A machine learning approach to identify clinical trials involving nanodrugs and nanodevices from ClinicalTrials.gov

BACKGROUND: Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano), and CTs that do not involve nanotechnology (non-nano). Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs-even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results. METHODS: We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i) extraction and manual annotation of CTs as nano vs. non-nano, ii) pre-processing and automatic classification, and iii) performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset. RESULTS AND CONCLUSIONS: The performance of the best automated classifier closely matches that of experts (AUC over 0.95), suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a particular nanoparticle or nanodevice, which is essential to discover any precedents for nanotoxicity events or advantages for targeted drug therapy.

A User Centered Design Approach for Patient Interfaces to a Diabetes IT Platform

Improving patient self-management can have a greater impact than improving any clinical treatment (WHO). We propose here a systematic and comprehensive user centered design approach for delivering a technological platform for diabetes disease management. The system was developed under the METABO research project framework, involving patients from 3 different clinical centers in Parma, Modena and Madrid.

Epidemiological characteristics and diagnostic approach in patients admitted to the emergency room for transient loos of consciousness: Group for Syncope Study in the Emergency Room (GESINUR) study

Aims: To assess the clinical presentation and acute management of patients with transient loss of consciousness (T-LOC) in the emergency department (ED). Methods and results: A multi-centre prospective observational study was carried out in 19 Spanish hospitals over 1 month. The patients included were 14 years old and were admitted to the ED because of an episode of T-LOC. Questionnaires and corresponding electrocardiograms (ECGs) were reviewed by a Steering Committee (SC) to unify diagnostic criteria, evaluate adherence to guidelines, and diagnose correctly the ECGs. We included 1419 patients (prevalence, 1.14%).ECG was performed in 1335 patients (94%) in the ED: 498 (37.3%) ECGs were classified as abnormal. The positive diagnostic yield ranged from 0% for the chest X-ray to 12% for the orthostatic test. In the ED, 1217 (86%) patients received a final diagnosis of syncope, whereas the remaining 202 (14%) were diagnosed of non-syncopal transient lossof consciousness (NST-LOC). After final review by the SC, 1080 patients (76%) were diagnosed of syncope, whereas 339 (24%) were diagnosed of NST-LOC (P , 0.001). Syncope was diagnosed correctly in 84% of patients. Only 25% of patients with T-LOC were admitted to hospitals. Conclusion Adherence to clinical guidelines for syncope management was low; many diagnostic tests were performed with low diagnostic yield. Important differences were observed between syncope diagnoses at the ED and by SC decision.

Nutrition and physical activity programs for obesity treatment (PRONAF study). methodological approach of the project

Este trabajo aborda la metodología seguida para llevar a cabo el proyecto de investigación PRONAF (Clinical Trials Gov.: number NCT01116856.) Background: At present, scientific consensus exists on the multifactorial etiopatogenia of obesity. Both professionals and researchers agree that treatment must also have a multifactorial approach, including diet, physical activity, pharmacology and/or surgical treatment. These two last ones should be reserved for those cases of morbid obesities or in case of failure of the previous ones. The aim of the PRONAF study is to determine what type of exercise combined with caloric restriction is the most appropriate to be included in overweigth and obesity intervention programs, and the aim of this paper is to describe the design and the evaluation methods used to carry out the PRONAF study. Methods/design: One-hundred nineteen overweight (46 males) and 120 obese (61 males) subjects aged 18–50 years were randomly assigned to a strength training group, an endurance training group, a combined strength + endurance training group or a diet and physical activity recommendations group. The intervention period was 22 weeks (in all cases 3 times/wk of training for 22 weeks and 2 weeks for pre and post evaluation). All subjects followed a hypocaloric diet (25-30% less energy intake than the daily energy expenditure estimated by accelerometry). 29–34% of the total energy intake came from fat, 14–20% from protein, and 50–55% from carbohydrates. The mayor outcome variables assesed were, biochemical and inflamatory markers, body composition, energy balance, physical fitness, nutritional habits, genetic profile and quality of life. 180 (75.3%) subjects finished the study, with a dropout rate of 24.7%. Dropout reasons included: personal reasons 17 (28.8%), low adherence to exercise 3 (5.1%), low adherence to diet 6 (10.2%), job change 6 (10.2%), and lost interest 27 (45.8%). Discussion: Feasibility of the study has been proven, with a low dropout rate which corresponds to the estimated sample size. Transfer of knowledge is foreseen as a spin-off, in order that overweight and obese subjects can benefit from the results. The aim is to transfer it to sports centres. Effectiveness on individual health-related parameter in order to determine the most effective training programme will be analysed in forthcoming publications.

Identifying the semantics of eligibility criteria of clinical trials based on relevant medical ontologies

An important objective of the INTEGRATE project1 is to build tools that support the efficient execution of post-genomic multi-centric clinical trials in breast cancer, which includes the automatic assessment of the eligibility of patients for available trials. The population suited to be enrolled in a trial is described by a set of free-text eligibility criteria that are both syntactically and semantically complex. At the same time, the assessment of the eligibility of a patient for a trial requires the (machineprocessable) understanding of the semantics of the eligibility criteria in order to further evaluate if the patient data available for example in the hospital EHR satisfies these criteria. This paper presents an analysis of the semantics of the clinical trial eligibility criteria based on relevant medical ontologies in the clinical research domain: SNOMED-CT, LOINC, MedDRA. We detect subsets of these widely-adopted ontologies that characterize the semantics of the eligibility criteria of trials in various clinical domains and compare these sets. Next, we evaluate the occurrence frequency of the concepts in the concrete case of breast cancer (which is our first application domain) in order to provide meaningful priorities for the task of binding/mapping these ontology concepts to the actual patient data. We further assess the effort required to extend our approach to new domains in terms of additional semantic mappings that need to be developed.

Control motion approach of a lower limb orthosis to reduce energy consumption

By analysing the dynamic principles of the human gait, an economic gait‐control analysis is performed, and passive elements are included to increase the energy efficiency in the motion control of active orthoses. Traditional orthoses use position patterns from the clinical gait analyses (CGAs) of healthy people, which are then de‐normalized and adjusted to each user. These orthoses maintain a very rigid gait, and their energy cosT is very high, reducing the autonomy of the user. First, to take advantage of the inherent dynamics of the legs, a state machine pattern with different gains in eachstate is applied to reduce the actuator energy consumption. Next, different passive elements, such as springs and brakes in the joints, are analysed to further reduce energy consumption. After an off‐line parameter optimization and a heuristic improvement with genetic algorithms, a reduction in energy consumption of 16.8% is obtained by applying a state machine control pattern, and a reduction of 18.9% is obtained by using passive elements. Finally, by combining both strategies, a more natural gait is obtained, and energy consumption is reduced by 24.6%compared with a pure CGA pattern.

A guided heuristic approach to the MEG inverse problem.

There is general agreement within the scientific community in considering Biology as the science with more potential to develop in the XXI century. This is due to several reasons, but probably the most important one is the state of development of the rest of experimental and technological sciences. In this context, there are a very rich variety of mathematical tools, physical techniques and computer resources that permit to do biological experiments that were unbelievable only a few years ago. Biology is nowadays taking advantage of all these newly developed technologies, which are been applied to life sciences opening new research fields and helping to give new insights in many biological problems. Consequently, biologists have improved a lot their knowledge in many key areas as human function and human diseases. However there is one human organ that is still barely understood compared with the rest: The human brain. The understanding of the human brain is one of the main challenges of the XXI century. In this regard, it is considered a strategic research field for the European Union and the USA. Thus, there is a big interest in applying new experimental techniques for the study of brain function. Magnetoencephalography (MEG) is one of these novel techniques that are currently applied for mapping the brain activity1. This technique has important advantages compared to the metabolic-based brain imagining techniques like Functional Magneto Resonance Imaging2 (fMRI). The main advantage is that MEG has a higher time resolution than fMRI. Another benefit of MEG is that it is a patient friendly clinical technique. The measure is performed with a wireless set up and the patient is not exposed to any radiation. Although MEG is widely applied in clinical studies, there are still open issues regarding data analysis. The present work deals with the solution of the inverse problem in MEG, which is the most controversial and uncertain part of the analysis process3. This question is addressed using several variations of a new solving algorithm based in a heuristic method. The performance of those methods is analyzed by applying them to several test cases with known solutions and comparing those solutions with the ones provided by our methods.