Assessing plantar sensation in the foot using the FOot Roughness Discrimination Test (FoRDT™): a reliability and validity study in stroke

BACKGROUND: The foot sole represents a sensory dynamometric map and is essential for balance and gait control. Sensory impairments are common, yet often difficult to quantify in neurological conditions, particularly stroke. A functionally oriented and quantifiable assessment, the Foot Roughness Discrimination Test (FoRDT™), was developed to address these shortcomings. OBJECTIVE: To evaluate inter- and intra-rater reliability, convergent and discriminant validity of the Foot Roughness Discrimination Test (FoRDT™). DESIGN: Test-retest design. SETTING: Hospital Outpatient. PARTICIPANTS: Thirty-two people with stroke (mean age 70) at least 3 months after stroke, and 32 healthy, age-matched controls (mean age 70). MAIN OUTCOME MEASURES: Roughness discrimination thresholds were quantified utilising acrylic foot plates, laser-cut to produce graded spatial gratings. Stroke participants were tested on three occasions, and by two different raters. Inter- and intra-rater reliability and agreement were evaluated with Intraclass Correlation Coefficients and Bland-Altman plots. Convergent validity was evaluated through Spearman rank correlation coefficients (rho) between the FoRDT™ and the Erasmus modified Nottingham Sensory Assessment (EmNSA). RESULTS: Intra- and inter rater reliability and agreement were excellent (ICC =.86 (95% CI .72-.92) and .90 (95% CI .76 -.96)). Discriminant validity was demonstrated through significant differences in FoRDT™ between stroke and control participants (p.05). CONCLUSIONS: This simple and functionally oriented test of plantar sensation is reliable, valid and clinically feasible for use in an ambulatory, chronic stroke and elderly population. It offers clinicians and researchers a sensitive and robust sensory measure and may further support the evaluation of rehabilitation targeting foot sensation. This article is protected by copyright. All rights reserved

N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study

Background Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. Objectives This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. Methods Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (−) likelihood ratios (LRs) for acute HF. Results Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR− was 0.09 (95% CI: 0.05 to 0.13). Conclusions In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF

Routine use of completion imaging after infrainguinal bypass is not associated with higher bypass graft patency

BackgroundSignificant variability exists in completion imaging (CIM) after infrainguinal lower extremity bypass (LEB). We evaluated the use of CIM and compared graft patency in patients treated by surgeons who performed routine CIM vs those who performed selective CIM.MethodsWe reviewed the Vascular Study Group of New England database (2003-2010) and assessed the use of CIM (angiography or duplex ultrasound) among patients undergoing LEB. The surgeon-specific CIM strategy was categorized as routine (≥80% of LEBs) vs selective (<80% of LEBs). Exclusion criteria included acute limb ischemia, bilateral procedures, and surgeon volume <10 cases per study period. Primary graft patency at discharge and at 1 year was analyzed on the basis of CIM use and surgeon-specific CIM strategy. Multivariable analyses were performed using Poisson regression.ResultsAmong 2032 LEB procedures performed by 48 surgeons, CIM was used in 1368 cases (67.3%). CIM was performed in 72% of autogenous LEBs and 52% of prosthetic grafts. Dialysis (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.6; P = .01), elective LEB (OR, 2.6; 95% CI, 1.4-4.8; P = .002), great saphenous vein conduit (OR, 2.0; 95% CI, 1.6-2.5; P < .001), and tibial or pedal target artery (OR, 1.8; 95% CI, 1.4-2.3; P < .001) were associated with CIM use. In multivariate models, CIM was not associated with improved primary graft patency at discharge (OR, 1.1; 95% CI, 0.7-1.7; P = .64) or at 1 year (OR, 0.9; 95% CI, 0.7-1.2; P = .47). Sixteen surgeons (33%) were routine users and 32 (67%) were selective users of CIM. Among patients of routine vs selective CIM users, primary graft patency at discharge and at 1 year was 96% vs 94% (P = .21) and 68% vs 72% (P = .09), respectively. In multivariate analysis, routine or selective CIM strategy was not associated with improved discharge (rate ratio, 0.8; 95% CI, 0.6-1.1; P = .31) or 1-year (rate ratio, 1.1; 95% CI, 0.9-1.2; P = .56) graft patency.ConclusionsIn our observational cohort, CIM does not improve short-term and 1-year bypass graft patency in infrainguinal LEB. The surgeon-specific strategy of selective CIM after LEB has outcomes comparable to those of routine CIM

Caregiving, Metabolic Syndrome Indicators, and 1-year Decline in Walking Speed: Results of Caregiver-SOF

BACKGROUND Chronic stress may lead to health decline through metabolic syndrome. Thus, persons in stressful caregiving situations who also have more indicators of metabolic syndrome may experience more decline than other caregivers or noncaregivers. METHODS The sample included 921 women (338 caregivers and 583 noncaregivers) from the Caregiver-Study of Osteoporotic Fractures study. Participants had home-based baseline and 1-year follow-up interviews between 1999 and 2003. At baseline, caregivers were categorized as long term (³4 years) versus short term (<4 years), and caring for someone with Alzheimer's disease/dementia or not. A metabolic risk composite score was the sum of four indicators: body mass index ³30, and diagnosis or using medications for hypertension, diabetes, or high cholesterol. Walking speed (m/second) was measured at both interviews. RESULTS Walking speed declined for the total sample (adjusted mean = −0.005 m/second, ±0.16) over an average of 1.04 years (±0.16). Overall, caregiving was not associated with decline. Increasing metabolic risk score was associated with greater decline for the total sample and long-term and dementia caregivers, but not other caregivers or noncaregivers. Metabolic risk score modified the adjusted associations between years of caregiving and dementia caregiving with walking speed decline (p values for interaction terms were 0.039 and 0.057, respectively). The biggest declines were in long-term caregivers and dementia caregivers who also had 3–4 metabolic indicators (−0.10 m/second and −0.155 m/second, respectively). CONCLUSIONS Walking speed declined the most among older women who had both stressful caregiving situations and more metabolic syndrome indicators, suggesting these caregiver subgroups may have increased risk of health decline.AG18037, AG05407, AR35582, AG05394, AR35584, and AR3558

Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences

Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells that can remain dormant as epithelial cysts or progress to high-grade sarcoma. Predisposing germline loss-of-function DICER1 variants have been described. We sought to uncover additional contributors through whole exome sequencing of 15 tumor/normal pairs, followed by targeted resequencing, miRNA analysis and immunohistochemical analysis of additional tumors. In addition to frequent biallelic loss of TP53 and mutations of NRAS or BRAF in some cases, each case had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases) loss-of-function variant plus a somatic missense mutation in the RNase IIIb domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA loop sequences normally removed by DICER1. This work both defines a genetic interaction landscape with DICER1 mutation and provides evidence for alteration in miRNA transcripts as a consequence of DICER1 disruption in cancer

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen

Background Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care

Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma

A number of genetic syndromes have been linked to increased risk for Wilms tumor (WT), hepatoblastoma (HB), and other embryonal tumors. Here, we outline these rare syndromes with at least a 1% risk to develop these tumors and recommend uniform tumor screening recommendations for North America. Specifically, for syndromes with increased risk for WT, we recommend renal ultrasounds every 3 months from birth (or the time of diagnosis) through the seventh birthday. For HB, we recommend screening with full abdominal ultrasound and alpha-fetoprotein serum measurements every 3 months from birth (or the time of diagnosis) through the fourth birthday. We recommend that when possible, these patients be evaluated and monitored by cancer predisposition specialists. At this time, these recommendations are not based on the differential risk between different genetic or epigenetic causes for each syndrome, which some European centers have implemented. This differentiated approach largely represents distinct practice environments between the United States and Europe, and these guidelines are designed to be a broad framework within which physicians and families can work together to implement specific screening. Further study is expected to lead to modifications of these recommendations.This study was supported by NCI K08 CA1939915, Alex's Lemonade Stand Foundation for Childhood Cancer, and St. Baldrick's Foundation (to J.M. Kalish); European Research Council Advanced Researcher Award (to E.R. Maher); and NCI 5P30CA054174-21 (to G.E. Tomlinson)

Quantitative imaging biomarkers of coronary plaque morphology: insights from EVAPORATE

AimsResidual cardiovascular risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total events, but the mechanisms of benefit are not fully understood. EVAPORATE evaluated the effects of IPE on plaque characteristics by coronary computed tomography angiography (CCTA). Given the conclusion that the IPE-treated patients demonstrate that plaque burden decreases has already been published in the primary study analysis, we aimed to demonstrate whether the use of an analytic technique defined and validated in histological terms could extend the primary study in terms of whether such changes could be reliably seen in less time on drug, at the individual (rather than only at the cohort) level, or both, as neither of these were established by the primary study result.Methods and ResultsEVAPORATE randomized the patients to IPE 4 g/day or placebo. Plaque morphology, including lipid-rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH), was assessed using the ElucidVivo® (Elucid Bioimaging Inc.) on CCTA. The changes in plaque morphology between the treatment groups were analyzed. A neural network to predict treatment assignment was used to infer patient representation that encodes significant morphological changes. Fifty-five patients completed the 18-month visit in EVAPORATE with interpretable images at each of the three time points. The decrease of LRNC between the patients on IPE vs. placebo at 9 months (reduction of 2 mm3 vs. an increase of 41 mm3, p = 0.008), widening at 18 months (6 mm3 vs. 58 mm3 increase, p = 0.015) were observed. While not statistically significant on a univariable basis, reductions in wall thickness and increases in cap thickness motivated multivariable modeling on an individual patient basis. The per-patient response assessment was possible using a multivariable model of lipid-rich phenotype at the 9-month follow-up, p &lt; 0.01 (sustained at 18 months), generalizing well to a validation cohort.ConclusionPlaques in the IPE-treated patients acquired more characteristics of stability. Reliable assessment using histologically validated analysis of individual response is possible at 9 months, with sustained stabilization at 18 months, providing a quantitative basis to elucidate drug mechanism and assess individual patient response

Paediatric and adult congenital cardiology education and training in Europe

Background: Limited data exist on training of European paediatric and adult congenital cardiologists. Methods: A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries. Results: Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87-9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63-10.72 million), and one training centre per 4.29 million population (range 1.63-10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1-17), and duration of training was 3 years (range 2-5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R-2 = 0.41). Conclusion: Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.Developmen