Discrimination and anatomical mapping of PET-positive lesions: comparison of CT attenuation-corrected PET images with coregistered MR and CT images in the abdomen

Purpose: PET/MR has the potential to become a powerful tool in clinical oncological imaging. The purpose of this prospective study was to evaluate the performance of a single T1-weighted (T1w) fat-suppressed unenhanced MR pulse sequence of the abdomen in comparison with unenhanced low-dose CT images to characterize PET-positive lesions. Methods: A total of 100 oncological patients underwent sequential whole-body 18F-FDG PET with CT-based attenuation correction (AC), 40mAs low-dose CT and two-point Dixon-based T1w 3D MRI of the abdomen in a trimodality PET/CT-MR system. PET-positive lesions were assessed by CT and MRI with regard to their anatomical location, conspicuity and additional relevant information for characterization. Results: From among 66 patients with at least one PET-positive lesion, 147 lesions were evaluated. No significant difference between MRI and CT was found regarding anatomical lesion localization. The MR pulse sequence used performed significantly better than CT regarding conspicuity of liver lesions (p < 0.001, Wilcoxon signed ranks test), whereas no difference was noted for extrahepatic lesions. For overall lesion characterization, MRI was considered superior to CT in 40% of lesions, equal to CT in 49%, and inferior to CT in 11%. Conclusion: Fast Dixon-based T1w MRI outperformed low-dose CT in terms of conspicuity and characterization of PET-positive liver lesions and performed similarly in extrahepatic tumour manifestations. Hence, under the assumption that the technical issue of MR AC for whole-body PET examinations is solved, in abdominal PET/MR imaging the replacement of low-dose CT by a single Dixon-based MR pulse sequence for anatomical lesion correlation appears to be valid and robus

Prescription of concomitant medications in patients treated with Nifurtimox Eflornithine Combination Therapy (NECT) for T.b. gambiense second stage sleeping sickness in the Democratic Republic of the Congo

Nifurtimox eflornithine combination therapy (NECT) to treat human African trypanosomiasis (HAT), commonly called sleeping sickness, was added to the World Health Organisation's (WHO) Essential Medicines List in 2009 and to the Paediatric List in 2012. NECT was further tested and documented in a phase IIIb clinical trial in the Democratic Republic of Congo (DRC) assessing the safety, effectiveness, and feasibility of implementation under field conditions (NECT-FIELD study). This trial brought a unique possibility to examine concomitant drug management.; This is a secondary analysis of the NECT-FIELD study where 629 second stage gambiense HAT patients were treated with NECT, including children and pregnant and breastfeeding women in six general reference hospitals located in two provinces. Concomitant drugs were prescribed by the local investigators as needed. Patients underwent daily evaluations, including vital signs, physical examination, and adverse event monitoring. Concomitant medication was documented from admission to discharge. Patients' clinical profiles on admission and safety profile during specific HAT treatment were similar to previously published reports. Prescribed concomitant medications administered during the hospitalization period, before, during, and immediately after NECT treatment, were mainly analgesics/antipyretics, anthelmintics, antimalarials, antiemetics, and sedatives. Use of antibiotics was reasonable and antibiotics were often prescribed to treat cellulitis and respiratory tract infections. Prevention and treatment of neurological conditions such as convulsions, loss of consciousness, and coma was used in approximately 5% of patients.; The prescription of concomitant treatments was coherent with the clinical and safety profile of the patients. However, some prescription habits would need to be adapted in the future to the evolving available pharmacopoeia. A list of minimal essential medication that should be available at no cost to patients in treatment wards is proposed to help the different actors to plan, manage, and adequately fund drug supplies for advanced HAT infected patients.; The initial study was registered at ClinicalTrials.gov, number NCT00906880

In-hospital safety in field conditions of Nifurtimox Eflornithine Combination Therapy (NECT) for T. B. Gambiense Sleeping Sickness

Trypanosoma brucei (T.b.) gambiense Human African trypanosomiasis (HAT; sleeping sickness) is a fatal disease. Until 2009, available treatments for 2(nd) stage HAT were complicated to use, expensive (eflornithine monotherapy), or toxic, and insufficiently effective in certain areas (melarsoprol). Recently, nifurtimox-eflornithine combination therapy (NECT) demonstrated good safety and efficacy in a randomised controlled trial (RCT) and was added to the World Health Organisation (WHO) essential medicines list (EML). Documentation of its safety profile in field conditions will support its wider use

Effectiveness of a 10-Day Melarsoprol Schedule for the Treatment of Late-Stage Human African Trypanosomiasis: Confirmation from a Multinational Study (Impamel II)

BackgroundTreatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study MethodsA total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up ResultsThe cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively ConclusionsThe 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiens

European survey on national harmonization in clinical research

Background: Clinical trials remain key to the development of evidence-based medical practice. However, they are becoming increasingly complex, mainly in a multinational setting. To address these challenges, the European Union (EU) adopted the Clinical Trial Regulation EU No. 536/2014 (CTR). Once in force, the CTR will lead to more consistent rules and simplification of procedures for conducting clinical trials through-out the EU. Existing harmonization initiatives and “research infrastructures” for clinical trials may facilitate this process. This publication offers a snapshot of the current level of harmonization activities in academic clinical research in Europe. Methods: A survey was performed among the member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardizedpublishersversionpublishe

Cardiac Alterations in Human African Trypanosomiasis (T.b. gambiense) with Respect to the Disease Stage and Antiparasitic Treatment

In Human African Trypanosomiasis (HAT), neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The electrocardiogram (ECG) is a tool to evaluate cardiac involvement and the risk of arrythmias. We analysed the ECG of 465 HAT patients and compared them with the ECG of 61 healthy volunteers. In HAT patients the QTc interval was prolonged. This comprises a risk of fatal arrhythmias if new drugs with antiarrhythmic potential will be used. Further, repolarization changes and low voltage were more frequent than in healthy controls. This could be explained by an inflammation of the heart. Treatment of HAT was associated with appearance of repolarization changes but not with a QTc prolongation. These changes appear to be associated with the disease, but not with a specific drug. The main conclusion of this study is that heart involvement is frequent in HAT and mostly well tolerated. However, it can become relevant, if new compounds with antiarrhythmic potential will be used

Multimedia application to the simulation of human musculoskeletal system: A visual lower limb model from multimodal captured data

Abstract-Musculoskeletal disorders are the most notorious and common causes of severe long-term pain and physical disability, affecting hundreds of millions of people across the world. To prevent and treat these disabling conditions, we are building an accurate generic lower limb model (consisting of bones and soft tissues) that can be simulated in motion, using individual multimodal data. For clinical every-day use, medically relevant validation and an efficient interactive visualization framework are required. Relevant patient&apos;s anatomical, kinematical and mechanical data extracted from images (MRI), motion capture (dynamic MRI, optical motion capture) and other modalities (body scanning, EMG, mechanical properties measuring device), as well as statistical data, are adjusting the generic model to the patient. A fully functional model will be presented with some individual case studies and medical validation

Analysis of hip range of motion in everyday life ::a pilot study

Patients undergoing total hip arthroplasty are increasingly younger and have a higher demand concerning hip range of motion. To date, there is no clear consensus as to the amplitude of the “normal hip” in everyday life. It is also unknown if the physical examination is an accurate test for setting the values of true hip motion. The purpose of this study was: 1) to precisely determine the necessary hip joint mobility for everyday tasks in young active subjects to be used in computer simulations of prosthetic models in order to evaluate impingement and instability during their practice; 2) to assess the accuracy of passive hip range of motion measurements during clinical examination. A total of 4 healthy volunteers underwent Magnetic Resonance Imaging and 2 motion capture experiments. During experiment 1, routine activities were recorded and applied to prosthetic hip 3D models including nine cup configurations. During experiment 2, a clinical examination was performed, while the motion of the subjects was simultaneously captured. Important hip flexion (mean range 95°-107°) was measured during daily activities that could expose the prosthetic hip to impingement and instability. The error made by the clinicians during physical examination varied in the range of ±10°, except for flexion and abduction where the error was higher. This study provides useful information for the surgical planning to help restore hip mobility and stability, when dealing with young active patients. The physical examination seems to be a precise method for determining passive hip motion, if care is taken to stabilise the pelvis during hip flexion and abduction

Analysis of hip range of motion in everyday life: a pilot study

Patients undergoing total hip arthroplasty are increasingly younger and have a higher demand concerning hip range of motion. To date, there is no clear consensus as to the amplitude of the "normal hip" in everyday life. It is also unknown if the physical examination is an accurate test for setting the values of true hip motion. The purpose of this study was: 1) to precisely determine the necessary hip joint mobility for everyday tasks in young active subjects to be used in computer simulations of prosthetic models in order to evaluate impingement and instability during their practice; 2) to assess the accuracy of passive hip range of motion measurements during clinical examination. A total of 4 healthy volunteers underwent Magnetic Resonance Imaging and 2 motion capture experiments. During experiment 1, routine activities were recorded and applied to prosthetic hip 3D models including nine cup configurations. During experiment 2, a clinical examination was performed, while the motion of the subjects was simultaneously captured. Important hip flexion (mean range 95°-107°) was measured during daily activities that could expose the prosthetic hip to impingement and instability. The error made by the clinicians during physical examination varied in the range of ±10°, except for flexion and abduction where the error was higher. This study provides useful information for the surgical planning to help restore hip mobility and stability, when dealing with young active patients. The physical examination seems to be a precise method for determining passive hip motion, if care is taken to stabilise the pelvis during hip flexion and abduction

MyHip: supporting planning and surgical guidance for a better total hip arthroplasty: A pilot study

Purpose: Total hip arthroplasty (THA) aims to restore patient mobility by providing a pain-free and stable artificial joint. A successful THA depends on the planning and its execution during surgery. Both tasks rely on the experience of the surgeon to understand the complex biomechanical behavior of the hip. We investigate the hypothesis that a computer-assisted solution for THA effectively supports the preparation and execution of the planning. Methods: We devised MyHip as a computer-assisted framework for THA. The framework provides pre-operative planning based on medical imaging and optical motion capture to optimally select and position the implant. The planning considers the morphology and range of motion of the patient's hip to reduce the risk of impingements and joint instability. The framework also provides intra-operative support based on patient-specific surgical guides. We performed a post-operative analysis on three patients who underwent THA. Based on post-operative radiological images, we reconstructed a patient-specific model of the prosthetic hip to compare planned and effective positioning of the implants. Results: When the guides were used, we measured non-significant variations of planned executions such as bone cutting. Moreover, patients' hip motions were acquired and used in a dynamic simulation of the prosthetic hip. Conflicts prone to implant failure, such as impingements or subluxations, were not detected. Conclusions: The results show that MyHip provides a promising computer assistance for THA. The results of the dynamic simulation highlighted the quality of the surgery and especially of its planning. The planning was properly executed since non-significant variations were detected during the radiological analysis