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NeuroImage Nov 2017Diffusion tensor imaging (DTI) is a well-established magnetic resonance imaging (MRI) technique used for studying microstructural changes in the white matter. As with...
Diffusion tensor imaging (DTI) is a well-established magnetic resonance imaging (MRI) technique used for studying microstructural changes in the white matter. As with many other imaging modalities, DTI images suffer from technical between-scanner variation that hinders comparisons of images across imaging sites, scanners and over time. Using fractional anisotropy (FA) and mean diffusivity (MD) maps of 205 healthy participants acquired on two different scanners, we show that the DTI measurements are highly site-specific, highlighting the need of correcting for site effects before performing downstream statistical analyses. We first show evidence that combining DTI data from multiple sites, without harmonization, may be counter-productive and negatively impacts the inference. Then, we propose and compare several harmonization approaches for DTI data, and show that ComBat, a popular batch-effect correction tool used in genomics, performs best at modeling and removing the unwanted inter-site variability in FA and MD maps. Using age as a biological phenotype of interest, we show that ComBat both preserves biological variability and removes the unwanted variation introduced by site. Finally, we assess the different harmonization methods in the presence of different levels of confounding between site and age, in addition to test robustness to small sample size studies.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Cohort Studies; Diffusion Tensor Imaging; Female; Humans; Image Processing, Computer-Assisted; Male; Multicenter Studies as Topic; White Matter; Young Adult
PubMed: 28826946
DOI: 10.1016/j.neuroimage.2017.08.047 -
Epilepsia Mar 2013The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long-term efficacy or... (Review)
Review
The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long-term efficacy or effectiveness for antiepileptic drugs (AEDs) as initial monotherapy for patients with newly diagnosed or untreated epilepsy. All applicable articles from July 2005 until March 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update. The prior analysis methodology was utilized with three modifications: (1) the detectable noninferiority boundary approach was dropped and both failed superiority studies and prespecified noninferiority studies were analyzed using a noninferiority approach, (2) the definition of an adequate comparator was clarified and now includes an absolute minimum point estimate for efficacy/effectiveness, and (3) the relationship table between clinical trial ratings, level of evidence, and conclusions no longer includes a recommendation column to reinforce that this review of efficacy/evidence for specific seizure types does not imply treatment recommendations. This evidence review contains one clarification: The commission has determined that class I superiority studies can be designed to detect up to a 20% absolute (rather than relative) difference in the point estimate of efficacy/effectiveness between study treatment and comparator using an intent-to-treat analysis. Since July, 2005, three class I randomized controlled trials (RCT) and 11 class III RCTs have been published. The combined analysis (1940-2012) now includes a total of 64 RCTs (7 with class I evidence, 2 with class II evidence) and 11 meta-analyses. New efficacy/effectiveness findings include the following: levetiracetam and zonisamide have level A evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level A evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence for any other subgroup. Levetiracetam and zonisamide join carbamazepine and phenytoin with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures. Although ethosuximide and valproic acid now have level A efficacy/effectiveness evidence as initial monotherapy for children with absence seizures, there continues to be an alarming lack of well designed, properly conducted epilepsy RCTs for patients with generalized seizures/epilepsies and in children in general. These findings reinforce the need for multicenter, multinational efforts to design, conduct, and analyze future clinically relevant adequately designed RCTs. When selecting a patient's AED, all relevant variables and not just efficacy and effectiveness should be considered.
Topics: Anticonvulsants; Epilepsy; Humans; Internationality; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Syndrome; Treatment Outcome
PubMed: 23350722
DOI: 10.1111/epi.12074 -
International Heart Journal Apr 2017The FMDJ study, a multicenter prospective observational study conducted in Japan, demonstrated the acceptable reliability of measurement of flow-mediated vasodilatation... (Review)
Review
The FMDJ study, a multicenter prospective observational study conducted in Japan, demonstrated the acceptable reliability of measurement of flow-mediated vasodilatation (FMD) using a semi-automatic device in individual institutions. However, in about 10% of Japanese subjects, adequate scans to determine the brachial arterial diameter failed to be obtained. The prevalence of inadequate scans was higher in women than in men, while obesity had no influence on the inadequate scan rate. The FMDJ study also proposed that attending periodic refresher courses on the measurement of FMD is needed for maintaining competency. Finally, the FMDJ study proposed reference values for FMD. Thus, FMD measurement may be categorized as a clinically applicable tool on the basis of class IIb (exploratory cohort study with good reference standards) evidence.
Topics: Diagnostic Techniques, Cardiovascular; Humans; Multicenter Studies as Topic; Observational Studies as Topic; Reference Values; Vasodilation
PubMed: 28367852
DOI: 10.1536/ihj.17-013 -
Rheumatic Diseases Clinics of North... Nov 2021This article provides an overview of the clinical presentation and diagnosis of select pediatric primary systemic vasculitides. Important advances in understanding the... (Review)
Review
This article provides an overview of the clinical presentation and diagnosis of select pediatric primary systemic vasculitides. Important advances in understanding the pathogenesis of these rare diseases also are discussed and efforts to harmonize treatment through consensus-based guidelines and multicenter and international collaborations highlighted.
Topics: Child; Humans; Multicenter Studies as Topic; Vasculitis
PubMed: 34635304
DOI: 10.1016/j.rdc.2021.07.007 -
Brazilian Journal of Cardiovascular... Aug 2022Congenitally corrected transposition of the great arteries (CCTGA) is a rare anomaly. Current data available regarding adult cases is derived from small series,... (Review)
Review
INTRODUCTION
Congenitally corrected transposition of the great arteries (CCTGA) is a rare anomaly. Current data available regarding adult cases is derived from small series, information simultaneously presented in pediatric publications, and one classical multicenter study. This review, not aimed to exhaust the subject, has the purpose to examine the literature addressing presentation, diagnostic methodology, and management of afflicted adult patients.
METHODS
A comprehensive search was undertaken in three major databases (PubMed, Cochrane, SciELO), using the keywords "congenitally corrected transposition of the great arteries" and "adults". Relevant articles in English, Spanish, and Portuguese were extracted and critically appraised in this review. Steps for study selection were: (1) identification of titles of records through databases searching, (2) removal of duplicates, (3) screening and selection of abstracts, (4) final inclusion in the study.
RESULTS
Four hundred sixty-five publications on CCTGA in adult patients were retrieved, and 166 were excluded; 299 studies were used for this review including 76 full-text articles, 70 studies related to general aspects of the subject, and, due to the small number of publications, 153 case reports. Sixty-one articles referring to combined experiences in pediatric and adult patients and judged to be relevant, but retrieved from another sources, were also included.
CONCLUSION
Albeit clinical presentation and diagnostic criteria have been well stablished, there seems to be room for discussion related to clinical and surgical management of CCTGA in adults. Considering the rarity of the disease, well designed multicenter studies may provide answers.
Topics: Adult; Congenitally Corrected Transposition of the Great Arteries; Humans; Multicenter Studies as Topic
PubMed: 35895985
DOI: 10.21470/1678-9741-2021-0528 -
Pituitary Oct 2022Exposure to cortisol excess in Cushing's disease (CD) results in increased cardiovascular morbidity and reduces survival, with cardiovascular disease being a leading... (Review)
Review
Exposure to cortisol excess in Cushing's disease (CD) results in increased cardiovascular morbidity and reduces survival, with cardiovascular disease being a leading cause of death. At diagnosis, a significant number of patients have adverse cardiovascular profiles (e.g., obesity, diabetes or impaired glucose tolerance, dyslipidemia, hypertension, cardiac abnormalities and vascular disease). Remission of hypercortisolemia reduces but does not completely eliminate the cardiovascular complications; hazard ratios for myocardial infarction and stroke are high during long-term monitoring, highlighting the long-lasting effects of hypercortisolism and the importance of the timely diagnosis and successful management of this condition. Data on mortality of patients in remission are not consistent but in a multicenter study, an increased all-cause and circulatory mortality in patients with CD in remission for at least 10 years has been demonstrated. Cardiovascular morbidity requires particular focus and effective management during the care of patients with CD, from their presentation until long-term follow up.
Topics: Humans; Pituitary ACTH Hypersecretion; Hydrocortisone; Hypertension; Cardiovascular Diseases; Diabetes Mellitus; Multicenter Studies as Topic
PubMed: 35869339
DOI: 10.1007/s11102-022-01258-4 -
British Journal of Cancer Oct 2019International collaboration in oncology trials has the potential to enhance clinical trial activity by expediting the recruitment of large patient populations, testing... (Review)
Review
International collaboration in oncology trials has the potential to enhance clinical trial activity by expediting the recruitment of large patient populations, testing treatments in diverse populations and facilitating the study of rare tumours or specific molecular subtypes. However, a number of challenges continue to hinder the efficient and productive conduct of both commercial and non-commercial international clinical trials. These challenges include complex and burdensome regulatory requirements, the high cost of conducting trials, and logistical challenges associated with ethics review, drug supply and biospecimen collection and management. We propose solutions to promote oncology trial collaboration, such as regulatory reform, harmonisation of trial initiation and management processes and greater recognition and funding of academic (non-commercial) clinical trials. It is only through coordinated effort and leadership from researchers, regulators and those responsible for health systems that the full potential of international trial collaboration can be realised.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Government Regulation; Humans; Information Dissemination; International Cooperation; Medical Oncology; Multicenter Studies as Topic; Neoplasms; Research Support as Topic; Specimen Handling
PubMed: 31378784
DOI: 10.1038/s41416-019-0532-4 -
Sao Paulo Medical Journal = Revista... 2013CONTEXT AND OBJECTIVE Orthopedic research agendas should be considered from a worldwide perspective. Efforts should be planned as the means for obtaining evidence that... (Review)
Review
CONTEXT AND OBJECTIVE Orthopedic research agendas should be considered from a worldwide perspective. Efforts should be planned as the means for obtaining evidence that is valid for health promotion with global outreach. DESIGN AND SETTING Exploratory study conducted at Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil, and McMaster University, Hamilton, Canada. METHODS We identified and analyzed collaborative and multicenter research in Latin America, taking into account American and Canadian efforts as the reference points. We explored aspects of the data available from official sources and used data from traffic accidents as a model for discussing collaborative research in these countries. RESULTS The evaluation showed that the proportion of collaborative and multicenter studies in our setting is small. A brief analysis showed that the death rate due to traffic accidents is very high. Thus, it seems clear to us that initiatives involving collaborative studies are important for defining and better understanding the patterns of injuries resulting from orthopedic trauma and the forms of treatment. Orthopedic research may be an important tool for bringing together orthopedic surgeons, researchers and medical societies for joint action. CONCLUSIONS We have indicated some practical guidelines for initiatives in collaborative research and have proposed some solutions with a summarized plan of action for conducting evidence-based research involving orthopedic trauma.
Topics: Accidents, Traffic; Canada; Humans; Latin America; Multicenter Studies as Topic; Orthopedics; Randomized Controlled Trials as Topic; Traumatology; United States; Wounds and Injuries
PubMed: 23903268
DOI: 10.1590/1516-3180.2013.1313555 -
Nature Reviews. Neurology Apr 2016Each of the thousands of rare neurological diseases requires a widely distributed network of centres, investigators and patients, so as to foster multidisciplinary... (Review)
Review
Each of the thousands of rare neurological diseases requires a widely distributed network of centres, investigators and patients, so as to foster multidisciplinary investigations and involve sufficient numbers of patients in the discovery of disease pathogenesis and novel treatment. In this Review, we highlight the value of this collaborative approach in patient-oriented research into rare neurological channelopathies. Two networks, the Consortium for Clinical Investigations of Neurological Channelopathies (CINCH) and the Clinical Research Consortium for Studies of Cerebellar Ataxias (CRC-SCA), provide a link between patients with rare channelopathies and investigators who are studying disease pathogenesis and developing novel treatments. Interactions between patients, researchers and advocacy groups promote shared agendas that benefit patient education and recruitment, research collaboration and funding, and training and mentoring of junior investigators who are attracted to the study of the diseases that provide the focus for the two networks. Here, we discuss how linkage of national and international centres has enabled recruitment of study participants, provided opportunities for novel studies of pathogenesis, and facilitated successful clinical trials.
Topics: Biomedical Research; Channelopathies; Clinical Trials as Topic; Humans; Multicenter Studies as Topic; Patient Selection; Treatment Outcome
PubMed: 26943780
DOI: 10.1038/nrneurol.2016.18 -
Current Opinion in Neurology Aug 2009The intent of this study is to review trends in multicenter neuroimaging trials and their value for research and implications for clinical treatment. (Review)
Review
PURPOSE OF REVIEW
The intent of this study is to review trends in multicenter neuroimaging trials and their value for research and implications for clinical treatment.
RECENT FINDINGS
The rise in availability of MRI for detecting disorders in the living brain has made it an attractive technology for assessing neural structure and function in a number of prominent diseases. Geographic factors underlying diseased populations coupled with complementary neuroimaging research programs have led to an increase in multicenter neuroimaging trials and consortia. Neuroimaging has become a major focus for multiinstitutional research in progressive changes in brain architecture, proxy biomarkers of treatment response, and the effects of disease on patterns of cognitive activation and connectivity. Notable consortia and research trial studies have focused on Alzheimer's disease, pediatric brain cancer, and fetal alcohol syndrome, in addition to multiinstitutional collaborative programs for mapping the normal brain. Such large-scale efforts necessitate close coordination of image data collection protocols, ontology development, computational requirements, concerted data archiving, and sharing.
SUMMARY
Multicenter neuroimaging trials, consortia, and collaboratives enable the acquisition of large-scale, purpose-driven datasets that can then be used by the broader community to model and predict clinical outcomes as well as guide clinicians in selecting treatment options for neurological disease.
Topics: Brain Diseases; Clinical Trials as Topic; Cooperative Behavior; Databases, Factual; Humans; Magnetic Resonance Imaging; Multicenter Studies as Topic
PubMed: 19506479
DOI: 10.1097/WCO.0b013e32832d92de