remains the only directly disease-modifying drug. In addition, we discuss antisense oligonucleotides (ASOs) as a new and potentially causal treatment option. Progress in symptomatic treatments has been more important. Nutrition and ventilation are now an important focus of ALS therapy. Several studies have firmly established that noninvasive ventilation improves patients’ quality of life and prolongs survival. On the other hand, there is still no consensus regarding best nutritional management, but big multicenter trials addressing this issue are currently ongoing. Evidence regarding secondary symptoms like spasticity, muscle cramps or sialorrhea remains generally scarce, but some new insights will also be discussed. Growing evidence suggests that multidisciplinary care in specialized clinics improves survival. PMID:29399045

Evaluation of magnesium ions release, biocorrosion, and hemocompatibility of MAO/PLLA-modified magnesium alloy WE42.

PubMed

Lu, Ping; Cao, Lu; Liu, Yin; Xu, Xinhua; Wu, Xiangfeng

2011-01-01

Magnesium alloys may potentially be applied as biodegradable metallic materials in cardiovascular stent. However, the high corrosion rate hinders its clinical application. In this study, a new approach was adopted to control the corrosion rate by fabricating a biocompatible micro-arc oxidation/poly-L-lactic acid (MAO/PLLA) composite coating on the magnesium alloy WE42 substrate and the biocompatibility of the modified samples was investigated. The scanning electronic microscope (SEM) images were used to demonstrate the morphology of the samples before and after being submerged in hanks solution for 4 weeks. The degradation was evaluated through the magnesium ions release rate and electrochemical impedance spectroscopy (EIS) test. The biocompatibility of the samples was demonstrated by coagulation time and hemolysis behavior. The result shows that the poly-L-lactic acid (PLLA) effectively improved the corrosion resistance by sealing the microcracks and microholes on the surface of the MAO coating. The modified samples had good compatibility. © 2010 Wiley Periodicals, Inc.

Videos to influence: a systematic review of effectiveness of video-based education in modifying health behaviors.

PubMed

Tuong, William; Larsen, Elizabeth R; Armstrong, April W

2014-04-01

This systematic review examines the effectiveness of videos in modifying health behaviors. We searched PubMed (1975-2012), PsycINFO (1975-2012), EMBASE (1975-2012), and CINAHL (1983-2012) for controlled clinical trials that examined the effectiveness of video interventions in changing health behaviors. Twenty-eight studies comprised of 12,703 subjects were included in the systematic review. Video interventions were variably effective for modifying health behaviors depending on the target behaviors to be influenced. Video interventions appear to be effective in breast self-examination, prostate cancer screening, sunscreen adherence, self-care in patients with heart failure, HIV testing, treatment adherence, and female condom use. However, videos have not shown to be effective in influencing addiction behaviors when they are not tailored. Compared to loss-framing, gain-framed messages may be more effective in promoting certain types of health behavior change. Also, video modeling may facilitate learning of new behaviors and can be an important consideration in future video interventions.

What are the real risks of sport-related concussion, and are they modifiable?

PubMed

Randolph, Christopher; Kirkwood, Michael W

2009-07-01

Over the past two decades, the management of sport-related concussion has been the topic of increased attention in the scientific literature and in the popular media. Despite a proliferation of competing guidelines for concussion management, the widespread use of neuropsychological "baseline" testing designed to monitor postinjury recovery, and several prospective controlled studies of the natural history of concussion, there has been virtually no attempt to quantify the risks associated with sport-related concussion or to determine whether these risks are modifiable via management strategies. Using American football as a model, the short- and long-term risks of sport-related concussion are reviewed. It is concluded that serious short-term consequences of sport-related concussion are extremely rare and unlikely to be significantly modified via management strategies that rely on baseline testing. Other less serious short-term adverse outcomes are also quite rare, transient, and not likely to be altered by specific management guidelines. The long-term consequences of multiple sport-related head trauma remain unclear but are potentially of greater public health concern and should be the focus of increased research. Based on available evidence, there is little rationale for the use of rigid strategies or guidelines in the place of individual clinical decision-making in the management of these injuries.

No Clinically Significant Difference Between Adult and Pediatric IKDC Subjective Knee Evaluation Scores in Adults

PubMed Central

Stegmeier, Nicole; Oak, Sameer R.; O’Rourke, Colin; Strnad, Greg; Spindler, Kurt P.; Jones, Morgan; Farrow, Lutul D.; Andrish, Jack; Saluan, Paul

2017-01-01

Background: Two versions of the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form currently exist: the original version (1999) and a recently modified pediatric-specific version (2011). Comparison of the pediatric IKDC with the adult version in the adult population may reveal that either version could be used longitudinally. Hypothesis: We hypothesize that the scores for the adult IKDC and pediatric IKDC will not be clinically different among adult patients aged 18 to 50 years. Study Design: Randomized crossover study design. Level of Evidence: Level 2. Methods: The study consisted of 100 participants, aged 18 to 50 years, who presented to orthopaedic outpatient clinics with knee problems. All participants completed both adult and pediatric versions of the IKDC in random order with a 10-minute break in between. We used a paired t test to test for a difference between the scores and a Welch’s 2-sample t test to test for equivalence. A least-squares regression model was used to model adult scores as a function of pediatric scores, and vice versa. Results: A paired t test revealed a statistically significant 1.6-point difference between the mean adult and pediatric scores. However, the 95% confidence interval (0.54-2.66) for this difference did not exceed our a priori threshold of 5 points, indicating that this difference was not clinically important. Equivalence testing with an equivalence region of 5 points further supported this finding. The adult and pediatric scores had a linear relationship and were highly correlated with an R2 of 92.6%. Conclusion: There is no clinically relevant difference between the scores of the adult and pediatric IKDC forms in adults, aged 18 to 50 years, with knee conditions. Clinical Relevance: Either form, adult or pediatric, of the IKDC can be used in this population for longitudinal studies. If the pediatric version is administered in adolescence, it can be used for follow-up into adulthood. PMID:28080306

Comparison between the Effects of Rocuronium, Vecuronium, and Cisatracurium Using Train-of-Four and Clinical Tests in Elderly Patients

PubMed Central

Sagir, Ozlem; Yucesoy Noyan, Funda; Koroglu, Ahmet; Cicek, Muslum; Ilksen Toprak, Huseyin

2013-01-01

Background Postoperative residual blockade, longer duration of action for neuromuscular blockade, and slower recovery were relatively common in elderly patients. Objectives We aimed to investigate the safety of train-of-four ratio and clinical tests in the assessment of patient recovery, and to determine the effects of the rocuronium, vecuronium, and cisatracurium on intubation, extubation and recovery times in elderly patients undergoing abdominal surgery. Patients and Methods After obtaining institutional approval and informed consent, 60 patients over 60 years old and undergoing elective abdominal operations were included in this double-blind, randomized clinical trial. Following a standard anesthesia induction, 0.6mg kg-1 rocuronium, 0.1mg kg-1 vecuronium, and 0.1mg kg-1 cisatracurium were administered to the patients in Group R, Group V, and Group C, respectively. Train-of-four (TOF) ratios were recorded at 10-minute intervals during and after the operation. Modified Aldrete Score (MAS) and clinical tests were recorded in the recovery room at 10-minute intervals. In addition, intubation and extubation times, duration of recovery room stay, and any complications were recorded. Results Intubation time was found to be shorter in Group R than that in Groups V and C (P ˂ 0.001). Times to positive visual disturbances and grip strength tests were shorter in Group C than that in Group V (P = 0.016 and P = 0.011, respectively). In Group R and group C, time to TOF ≥ 0.9 was significantly longer than all positive clinical test times except grip strength (P < 0.05). Conclusions We hold the opinion that cisatracurium is safer in elderly patients compared to other drugs. We also concluded that the usage of TOF ratio together with clinical tests is suitable for assessment of neuromuscular recovery in these patients. PMID:24223350

Evaluation of two flap designs on the mandibular second molar after third molar extractions

PubMed Central

Alqahtani, Nabeeh A; Khaleelahmed, S; Desai, Farheen

2017-01-01

Background: The extraction of third molars is associated with some clinical outcomes and periodontal problems. It is imperative to note that the type of incision used in the surgery for the removal of the impacted third molar is critical. The design of the flap influences the healing of the surgically created defect and damage to the distal periodontal area of the adjacent second molar. However, till date, there have been conflicting reports on the influence of different flap designs used for the surgical removal of impacted third molars. Aim: The present study aimed to comparatively evaluate the clinical outcomes and periodontal status of the adjacent second molar, when two different flap designs, namely, the envelope and the modified triangular flap designs were used. Materials and Methods: Sixty female patients with bilateral impacted third molars completed the study with envelope flap on one side and modified triangular flap design on the other side of the mandible for third molar removal. Clinical parameters including pain, dehiscence and swelling were assessed postoperatively and periodontal probing depth (PPD) on the distal aspect of adjacent second molar were assessed both pre- and post-operatively. Results: The results were assessed on 1, 3 and 8 days for pain using visual analog scale. The subjective perception of swelling was evaluated on 3, 7 and 15 days postoperatively in a similar manner. The results of the periodontal parameters were evaluated both preoperatively and 3 months postoperatively, with cautious exploration using a University of North Carolina (UNC)-15 periodontal probe. The statistically significant results for swelling and PPD were noted for the two flap groups using the Chi-square test (P < 0.05). Conclusion: The study revealed that the modified triangular flap had lesser postoperative PPDs and dehiscence. The envelope flap was better when swelling was analyzed. The pain scores, though slightly higher for the modified triangular flap group, were not statistically significant. PMID:28932049

NIKE: a new clinical tool for establishing levels of indications for cataract surgery.

PubMed

Lundström, Mats; Albrecht, Susanne; Håkansson, Ingemar; Lorefors, Ragnhild; Ohlsson, Sven; Polland, Werner; Schmid, Andrea; Svensson, Göran; Wendel, Eva

2006-08-01

The purpose of this study was to construct a new clinical tool for establishing levels of indications for cataract surgery, and to validate this tool. Teams from nine eye clinics reached an agreement about the need to develop a clinical tool for setting levels of indications for cataract surgery and about the items that should be included in the tool. The tool was to be called 'NIKE' (Nationell Indikationsmodell för Kataraktextraktion). The Canadian Cataract Priority Criteria Tool served as a model for the NIKE tool, which was modified for Swedish conditions. Items included in the tool were visual acuity of both eyes, patients' perceived difficulties in day-to-day life, cataract symptoms, the ability to live independently, and medical/ophthalmic reasons for surgery. The tool was validated and tested in 343 cataract surgery patients. Validity, stability and reliability were tested and the outcome of surgery was studied in relation to the indication setting. Four indication groups (IGs) were suggested. The group with the greatest indications for surgery was named group 1 and that with the lowest, group 4. Validity was proved to be good. Surgery had the greatest impact on the group with the highest indications for surgery. Test-retest reliability test and interexaminer tests of indication settings showed statistically significant intraclass correlations (intraclass correlation coefficients [ICCs] 0.526 and 0.923, respectively). A new clinical tool for indication setting in cataract surgery is presented. This tool, the NIKE, takes into account both visual acuity and the patient's perceived problems in day-to-day life because of cataract. The tool seems to be stable and reliable and neutral towards different examiners.

Validation and Development of a Modified Breast Graded Prognostic Assessment As a Tool for Survival in Patients With Breast Cancer and Brain Metastases.

PubMed

Subbiah, Ishwaria M; Lei, Xiudong; Weinberg, Jeffrey S; Sulman, Erik P; Chavez-MacGregor, Mariana; Tripathy, Debu; Gupta, Rohan; Varma, Ankur; Chouhan, Jay; Guevarra, Richard P; Valero, Vicente; Gilbert, Mark R; Gonzalez-Angulo, Ana M

2015-07-10

Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P < .001). In multivariable analysis of the breast-GPA and number of brain metastases (> three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001). The modified breast-GPA incorporates four simple clinical parameters of high prognostic significance. This index has an immediate role in the clinic as a formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials. © 2015 by American Society of Clinical Oncology.

Development and validation of Dutch version of Lasater Clinical Judgment Rubric in hospital practice: An instrument design study.

PubMed

Vreugdenhil, Jettie; Spek, Bea

2018-03-01

Clinical reasoning in patient care is a skill that cannot be observed directly. So far, no reliable, valid instrument exists for the assessment of nursing students' clinical reasoning skills in hospital practice. Lasater's clinical judgment rubric (LCJR), based on Tanner's model "Thinking like a nurse" has been tested, mainly in academic simulation settings. The aim is to develop a Dutch version of the LCJR (D-LCJR) and to test its psychometric properties when used in a hospital traineeship context. A mixed-model approach was used to develop and to validate the instrument. Ten dedicated educational units in a university hospital. A well-mixed group of 52 nursing students, nurse coaches and nurse educators. A Delphi panel developed the D-LCJR. Students' clinical reasoning skills were assessed "live" by nurse coaches, nurse educators and students who rated themselves. The psychometric properties tested during the assessment process are reliability, reproducibility, content validity and construct validity by testing two hypothesis: 1) a positive correlation between assessed and self-reported sum scores (convergent validity) and 2) a linear relation between experience and sum score (clinical validity). The obtained D-LCJR was found to be internally consistent, Cronbach's alpha 0.93. The rubric is also reproducible with intraclass correlations between 0.69 and 0.78. Experts judged it to be content valid. The two hypothesis were both tested significant, supporting evidence for construct validity. The translated and modified LCJR, is a promising tool for the evaluation of nursing students' development in clinical reasoning in hospital traineeships, by students, nurse coaches and nurse educators. More evidence on construct validity is necessary, in particular for students at the end of their hospital traineeship. Based on our research, the D-LCJR applied in hospital traineeships is a usable and reliable tool. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnostic accuracy of intracellular mycobacterium tuberculosis detection for tuberculous meningitis.

PubMed

Feng, Guo-dong; Shi, Ming; Ma, Lei; Chen, Ping; Wang, Bing-ju; Zhang, Min; Chang, Xiao-lin; Su, Xiu-chu; Yang, Yi-ning; Fan, Xin-hong; Dai, Wen; Liu, Ting-ting; He, Ying; Bian, Ting; Duan, Li-xin; Li, Jin-ge; Hao, Xiao-ke; Liu, Jia-yun; Xue, Xin; Song, Yun-zhang; Wu, Hai-qin; Niu, Guo-qiang; Zhang, Li; Han, Cui-juan; Lin, Hong; Lin, Zhi-hui; Liu, Jian-jun; Jian, Qian; Zhang, Jin-she; Tian, Ye; Zhou, Bai-yu; Wang, Jing; Xue, Chang-hu; Han, Xiao-fang; Wang, Jian-feng; Wang, Shou-lian; Thwaites, Guy E; Zhao, Gang

2014-02-15

Early diagnosis and treatment of tuberculous meningitis saves lives, but current laboratory diagnostic tests lack sensitivity. We investigated whether the detection of intracellular bacteria by a modified Ziehl-Neelsen stain and early secretory antigen target (ESAT)-6 in cerebrospinal fluid leukocytes improves tuberculous meningitis diagnosis. Cerebrospinal fluid specimens from patients with suspected tuberculous meningitis were stained by conventional Ziehl-Neelsen stain, a modified Ziehl-Neelsen stain involving cytospin slides with Triton processing, and an ESAT-6 immunocytochemical stain. Acid-fast bacteria and ESAT-6-expressing leukocytes were detected by microscopy. All tests were performed prospectively in a central laboratory by experienced technicians masked to the patients' final diagnosis. Two hundred and eighty patients with suspected tuberculous meningitis were enrolled. Thirty-seven had Mycobacterium tuberculosis cultured from cerebrospinal fluid; 40 had a microbiologically confirmed alternative diagnosis; the rest had probable or possible tuberculous meningitis according to published criteria. Against a clinical diagnostic gold standard the sensitivity of conventional Ziehl-Neelsen stain was 3.3% (95% confidence interval, 1.6-6.7%), compared with 82.9% (95% confidence interval, 77.4-87.3%) for modified Ziehl-Neelsen stain and 75.1% (95% confidence interval, 68.8-80.6%) for ESAT-6 immunostain. Intracellular bacteria were seen in 87.8% of the slides positive by the modified Ziehl-Neelsen stain. The specificity of modified Ziehl-Neelsen and ESAT-6 stain was 85.0% (95% confidence interval, 69.4-93.8%) and 90.0% (95% confidence interval, 75.4-96.7%), respectively. Enhanced bacterial detection by simple modification of the Ziehl-Neelsen stain and an ESAT-6 intracellular stain improve the laboratory diagnosis of tuberculous meningitis.

Exercise Improves Cognition in Parkinson’s Disease: the PRET-PD Randomized Clinical Trial

PubMed Central

David, Fabian J.; Robichaud, Julie A.; Leurgans, Sue E.; Poon, Cynthia; Kohrt, Wendy M.; Goldman, Jennifer G.; Comella, Cynthia L.; Vaillancourt, David E.; Corcos, Daniel M.

2015-01-01

Background This paper reports on the findings of the effect of two structured exercise interventions on secondary cognitive outcomes which were gathered as part of the Progressive Resistance Exercise Training in Parkinson’s disease randomized controlled trial. Methods This study was a prospective, parallel-group, single-center trial. Fifty-one non-demented patients with mild-to-moderate Parkinson’s disease were randomly assigned either to modified Fitness Counts or to Progressive Resistance Exercise, and were followed for 24 months. Cognitive outcomes were the Digit Span, Stroop, and Brief Test of Attention. Results Eighteen patients in modified Fitness Counts and 20 patients in Progressive Resistance Exercise completed the trial. At 12 and at 24 months no differences between groups were observed. At 12 months, relative to baseline, modified Fitness Counts improved on the Digit Span (estimated change, 0.3; Inter-Quartile Range, 0, 0.7; p=0.04) and Stroop (0.3; 0, 0.6; p=0.04), and Progressive Resistance Exercise improved only on the Digit Span (0.7; 0.3, 1; p<0.01). At 24 months, relative to baseline, modified Fitness Counts improved on the Digit Span (0.7; 0.3, 1.7; p<0.01) and Stroop (0.3; 0.1, 0.5; p=0.03), while Progressive Resistance Exercise improved on the Digit Span (0.5; 0.2, 0.8; p<0.01), Stroop (0.2; −0.1, 0.6; p=0.048), and Brief Test of Attention (0.3; 0, 0.8; p=0.048). No neurologic or cognitive adverse events were seen. Conclusions This study provides Class IV level of evidence that 24 months of Progressive Resistance Exercise or modified Fitness Counts may improve attention and working memory in non-demented patients with mild-to-moderate Parkinson’s disease. PMID:26148003

Inhibition of Embryonic Genes to Control Colorectal Cancer Metastasis

DTIC Science & Technology

2013-09-01

JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia . N Engl J Med. 368:1509-18, 2013. 12...was difficult because the cases are spread over 8 slides that have different levels of oxidation and hydrolysis that appear to effect NEDD9 expression...was significantly associated with each other in the training and test sets (Figure 2, Appendix I). The clinical outcome data show that while the

Retrospective Analysis of an Ongoing Group-Based Modified Constraint-Induced Movement Therapy Program for Children with Acquired Brain Injury.

PubMed

Komar, Alyssa; Ashley, Kelsey; Hanna, Kelly; Lavallee, Julia; Woodhouse, Janet; Bernstein, Janet; Andres, Matthew; Reed, Nick

2016-01-01

A pretest-posttest retrospective design was used to evaluate the impact of a group-based modified constraint-induced movement therapy (mCIMT) program on upper extremity function and occupational performance. 20 children ages 3 to 18 years with hemiplegia following an acquired brain injury participated in a 2-week group mCIMT program. Upper extremity function was measured with the Assisting Hand Assessment (AHA) and subtests from the Quality of Upper Extremity Skills Test (QUEST). Occupational performance and satisfaction were assessed using the Canadian Occupational Performance Measure (COPM). Data were analyzed using a Wilcoxon signed-ranks test. Group-based analysis revealed upper extremity function and occupational performance attained statistically significant improvements from pre- to postintervention on all outcome measures (AHA: Z = -3.63, p = <.001; QUEST Grasps: Z = -3.10, p = .002; QUEST Dissociated Movement: Z = -2.51, p = .012; COPM Performance: Z = -3.64, p = <.001; COPM Satisfaction: Z = -3.64, p = <.001). Across individuals, clinically significant improvements were found in 65% of participants' AHA scores. 80% of COPM Performance scores and 70% of COPM Satisfaction scores demonstrated clinically significant improvements in at least one identified goal. This study is an initial step in evaluating and providing preliminary evidence supporting the effectiveness of a group-based mCIMT program for children with hemiplegia following an acquired brain injury.

Differences in the perception of seven behaviour-modifying techniques in paediatric dentistry by undergraduate students using lecturing and video sequences for teaching.

PubMed

Kalwitzki, M; Beyer, C; Meller, C

2010-11-01

Whilst preparing undergraduate students for a clinical course in paediatric dentistry, four consecutive classes (n = 107) were divided into two groups. Seven behaviour-modifying techniques were introduced: systematic desensitization, operant conditioning, modelling, Tell, Show, Do-principle, substitution, change of roles and the active involvement of the patient. The behaviour-modifying techniques that had been taught to group one (n = 57) through lecturing were taught to group two (n = 50) through video sequences and vice versa in the following semester. Immediately after the presentations, students were asked by means of a questionnaire about their perceptions of ease of using the different techniques and their intention for clinical application of each technique. After completion of the clinical course, they were asked about which behaviour-modifying techniques they had actually used when dealing with patients. Concerning the perception of ease of using the different techniques, there were considerable differences for six of the seven techniques (P < 0.05). Whilst some techniques seemed more difficult to apply clinically after lecturing, others seemed more difficult after video-based teaching. Concerning the intention for clinical application and the actual clinical application, there were higher percentages for all techniques taught after video-based teaching. However, the differences were significant only for two techniques in each case (P < 0.05). It is concluded that the use of video based teaching enhances the intention for application and the actual clinical application only for a limited number of behaviour-modifying techniques. © 2010 John Wiley & Sons A/S.

[Clinical and spirometric correlation with home allergens and with pollutants].

PubMed

Varela Delgado, A L; Segura Méndez, N H; Salas Ramírez, M; Espínola Reyna, G; Torres Salazar, A B

2001-01-01

Environmental contamination causes an increase in respiratory symptoms, especially in patients with asthma. The severity of allergic asthma in children is associated with the presence of intradomicilliary aeroallergens and intramural contaminants. Correlation to clinical abnormalities, spyrometryand skin test with the intradomiciliary pollution. Children who participated ranged in age from 6 to 15 years, attended public schools, and were classified as healthy and asthmatic. A questionnaire was applied to them, as well as a clinical history, spirometry, skin tests, and an environmental study at home. Fifty-seven children were studied, of 10 years of age (+/- 3). Group 1 (23 healthy children): Positive skin tests, dust 66.6%, cockroaches 66.6%, mites 33.3%, cat 33.3%, dog 4.3%. Principal clinical symptoms were cough 91.3%, wheezing 78.3%, respiratory difficulty 39.1% with a morning predominance of 78.3%. Spirometry showed an obstructive pattern in 30.5%. Group 2 (34 asthmatic children): Positive skin tests, mites 52.1%, dust 47.8%, cockroach 21.7%, cat 21.7%, dog 4.3%, passive exposure to tobacco smoke 79.5%. Principal clinical symptoms were cough 91.3%, respiratory 82.3%, wheezing 79.4%, predominantly at night 70.5%. Spirometry showed obstructive pattern in 67.7%. Children with asthma present great contact and sensitivity for intradomicilliary allergens such as mites in household dust, proteins from cat, dog, and cockroach feces, in addition to greater frequency of passive smoking. It is important to point out that these factors can be modifiable at low cost, thus presenting the conditions for a better quality of life for the patient and diminishing costs of medical attention.

[Modified polyurethane foam as a local hemostatic agent after dental extractions].

PubMed

Selten, M H A; Broekema, F I; Zuidema, J; van Oeveren, W; Bos, R R M

2013-01-01

In this split mouth experiment, the feasibility ofpolyurethane foam as a local hemostatic agent after dental extractions was studied. Ten healthy patients underwent 2 extractions ofa dental element in 1 treatment session. The 10 patients were subsequently randomly divided in a gelatin group and a collagen group. In the gelatin group, a polyurethane foam (PU) was applied in 1 extraction socket, while in the other socket a commercially available gelatin foam was applied. In the collagen group, a PU was applied in 1 socket, and a collagen wadding in the other. All hemostats were removed after 2 minutes, after which the degree of coagulation was measured using a thrombin/antithrombin test and a fibrinogen test. This study suggests that polyurethane foam has hemostatic capacity. Large scale clinical research is needed to confirm this finding, and should indicate whether this hemostatic capacity is clinically relevant.

Pharmacogenetic Predictors of Treatment-Related Toxicity Among Children With Acute Lymphoblastic Leukemia.

PubMed

Maxwell, Rochelle R; Cole, Peter D

2017-06-01

The aim of this review is to summarize the most recent and most robust pharmacogenetic predictors of treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL). Multiple studies have examined the toxicities of the primary chemotherapeutic agents used to treat childhood ALL in relation to host genetic factors. However, few results have been replicated independently, largely due to cohort differences in ancestry, chemotherapy treatment protocols, and definitions of toxicities. To date, there is only one widely accepted clinical guideline for dose modification based on gene status: thiopurine dosing based on TPMT genotype. Based on recent data, it is likely that this guideline will be modified to incorporate other gene variants, such as NUDT15. We highlight genetic variants that have been consistently associated with TRT across treatment groups, as well as those that best illustrate the underlying pathophysiology of TRT. In the coming decade, we expect that survivorship care will routinely specify screening recommendations based on genetics. Furthermore, clinical trials testing protective interventions may modify inclusion criteria based on genetically determined risk of specific TRTs.

Rapid and highly sensitive detection of Enterovirus 71 by using nanogold-enhanced electrochemical impedance spectroscopy

NASA Astrophysics Data System (ADS)

Li, Hsing-Yuan; Tseng, Shing-Hua; Cheng, Tsai-Mu; Chu, Hsueh-Liang; Lu, Yu-Ning; Wang, Fang-Yu; Tsai, Li-Yun; Shieh, Juo-Yu; Yang, Jyh-Yuan; Juan, Chien-Chang; Tu, Lung-Chen; Chang, Chia-Ching

2013-07-01

Enterovirus 71 (EV71) infection is an emerging infectious disease causing neurological complications and/or death within two to three days after the development of fever and rash. A low viral titre in clinical specimens makes the detection of EV71 difficult. Conventional approaches for detecting EV71 are time consuming, poorly sensitive, or complicated, and cannot be used effectively for clinical diagnosis. Furthermore, EV71 and Coxsackie virus A16 (CA16) may cross react in conventional assays. Therefore, a rapid, highly sensitive, specific, and user-friendly test is needed. We developed an EV71-specific nanogold-modified working electrode for electrochemical impedance spectroscopy in the detection of EV71. Our results show that EV71 can be distinguished from CA16, Herpes simplex virus, and lysozyme, with the modified nanogold electrode being able to detect EV71 in concentrations as low as 1 copy number/50 μl reaction volume, and the duration between sample preparation and detection being 11 min. This detection platform may have the potential for use in point-of-care diagnostics.

Strategy escalation: an emerging paradigm for safe clinical development of T cell gene therapies.

PubMed

Junghans, Richard Paul

2010-06-10

Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs) for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications.

Evidence for early neurodegeneration in the cervical cord of patients with primary progressive multiple sclerosis.

PubMed

Abdel-Aziz, Khaled; Schneider, Torben; Solanky, Bhavana S; Yiannakas, Marios C; Altmann, Dan R; Wheeler-Kingshott, Claudia A M; Peters, Amy L; Day, Brian L; Thompson, Alan J; Ciccarelli, Olga

2015-06-01

Spinal neurodegeneration is an important determinant of disability progression in patients with primary progressive multiple sclerosis. Advanced imaging techniques, such as single-voxel (1)H-magnetic resonance spectroscopy and q-space imaging, have increased pathological specificity for neurodegeneration, but are challenging to implement in the spinal cord and have yet to be applied in early primary progressive multiple sclerosis. By combining these imaging techniques with new clinical measures, which reflect spinal cord pathology more closely than conventional clinical tests, we explored the potential for spinal magnetic resonance spectroscopy and q-space imaging to detect early spinal neurodegeneration that may be responsible for clinical disability. Data from 21 patients with primary progressive multiple sclerosis within 6 years of disease onset, and 24 control subjects were analysed. Patients were clinically assessed on grip strength, vibration perception thresholds and postural stability, in addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25-Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale. All subjects underwent magnetic resonance spectroscopy and q-space imaging of the cervical cord and conventional brain and spinal magnetic resonance imaging at 3 T. Multivariate analyses and multiple regression models were used to assess the differences in imaging measures between groups and the relationship between magnetic resonance imaging measures and clinical scores, correcting for age, gender, spinal cord cross-sectional area, brain T2 lesion volume, and brain white matter and grey matter volume fractions. Although patients did not show significant cord atrophy when compared with healthy controls, they had significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P = 0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than controls. Patients showed an increase in q-space imaging-derived indices of perpendicular diffusivity in both the whole cord and major columns compared with controls (P < 0.05 for all indices). Lower total N-acetyl-aspartate was associated with higher disability, as assessed by the Expanded Disability Status Scale (coefficient = -0.41, 0.01 < P < 0.05), Modified Ashworth Scale (coefficient = -3.78, 0.01 < P < 0.05), vibration perception thresholds (coefficient = -4.37, P = 0.021) and postural sway (P < 0.001). Lower glutamate-glutamine predicted increased postural sway (P = 0.017). Increased perpendicular diffusivity in the whole cord and columns was associated with increased scores on the Modified Ashworth Scale, vibration perception thresholds and postural sway (P < 0.05 in all cases). These imaging findings indicate reduced structural integrity of neurons, demyelination, and abnormalities in the glutamatergic pathways in the cervical cord of early primary progressive multiple sclerosis, in the absence of extensive spinal cord atrophy. The observed relationship between imaging measures and disability suggests that early spinal neurodegeneration may underlie clinical impairment, and should be targeted in future clinical trials with neuroprotective agents to prevent the development of progressive disability. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program

PubMed Central

Mazuski, John E.; Gasink, Leanne B.; Armstrong, Jon; Broadhurst, Helen; Stone, Greg G.; Rank, Douglas; Llorens, Lily; Newell, Paul; Pachl, Jan

2016-01-01

Background. When combined with ceftazidime, the novel non–β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239). Methods. The primary end point was clinical cure at test-of-cure visit 28–35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of −12.5%. Results. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, −3.5%; 95% confidence interval −8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (−2.4%; −6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (−0.8%; −4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen's own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups. Conclusions. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal infections. Efficacy was similar against infections caused by ceftazidime-susceptible and ceftazidime-resistant pathogens. The safety profile of ceftazidime-avibactam plus metronidazole was consistent with that previously observed with ceftazidime alone. Clinical Trials Registration. NCT01499290 and NCT01500239. PMID:26962078

Antibacterial activity of resin adhesives, glass ionomer and resin-modified glass ionomer cements and a compomer in contact with dentin caries samples.

PubMed

Herrera, M; Castillo, A; Bravo, M; Liébana, J; Carrión, P

2000-01-01

A total of 103 clinical samples of carious dentin were used to study the antibacterial action of different dental resin adhesive materials (Gluma 2000, Syntac, Prisma Universal Bond 3, Scotchbond Multi-Purpose and Prime&Bond 2.0) glass ionomer cements (Ketac-Cem, Ketac-Bond, Ketac-Silver, Ketac-Fil) resin-modified glass ionomer cements (Fuji II LC, Vitremer and Vitrebond) and a compomer (Dyract). The agar plate diffusion method was used for the microbial cultures and a chlorhexidine control. The growth of the caries-producing microorganisms was effectively inhibited by the Vitremer and Vitrebond cements, and to a lesser extent by the Scotchbond Multi-Purpose adhesive system. Overall, there were statistically significant differences in the antibacterial activity of the products tested.

A Novel Method to Generate and Expand Clinical-Grade, Genetically Modified, Tumor-Infiltrating Lymphocytes

PubMed Central

Forget, Marie-Andrée; Tavera, René J.; Haymaker, Cara; Ramachandran, Renjith; Malu, Shuti; Zhang, Minying; Wardell, Seth; Fulbright, Orenthial J.; Toth, Chistopher Leroy; Gonzalez, Audrey M.; Thorsen, Shawne T.; Flores, Esteban; Wahl, Arely; Peng, Weiyi; Amaria, Rodabe N.; Hwu, Patrick; Bernatchez, Chantale

2017-01-01

Following the clinical success achieved with the first generation of adoptive cell therapy (ACT) utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs), the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP) environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center. PMID:28824634

Modified jailed balloon technique for bifurcation lesions.

PubMed

Saito, Shigeru; Shishido, Koki; Moriyama, Noriaki; Ochiai, Tomoki; Mizuno, Shingo; Yamanaka, Futoshi; Sugitatsu, Kazuya; Tobita, Kazuki; Matsumi, Junya; Tanaka, Yutaka; Murakami, Masato

2017-12-04

We propose a new systematic approach in bifurcation lesions, modified jailed balloon technique (M-JBT), and report the first clinical experience. Side branch occlusion brings with a serious complication and occurs in more than 7.0% of cases during bifurcation stenting. A jailed balloon (JB) is introduced into the side branch (SB), while a stent is placed in the main branch (MB) as crossing SB. The size of the JB is half of the MB stent size. While the proximal end of JB attaching to MB stent, both stent and JB are simultaneously inflated with same pressure. JB is removed and then guidewires are recrossed. Kissing balloon dilatation (KBD) and/or T and protrusion (TAP) stenting are applied as needed. Between February 2015 and February 2016, 233 patients (254 bifurcation lesions including 54 left main trunk disease) underwent percutaneous coronary intervention (PCI) using this technique. Procedure success was achieved in all cases. KBD was performed for 183 lesions and TAP stenting was employed for 31 lesions. Occlusion of SV was not observed in any of the patients. Bench test confirmed less deformity of MB stent in M-JBT compared with conventional-JBT. This is the first report for clinical experiences by using modified jailed balloon technique. This novel M-JBT is safe and effective in the preservation of SB patency during bifurcation stenting. © 2017 Wiley Periodicals, Inc.

Effects of Pilates exercises on sensory interaction, postural control and fatigue in patients with multiple sclerosis.

PubMed

Soysal Tomruk, Melda; Uz, Muhammed Zahid; Kara, Bilge; İdiman, Egemen

2016-05-01

Decreased postural control, sensory integration deficits and fatigue are important problems that cause functional impairments in patients with multiple sclerosis (pwMS). To examine the effect of modified clinical Pilates exercises on sensory interaction and balance, postural control and fatigue in pwMS. Eleven patients with multiple sclerosis and 12 healthy matched controls were recruited in this study. Limits of stability and postural stability tests were used to evaluate postural control by Biodex Balance System and sensory interaction assessed. Fatigue was assessed by Modified Fatigue Impact Scale. Pilates exercises were applied two times a week for 10 weeks and measurements were repeated to pwMS after exercise training. Postural control and fatigue (except psychosocial parameter) of pwMS were significantly worser than healthy controls (p<0.05). Significant improvements occurred in sensory interaction (eyes open, foam surface) and total, physical and cognitive scores of fatigue after 10-week modified clinical Pilates training (p<0.05). No significant changes were detected in postural control after the pilates exercises (p>0.05). Ten-week Pilates training is effective to improve sensory interaction and to decrease fatigue. Pilates exercises can be applied safely in ambulatory pwMS for enhance sensory interaction and balance and combat fatigue. More investigations are needed. Copyright © 2016 Elsevier B.V. All rights reserved.

Modified Newcastle disease virus vectors expressing the H5 hemagglutinin induce enhanced protection against highly pathogenic H5N1 avian influenza virus in chickens

PubMed Central

Kim, Shin-Hee; Paldurai, Anandan; Xiao, Sa; Collins, Peter L.; Samal, Siba K.

2016-01-01

Naturally-occurring attenuated strains of Newcastle disease virus (NDV) are being developed as vaccine vectors for use in poultry and humans. However, some NDV strains, such as Beaudette C (BC), may retain too much virulence in poultry for safe use, and more highly attenuated strains may be suboptimally immunogenic. We therefore modified the BC strain by changing the multibasic cleavage site sequence of the F protein to the dibasic sequence of avirulent strain LaSota. Additionally, the BC, F, and HN proteins were modified in several ways to enhance virus replication. These modified BC-derived vectors and the LaSota strain were engineered to express the hemagglutin (HA) protein of H5N1 highly pathogenic influenza virus (HPAIV). In general, the modified BC-based vectors expressing HA replicated better than LaSota/HA, and expressed higher levels of HA protein. Pathogenicity tests indicated that all the modified viruses were highly attenuated in chickens. Based on in vitro characterization, two of the modified BC vectors were chosen for evaluation in chickens as vaccine vectors against H5N1 HPAIV A/Vietnam/1203/04. Immunization of chickens with rNDV vector vaccines followed by challenge with HPAIV demonstrated high levels of protection against clinical disease and mortality. However, only those chickens immunized with modified BC/HA in which residues 271–330 from the F protein had been replaced with the corresponding sequence from the NDV AKO strain conferred complete protection against challenge virus shedding. Our findings suggest that this modified rNDV can be used safely as a vaccine vector with enhanced replication, expression, and protective efficacy in avian species, and potentially in humans. PMID:24968158

Screening for New Delhi metallo-β-lactamase-1 in Enterobacteriaceae: Is there a role for the modified Hodge test?

PubMed

Abidin, Nor Zanariah Zainol; Sulong, Anita; Alfizah, Hanafiah; Ding, Chuan Hun; Muttaqillah, Najihan Abdul Samat; Rahman, Md Mostafizur

2015-01-01

The New Delhi metallo-β-lactamase-1 (NDM-1) enzyme is a plasmid-encoded enzyme that inactivates carbapenem antibiotics. This study aims to ascertain if the modified Hodge test (MHT) has a role in screening for NDM-1 in Enterobacteriaceae with reduced carbapenem susceptibility. Over a period of one year, all Enterobacteriaceae isolates from all clinical specimens with reduced susceptibility to at least one carbapenem were subjected to MHT and conventional polymerase chain reaction (PCR) detection of the NDM-1 gene. A total of 13,098 Enterobacteriaceae isolates were screened and 63 (0.48%) had reduced susceptibility to at least one carbapenem. Out of the 63 isolates, 45 (71.4%) were MHT-positive. The NDM-1 gene was detected in 18 of the 63 isolates (28.6%). All 18 PCR-positive isolates were also MHT-positive. Thus, the sensitivity and specificity of the MHT in detecting NDM-1 in Enterobacteriaceae with reduced carbapenem susceptibility are 100% and 40%, respectively. The MHT is a useful test to screen for the presence of NDM-1 in Enterobacteriaceae with reduced carbapenem susceptibility. However, due to its rather low specificity, all MHT-positive isolates should be subjected to alternative tests (e.g. PCR) for confirmation, especially if other types of carbapenemases (e.g. KPC) are prevalent.

A short version of the revised 'experience of close relationships questionnaire': investigating non-clinical and clinical samples.

PubMed

Wongpakaran, Tinakon; Wongpakaran, Nahathai

2012-01-01

This study seeks to investigate the psychometric properties of the short version of the revised 'Experience of Close Relationships' questionnaire, comparing non-clinical and clinical samples. In total 702 subjects participated in this study, of whom 531 were non-clinical participants and 171 were psychiatric patients. They completed the short version of the revised 'Experience of Close Relationships' questionnaire (ECR-R-18), the Perceived Stress Scale-10(PSS-10), the Rosenberg Self-Esteem Scale (RSES) and the UCLA Loneliness scale. A retest of the ECR-R-18 was then performed at four-week intervals. Then, confirmatory factor analyses were performed to test the validity of the new scale. The ECR-R-18 showed a fair to good internal consistency (α 0.77 to 0.87) for both samples, and the test-retest reliability was found to be satisfactory (ICC = 0.75). The anxiety sub-scale demonstrated concurrent validity with PSS-10 and RSES, while the avoidance sub-scale showed concurrent validity with the UCLA Loneliness Scale. Confirmatory factor analysis using method factors yielded two factors with an acceptable model fit for both groups. An invariance test revealed that the ECR-R-18 when used on the clinical group differed from when used with the non-clinical group. The ECR-R-18 questionnaire revealed an overall better level of fit than the original 36 item questionnaire, indicating its suitability for use with a broader group of samples, including clinical samples. The reliability of the ECR-R- 18 might be increased if a modified scoring system is used and if our suggestions with regard to future studies are followed up.

Immunoglobulin E mediated food allergy.Modelling and application of diagnostic and predictive tests for existing and novel foods.

PubMed

Elizabeth I Opara Sarah L Oehlschlager A Bryan Hanley

1998-01-01

It is known that some foods cause an allergenic response in certain individuals. Clinical and immunological tests are available for the diagnosis of food allergy and identification of food allergens. However, there are no valid tests for the prediction of the allergenic potential of foods not normally recognized as allergenic. Such foods include: food products developed from foods which may not be recognizable as allergenic in their modified forms; foods produced using novel processes (novel foods), for example genetically modified foods; and foods not normally consumed but that are being used increasingly as alternatives to more traditional foods. Both the risks associated with food allergy and the fact that foods such as the ones described above will become available to the consumer, highlight the need for methods to screen for potential food allergens. This review provides a general overview of food allergy including mechanism, development and prevalence, but focuses on and discusses: 1) the possible risks (with specific reference to food allergy) associated with new and novel foods; and 2) the development/use of food allergy models (in vivo and in vitro) to assess the allergenic potential of new and novel foods.

TROCAI (Tropism Coreceptor Assay Information): a New Phenotypic Tropism Test and Its Correlation with Trofile Enhanced Sensitivity and Genotypic Approaches▿ †

PubMed Central

Gonzalez-Serna, Alejandro; Leal, Manuel; Genebat, Miguel; Abad, Maria Antonia; Garcia-Perganeda, Antonio; Ferrando-Martinez, Sara; Ruiz-Mateos, Ezequiel

2010-01-01

The only clinically validated assay available to determine HIV tropism is Trofile, an assay that possesses some limitations. Our first aim was to develop a new phenotypic tropism test (TROCAI [tropism coreceptor assay information]) and to categorize results generated by this test according to the virological response to a short-term exposure to the CCR5 receptor antagonist maraviroc (maraviroc clinical test). Our second aim was to compare TROCAI results to those obtained by Trofile enhanced sensitivity (ES) and to different genotypic algorithms. TROCAI assayed HIV tropism in 33 HIV-infected patient viral isolates obtained from a modified coculture, followed by multiple infection cycles of indicator cells. TROCAI obtained a reportable result in all patients with viral loads of >500 HIV RNA copies/ml and in 3/6 patients with <500 HIV RNA copies/ml (30/33 patients, 91.9%). Patients who responded to maraviroc had an X4-using virus proportion in indicator cell supernatant of 0 to 0.41%. Hence, we used the threshold of 0.5% to categorize TROCAI results as R5 (<0.5%) or dual/mixed (>0.5%). The concordance between TROCAI and Trofile (ES) was 22/24 (91.6%), and with genotypic approaches it was 22/26 (84.6%). TROCAI results, which were categorized in this study by the maraviroc clinical test, could be used as a test in addition to those currently used to select patients for treatment with CCR5 antagonists. PMID:20943871

SU-E-I-65: The Joint Commission's Requirements for Annual Diagnostic Physics Testing of Nuclear Medicine Equipment, and a Clinically Relevant Methodology for Testing Low-Contrast Resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

West, W. Geoffrey; Gray, David Clinton

Purpose: To introduce the Joint Commission's requirements for annual diagnostic physics testing of all nuclear medicine equipment, effective 7/1/2014, and to highlight an acceptable methodology for testing lowcontrast resolution of the nuclear medicine imaging system. Methods: The Joint Commission's required diagnostic physics evaluations are to be conducted for all of the image types produced clinically by each scanner. Other accrediting bodies, such as the ACR and the IAC, have similar imaging metrics, but do not emphasize testing low-contrast resolution as it relates clinically. The proposed method for testing low contrast resolution introduces quantitative metrics that are clinically relevant. The acquisitionmore » protocol and calculation of contrast levels will utilize a modified version of the protocol defined in AAPM Report #52. Results: Using the Rose criterion for lesion detection with a SNRpixel = 4.335 and a CNRlesion = 4, the minimum contrast levels for 25.4 mm and 31.8 mm cold spheres were calculated to be 0.317 and 0.283, respectively. These contrast levels are the minimum threshold that must be attained to guard against false positive lesion detection. Conclusion: Low contrast resolution, or detectability, can be properly tested in a manner that is clinically relevant by measuring the contrast level of cold spheres within a Jaszczak phantom using pixel values within ROI's placed in the background and cold sphere regions. The measured contrast levels are then compared to a minimum threshold calculated using the Rose criterion and a CNRlesion = 4. The measured contrast levels must either meet or exceed this minimum threshold to prove acceptable lesion detectability. This research and development activity was performed by the authors while employed at West Physics Consulting, LLC. It is presented with the consent of West Physics, which has authorized the dissemination of the information and/or techniques described in the work.« less

[Scores and stages in pneumology].

PubMed

Kuhn, Max

2013-10-01

Useful scales and classifications for patients with pulmonary diseases are discussed. The modified Medical Research Council breathlessness scale (mMRC) is a measure of disability in lung patients. The GOLD classifications, the COPD-Assessment Test (CAT) and the BODE Index are important to classify the severity of COPD and to measure the disability of these patients. The Geneva score is a clinical prediction rule used in determining the pre-test probability of pulmonary embolism. The Pulmonary Embolism Severity Index (PESI) is a scoring system used to predict 30 day mortality in patients with pulmonary embolism. The Epworth Sleepiness Scale is intended to measure daytime sleepiness in patients with sleep apnea syndrome. The Asthma Controll Test (ACT) determines if asthma symptoms are well controlled.

Linking Nurses' Clinical Leadership to Patient Care Quality: The Role of Transformational Leadership and Workplace Empowerment.

PubMed

Boamah, Sheila

2018-03-01

Background While improving patient safety requires strong nursing leadership, there has been little empirical research that has examined the mechanisms by which leadership influences patient safety outcomes. Aim To test a model examining relationships among transformational leadership, structural empowerment, staff nurse clinical leadership, and nurse-assessed adverse patient outcomes. Methods A cross-sectional survey was conducted with a randomly selected sample of 378 registered nurses working in direct patient care in acute care hospitals across Ontario, Canada. Structural equation modeling was used to test the hypothesized model. Results The model had an acceptable fit, and all paths were significant. Transformational leadership was significantly associated with decreased adverse patient outcomes through structural empowerment and staff nurse clinical leadership. Discussion This study highlights the importance of transformational leadership in creating empowering practice environments that foster high-quality care. The findings indicate that a more complete understanding of what drives desired patient outcomes warrants the need to focus on how to empower nurses and foster clinical leadership practices at the point of care. Conclusion In planning safety strategies, managers must demonstrate transformational leadership behaviors in order to modify the work environment to create better defenses for averting adverse events.

Towards the concept of disease-modifier in post-stroke or vascular cognitive impairment: a consensus report.

PubMed

Bordet, Régis; Ihl, Ralf; Korczyn, Amos D; Lanza, Giuseppe; Jansa, Jelka; Hoerr, Robert; Guekht, Alla

2017-05-24

Vascular cognitive impairment (VCI) is a complex spectrum encompassing post-stroke cognitive impairment (PSCI) and small vessel disease-related cognitive impairment. Despite the growing health, social, and economic burden of VCI, to date, no specific treatment is available, prompting the introduction of the concept of a disease modifier. Within this clinical spectrum, VCI and PSCI remain advancing conditions as neurodegenerative diseases with progression of both vascular and degenerative lesions accounting for cognitive decline. Disease-modifying strategies should integrate both pharmacological and non-pharmacological multimodal approaches, with pleiotropic effects targeting (1) endothelial and brain-blood barrier dysfunction; (2) neuronal death and axonal loss; (3) cerebral plasticity and compensatory mechanisms; and (4) degenerative-related protein misfolding. Moreover, pharmacological and non-pharmacological treatment in PSCI or VCI requires valid study designs clearly stating the definition of basic methodological issues, such as the instruments that should be used to measure eventual changes, the biomarker-based stratification of participants to be investigated, and statistical tests, as well as the inclusion and exclusion criteria that should be applied. A consensus emerged to propose the development of a disease-modifying strategy in VCI and PSCI based on pleiotropic pharmacological and non-pharmacological approaches.

Wound healing outcomes: Using big data and a modified intent-to-treat method as a metric for reporting healing rates.

PubMed

Ennis, William J; Hoffman, Rachel A; Gurtner, Geoffrey C; Kirsner, Robert S; Gordon, Hanna M

2017-08-01

Chronic wounds are increasing in prevalence and are a costly problem for the US healthcare system and throughout the world. Typically outcomes studies in the field of wound care have been limited to small clinical trials, comparative effectiveness cohorts and attempts to extrapolate results from claims databases. As a result, outcomes in real world clinical settings may differ from these published studies. This study presents a modified intent-to-treat framework for measuring wound outcomes and measures the consistency of population based outcomes across two distinct settings. In this retrospective observational analysis, we describe the largest to date, cohort of patient wound outcomes derived from 626 hospital based clinics and one academic tertiary care clinic. We present the results of a modified intent-to-treat analysis of wound outcomes as well as demographic and descriptive data. After applying the exclusion criteria, the final analytic sample includes the outcomes from 667,291 wounds in the national sample and 1,788 wounds in the academic sample. We found a consistent modified intent to treat healing rate of 74.6% from the 626 clinics and 77.6% in the academic center. We recommend that a standard modified intent to treat healing rate be used to report wound outcomes to allow for consistency and comparability in measurement across providers, payers and healthcare systems. © 2017 by the Wound Healing Society.

RECENT ADVANCES IN STRATEGIES FOR IMMUNOTHERAPY OF HUMAN PAPILLOMAVIRUS-INDUCED LESIONS

PubMed Central

Kanodia, Shreya; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. PMID:17973257

46 CFR 54.10-15 - Pneumatic test (modifies UG-100).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Pneumatic test (modifies UG-100). 54.10-15 Section 54.10-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-15 Pneumatic test (modifies UG-100). (a) Pneumatic testing of welded pressure vessels shall be...

46 CFR 54.10-15 - Pneumatic test (modifies UG-100).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Pneumatic test (modifies UG-100). 54.10-15 Section 54.10-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-15 Pneumatic test (modifies UG-100). (a) Pneumatic testing of welded pressure vessels shall be...

46 CFR 54.10-15 - Pneumatic test (modifies UG-100).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Pneumatic test (modifies UG-100). 54.10-15 Section 54.10-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-15 Pneumatic test (modifies UG-100). (a) Pneumatic testing of welded pressure vessels shall be...

Corrosion Control Test Method for Avionic Components

DTIC Science & Technology

1981-09-25

pin conn’ecLor adsemblies *Electronic test articles exposed in an avionic box The following test parameters were used: Environment A - Modified Sulfur Dic...carrier correlation criteria in Table IV. The modified sulfur dioxide/salt fog test showed the best correlation with the carrier exposed test arti...capacitor. The HCl/H 2 SO3 environment and the S2C12 environment, as expected, produced more electrical failures than the modified sulfur dioxide test

Standards for gene therapy clinical trials based on pro-active risk assessment in a London NHS Teaching Hospital Trust.

PubMed

Bamford, K B; Wood, S; Shaw, R J

2005-02-01

Conducting gene therapy clinical trials with genetically modified organisms as the vectors presents unique safety and infection control issues. The area is governed by a range of legislation and guidelines, some unique to this field, as well as those pertinent to any area of clinical work. The relevant regulations covering gene therapy using genetically modified vectors are reviewed and illustrated with the approach taken by a large teaching hospital NHS Trust. Key elements were Trust-wide communication and involvement of staff in a pro-active approach to risk management, with specific emphasis on staff training and engagement, waste management, audit and record keeping. This process has led to the development of proposed standards for clinical trials involving genetically modified micro-organisms.

Reliability and measurement error of active knee extension range of motion in a modified slump test position: a pilot study.

PubMed

Tucker, Neil; Reid, Duncan; McNair, Peter

2007-01-01

The slump test is a tool to assess the mechanosensitivity of the neuromeningeal structures within the vertebral canal. While some studies have investigated the reliability of aspects of this test within the same day, few have assessed the reliability across days. Therefore, the purpose of this pilot study was to investigate reliability when measuring active knee extension range of motion (AROM) in a modified slump test position within trials on a single day and across days. Ten male and ten female asymptomatic subjects, ages 20-49 (mean age 30.1, SD 6.4) participated in the study. Knee extension AROM in a modified slump position with the cervical spine in a flexed position and then in an extended position was measured via three trials on two separate days. Across three trials, knee extension AROM increased significantly with a mean magnitude of 2 degrees within days for both cervical spine positions (P>0.05). The findings showed that there was no statistically significant difference in knee extension AROM measurements across days (P>0.05). The intraclass correlation coefficients for the mean of the three trials across days were 0.96 (lower limit 95% CI: 0.90) with the cervical spine flexed and 0.93 (lower limit 95% CI: 0.83) with cervical extension. Measurement error was calculated by way of the typical error and 95% limits of agreement, and visually represented in Bland and Altman plots. The typical error for the cervical flexed and extended positions averaged across trials was 2.6 degrees and 3.3 degrees , respectively. The limits of agreement were narrow, and the Bland and Altman plots also showed minimal bias in the joint angles across days with a random distribution of errors across the range of measured angles. This study demonstrated that knee extension AROM could be reliably measured across days in subjects without pathology and that the measurement error was acceptable. Implications of variability over multiple trials are discussed. The modified set-up for the test using the Kincom dynamometer and elevated thigh position may be useful to clinical researchers in determining the mechanosensitivity of the nervous system.

Reliability and Measurement Error of Active Knee Extension Range of Motion in a Modified Slump Test Position: A Pilot Study

PubMed Central

Tucker, Neil; Reid, Duncan; McNair, Peter

2007-01-01

The slump test is a tool to assess the mechanosensitivity of the neuromeningeal structures within the vertebral canal. While some studies have investigated the reliability of aspects of this test within the same day, few have assessed the reliability across days. Therefore, the purpose of this pilot study was to investigate reliability when measuring active knee extension range of motion (AROM) in a modified slump test position within trials on a single day and across days. Ten male and ten female asymptomatic subjects, ages 20–49 (mean age 30.1, SD 6.4) participated in the study. Knee extension AROM in a modified slump position with the cervical spine in a flexed position and then in an extended position was measured via three trials on two separate days. Across three trials, knee extension AROM increased significantly with a mean magnitude of 2° within days for both cervical spine positions (P>0.05). The findings showed that there was no statistically significant difference in knee extension AROM measurements across days (P>0.05). The intraclass correlation coefficients for the mean of the three trials across days were 0.96 (lower limit 95% CI: 0.90) with the cervical spine flexed and 0.93 (lower limit 95% CI: 0.83) with cervical extension. Measurement error was calculated by way of the typical error and 95% limits of agreement, and visually represented in Bland and Altman plots. The typical error for the cervical flexed and extended positions averaged across trials was 2.6° and 3.3°, respectively. The limits of agreement were narrow, and the Bland and Altman plots also showed minimal bias in the joint angles across days with a random distribution of errors across the range of measured angles. This study demonstrated that knee extension AROM could be reliably measured across days in subjects without pathology and that the measurement error was acceptable. Implications of variability over multiple trials are discussed. The modified set-up for the test using the Kincom dynamometer and elevated thigh position may be useful to clinical researchers in determining the mechanosensitivity of the nervous system. PMID:19066666

2017 Multimodality Appropriate Use Criteria for Noninvasive Cardiac Imaging: Expert Consensus of the Asian Society of Cardiovascular Imaging.

PubMed

Beck, Kyongmin Sarah; Kim, Jeong A; Choe, Yeon Hyeon; Hian, Sim Kui; Hoe, John; Hong, Yoo Jin; Kim, Sung Mok; Kim, Tae Hoon; Kim, Young Jin; Kim, Yun Hyeon; Kuribayashi, Sachio; Lee, Jongmin; Leong, Lilian; Lim, Tae-Hwan; Lu, Bin; Park, Jae Hyung; Sakuma, Hajime; Yang, Dong Hyun; Yaw, Tan Swee; Wan, Yung-Liang; Zhang, Zhaoqi; Zhao, Shihua; Yong, Hwan Seok

2017-01-01

In 2010, the Asian Society of Cardiovascular Imaging (ASCI) provided recommendations for cardiac CT and MRI, and this document reflects an update of the 2010 ASCI appropriate use criteria (AUC). In 2016, the ASCI formed a new working group for revision of AUC for noninvasive cardiac imaging. A major change that we made in this document is the rating of various noninvasive tests (exercise electrocardiogram, echocardiography, positron emission tomography, single-photon emission computed tomography, radionuclide imaging, cardiac magnetic resonance, and cardiac computed tomography/angiography), compared side by side for their applications in various clinical scenarios. Ninety-five clinical scenarios were developed from eight selected pre-existing guidelines and classified into four sections as follows: 1) detection of coronary artery disease, symptomatic or asymptomatic; 2) cardiac evaluation in various clinical scenarios; 3) use of imaging modality according to prior testing; and 4) evaluation of cardiac structure and function. The clinical scenarios were scored by a separate rating committee on a scale of 1-9 to designate appropriate use, uncertain use, or inappropriate use according to a modified Delphi method. Overall, the AUC ratings for CT were higher than those of previous guidelines. These new AUC provide guidance for clinicians choosing among available testing modalities for various cardiac diseases and are also unique, given that most previous AUC for noninvasive imaging include only one imaging technique. As cardiac imaging is multimodal in nature, we believe that these AUC will be more useful for clinical decision making.

Reliability and validity of three pain provocation tests used for the diagnosis of chronic proximal hamstring tendinopathy.

PubMed

Cacchio, Angelo; Borra, Fabrizio; Severini, Gabriele; Foglia, Andrea; Musarra, Frank; Taddio, Nicola; De Paulis, Fosco

2012-09-01

The clinical assessment of chronic proximal hamstring tendinopathy (PHT) in athletes is a challenge to sports medicine. To be able to compare the results of research and treatments, the methods used to diagnose and evaluate PHT must be clearly defined and reproducible. To assess the reliability and validity of three pain provocation tests used for the diagnosis of PHT. Ninety-two athletes with (N=46) and without (N=46) PHT were examined by one physician and two physiotherapists, who were trained in the examination techniques before the study. The examiners were blinded to the symptoms and identity of the athletes. The three pain provocation tests examined were the Puranen-Orava, bent-knee stretch and modified bent-knee stretch tests. Intraclass correlation coefficients (ICCs) based on the repeated measures analysis of variance were used to analyse the intraexaminer and interexaminer reliability, while sensitivity, specificity, predictive values and likelihood ratios were used to determine the validity of the three tests. The ICC values in all three tests revealed a high correlation (range 0.82 to 0.88) for the interexaminer reliability and a high-to-very high correlation (range 0.87 to 0.93) for the intraexaminer reliability. All three tests displayed a moderate-to-high validity, with the highest degree of validity being yielded by the modified bent-knee stretch test. All three pain provocation tests proved to be of potential value in assessing chronic PHT in athletes. However, we recommend that they be used in conjunction with other objective measures, such as MRI.

Physical tests for shoulder impingements and local lesions of bursa, tendon or labrum that may accompany impingement.

PubMed

Hanchard, Nigel C A; Lenza, Mário; Handoll, Helen H G; Takwoingi, Yemisi

2013-04-30

Impingement is a common cause of shoulder pain. Impingement mechanisms may occur subacromially (under the coraco-acromial arch) or internally (within the shoulder joint), and a number of secondary pathologies may be associated. These include subacromial-subdeltoid bursitis (inflammation of the subacromial portion of the bursa, the subdeltoid portion, or both), tendinopathy or tears affecting the rotator cuff or the long head of biceps tendon, and glenoid labral damage. Accurate diagnosis based on physical tests would facilitate early optimisation of the clinical management approach. Most people with shoulder pain are diagnosed and managed in the primary care setting. To evaluate the diagnostic accuracy of physical tests for shoulder impingements (subacromial or internal) or local lesions of bursa, rotator cuff or labrum that may accompany impingement, in people whose symptoms and/or history suggest any of these disorders. We searched electronic databases for primary studies in two stages. In the first stage, we searched MEDLINE, EMBASE, CINAHL, AMED and DARE (all from inception to November 2005). In the second stage, we searched MEDLINE, EMBASE and AMED (2005 to 15 February 2010). Searches were delimited to articles written in English. We considered for inclusion diagnostic test accuracy studies that directly compared the accuracy of one or more physical index tests for shoulder impingement against a reference test in any clinical setting. We considered diagnostic test accuracy studies with cross-sectional or cohort designs (retrospective or prospective), case-control studies and randomised controlled trials. Two pairs of review authors independently performed study selection, assessed the study quality using QUADAS, and extracted data onto a purpose-designed form, noting patient characteristics (including care setting), study design, index tests and reference standard, and the diagnostic 2 x 2 table. We presented information on sensitivities and specificities with 95% confidence intervals (95% CI) for the index tests. Meta-analysis was not performed. We included 33 studies involving 4002 shoulders in 3852 patients. Although 28 studies were prospective, study quality was still generally poor. Mainly reflecting the use of surgery as a reference test in most studies, all but two studies were judged as not meeting the criteria for having a representative spectrum of patients. However, even these two studies only partly recruited from primary care.The target conditions assessed in the 33 studies were grouped under five main categories: subacromial or internal impingement, rotator cuff tendinopathy or tears, long head of biceps tendinopathy or tears, glenoid labral lesions and multiple undifferentiated target conditions. The majority of studies used arthroscopic surgery as the reference standard. Eight studies utilised reference standards which were potentially applicable to primary care (local anaesthesia, one study; ultrasound, three studies) or the hospital outpatient setting (magnetic resonance imaging, four studies). One study used a variety of reference standards, some applicable to primary care or the hospital outpatient setting. In two of these studies the reference standard used was acceptable for identifying the target condition, but in six it was only partially so. The studies evaluated numerous standard, modified, or combination index tests and 14 novel index tests. There were 170 target condition/index test combinations, but only six instances of any index test being performed and interpreted similarly in two studies. Only two studies of a modified empty can test for full thickness tear of the rotator cuff, and two studies of a modified anterior slide test for type II superior labrum anterior to posterior (SLAP) lesions, were clinically homogenous. Due to the limited number of studies, meta-analyses were considered inappropriate. Sensitivity and specificity estimates from each study are presented on forest plots for the 170 target condition/index test combinations grouped according to target condition. There is insufficient evidence upon which to base selection of physical tests for shoulder impingements, and local lesions of bursa, tendon or labrum that may accompany impingement, in primary care. The large body of literature revealed extreme diversity in the performance and interpretation of tests, which hinders synthesis of the evidence and/or clinical applicability.

Field test method to determine presence and quantity of modifiers in liquid asphalt.

DOT National Transportation Integrated Search

2015-05-01

Asphalt modified with styrene butadiene styrene (SBS) polymer and/or ground tire rubber (GTR) is widely used in the U.S. : to enhance its performance. However, there are very few field tests developed to verify the content of modifier(s) in asphalt :...

A Sensitive Branched DNA HIV-1 Signal Amplification Viral Load Assay with Single Day Turnaround

PubMed Central

Baumeister, Mark A.; Zhang, Nan; Beas, Hilda; Brooks, Jesse R.; Canchola, Jesse A.; Cosenza, Carlo; Kleshik, Felix; Rampersad, Vinod; Surtihadi, Johan; Battersby, Thomas R.

2012-01-01

Branched DNA (bDNA) is a signal amplification technology used in clinical and research laboratories to quantitatively detect nucleic acids. An overnight incubation is a significant drawback of highly sensitive bDNA assays. The VERSANT® HIV-1 RNA 3.0 Assay (bDNA) (“Versant Assay”) currently used in clinical laboratories was modified to allow shorter target incubation, enabling the viral load assay to be run in a single day. To dramatically reduce the target incubation from 16–18 h to 2.5 h, composition of only the “Lysis Diluent” solution was modified. Nucleic acid probes in the assay were unchanged. Performance of the modified assay (assay in development; not commercially available) was evaluated and compared to the Versant Assay. Dilution series replicates (>950 results) were used to demonstrate that analytical sensitivity, linearity, accuracy, and precision for the shorter modified assay are comparable to the Versant Assay. HIV RNA-positive clinical specimens (n = 135) showed no significant difference in quantification between the modified assay and the Versant Assay. Equivalent relative quantification of samples of eight genotypes was demonstrated for the two assays. Elevated levels of several potentially interfering endogenous substances had no effect on quantification or specificity of the modified assay. The modified assay with drastically improved turnaround time demonstrates the viability of signal-amplifying technology, such as bDNA, as an alternative to the PCR-based assays dominating viral load monitoring in clinical laboratories. Highly sensitive bDNA assays with a single day turnaround may be ideal for laboratories with especially stringent cost, contamination, or reliability requirements. PMID:22479381

A sensitive branched DNA HIV-1 signal amplification viral load assay with single day turnaround.

PubMed

Baumeister, Mark A; Zhang, Nan; Beas, Hilda; Brooks, Jesse R; Canchola, Jesse A; Cosenza, Carlo; Kleshik, Felix; Rampersad, Vinod; Surtihadi, Johan; Battersby, Thomas R

2012-01-01

Branched DNA (bDNA) is a signal amplification technology used in clinical and research laboratories to quantitatively detect nucleic acids. An overnight incubation is a significant drawback of highly sensitive bDNA assays. The VERSANT® HIV-1 RNA 3.0 Assay (bDNA) ("Versant Assay") currently used in clinical laboratories was modified to allow shorter target incubation, enabling the viral load assay to be run in a single day. To dramatically reduce the target incubation from 16-18 h to 2.5 h, composition of only the "Lysis Diluent" solution was modified. Nucleic acid probes in the assay were unchanged. Performance of the modified assay (assay in development; not commercially available) was evaluated and compared to the Versant Assay. Dilution series replicates (>950 results) were used to demonstrate that analytical sensitivity, linearity, accuracy, and precision for the shorter modified assay are comparable to the Versant Assay. HIV RNA-positive clinical specimens (n = 135) showed no significant difference in quantification between the modified assay and the Versant Assay. Equivalent relative quantification of samples of eight genotypes was demonstrated for the two assays. Elevated levels of several potentially interfering endogenous substances had no effect on quantification or specificity of the modified assay. The modified assay with drastically improved turnaround time demonstrates the viability of signal-amplifying technology, such as bDNA, as an alternative to the PCR-based assays dominating viral load monitoring in clinical laboratories. Highly sensitive bDNA assays with a single day turnaround may be ideal for laboratories with especially stringent cost, contamination, or reliability requirements.

Discovering body site and severity modifiers in clinical texts

PubMed Central

Dligach, Dmitriy; Bethard, Steven; Becker, Lee; Miller, Timothy; Savova, Guergana K

2014-01-01

Objective To research computational methods for discovering body site and severity modifiers in clinical texts. Methods We cast the task of discovering body site and severity modifiers as a relation extraction problem in the context of a supervised machine learning framework. We utilize rich linguistic features to represent the pairs of relation arguments and delegate the decision about the nature of the relationship between them to a support vector machine model. We evaluate our models using two corpora that annotate body site and severity modifiers. We also compare the model performance to a number of rule-based baselines. We conduct cross-domain portability experiments. In addition, we carry out feature ablation experiments to determine the contribution of various feature groups. Finally, we perform error analysis and report the sources of errors. Results The performance of our method for discovering body site modifiers achieves F1 of 0.740–0.908 and our method for discovering severity modifiers achieves F1 of 0.905–0.929. Discussion Results indicate that both methods perform well on both in-domain and out-domain data, approaching the performance of human annotators. The most salient features are token and named entity features, although syntactic dependency features also contribute to the overall performance. The dominant sources of errors are infrequent patterns in the data and inability of the system to discern deeper semantic structures. Conclusions We investigated computational methods for discovering body site and severity modifiers in clinical texts. Our best system is released open source as part of the clinical Text Analysis and Knowledge Extraction System (cTAKES). PMID:24091648

Discovering body site and severity modifiers in clinical texts.

PubMed

Dligach, Dmitriy; Bethard, Steven; Becker, Lee; Miller, Timothy; Savova, Guergana K

2014-01-01

To research computational methods for discovering body site and severity modifiers in clinical texts. We cast the task of discovering body site and severity modifiers as a relation extraction problem in the context of a supervised machine learning framework. We utilize rich linguistic features to represent the pairs of relation arguments and delegate the decision about the nature of the relationship between them to a support vector machine model. We evaluate our models using two corpora that annotate body site and severity modifiers. We also compare the model performance to a number of rule-based baselines. We conduct cross-domain portability experiments. In addition, we carry out feature ablation experiments to determine the contribution of various feature groups. Finally, we perform error analysis and report the sources of errors. The performance of our method for discovering body site modifiers achieves F1 of 0.740-0.908 and our method for discovering severity modifiers achieves F1 of 0.905-0.929. Results indicate that both methods perform well on both in-domain and out-domain data, approaching the performance of human annotators. The most salient features are token and named entity features, although syntactic dependency features also contribute to the overall performance. The dominant sources of errors are infrequent patterns in the data and inability of the system to discern deeper semantic structures. We investigated computational methods for discovering body site and severity modifiers in clinical texts. Our best system is released open source as part of the clinical Text Analysis and Knowledge Extraction System (cTAKES).

Evaluating Trauma Sonography for Operational Use in the Microgravity Environment

NASA Technical Reports Server (NTRS)

Kirkpatrick, Andrew W.; Jones, Jeffrey A.; Sargsyan, Ashot; Hamilton, Douglas; Melton, Shannon; Beck, George; Nicolaou, Savvas; Campbell, Mark; Dulchavsky, Scott

2007-01-01

Sonography is the only medical imaging modality aboard the ISS, and is likely to remain the leading imaging modality in future human space flight programs. While trauma sonography (TS) has been well recognized for terrestrial trauma settings, the technique had to be evaluated for suitability in space flight prior to adopting it as an operational capability. The authors found the following four-phased evaluative approach applicable to this task: 1) identifying standard or novel terrestrial techniques for potential use in space medicine; 2) developing and testing these techniques with suggested modifications on the ground (1g) either in clinical settings or in animal models, as appropriate; 3) evaluating and refining the techniques in parabolic flight (0g); and 4) validating and implementing for clinical use in space. In Phase I of the TS project, expert opinion and literature review suggested TS to be a potential screening tool for trauma in space. In Phase II, animal models were developed and tested in ground studies, and clinical studies were carried out in collaborating trauma centers. In Phase III, animal models were flight-tested in the NASA KC-135 Reduced Gravity Laboratory. Preliminary results of the first three phases demonstrated potential clinical utility of TS in microgravity. Phase IV studies have begun to address crew training issues, on-board imaging protocols, and data transfer procedures necessary to offer the modified TS technique for space use.

Inter-Rater Reliability of the Modified Ashworth Scale and Modified Modified Ashworth Scale in Assessing Poststroke Elbow Flexor Spasticity

ERIC Educational Resources Information Center

Kaya, Taciser; Goksel Karatepe, Altinay; Gunaydin, Rezzan; Koc, Aysegul; Altundal Ercan, Ulku

2011-01-01

The Modified Ashworth Scale (MAS) is commonly used in clinical practice for grading spasticity. However, it was modified recently by omitting grade "1+" of the MAS and redefining grade "2". The aim of this study was to investigate the inter-rater reliability of MAS and modified MAS (MMAS) for the assessment of poststroke elbow flexor spasticity.…

Adaptive clinical trial design.

PubMed

Chow, Shein-Chung

2014-01-01

In recent years, the use of adaptive design methods in clinical trials based on accumulated data at interim has received much attention because of its flexibility and efficiency in pharmaceutical/clinical development. In practice, adaptive design may provide the investigators a second chance to modify or redesign the trial while the study is still ongoing. However, it is a concern that a shift in target patient population may occur after significant adaptations are made. In addition, the overall type I error rate may not be preserved. Moreover, the results may not be reliable and hence are difficult to interpret. As indicated by the US Food and Drug Administration draft guidance on adaptive design clinical trials, the adaptive design has to be a prospectively planned opportunity and should be based on information collected within the study, with or without formal statistical hypothesis testing. This article reviews the relative advantages, limitations, and feasibility of commonly considered adaptive designs in clinical trials. Statistical concerns when implementing adaptive designs are also discussed.

Repurposing the clinical record: can an existing natural language processing system de-identify clinical notes?

PubMed

Morrison, Frances P; Li, Li; Lai, Albert M; Hripcsak, George

2009-01-01

Electronic clinical documentation can be useful for activities such as public health surveillance, quality improvement, and research, but existing methods of de-identification may not provide sufficient protection of patient data. The general-purpose natural language processor MedLEE retains medical concepts while excluding the remaining text so, in addition to processing text into structured data, it may be able provide a secondary benefit of de-identification. Without modifying the system, the authors tested the ability of MedLEE to remove protected health information (PHI) by comparing 100 outpatient clinical notes with the corresponding XML-tagged output. Of 809 instances of PHI, 26 (3.2%) were detected in output as a result of processing and identification errors. However, PHI in the output was highly transformed, much appearing as normalized terms for medical concepts, potentially making re-identification more difficult. The MedLEE processor may be a good enhancement to other de-identification systems, both removing PHI and providing coded data from clinical text.

Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.

PubMed

Krackhardt, Angela M; Anliker, Brigitte; Hildebrandt, Martin; Bachmann, Michael; Eichmüller, Stefan B; Nettelbeck, Dirk M; Renner, Matthias; Uharek, Lutz; Willimsky, Gerald; Schmitt, Michael; Wels, Winfried S; Schüssler-Lenz, Martina

2018-04-01

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

Clinical learning environments (actual and expected): perceptions of Iran University of Medical Sciences nursing students

PubMed Central

Bigdeli, Shoaleh; Pakpour, Vahid; Aalaa, Maryam; Shekarabi, Robabeh; Sanjari, Mahnaz; Haghani, Hamid; Mehrdad, Neda

2015-01-01

Background: Educational clinical environment has an important role in nursing students' learning. Any difference between actual and expected clinical environment will decrease nursing students’ interest in clinical environments and has a negative correlation with their clinical performance. Methods: This descriptive cross-sectional study is an attempt to compare nursing students' perception of the actual and expected status of clinical environments in medical-surgical wards. Participants of the study were 127 bachelor nursing students of Iran University of Medical Sciences in the internship period. Data gathering instruments were a demographic questionnaire (including sex, age, and grade point average), and the Clinical Learning Environment Inventory (CLEI) originally developed by Professor Chan (2001), in which its modified Farsi version (Actual and Preferred forms) consisting 42 items, 6 scales and 7 items per scale was used. Descriptive and inferential statistics (t-test, paired t-test, ANOVA) were used for data analysis through SPSS version 16. Results: The results indicated that there were significant differences between the preferred and actual form in all six scales. In other word, comparing with the actual form, the mean scores of all items in the preferred form were higher. The maximum mean difference was in innovation and the highest mean difference was in involvement scale. Conclusion: It is concluded that nursing students do not have a positive perception of their actual clinical teaching environment and this perception is significantly different from their perception of their expected environment. PMID:26034726

Reduced brightness contrast as a reading aid.

PubMed

Giddings, E H; Carmean, S L

1989-10-01

A standard reading comprehension test, modified by printing half of the material on medium grey paper to lower the contrast of print-to-page, was administered to 54 college students, 21 of whom had previously been diagnosed as learning disabled. Comprehension of the control group was little affected by the contrast, but the mean score for the learning disabled students was 10% higher on the pages with reduced contrast. This is congruent with Meares's 1980 clinical observations that reducing contrast significantly aids some readers.

46 CFR 56.97-30 - Hydrostatic tests (modifies 137.4).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Hydrostatic tests (modifies 137.4). 56.97-30 Section 56.97-30 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Pressure Tests § 56.97-30 Hydrostatic tests (modifies 137.4). (a) Provision of air vents at high points. Vents must be...

Presentation of Diagnostic Information to Doctors May Change Their Interpretation and Clinical Management: A Web-Based Randomised Controlled Trial.

PubMed

Ben-Shlomo, Yoav; Collin, Simon M; Quekett, James; Sterne, Jonathan A C; Whiting, Penny

2015-01-01

There is little evidence on how best to present diagnostic information to doctors and whether this makes any difference to clinical management. We undertook a randomised controlled trial to see if different data presentations altered clinicians' decision to further investigate or treat a patient with a fictitious disorder ("Green syndrome") and their ability to determine post-test probability. We recruited doctors registered with the United Kingdom's largest online network for medical doctors between 10 July and 6" November 2012. Participants were randomised to one of four arms: (a) text summary of sensitivity and specificity, (b) Fagan's nomogram, (c) probability-modifying plot (PMP), (d) natural frequency tree (NFT). The main outcome measure was the decision whether to treat, not treat or undertake a brain biopsy on the hypothetical patient and the correct post-test probability. Secondary outcome measures included knowledge of diagnostic tests. 917 participants attempted the survey and complete data were available from 874 (95.3%). Doctors randomized to the PMP and NFT arms were more likely to treat the patient than those randomized to the text-only arm. (ORs 1.49, 95% CI 1.02, 2.16) and 1.43, 95% CI 0.98, 2.08 respectively). More patients randomized to the PMP (87/218-39.9%) and NFT (73/207-35.3%) arms than the nomogram (50/194-25.8%) or text only (30/255-11.8%) arms reported the correct post-test probability (p <0.001). Younger age, postgraduate training and higher self-rated confidence all predicted better knowledge performance. Doctors with better knowledge were more likely to view an optional learning tutorial (OR per correct answer 1.18, 95% CI 1.06, 1.31). Presenting diagnostic data using a probability-modifying plot or natural frequency tree influences the threshold for treatment and improves interpretation of tests results compared to text summary of sensitivity and specificity or Fagan's nomogram.

Can postural modification reduce kinetic and kinematic loading during the bowing postures of Islamic prayer?

PubMed

AbouHassan, J; Milosavljevic, S; Carman, A

2010-12-01

As stooped postures are known to increase kinematic and kinetic loading on the lumbar spine they can be problematic for people with low back pain and postural task modification is often recommended. For the Muslim with low back pain, the bowing postures during prayer can aggravate low back symptoms. The aims of this study were to describe lumbo-sacral and pelvic tilt kinematics and lumbo-sacral kinetics during the standard bowing postures of Islam and to compare these to kinematic and kinetic data gathered during a clinically recommended modified bowing posture. The study was a repeated measures within subject cross-over design with 33 healthy male Muslim participants. 3-D motion analysis data were gathered to calculate body joint angles during the two bowing postures. A 3-D biomechanical model was then used to calculate spinal loads. Paired t-test analyses showed that the use of the modified posture resulted in significantly less pelvic tilt range of motion and anterior shear force and compressive force L5/S1, at stages 1 and 5 of bowing. Although this study was conducted with healthy young Muslim males, the use of this modified bent knee posture is recommended for all Muslims with low back pain. Clinical trials are being considered to determine the clinical utility of this postural manoeuvre as an intervention. STATEMENT OF RELEVANCE: The presence of low back pain may hinder a Muslim's ability to use the traditional Islamic bowing posture. Muslims who have low back pain may benefit from adopting a modification to the traditional bowing posture, which has been found to reduce the loads and postural demands on the lower back.

Epidemiology and Factors Related to Clinical Severity of Acute Gastroenteritis in Hospitalized Children after the Introduction of Rotavirus Vaccination.

PubMed

Kim, Ahlee; Chang, Ju Young; Shin, Sue; Yi, Hana; Moon, Jin Soo; Ko, Jae Sung; Oh, Sohee

2017-03-01

We aimed to investigate epidemiology and host- and pathogen-related factors associated with clinical severity of acute gastroenteritis (AGE) in children after rotavirus vaccination introduction. Factors assessed included age, co-infection with more than 2 viruses, and virus-toxigenic Clostridium difficile co-detection. Fecal samples and clinical information, including modified Vesikari scores, were collected from hospitalized children with AGE. The presence of enteric viruses and bacteria, including toxigenic C. difficile, was detected by polymerase chain reaction (PCR). Among the 415 children included, virus was detected in stool of 282 (68.0%) children. Co-infection with more than 2 viruses and toxigenic C. difficile were found in 24 (8.5%) and 26 (9.2%) children with viral AGE, respectively. Norovirus (n = 130) infection, including norovirus-associated co-infection, was the most frequent infection, especially in children aged < 24 months (P < 0.001). In the severity-related analysis, age < 24 months was associated with greater diarrheal severity (P < 0.001) and modified Vesikari score (P = 0.001), after adjustment for other severity-related factors including rotavirus status. Although the age at infection with rotavirus was higher than that for other viruses (P = 0.001), rotavirus detection was the most significant risk factor for all severity parameters, including modified Vesikari score (P < 0.001). Viral co-infection and toxigenic C. difficile co-detection were not associated with any severity-related parameter. This information will be helpful in the management of childhood AGE in this era of rotavirus vaccination and availability of molecular diagnostic tests, which often lead to the simultaneous detection of multiple pathogens.

Overcoming translational barriers impeding development of Alzheimer's disease modifying therapies.

PubMed

Golde, Todd E

2016-10-01

It has now been ~ 30 years since the Alzheimer's disease (AD) research entered what may be termed the 'molecular era' that began with the identification of the amyloid β protein (Aβ) as the primary component of amyloid within senile plaques and cerebrovascular amyloid and the microtubule-associated protein tau as the primary component of neurofibrillary tangles in the AD brain. These pivotal discoveries and the subsequent genetic, pathological, and modeling studies supporting pivotal roles for tau and Aβ aggregation and accumulation have provided firm rationale for a new generation of AD therapies designed not to just provide symptomatic benefit, but as disease modifying agents that would slow or even reverse the disease course. Indeed, over the last 20 years numerous therapeutic strategies for disease modification have emerged, been preclinically validated, and advanced through various stages of clinical testing. Unfortunately, no therapy has yet to show significant clinical disease modification. In this review, I describe 10 translational barriers to successful disease modification, highlight current efforts addressing some of these barriers, and discuss how the field could focus future efforts to overcome barriers that are not major foci of current research efforts. Seminal discoveries made over the past 25 years have provided firm rationale for a new generation of Alzheimer's disease (AD) therapies designed as disease modifying agents that would slow or even reverse the disease course. Unfortunately, no therapy has yet to show significant clinical disease modification. In this review, I describe 10 translational barriers to successful AD disease modification, highlight current efforts addressing some of these barriers, and discuss how the field could focus future efforts to overcome these barriers. This article is part of the 60th Anniversary special issue. © 2016 International Society for Neurochemistry.

Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy

PubMed Central

Vickery, Brian P.; Scurlock, Amy M.; Kulis, Michael; Steele, Pamela H.; Kamilaris, Janet; Berglund, Jelena P.; Burk, Caitlin; Hiegel, Anne; Carlisle, Suzanna; Christie, Lynn; Perry, Tamara T.; Pesek, Robbie D.; Sheikh, Saira; Virkud, Yamini; Smith, P. Brian; Shamji, Mohamed H.; Durham, Stephen R.; Jones, Stacie M.; Burks, A. Wesley

2013-01-01

Background Although peanut oral immunotherapy (OIT) has been conclusively shown to cause desensitization, it is currently unknown whether clinical protection persists after stopping therapy. Objective Our primary objective was to determine whether peanut OIT can induce sustained unresponsiveness following withdrawal of OIT. Methods We conducted a pilot clinical trial of peanut OIT at two U.S. centers. Subjects aged 1–16 were recruited and treated for up to five years with peanut OIT. The protocol was modified over time to permit dose increases to a maximum of 4000 mg peanut protein/day. Blood was collected at multiple time points. Clinical endpoints were measured with 5000 mg double-blinded, placebo-controlled food challenges once specific criteria were met. Results Of the 39 subjects originally enrolled, 24 completed the protocol and had evaluable outcomes. 12/24 (50%) successfully passed a challenge one month after stopping OIT and achieved sustained unresponsiveness. Peanut was added to the diet. At baseline and the time of challenge, such subjects had smaller skin tests as well as lower IgE levels specific for peanut, Ara h 1, and Ara h 2, and lower ratios of peanut-specific:total IgE, compared to subjects not passing. There were no differences in peanut IgG4 levels or functional activity at end-of-study. Conclusions This is the first demonstration of sustained unresponsiveness after peanut OIT, occurring in half of subjects treated up to five years. OIT favorably modified the peanut-specific immune response in all subjects completing the protocol. Smaller skin tests and lower allergen-specific IgE levels were predictive of successful outcome. PMID:24361082

Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE): epidemiology, emerging organisms, and economics.

PubMed

Freedman, Stephen B; Lee, Bonita E; Louie, Marie; Pang, Xiao-Li; Ali, Samina; Chuck, Andy; Chui, Linda; Currie, Gillian R; Dickinson, James; Drews, Steven J; Eltorki, Mohamed; Graham, Tim; Jiang, Xi; Johnson, David W; Kellner, James; Lavoie, Martin; MacDonald, Judy; MacDonald, Shannon; Svenson, Lawrence W; Talbot, James; Tarr, Phillip; Tellier, Raymond; Vanderkooi, Otto G

2015-07-31

Each year in Canada there are 5 million episodes of acute gastroenteritis (AGE) with up to 70% attributed to an unidentified pathogen. Moreover, 90% of individuals with AGE do not seek care when ill, thus, burden of disease estimates are limited by under-diagnosing and under-reporting. Further, little is known about the pathogens causing AGE as the majority of episodes are attributed to an "unidentified" etiology. Our team has two main objectives: 1) to improve health through enhanced enteric pathogen identification; 2) to develop economic models incorporating pathogen burden and societal preferences to inform enteric vaccine decision making. This project involves multiple stages: 1) Molecular microbiology experts will participate in a modified Delphi process designed to define criteria to aid in interpreting positive molecular enteric pathogen test results. 2) Clinical data and specimens will be collected from children aged 0-18 years, with vomiting and/or diarrhea who seek medical care in emergency departments, primary care clinics and from those who contact a provincial medical advice line but who do not seek care. Samples to be collected will include stool, rectal swabs (N = 2), and an oral swab. Specimens will be tested employing 1) stool culture; 2) in-house multiplex (N = 5) viral polymerase chain reaction (PCR) panel; and 3) multi-target (N = 15) PCR commercially available array. All participants will have follow-up data collected 14 days later to enable calculation of a Modified Vesikari Scale score and a Burden of Disease Index. Specimens will also be collected from asymptomatic children during their well child vaccination visits to a provincial public health clinic. Following the completion of the initial phases, discrete choice experiments will be conducted to enable a better understanding of societal preferences for diagnostic testing and vaccine policy. All of the results obtained will be integrated into economic models. This study is collecting novel samples (e.g., oral swabs) from previously untested groups of children (e.g., those not seeking medical care) which are then undergoing extensive molecular testing to shed a new perspective on the epidemiology of AGE. The knowledge gained will provide the broadest understanding of the epidemiology of vomiting and diarrhea of children to date.

Alzheimer’s Prevention Initiative: A Plan to Accelerate the Evaluation of Presymptomatic Treatments

PubMed Central

Reiman, Eric M.; Langbaum, Jessica B.S.; Fleisher, Adam S.; Caselli, Richard J.; Chen, Kewei; Ayutyanont, Napatkamon; Quiroz, Yakeel T.; Kosik, Kenneth S.; Lopera, Francisco; Tariot, Pierre N.

2012-01-01

There is an urgent need to find effective presymptomatic Alzheimer’s disease (AD) treatments that reduce the risk of AD symptoms or prevent them completely. It currently takes too many healthy people, too much money and too many years to evaluate the range of promising presymptomatic treatments using clinical endpoints. We have used brain imaging and other measurements to track some of the earliest changes associated with the predisposition to AD. We have proposed the Alzheimer’s Prevention Initiative (API) to evaluate investigational amyloid-modifying treatments in healthy people who, based on their age and genetic background, are at the highest imminent risk of developing symptomatic AD using brain imaging, cerebrospinal fluid (CSF), and cognitive endpoints. In one trial, we propose to study AD-causing presenilin 1 [PS1] mutation carriers from the world’s largest early-onset AD kindred in Antioquia, Colombia, close to their estimated average age at clinical onset. In another trial, we propose to study apolipoprotein E (APOE)ε4 homozygotes (and possibly heterozygotes) close to their estimated average age at clinical onset. The API has several goals: 1) to evaluate investigational AD-modifying treatments sooner than otherwise possible; 2) to determine the extent to which the treatment’s brain imaging and other biomarker effects predict a clinical benefit—information needed to help qualify biomarker endpoints for use in pivotal prevention trials; 3) to provide a better test of the amyloid hypothesis than clinical trials in symptomatic patients, when these treatments may be too little too late to exert their most profound effect; 4) to establish AD prevention registries needed to support these and other presymptomatic AD trials; and 5) to give those individuals at highest imminent risk of AD symptoms access to the most promising investigational treatments in clinical trials. PMID:21971471

A new era in clinical genetic testing for hypertrophic cardiomyopathy.

PubMed

Wheeler, Matthew; Pavlovic, Aleksandra; DeGoma, Emil; Salisbury, Heidi; Brown, Colleen; Ashley, Euan A

2009-12-01

Building on seminal studies of the last 20 years, genetic testing for hypertrophic cardiomyopathy (HCM) has become a clinical reality in the form of targeted exonic sequencing of known disease-causing genes. This has been driven primarily by the decreasing cost of sequencing, but the high profile of genome-wide association studies, the launch of direct-to-consumer genetic testing, and new legislative protection have also played important roles. In the clinical management of hypertrophic cardiomyopathy, genetic testing is primarily used for family screening. An increasing role is recognized, however, in diagnostic settings: in the differential diagnosis of HCM; in the differentiation of HCM from hypertensive or athlete's heart; and more rarely in preimplantation genetic diagnosis. Aside from diagnostic clarification and family screening, use of the genetic test for guiding therapy remains controversial, with data currently too limited to derive a reliable mutation risk prediction from within the phenotypic noise of different modifying genomes. Meanwhile, the power of genetic testing derives from the confidence with which a mutation can be called present or absent in a given individual. This confidence contrasts with our more limited ability to judge the significance of mutations for which co-segregation has not been demonstrated. These variants of "unknown" significance represent the greatest challenge to the wider adoption of genetic testing in HCM. Looking forward, next-generation sequencing technologies promise to revolutionize the current approach as whole genome sequencing will soon be available for the cost of today's targeted panel. In summary, our future will be characterized not by lack of genetic information but by our ability to effectively parse it.

Effect of heterophoria measurement technique on the clinical accommodative convergence to accommodation ratio.

PubMed

Escalante, Jaime Bernal; Rosenfield, Mark

2006-05-01

Measurement of the stimulus accommodative convergence to accommodation (AC/A) ratio is a standard procedure in clinical optometric practice. Typically, heterophoria is assessed at several accommodative stimulus levels, and the gradient of the vergence to accommodation function computed. A number of procedures are available for the subjective measurement of heterophoria, but it is unclear whether the use of different vergence measurement techniques will alter the obtained AC/A value. Accordingly, the current study compared AC/A ratios measured using 3 clinical subjective heterophoria tests, namely the von Graefe (VG), Maddox Rod (MR), and Modified Thorington (MT) procedures. The AC/A ratio was measured in 60 visually normal subjects between 20 and 25 years of age using each of the 3 procedures listed above. The accommodative stimulus was varied by the introduction of +/-1.00 diopter (D) spherical lenses over the distance refractive correction while subjects viewed a target at a viewing distance of 40 cm. To examine the repeatability of each procedure, the AC/A ratio was measured on 2 separate occasions for each measurement technique, with the 2 sessions being separated by at least 24 hours. Mean values of stimulus AC/A ratio measured using the VG, MR, and MT procedures were 3.47, 2.99, and 2.46Delta/D, respectively. These differences were significant (p=0.0001). In addition, the coefficient of repeatability for the 3 techniques was 2.22, 1.99, and 1.20 Delta/D, respectively. Ratios obtained using the Modified Thorington technique with +/-1.00 D lenses showed the best repeatability, whereas the poorest repeatability was found with the von Graefe technique when only +1.00 D lenses were used to vary the accommodative stimulus. Accordingly, we recommend that that Modified Thorington procedure with +/-1.00 D lenses be used to quantify heterophoria during clinical measurement of the stimulus AC/A ratio.

Effects of walkbot gait training on kinematics, kinetics, and clinical gait function in paraplegia and quadriplegia.

PubMed

Hwang, Jongseok; Shin, Yongil; Park, Ji-Ho; Cha, Young Joo; You, Joshua Sung H

2018-04-07

The robotic-assisted gait training (RAGT) system has gained recognition as an innovative, effective paradigm to improve functional ambulation and activities of daily living in spinal cord injury and stroke. However, the effects of the Walkbot robotic-assisted gait training system with a specialized hip-knee-ankle actuator have never been examined in the paraplegia and quadriplegia population. The aim of this study was to determine the long-term effects of Walkbot training on clinical for hips and knee stiffness in individuals with paraplegia or quadriplegia. Nine adults with subacute or chronic paraplegia resulting from spinal cord injury or quadriplegia resulting from cerebral vascular accident (CVA) and/or hypoxia underwent progressive conventional gait retraining combined with the Walkbot RAGT for 5 days/week over an average of 43 sessions for 8 weeks. Clinical outcomes were measured with the Functional Ambulation Category (FAC), Modified Rankin Scale (MRS), Korean version of the Modified Barthel Index (K-MBI), Modified Ashworth Scale (MAS). Kinetic and kinematic data were collected via a built-in Walkbot program. Wilcoxon signed-rank tests showed significant positive intervention effects on K-MBI, maximal hip flexion and extension, maximal knee flexion, active torque in the knee joint, resistive torque, and stiffness in the hip joint (P <  0.05). These findings suggest that the Walkbot RAGT was effective for improving knee and hip kinematics and the active knee joint moment while decreasing hip resistive force. These improvements were associated with functional recovery in gait, balance, mobility and daily activities. These findings suggest that the Walkbot RAGT was effective for improving knee and hip kinematics and the active knee joint moment while decreasing hip resistive force. This is the first clinical evidence for intensive, long-term effects of the Walkbot RAGT on active or resistive moments and stiffness associated with spasticity and functional mobility in individuals with subacute or chronic paraplegia or quadriplegia who had reached a plateau in motor recovery after conventional therapy.

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia.

PubMed

Lucas, Jane S; Barbato, Angelo; Collins, Samuel A; Goutaki, Myrofora; Behan, Laura; Caudri, Daan; Dell, Sharon; Eber, Ernst; Escudier, Estelle; Hirst, Robert A; Hogg, Claire; Jorissen, Mark; Latzin, Philipp; Legendre, Marie; Leigh, Margaret W; Midulla, Fabio; Nielsen, Kim G; Omran, Heymut; Papon, Jean-Francois; Pohunek, Petr; Redfern, Beatrice; Rigau, David; Rindlisbacher, Bernhard; Santamaria, Francesca; Shoemark, Amelia; Snijders, Deborah; Tonia, Thomy; Titieni, Andrea; Walker, Woolf T; Werner, Claudius; Bush, Andrew; Kuehni, Claudia E

2017-01-01

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia. Copyright ©ERS 2017.

Sealant retention is better assessed through colour photographs than through the replica and the visual examination methods.

PubMed

Hu, Xuan; Fan, Mingwan; Rong, Wensheng; Lo, Edward C M; Bronkhorst, Ewald; Frencken, Jo E

2014-08-01

The aim of this study was to test the hypothesis that the colour photograph method has a higher level of validity for assessing sealant retention than the visual clinical examination and replica methods. Sealed molars were assessed by two evaluators. The scores for the three methods were compared against consensus scores derived through assessing retention from scanning electron microscopy images (reference standard). The presence/absence (survival) of retained sealants on occlusal surfaces was determined according to the traditional and modified categorizations of retention. Sensitivity, specificity, and Youden-index scores were calculated. Sealant retention assessment scores for visual clinical examinations and for colour photographs were compared with those of the reference standard on 95 surfaces, and sealant retention assessment scores for replicas were compared with those of the reference standard on 33 surfaces. The highest mean Youden-index score for the presence/absence of sealant material was observed for the colour photograph method, followed by that for the replica method; the visual clinical examination method scored lowest. The mean Youden-index score for the survival of retained sealants was highest for the colour photograph method for both the traditional (0.882) and the modified (0.768) categories of sealant retention, whilst the visual clinical examination method had the lowest Youden-index score for these categories (0.745 and 0.063, respectively). The colour photograph method had a higher validity than the replica and the visual examination methods for assessing sealant retention. © 2014 Eur J Oral Sci.

Manufacture of Clinical-Grade CD19-Specific T Cells Stably Expressing Chimeric Antigen Receptor Using Sleeping Beauty System and Artificial Antigen Presenting Cells

PubMed Central

Singh, Harjeet; Figliola, Matthew J.; Dawson, Margaret J.; Olivares, Simon; Zhang, Ling; Yang, Ge; Maiti, Sourindra; Manuri, Pallavi; Senyukov, Vladimir; Jena, Bipulendu; Kebriaei, Partow; Champlin, Richard E.; Huls, Helen; Cooper, Laurence J. N.

2013-01-01

Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28) that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB) transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC) in the presence of interleukin (IL)-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT). We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼1010 T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion. PMID:23741305

The Relationship Between Serum Neuron-Specific Enolase Levels and Severity of Bleeding and Functional Outcomes in Patients With Nontraumatic Subarachnoid Hemorrhage.

PubMed

Tawk, Rabih G; Grewal, Sanjeet S; Heckman, Michael G; Rawal, Bhupendra; Miller, David A; Edmonston, Drucilla; Ferguson, Jennifer L; Navarro, Ramon; Ng, Lauren; Brown, Benjamin L; Meschia, James F; Freeman, William D

2016-04-01

The value of neuron-specific enolase (NSE) in predicting clinical outcomes has been investigated in a variety of neurological disorders. To investigate the associations of serum NSE with severity of bleeding and functional outcomes in patients with subarachnoid hemorrhage (SAH). We retrospectively reviewed the records of patients with SAH from June 2008 to June 2012. The severity of SAH bleeding at admission was measured radiographically with the Fisher scale and clinically with the Glasgow Coma Scale, Hunt and Hess grade, and World Federation of Neurologic Surgeons scale. Outcomes were assessed with the modified Rankin Scale at discharge. We identified 309 patients with nontraumatic SAH, and 71 had NSE testing. Median age was 54 years (range, 23-87 years), and 44% were male. In multivariable analysis, increased NSE was associated with a poorer Hunt and Hess grade (P = .003), World Federation of Neurologic Surgeons scale score (P < .001), and Glasgow Coma Scale score (P = .003) and worse outcomes (modified Rankin Scale at discharge; P = .001). There was no significant association between NSE level and Fisher grade (P = .81) in multivariable analysis. We found a significant association between higher NSE levels and poorer clinical presentations and worse outcomes. Although it is still early for any relevant clinical conclusions, our results suggest that NSE holds promise as a tool for screening patients at increased risk of poor outcomes after SAH.

Age estimation by modified Demirjian's method (2004) and its applicability in Tibetan young adults: A digital panoramic study.

PubMed

Bijjaragi, Shobha C; Sangle, Varsha A; Saraswathi, F K; Patil, Veerendra S; Ashwini Rani, S R; Bapure, Sunil K

2015-01-01

Estimation of the age is a procedure adopted by anthropologists, archeologists and forensic scientists. Different methods have been undertaken. However none of them meet the standards as Demirjian's method since 1973. Various researchers have applied this method, in both original and modified form (Chaillet and Demirjian in 2004) in different ethnic groups and the results obtained were not satisfactory. To determine the applicability and accuracy of modified Demirjian's method of dental age estimation (AE) in 8-18 year old Tibetan young adults to evaluate the interrelationship between dental and chronological age and the reliability between intra- and inter observer relationship. Clinical setting and computerized design. A total of 300 Tibetan young adults with an age range from 8 to 18 years were recruited in the study. Digital panoramic radiographs (DPRs) were evaluated as per the modified Demirjian's method (2004). Pearson correlation, paired t-test, linear regression analysis. Inter -and intraobserver reliability revealed a strong agreement. A positive and strong association was found between chronological age and estimated dental age (r = 0.839) with P < 0.01. Modified Demirjian method (2004) overestimated the age by 0.04 years (2.04 months)in Tibetan young adults. Results suggest that, the modified Demirjian method of AE is not suitable for Tibetan young adults. Further studies: With larger sample size and comparision with different methods of AE in a given population would be an interesting area for future research.

A comparison of DNA extraction procedures for the detection of Mycobacterium ulcerans, the causative agent of Buruli ulcer, in clinical and environmental specimens.

PubMed

Durnez, Lies; Stragier, Pieter; Roebben, Karen; Ablordey, Anthony; Leirs, Herwig; Portaels, Françoise

2009-02-01

Mycobacterium ulcerans is the causative agent of Buruli ulcer, the third most common mycobacterial disease in humans after tuberculosis and leprosy. Although the disease is associated with aquatic ecosystems, cultivation of the bacillus from the environment is difficult to achieve. Therefore, at the moment, research is based on the detection by PCR of the insertion sequence IS2404 present in M. ulcerans and some closely related mycobacteria. In the present study, we compared four DNA extraction methods for detection of M. ulcerans DNA, namely the one tube cell lysis and DNA extraction procedure (OT), the FastPrep procedure (FP), the modified Boom procedure (MB), and the Maxwell 16 Procedure (M16). The methods were performed on serial dilutions of M. ulcerans, followed by PCR analysis with different PCR targets in M. ulcerans to determine the detection limit (DL) of each method. The purity of the extracted DNA and the time and effort needed were compared as well. All methods were performed on environmental specimens and the two best methods (MB and M16) were tested on clinical specimens for detection of M. ulcerans DNA. When comparing the DLs of the DNA extraction methods, the MB and M16 had a significantly lower DL than the OT and FP. For the different PCR targets, IS2404 showed a significantly lower DL than mlsA, MIRU1, MIRU5 and VNTR6. The FP and M16 were considerably faster than the MB and OT, while the purity of the DNA extracted with the MB was significantly higher than the DNA extracted with the other methods. The MB performed best on the environmental and clinical specimens. This comparative study shows that the modified Boom procedure, although lengthy, provides a better method of DNA extraction than the other methods tested for detection and identification of M. ulcerans in both clinical and environmental specimens.

Beyond signal functions in global obstetric care: Using a clinical cascade to measure emergency obstetric readiness

PubMed Central

Dettinger, Julia; Calkins, Kimberly; Kibore, Minnie; Gachuno, Onesmus; Walker, Dilys

2018-01-01

Background Globally, the rate of reduction in delivery-associated maternal and perinatal mortality has been slow compared to improvements in post-delivery mortality in children under five. Improving clinical readiness for basic obstetric emergencies is crucial for reducing facility-based maternal deaths. Emergency readiness is commonly assessed using tracers derived from the maternal signal functions model. Objective-method We compare emergency readiness using the signal functions model and a novel clinical cascade. The cascades model readiness as the proportion of facilities with resources to identify the emergency (stage 1), treat it (stage 2) and monitor-modify therapy (stage 3). Data were collected from 44 Kenyan clinics as part of an implementation trial. Findings Although most facilities (77.0%) stock maternal signal function tracer drugs, far fewer have resources to practically identify and treat emergencies. In hypertensive emergencies for example, 38.6% of facilities have resources to identify the emergency (Stage 1 readiness, including sphygmomanometer, stethoscope, urine collection device, protein test). 6.8% have the resources to treat the emergency (Stage 2, consumables (IV Kit, fluids), durable goods (IV pole) and drugs (magnesium sulfate and hydralazine). No facilities could monitor or modify therapy (Stage 3). Across five maternal emergencies, the signal functions overestimate readiness by 54.5%. A consistent, step-wise pattern of readiness loss across signal functions and care stage emerged and was profoundly consistent at 33.0%. Significance Comparing estimates from the maternal signal functions and cascades illustrates four themes. First, signal functions overestimate practical readiness by 55%. Second, the cascade’s intuitive indicators can support cross-sector health system or program planners to more precisely measure and improve emergency care. Third, adding few variables to existing readiness inventories permits step-wise modeling of readiness loss and can inform more precise interventions. Fourth, the novel aggregate readiness loss indicator provides an innovative and intuitive approach for modeling health system emergency readiness. Additional testing in diverse contexts is warranted. PMID:29474397

46 CFR 52.01-135 - Inspection and tests (modifies PG-90 through PG-100).

Code of Federal Regulations, 2014 CFR

2014-10-01

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46 CFR 53.10-3 - Inspection and tests (modifies HG-500 through HG-540).

Code of Federal Regulations, 2012 CFR

2012-10-01

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46 CFR 53.10-3 - Inspection and tests (modifies HG-500 through HG-540).

Code of Federal Regulations, 2011 CFR

2011-10-01

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46 CFR 53.10-3 - Inspection and tests (modifies HG-500 through HG-540).

Code of Federal Regulations, 2014 CFR

2014-10-01

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46 CFR 52.01-135 - Inspection and tests (modifies PG-90 through PG-100).

Code of Federal Regulations, 2011 CFR

2011-10-01

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46 CFR 53.10-3 - Inspection and tests (modifies HG-500 through HG-540).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Inspection and tests (modifies HG-500 through HG-540). 53.10-3 Section 53.10-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING HEATING BOILERS Tests, Inspection, Stamping, and Reporting (Article 5) § 53.10-3 Inspection and tests (modifies HG-500 through HG-540). (a)...

46 CFR 52.01-135 - Inspection and tests (modifies PG-90 through PG-100).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Inspection and tests (modifies PG-90 through PG-100). 52.01-135 Section 52.01-135 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-135 Inspection and tests (modifies PG-90 through PG-100). (a) Requirements. Inspection and test...

46 CFR 53.10-3 - Inspection and tests (modifies HG-500 through HG-540).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Inspection and tests (modifies HG-500 through HG-540). 53.10-3 Section 53.10-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING HEATING BOILERS Tests, Inspection, Stamping, and Reporting (Article 5) § 53.10-3 Inspection and tests (modifies HG-500 through HG-540). (a)...

46 CFR 52.01-135 - Inspection and tests (modifies PG-90 through PG-100).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Inspection and tests (modifies PG-90 through PG-100). 52.01-135 Section 52.01-135 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-135 Inspection and tests (modifies PG-90 through PG-100). (a) Requirements. Inspection and test...

No Clinically Significant Difference Between Adult and Pediatric IKDC Subjective Knee Evaluation Scores in Adults.

PubMed

Stegmeier, Nicole; Oak, Sameer R; O'Rourke, Colin; Strnad, Greg; Spindler, Kurt P; Jones, Morgan; Farrow, Lutul D; Andrish, Jack; Saluan, Paul

Two versions of the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form currently exist: the original version (1999) and a recently modified pediatric-specific version (2011). Comparison of the pediatric IKDC with the adult version in the adult population may reveal that either version could be used longitudinally. We hypothesize that the scores for the adult IKDC and pediatric IKDC will not be clinically different among adult patients aged 18 to 50 years. Randomized crossover study design. Level 2. The study consisted of 100 participants, aged 18 to 50 years, who presented to orthopaedic outpatient clinics with knee problems. All participants completed both adult and pediatric versions of the IKDC in random order with a 10-minute break in between. We used a paired t test to test for a difference between the scores and a Welch's 2-sample t test to test for equivalence. A least-squares regression model was used to model adult scores as a function of pediatric scores, and vice versa. A paired t test revealed a statistically significant 1.6-point difference between the mean adult and pediatric scores. However, the 95% confidence interval (0.54-2.66) for this difference did not exceed our a priori threshold of 5 points, indicating that this difference was not clinically important. Equivalence testing with an equivalence region of 5 points further supported this finding. The adult and pediatric scores had a linear relationship and were highly correlated with an R 2 of 92.6%. There is no clinically relevant difference between the scores of the adult and pediatric IKDC forms in adults, aged 18 to 50 years, with knee conditions. Either form, adult or pediatric, of the IKDC can be used in this population for longitudinal studies. If the pediatric version is administered in adolescence, it can be used for follow-up into adulthood.

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance Report and Clinical Checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group.

PubMed

Neuberger, James M; Bechstein, Wolf O; Kuypers, Dirk R J; Burra, Patrizia; Citterio, Franco; De Geest, Sabina; Duvoux, Christophe; Jardine, Alan G; Kamar, Nassim; Krämer, Bernhard K; Metselaar, Herold J; Nevens, Frederik; Pirenne, Jacques; Rodríguez-Perálvarez, Manuel L; Samuel, Didier; Schneeberger, Stefan; Serón, Daniel; Trunečka, Pavel; Tisone, Giuseppe; van Gelder, Teun

2017-04-01

Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes.COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant.The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting.

Lentiviral-induced high-grade gliomas in rats: the effects of PDGFB, HRAS-G12V, AKT, and IDH1-R132H.

PubMed

Lynes, John; Wibowo, Mia; Koschmann, Carl; Baker, Gregory J; Saxena, Vandana; Muhammad, A K M G; Bondale, Niyati; Klein, Julia; Assi, Hikmat; Lieberman, Andrew P; Castro, Maria G; Lowenstein, Pedro R

2014-07-01

In human gliomas, the RTK/RAS/PI(3)K signaling pathway is nearly always altered. We present a model of experimental gliomagenesis that elucidates the contributions of genes involved in this pathway (PDGF-B ligand, HRAS-G12V, and AKT). We also examine the effect on gliomagenesis by the potential modifier gene, IDH1-R132H. Injections of lentiviral-encoded oncogenes induce de novo gliomas of varying penetrance, tumor progression, and histological grade depending on the specific oncogenes used. Our model mimics hallmark histological structures of high-grade glioma, such as pseudopalisades, glomeruloid microvascular proliferation, and diffuse tumor invasion. We use our model of gliomagenesis to test the efficacy of an experimental brain tumor gene therapy. Our model allowed us to test the contributions of oncogenes in the RTK/RAS/PI(3)K pathway, and their potential modification by over-expression of mutated IDH1, in glioma development and progression in rats. Our model constitutes a clinically relevant system to study gliomagenesis, the effects of modifier genes, and the efficacy of experimental therapeutics.

Neuropathic pain screening questionnaires have limited measurement properties. A systematic review.

PubMed

Mathieson, Stephanie; Maher, Christopher G; Terwee, Caroline B; Folly de Campos, Tarcisio; Lin, Chung-Wei Christine

2015-08-01

The Douleur Neuropathique 4 (DN4), ID Pain, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), PainDETECT, and Neuropathic Pain Questionnaire have been recommended as screening questionnaires for neuropathic pain. This systematic review aimed to evaluate the measurement properties (eg, criterion validity and reliability) of these questionnaires. Online database searches were conducted and two independent reviewers screened studies and extracted data. Methodological quality of included studies and the measurement properties were assessed against established criteria. A modified Grading of Recommendations Assessment, Development and Evaluation approach was used to summarize the level of evidence. Thirty-seven studies were included. Most studies recruited participants from pain clinics. The original version of the DN4 (French) and Neuropathic Pain Questionnaire (English) had the most number of satisfactory measurement properties. The ID Pain (English) demonstrated satisfactory hypothesis testing and reliability, but all other properties tested were unsatisfactory. The LANSS (English) was unsatisfactory for all properties, except specificity. The PainDETECT (English) demonstrated satisfactory hypothesis testing and criterion validity. In general, the cross-cultural adaptations had less evidence than the original versions. Overall, the DN4 and Neuropathic Pain Questionnaire were most suitable for clinical use. These screening questionnaires should not replace a thorough clinical assessment. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Modified Allergens for Immunotherapy.

PubMed

Satitsuksanoa, Pattraporn; Głobińska, Anna; Jansen, Kirstin; van de Veen, Willem; Akdis, Mübeccel

2018-02-16

During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT. In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens. The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT.

[Randomized double-blind comparative study of minaprine (200mg/j) and of placebo on memory loss].

PubMed

Allain, H; Belliard, S; Lieury, A; Menard, G; Patat, A; Le Coz, F; Gandon, J M

1996-01-01

Thirty five subjects (age: 45-69 years) with subjective memory loss, without any other neuropsychiatric or somatic disease, were recruited in a phase II study. This double blind randomized versus placebo controlled study compared the effects of minaprine (200 mg/d) with placebo, in two parallel groups, during 2 months, on memory, attention and vigilance. Three psychometric tests were the main criteria of assessment: a standardized battery of memory tests (SM 5), the dual-coding test, the analysis of choice reaction times (CRT) and the critical flicker fusion point (CFF). A positive effect of minaprine was detected on words delayed recall (p = 0.028) and immediate recognition of words (p = 0.049). The global clinical tests (CGI, MacNair scale) were not statistically modified. Tolerability of minaprine and placebo were comparable. A positive pharmacodynamic activity on mnemonic performance is thus demonstrated in favour of minaprine (200 mg/d) in this specific population characterized by a memory complaint. These results would lead to a phase III study in which the main criteria would be global scales in order to confirm the clinical reliability of the present results.

Rapid genetic typing of diarrheagenic Escherichia coli using a two-tube modified molecular beacon based multiplex real-time PCR assay and its clinical application

PubMed Central

2014-01-01

Background Diarrheagenic Escherichia coli (DEC), including Enterotoxigenic E.coli (ETEC), Enteroaggregative E.coli (EAEC), Enteropathogenic E.coli (EPEC), Enterohemolysin E.coli (EHEC) and Enteroinvasive E.coli (EIEC) causes diarrhea or hemolytic uremic syndromes among infants and travelers around the world. A rapid, reliable and repeatable method is urgent for identifying DEC so as to provide the reference for responding to diarrheal disease outbreak and the treatment of the diarrheal patients associated with DEC. Methods In this study, specific primers and modified molecular beacon probes of nine specific virulence genes, whose 5′end were added with homo tail sequence, were designed; and a two-tube modified molecular beacon based multiplex real–time PCR (rtPCR) assay for the identification of five Escherichia coli pathotypes, including ETEC, EAEC, EPEC, EHEC and EIEC was developed and optimized. Totally 102 bacterial strains, including 52 reference bacterial strains and 50 clinical strains were detected to confirm whether the target genes selected were specific. Then detection limits of the assay were tested. Lastly, the assay was applied to the detection of 11860 clinical samples to evaluate the specificity and sensitivity of the developed assay compared with the conventional PCR. Results The target genes were 100% specific as assessed on 102 bacterial strains since no cross-reactions were observed. The detection limits ranged from 88 CFU/mL (EHEC) to 880 CFU/mL (EPEC). Compared with the conventional PCR, the specificity and sensitivity of the multiplex rtPCR was 100% and over 99%, respectively. The coefficient of variation (CV) for each target gene ranged from 0.45% to 1.53%. 171 positive clinical samples were mostly identified as ETEC (n = 111, 64.9%) and EPEC (n = 38, 22.2%), which were the dominating pathotypes of DEC strains. Conclusion The developed multiplex rtPCR assay for the identification of DEC was high sensitive and specific and could be applied to the rapid identification of DEC in clinical and public health laboratories. PMID:25023669

The modified Hodge test is a useful tool for ruling out Klebsiella pneumoniae carbapenemase.

PubMed

Cury, Ana Paula; Andreazzi, Denise; Maffucci, Márcia; Caiaffa-Junior, Hélio Hehl; Rossi, Flávia

2012-12-01

Enterobacteriaceae bacteria harboring Klebsiella pneumoniae carbapenemase are a serious worldwide threat. The molecular identification of these pathogens is not routine in Brazilian hospitals, and a rapid phenotypic screening test is desirable. This study aims to evaluate the modified Hodge test as a phenotypic screening test for Klebsiella pneumoniae carbapenemase. From April 2009 to July 2011, all Enterobacteriaceae bacteria that were not susceptible to ertapenem according to Vitek2 analysis were analyzed with the modified Hodge test. All positive isolates and a random subset of negative isolates were also assayed for the presence of blaKPC. Isolates that were positive in modified Hodge tests were sub-classified as true-positives (E. coli touched the ertapenem disk) or inconclusive (distortion of the inhibition zone of E. coli, but growth did not reach the ertapenem disk). Negative results were defined as samples with no distortion of the inhibition zone around the ertapenem disk. Among the 1521 isolates of Enterobacteriaceae bacteria that were not susceptible to ertapenem, 30% were positive for blaKPC, and 35% were positive according to the modified Hodge test (81% specificity). Under the proposed sub-classification, true positives showed a 98% agreement with the blaKPC results. The negative predictive value of the modified Hodge test for detection was 100%. KPC producers showed high antimicrobial resistance rates, but 90% and 77% of these isolates were susceptible to aminoglycoside and tigecycline, respectively. Standardizing the modified Hodge test interpretation may improve the specificity of KPC detection. In this study, negative test results ruled out 100% of the isolates harboring Klebsiella pneumoniae carbapenemase 2. The test may therefore be regarded as a good epidemiological tool.

Randomized and controlled clinical study of modified prescriptions of Simiao Pill in the treatment of acute gouty arthritis.

PubMed

Shi, Xin-de; Li, Guo-chun; Qian, Zu-xi; Jin, Ze-qiu; Song, Yan

2008-03-01

To investigate the compatibility of a modified prescription of Simiao Pill in the treatment of acute gouty arthritis and to verify the clinical efficacy and safety of the drug through a clinical trial. A randomized and controlled clinical trial was designed based on clinical epidemiological principles. A total of 107 patients with acute gouty arthritis were enrolled and randomly assigned to four groups. The first group (Group I) included 27 patients taking gout prescription I; the second group (Group II) included 27 patients taking gout prescription II; the third group (Group III) included 28 patients taking gout prescription III; and the fourth group (control group) included 25 patients taking indomethacin and Benzobromarone as a control group. The duration of the treatment in all 4 groups was two weeks. After the treatment, the index of blood uric acid, blood leukocyte count, score of clinical symptoms, etc. were observed and measured. The total clinical effective rate of the three different modified prescriptions of the Simiao Pill was above 96%, significantly superior to that of the control group (68%, P<0.05). In terms of the improvement of main symptoms, the scores of four symptoms in all TCM treatment and control groups decreased after treatment, with statistically significant differences (P<0.05). Moreover, the scores markedly fell more so in the three Chinese herb groups than in the control group, and especially in Group III (P<0.05). There was a statistically significant difference in blood uric acid values before and after the treatment in the same group but no significant inter-group difference was seen. The modified prescriptions, based on the clinical research, clinical experience and traditional Chinese medicine theory, did show a better effect than Western medicine in this clinical study. Moreover, the prescriptions were precise, with the herbs inexpensive and readily available. The patients had good compliance with less adverse reactions noted. The modified prescription has a favorable prospect for future development and is worthy of further blind trials with larger samples.

A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder

PubMed Central

Lee, Ryan W.Y.; Corley, Michael J.; Pang, Alina; Arakaki, Gaye; Abbott, Lisa; Nishimoto, Michael; Miyamoto, Rob; Lee, Erica; Yamamoto, Susan; Maunakea, Alika K.; Lum-Jones, Annette; Wong, Miki

2018-01-01

Purpose The ketogenic diet is a low-carbohydrate, moderate protein, high-fat diet that has emerged as a potential treatment for autism spectrum disorder. Autism spectrum disorder is a neurodevelopmental disorder of social communication, and restricted, repetitive behaviors and interests in need of novel therapies. An open-label clinical trial was done in Honolulu, Hawaii to test a modified ketogenic diet for improvement of core clinical impairments in children with ASD. Intervention A modified ketogenic gluten-free diet regimen with supplemental MCT was completed in 15 children ages 2 to 17 years for 3 months. Clinical (ADOS-2, CARS-2) and biochemical measures were performed at baseline and 3-months on the ketogenic diet. Main outcome Children administered a modified ketogenic gluten-free diet with supplemental MCT significantly improved core autism features assessed from the ADOS-2 after 3 months on diet (P = 0.006). No significant difference was observed in restricted and repetitive behavior score (P = 0.125) after 3 months on the diet protocol. Substantial improvement (> 30% decrease ADOS-2 total score) was observed in six participants, moderate improvement (> 3 units) in two participants, and minor/no improvement in seven participants. Ten participants assessed at a six-month time point sustained improvement in total ADOS-2 and social affect subdomain scores comparing baseline and 6 months (P = 0.019; P = 0.023), but no significant improvement in restricted and repetitive behavior scores were noted (P = 0.197). Significant improvements in CARS-2 items after 3 months of the modified ketogenic protocol were observed in imitation, body use, and fear or nervousness (P = 0.031, P = 0.008, P = 0.039). The percent change on ADOS-2 score from baseline to 3 months was associated with baseline high-density lipoprotein levels (ρ = −0.67, P = 0.007) and albumin levels (ρ = −0.60, P = 0.019). Moreover, the percent change from baseline to 3 months in ADOS-2 scores was significantly associated with percent change in high-density lipoprotein levels (ρ = 0.54, P = 0.049) and albumin levels (ρ = 0.67, P = 0.010). Conclusions A modified gluten-free ketogenic diet with supplemental MCT is a potentially beneficial treatment option to improve the core features of autism spectrum disorder and warrants further investigation. Trial registration Trial Registry: Clinicaltrials.gov Registration Number: NCT02477904URL: https://www.clinicaltrials.gov/ct2/show/NCT02477904?term=ketogenic+diet&cond=Autism&rank=1 PMID:29421589

Utility of behavioral versus cognitive measures in differentiating between subtypes of frontotemporal lobar degeneration and Alzheimer's disease.

PubMed

Heidler-Gary, Jennifer; Gottesman, Rebecca; Newhart, Melissa; Chang, Shannon; Ken, Lynda; Hillis, Argye E

2007-01-01

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer's disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of 'executive functioning'). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.

New advanced surface modification technique: titanium oxide ceramic surface implants: long-term clinical results

NASA Astrophysics Data System (ADS)

Szabo, Gyorgy; Kovacs, Lajos; Barabas, Jozsef; Nemeth, Zsolt; Maironna, Carlo

2001-11-01

The purpose of this paper is to discuss the background to advanced surface modification technologies and to present a new technique, involving the formation of a titanium oxide ceramic coating, with relatively long-term results of its clinical utilization. Three general techniques are used to modify surfaces: the addition or removal of material and the change of material already present. Surface properties can also be changed without the addition or removal of material, through the laser or electron beam thermal treatment. The new technique outlined in this paper relates to the production of a corrosion-resistant 2000-2500 A thick, ceramic oxide layer with a coherent crystalline structure on the surface of titanium implants. The layer is grown electrochemically from the bulk of the metal and is modified by heat treatment. Such oxide ceramic-coated implants have a number of advantageous properties relative to implants covered with various other coatings: a higher external hardness, a greater force of adherence between the titanium and the oxide ceramic coating, a virtually perfect insulation between the organism and the metal (no possibility of metal allergy), etc. The coated implants were subjected to various physical, chemical, electronmicroscopic, etc. tests for a qualitative characterization. Finally, these implants (plates, screws for maxillofacial osteosynthesis and dental root implants) were applied in surgical practice for a period of 10 years. Tests and the experience acquired demonstrated the good properties of the titanium oxide ceramic-coated implants.

Developing new drugs for ovarian cancer: a challenging task in a changing reality.

PubMed

Canetta, R M; Carter, S K

1984-01-01

Recent therapeutic and technological advances have profoundly modified the parameters of new drug testing in ovarian cancer. The potential of compounds tested today in this disease therefore needs to be assessed according to this changing reality. Previous treatment with or without cisplatin is the criterion we have applied in our review of the single agent clinical data. Results obtained with older compounds have also been, when possible, reassessed in order to facilitate a comparative interpretation of recent trials. A brief overview of the most recently developed laboratory screening models has been conducted in order to stress their close relationship and their crucial role in future new drug development.

The Validity of the Modified Sit-and-Reach Test in College-Age Students.

ERIC Educational Resources Information Center

Minkler, Sharin; Patterson, Patricia

1994-01-01

Reports a study that examined the criterion-related validity of the modified sit-and-reach test against criterion measures of hamstring and low back flexibility in college students. Results indicated the modified sit-and-reach test moderately related to hamstring flexibility, but its relation to low back flexibility was low. (SM)

Use of the script concordance approach to evaluate clinical reasoning in food-ruminant practitioners.

PubMed

Dufour, Simon; Latour, Sylvie; Chicoine, Yvan; Fecteau, Gilles; Forget, Sylvain; Moreau, Jean; Trépanier, André

2012-01-01

A script concordance test (SCT) was developed measuring clinical reasoning of food-ruminant practitioners for whom potential clinical competence difficulties were identified by their provincial professional organization. The SCT was designed to be used as part of a broader evaluation procedure. A scoring key was developed based on answers from a reference panel of 12 experts and using the modified aggregate method commonly used for SCTs. A convenient sample of 29 food-ruminant practitioners was constituted to assess the reliability and precision of the SCT and to determine a fair threshold value for success. Cronbach's α coefficients were computed to evaluate internal reliability. To evaluate SCT precision, a test-retest methodology was used and measures of agreement beyond chance were computed at question and test levels. After optimization, the 36-question SCT yielded acceptable internal reliability (Cronbach's α=0.70). Precision of the SCT at question level was excellent with 33 questions (92%) yielding moderate to almost perfect agreement between administrations. At test level, fair agreement (concordance correlation coefficient=0.32) was observed between administrations. A slight SCT score improvement (M=+2.8 points) on the second administration was in part responsible for some of the disagreement and was potentially a result of an adaptation to the SCT format. Scores distribution was used to determine a fair threshold value for success, while considering the underlying objectives of the examination. The data suggest that the developed SCT can be used as a reliable and precise measurement of clinical reasoning of food-ruminant practitioners.

Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations.

PubMed

Tessier, C; Sweers, K; Frajerman, A; Bergaoui, H; Ferreri, F; Delva, C; Lapidus, N; Lamaziere, A; Roiser, J P; De Hert, M; Nuss, P

2016-10-04

Schizophrenia is a severe mental condition in which several lipid abnormalities-either structural or metabolic-have been described. We tested the hypothesis that an abnormality in membrane lipid composition may contribute to aberrant dopamine signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ) patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74) were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was performed in red blood cell (RBC) membranes examining the major phospholipid (PL) classes and their associated fatty acids (FAs). Clinical manifestations were examined using the positive and negative syndrome scale (PANSS). Cognitive function was assessed using the Continuous Performance Test, Salience Attribution Test and Wisconsin Card Sorting Test. Sphingomyelin (SM) percentage was the lipid abnormality most robustly associated with a schizophrenia diagnosis. Two groups of patients were defined. The first group (SCZ c/SM-) is characterized by a low SM membrane content. In this group, all other PL classes, plasmalogen and key polyunsaturated FAs known to be involved in brain function, were significantly modified, identifying a very specific membrane lipid cluster. The second patient group (SCZ c/SM+) was similar to HCs in terms of RBC membrane SM composition. Compared with SCZ c/SM+, SCZ c/SM- patients were characterized by significantly more severe PANSS total, positive, disorganized/cognitive and excited psychopathology. Cognitive performance was also significantly poorer in this subgroup. These data show that a specific RBC membrane lipid cluster is associated with clinical and cognitive manifestations of dopamine dysfunction in schizophrenia patients. We speculate that this membrane lipid abnormality influences presynaptic dopamine signaling.

The inter-rater reliability test of the modified Morse Fall Scale among patients ≥ 55 years old in an acute care hospital in Singapore.

PubMed

Tang, Wing Sze; Chow, Yeow Leng; Koh, Serena Siew Lin

2014-02-01

A prospective, descriptive study was conducted in an acute care hospital in Singapore to determine the inter-rater reliability of the modified Morse Fall Scale by evaluating the degrees of agreement on the ratings of the individual items and overall score between the 'gold standard' assessor and the facility assessors. One hundred and forty-two subjects were recruited during the 1.5 month data collection period. The simple and weighted κ-values were all > 0.8 except for the item 'effects of medications' (κ and κw  = 0.63), and the correlation coefficient (rs  = 0.89) was significantly high at a significance level of < 0.001. The modified Morse Fall Scale was shown to be a reliable fall risk assessment tool having a relative high inter-rater reliability level for the overall score and individual items. This study provides evidence-based psychometric support for the clinical application of this tool. © 2013 Wiley Publishing Asia Pty Ltd.

Detection of novel Betapapillomaviruses and Gammapapillomaviruses in eyebrow hair follicles using a single-tube 'hanging droplet' PCR assay with modified pan-PV CODEHOP primers.

PubMed

Chouhy, Diego; Kocjan, Boštjan J; Staheli, Jeannette P; Bolatti, Elisa M; Hošnjak, Lea; Sagadin, Martin; Giri, Adriana A; Rose, Timothy M; Poljak, Mario

2018-01-01

A modified pan-PV consensus-degenerate hybrid oligonucleotide primer (CODEHOP) PCR was developed for generic and sensitive detection of a broad-spectrum of human papillomaviruses (HPVs) infecting the cutaneous epithelium. To test the analytical sensitivity of the assay we examined 149 eyebrow hair follicle specimens from immunocompetent male patients. HPV DNA was detected in 60 % (89/149) of analysed eyebrow samples with a total of 48 different HPV sequences, representing 21 previously described HPVs and 27 putative novel HPV types. Evidence for ten novel HPV subtypes and seven viral variants, clustering to three out of five genera containing cutaneous HPVs, was also obtained. Thus, we have shown that the modified pan-PV CODEHOP PCR assay is able to identify multiple HPV types, even from different genera, in the same clinical sample. Overall, these results demonstrate that the pan-PV CODEHOP PCR is an excellent tool for screening and identification of novel cutaneous HPVs, even in samples with low viral loads.

Effectiveness of Brief Abstinence for Modifying Problematic Internet Gaming Cognitions and Behaviors.

PubMed

King, Daniel L; Kaptsis, Dean; Delfabbro, Paul H; Gradisar, Michael

2017-12-01

This pilot study tested the efficacy of a voluntary 84-hour abstinence protocol for modifying problematic Internet gaming cognitions and behaviors METHOD: Twenty-four adults from online gaming communities, including 9 individuals who screened positively for Internet gaming disorder (IGD), abstained from Internet games for 84 hours. Surveys were collected at baseline, at daily intervals during abstinence, and at 7-day and 28-day follow-up RESULTS: Brief voluntary abstinence was successful in reducing hours of gaming, maladaptive gaming cognitions, and IGD symptoms. Abstinence was highly acceptable to participants with total compliance and no study attrition. Clinically significant improvement in IGD symptoms occurred in 75% of the IGD group at 28-day follow-up. Reliable improvement in maladaptive gaming cognitions occurred in 63% of the IGD group, whose cognition score reduced by 50% and was comparable to the non-IGD group at 28-day follow-up CONCLUSIONS: Despite limitations of sample size, this study provides promising support for brief abstinence as a simple, practical, and cost-effective treatment technique for modifying unhelpful gaming cognitions and reducing Internet gaming problems. © 2017 Wiley Periodicals, Inc.

Treating respiratory viral diseases with chemically modified, second generation intranasal siRNAs.

PubMed

Barik, Sailen

2009-01-01

Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2'-O-methyl (2'-O-Me) and 2'-deoxy-2'-fluoro (2'-F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19-27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2'-OMe and 2'-F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.

Long-term treatment with low dose naltrexone maintains stable health in patients with multiple sclerosis.

PubMed

Ludwig, Michael D; Turel, Anthony P; Zagon, Ian S; McLaughlin, Patricia J

2016-01-01

A retrospective study was conducted on patients at Penn State Hershey Medical Center diagnosed with relapsing-remitting multiple sclerosis between 2006 and 2015. Laboratory and clinical data collected over this 10-year period were reviewed. Two cohorts of patients were established based on their relapsing-remitting multiple sclerosis therapy at the time of their first visit to Penn State. One group of patients ( n  = 23) was initially prescribed low dose naltrexone at the time first seen at Hershey. This group was offered low dose naltrexone because of symptoms of fatigue or refusal to take an available disease-modifying therapy. The second group of patients ( n  = 31) was treated with the glatiramer acetate (Copaxone) and offered low dose naltrexone as an adjunct therapy to their disease-modifying therapy. Patient data from visits after 1-50 months post-diagnosis were evaluated in a retrospective manner. Data obtained from patient charts included clinical laboratory values from standard blood tests, timed 25-foot walking trials, and changes in magnetic resonance imaging reports. Statistical analyses between the groups and for each patient over time indicated no significant differences in clinical laboratory values, timed walking, or changes in magnetic resonance imaging. These data suggest that the apparently non-toxic, inexpensive, biotherapeutic is safe and if taken alone did not result in an exacerbation of disease symptoms.

A unified approach to the design of clinical reporting systems.

PubMed

Gouveia-Oliveira, A; Salgado, N C; Azevedo, A P; Lopes, L; Raposo, V D; Almeida, I; de Melo, F G

1994-12-01

Computer-based Clinical Reporting Systems (CRS) for diagnostic departments that use structured data entry have a number of functional and structural affinities suggesting that a common software architecture for CRS may be defined. Such an architecture should allow easy expandability and reusability of a CRS. We report the development methodology and the architecture of SISCOPE, a CRS originally designed for gastrointestinal endoscopy that is expandable and reusable. Its main components are a patient database, a knowledge base, a reports base, and screen and reporting engines. The knowledge base contains the description of the controlled vocabulary and all the information necessary to control the menu system, and is easily accessed and modified with a conventional text editor. The structure of the controlled vocabulary is formally presented as an entity-relationship diagram. The screen engine drives a dynamic user interface and the reporting engine automatically creates a medical report; both engines operate by following a set of rules and the information contained in the knowledge base. Clinical experience has shown this architecture to be highly flexible and to allow frequent modifications of both the vocabulary and the menu system. This structure provided increased collaboration among development teams, insulating the domain expert from the details of the database, and enabling him to modify the system as necessary and to test the changes immediately. The system has also been reused in several different domains.

The effect of abused substances on antenatal and intrapartum fetal testing and well-being.

PubMed

Kopel, Ellen; Hill, Washington C

2013-03-01

Recognition that use and abuse of substances by pregnant patients perpetuates, despite ongoing efforts to educate the public, necessitates clinicians to integrate understanding of potential effects on antepartum and intrapartum fetal testing into their interpretation and implementation of clinical findings. This includes acknowledging some anticipated alterations in results and selecting the appropriate type and frequency of testing methods and interventions. Certain substances are well documented in terms of expected variations in test results; others are not as clearly defined. An overview of information that may be helpful to the clinician is presented to promote understanding of fetal evaluation performed through common tests such as contraction stress test, the nonstress test, the biophysical profile, the modified biophysical profile, fetal movement counting, and Doppler velocimetry. What evidence is available should be used to assist in defining the actual status of the fetus as best as possible, even when the effects of substances may be unknown or have obscure results.

Development of a test battery for evaluating speech perception in complex listening environments.

PubMed

Brungart, Douglas S; Sheffield, Benjamin M; Kubli, Lina R

2014-08-01

In the real world, spoken communication occurs in complex environments that involve audiovisual speech cues, spatially separated sound sources, reverberant listening spaces, and other complicating factors that influence speech understanding. However, most clinical tools for assessing speech perception are based on simplified listening environments that do not reflect the complexities of real-world listening. In this study, speech materials from the QuickSIN speech-in-noise test by Killion, Niquette, Gudmundsen, Revit, and Banerjee [J. Acoust. Soc. Am. 116, 2395-2405 (2004)] were modified to simulate eight listening conditions spanning the range of auditory environments listeners encounter in everyday life. The standard QuickSIN test method was used to estimate 50% speech reception thresholds (SRT50) in each condition. A method of adjustment procedure was also used to obtain subjective estimates of the lowest signal-to-noise ratio (SNR) where the listeners were able to understand 100% of the speech (SRT100) and the highest SNR where they could detect the speech but could not understand any of the words (SRT0). The results show that the modified materials maintained most of the efficiency of the QuickSIN test procedure while capturing performance differences across listening conditions comparable to those reported in previous studies that have examined the effects of audiovisual cues, binaural cues, room reverberation, and time compression on the intelligibility of speech.

Swallowing Disorders in Severe Brain Injury in the Arousal Phase.

PubMed

Bremare, A; Rapin, A; Veber, B; Beuret-Blanquart, F; Verin, E

2016-08-01

The objective of this study was to determine the clinical characteristics of swallowing disorders in severe brain injury in the arousal phase after coma. Between December 1, 2013 and June 30, 2014, eleven patients with severe acquired brain injury who were admitted to rehabilitation center (Male 81.8 %; 40.7 ± 14.6 years) were included in the study. Evaluation of swallowing included a functional examination, clinical functional swallowing test, and naso-endoscopic swallowing test. All patients had swallowing disorders at admission. The first functional swallowing test showed oral (77.8 %) and pharyngeal (66.7 %) food bolus transport disorders; and alterations in airway protection mechanisms (80 %). Swallowing test under endoscopic control showed a disorder in swallowing coordination in 55.6 % of patients tested. Seven (63.6 %) patients resumed oral feeding within an average of 6 weeks after admission to rehabilitation center and 14 weeks after acquired brain injury. Six (85.7 %) of these seven patients continued to require modified solid and liquid textures. Swallowing disorders are a major concern in severe brain injury in the arousal phase. Early bedside assessment of swallowing is essential for detection of swallowing disorders to propose appropriate medical rehabilitation care to these patients in a state of altered consciousness.

Comparison of Medical and Consumer Wireless EEG Systems for Use in Clinical Trials.

PubMed

Ratti, Elena; Waninger, Shani; Berka, Chris; Ruffini, Giulio; Verma, Ajay

2017-01-01

Objectives: To compare quantitative EEG signal and test-retest reliability of medical grade and consumer EEG systems. Methods: Resting state EEG was acquired by two medical grade (B-Alert, Enobio) and two consumer (Muse, Mindwave) EEG systems in five healthy subjects during two study visits. EEG patterns, power spectral densities (PSDs) and test/retest reliability in eyes closed and eyes open conditions were compared across the four systems, focusing on Fp1, the only common electrode. Fp1 PSDs were obtained using Welch's modified periodogram method and averaged for the five subjects for each visit. The test/retest results were calculated as a ratio of Visit 1/Visit 2 Fp1 channel PSD at each 1 s epoch. Results: B-Alert, Enobio, and Mindwave Fp1 power spectra were similar. Muse showed a broadband increase in power spectra and the highest relative variation across test-retest acquisitions. Consumer systems were more prone to artifact due to eye blinks and muscle movement in the frontal region. Conclusions: EEG data can be successfully collected from all four systems tested. Although there was slightly more time required for application, medical systems offer clear advantages in data quality, reliability, and depth of analysis over the consumer systems. Significance: This evaluation provides evidence for informed selection of EEG systemsappropriate for clinical trials.

[Effect of oral administration of ascorbic acid on insulin sensitivity and lipid profile in obese individuals].

PubMed

Martínez-Abundis, E; Pascoe-González, S; González-Ortiz, M; Mora-Martínez, J M; Cabrera-Pivaral, C E

2001-01-01

The aim of this study was to identify the effect of an oral ascorbic acid (AA) supplement on lipid profile and insulin sensitivity in obese people. A randomized double-blind clinical trial placebo controlled was performed in 16 obese male volunteers [body mass index (BMI) 30-40 kg/m2]. Eight received orally 1 g of AA daily for four weeks and the other eight volunteers received placebo by the same scheme and period of time. Before and after the pharmacological intervention were measured total cholesterol, high-density-lipoprotein (HDL) cholesterol, triglycerides, glucose, creatinine and uric acid. Low-density-lipoprotein (LDL) cholesterol and very-low-density-lipoprotein (VLDL) triglycerides were calculated using formulas. In order to assess insulin sensitivity before and after the intervention, the steady-state glucose (SSG) was calculated from the insulin suppression test modified with octreotide. There were not significant differences in clinical characteristics between both groups. Basal metabolic profile and SSG were similar between both groups. There were not significant differences in both groups between before and after the intervention in metabolic profile and insulin sensitivity. AA did not modify the lipid profile nor insulin sensitivity in the group of obese people studied.

2017 Multimodality Appropriate Use Criteria for Noninvasive Cardiac Imaging: Expert Consensus of the Asian Society of Cardiovascular Imaging

PubMed Central

Beck, Kyongmin Sarah; Kim, Jeong A; Choe, Yeon Hyeon; Hian, Sim Kui; Hoe, John; Hong, Yoo Jin; Kim, Sung Mok; Kim, Tae Hoon; Kim, Young Jin; Kim, Yun Hyeon; Kuribayashi, Sachio; Lee, Jongmin; Leong, Lilian; Lim, Tae-Hwan; Lu, Bin; Park, Jae Hyung; Sakuma, Hajime; Yang, Dong Hyun; Yaw, Tan Swee; Wan, Yung-Liang; Zhang, Zhaoqi; Zhao, Shihua

2017-01-01

In 2010, the Asian Society of Cardiovascular Imaging (ASCI) provided recommendations for cardiac CT and MRI, and this document reflects an update of the 2010 ASCI appropriate use criteria (AUC). In 2016, the ASCI formed a new working group for revision of AUC for noninvasive cardiac imaging. A major change that we made in this document is the rating of various noninvasive tests (exercise electrocardiogram, echocardiography, positron emission tomography, single-photon emission computed tomography, radionuclide imaging, cardiac magnetic resonance, and cardiac computed tomography/angiography), compared side by side for their applications in various clinical scenarios. Ninety-five clinical scenarios were developed from eight selected pre-existing guidelines and classified into four sections as follows: 1) detection of coronary artery disease, symptomatic or asymptomatic; 2) cardiac evaluation in various clinical scenarios; 3) use of imaging modality according to prior testing; and 4) evaluation of cardiac structure and function. The clinical scenarios were scored by a separate rating committee on a scale of 1–9 to designate appropriate use, uncertain use, or inappropriate use according to a modified Delphi method. Overall, the AUC ratings for CT were higher than those of previous guidelines. These new AUC provide guidance for clinicians choosing among available testing modalities for various cardiac diseases and are also unique, given that most previous AUC for noninvasive imaging include only one imaging technique. As cardiac imaging is multimodal in nature, we believe that these AUC will be more useful for clinical decision making. PMID:29089819

Immediate Effects of a Single Session of Motor Skill Training on the Lumbar Movement Pattern During a Functional Activity in People With Low Back Pain: A Repeated-Measures Study.

PubMed

Marich, Andrej V; Lanier, Vanessa M; Salsich, Gretchen B; Lang, Catherine E; Van Dillen, Linda R

2018-04-06

People with low back pain (LBP) may display an altered lumbar movement pattern of early lumbar motion compared to people with healthy backs. Modifying this movement pattern during a clinical test decreases pain. It is unknown whether similar effects would be seen during a functional activity. The objective of this study is was to examine the lumbar movement patterns before and after motor skill training, effects on pain, and characteristics that influenced the ability to modify movement patterns. The design consisted of a repeated-measures study examining early-phase lumbar excursion in people with LBP during a functional activity test. Twenty-six people with chronic LBP received motor skill training, and 16 people with healthy backs were recruited as a reference standard. Twenty minutes of motor skill training to decrease early-phase lumbar excursion during the performance of a functional activity were used as a treatment intervention. Early-phase lumbar excursion was measured before and after training. Participants verbally reported increased pain, decreased pain, or no change in pain during performance of the functional activity test movement in relation to their baseline pain. The characteristics of people with LBP that influenced the ability to decrease early-phase lumbar excursion were examined. People with LBP displayed greater early-phase lumbar excursion before training than people with healthy backs (LBP: mean = 11.2°, 95% CI = 9.3°-13.1°; healthy backs: mean = 7.1°, 95% CI = 5.8°-8.4°). Following training, the LBP group showed a decrease in the amount of early-phase lumbar excursion (mean change = 4.1°, 95% CI = 2.4°-5.8°); 91% of people with LBP reported that their pain decreased from baseline following training. The longer the duration of LBP (β = - 0.22) and the more early-phase lumbar excursion before training (β = - 0.82), the greater the change in early-phase lumbar excursion following training. The long-term implications of modifying the movement pattern and whether the decrease in pain attained was clinically significant are unknown. People with LBP were able to modify their lumbar movement pattern and decrease their pain with the movement pattern within a single session of motor skill training.

Effect of Modified Otago Exercises on Postural Balance, Fear of Falling, and Fall Risk in Older Fallers With Knee Osteoarthritis and Impaired Gait and Balance: A Secondary Analysis.

PubMed

Mat, Sumaiyah; Ng, Chin Teck; Tan, Pey June; Ramli, Norlisah; Fadzli, Farhana; Rozalli, Faizatul Izza; Mazlan, Mazlina; Hill, Keith D; Tan, Maw Pin

2018-03-01

Osteoarthritis (OA) is considered an established risk factor for falls. Published studies evaluating secondary falls prevention strategies among individuals with OA are limited. To evaluate the effect of a personalized home-based exercise program to improve postural balance, fear of falling, and falls risk in older fallers with knee OA and gait and balance problems. Randomized controlled trial. University of Malaya Medical Centre. Fallers who had both radiological OA and a Timed Up and Go (TUG) score of over 13.5 seconds. Postural sway (composite sway) was quantified with the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB) under 4 different sensory conditions: eyes open on firm surface, eyes closed on firm surface, eyes open on unstable foam surface, and eyes closed on unstable foam surface. Participants were asked to stand upright and to attempt to hold their position for 10 seconds for each test condition. The average reading for all conditions were calculated. Participants randomized to the intervention arm received a home-based modified Otago Exercise Program (OEP) as part of a multifactorial intervention, whereas control participants received general health advice and conventional treatment. This was a secondary subgroup analysis from an original randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT) (trial registration number: ISRCTN11674947). Posturography using a long force plate balance platform (Balancemaster, NeuroCom, USA), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the short-form Falls Efficacy Scale-International (short FES-I) were assessed at baseline and 6 months. Results of 41 fallers with radiological evidence of OA and impaired TUG (intervention, 17; control, 24) were available for the final analysis. Between-group analysis revealed significant improvements in the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB), Limits of Stability (LOS), and short FES-I scores by the intervention group compared to the control group at 6 months. No significant difference in time to first fall or in fall-free survival between the intervention and control groups was found. Home-based balance and strength exercises benefited older fallers with OA and gait and balance disorders by improving postural control, with no observable trend in reduction of fall recurrence. Our findings will now inform a future, adequately powered, randomized controlled study using fall events as definitive outcomes. I. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Construct Related Validity for the Baumgartner Modified Pull-Up Test

ERIC Educational Resources Information Center

Baumgartner, Ted A.; Gaunt, Sharon j.

2005-01-01

Traditionally the pull-up was used as a measure of arm and shoulder girdle strength and endurance. This measure did not discriminate among ability levels because many zero scores occur. Baumgartner (1978) developed a modified pull-up test that was easier than the traditional pull-up test. The Baumgartner Modified Pull-Up (BMPU) has been used as an…

Type 1 Diabetes TrialNet: A Multifaceted Approach to Bringing Disease-Modifying Therapy to Clinical Use in Type 1 Diabetes.

PubMed

Bingley, Polly J; Wherrett, Diane K; Shultz, Ann; Rafkin, Lisa E; Atkinson, Mark A; Greenbaum, Carla J

2018-04-01

What will it take to bring disease-modifying therapy to clinical use in type 1 diabetes? Coordinated efforts of investigators involved in discovery, translational, and clinical research operating in partnership with funders and industry and in sync with regulatory agencies are needed. This Perspective describes one such effort, Type 1 Diabetes TrialNet, a National Institutes of Health-funded and JDRF-supported international clinical trials network that emerged from the Diabetes Prevention Trial-Type 1 (DPT-1). Through longitudinal natural history studies, as well as trials before and after clinical onset of disease combined with mechanistic and ancillary investigations to enhance scientific understanding and translation to clinical use, TrialNet is working to bring disease-modifying therapies to individuals with type 1 diabetes. Moreover, TrialNet uses its expertise and experience in clinical studies to increase efficiencies in the conduct of trials and to reduce the burden of participation on individuals and families. Herein, we highlight key contributions made by TrialNet toward a revised understanding of the natural history of disease and approaches to alter disease course and outline the consortium's plans for the future. © 2018 by the American Diabetes Association.

Long-term viremia and fecal shedding in pups after modified-live canine parvovirus vaccination.

PubMed

Decaro, Nicola; Crescenzo, Giuseppe; Desario, Costantina; Cavalli, Alessandra; Losurdo, Michele; Colaianni, Maria Loredana; Ventrella, Gianpiero; Rizzi, Stefania; Aulicino, Stefano; Lucente, Maria Stella; Buonavoglia, Canio

2014-06-24

Canine parvovirus (CPV) modified live virus vaccines are able to infect vaccinated dogs replicating in the bloodstream and enteric mucosa. However, the exact duration and extent of CPV vaccine-induced viremia and fecal shedding are not known. With the aim to fill this gap, 26 dogs were administered two commercial vaccines containing a CPV-2 or CPV-2b strain and monitored for 28 days after vaccination. By using real-time PCR, vaccine-induced viremia and shedding were found to be long lasting for both vaccinal strains. Vaccinal CPV-2b shedding was detected for a shorter period than CPV-2 (12 against 19 mean days) but with greater viral loads, whereas viremia occurred for a longer period (22 against 19 mean days) and with higher titers for CPV-2b. Seroconversion appeared as early as 7 and 14 days post-vaccination for CPV-2b and CPV-2 vaccines, respectively. With no vaccine there was any diagnostic interference using in-clinic or hemagglutination test, since positive results were obtained only by fecal real-time PCR testing. The present study adds new insights into the CPV vaccine persistence in the organism and possible interference with diagnostic tests. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative study of mechanical properties of direct core build-up materials

PubMed Central

Kumar, Girish; Shivrayan, Amit

2015-01-01

Background and Objectives: The strength greatly influences the selection of core material because core must withstand forces due to mastication and para-function for many years. This study was conducted to evaluate certain mechanical properties of commonly used materials for direct core build-up, including visible light cured composite, polyacid modified composite, resin modified glass ionomer, high copper amalgam, and silver cermet cement. Materials and Methods: All the materials were manipulated according to the manufacturer's recommendations and standard test specimens were prepared. A universal testing machine at different cross-head speed was used to determine all the four mechanical properties. Mean compressive strength, diametral tensile strength, flexural strength, and elastic modulus with standard deviations were calculated. Multiple comparisons of the materials were also done. Results: Considerable differences in compressive strength, diametral tensile strength, and flexural strength were observed. Visible light cured composite showed relatively high compressive strength, diametral tensile strength, and flexural strength compared with the other tested materials. Amalgam showed the highest value for elastic modulus. Silver cermet showed less value for all the properties except for elastic modulus. Conclusions: Strength is one of the most important criteria for selection of a core material. Stronger materials better resist deformation and fracture provide more equitable stress distribution, greater stability, and greater probability of clinical success. PMID:25684905

What Can We Learn about Auditory Processing from Adult Hearing Questionnaires?

PubMed

Bamiou, Doris-Eva; Iliadou, Vasiliki Vivian; Zanchetta, Sthella; Spyridakou, Chrysa

2015-01-01

Questionnaires addressing auditory disability may identify and quantify specific symptoms in adult patients with listening difficulties. (1) To assess validity of the Speech, Spatial, and Qualities of Hearing Scale (SSQ), the (Modified) Amsterdam Inventory for Auditory Disability (mAIAD), and the Hyperacusis Questionnaire (HYP) in adult patients experiencing listening difficulties in the presence of a normal audiogram. (2) To examine which individual questionnaire items give the worse scores in clinical participants with an auditory processing disorder (APD). A prospective correlational analysis study. Clinical participants (N = 58) referred for assessment because of listening difficulties in the presence of normal audiometric thresholds to audiology/ear, nose, and throat or audiovestibular medicine clinics. Normal control participants (N = 30). The mAIAD, HYP, and the SSQ were administered to a clinical population of nonneurological adults who were referred for auditory processing (AP) assessment because of hearing complaints, in the presence of normal audiogram and cochlear function, and to a sample of age-matched normal-hearing controls, before the AP testing. Clinical participants with abnormal results in at least one ear and in at least two tests of AP (and at least one of these tests to be nonspeech) were classified as clinical APD (N = 39), and the remaining (16 of whom had a single test abnormality) as clinical non-APD (N = 19). The SSQ correlated strongly with the mAIAD and the HYP, and correlation was similar within the clinical group and the normal controls. All questionnaire total scores and subscores (except sound distinction of mAIAD) were significantly worse in the clinical APD versus the normal group, while questionnaire total scores and most subscores indicated greater listening difficulties for the clinical non-APD versus the normal subgroups. Overall, the clinical non-APD group tended to give better scores than the APD in all questionnaires administered. Correlation was strong for the worse-ear gaps-in-noise threshold with the SSQ, mAIAD, and HYP; strong to moderate for the speech in babble and left-ear dichotic digit test scores (at p < 0.01); and weak to moderate for the remaining AP tests except the frequency pattern test that did not correlate. The worse-scored items in all three questionnaires concerned speech-in-noise questions. This is similar to worse-scored items by hearing-impaired participants as reported in the literature. Worse-scored items of the clinical group also included quality aspects of listening questions from the SSQ, which most likely pertain to cognitive aspects of listening, such as ability to ignore other sounds and listening effort. Hearing questionnaires may help assess symptoms of adults with APD. The listening difficulties and needs of adults with APD to some extent overlap with those of hearing-impaired listeners, but there are significant differences. The correlation of the gaps-in-noise and duration pattern (but not frequency pattern) tests with the questionnaire scores indicates that temporal processing deficits may play an important role in clinical presentation. American Academy of Audiology.

COPD management: role of symptom assessment in routine clinical practice

PubMed Central

van der Molen, Thys; Miravitlles, Marc; Kocks, Janwillem WH

2013-01-01

Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life. Despite this, COPD treatment and its management are mainly based on lung function assessments. There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives. Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD. Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice. In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. PMID:24143085

The fuzzy cube and causal efficacy: representation of concomitant mechanisms in stroke.

PubMed

Jobe, Thomas H.; Helgason, Cathy M.

1998-04-01

Twentieth century medical science has embraced nineteenth century Boolean probability theory based upon two-valued Aristotelian logic. With the later addition of bit-based, von Neumann structured computational architectures, an epistemology based on randomness has led to a bivalent epidemiological methodology that dominates medical decision making. In contrast, fuzzy logic, based on twentieth century multi-valued logic, and computational structures that are content addressed and adaptively modified, has advanced a new scientific paradigm for the twenty-first century. Diseases such as stroke involve multiple concomitant causal factors that are difficult to represent using conventional statistical methods. We tested which paradigm best represented this complex multi-causal clinical phenomenon-stroke. We show that the fuzzy logic paradigm better represented clinical complexity in cerebrovascular disease than current probability theory based methodology. We believe this finding is generalizable to all of clinical science since multiple concomitant causal factors are involved in nearly all known pathological processes.

Correlation between mobility assessed by the Modified Rivermead Mobility Index and physical function in stroke patients

PubMed Central

Park, Gi-Tae; Kim, Mihyun

2016-01-01

[Purpose] The purpose of this study was to investigate the relationship between mobility assessed by the Modified Rivermead Mobility Index and variables associated with physical function in stroke patients. [Subjects and Methods] One hundred stroke patients (35 males and 65 females; age 58.60 ± 13.91 years) participated in this study. Modified Rivermead Mobility Index, muscle strength (manual muscle test), muscle tone (Modified Ashworth Scale), range of motion of lower extremity, sensory function (light touch and proprioception tests), and coordination (heel to shin and lower-extremity motor coordination tests) were assessed. [Results] The Modified Rivermead Mobility Index was correlated with all the physical function variables assessed, except the degree of knee extension. In addition, stepwise linear regression analysis revealed that coordination (heel to shin test) was the explanatory variable closely associated with mobility in stroke patients. [Conclusion] The Modified Rivermead Mobility Index score was significantly correlated with all the physical function variables. Coordination (heel to shin test) was closely related to mobility function. These results may be useful in developing rehabilitation programs for stroke patients. PMID:27630440

Genetic Literacy and Patient Perceptions of IBD Testing Utility and Disease Control: A Randomized Vignette Study of Genetic Testing

PubMed Central

Hooker, Gillian W.; Peay, Holly; Erby, Lori; Bayless, Theodore; Biesecker, Barbara B.; Roter, Debra L.

2014-01-01

Background Findings from inflammatory bowel disease (IBD) genome-wide association studies are being translated clinically into prognostic and diagnostic indicators of disease. Yet, patient perception and understanding of these tests and their applicability to providing risk information is unclear. The goal of this study was to determine, using hypothetical scenarios, whether patients with IBD perceive genetic testing to be useful for risk assessment, whether genetic test results impact perceived control, and whether low genetic literacy may be a barrier to patient understanding of these tests. Methods Two hundred fifty seven patients with IBD from the Johns Hopkins gastroenterology clinics were randomized to receive a vignette depicting either a genetic testing scenario or a standard blood testing scenario. Participants were asked questions about the vignette and responses were compared between groups. Results Perceptions of test utility for risk assessment were higher among participants responding to the genetic vignette (P < 0.001). There were no significant differences in perceptions of control over IBD after hypothetical testing between vignettes (P = 0.24). Participant responses were modified by genetic literacy, measured using a scale developed for this study. Participants randomized to the genetic vignette who scored higher on the genetic literacy scale perceived greater utility of testing for risk assessment (P = 0.008) and more control after testing (P = 0.02). Conclusions Patients with IBD perceive utility in genetic testing for providing information relevant to family members, and this appreciation is promoted by genetic literacy. Low genetic literacy among patients poses a potential threat to effective translation of genetic and genomic tests. PMID:24691112

Associations of medical student personality and health/wellness characteristics with their medical school performance across the curriculum.

PubMed

Haight, Scott J; Chibnall, John T; Schindler, Debra L; Slavin, Stuart J

2012-04-01

To assess the relationships of cognitive and noncognitive performance predictors to medical student preclinical and clinical performance indicators across medical school years 1 to 3 and to evaluate the association of psychological health/wellness factors with performance. In 2010, the authors conducted a cross-sectional, correlational, retrospective study of all 175 students at the Saint Louis University School of Medicine who had just completed their third (first clinical) year. Students were asked to complete assessments of personality, stress, anxiety, depression, social support, and community cohesion. Performance measures included total Medical College Admission Test (MCAT) score, preclinical academic grades, National Board of Medical Examiners subject exam scores, United States Medical Licensing Examination Step 1 score, clinical evaluations, and Humanism in Medicine Honor Society nominations. A total of 152 students (87%) participated. MCAT scores predicted cognitive performance indicators (academic tests), whereas personality variables (conscientiousness, extraversion, empathy) predicted noncognitive indicators (clinical evaluations, humanism nominations). Conscientiousness predicted all clinical skills, extraversion predicted clinical skills reflecting interpersonal behavior, and empathy predicted motivation. Health/wellness variables had limited associations with performance. In multivariate analyses that included control for shelf exam scores, conscientiousness predicted clinical evaluations, and extraversion and empathy predicted humanism nominations. This study identified two sets of skills (cognitive, noncognitive) used during medical school, with minimal overlap across the types of performance (e.g., exam performance versus clinical interpersonal skills) they predict. Medical school admission and evaluation efforts may need to be modified to reflect the importance of personality and other noncognitive factors.

Do Diagnosis Delays Impact Receipt of Test Results? Evidence from the HIV Early Infant Diagnosis Program in Uganda

PubMed Central

Mugambi, Melissa Latigo; Deo, Sarang; Kekitiinwa, Adeodata; Kiyaga, Charles; Singer, Mendel E.

2013-01-01

Background There is scant evidence on the association between diagnosis delays and the receipt of test results in HIV Early Infant Diagnosis (EID) programs. We determine the association between diagnosis delays and other health care system and patient factors on result receipt. Methods We reviewed 703 infant HIV test records for tests performed between January 2008 and February 2009 at a regional referral hospital and level four health center in Uganda. The main outcome was caregiver receipt of the test result. The primary study variable was turnaround time (time between sample collection and result availability at the health facility). Additional variables included clinic entry point, infant age at sample collection, reported HIV status and receipt of antiretroviral prophylaxis for prevention of mother-to-child transmission. We conducted a pooled analysis in addition to separate analyses for each facility. We estimated the relative risk of result receipt using modified Poisson regression with robust standard errors. Results Overall, the median result turnaround time, was 38 days. 59% of caregivers received infant test results. Caregivers were less likely to receive results at turnaround times greater than 49 days compared to 28 days or fewer (ARR = 0.83; 95% CI = 0.70–0.98). Caregivers were more likely to receive results at the PMTCT clinic (ARR = 1.81; 95% CI = 1.40–2.33) and less likely at the pediatric ward (ARR = 0.54; 95% CI = 0.37–0.81) compared to the immunization clinic. At the level four health center, result receipt was half as likely among infants older than 9 months compared to 3 months and younger (ARR= 0.47; 95% CI = 0.25–0.93). Conclusion In this study setting, we find evidence that longer turnaround times, clinic entry point and age at sample collection may be associated with receipt of infant HIV test results. PMID:24282502

Targeted therapies for Parkinson's disease: From genetics to the clinic.

PubMed

Sardi, S Pablo; Cedarbaum, Jesse M; Brundin, Patrik

2018-04-27

The greatest unmet medical need in Parkinson's disease (PD) is treatments that slow the relentless progression of symptoms. The discovery of genetic variants causing and/or increasing the risk for PD has provided the field with a new arsenal of potential therapies ready to be tested in clinical trials. We highlight 3 of the genetic discoveries (α-synuclein, glucocerebrosidase, and leucine-rich repeat kinase) that have prompted new therapeutic approaches now entering the clinical stages. We are at an exciting juncture in the journey to developing disease-modifying treatments based on knowledge of PD genetics and pathology. This review focuses on therapeutic paradigms that are under clinical development and highlights a wide range of key outstanding questions in PD. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Polymer modified asphalt in hot mix pavement : interim report, executive summary.

DOT National Transportation Integrated Search

1988-11-01

This report presents a summary of a literature review to determine the most appropriate testing procedures for use with polymer modified asphalts. In examining testing procedures, it was necessary to study the effects of polymer modifiers on both bin...

My46: a web-based tool for self-guided management of genomic test results in research and clinical settings

PubMed Central

Tabor, Holly K.; Jamal, Seema M.; Yu, Joon-Ho; Crouch, Julia M.; Shankar, Aditi G.; Dent, Karin M.; Anderson, Nick; Miller, Damon A.; Futral, Brett T.; Bamshad, Michael J.

2016-01-01

A major challenge to implementing precision medicine is the need for an efficient and cost-effective strategy for returning individual genomic test results that is easily scalable and can be incorporated into multiple models of clinical practice. My46 is a web-based tool for managing the return of genetic results that was designed and developed to support a wide range of approaches to results disclosure, ranging from traditional face-to-face disclosure to self-guided models. My46 has five key functions: set and modify results return preferences, return results, educate, manage return of results, and assess return of results. These key functions are supported by six distinct modules and a suite of features that enhance the user experience, ease site navigation, facilitate knowledge sharing, and enable results return tracking. My46 is a potentially effective solution for returning results and supports current trends toward shared decision-making between patient and provider and patient-driven health management. PMID:27632689

IPS Empress inlays luted with a self-adhesive resin cement after 1 year.

PubMed

Taschner, Michael; Frankenberger, Roland; García-Godoy, Franklin; Rosenbusch, Silke; Petschelt, Anselm; Krämer, Norbert

2009-02-01

To prospectively compare the clinical performance of two different resin composites for luting IPS Empress inlays and onlays. 83 IPS Empress restorations were placed in 30 subjects. All restorations were inserted under rubber dam. 43 inlays/onlays were luted with a self-adhesive resin cement [RelyX Unicem (RX)]. A multistep adhesive (Syntac) was used with Variolink II low viscosity (SV) and served as control (n=40). The restorations were evaluated after 2 weeks: Baseline = 1st recall (R1), after 6 months (R2) and after 1 year (R3) by two calibrated examiners using the modified USPHS criteria. From R1 to R3, one failure was noticed in the SV group (R2) due to marginal enamel chipping. After 1 year of clinical service, SV revealed significantly better results regarding color match and integrity inlay (Mann-Whitney U-test, P< 0.05). No statistically significant differences were observed between SV and RX for the remaining criteria (Mann-Whitney U-test, P>0.05).

Facilitating aerobic exercise training in older adults with Alzheimer's disease.

PubMed

Yu, Fang; Kolanowski, Ann

2009-01-01

Emerging science suggests that aerobic exercise might modify the pathophysiology of Alzheimer's disease (AD) and improve cognition. However, there are no clinical practice guidelines for aerobic exercise prescription and training in older adults with AD. A few existing studies showed that older adults with AD can participate in aerobic exercise and improve dementia symptoms, but lack adequate descriptions of their aerobic exercise training programs and their clinical applicability. In this paper, we summarize current knowledge about the potential benefits of aerobic exercise in older adults with AD. We then describe the development of a moderate-intensity aerobic exercise program for this population and report results from its initial testing in a feasibility trial completed by two persons with AD. Two older adults with AD completed the aerobic exercise program. Barriers to the program's implementation are described, and methods to improve more wide-spread adoption of such programs and the design of future studies that test them are suggested.

Adjunctive Systemic Antimicrobial Therapy vs Asepsis in Conjunction with Guided Tissue Regeneration: A Randomized, Controlled Clinical Trial.

PubMed

Abu-Ta'a, Mahmoud

2016-01-01

This randomized clinical trial compares the usefulness of adjunctive antibiotics, while strict asepsis was followed during periodontal surgery involving guided tissue regeneration. Two groups of 20 consecutive patients each with advanced periodontal disease were randomly assigned to treatment. They displayed one angular defect each with an intrabony component ≥3 mm, probing pocket depth and probing attachment level (PAL) ≥7 mm. Test group included 13 males, mean age 60 years, treated with enamel matrix derivative (EMD) and demineralized freeze-dried bone allograft with modified papilla preservation technique, received oral amoxicillin 1 gm, 1 hour preoperatively and 2 gm for 2 days postoperatively. Control group included 10 males, mean age 57 years, treated with EMD and demineralized freeze-dried bone allograft with modified papilla preservation technique, received no antibiotics. Outcome measures were clinical attachment level (CAL) gain, residual periodontal pocket depth (res. PD), gingival recession (GR), bleeding on probing (BOP), adverse events and postoperative complications. Patients were followed up to 12 months after periodontal surgery involving guided tissue regeneration. There were no significant differences between both groups for CAL gain, res. PD, GR, BOP nor other clinical parameters, though patients' subjective perception of postoperative discomfort was significantly smaller in the group receiving antibiotics. Antibiotics do not provide significant advantages concerning clinical periodontal parameters nor concerning postoperative infections in case of proper asepsis. It does, on the contrary, reduce postoperative discomfort. Regarding the results of this study, adjunc-tive systemic antibiotics in combination with guided tissue regeneration may be useful in reducing postoperative discomfort but may not be helpful for improving periodontal regeneration outcomes.

A Phase 1, Single-center, Double-blind, Placebo-controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Clinical Effects, and Pharmacokinetics-Pharmacodynamics of Intravenous Cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a Single Ascending Bolus Dose.

PubMed

Struys, Michel M R F; Valk, Beatrijs I; Eleveld, Douglas J; Absalom, Anthony R; Meyer, Peter; Meier, Sascha; den Daas, Izaak; Chou, Thomas; van Amsterdam, Kai; Campagna, Jason A; Sweeney, Steven P

2017-07-01

Cyclopropyl-methoxycarbonylmetomidate (ABP-700) is a new "soft" etomidate analog. The primary objectives of this first-in-human study were to describe the safety and efficacy of ABP-700 and to determine its maximum tolerated dose. Secondary objectives were to characterize the pharmacokinetics of ABP-700 and its primary metabolite (cyclopropyl-methoxycarbonyl acid), to assess the clinical effects of ABP-700, and to investigate the dose-response and pharmacokinetic/pharmacodynamic relationships. Sixty subjects were divided into 10 cohorts and received an increasing, single bolus of either ABP-700 or placebo. Safety was assessed by clinical laboratory evaluations, infusion-site reactions, continuous monitoring of vital signs, physical examination, adverse event monitoring, and adrenocorticotropic hormone stimulation testing. Clinical effects were assessed with modified observer's assessment of alertness/sedation and Bispectral Index monitoring. Pharmacokinetic parameters were calculated. Stopping criteria were met at 1.00 mg/kg dose. No serious adverse events were reported. Adverse events were dose-dependent and comprised involuntary muscle movement, tachycardia, and ventilatory effects. Adrenocorticotropic hormone stimulation evoked a physiologic cortisol response in all subjects, no different from placebo. Pharmacokinetics were dose-proportional. A three-compartment pharmacokinetic model described the data well. A rapid onset of anesthesia/sedation after bolus administration and also a rapid recovery were observed. A quantitative concentration-effect relationship was described for the modified observer's assessment of alertness/sedation and Bispectral Index. This first-in-human study of ABP-700 shows that ABP-700 was safe and well tolerated after single-bolus injections up to 1.00 mg/kg. Bolus doses of 0.25 and 0.35 mg/kg were found to provide the most beneficial clinical effect versus side-effect profile.

Adjunctive Effect of Autologus Platelet-Rich Fibrin to Barrier Membrane in the Treatment of Periodontal Intrabony Defects.

PubMed

Panda, Saurav; Sankari, Malaiappan; Satpathy, Anurag; Jayakumar, Doraiswamy; Mozzati, Marco; Mortellaro, Carmen; Gallesio, Giorgia; Taschieri, Silvio; Del Fabbro, Massimo

2016-05-01

Autologous platelet-rich fibrin (PRF) and barrier membranes in the treatment of intrabony defects in chronic periodontitis patients have shown significant clinical benefits. This study evaluates the additive effect of autologous PRF in combination with a barrier membrane versus the use of barrier membrane alone for the treatment of intrabony defects in chronic periodontitis patients. A randomized split-mouth design was used. Sixteen patients with 32 paired intrabony defects were included. In each patient 1 defect was treated using a resorbable collagen membrane along with PRF (test group) and the other defect by guided tissue regeneration alone (control group). The following clinical parameters were measured at baseline and after 9 months: plaque index, modified sulcus bleeding index, probing pocket depth, clinical attachment level, and gingival marginal level. The radiographic defect depth was also assessed at baseline and after 9 months. Test group showed a statistically significant improvement for probing depth (P = 0.002), clinical attachment level (P = 0.001), and radiographic defect depth (P < 0.001) after 9 months as compared with the control sites. Radiographic defect depth reduction was 58.19 ± 13.24% in the test group as compared with 24.86 ± 9.94% reduction in the control group. The adjunctive use of PRF in combination with barrier membrane is more effective in the treatment of intrabony defects in chronic periodontitis as compared with barrier membrane alone.

Reduced in vitro T-cell responses induced by glutaraldehyde-modified allergen extracts are caused mainly by retarded internalization of dendritic cells

PubMed Central

Heydenreich, Bärbel; Bellinghausen, Iris; Lorenz, Steffen; Henmar, Helene; Strand, Dennis; Würtzen, Peter A; Saloga, Joachim

2012-01-01

Although allergen-specific immunotherapy is a clinically effective therapy for IgE-mediated allergic diseases, the risk of IgE-mediated adverse effects still exists. For this reason, chemically modified allergoids have been introduced, which may destroy IgE-binding sites while T-cell activation should be retained. The aim of the study was to analyse the differences between intact allergens and differently modified/aggregated allergoids concerning their internalization as well as T-cell and basophil activation. For this purpose human monocyte-derived immature dendritic cells (DC) were incubated with Phleum pratense or Betula verrucosa pollen extract or with the corresponding allergoids, modified with formaldehyde or glutaraldehyde. After an additional maturation process, the antigen-loaded mature DC were co-cultured with autologous CD4+ T cells. Allergenicity was tested by leukotriene release from basophils. In addition, the uptake of intact allergens and allergoids by immature DC was analysed. The proliferation of, as well as the interleukin-4 (IL-4), IL-10, IL-13 and interferon-γ production by, CD4+ T cells which had been stimulated with glutaraldehyde allergoid-treated DC was reduced compared with CD4+ T cells stimulated with intact allergen-treated or formaldehyde allergoid-treated DC. In line with this, glutaraldehyde-modified allergoids were more aggregated and were internalized more slowly. Furthermore, only the allergoids modified with glutaraldehyde induced a decreased leukotriene release by activated basophils. These findings suggest that IgE-reactive epitopes were destroyed more efficiently by modification with glutaraldehyde than with formaldehyde under the conditions chosen for these investigations. Glutaraldehyde-modified allergoids also displayed lower T-cell stimulatory capacity, which is mainly the result of greater modification/aggregation and diminished uptake by DC. PMID:22348538

Reduced in vitro T-cell responses induced by glutaraldehyde-modified allergen extracts are caused mainly by retarded internalization of dendritic cells.

PubMed

Heydenreich, Bärbel; Bellinghausen, Iris; Lorenz, Steffen; Henmar, Helene; Strand, Dennis; Würtzen, Peter A; Saloga, Joachim

2012-06-01

Although allergen-specific immunotherapy is a clinically effective therapy for IgE-mediated allergic diseases, the risk of IgE-mediated adverse effects still exists. For this reason, chemically modified allergoids have been introduced, which may destroy IgE-binding sites while T-cell activation should be retained. The aim of the study was to analyse the differences between intact allergens and differently modified/aggregated allergoids concerning their internalization as well as T-cell and basophil activation. For this purpose human monocyte-derived immature dendritic cells (DC) were incubated with Phleum pratense or Betula verrucosa pollen extract or with the corresponding allergoids, modified with formaldehyde or glutaraldehyde. After an additional maturation process, the antigen-loaded mature DC were co-cultured with autologous CD4(+) T cells. Allergenicity was tested by leukotriene release from basophils. In addition, the uptake of intact allergens and allergoids by immature DC was analysed. The proliferation of, as well as the interleukin-4 (IL-4), IL-10, IL-13 and interferon-γ production by, CD4(+) T cells which had been stimulated with glutaraldehyde allergoid-treated DC was reduced compared with CD4(+) T cells stimulated with intact allergen-treated or formaldehyde allergoid-treated DC. In line with this, glutaraldehyde-modified allergoids were more aggregated and were internalized more slowly. Furthermore, only the allergoids modified with glutaraldehyde induced a decreased leukotriene release by activated basophils. These findings suggest that IgE-reactive epitopes were destroyed more efficiently by modification with glutaraldehyde than with formaldehyde under the conditions chosen for these investigations. Glutaraldehyde-modified allergoids also displayed lower T-cell stimulatory capacity, which is mainly the result of greater modification/aggregation and diminished uptake by DC. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

Accuracy of "Modified Checklist for Autism in Toddlers" ("M-CHAT") in Detecting Autism and Other Developmental Disorders in Community Clinics

ERIC Educational Resources Information Center

Toh, Teck-Hock; Tan, Vivian Wee-Yen; Lau, Peter Sie-Teck; Kiyu, Andrew

2018-01-01

This study determined the accuracy of "Modified Checklist for Autism in Toddlers" ("M-CHAT") in detecting toddlers with autism spectrum disorder (ASD) and other developmental disorders (DD) in community mother and child health clinics. We analysed 19,297 eligible toddlers (15-36 months) who had "M-CHAT" performed in…

Sensitivity of the activated partial thromboplastin time, the dilute Russell's viper venom time, and the kaolin clotting time for the detection of the lupus anticoagulant: a direct comparison using plasma dilutions.

PubMed

Martin, B A; Branch, D W; Rodgers, G M

1996-01-01

Increasing dilutions of lupus anticoagulant (LA) plasmas from twelve patients were used to directly compare the sensitivity of four tests for LA. The tests evaluated were the modified Bell and Alton activated partial thromboplastin time (APTT), an APTT using a commercially prepared partial thromboplastin (Platelin LS APTT), a modified dilute Russell's viper venom time (DRVVT), and a modified kaolin clotting time (KCT). LAs were detected in all twelve plasmas by each of three tests and eleven of twelve plasmas in a fourth test when undiluted patient plasma was used. Repeating the tests after diluting the LA plasmas with normal platelet-free plasma (PFP) showed that the KCT was the most sensitive test for LA, detecting eleven of twelve LAs at a dilution of 10% patient plasma and ten of twelve LAs at a dilution of 5% patient plasma. The modified Bell and Alton APTT and the modified DRVVT had similar sensitivities at a patient plasma concentration of 10%, detecting seven of twelve and eight of twelve LAs, respectively. The Platelin LS APTT detected only four of twelve LAs at a patient plasma concentration of 10%. Our results indicate that the modified KCT is a sensitive method for the detection of LAs. The modified Bell and Alton APTT and the DRVVT were less sensitive.

Turkish version of the modified Constant-Murley score and standardized test protocol: reliability and validity.

PubMed

Çelik, Derya

2016-01-01

The Constant-Murley score (CMS) is widely used to evaluate disabilities associated with shoulder injuries, but it has been criticized for relying on imprecise terminology and a lack of standardized methodology. A modified guideline, therefore, was published in 2008 with several recommendations. This new version has not yet been translated or culturally adapted for Turkish-speaking populations. The purpose of this study was to translate and cross-culturally adapt the modified CMS and its test protocol, as well as define and measure its reliability and validity. The modified CMS was translated into Turkish, consistent with published methodological guidelines. The measurement properties of the Turkish version of the modified CMS were tested in 30 patients (12 males, 18 females; mean age: 59.5±13.5 years) with a variety of shoulder pathologies. Intraclass correlation coefficients (ICC) were used to estimate test-retest reliability. Construct validity was analyzed with the Turkish version of the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form and Short-Form Health Survey (SF-12). No difficulties were found in the translation process. The Turkish version of the modified CMS showed excellent test-retest reliability (ICC=0.86). The correlation coefficients between the Turkish version of the modified CMS and the ASES, SF-12-physical component score, and SF-12 mental component scores were found to be 0.48, 0.35, and 0.05, respectively. No floor or ceiling effects were found. The translation and cultural adaptation of the modified CMS and its standardized test protocol into Turkish were successful. The Turkish version of the modified CMS has sufficient reliability and validity to measure a variety of shoulder disorders for Turkish-speaking individuals.

Occurrence of severe gastroenteritis in pups after canine parvovirus vaccine administration: a clinical and laboratory diagnostic dilemma.

PubMed

Decaro, Nicola; Desario, Costantina; Elia, Gabriella; Campolo, Marco; Lorusso, Alessio; Mari, Viviana; Martella, Vito; Buonavoglia, Canio

2007-01-26

A total of 29 faecal samples collected from dogs with diarrhoea following canine parvovirus (CPV) vaccination were tested by minor groove binder (MGB) probe assays for discrimination between CPV vaccine and field strains and by diagnostic tests for detection of other canine pathogens. Fifteen samples tested positive only for CPV field strains; however, both vaccine and field strains were detected in three samples. Eleven samples were found to contain only the vaccine strain, although eight of them tested positive for other pathogens of dogs. Only three samples were found to contain the vaccine strain without evidence of canine pathogens. The present study confirms that most cases of parvovirus-like disease occurring shortly after vaccination are related to infection with field strains of canine parvovirus type 2 (CPV-2) rather than to reversion to virulence of the modified live virus contained in the vaccine.

Cystic Fibrosis: A Review of Associated Phenotypes, Use of Molecular Diagnostic Approaches, Genetic Characteristics, Progress, and Dilemmas.

PubMed

Brennan, Marie-Luise; Schrijver, Iris

2016-01-01

Cystic fibrosis (CF) is an autosomal recessive disease with significant associated morbidity and mortality. It is now appreciated that the broad phenotypic CF spectrum is not explained by obvious genotype-phenotype correlations, suggesting that CF transmembrane conductance regulator (CFTR)-related disease may occur because of multiple additive effects. These contributing effects include complex CFTR alleles, modifier genes, mutations in alternative genes that produce CF-like phenotypes, epigenetic factors, and environmental influences. Most patients in the United States are now diagnosed through newborn screening and use of molecular testing methods. We review the molecular testing approaches and laboratory guidelines for carrier screening, prenatal testing, newborn screening, and clinical diagnostic testing, as well as recent developments in CF treatment, and reasons for the lack of a molecular diagnosis in some patients. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Gender Difference of Gastric Emptying in Healthy Volunteers and Patients with Functional Dyspepsia.

PubMed

Mori, Hideki; Suzuki, Hidekazu; Matsuzaki, Juntaro; Taniguchi, Kanami; Shimizu, Toshiyuki; Yamane, Tsuyoshi; Masaoka, Tatsuhiro; Kanai, Takanori

2017-01-01

Delayed gastric emptying is one of the reasons why functional dyspepsia (FD) occurs. The 13C-acetate breath test is widely used to evaluate gastric emptying. Nevertheless, the standard value of 13C-acetate breath test has not taken into account the gender difference of gastric emptying among healthy individuals. The main aim of this study was to readjust the standard value of 13C-acetate breath test in the light of gender differences. In addition, we clarified the prevalence and clinical characteristics of delayed gastric emptying in patients with FD using the modified standard values of 13C-acetate breath test. Fifty-two healthy individuals and 126 patients with patients with FD were enrolled. Gastric emptying was evaluated by the 13C-acetate breath test. The cut-off points of Tmax for the diagnosis of delayed gastric emptying were determined on the basis of results from healthy individuals making a distinction of genders. Gastroesophageal reflux symptoms, dyspeptic symptoms, scores of anxiety and depression, age, body mass index (BMI), smoking and alcohol consumption were compared between the delayed gastric emptying group and the non-delayed gastric emptying group. Since gastric emptying was delayed in healthy women compared with that in healthy men (Tmax, 53.6 ± 19.3 vs. 42.7 ± 16.9 min, p = 0.04), we set the cut-off points of Tmax at 60 min in men and at 75 min in women. In patients with FD, the prevalence of delayed gastric emptying was not different between men and women with the modified standard values of 13C-acetate breath test. (31.0 vs. 27.4%, p = 0.68). BMI was lower in the delayed gastric emptying group than in the non-delayed group among the male patients. Reflux symptoms were more severe in delayed gastric emptying group than in the non-delayed group among the female patients. The standard values of 13C-acetate breath test should be modified bearing the gender difference in mind. It provides us more appropriate information to understand the mechanisms of FD. © 2016 S. Karger AG, Basel.

External Validation and Evaluation of Reliability and Validity of the Modified Seoul National University Renal Stone Complexity Scoring System to Predict Stone-Free Status After Retrograde Intrarenal Surgery.

PubMed

Park, Juhyun; Kang, Minyong; Jeong, Chang Wook; Oh, Sohee; Lee, Jeong Woo; Lee, Seung Bae; Son, Hwancheol; Jeong, Hyeon; Cho, Sung Yong

2015-08-01

The modified Seoul National University Renal Stone Complexity scoring system (S-ReSC-R) for retrograde intrarenal surgery (RIRS) was developed as a tool to predict stone-free rate (SFR) after RIRS. We externally validated the S-ReSC-R. We retrospectively reviewed 159 patients who underwent RIRS. The S-ReSC-R was assigned from 1 to 12 according to the location and number of sites involved. The stone-free status was defined as no evidence of a stone or with clinically insignificant residual fragment stones less than 2 mm. Interobserver and test-retest reliabilities were evaluated. Statistical performance of the prediction model was assessed by its predictive accuracy, predictive probability, and clinical usefulness. Overall SFR was 73.0%. The SFRs were 86.7%, 70.2%, and 48.6% in low-score (1-2), intermediate-score (3-4), and high-score (5-12) groups, respectively (p<0.001). External validation of S-ReSC-R revealed an area under the curve (AUC) of 0.731 (95% CI 0.650-0.813). The AUC of the three-titered S-ReSC-R was 0.701 (95% CI 0.609-0.794). The calibration plot showed that the predicted probability of SFR had a concordance comparable to that of observed frequency. The Hosmer-Lemeshow goodness of fit test revealed a p-value of 0.01 for the S-ReSC-R and 0.90 for the three-titered S-ReSC-R. Interobserver and test-retest reliabilities revealed an almost perfect level of agreement. The present study proved the predictive value of S-ReSC-R to predict SFR following RIRS in an independent cohort. Interobserver and test-retest reliabilities confirmed that S-ReSC-R was reliable and valid.

Modifying the test of understanding graphs in kinematics

NASA Astrophysics Data System (ADS)

Zavala, Genaro; Tejeda, Santa; Barniol, Pablo; Beichner, Robert J.

2017-12-01

In this article, we present several modifications to the Test of Understanding Graphs in Kinematics. The most significant changes are (i) the addition and removal of items to achieve parallelism in the objectives (dimensions) of the test, thus allowing comparisons of students' performance that were not possible with the original version, and (ii) changes to the distractors of some of the original items that represent the most frequent alternative conceptions. The final modified version (after an iterative process involving four administrations of test variations over two years) was administered to 471 students of an introductory university physics course at a large private university in Mexico. When analyzing the final modified version of the test it was found that the added items satisfied the statistical tests of difficulty, discriminatory power, and reliability; also, that the great majority of the modified distractors were effective in terms of their frequency selection and discriminatory power; and, that the final modified version of the test satisfied the reliability and discriminatory power criteria as well as the original test. Here, we also show the use of the new version of the test, presenting a new analysis of students' understanding not possible to do before with the original version of the test, specifically regarding the objectives and items that in the new version meet parallelisms. Finally, in the PhysPort project (physport.org), we present the final modified version of the test. It can be used by teachers and researchers to assess students' understanding of graphs in kinematics, as well as their learning about them.

Effectiveness of Plaque Control with Novel Pediatric Oral Hygiene Need Station (Modified Oral Irrigation Device) as Compared with Manual Brushing and Flossing: Randomized Controlled Pilot Trial.

PubMed

Murthy, Prashanth Sadashiva; Shaik, Naseemoon; Deshmukh, Seema; Girish, M S

2018-01-01

Establishing good hygiene habits are valuable for present and future oral health. Below 6 years, tooth brushing should be performed by parents, as increasing dexterity and cognition may permit supervised brushing until the child is capable of independent brushing. The aim of the present study was to evaluate the effectiveness of modified oral irrigation device in children in terms of plaque control and to compare the effectiveness of plaque control with manual brushing with the modified oral irrigation device in children. A randomized clinical trial was performed on 12 subjects who were allocated to the two study groups. After obtaining the consent, the control group was instructed tooth brushing with regular pediatric commercially available toothbrush and the intervention group with modified oral irrigation device. Plaque scores in both groups were assessed pre- and post-brushing using modified navy plaque index. The data were subjected to Descriptive statistics and Paired t -test using SPSS version 22. Intragroup comparison of mean difference of plaque score in control group and intervention group pre- and post-brushing was statistically significant. Intergroup comparison of manual brushing group with modified oral irrigation group shows P < 0.05 was statistically significant. Within the limitation of the present study, it has been found novel pediatric oral hygiene need Station is more effective than manual brushing since it combined the effect of brushing, flossing (water floss), and rinsing in children simultaneously and at the same time did not demand any special motor skill.

Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens

PubMed Central

Vojdani, Aristo

2009-01-01

Background Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. Methods We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE) such as AGE-human serum albumin and AGE-hemoglobin. Results Compared to raw food antigens, IgE antibodies showed a 3–8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. Conclusion We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity. PMID:19435515

Best practice in the use of natalizumab in multiple sclerosis.

PubMed

Fernández, Oscar

2013-03-01

Natalizumab is approved for the treatment of patients with relapsing-remitting multiple sclerosis who have failed first-line treatment with traditional disease-modifying therapies or who have highly active disease. The drug has proved highly effective, both in a clinical trial setting and in clinical practice, with marked reductions in the rate of clinical relapses and slowed disease progression. These clinical outcomes are mirrored by a marked reduction in disease activity as evidenced by magnetic resonance imaging of the brain. However, natalizumab treatment has been associated with a risk of progressive multifocal leukoencephalopathy (PML), a potentially fatal condition caused by JC virus (JCV) activation. When this condition was detected in a clinical trial shortly after approval, the drug was immediately and voluntarily withdrawn from the market. As a condition of its reinstatement, stringent pharmacovigilance measures and a risk management plan were enforced. The recent availability of a two-step enzyme-linked immunosorbent assay (ELISA) test for the presence of anti-JCV antibodies (free testing is available in a central laboratory for registered centers), along with an ever-improving understanding of other risk factors such as prior immunosuppressant use and duration of treatment, allow an increasingly refined stratification of the risk of PML. This improved stratification of risk can help guide decisions about treatment. This review will also deal with other topics of relevance to clinical practice such as the development of antinatalizumab antibodies and their negative implications in terms of hypersensitivity reactions and loss of efficacy, withdrawal of treatment, and compassionate pediatric use.

Translation, adaptation and validation of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) for an Arab population: the Sfax modified WOMAC.

PubMed

Guermazi, Mohammad; Poiraudeau, Serge; Yahia, Monem; Mezganni, Monia; Fermanian, Jacques; Habib Elleuch, M; Revel, Michel

2004-06-01

To translate into Arabic and validate the Western Ontario and McMaster Universities (WOMAC) index. Arabic translation was obtained with use of the forward and backward translation method. Adaptations were made after a pilot study. Patients with symptomatic knee OA fulfilling the revised criteria of the American College of Rheumatology were included. Impairment outcome measures (pain as measured on a visual analog scale, the maximum distance walked, Kellgren's radiological score), Lequesne index score and Beck depression scale score were recorded. Each item was analyzed. Test-retest reliability was assessed with use of the intra-class correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated with use of Spearman's rank correlation coefficient, and a factor analysis was performed. One hundred and three patients were included in the study. Eight questions of the WOMAC physical function subscale (PF) had insufficient psychometric properties and were excluded. Although test-retest reliability of the questionnaire was good (0.84, 0.84, and 0.92 for pain, stiffness, and modified PF subscales respectively), construct validity could not be demonstrated. Factor analysis of the modified form of the WOMAC extracted four factors, which differed from the a priori triple stratification. However, factor analysis of the modified PF subscales extracted two factors, which accounted for 68.4% of the total variance and could be clinically characterized (disability during activities requiring knee flexion within the first 90 degrees and activities requiring knee flexion over more than 90 degrees ). We translated and adapted the WOMAC index into Arabic to suit Tunisian people. The translated questionnaire is reliable but not valid in its original form. We propose the use of a modified version of PF subscale of the WOMAC, although the psychometric properties of this instrument must be examined in a larger population.

Reliability and validity of an audio signal modified shuttle walk test.

PubMed

Singla, Rupak; Rai, Richa; Faye, Abhishek Anil; Jain, Anil Kumar; Chowdhury, Ranadip; Bandyopadhyay, Debdutta

2017-01-01

The audio signal in the conventionally accepted protocol of shuttle walk test (SWT) is not well-understood by the patients and modification of the audio signal may improve the performance of the test. The aim of this study is to study the validity and reliability of an audio signal modified SWT, called the Singla-Richa modified SWT (SWTSR), in healthy normal adults. In SWTSR, the audio signal was modified with the addition of reverse counting to it. A total of 54 healthy normal adults underwent conventional SWT (CSWT) at one instance and two times SWTSRon the same day. The validity was assessed by comparing outcomes of the SWTSRto outcomes of CSWT using the Pearson correlation coefficient and Bland-Altman plot. Test-retest reliability of SWTSRwas assessed using the intraclass correlation coefficient (ICC). The acceptability of the modified test in comparison to the conventional test was assessed using Likert scale. The distance walked (mean ± standard deviation) in the CSWT and SWTSRtest was 853.33 ± 217.33 m and 857.22 ± 219.56 m, respectively (Pearson correlation coefficient - 0.98; P < 0.001) indicating SWTSRto be a valid test. The SWTSRwas found to be a reliable test with ICC of 0.98 (95% confidence interval: 0.97-0.99). The acceptability of SWTSRwas significantly higher than CSWT. The SWTSRwith modified audio signal with reverse counting is a reliable as well as a valid test when compared with CSWT in healthy normal adults. It better understood by subjects compared to CSWT.

Phenotypic detection of broad-spectrum beta-lactamases in microbiological practice.

PubMed

Htoutou Sedlakova, Miroslava; Hanulik, Vojtech; Chroma, Magdalena; Hricova, Kristyna; Kolar, Milan; Latal, Tomas; Schaumann, Reiner; Rodloff, Arne C

2011-05-01

Enterobacteriaceae producing ESBL and AmpC enzymes can be associated with failure of antibiotic therapy and related morbidity and mortality. Their routine detection in microbiology laboratories is still a problem. The aim of this study was to compare the sensitivity of selected phenotypic methods. A total of 106 strains of the Enterobacteriaceae family were tested, in which molecular biology methods confirmed the presence of genes encoding ESBL or AmpC. In ESBL-positive strains, the sensitivity of the ESBL Etest (AB Biodisk) and a modified double-disk synergy test (DDST) were evaluated. AmpC strains were tested by a modified AmpC disk method using 3-aminophenylboronic acid. For simultaneous detection of ESBL and AmpC, the microdilution method with a modified set of antimicrobial agents was used. The sensitivity of the ESBL Etest was 95%; the modified DDST yielded 100% sensitivity for ESBL producers and the AmpC test correctly detected 95% of AmpC-positive strains. The sensitivity of the modified microdilution method was 87% and 95% for ESBL and AmpC beta lactamases, respectively. The detection of ESBL and AmpC beta lactamases should be based on specific phenotypic methods such as the modified DDST, ESBL Etest, AmpC disk test and the modified microdilution method.

Phenotypic detection of broad-spectrum beta-lactamases in microbiological practice

PubMed Central

Sedlakova, Miroslava Htoutou; Hanulik, Vojtech; Chroma, Magdalena; Hricova, Kristyna; Kolar, Milan; Latal, Tomas; Schaumann, Reiner; Rodloff, Arne C.

2011-01-01

Summary Background Enterobacteriaceae producing ESBL and AmpC enzymes can be associated with failure of antibiotic therapy and related morbidity and mortality. Their routine detection in microbiology laboratories is still a problem. The aim of this study was to compare the sensitivity of selected phenotypic methods. Material/Methods A total of 106 strains of the Enterobacteriaceae family were tested, in which molecular biology methods confirmed the presence of genes encoding ESBL or AmpC. In ESBL-positive strains, the sensitivity of the ESBL Etest (AB Biodisk) and a modified double-disk synergy test (DDST) were evaluated. AmpC strains were tested by a modified AmpC disk method using 3-aminophenylboronic acid. For simultaneous detection of ESBL and AmpC, the microdilution method with a modified set of antimicrobial agents was used. Results The sensitivity of the ESBL Etest was 95%; the modified DDST yielded 100% sensitivity for ESBL producers and the AmpC test correctly detected 95% of AmpC-positive strains. The sensitivity of the modified microdilution method was 87% and 95% for ESBL and AmpC beta lactamases, respectively. Conclusions The detection of ESBL and AmpC beta lactamases should be based on specific phenotypic methods such as the modified DDST, ESBL Etest, AmpC disk test and the modified microdilution method. PMID:21525803

The integrity of bonded amalgam restorations: a clinical evaluation after five years.

PubMed

Mach, Zbynek; Regent, Jan; Staninec, Michal; Mrklas, Lubor; Setcos, James C

2002-04-01

Bonded amalgam restorations have been studied extensively in vitro, but few long term clinical studies exist. The authors examined the clinical performance of bonded amalgam restorations after five years of clinical service an compared it with that of nonbonded amalgam restorations. The authors placed 75 bonded and 62 nonbonded amalgam restorations in patients needing restorations. Most of the restorations were placed in conventional preparations; six bonded restorations were placed in nonretentive cavities. They were evaluated after a five-year period of clinical service by two trained dentists using a mirror and explorer and following modified U.S. Public Health Service criteria. Statistical analysis (via Fisher exact test) showed no significant differences between the two techniques when conventional preparations were used. Restorations in nonretentive preparations were successful during this period. Bonded and nonbonded amalgam restorations yielded similar results in conventional preparations after five years of clinical service. Bonded amalgam restorations were clinically successful in a limited number of nonretentive preparations over a five-year period. Bonded amalgam restorations can be used successfully in conventional preparations and possibly in nonretentive preparations as well, and can be expected to last at least five years.

Surprising Alteration of Antibacterial Activity of 5″-Modified Neomycin against Resistant Bacteria

PubMed Central

Zhang, Jianjun; Chiang, Fang-I; Wu, Long; Czyryca, Przemyslaw Greg; Li, Ding; Chang, Cheng-Wei Tom

2009-01-01

A facile synthetic protocol for the production of neomycin B derivatives with various modifications at the 5″ position has been developed. Structural activity relationship (SAR) against aminoglycoside resistant bacteria equipped with various aminoglycoside-modifying enzymes (AME's) was investigated. Enzymatic and molecular modeling studies reveal that the superb substrate promiscuity of AME's allows the resistant bacteria to cope with diverse structural modifications despite the observation that several derivatives show enhanced antibacterial activity than the parent neomycin. Surprisingly, when testing synthetic neomycin derivatives against other human pathogens, two leads exhibit prominent activity against both Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) that are known to exert high level of resistance against clinically used aminoglycosides. These findings can be extremely useful in developing new aminoglycoside antibiotics against resistant bacteria. Our result also suggests that new biological and antimicrobial activities can be obtained by chemical modifications of old drugs. PMID:19012394

Clinical Characteristics of Proper Robot-Assisted Gait Training Group in Non-ambulatory Subacute Stroke Patients

PubMed Central

Kim, Soo Jeong; Lee, Hye Jin; Hwang, Seung Won; Pyo, Hannah; Yang, Sung Phil; Lim, Mun-Hee; Park, Gyu Lee

2016-01-01

Objective To identify the clinical characteristics of proper robot-assisted gait training group using exoskeletal locomotor devices in non-ambulatory subacute stroke patients. Methods A total of 38 stroke patients were enrolled in a 4-week robotic training protocol (2 sessions/day, 5 times/week). All subjects were evaluated for their general characteristics, Functional Ambulatory Classification (FAC), Fugl-Meyer Scale (FMS), Berg Balance Scale (BBS), Modified Rankin Scale (MRS), Modified Barthel Index (MBI), and Mini-Mental Status Examination (MMSE) at 0, 2, and 4 weeks. Statistical analysis were performed to determine significant clinical characteristics for improvement of gait function after robot-assisted gait training. Results Paired t-test showed that all functional parameters except MMSE were improved significantly (p<0.05). The duration of disease and baseline BBS score were significantly (p<0.05) correlated with FAC score in multiple regression models. Receiver operating characteristic (ROC) curve showed that a baseline BBS score of '9' was a cutoff value (AUC, 0.966; sensitivity, 91%–100%; specificity, 85%). By repeated-measures ANOVA, the differences in improved walking ability according to time were significant between group of patients who had baseline BBS score of '9' and those who did not have baseline BBS score of '9' Conclusion Our results showed that a baseline BBS score above '9' and a short duration of disease were highly correlated with improved walking ability after robot-assisted gait training. Therefore, baseline BBS and duration of disease should be considered clinically for gaining walking ability in robot-assisted training group. PMID:27152266

Modification of the Peabody Picture Vocabulary Test.

ERIC Educational Resources Information Center

Faizunisa, Ali; Costello, Joan

This study reports an attempt to improve the administration of the Peabody Picture Vocabulary Test (PPVT) by identifying and modifying aspects of the test which adversely affect disadvantaged preschoolers' performance. The resultant test was called the Modified Peabody Picture Vocabulary Test (M-PPVT). Two samples from the same lower class…

Interlaboratory Study of Quality Control Isolates for a Broth Microdilution Method (Modified CLSI M38-A) for Testing Susceptibilities of Dermatophytes to Antifungals▿

PubMed Central

Ghannoum, M. A.; Arthington-Skaggs, B.; Chaturvedi, V.; Espinel-Ingroff, A.; Pfaller, M. A.; Rennie, R.; Rinaldi, M. G.; Walsh, T. J.

2006-01-01

The Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards, or NCCLS) M38-A standard for the susceptibility testing of filamentous fungi does not specifically address the testing of dermatophytes. In 2003, a multicenter study investigated the reproducibility of the microdilution method developed at the Center for Medical Mycology, Cleveland, Ohio, for testing the susceptibility of dermatophytes. Data from that study supported the introduction of this method for testing dermatophytes in the future version of the CLSI M38-A standard. In order for the method to be accepted by CLSI, appropriate quality control isolates needed to be identified. To that end, an interlaboratory study, involving the original six laboratories plus two additional sites, was conducted to evaluate potential candidates for quality control isolates. These candidate strains included five Trichophyton rubrum strains known to have elevated MICs to terbinafine and five Trichophyton mentagrophytes strains. Antifungal agents tested included ciclopirox, fluconazole, griseofulvin, itraconazole, posaconazole, terbinafine, and voriconazole. Based on the data generated, two quality control isolates, one T. rubrum isolate and one T. mentagrophytes isolate, were identified and submitted to the American Type Culture Collection (ATCC) for inclusion as reference strains. Ranges encompassing 95.2 to 97.9% of all data points for all seven drugs were established. PMID:17050812

Clinical efficacy of moxifloxacin versus comparator therapies for community-acquired pneumonia caused by Legionella spp.

PubMed

Garau, J; Fritsch, A; Arvis, P; Read, R C

2010-08-01

The aim of this study was to compare outcomes for patients with community-acquired pneumonia (CAP) caused by Legionella spp. following treatment with moxifloxacin or a range of comparator antimicrobial agents. Data were pooled from four sequential I.V./P.O. trials of moxifloxacin in the treatment of CAP. Comparators were ceftriaxone +/- erythromycin, amoxicillin/clavulanate +/- clarithromycin, trovafloxacin, levofloxacin, or ceftriaxone + levofloxacin. Legionella infection was diagnosed by culture, urine antigen testing and/or serology. Clinical success rates for the efficacy-valid (per protocol) populations were recorded at the test-of-cure visit (5-30 days post-therapy). Severity of CAP was determined using the modified American Thoracic Society criteria.Of 1786 efficacy-valid patients, 33 (1.8%) had documented infection with Legionella spp. (moxifloxacin: n=13; comparator: n=20). Of these, 30 cases were identified by serology and/or urine antigen detection and 3 by respiratory culture. The success rate of moxifloxacin vs. comparator therapy was 92.3% vs. 80.0% for the I.V./P.O. trials.Sequential (I.V./P.O.) moxifloxacin demonstrated clinical efficacy that was at least as good as that of comparator treatments for the treatment of CAP due to Legionella.

Dental enamel defect diagnosis through different technology-based devices.

PubMed

Kobayashi, Tatiana Yuriko; Vitor, Luciana Lourenço Ribeiro; Carrara, Cleide Felício Carvalho; Silva, Thiago Cruvinel; Rios, Daniela; Machado, Maria Aparecida Andrade Moreira; Oliveira, Thais Marchini

2018-06-01

Dental enamel defects (DEDs) are faulty or deficient enamel formations of primary and permanent teeth. Changes during tooth development result in hypoplasia (a quantitative defect) and/or hypomineralisation (a qualitative defect). To compare technology-based diagnostic methods for detecting DEDs. Two-hundred and nine dental surfaces of anterior permanent teeth were selected in patients, 6-11 years of age, with cleft lip with/without cleft palate. First, a conventional clinical examination was conducted according to the modified Developmental Defects of Enamel Index (DDE Index). Dental surfaces were evaluated using an operating microscope and a fluorescence-based device. Interexaminer reproducibility was determined using the kappa test. To compare groups, McNemar's test was used. Cramer's V test was used for comparing the distribution of index codes obtained after classification of all dental surfaces. Cramer's V test revealed statistically significant differences (P < .0001) in the distribution of index codes obtained using the different methods; the coefficients were 0.365 for conventional clinical examination versus fluorescence, 0.961 for conventional clinical examination versus operating microscope and 0.358 for operating microscope versus fluorescence. The sensitivity of the operating microscope and fluorescence method was statistically significant (P = .008 and P < .0001, respectively). Otherwise, the results did not show statistically significant differences in accuracy and specificity for either the operating microscope or the fluorescence methods. This study suggests that the operating microscope performed better than the fluorescence-based device and could be an auxiliary method for the detection of DEDs. © 2017 FDI World Dental Federation.

Rapid identification and validation of novel targeted approaches for Glioblastoma: A combined ex vivo-in vivo pharmaco-omic model.

PubMed

Daher, Ahmad; de Groot, John

2018-01-01

Tumor heterogeneity is a major factor in glioblastoma's poor response to therapy and seemingly inevitable recurrence. Only two glioblastoma drugs have received Food and Drug Administration approval since 1998, highlighting the urgent need for new therapies. Profiling "omics" analyses have helped characterize glioblastoma molecularly and have thus identified multiple molecular targets for precision medicine. These molecular targets have influenced clinical trial design; many "actionable" mutation-focused trials are underway, but because they have not yet led to therapeutic breakthroughs, new strategies for treating glioblastoma, especially those with a pharmacological functional component, remain in high demand. In that regard, high-throughput screening that allows for expedited preclinical drug testing and the use of GBM models that represent tumor heterogeneity more accurately than traditional cancer cell lines is necessary to maximize the successful translation of agents into the clinic. High-throughput screening has been successfully used in the testing, discovery, and validation of potential therapeutics in various cancer models, but it has not been extensively utilized in glioblastoma models. In this report, we describe the basic aspects of high-throughput screening and propose a modified high-throughput screening model in which ex vivo and in vivo drug testing is complemented by post-screening pharmacological, pan-omic analysis to expedite anti-glioma drugs' preclinical testing and develop predictive biomarker datasets that can aid in personalizing glioblastoma therapy and inform clinical trial design. Copyright © 2017 Elsevier Inc. All rights reserved.

Reality of Dental Implant Surface Modification: A Short Literature Review

PubMed Central

Yeo, In-Sung

2014-01-01

Screw-shaped endosseous implants that have a turned surface of commercially pure titanium have a disadvantage of requiring a long time for osseointegration while those implants have shown long-term clinical success in single and multiple restorations. Titanium implant surfaces have been modified in various ways to improve biocompatibility and accelerate osseointegration, which results in a shorter edentulous period for a patient. This article reviewed some important modified titanium surfaces, exploring the in vitro, in vivo and clinical results that numerous comparison studies reported. Several methods are widely used to modify the topography or chemistry of titanium surface, including blasting, acid etching, anodic oxidation, fluoride treatment, and calcium phosphate coating. Such modified surfaces demonstrate faster and stronger osseointegration than the turned commercially pure titanium surface. However, there have been many studies finding no significant differences in in vivo bone responses among the modified surfaces. Considering those in vivo results, physical properties like roughening by sandblasting and acid etching may be major contributors to favorable bone response in biological environments over chemical properties obtained from various modifications including fluoride treatment and calcium phosphate application. Recently, hydrophilic properties added to the roughened surfaces or some osteogenic peptides coated on the surfaces have shown higher biocompatibility and have induced faster osseointegration, compared to the existing modified surfaces. However, the long-term clinical studies about those innovative surfaces are still lacking. PMID:25400716

Disposable L-lactate biosensor based on a screen-printed carbon electrode enhanced by graphene

NASA Astrophysics Data System (ADS)

Tu, Dandan; He, Yu; Rong, Yuanzhen; Wang, You; Li, Guang

2016-04-01

In this work, an amperometric L-lactate biosensor based on a graphene-modified screen-printed carbon electrode (SPCE) was constructed. First, the electrocatalytic performance of the SPCE modified with graphene by a one-step electrodeposition process (OerGO/SPCE) was investigated. The cyclic voltammogram of OerGO/SPCE, which showed a well-defined redox peak, had a smaller peak potential separation than that of SPCE, revealing the improvement in electron transfer speed brought about by modifying with graphene. Next, lactate oxidase and potassium ferricyanide were dropped on the OerGO/SPCE to construct a graphene-modified L-lactate biosensor (LOD/K3[Fe(CN)6]/OerGO/SPCE). The proposed biosensor, with a detection limit of 60 μM, had a high sensitivity (42.42 μA mM-1 cm-2) when working at a low working potential (0.15 V). The linear range was 0.5 mM-15 mM, covering the detecting range of L-lactate in clinical applications. The L-lactate biosensor had a short response time (10 s) and required only 10 μl of the sample. This L-lactate sensor modified with electrodeposited graphene had a larger sensitivity than that based on the bare SPCE. Thus, our low-cost and disposable L-lactate biosensor enhanced by graphene can perform as an attractive electrochemical device that can be manufactured for point-of-care testing (POCT) devices and be employed in POCT applications.

The utility of the AusEd driving simulator in the clinical assessment of driver fatigue.

PubMed

Desai, Anup V; Wilsmore, Brad; Bartlett, Delwyn J; Unger, Gunnar; Constable, Ben; Joffe, David; Grunstein, Ronald R

2007-08-01

Several driving simulators have been developed which range in complexity from PC based driving tasks to advanced "real world" simulators. The AusEd driving simulator is a PC based task, which was designed to be conducive to and test for driver fatigue. This paper describes the AusEd driving simulator in detail, including the technical requirements, hardware, screen and file outputs, and analysis software. Some aspects of the test are standardized, while others can be modified to suit the experimental situation. The AusEd driving simulator is sensitive to performance decrement from driver fatigue in the laboratory setting, potentially making it useful as a laboratory or office based test for driver fatigue risk management. However, more research is still needed to correlate laboratory based simulator performance with real world driving performance and outcomes.

Japanese Clinical Guidelines for Endoscopic Treatment of Pancreatolithiasis.

PubMed

Inui, Kazuo; Igarashi, Yoshinori; Irisawa, Atsushi; Ohara, Hirotaka; Tazuma, Susumu; Hirooka, Yoshiki; Fujita, Naotaka; Miyakawa, Hiroyuki; Sata, Naohiro; Shimosegawa, Tooru; Tanaka, Masao; Shiratori, Keiko; Sugiyama, Masanori; Takeyama, Yoshifumi

2015-10-01

In addition to surgery, procedures for patients with pancreatolithiasis are developing; therefore, establishing practical guidelines for the management of pancreatolithiasis is required. Three committees (the professional committee for asking clinical questions (CQs) and statements by Japanese endoscopists, the expert panel committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Eight endoscopists and a surgeon for pancreatolithiasis made the CQs and statements from a total of 694 reports of published literature by PubMed search (from 1983 to 2012). The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. The professional committee made 3, 7, and 10 CQs and statements for the concept and pathogenesis, diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach. After evaluation by the moderators, the Japanese clinical guidelines for pancreatolithiasis were established. Further discussions and studies for international guidelines are needed.

Detection and characterization of multidrug-resistant enterobacteria bearing aminoglycoside-modifying gene in a university hospital at Rio de Janeiro, Brazil, along three decades.

PubMed

Dias-Gonçalves, Verônica; Bohrer-Lengruber, Françoise; Oliveira-Fonseca, Bianca; Santos-Pereira, Renata Meirelles; Barbosa de Melo, Luis Dione; Gazos-Lopes, Ulisses; Ribeiro-Bello, Alexandre; Adler-Pereira, José Augusto

2015-01-01

Multidrug-resistant Enterobacteriaceae, particularly those resistant to gentamicin, have become one of the most important causes of nosocomial infections. We sought to investigate the presence of genes conferring resistance to aminoglycosides, specially to gentamicin, in Klebsiella pneumoniae and Escherichia coli multidrug-resistant strains isolated from different clinical materials among patients hospitalized in a university hospital in Rio de Janeiro, Brazil. Ten colonization strains and 20 infection strains were evaluated during three decades (1980 to 2010) using selective media containing 8 µg/ml of gentamicin. Thirty strains were tested for antimicrobial susceptibility. Twenty two strains were subjected to plasmid DNA extraction and 12 to hybridization assays using as probe a 1.9 kb plasmid DNA fragment from one of the K. pneumoniae strains isolated from faecal samples. This fragment was sequenced and assigned to the GQ422439 GenBank record. PCR was also performed using oligonucleotides designed for aminoglycoside-modifying enzymes. An accC2 acetylase, besides transposons and insertion sequences, were evidenced. Twenty-four (80%) of the isolates were positive for the aacC2 gene in agreement with antibiotic susceptibility testing profiles, indicating the persistent presence of this gene throughout the three decades. We detected high molecular weight plasmids in 54,5% of the strains. Of the tested strains, 91% showed positive signal in the hybridization assays. A gene codifying for one specific aminoglycoside-modifying enzyme was detected all throughout the three decades. Our data back the adoption of preventive measures, such as a more conscious use of antimicrobial agents in hospital environments, which can contribute to control the dissemination of microorganisms harboring resistance gene plasmids.

Paroxetine-induced reduction of sexual incentive motivation in female rats is not modified by 5-HT1B or 5-HT2C antagonists.

PubMed

Kaspersen, Helge; Agmo, Anders

2012-03-01

Clinical data show that paroxetine causes sexual dysfunction in a substantial proportion of women taking this compound. This work was conducted to determine whether chronic paroxetine reduces sexual incentive motivation in female rats and whether this compound can modify any aspect of paced mating. The role of the 5-HT(1B) and 5-HT(2C) receptors in any potential effects was also evaluated. Ovariectomized female rats were implanted with osmotic minipumps releasing 10 mg/kg per day of paroxetine or vehicle for 28 days. Tests for sexual incentive motivation and paced mating were performed just before implantation and at regular intervals thereafter. The females were primed with estradiol benzoate (25 μg/rat) and progesterone (1 mg/rat) before each of these tests. On days 25-27 of treatment, the females were injected with the 5-HT(1B) antagonist GR125,743 (5 mg/kg), the 5-HT(2C) antagonist SB206,553 (5 mg/kg) and vehicle in counterbalanced order. Preinjection time was 30 min. Paroxetine reduced sexual incentive motivation on day 20 of treatment without affecting any aspect of paced mating. None of the antagonists modified the inhibitory effect of paroxetine on sexual incentive motivation. In the group chronically treated with vehicle, SB206,553 reduced proceptive behaviors in the paced mating test. No other effect was obtained. The effects of paroxetine seen in female rats are similar to those observed in women, suggesting that disturbances of sexual incentive motivation in rats are predictive of sexual dysfunction in women. The 5-HT(1B) and 5-HT(2C) receptors do not seem to be of any importance for paroxetine's inhibitory effect.

Resource utilization after introduction of a standardized clinical assessment and management plan.

PubMed

Friedman, Kevin G; Rathod, Rahul H; Farias, Michael; Graham, Dionne; Powell, Andrew J; Fulton, David R; Newburger, Jane W; Colan, Steven D; Jenkins, Kathy J; Lock, James E

2010-01-01

A Standardized Clinical Assessment and Management Plan (SCAMP) is a novel quality improvement initiative that standardizes the assessment and management of all patients who carry a predefined diagnosis. Based on periodic review of systemically collected data the SCAMP is designed to be modified to improve its own algorithm. One of the objectives of a SCAMP is to identify and reduce resource utilization and patient care costs. We retrospectively reviewed resource utilization in the first 93 arterial switch operation (ASO) SCAMP patients and 186 age-matched control ASO patients. We compared diagnostic and laboratory testing obtained at the initial SCAMP clinic visit and control patient visits. To evaluate the effect of the SCAMP over time, the number of clinic visits per patient year and echocardiograms per patient year in historical control ASO patients were compared to the projected rates for ASO SCAMP participants. Cardiac magnetic resonance imaging (MRI), stress echocardiogram, and lipid profile utilization were higher in the initial SCAMP clinic visit group than in age-matched control patients. Total echocardiogram and lung scan usage were similar. Chest X-ray and exercise stress testing were obtained less in SCAMP patients. ASO SCAMP patients are projected to have 0.5 clinic visits and 0.5 echocardiograms per year. Historical control patients had more clinic visits (1.2 vs. 0.5 visits/patient year, P<.01) and a higher echocardiogram rate (0.92 vs. 0.5 echocardiograms/patient year, P<.01) Implementation of a SCAMP may initially lead to increased resource utilization, but over time resource utilization is projected to decrease.

Toxicity of fluoride to aquatic species and evaluation of toxicity modifying factors.

PubMed

Pearcy, Krysta; Elphick, James; Burnett-Seidel, Charlene

2015-07-01

The present study was performed to investigate the toxicity of fluoride to a variety of freshwater aquatic organisms and to establish whether water quality variables contribute substantively to modifying its toxicity. Water hardness, chloride, and alkalinity were tested as possible toxicity modifying factors for fluoride using acute toxicity tests with Hyalella azteca and Oncorhynchus mykiss. Chloride appeared to be the major toxicity modifying factor for fluoride in these acute toxicity tests. The chronic toxicity of fluoride was evaluated with a variety of species, including 3 fish (Pimephales promelas, O. mykiss, and Salvelinus namaycush), 3 invertebrates (Ceriodaphnia dubia, H. azteca, and Chironomus dilutus), 1 plant (Lemna minor), and 1 alga (Pseudokirchneriella subcapitata). Hyalella azteca was the most sensitive species overall, and O. mykiss was the most sensitive species of fish. The role of chloride as a toxicity modifying factor was inconsistent between species in the chronic toxicity tests. © 2015 SETAC.

Evaluation of different phenotypic tests for detection of metallo-β-lactamases in imipenem-resistant Pseudomonas aeruginosa.

PubMed

Sachdeva, Rohit; Sharma, Babita; Sharma, Rajni

2017-01-01

Pseudomonas aeruginosa causes a wide spectrum of infections including bacteremia, pneumonia, urinary tract infection, etc., Metallo-beta-lactamase (MBL) producing P. aeruginosa is an emerging threat and cause of concern as they have emerged as one of the most feared resistance mechanisms. This study was designed to know the prevalence of MBL production in P. aeruginosa and to evaluate the four phenotypic tests for detection of MBL production in imipenem-resistant clinical isolates of P. aeruginosa . Totally, 800 isolates of P. aeruginosa isolated from various clinical samples were evaluated for carbapenem resistance and MBL production. All imipenem-resistant strains were tested for carabapenemase production by modified Hodge test. Screening for MBL production was done by double-disc synergy test and combined disc test (CDT). Confirmation of MBL production was done by the E-test (Ab BioDisk, Solna, Sweden). Out of the 800 isolates of P. aeruginosa , 250 isolates were found resistant to imipenem. Based on the results of E-test, 147 (18.37%) isolates of P. aeruginosa were positive for MBL production. The CDT has the highest sensitivity and specificity for the detection of MBL production as compared to other tests. The results of this study are indicative that MBL production is an important mechanism of carbapenem resistance among P. aeruginosa . Use of simple screening test like CDT will be crucial step toward large-scale monitoring of these emerging resistant determinants. Phenotypic test for MBL production has to be standardized, and all the isolates should be routinely screened for MBL production.

Evaluation of different phenotypic tests for detection of metallo-β-lactamases in imipenem-resistant Pseudomonas aeruginosa

PubMed Central

Sachdeva, Rohit; Sharma, Babita; Sharma, Rajni

2017-01-01

PURPOSE: Pseudomonas aeruginosa causes a wide spectrum of infections including bacteremia, pneumonia, urinary tract infection, etc., Metallo-beta-lactamase (MBL) producing P. aeruginosa is an emerging threat and cause of concern as they have emerged as one of the most feared resistance mechanisms. This study was designed to know the prevalence of MBL production in P. aeruginosa and to evaluate the four phenotypic tests for detection of MBL production in imipenem-resistant clinical isolates of P. aeruginosa. METHODS: Totally, 800 isolates of P. aeruginosa isolated from various clinical samples were evaluated for carbapenem resistance and MBL production. All imipenem-resistant strains were tested for carabapenemase production by modified Hodge test. Screening for MBL production was done by double-disc synergy test and combined disc test (CDT). Confirmation of MBL production was done by the E-test (Ab BioDisk, Solna, Sweden). RESULTS: Out of the 800 isolates of P. aeruginosa, 250 isolates were found resistant to imipenem. Based on the results of E-test, 147 (18.37%) isolates of P. aeruginosa were positive for MBL production. The CDT has the highest sensitivity and specificity for the detection of MBL production as compared to other tests. CONCLUSION: The results of this study are indicative that MBL production is an important mechanism of carbapenem resistance among P. aeruginosa. Use of simple screening test like CDT will be crucial step toward large-scale monitoring of these emerging resistant determinants. Phenotypic test for MBL production has to be standardized, and all the isolates should be routinely screened for MBL production. PMID:28966485

Clinical outcomes and repair integrity after arthroscopic full-thickness rotator cuff repair: suture-bridge versus double-row modified Mason-Allen technique.

PubMed

Lee, Kwang Won; Yang, Dae Suk; Lee, Gyu Sang; Ma, Chang Hyun; Choy, Won Sik

2018-05-23

This retrospective study compared the clinical and radiologic outcomes of patients who underwent arthroscopic rotator cuff repairs by the suture-bridge and double-row modified Mason-Allen techniques. From January 2012 to May 2013, 76 consecutive cases of full-thickness rotator cuff tear, 1 to 4 cm in the sagittal plane, for which arthroscopic rotator cuff repair was performed, were included. The suture-bridge technique was used in 37 consecutive shoulders; and the double-row modified Mason-Allen technique, in 39 consecutive shoulders. Clinical outcomes at a minimum of 2 years (mean, 35.7 months) were evaluated postoperatively using the visual analog scale; University of California, Los Angeles Shoulder Scale; American Shoulder and Elbow Surgeons Subjective Shoulder Scale; and Constant score. Postoperative cuff integrity was evaluated at a mean of 17.7 months by magnetic resonance imaging. At the final follow-up, the clinical outcomes improved in both groups (all P < .001) but with no significant differences between the 2 groups (all P > .05). The retear rate was 18.9% in the shoulders subjected to suture-bridge repair and 12.8% in the double-row modified Mason-Allen group; the difference was not significant (P = .361). Despite the presence of fewer suture anchors, the patients who underwent double-row modified Mason-Allen repair had comparable shoulder functional outcomes and a comparable retear rate with those who underwent suture-bridge repair. Therefore, the double-row modified Mason-Allen repair technique can be considered an effective treatment for patients with medium- to large-sized full-thickness rotator cuff tears. Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

THE NAVICULAR POSITION TEST – A RELIABLE MEASURE OF THE NAVICULAR BONE POSITION DURING REST AND LOADING

PubMed Central

Spörndly-Nees, Søren; Dåsberg, Brian; Nielsen, Rasmus Oestergaard; Boesen, Morten Ilum

2011-01-01

Background: Lower limb injuries are a large problem in athletes. However, there is a paucity of knowledge on the relationship between alignment of the medial longitudinal arch (MLA) of the foot and development of such injuries. A reliable and valid test to quantify foot type is needed to be able to investigate the relationship between arch type and injury likelihood. Feiss Line is a valid clinical measure of the MLA. However, no study has investigated the reliability of the test. Objectives: The purpose was to describe a modified version of the Feiss Line test and to determine the intra- and inter-tester reliability of this new foot alignment test. To emphasize the purpose of the modified test, the authors have named it The Navicular Position Test. Methods: Intra- and inter-tester reliability were evaluated of The Navicular Position Test with the use of ICC (interclass correlation coefficient) and Bland-Altman limits of agreement on 43 healthy, young, subjects. Results: Inter-tester mean difference -0.35 degrees [–1.32; 0.62] p = 0.47. Bland-Altman limits of agreement –6.55 to 5.85 degrees, ICC = 0.94. Intra-tester mean difference 0.47 degrees [–0.57; 1.50] p = 0.37. Bland-Altman limits of agreement –6.15 to 7.08 degrees, ICC = 0.91. Discussion: The present data support The Navicular Position Test as a reliable test of the navicular bone position during rest and loading measured in a simple test set-up. Conclusion: The Navicular Position Test was shown to have a high intraday-, intra- and inter-tester reliability. When cut off values to categorize the MLA into planus, rectus, or cavus feet, has been determined and presented, the test could be used in prospective observational studies investigating the role of the arch type on the development of various lower limb injuries. PMID:21904698

Clinical evaluation of flowable resins in non-carious cervical lesions: two-year results.

PubMed

Celik, Cigdem; Ozgünaltay, Gül; Attar, Nuray

2007-01-01

This study evaluated the two-year clinical performance of one microhybrid composite and three different types of flowable resin materials in non-carious cervical lesions. A total of 252 noncarious cervical lesions were restored in 37 patients (12 male, 25 female) with Admira Flow, Dyract Flow, Filtek Flow and Filtek Z250, according to manufacturers' instructions. All the restorations were placed by one operator, and two other examiners evaluated the restorations clinically within one week after placement and after 6, 12, 18 and 24 months, using modified USPHS criteria. At the end of 24 months, 172 restorations were evaluated in 26 patients, with a recall rate of 68%. Statistical analysis was completed using the Pearson Chi-square and Fisher-Freeman-Halton tests (p < 0.05). Additionally, survival rates were analyzed with the Kaplan-Meier estimator and the Log-Rank test (p < 0.05). The Log-Rank test indicated statistically significant differences between the survival rates of Dyract Flow/Admira Flow and Dyract Flow/Filtek Z250 (p < 0.05). While there was a statistically significant difference between Dyract Flow and the other materials for color match at 12 and 18 months, no significant difference was observed among all of the materials tested at 24 months. Significant differences were revealed between Filtek Z250 and the other materials for marginal adaptation at 18 and 24 months (p < 0.05). With respect to marginal discoloration, secondary caries, surface texture and anatomic form, no significant differences were found between the resin materials (p > 0.05). It was concluded that different types of resin materials demonstrated acceptable clinical performance in non-carious cervical lesions, except for the retention rates of the Dyract Flow restorations.

Comparison of Marginal and Internal Adaptation of Heat-Pressed and CAD/CAM Porcelain Laminate Veneers and a 2-Year Follow-Up.

PubMed

Yuce, Mert; Ulusoy, Mubin; Turk, Ayse Gozde

2017-12-22

To compare marginal and internal adaptations of porcelain laminate veneers fabricated with heat-pressed and CAD/CAM techniques, and to evaluate the clinical performances 2 years after cementation. Thirty heat-pressed and 31 CAD/CAM porcelain laminate veneers were fabricated for 12 patients. Silicone replicas of each veneer were obtained. Replicas were sectioned into 4 parts to measure adaptations of the veneers. A stereomicroscope was used to measure from 3 locations of replicas for marginal, and 9 locations for internal adaptations at 40x magnification. Clinical evaluations were done at baseline and 6, 12, 18, and 24 months after cementation according to the modified United States Public Health Service (USPHS) criteria. Independent samples t-test compared the adaptation values between heat-pressed and CAD/CAM groups. Paired t-test was used to evaluate marginal and internal adaptations of each group. Differences between the modified USPHS criteria ratings of heat-pressed and CAD/CAM groups were determined by the Mann-Whitney U test. Kaplan-Meier analysis was used to analyze the survival ratings of the veneers (p < 0.05). The mean marginal adaptation values of heat-pressed and CAD/CAM veneers were 295 and 314.98 μm, respectively, and there was no statistically significant difference (p = 0.541). Internal adaptation values of groups were not statistically different either (201.82 μm for heat pressed; 195.47 μm for CAD/CAM p = 0.734). When marginal and internal adaptation values were compared within groups, there were significant differences both for heat-pressed (p < 0.001) and CAD/CAM (p < 0.001). All veneers were rated 100% satisfactory during the 2-year period. Within the limitations of this study, fabrication method, whether CAD/CAM or heat-pressed, had no effect on the marginal and internal adaptation of porcelain laminate veneers. The results showed that both fabrication techniques performed well after 2 years of clinical performance. © 2017 by the American College of Prosthodontists.

Diagnosis of multiple system atrophy

PubMed Central

Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

2017-01-01

Multiple system atrophy (MSA) may be difficult to distinguish clinically from other disorders, particularly in the early stages of the disease. An autonomic-only presentation can be indistinguishable from pure autonomic failure. Patients presenting with parkinsonism may be misdiagnosed as having Parkinson disease. Patients presenting with the cerebellar phenotype of MSA can mimic other adult-onset ataxias due to alcohol, chemotherapeutic agents, lead, lithium, and toluene, or vitamin E deficiency, as well as paraneoplastic, autoimmune, or genetic ataxias. A careful medical history and meticulous neurological examination remain the cornerstone for the accurate diagnosis of MSA. Ancillary investigations are helpful to support the diagnosis, rule out potential mimics, and define therapeutic strategies. This review summarizes diagnostic investigations useful in the differential diagnosis of patients with suspected MSA. Currently used techniques include structural and functional brain imaging, cardiac sympathetic imaging, cardiovascular autonomic testing, olfactory testing, sleep study, urological evaluation, and dysphagia and cognitive assessments. Despite advances in the diagnostic tools for MSA in recent years and the availability of consensus criteria for clinical diagnosis, the diagnostic accuracy of MSA remains sub-optimal. As other diagnostic tools emerge, including skin biopsy, retinal biomarkers, blood and cerebrospinal fluid biomarkers, and advanced genetic testing, a more accurate and earlier recognition of MSA should be possible, even in the prodromal stages. This has important implications as misdiagnosis can result in inappropriate treatment, patient and family distress, and erroneous eligibility for clinical trials of disease-modifying drugs. PMID:29111419

Opening the Blood-Brain Barrier with MR Imaging-guided Focused Ultrasound: Preclinical Testing on a Trans-Human Skull Porcine Model.

PubMed

Huang, Yuexi; Alkins, Ryan; Schwartz, Michael L; Hynynen, Kullervo

2017-01-01

Purpose To develop and test a protocol in preparation for a clinical trial on opening the blood-brain barrier (BBB) with magnetic resonance (MR) imaging-guided focused ultrasound for the delivery of chemotherapy drugs to brain tumors. Materials and Methods The procedures were approved by the institutional animal care committee. A trans-human skull porcine model was designed for the preclinical testing. Wide craniotomies were applied in 11 pigs (weight, approximately 15 kg). A partial human skull was positioned over the animal's brain. A modified clinical MR imaging-guided focused ultrasound brain system was used with a 3.0-T MR unit. The ultrasound beam was steered during sonications over a 3 × 3 grid at 3-mm spacing. Acoustic power levels of 3-20 W were tested. Bolus injections of microbubbles at 4 μL/kg were tested for each sonication. Levels of BBB opening, hemorrhage, and cavitation signal were measured with MR imaging, histologic examination, and cavitation receivers, respectively. A cavitation safety algorithm was developed on the basis of logistic regression of the measurements and tested to minimize the risk of hemorrhage. Results BBB openings of approximately 1 cm 3 in volume were visualized with gadolinium-enhanced MR imaging after sonication at an acoustic power of approximately 5 W. Gross examination of histologic specimens helped confirm Evans blue (bound to macromolecule albumin) extravasation, and hematoxylin-eosin staining helped detect only scattered extravasation of red blood cells. In cases where cavitation signals were higher than thresholds, sonications were terminated immediately without causing hemorrhage. Conclusion With a trans-human skull porcine model, this study demonstrated BBB opening with a 230-kHz system in preparation for a clinical trial. © RSNA, 2016 Online supplemental material is available for this article.

Methodological issues with adaptation of clinical trial design.

PubMed

Hung, H M James; Wang, Sue-Jane; O'Neill, Robert T

2006-01-01

Adaptation of clinical trial design generates many issues that have not been resolved for practical applications, though statistical methodology has advanced greatly. This paper focuses on some methodological issues. In one type of adaptation such as sample size re-estimation, only the postulated value of a parameter for planning the trial size may be altered. In another type, the originally intended hypothesis for testing may be modified using the internal data accumulated at an interim time of the trial, such as changing the primary endpoint and dropping a treatment arm. For sample size re-estimation, we make a contrast between an adaptive test weighting the two-stage test statistics with the statistical information given by the original design and the original sample mean test with a properly corrected critical value. We point out the difficulty in planning a confirmatory trial based on the crude information generated by exploratory trials. In regards to selecting a primary endpoint, we argue that the selection process that allows switching from one endpoint to the other with the internal data of the trial is not very likely to gain a power advantage over the simple process of selecting one from the two endpoints by testing them with an equal split of alpha (Bonferroni adjustment). For dropping a treatment arm, distributing the remaining sample size of the discontinued arm to other treatment arms can substantially improve the statistical power of identifying a superior treatment arm in the design. A common difficult methodological issue is that of how to select an adaptation rule in the trial planning stage. Pre-specification of the adaptation rule is important for the practicality consideration. Changing the originally intended hypothesis for testing with the internal data generates great concerns to clinical trial researchers.

Assessing genetically modified crops to minimize the risk of increased food allergy: a review.

PubMed

Goodman, Richard E; Hefle, Susan L; Taylor, Steven L; van Ree, Ronald

2005-06-01

The first genetically modified (GM) crops approved for food use (tomato and soybean) were evaluated for safety by the United States Food and Drug Administration prior to commercial production. Among other factors, those products and all additional GM crops that have been grown commercially have been evaluated for potential increases in allergenic properties using methods that are consistent with the current understanding of food allergens and knowledge regarding the prediction of allergenic activity. Although there have been refinements, the key aspects of the evaluation have not changed. The allergenic properties of the gene donor and the host (recipient) organisms are considered in determining the appropriate testing strategy. The amino acid sequence of the encoded protein is compared to all known allergens to determine whether the protein is a known allergen or is sufficiently similar to any known allergen to indicate an increased probability of allergic cross-reactivity. Stability of the protein in the presence of acid with the stomach protease pepsin is tested as a risk factor for food allergenicity. In vitro or in vivo human IgE binding are tested when appropriate, if the gene donor is an allergen or the sequence of the protein is similar to an allergen. Serum donors and skin test subjects are selected based on their proven allergic responses to the gene donor or to material containing the allergen that was matched in sequence. While some scientists and regulators have suggested using animal models, performing broadly targeted serum IgE testing or extensive pre- or post-market clinical tests, current evidence does not support these tests as being predictive or practical. Based on the evidence to date, the current assessment process has worked well to prevent the unintended introduction of allergens in commercial GM crops.

Unstable Binocular Fixation Affects Reaction Times But Not Implicit Motor Learning in Dyslexia.

PubMed

Przekoracka-Krawczyk, Anna; Brenk-Krakowska, Alicja; Nawrot, Pawel; Rusiak, Patrycja; Naskrecki, Ryszard

2017-12-01

Individuals with developmental dyslexia suffer not only from reading problems as more general motor deficits can also be observed in this patient group. Both psychometric clinical tests and objective eyetracking methods suggest that unstable binocular fixation may contribute to reading problems. Because binocular instability may cause poor eye-hand coordination and impair motor control, the primary aim of this study was to explore in dyslexic subjects the influence of unstable binocular fixation on reaction times (RTs) and implicit motor learning (IML), which is one of the fundamental cerebellar functions. Fixation disparity (FD) and instability of FD were assessed subjectively using the Wesson card and a modified Mallett test. A modified version of the Serial Reaction Time Task (SRTT) was used to measure the RTs and IML skills. The results for the dyslexic group (DG), which included 29 adult subjects (15 were tested binocularly, DGbin; 14 were tested monocularly, DGmono), were compared with data from the control group (CG), which consisted of 30 age-matched nondyslexic subjects (15 tested binocularly, CGbin; and the other 15 tested monocularly, CGmono). The results indicated that the DG showed poorer binocular stability and longer RTs in the groups tested binocularly (RTs: 534 vs. 411 ms for DGbin and CGbin, respectively; P < 0.001) as compared with the groups examined monocularly (RTs: 431 vs. 424 ms for DGmono and CGmono, respectively; P = 0.996). The DG also exhibited impaired IML when compared with the CG (EFIML: 25 vs. 50 ms for DG and CG, respectively; P = 0.012). Unstable binocularity in dyslexia may affect RTs but was not related to poor IML skills. Impaired IML in dyslexia was independent of the viewing conditions (monocular versus binocular) and may be related to cerebellar deficits.

Interactive Book Reading to Accelerate Word Learning by Kindergarten Children With Specific Language Impairment: Identifying Adequate Progress and Successful Learning Patterns.

PubMed

Storkel, Holly L; Komesidou, Rouzana; Fleming, Kandace K; Romine, Rebecca Swinburne

2017-04-20

The goal of this study was to provide guidance to clinicians on early benchmarks of successful word learning in an interactive book reading treatment and to examine how encoding and memory evolution during treatment contribute to word learning outcomes by kindergarten children with specific language impairment (SLI). Twenty-seven kindergarten children with SLI participated in a preliminary clinical trial using interactive book reading to teach 30 new words. Word learning was assessed at 4 points during treatment through a picture naming test. The results indicate that the following performance during treatment was cause for concern, indicating a need to modify the treatment: naming 0-1 treated words correctly at Naming Test 1; naming 0-2 treated words correctly at Naming Test 2; naming 0-3 treated words correctly at Naming Test 3. In addition, the results showed that encoding was the primary limiting factor in word learning, but rmemory evolution also contributed (albeit to a lesser degree) to word learning success. Case illustrations demonstrate how a clinician's understanding of a child's word learning strengths and weaknesses develop over the course of treatment, substantiating the importance of regular data collection and clinical decision-making to ensure the best possible outcomes for each individual child.

A simple micro-photometric method for urinary iodine determination.

PubMed

Grimm, Gabriele; Lindorfer, Heidelinde; Kieweg, Heidi; Marculescu, Rodrig; Hoffmann, Martha; Gessl, Alois; Sager, Manfred; Bieglmayer, Christian

2011-10-01

Urinary iodide concentration (UIC) is useful to evaluate nutritional iodine status. In clinical settings UIC helps to exclude blocking of the thyroid gland by excessive endogenous iodine, if diagnostic or therapeutic administration of radio-iodine is indicated. Therefore, this study established a simple test for the measurement of UIC. UIC was analyzed in urine samples of 200 patients. Samples were pre-treated at 95°C for 45 min with ammonium persulfate in a thermal cycler, followed by a photometric Sandell-Kolthoff reaction (SK) carried out in microtiter plates. For method comparison, UIC was analyzed in 30 samples by inductivity coupled plasma mass spectro-metry (ICP-MS) as a reference method. Incubation conditions were optimized concerning recovery. The photometric test correlated well to the reference method (SK=0.91*ICP-MS+1, r=0.962) and presented with a functional sensitivity of 20 μg/L. UIC of patient samples ranged from <20 to 750 μg/L (median 110 μg/L); 90% of the urine samples had iodide concentrations below 210 μg/L. The modified SK-test takes approximately 90 min for analyses of 20 urine samples compared with 27 h for ICP-MS. The photometric test provides satisfactory results and can be performed with the basic equipment of a clinical laboratory.

The validation of Implicit Association Test measures for smartphone and Internet addiction in at-risk children and adolescents.

PubMed

Roh, Daeyoung; Bhang, Soo-Young; Choi, Jung-Seok; Kweon, Yong Sil; Lee, Sang-Kyu; Potenza, Marc N

2018-03-01

Background Potential concerns are increasing that smartphone and Internet addictions may have deleterious effects on the mental health. Despite the recognition of the important role that implicit associations may have over explicit processes in addiction, such implicit associations have not been comprehensively investigated with respect to Internet addiction. Therefore, we modified the Implicit Association Test (IAT) for smartphone and Internet addictions and investigated its validity in children and adolescents. Methods In this experimental study, 78 at-risk children and adolescents ranging in age from 7 to 17 years completed an IAT modified with pictures captured from the most popular Internet games among youth. Furthermore, measures of Internet and smartphone addictions, mental health and problem behaviors, impulsive tendencies, self-esteem, daily stress, and quality of life were assessed simultaneously. Results Significant correlations were found between IAT D2SD scores and standardized scales for Internet (r = .28, p < .05) and smartphone (r = .33, p < .01) addictions. There were no significant correlations between IAT parameters and other scales measuring the constructs that are less relevant to the features of addiction, such as daily stress levels, impulsivity, and quality of life. Multiple regression analysis revealed that the IAT D2SD was independently and positively associated with smartphone addiction (p = .03) after controlling for other clinical correlates. Conclusions This study demonstrated good convergent and discriminant validity of this IAT as a novel measurement relating to Internet and smartphone addictions. Further longitudinal and prospective studies are needed to evaluate its potential utility in clinical and community settings.

Does the Sex Risk Quiz Predict Mycoplasma genitalium Infection in Urban Adolescents and Young Adult Women?

PubMed

Ronda, Jocelyn; Gaydos, Charlotte A; Perin, Jamie; Tabacco, Lisa; Coleman, Jenell; Trent, Maria

2018-06-04

Mycoplasma genitalium (MG) is a common sexually transmitted infection (STI) but there are limited strategies to identify individuals at risk of MG. Previously a sex risk quiz was used to predict STIs including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC), and/or Trichomonas vaginalis (TV). The original quiz categorized individuals ≤25 years old as at risk of STIs, but the Centers for Disease Control identifies females <25 years old as at risk of STIs. In this study, the quiz was changed to categorize females <25 years old as high risk. The objective was to determine if the age-modified risk quiz predicted MG infection. A cross-sectional analysis of a prospective longitudinal study was performed including female adolescents and young adults (AYA) evaluated in multiple outpatient clinics. Participants completed an age-modified risk quiz about sexual practices. Scores ranged from 0 to 10 and were categorized as low-risk (0-3), medium-risk (4-7), and high-risk (8-10) based upon the STI prevalence for each score. Vaginal and/or endocervical specimens were tested for MG, TV, CT, and GC using the Aptima Gen-Probe nucleic amplification test. There were 693 participants. Most participants reported having 0-1 sexual partners in the last 90 days (91%) and inconsistent condom use (84%). Multivariable logistic regression analysis controlling for race, education, and symptom status demonstrated that a medium-risk score predicted MG infection among AYA <25 years old (adjusted OR 2.56 [95% CI 1.06-6.18]). A risk quiz may be useful during clinical encounters to identify AYA at risk of MG.

Red Blood Cell Mechanical Fragility Test for Clinical Research Applications.

PubMed

Ziegler, Luke A; Olia, Salim E; Kameneva, Marina V

2017-07-01

Red blood cell (RBC) susceptibility to mechanically induced hemolysis, or RBC mechanical fragility (MF), is an important parameter in the characterization of erythrocyte membrane health. The rocker bead test (RBT) and associated calculated mechanical fragility index (MFI) is a simple method for the assessment of RBC MF. Requiring a minimum of 15.5 mL of blood and necessitating adjustment of hematocrit (Ht) to a "standard" value (40%), the current RBT is not suitable for use in most studies involving human subjects. To address these limitations, we propose a 6.5 mL reduced volume RBT and corresponding modified MFI (MMFI) that does not require prior Ht adjustment. This new method was assessed for i) correlation to the existing text, ii) to quantify the effect of Ht on MFI, and iii) validation by reexamining the protective effect of plasma proteins on RBC MF. The reduced volume RBT strongly correlated (r = 0.941) with the established large volume RBT at matched Hts, and an equation was developed to calculate MMFI: a numerical estimation (R 2  = 0.923) of MFI if performed with the reduced volume RBT at "standard" (40%) Ht. An inversely proportional relationship was found between plasma protein concentration and RBC MF using the MMFI-reduced volume method, supporting previous literature findings. The new reduced volume RBT and modified MFI will allow for the measurement of RBC MF in clinical and preclinical studies involving humans or small animals. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Etiology and characteristics of large symptomatic pericardial effusion in a community hospital in the contemporary era.

PubMed

Abdallah, R; Atar, S

2014-05-01

The etiology and laboratory characteristics of large symptomatic pericardial effusion (LSPE) in the Western world have evolved over the years, and vary between regions, community and tertiary hospitals. We reviewed data of 86 consecutive patients who underwent pericardiocentesis or pericardial window due to LSPE in a community hospital from 2001 to 2010. The characteristics of the PE including chemistry, hematology, bacteriology, serology and cytology have been analyzed. We correlated the etiologies of PE with age, gender and clinical presentation. The most frequent etiology of LSPE was idiopathic [36% (77% with a clinical diagnosis of pericarditis)], followed by malignancy (31.4%), ischemic heart disease (16.3%), renal failure (4.6%), trauma (4.6%) and autoimmune disease (4.6%). The average age of all the etiological groups excluding trauma was over 50 years. Laboratory tests did not modify the pre-procedure diagnosis in any of the patients. The most frequent presenting symptom was dyspnea (76.6%). Chest pain was mostly common in patients with idiopathic etiology (58.06%). The most frequent medical condition associated with LSPE was the use of anticoagulant or antiplatelet drugs (31.40%), especially aspirin, and in those, the PE tended to be bloody (73%, P = 0.11). Most of the effusions were exudates (70.9%). PE due to renal failure was the largest (1467 ± 1387 ml). The spectrum of etiologies of LSPE in a community hospital in the Western world in the contemporary era is continuously evolving. The most frequent etiology is now idiopathic, followed by malignancy. Routine laboratory testing still rarely modifies the pre-procedure diagnosis.

Robots integrated with virtual reality simulations for customized motor training in a person with upper extremity hemiparesis: a case report

PubMed Central

Fluet, Gerard G.; Merians, Alma S.; Qiu, Qinyin; Lafond, Ian; Saleh, Soha; Ruano, Viviana; Delmonico, Andrea R.; Adamovich, Sergei V.

2014-01-01

Background and Purpose A majority of studies examining repetitive task practice facilitated by robots for the treatment of upper extremity paresis utilize standardized protocols applied to large groups. Others utilize interventions tailored to patients but don't describe the clinical decision making process utilized to develop and modify interventions. This case report will describe a robot-based intervention customized to match the goals and clinical presentation of a gentleman with upper extremity hemiparesis secondary to stroke. Methods PM is an 85 year-old man with left hemiparesis secondary to an intracerebral hemorrhage five years prior to examination. Outcomes were measured before and after a one month period of home therapy and after a one month robotic intervention. The intervention was designed to address specific impairments identified during his PT examination. When necessary, activities were modified based on the patient's response to his first week of treatment. Outcomes PM trained twelve sessions using six virtually simulated activities. Modifications to original configurations of these activities resulted in performance improvements in five of these activities. PM demonstrated a 35 second improvement in Jebsen Test of Hand Function time and a 44 second improvement in Wolf Motor Function Test time subsequent to the robotic training intervention. Reaching kinematics, 24 hour activity measurement and the Hand and Activities of Daily Living scales of the Stroke Impact Scale all improved as well. Discussion A customized program of robotically facilitated rehabilitation resulted in large short-term improvements in several measurements of upper extremity function in a patient with chronic hemiparesis. PMID:22592063

Regulatory framework on bioequivalence criteria for locally acting gastrointestinal drugs: the case for oral modified release mesalamine formulations.

PubMed

Sferrazza, Gianluca; Siviero, Paolo D; Nicotera, Giuseppe; Turella, Paola; Serafino, Annalucia; Blandizzi, Corrado; Pierimarchi, Pasquale

2017-09-01

Bioequivalence testing for locally acting gastrointestinal drugs is a challenging issue for both regulatory authorities and pharmaceutical industries. The international regulatory framework has been characterized by the lack of specific bioequivalence tests that has generated a negative impact on the market competition and drug use in clinical practice. Areas covered: This review article provides an overview of the European Union and United States regulatory frameworks on bioequivalence criteria for locally acting gastrointestinal drugs, also discussing the most prominent scientific issues and advances that has been made in this field. A focus on oral modified release mesalamine formulations will be also provided, with practical examples of the regulatory pathways followed by pharmaceutical companies to determine bioequivalence. Expert commentary: The development of a scientific rationale to demonstrate bioequivalence in this field has been complex and often associated with uncertainties related to scientific and regulatory aspects. Only in recent years, thanks to advanced knowledge in this field, the criteria for bioequivalence assessment are undergoing substantial changes. This new scenario will likely result in a significant impact on pharmaceutical companies, promoting more competition through a clearer regulatory approach, conceived for streamlining the demonstration of therapeutic equivalence for locally acting gastrointestinal drugs.

A feasibility study for a clinical decision support system prompting HIV testing.

PubMed

Chadwick, D R; Hall, C; Rae, C; Rayment, Ml; Branch, M; Littlewood, J; Sullivan, A

2017-07-01

Levels of undiagnosed HIV infection and late presentation remain high globally despite attempts to increase testing. The objective of this study was to evaluate a risk-based prototype application to prompt HIV testing when patients undergo routine blood tests. Two computer physician order entry (CPOE) systems were modified using the application to prompt health care workers (HCWs) to add an HIV test when other tests selected suggested that the patient was at higher risk of HIV infection. The application was applied for a 3-month period in two areas, in a large London hospital and in general practices in Teesside/North Yorkshire. At the end of the evaluation period, HCWs were interviewed to assess the usability and acceptability of the prompt. Numbers of HIV tests ordered in the general practice areas were also compared before and after the prompt's introduction. The system was found to be both useable and generally acceptable to hospital doctors, general practitioners and nurse practitioners, with little evidence of prompt/alert fatigue. The issue of the prompt appearing late in the patient consultation did lead to some difficulties, particularly around discussion of the test and consent. In the general practices, around 1 in 10 prompts were accepted and there was a 6% increase in testing rates over the 3-month study period (P = 0.169). Using a CPOE-based clinical decision support application to prompt HIV testing appears both feasible and acceptable to HCWs. Refining the application to provide more accurate risk stratification is likely to make it more effective. © 2016 British HIV Association.

Generated effect modifiers (GEM's) in randomized clinical trials.

PubMed

Petkova, Eva; Tarpey, Thaddeus; Su, Zhe; Ogden, R Todd

2017-01-01

In a randomized clinical trial (RCT), it is often of interest not only to estimate the effect of various treatments on the outcome, but also to determine whether any patient characteristic has a different relationship with the outcome, depending on treatment. In regression models for the outcome, if there is a non-zero interaction between treatment and a predictor, that predictor is called an "effect modifier". Identification of such effect modifiers is crucial as we move towards precision medicine, that is, optimizing individual treatment assignment based on patient measurements assessed when presenting for treatment. In most settings, there will be several baseline predictor variables that could potentially modify the treatment effects. This article proposes optimal methods of constructing a composite variable (defined as a linear combination of pre-treatment patient characteristics) in order to generate an effect modifier in an RCT setting. Several criteria are considered for generating effect modifiers and their performance is studied via simulations. An example from a RCT is provided for illustration. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Postoperative pain intensity after using different instrumentation techniques: a randomized clinical study

PubMed Central

ÇIÇEK, Ersan; KOÇAK, Mustafa Murat; KOÇAK, Sibel; SAĞLAM, Baran Can; TÜRKER, Sevinç Aktemur

2017-01-01

Abstract Postoperative pain is a frequent complication associated with root canal treatment, especially during apical instrumentation of tooth with preexisting periradicular inflammation Objectives The aim of this clinical study was to evaluate the influence of the instrumentation techniques on the incidence and intensity of postoperative pain in single-visit root canal treatment. Material and Methods Ninety patients with single root/canal and non-vital pulps were included. The patients were assigned into 3 groups according to root canal instrumentation technique used; modified step-back, reciprocal, and rotational techniques. Root canal treatment was carried out in a single visit and the severity of postoperative pain was assessed via 4-point pain intensity scale. All the participants were called through the phone at 12, 24 and 48 h to obtain the pain scores. Data were analyzed through the Kruskal–Wallis test. Results There was significant difference between all groups (p<0.05). The modified step-back technique produced postoperative pain significantly lower than the rotational (p=0.018) and reciprocal (p=0.020) techniques. No difference was found between the reciprocal and rotational techniques (p=0.868). Postoperative pain in the first 12 h period (p=0.763) and in the 24 h period (p=0.147) was not significantly different between the groups. However, the difference in the 48 h period was statistically different between the groups (p=0.040). Conclusion All instrumentation techniques caused postoperative pain. The modified step-back technique produced less pain compared to the rotational and reciprocal techniques. PMID:28198972

Regulated Apoptosis of Genetically-Modified Hematopoietic Stem and Progenitor Cells via an Inducible Caspase-9 Suicide Gene in Rhesus Macaques

PubMed Central

Barese, Cecilia N.; Felizardo, Tania C.; Sellers, Stephanie E.; Keyvanfar, Keyvan; Di Stasi, Antonio; Metzger, Mark E.; Krouse, Allen E.; Donahue, Robert E.; Spencer, David M.; Dunbar, Cynthia E.

2014-01-01

The high risk of insertional oncogenesis reported in clinical trials utilizing integrating retroviral vectors to genetically-modify hematopoietic stem and progenitor cells (HSPC) requires the development of safety strategies to minimize risks associated with novel cell and gene therapies. The ability to ablate genetically modified cells in vivo is desirable, should an abnormal clone emerge. Inclusion of “suicide genes” in vectors to facilitate targeted ablation of vector-containing abnormal clones in vivo is one potential safety approach. We tested whether the inclusion of the “inducible Caspase-9” (iCasp9) suicide gene in a gamma-retroviral vector facilitated efficient elimination of vector-containing HSPCs and their hematopoietic progeny in vivo long-term, in an autologous non-human primate transplantation model. Following stable engraftment of iCasp9 expressing hematopoietic cells in rhesus macaques, administration of AP1903, a chemical inducer of dimerization able to activate iCasp9, specifically eliminated vector-containing cells in all hematopoietic lineages long-term, suggesting activity at the HSPC level. Between 75–94% of vector-containing cells were eliminated by well-tolerated AP1903 dosing, but lack of complete ablation was linked to lower iCasp9 expression in residual cells. Further investigation of resistance mechanisms demonstrated upregulation of Bcl-2 in hematopoietic cell lines transduced with the vector and resistant to AP1903 ablation. These results demonstrate both the potential and the limitations of safety approaches utilizing iCasp9 to HSPC-targeted gene therapy settings, in a model with great relevance to clinical development. PMID:25330775

To Go or Not to Go: A Proof of Concept Study Testing Food-Specific Inhibition Training for Women with Eating and Weight Disorders.

PubMed

Turton, Robert; Nazar, Bruno P; Burgess, Emilee E; Lawrence, Natalia S; Cardi, Valentina; Treasure, Janet; Hirsch, Colette R

2018-01-01

Inefficient food-specific inhibitory control is a potential mechanism that underlies binge eating in bulimia nervosa and binge eating disorder. Go/no-go training tools have been developed to increase inhibitory control over eating impulses. Using a within-subjects design, this study examined whether one session of food-specific go/no-go training, versus general inhibitory control training, modifies eating behaviour. The primary outcome measure was food consumption on a taste test following each training session. Women with bulimia nervosa and binge eating disorder had small non-significant reductions in high-calorie food consumption on the taste test following the food-specific compared with the general training. There were no effects on eating disorder symptomatic behaviour (i.e. binge eating/purging) in the 24 h post-training. The training task was found to be acceptable by the clinical groups. More research is needed with larger sample sizes to determine the effectiveness of this training approach for clinical populations. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention: A Subgroup Analysis of a Randomized Clinical Trial.

PubMed

Solomon, Alina; Turunen, Heidi; Ngandu, Tiia; Peltonen, Markku; Levälahti, Esko; Helisalmi, Seppo; Antikainen, Riitta; Bäckman, Lars; Hänninen, Tuomo; Jula, Antti; Laatikainen, Tiina; Lehtisalo, Jenni; Lindström, Jaana; Paajanen, Teemu; Pajala, Satu; Stigsdotter-Neely, Anna; Strandberg, Timo; Tuomilehto, Jaakko; Soininen, Hilkka; Kivipelto, Miia

2018-04-01

The role of the apolipoprotein E (APOE) ε4 allele as an effect modifier in lifestyle interventions to prevent cognitive impairment is still unclear. To examine whether the APOE ε4 allele modifies the previously reported significant cognitive benefits of a multidomain lifestyle intervention (prespecified subgroup analysis). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a randomized clinical trial in 6 centers across Finland (screening and randomization performed from September 7, 2009, through November 24, 2011; intervention duration, 2 years). Data analysis was performed from August 1, 2015, to March 31, 2016. The study population was at-risk older individuals from the general population. Inclusion criteria were age of 60 to 77 years; Cardiovascular Risk Factors, Aging, and Dementia risk score of at least 6 points; and cognition at a mean level or slightly lower than expected for age. Individuals with dementia or substantial cognitive impairment and conditions that prevented cooperation or safe engagement in the intervention were excluded. APOE genotype data were available for 1175 of the 1260 participants. Participants were randomly assigned in a 1:1 ratio to a multidomain intervention group (diet, exercise, cognitive training, and vascular risk management) or a control group (general health advice). Group allocation was not actively disclosed to participants, and outcome assessors were masked to group allocation. Primary outcome was change in cognition measured through a comprehensive neuropsychological test battery. Analysis was based on modified intention to treat (participants with at least 1 postbaseline assessment). A total of 1109 participants (mean [SD] age, 69.3 [4.7] years; 514 [46.3%] female) were included in the analysis: 362 APOE ε4 allele carriers (173 intervention and 189 control) and 747 noncarriers (380 intervention and 367 control). The APOE ε4 carriers and noncarriers were not significantly different at baseline (except for serum cholesterol level). The difference between the intervention and control groups in annual neuropsychological test battery total score change was 0.037 (95% CI, 0.001 to 0.073) among carriers and 0.014 (95% CI, -0.011 to 0.039) among noncarriers. Intervention effect was not significantly different between carriers and noncarriers (0.023; 95% CI, -0.021 to 0.067). Healthy lifestyle changes may be beneficial for cognition in older at-risk individuals even in the presence of APOE-related genetic susceptibility to dementia. Whether such benefits are more pronounced in APOE ε4 carriers compared with noncarriers should be further investigated. The findings also emphasize the importance of early prevention strategies that target multiple modifiable risk factors simultaneously. ClinicalTrials.gov Identifier: NCT01041989.

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol of a controlled clinical trial developed by consensus of an international study group. Part one: rationale and hypothesis.

PubMed

Lorenz, W; Stinner, B; Bauhofer, A; Rothmund, M; Celik, I; Fingerhut, A; Koller, M; Lorijn, R H; Nyström, P O; Sitter, H; Schein, M; Solomkin, J S; Troidl, H; Wyatt, J; Wittmann, D H

2001-03-01

Presentation of a novel study protocol to evalue the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). The rationale and hypothesis are presented in this part of the protocol of the randomised, placebo controlled, double-blinded, single-centre study performed at an university hospital (n = 40 patients for each group). Part one of this protocol describes the concepts of three major sections of the study: Definition of optimum and sub-optimal recovery after operation. Recovery, as an outcome, is not a simple univariate endpoint, but a complex construction of mechanistic variables (i. e. death, complications and health status assessed by the surgeon), quality of life expressed by the patient, and finally a weighted outcome judgement by both the patient and the surgeon (true endpoint). Its conventional early assessment within 14-28 days is artificial: longer periods (such as 6 months) are needed for the patient to state: "I am now as well as I was before". Identification of suitable target patients: the use of biological response modifiers (immune modulators) in addition to traditional prophylaxes (i. e. antibiotics, heparin, volume substitutes) may improve postoperative outcome in appropriate selected patients with reduced host defence and increased immunological stress response, but these have to be defined. Patients classified as ASA 3 and 4 (American Society for Anaesthesiologists) and with colorectal cancer will be studied to prove this hypothesis. Choice of biological response modifier: Filgrastim has been chosen as an example of a biological response modifier because it was effective in a new study type, clinic-modelling randomised trials in rodents, and has shown promise in some clinical trials for indications other than preoperative prophylaxis. It has also enhanced host defence and has been anti-inflammatory in basic research. The following hypothesis will be tested in patients with operations for colorectal cancer and increased preoperative risk (ASA 3 and 4): is the outcome as evaluated by the hermeneutic endpoint (quality of life expressed by the patient) and mechanistic endpoints (mortality rate, complication rate, relative hospital stay, assessed by the doctor) improved in the group receiving filgrastim prophylaxis in comparison with the placebo group? Quality of life will be the first primary endpoint in the hierarchical, statistical testing of confirmatory analysis.

A task-specific interactive game-based virtual reality rehabilitation system for patients with stroke: a usability test and two clinical experiments.

PubMed

Shin, Joon-Ho; Ryu, Hokyoung; Jang, Seong Ho

2014-03-06

Virtual reality (VR) is not commonly used in clinical rehabilitation, and commercial VR gaming systems may have mixed effects in patients with stroke. Therefore, we developed RehabMaster™, a task-specific interactive game-based VR system for post-stroke rehabilitation of the upper extremities, and assessed its usability and clinical efficacy. A participatory design and usability tests were carried out for development of RehabMaster with representative user groups. Two clinical trials were then performed. The first was an observational study in which seven patients with chronic stroke received 30 minutes of RehabMaster intervention per day for two weeks. The second was a randomised controlled trial of 16 patients with acute or subacute stroke who received 10 sessions of conventional occupational therapy only (OT-only group) or conventional occupational therapy plus 20 minutes of RehabMaster intervention (RehabMaster + OT group). The Fugl-Meyer Assessment score (FMA), modified Barthel Index (MBI), adverse effects, and drop-out rate were recorded. The requirements of a VR system for stroke rehabilitation were established and incorporated into RehabMaster. The reported advantages from the usability tests were improved attention, the immersive flow experience, and individualised intervention. The first clinical trial showed that the RehabMaster intervention improved the FMA (P = .03) and MBI (P = .04) across evaluation times. The second trial revealed that the addition of RehabMaster intervention tended to enhance the improvement in the FMA (P = .07) but did not affect the improvement in the MBI. One patient with chronic stroke left the trial, and no adverse effects were reported. The RehabMaster is a feasible and safe VR system for enhancing upper extremity function in patients with stroke.

A task-specific interactive game-based virtual reality rehabilitation system for patients with stroke: a usability test and two clinical experiments

PubMed Central

2014-01-01

Background Virtual reality (VR) is not commonly used in clinical rehabilitation, and commercial VR gaming systems may have mixed effects in patients with stroke. Therefore, we developed RehabMaster™, a task-specific interactive game-based VR system for post-stroke rehabilitation of the upper extremities, and assessed its usability and clinical efficacy. Methods A participatory design and usability tests were carried out for development of RehabMaster with representative user groups. Two clinical trials were then performed. The first was an observational study in which seven patients with chronic stroke received 30 minutes of RehabMaster intervention per day for two weeks. The second was a randomised controlled trial of 16 patients with acute or subacute stroke who received 10 sessions of conventional occupational therapy only (OT-only group) or conventional occupational therapy plus 20 minutes of RehabMaster intervention (RehabMaster + OT group). The Fugl-Meyer Assessment score (FMA), modified Barthel Index (MBI), adverse effects, and drop-out rate were recorded. Results The requirements of a VR system for stroke rehabilitation were established and incorporated into RehabMaster. The reported advantages from the usability tests were improved attention, the immersive flow experience, and individualised intervention. The first clinical trial showed that the RehabMaster intervention improved the FMA (P = .03) and MBI (P = .04) across evaluation times. The second trial revealed that the addition of RehabMaster intervention tended to enhance the improvement in the FMA (P = .07) but did not affect the improvement in the MBI. One patient with chronic stroke left the trial, and no adverse effects were reported. Conclusions The RehabMaster is a feasible and safe VR system for enhancing upper extremity function in patients with stroke. PMID:24597650

Clinical Determinants of Incremental Shuttle Walk Test in Adults with Bronchiectasis.

PubMed

Yildiz, Sulenur; Inal-Ince, Deniz; Calik-Kutukcu, Ebru; Vardar-Yagli, Naciye; Saglam, Melda; Arikan, Hulya; Coplu, Lutfi

2018-06-01

Exercise capacity is impaired in patients with bronchiectasis. Incremental shuttle walk test (ISWT) stresses cardiorespiratory system physiologically to symptom-limited maximal exercise capacity. The purpose of this study was to investigate the clinical determinants of ISWT in adults with non-cystic fibrosis (CF) bronchiectasis. Forty-one clinically stable bronchiectasis patients aged 18-72 years (27 females, 14 males) participated in the study. Subjects' demographics and physical characteristics were recorded. Bronchiectasis Severity Index was used to identify disease severity. Pulmonary function test was performed. Dyspnea perception was assessed using the modified Medical Research Council Dyspnea Scale. Maximum inspiratory and expiratory pressures were measured. Peripheral muscle strength using a hand held dynamometer was measured. ISWT was performed to determine exercise capacity. Fatigue Severity Scale, Hospital Anxiety and Depression Scale, Leicester Cough Questionnaire were used to determine fatigue, psychosocial status, and quality of life. Patients' mean ISWT distance was 469.5 m. The ISWT distance was significantly related with age (r = - 0.472), height (r = 0.469), gender (r = 0.520), FEV 1 (r = 0.651), and FVC (r = 0.545, p < 0.05). Quadriceps muscle strength was higher in males (p = 0.001) as compared to females. Age and gender were identified as independent predictors of the ISWT, explaining 42% of variance in ISWT distance (r = 0.649, r 2  = 0.421, F (2,38)  = 13.794, p < 0.001). The clinical determinants of ISWT in clinically stable patients with non-CF bronchiectasis are age and gender. Pulmonary function, dyspnea perception, muscle strength, disease severity, fatigue, psychosocial factors, and health-related quality of life seems to have an independent effect on ISWT in this group of patients with bronchiectasis.

Genetically modified T cells in cancer therapy: opportunities and challenges

PubMed Central

Sharpe, Michaela; Mount, Natalie

2015-01-01

Tumours use many strategies to evade the host immune response, including downregulation or weak immunogenicity of target antigens and creation of an immune-suppressive tumour environment. T cells play a key role in cell-mediated immunity and, recently, strategies to genetically modify T cells either through altering the specificity of the T cell receptor (TCR) or through introducing antibody-like recognition in chimeric antigen receptors (CARs) have made substantial advances. The potential of these approaches has been demonstrated in particular by the successful use of genetically modified T cells to treat B cell haematological malignancies in clinical trials. This clinical success is reflected in the growing number of strategic partnerships in this area that have attracted a high level of investment and involve large pharmaceutical organisations. Although our understanding of the factors that influence the safety and efficacy of these therapies has increased, challenges for bringing genetically modified T-cell immunotherapy to many patients with different tumour types remain. These challenges range from the selection of antigen targets and dealing with regulatory and safety issues to successfully navigating the routes to commercial development. However, the encouraging clinical data, the progress in the scientific understanding of tumour immunology and the improvements in the manufacture of cell products are all advancing the clinical translation of these important cellular immunotherapies. PMID:26035842

Electrochemical impedance spectroscopy investigation on the clinical lifetime of ProTaper rotary file system.

PubMed

Penta, Virgil; Pirvu, Cristian; Demetrescu, Ioana

2014-01-01

The main objective of the current paper is to show that electrochemical impedance spectroscopy (EIS) could be a method for evaluating and predicting of ProTaper rotary file system clinical lifespan. This particular aspect of everyday use of the endodontic files is of great importance in each dental practice and has profound clinical implications. The method used for quantification resides in the electrochemical impedance spectroscopy theory and has in its main focus the characteristics of the surface titanium oxide layer. This electrochemical technique has been adapted successfully to identify the quality of the Ni-Ti files oxide layer. The modification of this protective layer induces changes in corrosion behavior of the alloy modifying the impedance value of the file. In order to assess the method, 14 ProTaper sets utilized on different patients in a dental clinic have been submitted for testing using EIS. The information obtained in regard to the surface oxide layer has offered an indication of use and proves that the said layer evolves with each clinical application. The novelty of this research is related to an electrochemical technique successfully adapted for Ni-Ti file investigation and correlation with surface and clinical aspects.

Presentation of Diagnostic Information to Doctors May Change Their Interpretation and Clinical Management: A Web-Based Randomised Controlled Trial

PubMed Central

Ben-Shlomo, Yoav; Collin, Simon M.; Quekett, James; Sterne, Jonathan A. C.; Whiting, Penny

2015-01-01

Background There is little evidence on how best to present diagnostic information to doctors and whether this makes any difference to clinical management. We undertook a randomised controlled trial to see if different data presentations altered clinicians’ decision to further investigate or treat a patient with a fictitious disorder (“Green syndrome”) and their ability to determine post-test probability. Methods We recruited doctors registered with the United Kingdom’s largest online network for medical doctors between 10 July and 6” November 2012. Participants were randomised to one of four arms: (a) text summary of sensitivity and specificity, (b) Fagan’s nomogram, (c) probability-modifying plot (PMP), (d) natural frequency tree (NFT). The main outcome measure was the decision whether to treat, not treat or undertake a brain biopsy on the hypothetical patient and the correct post-test probability. Secondary outcome measures included knowledge of diagnostic tests. Results 917 participants attempted the survey and complete data were available from 874 (95.3%). Doctors randomized to the PMP and NFT arms were more likely to treat the patient than those randomized to the text-only arm. (ORs 1.49, 95% CI 1.02, 2.16) and 1.43, 95% CI 0.98, 2.08 respectively). More patients randomized to the PMP (87/218–39.9%) and NFT (73/207–35.3%) arms than the nomogram (50/194–25.8%) or text only (30/255–11.8%) arms reported the correct post-test probability (p <0.001). Younger age, postgraduate training and higher self-rated confidence all predicted better knowledge performance. Doctors with better knowledge were more likely to view an optional learning tutorial (OR per correct answer 1.18, 95% CI 1.06, 1.31). Conclusions Presenting diagnostic data using a probability-modifying plot or natural frequency tree influences the threshold for treatment and improves interpretation of tests results compared to text summary of sensitivity and specificity or Fagan’s nomogram. PMID:26147744

Evidence of virtual patients as a facilitative learning tool on an anesthesia course.

PubMed

Leung, Joseph Y C; Critchley, Lester A H; Yung, Alex L K; Kumta, Shekhar M

2015-10-01

Virtual patients are computerised representations of realistic clinical cases. They were developed to teach clinical reasoning skills through delivery of multiple standardized patient cases. The anesthesia course at The Chinese University of Hong Kong developed two novel types of virtual patients, formative assessment cases studies and storyline, to teach its final year medical students on a 2 week rotational course. Acute pain management cases were used to test if these two types of virtual patient could enhance student learning. A 2 × 2 cross over study was performed in academic year 2010-2011 on 130 students divided into four groups of 32-34. Performance was evaluated by acute pain management items set within three examinations; an end of module 60-item multiple choice paper, a short answer modified essay paper and the end of year final surgery modified essay paper. The pain management case studies were found to enhanced student performance in all three examinations, whilst the storyline virtual patient had no demonstrable effect. Student-teaching evaluation questionnaires showed that the case studies were favored more than the storyline virtual patient. Login times showed that students on average logged onto the case studies for 6 h, whereas only half the students logged on and used the storyline virtual patient. Formative assessment case studies were well liked by the students and reinforced learning of clinical algorithms through repetition and feedback, whereas the educational role of the more narrative and less interactive storyline virtual patient was less clear .

Accounting for frailty when treating chronic diseases.

PubMed

Onder, Graziano; Vetrano, Davide L; Marengoni, Alessandra; Bell, J Simon; Johnell, Kristina; Palmer, Katie

2018-03-08

Chronic diseases are considered to be major determinants of frailty and it could be hypothesized that their treatment may counteract the development of frailty. However, the hypothesis that intensive treatment of chronic diseases might reduce the progression of frailty is poorly supported by existing studies. In contrast, some evidence suggests that intensive treatment of chronic diseases may increase negative health outcomes in frail older adults. In particular, if treatment of symptoms related to chronic diseases (i.e. pain in osteoarthritis, dyspnoea in respiratory disease, motor symptoms in Parkinson disease) might potentially reverse frailty, the benefits related to preventive pharmacological treatment of chronic diseases (i.e. antihypertensive treatment) in patients with prevalent frailty is not certain. In particular, several factors might alter the risk/benefit ratio of a given treatment in persons with frailty. These include: exclusion of frail persons from clinical studies, reduced life expectancy in frail persons, increased susceptibility to iatrogenic events, and functional deficits associated with frailty. Therefore, frailty acts as an effect modifier, by modifying the risks and benefits of chronic disease treatments. This hypothesis must be considered and tested in future clinical intervention studies and clinical guidelines should provide specific recommendations for the treatment of frail people, underlining the pros and the cons of pharmacological treatment and possible targets for therapy in this population. Meanwhile, in older patients, the prescribing process should be individualized and flexible. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV.

PubMed

Liu, Dongfang; Tian, Shuo; Zhang, Kai; Xiong, Wei; Lubaki, Ndongala Michel; Chen, Zhiying; Han, Weidong

2017-12-01

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cytotoxic cell-mediated immunotherapies are urgently needed. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the formation of the immunological synapse (IS) between CAR-modified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat cancer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus (HIV), and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-mediated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.

Comparative Evaluation of Multiplex PCR and Routine Laboratory Phenotypic Methods for Detection of Carbapenemases among Gram Negative Bacilli.

PubMed

Solanki, Rachana; Vanjari, Lavanya; Subramanian, Sreevidya; B, Aparna; E, Nagapriyanka; Lakshmi, Vemu

2014-12-01

Carbapenem resistant pathogens cause infections associated with significant morbidity and mortality. This study evaluates the use of Multiplex PCR for rapid detection of carbapenemase genes among carbapenem resistant Gram negative bacteria in comparison with the existing phenotypic methods like modified Hodge test (MHT), combined disc test (CDT) and automated methods. A total of 100 Carbapenem resistant clinical isolates, [Escherichia coli (25), Klebsiella pneumoniae (35) P. aeruginosa (18) and Acinetobacter baumannii (22)] were screened for the presence of carbapenemases (bla NDM-1, bla VIM , blaIMP and blaKPC genes) by phenotype methods such as the modified Hodge test (MHT) and combined disc test (CDT) and the molecular methods such as Multiplex PCR. Seventy of the 100 isolates were MHT positive while, 65 isolates were positive by CDT. All the CDT positive isolates with EDTA and APB were Metallo betalactamase (MBL) and K. pneumoniae carbapenemase (KPC) producers respectively. bla NDM-1 was present as a lone gene in 44 isolates. In 14 isolates bla NDM-1 gene was present with blaKPC gene, and in one isolate bla NDM-1 gene was present with blaVIM , gene. Only one E. coli isolate had a lone blaKPC gene. We didn't find bla IMP gene in any of the isolates. Neither of the genes could be detected in 35 isolates. Accurate detection of the genes related with carbapenemase production by Molecular methods like Multiplex PCR overcome the limitations of the phenotypic methods and Automated systems.

Optical fiber immunosensor based on a poly(pyrrole-benzophenone) film for the detection of antibodies to viral antigen.

PubMed

Konry, T; Novoa, A; Shemer-Avni, Y; Hanuka, N; Cosnier, S; Lepellec, Arielle; Marks, R S

2005-03-15

We describe herein a newly developed optical microbiosensor for the diagnosis of hepatitis C virus (HCV) by using a novel photoimmobilization methodology based on a photoactivable electrogenerated polymer film deposited upon surface-conductive fiber optics, which are then used to link a biological receptor to the fiber tip through light mediation. This fiber-optic electroconductive surface modification is done by the deposition of a thin layer of indium tin oxide on the silica surface of the fiber optics. Monomers are then electropolymerized onto the conductive metal oxide surface; thereafter, the fibers are immersed in a solution containing HCV-E2 envelope protein antigen and illuminated with UV light (wavelength approximately 345 nm). As a result of the photochemical reaction, a thin layer of the antigen becomes covalently bound to the benzophenone-modified surface. The photochemically modified fiber optics were tested as immunosensors for the detection of anti-E2 protein antibody analyte that was measured through chemiluminescence reaction. The biosensor was tested for sensitivity, specificity, and overall practicality. Our results suggest that the detection of anti-E2 antibodies with this microbiosensor may enhance significantly HCV serological standard testing especially among patients during dialysis, which were diagnosed as HCV negative, by standard immunological tests, but were known to carry the virus. If transformed into an easy to use procedure, this assay might be used in the future as an important clinical tool for HCV screening in blood banks.

Walking adaptability after a stroke and its assessment in clinical settings.

PubMed

Balasubramanian, Chitralakshmi K; Clark, David J; Fox, Emily J

2014-01-01

Control of walking has been described by a tripartite model consisting of stepping, equilibrium, and adaptability. This review focuses on walking adaptability, which is defined as the ability to modify walking to meet task goals and environmental demands. Walking adaptability is crucial to safe ambulation in the home and community environments and is often severely compromised after a stroke. Yet quantification of walking adaptability after stroke has received relatively little attention in the clinical setting. The objectives of this review were to examine the conceptual challenges for clinical measurement of walking adaptability and summarize the current state of clinical assessment for walking adaptability. We created nine domains of walking adaptability from dimensions of community mobility to address the conceptual challenges in measurement and reviewed performance-based clinical assessments of walking to determine if the assessments measure walking adaptability in these domains. Our literature review suggests the lack of a comprehensive well-tested clinical assessment tool for measuring walking adaptability. Accordingly, recommendations for the development of a comprehensive clinical assessment of walking adaptability after stroke have been presented. Such a clinical assessment will be essential for gauging recovery of walking adaptability with rehabilitation and for motivating novel strategies to enhance recovery of walking adaptability after stroke.

Walking Adaptability after a Stroke and Its Assessment in Clinical Settings

PubMed Central

Balasubramanian, Chitralakshmi K.; Clark, David J.; Fox, Emily J.

2014-01-01

Control of walking has been described by a tripartite model consisting of stepping, equilibrium, and adaptability. This review focuses on walking adaptability, which is defined as the ability to modify walking to meet task goals and environmental demands. Walking adaptability is crucial to safe ambulation in the home and community environments and is often severely compromised after a stroke. Yet quantification of walking adaptability after stroke has received relatively little attention in the clinical setting. The objectives of this review were to examine the conceptual challenges for clinical measurement of walking adaptability and summarize the current state of clinical assessment for walking adaptability. We created nine domains of walking adaptability from dimensions of community mobility to address the conceptual challenges in measurement and reviewed performance-based clinical assessments of walking to determine if the assessments measure walking adaptability in these domains. Our literature review suggests the lack of a comprehensive well-tested clinical assessment tool for measuring walking adaptability. Accordingly, recommendations for the development of a comprehensive clinical assessment of walking adaptability after stroke have been presented. Such a clinical assessment will be essential for gauging recovery of walking adaptability with rehabilitation and for motivating novel strategies to enhance recovery of walking adaptability after stroke. PMID:25254140

Conformity of modified O-ring test and maximal pinch strength for cross tape application direction.

PubMed

Lee, Jung-Hoon; Choi, Hyun-Su

2018-06-01

Although cross tape has recently been used by clinicians for various musculoskeletal conditions, scientific studies on the direction of cross tape application are lacking. The present study aimed to investigate whether the direction of cross tape application affected the outcomes of the modified O-ring test and maximal pinch strength using a pinch gauge and the conformity between these 2 tests when cross tape was applied to the forearm muscles of individuals with no upper extremity pain and no restriction of joint range of motion.This study used a single-blinding crossover design. The subjects comprised 39 adults (16 men and 23 women). Cross tape was applied to the dominant hand so that the 4 rows were at an angle of 45° to the right or left of the direction of the flexor digitorum superficialis muscle fibers, and then the subjects underwent a modified O-ring test and a test of maximal pinch strength using a pinch gauge. Both tests were performed in both directions, and the order of the directions and tests was randomized. SPSS 18.0 was used for statistical analysis. Cohen's kappa coefficient was used to analyze the conformity of the results from the 2 tests. The statistical significance level was P < .05. A positive response in the modified O-ring test and maximal pinch strength were both affected by cross tape direction. The modified O-ring test and maximal pinch strength using pinch gauge results were in agreement (P < .00), and the kappa coefficient was significant at 1.00. The direction of cross tape application that produced a positive response in the modified O-ring test also produced greater maximal pinch strength. Thus, we propose that when applying cross tape to muscles, the direction of the 4 lines of the cross tape should be 45° relative to the direction of the muscle fibers, toward the side that produces a positive response in the modified O-ring test or produces the greatest maximal pinch strength using a pinch gauge.

Comparisons of modified Vasco X-2 and AISI 9310 gear steels

NASA Technical Reports Server (NTRS)

Townsend, D. P.; Zaretsky, E. V.

1980-01-01

Endurance tests were conducted with four groups of spur gears manufactured from three heats of consumable electrode vacuum melted (CVM) modified Vasco X-2. Endurance tests were also conducted with gears manufactured from CVM AISI 9310. Bench type rolling element fatigue tests were conducted with both materials. Hardness measurements were made to 811 K. There was no statistically significant life difference between the two materials. Life differences between the different heats of modified Vasco X-2 can be attributed to heat treat variation and resultant hardness. Carburization of gear flanks only can eliminate tooth fracture as a primary failure mode for modified Vasco X-2. However, a tooth surface fatigue spall can act as a nucleus of a tooth fracture failure for the modified Vasco X-2.

Endurance and failure characteristics of modified Vasco X-2, CBS 600 and AISI 9310 spur gears. [aircraft construction materials

NASA Technical Reports Server (NTRS)

Townsend, D. P.; Zaretsky, E. V.

1980-01-01

Gear endurance tests and rolling-element fatigue tests were conducted to compare the performance of spur gears made from AISI 9310, CBS 600 and modified Vasco X-2 and to compare the pitting fatigue lives of these three materials. Gears manufactured from CBS 600 exhibited lives longer than those manufactured from AISI 9310. However, rolling-element fatigue tests resulted in statistically equivalent lives. Modified Vasco X-2 exhibited statistically equivalent lives to AISI 9310. CBS 600 and modified Vasco X-2 gears exhibited the potential of tooth fracture occurring at a tooth surface fatigue pit. Case carburization of all gear surfaces for the modified Vasco X-2 gears results in fracture at the tips of the gears.

Determination of the diagnostic value of the Modified Mallampati Score, Upper Lip Bite Test and Facial Angle in predicting difficult intubation: A prospective descriptive study.

PubMed

Mahmoodpoor, Ata; Soleimanpour, Hassan; Golzari, Samad Ej; Nejabatian, Arezoo; Pourlak, Tannaz; Amani, Masoumeh; Hajmohammadi, Saeed; Hosseinzadeh, Hamzeh; Esfanjani, Robab Mehdizadeh

2017-02-01

Difficult intubation is a significant cause of mortality and morbidity related to anesthesia. We decided to evaluate the value of Modified Mallampati Score, Upper Lip Bite Test and Facial Angle in the prediction of difficult intubation. In a prospective descriptive study, data from 132 patients who were candidates for elective maxillofacial surgeries under general anesthesia were gathered. Facial Angles were measured by a maxillofacial surgeon according to cephalometry. The Modified Mallampati Score and Upper Lip Bite Test were first measured by an anesthesiologist and then another anesthesiologist was assigned to record the Cormack and Lehane score during the intubation. Grades 3 and 4 were considered as difficult intubation. Sensitivity, specificity, positive predictive value, negative predictive value and Youden index were calculated for all tests. Difficult intubation was reported in 12% of the patients. Facial Angle≤82.5° can predict difficult intubation with 87.5% sensitivity and 88.8% specificity. Among the three tests, a high Modified Mallampati Score had the highest specificity (94.5%) and a high Modified Mallampati Score and Facial Angle (FA≤82.5°) had the highest sensitivity (87.5%). The highest NPV, sensitivity and Youden index were observed when using Facial Angle with the Modified Mallampati Score or with Upper Lip Bite Test. Facial Angle has a high sensitivity, NPV and Youden index for the prediction of difficult intubation, but the best result is achieved when Facial Angle is used in combination with either the Modified Mallampati Score or Upper Lip Bit Test. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a Modified Korean East Asian Student Stress Inventory by Comparing Stress Levels in Medical Students with Those in Non-Medical Students.

PubMed

Shin, Hee Kon; Kang, Seok Hoon; Lim, Sun-Hye; Yang, Jeong Hee; Chae, Sunguk

2016-01-01

Medical students are usually under more stress than that experienced by non-medical students. Stress testing tools for Korean medical students have not been sufficiently studied. Thus, we adapted and modified the East Asian Student Stress Inventory (EASSI), a stress testing tool for Korean students studying abroad, and verified its usefulness as a stress test in Korean university students. We also compared and analyzed stress levels between medical and non-medical students. A questionnaire survey was conducted on medical and non-medical students of a national university, and the responses of 224 students were analyzed for this study. Factor analysis and reliability testing were performed based on data collected for 25 adapted EASSI questions and those on the Korean version of the Global Assessment of Recent Stress Scale (GARSS). A correlation analysis was performed between the 13 modified EASSI questions and the GARSS, and validity of the modified EASSI was verified by directly comparing stress levels between the two student groups. The 13 questions adapted for the EASSI were called the modified EASSI and classified into four factors through a factor analysis and reliability testing. The Pearson's correlation analysis revealed a significant correlation between the modified EASSI and the Korean version of the GARSS, suggesting a complementary strategy of using both tests. The validity and reliability of the EASSI were verified. The modified Korean EASSI could be a useful stress test for Korean medical students. Our results show that medical students were under more stress than that of non-medical students. Thus, these results could be helpful for managing stress in medical students.

Effect of chromium picolinate on modified forced swimming test in diabetic rats: involvement of serotonergic pathways and potassium channels.

PubMed

Khanam, Razia; Pillai, K K

2006-02-01

Depression occurs frequently in patients with diabetes mellitus. Chromium picolinate, an essential trace element is recommended for diabetes and also has been reported to benefit depression, but its mechanism is still debated. To investigate the mechanism, we studied its effects on serum insulin, serum glucose and on modified forced swimming test, a behavioural paradigm for depression in rats. The study involving co-administration of sub-active doses of glimepiride, a K(+) channel blocker and chromium picolinate on blood glucose levels and modified forced swimming test was also performed to probe any role of K(+) channels in its antidiabetic and antidepressants effects. Streptozotocin (55 mg/kg, intraperitoneally) was injected in rats to induce diabetes (Type 1). After a week, chromium picolinate (8 microg/ml in drinking water) was administered for 4 weeks. Normal rats received similar drug treatment. The sub-active doses of chromium picolinate (4 microg/ml in drinking water) and glimeperide (2.5 mg/kg, orally) were co-administered and their effects on modified forced swimming test and on glucose levels were measured. Chromium picolinate (8 microg/ml in drinking water) produced hypoglycaemia in diabetic and normal rats. It had no effects on the streptozotocin-induced reduction in insulin levels. Chromium picolinate (8 microg/ml in drinking water) increased swimming with subsequent decrease in immobility. The sub-active doses of chromium picolinate and glimeperide showed significant additive effects in modified forced swimming test and reduction in serum glucose concentrations, though statistically insignificant. In conclusion chromium picolinate shows antidepressant action on modified forced swimming test affecting only swimming that suggests serotonergic pathways involvement. The additive effects on swimming in modified forced swimming test and reduction in serum glucose levels shows involvement of K(+) channels in antidiabetic and antidepressant actions of chromium picolinate.

Detection of Genetically Modified Food: Has Your Food Been Genetically Modified?

ERIC Educational Resources Information Center

Brandner, Diana L.

2002-01-01

Explains the benefits and risks of genetically-modified foods and describes methods for genetically modifying food. Presents a laboratory experiment using a polymerase chain reaction (PCR) test to detect foreign DNA in genetically-modified food. (Contains 18 references.) (YDS)

Pyocyanine Biosynthetic Genes in Clinical and Environmental Isolates of Pseudomonas aeruginosa and Detection of Pyocyanine’s Antimicrobial Effects with or without Colloidal Silver Nanoparticles

PubMed Central

Nowroozi, Jamileh; Akhavan Sepahi, Abbas; Rashnonejad, Afrooz

2012-01-01

Objective: Pyocyanine plays an important role in the pathogenesis of Pseudomonas aeruginosa, (P. aeruginosa) and is known to have inhibitory and bactericidal effects. This study has aimed to detect the phenazine biosynthetic operon (phz ABCDEFG) and two phenazine modifying genes (phzM and phzS) by polymerase chain reaction (PCR) and detection of its possible protein bands by sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE). The antimicrobial effects of pyocyanine alone and mixed with colloidal silver nanoparticles were studied. Materials and Methods: In this descriptive study, clinical and environmental species of P. aeruginosa were isolated by thioglycollate medium culture and cetrimide agar, respectively. The existence of a phenazine biosynthetic operon and two phenazine modifying genes as well as their protein products were confirmed by PCR and SDS-PAGE, respectively. Pyocyanine was extracted with chloroform and its antimicrobial effects against bacteria such as; Escherichia coli (E. coli), P. aeruginosaand Staphylococcus aureus (S. aureus) bacteria and yeast Candida albicans (C. albicans) were tested using well, spot and disk diffusion methods. Results: In this study, 3 out of 48 clinical strains were unable to produce pyocyanine on cetrimide and Mueller Hinton (MH) agar. Two strains did not have phenazine modifying gene bands. Another strain did not have the possible protein band of the phzM gene. Pyocyanine had antimicrobial effects against the microbial strains, which increased in the presence of silver nanoparticles. Conclusion: According to the results of the present study, some P. aeruginosa strains are unable to produce pyocyanine due to the absence of the phzM or phzS genes. Therefore, these genes have an important role in pyocyanine production in P. aeruginosa. Pyocyanine shows synergistic antimicrobial effects in the presence of silver nanoparticles against microbial strains. PMID:23626932

Generated effect modifiers (GEM’s) in randomized clinical trials

PubMed Central

Petkova, Eva; Tarpey, Thaddeus; Su, Zhe; Ogden, R. Todd

2017-01-01

In a randomized clinical trial (RCT), it is often of interest not only to estimate the effect of various treatments on the outcome, but also to determine whether any patient characteristic has a different relationship with the outcome, depending on treatment. In regression models for the outcome, if there is a non-zero interaction between treatment and a predictor, that predictor is called an “effect modifier”. Identification of such effect modifiers is crucial as we move towards precision medicine, that is, optimizing individual treatment assignment based on patient measurements assessed when presenting for treatment. In most settings, there will be several baseline predictor variables that could potentially modify the treatment effects. This article proposes optimal methods of constructing a composite variable (defined as a linear combination of pre-treatment patient characteristics) in order to generate an effect modifier in an RCT setting. Several criteria are considered for generating effect modifiers and their performance is studied via simulations. An example from a RCT is provided for illustration. PMID:27465235

Sinonasal organised haematoma: clinical features and successful application of modified transnasal endoscopic medial maxillectomy.

PubMed

Suzuki, M; Nakamura, Y; Ozaki, S; Yokota, M; Murakami, S

2017-08-01

Although organised haematoma often induces bone thinning and destruction similar to malignant diseases, the aetiology of organised haematoma and the optimal treatment remain unclear. This paper presents the clinical features of individuals with organised haematoma, and describes cases in which a novel modified approach was successfully applied for resection of organised haematoma in the maxillary sinus. Pre-operative examination data were evaluated retrospectively. Modified transnasal endoscopic medial maxillectomy was employed. Fourteen patients with organised haematoma were treated. Contrast-enhanced computed tomography showed heterogeneous enhancement in all patients. Eight patients underwent modified transnasal endoscopic medial maxillectomy, without complications such as facial numbness, tooth numbness, facial tingling, lacrimation and eye discharge. Dissection of the apertura piriformis and anterior maxillary wall was not necessary for any of these eight patients. No recurrence was observed. Pre-operative examinations can be helpful in determining the likelihood of organised haematoma. Modified transnasal endoscopic medial maxillectomy appears to be a safe and effective method for organised haematoma resection.

Reversible Venting Stitch for Fenestrating Valve-less Glaucoma Shunts.

PubMed

Akil, Handan; Vu, Priscilla Q; Nguyen, Anhtuan H; Nugent, Alexander; Chopra, Vikas; Francis, Brian A; Tan, James C

2017-12-01

The purpose of this is to describe a venting stitch modification for valveless glaucoma aqueous shunts and characterize early postoperative intraocular pressure (IOP) and glaucoma medication use following the modification. Retrospective chart review of 61 sequential patients undergoing Baerveldt glaucoma implant (BGI)-350 implantation at the Doheny Eye Institute. Twenty-four patients received a glaucoma shunt with venting stitch modification (modified BGI) and 37 patients received an unmodified shunt (BGI-only). IOP, number of glaucoma medications, and number of hypotony cases (intraocular pressure ≤5 mm Hg) were compared between the groups. T-tests were used for statistical analysis. At postoperative-day 1, mean IOP was significantly lower compared with preoperatively in the modified BGI group (14 mm Hg; reduced by 51%; P<0.0001) but not the BGI-only group (27 mm Hg; P=0.06). IOP difference between groups persisted till immediately before tube opening (P=0.005) and fewer IOP-lowering medications needed in the modified BGI group (P<0.0001). One case (4.2%) of postoperative hypotony was encountered with BGI modification, which resolved after the stitch was removed in clinic. The venting stitch valveless shunt modification allows for effective, reliable, and safe control of early postoperative IOP.

Further evidence for the reliability and validity of the Modified Dental Anxiety Scale.

PubMed

Humphris, G M; Freeman, R; Campbell, J; Tuutti, H; D'Souza, V

2000-12-01

To gain further evidence of the psychometric properties of the Modified Dental Anxiety Scale. Dental admission clinics. Consecutive sampling, cross-sectional survey. Patients (n = 800) in four cities (Belfast, Northern Ireland; Helsinki, Finland; Jyväskylä, Finland and Dubai, UAE). Questionnaire booklet handed to patients, attending clinics, for completion following an invitation by the researcher to be included in the study. Modified Dental Anxiety Scale (MDAS), together with further questions concerning dental attendance and nervousness about dental procedures. Overall 9.3 per cent of patients indicated high dental anxiety. MDAS showed high levels of internal consistency, and good construct validity. The relationship of dental anxiety with age was similar to previous reports and showed lowered anxiety levels in older patients. Data from three countries has supported the psychometric properties of this modified and brief dental anxiety scale.

Effectiveness of Plaque Control with Novel Pediatric Oral Hygiene Need Station (Modified Oral Irrigation Device) as Compared with Manual Brushing and Flossing: Randomized Controlled Pilot Trial

PubMed Central

Murthy, Prashanth Sadashiva; Shaik, Naseemoon; Deshmukh, Seema; Girish, M. S.

2018-01-01

Background: Establishing good hygiene habits are valuable for present and future oral health. Below 6 years, tooth brushing should be performed by parents, as increasing dexterity and cognition may permit supervised brushing until the child is capable of independent brushing. Aim and Objectives: The aim of the present study was to evaluate the effectiveness of modified oral irrigation device in children in terms of plaque control and to compare the effectiveness of plaque control with manual brushing with the modified oral irrigation device in children. Materials and Methods: A randomized clinical trial was performed on 12 subjects who were allocated to the two study groups. After obtaining the consent, the control group was instructed tooth brushing with regular pediatric commercially available toothbrush and the intervention group with modified oral irrigation device. Plaque scores in both groups were assessed pre- and post-brushing using modified navy plaque index. Results: The data were subjected to Descriptive statistics and Paired t-test using SPSS version 22. Intragroup comparison of mean difference of plaque score in control group and intervention group pre- and post-brushing was statistically significant. Intergroup comparison of manual brushing group with modified oral irrigation group shows P < 0.05 was statistically significant. Conclusion: Within the limitation of the present study, it has been found novel pediatric oral hygiene need Station is more effective than manual brushing since it combined the effect of brushing, flossing (water floss), and rinsing in children simultaneously and at the same time did not demand any special motor skill. PMID:29875555

Quality assessment of clinical education services in teaching hospitals located in Kerman, Iran.

PubMed

Yazdi-Feyzabadi, Vahid; Gozashti, Mohammad Hossein; Komsari, Samane; Mohammadtaghizadeh, Sedigheh; Amiresmaili, Mohammadreza

2015-11-01

Clinical education is one of the most important components of the resource generation function of health systems, and it has a very important role in graduates' competency with respect to effective, practical education. This study aimed to assess the quality of clinical services in Kerman's teaching hospitals located in southeastern Iran. This cross-sectional study was conducted in 2011 on 303 medical students at different levels of medical education at Kerman's teaching hospitals. A modified SERVQUAL instrument was used to collect the data after its validity and reliability were checked. The data were analyzed by SPSS 18.0 using the paired t-test, Kruskal-Wallis, and post hoc tests, when appropriate. In all five dimensions of quality, gaps were observed between students' perceptions and expectations as follows: Assurance (mean = -1.18), Responsiveness (-1.56), Empathy (-1.4), Reliability (-1.27), and Tangibles (-1.21). There was a significant difference between the quality perceptions and expectations of the medical students (p < 0.001). A significant difference was observed between three educational levels, including externships, internships, and assistantships regarding the dimensions of the quality gaps (p < 0.001). The clinical services provided by teaching hospitals in the study did not meet the students' expectations at any of the three educational levels. As we precisely assessed the dimensions and items that had the higher quality gaps, it was apparent that, for most part, clinical education officials could improve the quality by designing interventions, which would not be very difficult to do.

Theory-based modifications of an advanced notification letter improves screening for bowel cancer in men: A randomised controlled trial.

PubMed

Zajac, Ian T; Duncan, Amy C; Flight, Ingrid; Wittert, Gary A; Cole, Stephen R; Young, Graeme P; Wilson, Carlene J; Turnbull, Deborah A

2016-09-01

Male participation in screening for bowel cancer is sub-optimal. Theory-based interventions provide a means of improving screening uptake. To test the efficacy of modifying consumer invitation material in line with continuum and stage theories of health behaviour on screening participation. N = 9216 Australian men aged 50-74 years were randomised to one of four trial arms in a 2 × 2 factorial design randomised controlled trial. Participants received either standard invitation material (control group), or combinations of modified advance-notification and invitation letters. A subsample completed baseline and endpoint behavioural surveys. Participants who received the modified advance notification letter were 12% more likely to screen than those who received the standard version (RR = 1.12, χ(2)(1) = 10.38, p = 0.001). The modified invitation letter did not impact screening uptake (RR = 0.97, χ(2)(1) = 0.63, p = 0.424). No significant changes in psychological variables due to the intervention were observed. Modifications to advance notification letters in line with health behaviour theories significantly improves screening uptake in men. Australian New Zealand Clinical Trials Registry: ACTRN12612001122842 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362688. Copyright © 2016 Elsevier Ltd. All rights reserved.