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BACKGROUND: To understand our performance with respect to the collection and reporting of patient-reported outcome (PRO) measure (PROM) data, we examined the protocol content, data completeness and publication of PROs from interventional trials conducted at the Royal Marsden NHS Foundation Trust (RM) and explored factors associated with data missingness and PRO publication. DESIGN: From local records, we identified closed, intervention trials sponsored by RM that opened after 1995 and collected PROMs as primary, secondary or exploratory outcomes. Protocol data were extracted by two researchers and scored against the SPIRIT-PRO (PRO protocol content checklist; score 0-100, higher scores indicate better completeness). For studies with locally held datasets, the information team summarized for each study, PRO completion defined as the number of expected (as per protocol) PRO measurements versus the number of actual (i.e. completed) PRO measurements captured in the study data set. Relevant publications were identified by searching three online databases and chief investigator request. Data were extracted and each publication scored against the CONSORT-PRO (PRO manuscript content checklist; scored as SPIRIT-PRO above). Descriptive statistics are presented with exploratory comparisons of point estimates and 95% confidence intervals. RESULTS: Twenty-six of 65 studies were included in the review. Nineteen studies had accessible datasets and 18 studies published at least one article. Fourteen studies published PRO results. Most studies had a clinical (rather than PRO) primary outcome (16/26). Across all studies, responses in respect of 35 of 69 PROMs were published. Trial protocols scored on average 46.7 (range 7.1-92.9) on the SPIRIT-PRO. Among studies with accessible data, half (10/19) had less than 25% missing measurements. Publications scored on average 80.9 (range 36-100%) on the CONSORT-PRO. Studies that published PRO results had somewhat fewer missing measurements (19% [7-32%] vs 60% [- 26 to 146%]). For individual PROMs within studies, missing measurements were lower for those that were published (17% [10-24%] vs 41% [18-63%]). Studies with higher SPIRIT-PRO scores and PROs as primary endpoints (13% [4-22%] vs 39% [10-58%]) had fewer missing measurements. CONCLUSIONS: Missing data may affect publication of PROs. Extent of inclusion of SPIRIT-PRO protocol items and PROs as primary endpoints may improve data completeness. Preliminary evidence from the study suggests a future larger study examining the relationship between PRO completion and publication is warranted.
ABSTRACT
Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to diverse vascular brain lesions in people with cerebrovascular disease (CVD) and to examine associations between FA in NAWM and cerebrovascular risk factors. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in cerebral tissues and cerebrovascular anomalies from 152 people with CVD participating in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Ten cerebral tissue types were segmented including NAWM, and vascular lesions including stroke, periventricular and deep white matter hyperintensities, periventricular and deep lacunar infarcts, and perivascular spaces (PVS) using T1-weighted, proton density-weighted, T2-weighted, and fluid attenuated inversion recovery MRI scans. Mean DTI metrics were measured in each tissue region using a previously developed DTI processing pipeline and compared between tissues using multivariate analysis of covariance. Associations between FA in NAWM and several CVD risk factors were also examined. DTI metrics in vascular lesions differed significantly from healthy tissue. Specifically, all tissue types had significantly different MD values, while FA was also found to be different in most tissue types. FA in NAWM was inversely related to hypertension and modified Rankin scale (mRS). This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies. The association between FA within NAWM and clinical evaluation of hypertension and disability provides further evidence that white matter microstructural integrity is impacted by cerebrovascular function.
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This article explores how six Pakistani Muslim women interpret cultural concepts of izzat (honor and self-respect); what role, if any, it has in their lives; and whether there is interplay between upholding izzat and the participants' help-seeking strategies for mental health and well-being. Semistructured interviews were conducted and analyzed with an interpretative phenomenological analytic framework. Three themes were identified: (a) "the rules of izzat," (b) "negotiating tensions," and (c) "speaking out/breaking the 'rules.'" Findings highlighted new insights into the understanding of izzat and the implications these cultural concepts have for strategies in managing or silencing of psychological distress. Interviews illustrated tensions the participants experience when considering izzat, how these are negotiated to enable them to self-manage or seek help, and possible life experiences that might lead to self-harm and attempted suicide. Notably, cultural codes, in particular izzat, appear to vary over the life course and are influenced by migration.
Subject(s)
Adaptation, Psychological , Cultural Characteristics , Mental Health/ethnology , Stress, Psychological/ethnology , Stress, Psychological/psychology , Adult , Female , Humans , Interviews as Topic , Islam , London , Pakistan/ethnology , Respect , Self-Injurious Behavior/ethnology , Social Support , Suicide/ethnology , Women's Health/ethnology , Young AdultABSTRACT
BACKGROUND: Cognitive strategies are a set of psychologic behaviors used to modulate one's perception or interpretation of a sensation or situation. Although the effectiveness of each cognitive strategy seems to differ between individuals, they are commonly used clinically to help patients with chronic pain cope with their condition. The neural basis of commonly used cognitive strategies is not well understood. Understanding the neural correlates that underlie these strategies will enhance understanding of the analgesic network of the brain and the cognitive modulation of pain. METHODS: The current study examines patterns of brain activation during two common cognitive strategies, external focus of attention and reappraisal, in patients with chronic pain using functional magnetic resonance imaging. RESULTS: Behavioral results revealed interindividual variability in the effectiveness of one strategy versus another in the patients. Functional magnetic resonance imaging revealed distinct patterns of activity when the two strategies were used. During external focus of attention, activity was observed mainly in cortical areas including the postcentral gyrus, inferior parietal lobule, middle occipital gyrus, and precentral gyrus. The use of reappraisal evoked activity in the thalamus and amygdala in addition to cortical regions. Only one area, the postcentral gyrus, was observed to be active during both strategies. CONCLUSIONS: The results of this study suggest that different cognitive behavioral strategies recruit different brain regions to perform the same task: pain modulation.
Subject(s)
Cognitive Behavioral Therapy , Pain Management , Pain/psychology , Adult , Amygdala/physiology , Attention/physiology , Chronic Disease , Emotions/physiology , Female , Humans , Image Processing, Computer-Assisted , Individuality , Limbic System/physiology , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/pathology , Pain/pathology , Prefrontal Cortex/physiology , Young AdultABSTRACT
One of the strong trends in medical education today is the integration of the humanities into the basic medical curriculum. The anatomy program is an obvious choice for using the humanities to develop professionalism and ethical values. They can also be used to develop close observational skills. Many medical schools have developed formal art observation training in conjunction with nearby art museums to enhance the visual diagnostic skills of their medical students. We report here on an art and anatomy workshop that paired medical and art students who did drawing exercises from plastinated anatomical specimens and the animated face to hone observational skills. Each member of the pair brought a different perspective and expertise to the work that allowed each to be a mentor to the other. The workshop had three sessions: the first involved drawings of plastinated specimens that allowed an intimate experience with authentic human material; the second involved drawings of the human face; and the third included examination of anatomical texts of important anatomist-artists, a lecture on contemporary artists whose work involves anatomy, and a film demonstrating the facial muscles. We propose workshops such as these will help students increase their ability to detect details. This will assist the medical student in developing diagnostic skills for identifying disease and the art student in using the human body as subject. We further propose that these programs will help students develop humanistic sensitivities and provide an outlet for expression of the emotional aspects of dealing with disease and mortality.
Subject(s)
Anatomy, Artistic/education , Art , Education, Medical, Undergraduate/methods , Face/anatomy & histology , Humans , ObservationABSTRACT
Functional magnetic resonance imaging (fMRI) is a non-invasive neuroimaging tool that indirectly identifies areas of neural activity in the brain and more recently has been applied to the adult spinal cord (spinal fMRI). Spinal fMRI could clearly benefit pediatric populations as well. The purpose of this work was to characterize the response observed with spinal fMRI in the brainstem and cervical (C) spinal cord of awake, healthy children during thermal stimulation (17°C and 27°C) applied to the right hand. Functional MRI detected neuronal activity in the expected region of the spinal cord (C6 and C7) as well as in the brainstem and thalamus. The observed magnitudes of signal change of the responses to 17°C and 27°C were similar; however, the spatial distribution of active pixels was greater during 17°C stimulation. The results of this study indicate that fMRI can be used to assess activity in the spinal cords of children, with good sensitivity and reliability.
Subject(s)
Magnetic Resonance Imaging/methods , Spinal Cord/physiology , Adolescent , Brain Stem/physiology , Cervical Vertebrae , Child , Cold Temperature , Female , Hand/innervation , Humans , Linear Models , Male , Neural Conduction/physiology , Physical Stimulation , Sensitivity and Specificity , Software , Thalamus/physiology , ThermosensingABSTRACT
Previous literature has reported a wide range of anatomical correlates when participants are required to perform a visuomotor adaptation task. However, traditional adaptation tasks suffer a number of inherent limitations that may, in part, give rise to this variability. For instance, the sparse visual environment does not map well onto conditions in which a visuomotor transformation would normally be required in everyday life. To further clarify these neural underpinnings, functional magnetic resonance imaging (fMRI) was performed on 17 (6M, age range 20-45 years old; mean age=26) naive participants performing a viewing window task in which a visuomotor transformation was created by varying the relationship between the participant's movement and the resultant movement of the viewing window. The viewing window task more naturally replicates scenarios in which haptic and visual information would be combined to achieve a higher-level goal. Even though activity related to visuomotor adaptation was found within previously reported regions of the parietal lobes, frontal lobes, and occipital lobes, novel activation patterns were observed within the claustrum - a region well-established as multi-modal convergence zone. These results confirm the diversity in the number and location of neurological systems recruited to perform a required visuomotor adaptation, and provide the first evidence of participation of the claustrum to overcome a visuomotor transformation.
Subject(s)
Adaptation, Psychological/physiology , Basal Ganglia/physiology , Photic Stimulation , Psychomotor Performance/physiology , Adult , Aging/physiology , Data Interpretation, Statistical , Female , Functional Laterality/physiology , Humans , Image Processing, Computer-Assisted , Learning/physiology , Magnetic Resonance Imaging , Male , Middle Aged , Motor Skills , Nerve Net/physiology , Oxygen/blood , Recruitment, Neurophysiological/physiology , Young AdultABSTRACT
The development of noninvasive neuroimaging techniques, such as fMRI, has rapidly advanced our understanding of the neural systems underlying the integration of visual and motor information. However, the fMRI experimental design is restricted by several environmental elements, such as the presence of the magnetic field and the restricted view of the participant, making it difficult to monitor and measure behaviour. The present article describes a novel, specialized software package developed in our laboratory called Biometric Integration Recording and Analysis (BIRA). BIRA integrates video with kinematic data derived from the hand and eye, acquired using MRI-compatible equipment. The present article demonstrates the acquisition and analysis of eye and hand data using BIRA in a mock (0 Tesla) scanner. A method for collecting and integrating gaze and kinematic data in fMRI studies on visuomotor behaviour has several advantages: Specifically, it will allow for more sophisticated, behaviourally driven analyses and eliminate potential confounds of gaze or kinematic data.
Subject(s)
Eye Movements , Hand Strength , Hand , Magnetic Resonance Imaging/methods , Movement , Software , Biomechanical Phenomena , Brain Mapping/methods , Eye Movement Measurements , Humans , Image Processing, Computer-Assisted/methods , Psychomotor PerformanceABSTRACT
PURPOSE: To use spinal cord diffusion tensor imaging (DTI) for investigating human cervical funiculi, acquire axial diffusion magnetic resonance imaging (MRI) data with an in-plane resolution sufficient to delineate subquadrants within the spinal cord, obtain corresponding DTI metrics, and assess potential regional differences. MATERIALS AND METHODS: Healthy volunteers were studied with a 3 T Siemens Trio MRI scanner. DTI data were acquired using a single-shot spin echo EPI sequence. The spatial resolution allowed for the delineation of regions of interest (ROIs) in the ventral, dorsal, and lateral spinal cord funiculi. ROI-based and tractography-based analyses were performed. RESULTS: Significant fractional anisotropy (FA) differences were found between ROIs in the dorsal and ventral funiculi (P = 0.0001), dorsal and lateral funiculi (P = 0.015), and lateral and ventral funiculi (P = 0.0002). Transverse diffusivity was significantly different between ROIs in the ventral and dorsal funiculi (P = 0.003) and the ventral and lateral funiculi (P = 0.004). Tractography-based quantifications revealed DTI parameter regional differences that were generally consistent with the ROI-based analysis. CONCLUSION: Original contributions are: 1) the use of a tractography-based method to quantify DTI metrics in the human cervical spinal cord, and 2) reported DTI values in various funiculi at 3 T.
Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Nerve Fibers/pathology , Spinal Cord/pathology , Adolescent , Adult , Anisotropy , Female , Humans , Male , Spinal Cord/anatomy & histology , Whole Body Imaging/methodsABSTRACT
Rapidly developing, non-invasive, neuroimaging methods provide increasingly detailed structural and functional information about the nervous system, helping advance our understanding of pain processing, chronic pain conditions and the mechanisms of analgesia. However, effective treatment for many chronic pain conditions remains a large, unmet medical need. Neuroimaging techniques may enhance our understanding of why currently available analgesics are ineffective for so many patients and aid in identifying new neural targets for pharmacological interventions of pain. This review examines how neuroimaging has enhanced our understanding of the mechanisms of chronic pain, the neural correlates of pharmacological modulation of pain, and the role of neuroimaging in analgesic development. Rather than focusing on one method, we discuss the advantages and limitations of several techniques that may each serve a unique role in aiding drug development, and we discuss current issues that exist in the design and implementation of pharmacological neuroimaging studies. Particularly, experimental design must be carefully considered as there are limitations in terms of the pharmacokinetics of the drug of interest as well as in respect to the capabilities of the neuroimaging method in use. Finally, we identify future directions including novel approaches that may also play a role in furthering our knowledge of the neural basis of analgesia. In the future, neuroimaging will certainly impact the methodology of analgesic drug development as it may lead to quicker and more efficient methods of evaluating the neural modulation of chronic pain.
Subject(s)
Analgesics/therapeutic use , Diagnostic Imaging/methods , Drug Design , Pain/drug therapy , Animals , Biomedical Research/methods , Biomedical Research/trends , Clinical Trials as Topic , Diagnostic Imaging/trends , Humans , Models, Biological , Pain/diagnosisABSTRACT
INTRODUCTION: We investigated noninvasively areas of the healthy human spinal cord that become active in response to vibration stimulation of different dermatomes using functional magnetic resonance imaging (fMRI). The objectives of this study were to: (1) examine the patterns of consistent activity in the spinal cord during vibration stimulation of the skin, and (2) investigate the rostrocaudal distribution of active pixels when stimulation was applied to different dermatomes. METHODS: FMRI of the cervical and lumbar spinal cord of seven healthy human subjects was carried out during vibration stimulation of six different dermatomes. In separate experiments, vibratory stimulation (about 50 Hz) was applied to the right biceps, wrist, palm, patella, Achilles tendon and left palm. RESULTS: The segmental distribution of activity observed by fMRI corresponded well with known spinal cord neuroanatomy. The peak number of active pixels was observed at the expected level of the spinal cord with some activity in the adjacent segments. The rostrocaudal distribution of activity was observed to correspond to the dermatome being stimulated. Cross-sectional localization of activity was primarily in dorsal areas but also spread into ventral and intermediate areas of the gray matter and a distinct laterality ipsilateral to the stimulated limb was not observed. CONCLUSION: We demonstrated that fMRI can detect a dermatome-dependent pattern of spinal cord activity during vibratory stimulation and can be used as a passive stimulus for the noninvasive assessment of the functional integrity of the human spinal cord. Demonstration of cross-sectional selectivity of the activation awaits further methodological and experimental refinements.
Subject(s)
Magnetic Resonance Imaging , Spinal Cord/physiology , Adult , Arm/innervation , Female , Foot/innervation , Humans , Knee/innervation , Linear Models , Male , VibrationABSTRACT
Patterns of neuronal activity in the spinal cord using functional magnetic resonance imaging during noxious (48 degrees C) and innocuous (40 degrees C) thermal stimulation of the rat forepaw were examined. The patterns of functional activity elicited by thermal stimuli were compared in alpha-chloralose- and halothane-anesthetized rats. Although the locations of active pixels were similar during both types of stimulation, the mean percentage signal change was higher during noxious stimulation in both anesthetic groups. Ipsilateral dorsal horn activity was evident during both noxious and innocuous stimulation in all animals. The greatest consistency of ipsilateral dorsal horn activity occurred at the C3 to C5 spinal cord segments in all groups. Consistent contralateral dorsal horn activity appeared in segments C6 to C8 in all groups. C-fos immunohistochemical staining confirmed the presence of neural activity in the spinal cords of all animals.
Subject(s)
Chloralose/pharmacology , Halothane/pharmacology , Magnetic Resonance Imaging/methods , Spinal Cord/physiology , Anesthetics, Inhalation/pharmacology , Anesthetics, Intravenous/pharmacology , Animals , Blood Pressure/drug effects , Body Temperature , Carbon Dioxide/blood , Cervical Vertebrae , Electric Stimulation , Forelimb/innervation , Heart Rate/drug effects , Immunohistochemistry , Oxygen/blood , Rats , Rats, Sprague-DawleyABSTRACT
Alpha-chloralose is commonly used during animal fMRI studies for anesthesia, however, recovery of animals is difficult, limiting experimental design. The use of a less invasive anesthetic would enable chronic experiments. The present study compares functional activity in the spinal cord of the alpha-chloralose and halothane-anesthetized rat. Functional MRI of the rat cervical spinal cord was performed on 6 alpha-chloralose and 6 halothane-anesthetized rats in a Bruker 7 T MR system during electrical stimulation of the right forepaw. Following imaging, four animals from each group were perfused and spinal cords removed for immunohistochemical analysis. Areas of c-fos expression were identified with immunofluorescent labeling to confirm the presence of neuronal activity. Functional activity and c-fos expression were observed predominantly between the fifth and seventh cervical spinal cord segments. Areas of fMRI activation in the spinal cord correspond well with spinal cord physiology. Areas of c-fos expression confirmed that neuronal activity was present in the regions of fMRI activity. The regions and amount of fMRI activity observed were similar for both anesthetics. Functional magnetic resonance imaging of the spinal cord can be achieved using both alpha-chloralose and halothane anesthesia in rats. We therefore suggest that halothane may be used as an anesthetic agent for chronic fMRI studies of the spinal cord.
Subject(s)
Chloralose/pharmacology , Halothane/pharmacology , Spinal Cord/physiology , Anesthetics, Inhalation/pharmacology , Anesthetics, Intravenous/pharmacology , Animals , Blood Pressure/drug effects , Body Temperature , Carbon Dioxide/blood , Cervical Vertebrae , Electric Stimulation , Forelimb/innervation , Heart Rate/drug effects , Immunohistochemistry , Magnetic Resonance Imaging , Oxygen/blood , Rats , Rats, Sprague-DawleyABSTRACT
Functional magnetic resonance imaging based on a non-BOLD-contrast mechanism, which we have termed "SEEP" (Signal Enhancement by Extravascular water Protons), has previously been demonstrated. Here the reproducibility of areas of activity identified with both SEEP and BOLD contrast is assessed in duplicate experiments in healthy volunteers, with relatively high resolution (1.6 mm) image data at 1.5 T. These areas of activity are equally well localized to voxels containing primarily gray matter with the two contrast mechanisms. As in previous studies, areas of SEEP activity are observed to be immediately adjacent to areas of BOLD activity, with very little overlap. The response functions were estimated for both SEEP and BOLD contrast, and are observed to be distinct. The peak SEEP response is observed to lag the BOLD response by approximately 1 s and to decay more slowly with no poststimulus undershoot. Average BOLD signal changes (GE-EPI, TE=50 ms) were observed to be 3.4+/-1.2% (mean+/-S.D.), whereas SEEP signal changes (SE-EPI, TE=23 ms) were 1.9+/-0.5%, consistent with previous studies carried out at 0.2 and 3 T. These observations provide further support for the existence of a non-BOLD-contrast mechanism for fMRI, based on changes in extravascular spin density.
Subject(s)
Brain/anatomy & histology , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Signal Processing, Computer-Assisted , Humans , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Time FactorsABSTRACT
PURPOSE: To develop a spinal functional MRI (fMRI) method with three-dimensional coverage of a large extent of the spinal cord with minimal partial volume effects MATERIALS AND METHODS: fMRI data of the cervical spinal cord were obtained at 1.5 T with a single-shot fast spin-echo imaging method, from thin contiguous sagittal slices spanning the cord. Thermal stimulation was applied to the palm of the hand in a block pattern with 15 degrees C for stimulation and 32 degrees C during baseline periods. Prior to analysis, the image data at each time point were reformatted into three-dimensional volumes and resliced perfectly transverse to the spinal cord. Smoothing was applied only in the superior-inferior (S/I) direction across uniform tissue types. Active voxels were then identified by means of a correlation to a model paradigm. RESULTS: The resulting activity maps demonstrate activity primarily in ipsilateral sensory areas and in some motor areas, consistent with the spinal cord neuroanatomy. These data also demonstrate detail of the subsegmental organization of the spinal cord, as well as anatomical detail of the spinous processes and positions of nerve roots. CONCLUSION: The spinal fMRI method described enables large volume coverage of the spinal cord in three dimensions, with reliable and reproducible results.
Subject(s)
Magnetic Resonance Imaging/methods , Spinal Cord/physiology , Humans , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Spinal Cord/anatomy & histologyABSTRACT
The relationship between neuronal activity in the rat cervical and lumbar spinal cord was examined using functional magnetic resonance imaging (fMRI) and immunohistochemistry. Neuronal activity determined by c-fos staining was greatest between L4 and L6, and C5 to C7 spinal cord segments during noxious electrical stimulation of the rat hindpaw and forepaw, respectively. Areas of activity determined by fMRI are consistent with spinal cord physiology, and are predominantly found in regions of the spinal cord associated with pain, namely the dorsal horn. Activity in the ventral region of the cord was also observed, as expected. Combined results from repeated experiments demonstrated consistent areas of activity in response to stimulation, and show a high degree of reproducibility. Good correspondence was observed between functional MRI and sites of neuronal activity determined by c-fos labeling.