PRECISION: the Belgian molecular profiling program of metastatic cancer for clinical decision and treatment assignment.

PRECISION is an initiative from the Belgian Society of Medical Oncology (BSMO) in collaboration with several stakeholders, encompassing four programs that aim to boost genomic and clinical knowledge with the ultimate goal to offer patients with metastatic solid tumors molecularly guided treatments. The PRECISION 1 study has led to the creation of a clinico-genomic database. The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) and GeNeo studies will increase the number of patients with advanced cancer that have comprehensive genotyping of their cancer. The PRECISION 2 project consists of investigator-initiated phase II studies aiming to provide access to a targeted drug for patients whose tumors harbor actionable mutations in case the matched drug is not available through reimbursement or clinical trials in Belgium.

An intensive exercise-based training program reduces prefrontal activity during usual walking in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) leads to a progressive loss of locomotor automaticity. Consequently, PD patients rely more on executive resources for the control of gait, resulting in increased prefrontal activity while walking. Exercise-based training programs may improve automaticity of walking and reduce prefrontal activity in this population. This study aimed to assess the effect of an intensive multidisciplinary exercise-based training program on prefrontal activity and gait performance during usual walking in PD patients. METHOD: Fourteen patients (mean age: 67 ± 9; disease duration: 6 ± 5 years; Hoehn and Yahr score: 1.9 ± 0.6) were included in this study. They were assessed in ON stage at three different times at 5-week intervals: two times before the training program (T0 and T1) and once after the training program (T2). Gait performance (stride time, speed, stride length, cadence, and their respective coefficient of variation) and cortical activity in the dorsolateral prefrontal cortex (DLPFC) using functional near infrared spectroscopy (fNIRS) were measured during usual walking. RESULTS: Patients had reduced cortical activity of the DLPFC at T2 compared to T1 (p = 0.003). Patients had shorter stride time at T2 compared to T1 (p = 0.025) and tended to have longer stride length at T2 than at T1 (p = 0.056). CONCLUSION: The training program led to positive effects on prefrontal activity and gait performance. Reduced prefrontal activity during usual walking after training program suggests that patients may have a greater reserve capacity to face more challenging walking conditions. Further studies will investigate the effect of this training on cortical activity during dual-task walking..

Increased prefrontal activity during usual walking in aging.

Executive functions are important for successful accomplishment of walking tasks, particularly during a dual task. Over the past few years, several studies investigated prefrontal cortex activity under different walking conditions in older adults with functional near infrared spectroscopy (fNIRS). However, little is known about changes in dorsolateral prefrontal cortex (DLPFC) activity during walking in the early stages of aging. The main objective of this study was to compare changes in DLPFC activity during simple and dual task walking across three different age groups. Twenty-five young (age range = 18-37), twenty-five youngest-old (age range = 55-65), and twenty-five older adults (age range = 67-87) participated in this study. Main results showed that, during simple task walking, older adults had increased DLPFC activity with equivalent walking performance. This increased mainly concerned the right hemisphere. During dual task walking, older adults had increased right DLPFC activity but seemed to have enough resources to maintain their performance during DT walking. This result supports the idea that compensation mechanisms, due to loss of automaticity of walking in aging, appear already during simple task walking. Measuring cortical activity with fNIRS during a simple task walking might be used as valuable indicator for identifying individuals at risk of falling.

Concussion symptoms experienced during driving may influence driving habits.

Objective: To examine the symptoms experienced and the change in driving habits in individuals with concussion.Materials and methods: A survey was created by a team of rehabilitation professionals who see persons with concussion in their clinics. The survey captured demographics, mechanism of injury, date of injury, symptoms experienced during driving, if drivers felt safe when driving, and changes in driving habits since the concussion. Non-parametric tests were used to compare symptoms experienced and driving habits across three groups which were created based on time since injury.Results: Of the 140 participants, 74% (104/140) had resumed driving after concussion; of these 27% (28/104) reported that they felt unsafe while driving. Forty-four per cent (46/104) experienced symptoms while driving, of which headache, and difficulty concentrating were the most common symptoms experienced throughout the concussion spectrum (acute to chronic phase). Most drivers (78/104, 75%) with concussion had changed their driving habits by driving less often and shorter distances, and by avoiding nighttime driving and heavy traffic areas.Conclusions: Headache and concentration problems were experienced by drivers regardless of the time since injury. Most drivers had made changes to their driving habits. Clinicians should consider the symptom burden patients experience and discuss driving restrictions to ensure driving safety.

A multi-modal virtual reality treadmill intervention for enhancing mobility and cognitive function in people with multiple sclerosis: Protocol for a randomized controlled trial.

BACKGROUND: Gait and cognitive impairments are common in individuals with Multiple Sclerosis (MS) and can interfere with everyday function. Those with MS have difficulties executing cognitive tasks and walking simultaneously, a reflection of dual-task interference. Therefore, dual-task training may improve functional ambulation. Additionally, using technology such as virtual reality can provide personalized rehabilitation while mimicking real-world environments. The purpose of this randomized controlled trial is to establish the benefits of a combined cognitive-motor virtual reality training on MS symptoms compared to conventional treadmill training. METHODS: This study will be a single-blinded, two arm RCT with a six-week intervention period. 144 people with MS will be randomized into a treadmill training alone group or treadmill training with virtual reality group. Both groups will receive 18 sessions of training while walking on a treadmill, with the virtual reality group receiving feedback from the virtual system. Primary outcome measures include dual-task gait speed and information processing speed, which will be measured prior to training, one-week post-training, and three months following training. DISCUSSION: This study will provide insight into the ability of a multi-modal cognitive-motor intervention to reduce dual-task cost and to enhance information processing speed in those with MS. This is one of the first studies that is powered to understand whether targeted dual-task training can improve MS symptoms and increase functional ambulation. We anticipate that those in the virtual reality group will have a significantly greater increase in dual-task gait speed and information processing speed than those achieved via treadmill training alone.

Visual search and target detection during simulated driving in Parkinson's disease.

Patients with Parkinson's Disease (PD) often exhibit difficulties with visual search that may impede their ability to recognize landmarks and cars while driving. The main objective of this study was to investigate visual search performances of both billboards and cars in patients with PD using a driving simulator. A second objective was to examine the role of cognitive functions in performing the visual search task while driving. Nineteen patients with PD (age: 68 ±â€¯8yo, sex (Men/Women): 15/4) and 14 controls (age: 60 ±â€¯11yo, sex: 7/7) first performed a battery of cognitive tests. They then drove in a simulator and were instructed to follow a lead vehicle while searching for billboards with the letter A (stationary target) or red cars (moving target) among other distractors. Accuracy and response times of visual search were the main outcome variables. Standard deviation of lateral position (SDLP) was the secondary outcome. During driving, patients were less accurate in identifying the targets, particularly for the stationary billboards located in the outer periphery. Within the group of patients, significant correlations were found between several measures of cognitive tests and simulator-based visual search accuracy. By contrast, only the score on the MOCA test correlated significantly with visual search accuracy in controls. Findings suggest that patients with PD have impaired visual search for more eccentric stationary targets while driving a simulator, which is likely due to cognitive deficits. Difficulties identifying objects in the outer periphery may have implications for driving safety. Decreased functional field of view under increased cognitive load may have attributed to the difficulties identifying these landmarks. This may impact the ability to identify, anticipate, and respond to important information (e.g., pedestrians, navigation signs, landmarks), especially in complex driving situations (e.g. urban driving or intersections).Future studies should be conducted in a larger sample size to determine whether a visual search task on a driving simulator may predict on-road driving performances.

Validation of a short cognitive battery to screen for fitness-to-drive of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Some symptoms of multiple sclerosis (MS) affect driving. In a recent study, performance on five cognitive tests predicted the on-road test performance of individuals with relapsing-remitting MS with 91% accuracy, 70% sensitivity and 97% specificity. However, the accuracy with which the battery will predict the driving performance of a different cohort that includes all types of MS is unknown. METHODS: Participants (n = 118; 48 ± 9 years of age; 97 females) performed a comprehensive off-road evaluation that lasted about 3 h and a standardized on-road test that lasted approximately 45 min over a 2-day period within the same week. Performance on the five cognitive tests was used to predict participants' performance on the standardized on-road test. RESULTS: Performance on the five tests together predicted outcome of the on-road test with 82% accuracy, 42% sensitivity and 90% specificity. CONCLUSIONS: The accuracy of predicting the on-road performance of a new MS cohort using performance on the battery of five cognitive tests remained very high (82%). The battery, which was administrable in <45 min and cost ~$150, was better at identifying those who actually passed the on-road test (90% specificity). The sensitivity (42%) of the battery indicated that it should not be used as the sole determinant of poor driving-related cognitive skills. A fail performance on the battery should only imply that more comprehensive testing is warranted.

Pupillary response to cognitive workload during saccadic tasks in Parkinson's disease.

The relationship between cognitive workload and cognitive impairments in Parkinson's disease (PD) is currently not well known. This study compared cognitive workload during saccadic tasks between patients with PD and controls. Sixteen controls, 11 patients with no obvious cognitive impairment (PD-NCI) (MOCA score≥26), and 10 PD patients with cognitive impairment (PD-CI) (MOCA score<26) performed prosaccade and antisaccade tasks. Cognitive workload, extracted via pupil recording, and other eye metrics were compared between the three groups. PD-NCI patients exhibited greater cognitive workload than controls in the prosaccade task. PD-CI patients also showed more cognitive workload in the prosaccade task than PD-NCI patients and controls. No other differences in eye metrics were found between the three groups. Cognitive workload could be used to differentiate between different cognitive states in PD. The causal relationship between increased cognitive workload and cognitive decline in PD-NCI should be the focus of future studies.

Evaluation of two automated cell counters for the analysis of hematopoietic progenitor cell apheresis products.

INTRODUCTION: Routine hematology parameters in hematopoietic progenitor cell apheresis products (HPC-A) are usually determined using automated cell counters. These instruments, however, are designed to analyze whole blood samples, that differ considerably from HPC-A in blood cell composition. This study evaluates the performance of two automated cell counters for the analysis of HPC-A. METHODS: Routine hematology parameters [red blood cells (RBC), hematocrit (HCT), mean corpuscular volume (MCV), white blood cells (WBC), WBC differentiation, and platelets (PLT)] were determined on the Unicel DxH 800 instrument (Beckman Coulter) and the XN-350 instrument (Sysmex). Correlations with the reference methods, intrarun precision, and linearity of the analyses were studied. RESULTS: Good correlations were found for almost all parameters. However, RBC count was overestimated by XN-350, using the impedance technique, as was neutrophil percentage using DxH 800. Coefficients of variation for intrarun precision were below 10% on both analyzers for all parameters, except for neutrophil percentage (14.7%) and PLT (10%) on DxH 800. Both instruments showed good linearity for all parameters, except for RBC and HCT on DxH 800. CONCLUSION: With the exception of the measurement of neutrophils on DxH 800 and RBC by the impedance technique on the XN-350, routine hematology parameters in HPC-A can safely be determined using automated cell counters.

Evaluation of the Red Blood Cell Advanced Software Application on the CellaVision DM96.

INTRODUCTION: The CellaVision Advanced Red Blood Cell (RBC) Software Application is a new software for advanced morphological analysis of RBCs on a digital microscopy system. Upon automated precharacterization into 21 categories, the software offers the possibility of reclassification of RBCs by the operator. We aimed to define the optimal cut-off to detect morphological RBC abnormalities and to evaluate the precharacterization performance of this software. METHODS: Thirty-eight blood samples of healthy donors and sixty-eight samples of hospitalized patients were analyzed. Different methodologies to define a cut-off between negativity and positivity were used. Sensitivity and specificity were calculated according to these different cut-offs using the manual microscopic method as the gold standard. Imprecision was assessed by measuring analytical within-run and between-run variability and by measuring between-observer variability. RESULTS: By optimizing the cut-off between negativity and positivity, sensitivities exceeded 80% for 'critical' RBC categories (target cells, tear drop cells, spherocytes, sickle cells, and parasites), while specificities exceeded 80% for the other RBC morphological categories. Results of within-run, between-run, and between-observer variabilities were all clinically acceptable. CONCLUSION: The CellaVision Advanced RBC Software Application is an easy-to-use software that helps to detect most RBC morphological abnormalities in a sensitive and specific way without increasing work load, provided the proper cut-offs are chosen. However, evaluation of the images by an experienced observer remains necessary.

Fitness-to-drive agreements after stroke: medical versus practical recommendations.

BACKGROUND AND PURPOSE: Physicians often struggle to screen out patients who are no longer fit to drive after stroke. The agreement between the recommendations of physicians and on-road assessors with regard to fitness to drive after stroke was investigated. METHODS: In this retrospective study, 735 patients with stroke underwent medical, visual and road tests at an official fitness-to-drive center of the Belgian Road Safety Institute. Physicians provided medical fitness-to-drive recommendations using one of three categories (favorable, reserved or unfavorable). On-road assessors used the same three categories to make practical fitness-to-drive recommendations. Agreement between the medical and practical fitness-to-drive recommendations was calculated using the percentage of agreement and prevalence and bias adjusted kappa (PABAK). Area under the curve (AUC) was used to predict the medical and practical recommendations after stepwise logistic regression analyses. RESULTS: The percentage of agreement was 73% and the PABAK was 0.60 (P < 0.0001). Physicians disagreed on 92% of patients classified as unfavorable and 80% of those classified as reserved by the on-road assessor. Previous visits to the driving center and number of comorbidities predicted medical fitness-to-drive recommendations (AUC = 0.68). Age, previous visits to the center, binocular acuity and driving experience constituted the best model to predict practical fitness-to-drive recommendations (AUC = 0.70). CONCLUSIONS: Although there was a moderate agreement between the medical and practical fitness-to-drive recommendations, physicians were less likely to screen out those patients who may pose an actual risk on the road. Demographic, clinical and driving factors differently affected the medical and practical fitness-to-drive recommendations.

Effects of deep brain stimulation of the subthalamic nucleus on freezing of gait in Parkinson's disease: a prospective controlled study.

BACKGROUND: Freezing of gait (FOG) is a debilitating gait disorder in Parkinson's disease (PD) with partial responsiveness to dopaminergic medication. To date, notions about the effects of subthalamic deep brain stimulation (STN-DBS) on FOG remain controversial. OBJECTIVES: To compare the effects of bilateral STN-DBS and continued best medical treatment (BMT) on FOG occurrence, FOG severity and clinical outcomes in PD patients at 6 and 12 months follow-up. METHODS: In this prospective, controlled study, 41 PD patients with at least 5 years disease duration participated. Twenty-four subjects (20 with FOG) were treated with STN-DBS and seventeen (15 with FOG) continued BMT. The primary outcome was the New Freezing of Gait Questionnaire (NFOGQ) at 6 months postsurgery. Other outcomes were the NFOGQ at 12 months and clinical outcomes (Unified Parkinson's Disease Rating Scale III (UPDRS III), timed gait, falls and quality of life) at both time points. RESULTS: STN-DBS increased the likelihood to convert from being a freezer to a non-freezer at 6 and 12 months follow-up (relative risk reduction=0.4). However, 45% of baseline freezers still experienced FOG 6 and 12 months postsurgery although with reduced severity. Three baseline non-freezers (1/2 BMT-treated, 2/4 STN-DBS-treated) developed FOG during follow-up. STN-DBS-induced benefits on FOG were mostly mediated by baseline levodopa equivalent dose, altered medication-intake and reduced motor fluctuations. CONCLUSIONS: In contrast to continued BMT, STN-DBS reduced FOG occurrence and severity at 6 months postsurgery with largely sustained effects at 12 months follow-up. Longer follow-up periods are needed to test whether FOG improvements after STN-DBS persist with disease progression.

Screening for fitness to drive after stroke: a systematic review and meta-analysis.

OBJECTIVE: To identify the best determinants of fitness to drive after stroke, following a systematic review and meta-analysis. METHODS: Twenty databases were searched, from inception until May 1, 2010. Potentially relevant studies were reviewed by 2 authors for eligibility. Methodologic quality was assessed by Newcastle-Ottawa scores. The fitness-to-drive outcome was a pass-fail decision following an on-road evaluation. Differences in off-road performance between the pass and fail groups were calculated using weighted mean effect sizes (d(w)). Statistical heterogeneity was determined with the I² statistic. Random-effects models were performed when the assumption of homogeneity was not met. Cutoff scores of accurate determinants were estimated via receiver operating characteristic analyses. RESULTS: Thirty studies were included in the systematic review and 27 in the meta-analysis. Out of 1,728 participants, 938 (54%) passed the on-road evaluation. The best determinants were Road Sign Recognition (d(w) 1.22; 95% confidence interval [CI] 1.01-1.44; I(2), 58%), Compass (d(w) 1.06; 95% CI 0.74-1.39; I², 36%), and Trail Making Test B (TMT B; d(w) 0.81; 95% CI 0.48-1.15; I(2), 49%). Cutoff values of 8.5 points for Road Sign Recognition, 25 points for Compass, and 90 seconds for TMT B were identified to classify unsafe drivers with accuracies of 84%, 85%, and 80%, respectively. Three out of 4 studies found no increased risk of accident involvement in persons cleared to resume driving after stroke. CONCLUSIONS: The Road Sign Recognition, Compass, and TMT B are clinically administrable office-based tests that can be used to identify persons with stroke at risk of failing an on-road assessment.

Pelvic inflammatory disease due to Streptococcus pneumoniae: a usual pathogen at an unusual place.

We report three cases of pelvic inflammatory disease (PID) due to Streptococcus pneumoniae in previously healthy young women. S. pneumoniae frequently causes bacteremia, meningitis and respiratory infections, but it very rarely infects the genital tract. All our patients presented with an acute onset of severe abdominal pain and had an intrauterine device (IUD) present. No abnormal sexual behavior was noticed. Although the relation between PID due to S. pneumoniae and the use of an IUD has been a topic for discussions, culture of IUD in all our patients and blood culture in 2 of 3 of our patients revealed S. pneumoniae. All patients recovered well with intravenous antibiotic treatment and removal of the IUD.

Predictors of fitness to drive in people with Parkinson disease.

OBJECTIVE: To develop an efficient clinical screening battery to accurately predict the fitness to drive in people with Parkinson disease (PD). METHODS: This prospective study included 80 participants: 40 patients with PD and 40 healthy age- and sex-matched control subjects. All participants were assessed using a driving simulator, a driving history survey, and the Clinical Dementia Rating. The patients with PD also underwent a clinical test battery and an evaluation of fitness to drive performed by an official center, which included visual, cognitive, and on-road tests. A two-class decision from this driving assessment center was the main outcome measure. RESULTS: A screening battery assessing four clinical variables (disease duration, contrast sensitivity, Clinical Dementia Rating, and motor part of the Unified Parkinson's Disease Rating Scale) provided the best model (R(2) = 0.52) to predict the fitness to drive and correctly classified 36 (90%) of the patients with PD as pass or fail (sensitivity = 91%, specificity = 90%). The Test Ride for Investigating Practical fitness to drive (TRIP) driving simulator score discriminated significantly between drivers with PD and their healthy peers (p = 0.0008). When the TRIP driving simulator score was added to the clinical model, the total explained variance increased (R(2) = 0.60) and correctly classified 39 (97.5%) of drivers with PD into the pass/fail category (sensitivity = 91%, specificity = 100%). CONCLUSIONS: A short clinical screening battery that measures disease duration, contrast sensitivity, cognitive and motor functions can predict fitness to drive in people with Parkinson disease with a high degree of accuracy.

Physiological and psychological effects of active-alert hypnosis.

10 female physical education students were given posthypnotic suggestions alluding to economy of effort in exercise. These suggestions were affirmed under self-hypnosis over two weeks. Experimental subjects pedalled on an exercise bicycle for 20 min. at 60% of their maximal work capacity while listening to suggestions from a hypnotist. The Control group (n = 9) showed no differences between mean pretest and posttest scores on physical self-efficacy, trait anxiety, state anxiety, heart rate, blood pressure, and perceived rate of exertion. The average systolic blood pressure of the experimental group was the only positive significant difference between the pretest and posttest scores.

A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations.

Permanent primary congenital hypothyroidism (CH) can be caused by abnormal thyroid differentiation (athyreosis), migration (ectopy), or function (leading to goiter). Goiters follow an autosomal recessive pattern of inheritance, whereas ectopy and athyreosis are considered as a single sporadic entity with a female preponderance. On the other hand, a high prevalence of extrathyroidal malformations has been reported in CH, but without linking specific defects to specific types of CH. On the basis of TSH screening, 273 newborns were referred to an academic pediatric endocrinology clinic in the province of Quebec between 1988 and 1997. Of 230 patients with permanent primary CH who had scintigraphy at diagnosis, 141 had ectopy (104 girls), 36 had athyreosis (21 girls), 42 had goiter (18 girls), 10 (3 girls) had a normal scan, and 1 girl had hemiagenesis. Only in the ectopies was the proportion of girls significantly higher than 0.5 (P<0.001). Isolated cardiac malformations were observed in 7 patients (3.0%), a prevalence 5-fold higher than that in the general population; this was largely due to atrial and ventricular septal defects, which were only observed in ectopy and athyreosis. Our data suggest that the molecular mechanisms that lead to complete absence of thyroid differentiation or defective thyroid migration 1) may be similar, but are modulated by the genetic makeup of the embryo and/or the hormonal milieu of the fetus; and 2) may also be involved in septation of the embryonic heart.