From fall-risk assessment to fall detection: inertial sensors in the clinical routine and daily life

Falls are caused by complex interaction between multiple risk factors which may be modified by age, disease and environment. A variety of methods and tools for fall risk assessment have been proposed, but none of which is universally accepted. Existing tools are generally not capable of providing a quantitative predictive assessment of fall risk. The need for objective, cost-effective and clinically applicable methods would enable quantitative assessment of fall risk on a subject-specific basis. Tracking objectively falls risk could provide timely feedback about the effectiveness of administered interventions enabling intervention strategies to be modified or changed if found to be ineffective. Moreover, some of the fundamental factors leading to falls and what actually happens during a fall remain unclear. Objectively documented and measured falls are needed to improve knowledge of fall in order to develop more effective prevention strategies and prolong independent living. In the last decade, several research groups have developed sensor-based automatic or semi-automatic fall risk assessment tools using wearable inertial sensors. This approach may also serve to detect falls. At the moment, i) several fall-risk assessment studies based on inertial sensors, even if promising, lack of a biomechanical model-based approach which could provide accurate and more detailed measurements of interests (e.g., joint moments, forces) and ii) the number of published real-world fall data of older people in a real-world environment is minimal since most authors have used simulations with healthy volunteers as a surrogate for real-world falls. With these limitations in mind, this thesis aims i) to suggest a novel method for the kinematics and dynamics evaluation of functional motor tasks, often used in clinics for the fall-risk evaluation, through a body sensor network and a biomechanical approach and ii) to define the guidelines for a fall detection algorithm based on a real-world fall database availability.

Assessment of three frequently used blood glucose monitoring devices in clinical routine

Self-monitoring of blood glucose plays an important role in the management of diabetes and has been shown to improve metabolic control. The use of blood glucose meters in clinical practice requires sufficient reliability to allow adequate treatment. Direct comparison of different blood glucose meters in clinical practice, independent of the manufactures is scarce. We, therefore, aimed to evaluate three frequently used blood glucose meters in daily clinical practice.

Optimized quantitative magnetic resonance spectroscopy for clinical routine

Several practical obstacles in data handling and evaluation complicate the use of quantitative localized magnetic resonance spectroscopy (qMRS) in clinical routine MR examinations. To overcome these obstacles, a clinically feasible MR pulse sequence protocol based on standard available MR pulse sequences for qMRS has been implemented along with newly added functionalities to the free software package jMRUI-v5.0 to make qMRS attractive for clinical routine. This enables (a) easy and fast DICOM data transfer from the MR console and the qMRS-computer, (b) visualization of combined MR spectroscopy and imaging, (c) creation and network transfer of spectroscopy reports in DICOM format, (d) integration of advanced water reference models for absolute quantification, and (e) setup of databases containing normal metabolite concentrations of healthy subjects. To demonstrate the work-flow of qMRS using these implementations, databases for normal metabolite concentration in different regions of brain tissue were created using spectroscopic data acquired in 55 normal subjects (age range 6-61 years) using 1.5T and 3T MR systems, and illustrated in one clinical case of typical brain tumor (primitive neuroectodermal tumor). The MR pulse sequence protocol and newly implemented software functionalities facilitate the incorporation of qMRS and reference to normal value metabolite concentration data in daily clinical routine. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.

Control of muscle relaxation during anesthesia: a novel approach for clinical routine

During general anesthesia drugs are administered to provide hypnosis, ensure analgesia, and skeletal muscle relaxation. In this paper, the main components of a newly developed controller for skeletal muscle relaxation are described. Muscle relaxation is controlled by administration of neuromuscular blocking agents. The degree of relaxation is assessed by supramaximal train-of-four stimulation of the ulnar nerve and measuring the electromyogram response of the adductor pollicis muscle. For closed-loop control purposes, a physiologically based pharmacokinetic and pharmacodynamic model of the neuromuscular blocking agent mivacurium is derived. The model is used to design an observer-based state feedback controller. Contrary to similar automatic systems described in the literature this controller makes use of two different measures obtained in the train-of-four measurement to maintain the desired level of relaxation. The controller is validated in a clinical study comparing the performance of the controller to the performance of the anesthesiologist. As presented, the controller was able to maintain a preselected degree of muscle relaxation with excellent precision while minimizing drug administration. The controller performed at least equally well as the anesthesiologist.

[Sense and nonsense of toxicological analyses in the daily clinical routine]

Screening tests for drugs of abuse are regularly used in the clinical routine. These tests identify the targeted substances very differently if tests from different manufacturers are used and sometimes also react positive after the intake of drugs which are not intended to be detected. Therefore, implausible results have to be questioned. A test result can be falsely negative, if a patient has taken a compound which is not detected by the antibody used in the test system. Chromatographic confirmation and screening assays are more laborious to perform and more demanding for the interpretation and are therefore only offered by several specialized clinical laboratories. However, their specificity is excellent and many different compounds can be detected depending on the number of compounds which are part of the mass spectra library used. If the clinical evaluation results in the differential diagnosis of an acute intoxication, screening tests for drugs of abuse can help to identify a single compound or a group of substances. The clinical picture, however, can usually not been explained by a qualitative test result. In addition, there are no published data demonstrating that these tests meaningfully influence triage, treatment, diagnosis or further therapy of a poisoned patient. The quantitative determination of specific compounds in the blood allows for example an appraisal of the prognosis and helps to indicate a specific therapy after intake of acetaminophen or methanol. New designer drugs can not at all be detected by the classic screening tests for drugs of abuse. The have to be identified by chromatographic methods.

Diagnostic Performance and Additional Value of Elastosonography in Focal Breast Lesions: Statistical Correlation between Size-Dependant Strain Index Measurements, Multimodality-BI-RADS Score, and Histopathology in a Clinical Routine Setting

Objective. To evaluate the diagnostic benefit of real-time elastography (RTE) in clinical routine. Strain indices (SI) for benign and malignant tumors were assessed. Methods. 100 patients with 110 focal breast lesions were retrieved. Patients had mammography (MG), ultrasound (US), and, if necessary, MRI. RTE was conducted after ultrasound. Lesions were assessed with BI-RADS for mammography and ultrasound. Diagnosis was established with histology or follow-up. Results. SI for BI-RADS 2 was 1.71 ± 0.86. Higher SI (2.21 ± 1.96) was observed for BI-RADS 3 lesions. SI of BI-RADS 4 and 5 lesions were significantly higher (16.92 ± 20.89) and (19.54 ± 10.41). 31 malignant tumors exhibited an average SI of 16.13 ± 14.67; SI of benign lesions was 5.29 ± 11.87 (P value <0.0001). ROC analysis threshold was >3.8 for malignant disease. Sensitivity of sonography was 90.3% (specificity 78.5%). RTE showed a sensitivity of 87.1% (specificity 79.7%). Accuracy of all modalities combined was 96.8%. In BI-RADS 3 lesions RTE was able to detect all malignant lesions (sensitivity 100%, specificity 92.9%, and accuracy 93.9%). Conclusions. RTE increased sensitivity and specificity for breast cancer detection when used in combination with ultrasound.

On the validity of measuring change over time in routine clinical assessment: a close examination of item-level response shifts in psychosomatic inpatients

Objective: Significant life events such as severe health status changes or intensive medical treatment often trigger response shifts in individuals that may hamper the comparison of measurements over time. Drawing from the Oort model, this study aims at detecting response shift at the item level in psychosomatic inpatients and evaluating its impact on the validity of comparing repeated measurements. Study design and setting: Complete pretest and posttest data were available from 1188 patients who had filled out the ICD-10 Symptom Rating (ISR) scale at admission and discharge, on average 24 days after intake. Reconceptualization, reprioritization, and recalibration response shifts were explored applying tests of measurement invariance. In the item-level approach, all model parameters were constrained to be equal between pretest and posttest. If non-invariance was detected, these were linked to the different types of response shift. Results: When constraining across-occasion model parameters, model fit worsened as indicated by a significant Satorra–Bentler Chi-square difference test suggesting potential presence of response shifts. A close examination revealed presence of two types of response shift, i.e., (non)uniform recalibration and both higher- and lower-level reconceptualization response shifts leading to four model adjustments. Conclusions: Our analyses suggest that psychosomatic inpatients experienced some response shifts during their hospital stay. According to the hierarchy of measurement invariance, however, only one of the detected non-invariances is critical for unbiased mean comparisons over time, which did not have a substantial impact on estimating change. Hence, the use of the ISR can be recommended for outcomes assessment in clinical routine, as change score estimates do not seem hampered by response shift effects.

Clinical feasibility of cognitive testing in dogs (Canis lupus familiaris)

Several cognitive tests have been developed to evaluate specific aspects of human and animal learning and memory. These tests have been used for early detection of cognitive deficits and to monitor the treatment of dogs with cognitive impairment. Thus, this article evaluated the feasibility of cognitive tests for use in canine neurology clinical routines and the suitability of the different tests to accomplish this aim. Fifteen healthy adult dogs were used for the cognitive tests of reward approach learning, object approach learning, object discrimination learning, reversal learning, delayed non-matched to position, and delayed non-matched to sample to assess different aspects of memory. No difference was observed between tests of delayed non-matched to position (3.13 +/- 2.23 days) and delayed non-matched to sample (3.20 +/- 2.40 days) (P = 0.944). However, dogs had greater difficulty in reversal learning (8.47 +/- 2.61 days) than in object discrimination learning (4.60 +/- 1.64 days) (P <= 0.001). Based on the tests performed, the delayed non-matched to position test may be performed in clinical routine if the owner and the veterinarian have time available, because this test is sensitive to evaluate dogs with cognitive impairments, but requires approximately 10 days of training. Thus, elderly dogs are excellent experimental models to study pathological aging based on their similarities with some human brain diseases, such as Alzheimer disease. (C) 2014 Elsevier Inc. All rights reserved.

Simple and objective method for routine detection of the macular pigment xanthophyll

A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction function that depends on age. The reproducibility of parameters in a one-wavelength reflection method determined for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, meanODx = 4.6%, volume = 6%, and area = 6% already before stray-light correction. ODx was comparable in pseudophakic and in an eye with a crystalline lens of the same 11 subjects after stray-light correction. Significant correlation in ODx was found between the one-wavelength reflection method and the two-wavelength autofluorescence method for pseudophakic and cataract eyes of 19 patients suffering from dry age-related macular degeneration (AMD) (R(2) = 0.855). In pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx = 0.491±0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615±0.103 ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD (n = 125) (ODx = 0.610±0.093 ODU) than in healthy subjects (n = 45) (ODx = 0.674±0.098 ODU) (p = 0.00019). No dependence on age was found in the pseudophakic eyes both of healthy subjects and AMD patients.

CT-based intravenous thrombolysis 3-4.5 hours after acute ischemic stroke in clinical practice

Outcome of stroke patients selected with cerebral computed tomography for intravenous thrombolysis administered in clinical routine from 3 to 4.5 hours after symptoms onset is not well investigated. Aim of this single-center, prospective, observational study was to compare the safety and efficacy of intravenous alteplase given in routine clinical praxis 181-270 minutes (late) and within 180 minutes (early) after stroke onset in patients selected with cerebral computed tomography.

X-ray image calibration and its application to clinical orthopedics.

X-ray imaging is one of the most commonly used medical imaging modality. Albeit X-ray radiographs provide important clinical information for diagnosis, planning and post-operative follow-up, the challenging interpretation due to its 2D projection characteristics and the unknown magnification factor constrain the full benefit of X-ray imaging. In order to overcome these drawbacks, we proposed here an easy-to-use X-ray calibration object and developed an optimization method to robustly find correspondences between the 3D fiducials of the calibration object and their 2D projections. In this work we present all the details of this outlined concept. Moreover, we demonstrate the potential of using such a method to precisely extract information from calibrated X-ray radiographs for two different orthopedic applications: post-operative acetabular cup implant orientation measurement and 3D vertebral body displacement measurement during preoperative traction tests. In the first application, we have achieved a clinically acceptable accuracy of below 1° for both anteversion and inclination angles, where in the second application an average displacement of 8.06±3.71 mm was measured. The results of both applications indicate the importance of using X-ray calibration in the clinical routine.

Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice

OBJECTIVES To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making. METHODS AND MATERIALS Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays. RESULTS The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main reason that individual prediction of disease outcome is currently not reliable. CONCLUSIONS Molecular markers are promising to predict progression and survival, but not recurrence. However, none of these are used in the daily clinical routine because of reproducibility issues. Future studies should focus on reproducibility of marker assessment and consistency of study results by incorporating scoring systems to reduce heterogeneity of reporting. This may ultimately lead to incorporation of molecular markers in clinical practice.

Automatic quality control in clinical (1) H MRSI of brain cancer.

MRSI grids frequently show spectra with poor quality, mainly because of the high sensitivity of MRS to field inhomogeneities. These poor quality spectra are prone to quantification and/or interpretation errors that can have a significant impact on the clinical use of spectroscopic data. Therefore, quality control of the spectra should always precede their clinical use. When performed manually, quality assessment of MRSI spectra is not only a tedious and time-consuming task, but is also affected by human subjectivity. Consequently, automatic, fast and reliable methods for spectral quality assessment are of utmost interest. In this article, we present a new random forest-based method for automatic quality assessment of (1) H MRSI brain spectra, which uses a new set of MRS signal features. The random forest classifier was trained on spectra from 40 MRSI grids that were classified as acceptable or non-acceptable by two expert spectroscopists. To account for the effects of intra-rater reliability, each spectrum was rated for quality three times by each rater. The automatic method classified these spectra with an area under the curve (AUC) of 0.976. Furthermore, in the subset of spectra containing only the cases that were classified every time in the same way by the spectroscopists, an AUC of 0.998 was obtained. Feature importance for the classification was also evaluated. Frequency domain skewness and kurtosis, as well as time domain signal-to-noise ratios (SNRs) in the ranges 50-75 ms and 75-100 ms, were the most important features. Given that the method is able to assess a whole MRSI grid faster than a spectroscopist (approximately 3 s versus approximately 3 min), and without loss of accuracy (agreement between classifier trained with just one session and any of the other labelling sessions, 89.88%; agreement between any two labelling sessions, 89.03%), the authors suggest its implementation in the clinical routine. The method presented in this article was implemented in jMRUI's SpectrIm plugin. Copyright © 2016 John Wiley & Sons, Ltd.

Magnetic resonance spectroscopy. Data analysis for clinical applications

This text is taken from the postgraduate thesis, which one of the authors (A.B.) developed for the degree of Medical Physicist in the School on Medical Physics of the University of Florence. The text explores the feasibility of quantitative Magnetic Resonance Spectroscopy as a tool for daily clinical routine use. The results and analysis comes from two types of hyper spectral images: the first set are hyper spectral images coming from a standard phantom (reference images); and hyper spectral images obtained from a group of patients who have undergone MRI examinations at the Santa Maria Nuova Hospital. This interdisciplinary work stems from the IFAC-CNR know how in terms of data analysis and nanomedicine, and the clinical expertise of Radiologists and Medical Physicists. The results reported here, which were the subject of the thesis, are original, unpublished, and represent independent work.

Octavius 4D characterization for flattened and flattening filter free rotational deliveries

Purpose: In this study the Octavius detector 729 ionization chamber (IC) array with the Octavius 4D phantom was characterized for flattening filter (FF) and flattening filter free (FFF) static and rotational beams. The device was assessed for verification with FF and FFF RapidArc treatment plans.

Methods: The response of the detectors to field size, dose linearity, and dose rate were assessed for 6 MV FF beams and also 6 and 10 MV FFF beams. Dosimetric and mechanical accuracy of the detector array within the Octavius 4D rotational phantom was evaluated against measurements made using semiflex and pinpoint ionization chambers, and radiochromic film. Verification FF and FFF RapidArc plans were assessed using a gamma function with 3%/3 mm tolerances and 2%/2 mm tolerances and further analysis of these plans was undertaken using film and a second detector array with higher spatial resolution.

Results: A warm-up dose of >6 Gy was required for detector stability. Dose-rate measurements were stable across a range from 0.26 to 15 Gy/min and dose response was linear, although the device overestimated small doses compared with pinpoint ionization chamber measurements. Output factors agreed with ionization chamber measurements to within 0.6% for square fields of side between 3 and 25 cm and within 1.2% for 2 x 2 cm(2) fields. The Octavius 4D phantom was found to be consistent with measurements made with radiochromic film, where the gantry angle was found to be within 0.4. of that expected during rotational deliveries. RapidArc FF and FFF beams were found to have an accuracy of >97.9% and >90% of pixels passing 3%/3 mm and 2%/2 mm, respectively. Detector spatial resolution was observed to be a factor in determining the accurate delivery of each plan, particularly at steep dose gradients. This was confirmed using data from a second detector array with higher spatial resolution and with radiochromic film.

Conclusions: The Octavius 4D phantom with associated Octavius detector 729 ionization chamber array is a dosimetrically and mechanically stable device for pretreatment verification of FF and FFF RapidArc treatments. Further improvements may be possible through use of a detector array with higher spatial resolution (detector size and/or detector spacing). (C) 2013 American Association of Physicists in Medicine.