An analysis of ideal and actual time to surgery after traumatic spinal cord injury in Canada.

STUDY DESIGN: Retrospective analysis of a prospective registry and surgeon survey. OBJECTIVES: To identify surgeon opinion on ideal practice regarding the timing of decompression/stabilization for spinal cord injury and actual practice. Discrepancies in surgical timing and barriers to ideal timing of surgery were explored. SETTING: Canada. METHODS: Patients from the Rick Hansen Spinal Cord Registry (RHSCIR, 2004-2014) were reviewed to determine actual timing of surgical management. Following data collection, a survey was distributed to Canadian surgeons, asking for perceived to be the optimal and actual timings of surgery. Discrepancies between actual data and surgeon survey responses were then compared using χ2 tests and logistic regression. RESULTS: The majority of injury patterns identified in the registry were treated operatively. ASIA Impairment Scale (AIS) C/D injuries were treated surgically less frequently in the RHSCIR data and surgeon survey (odds ratio (OR)= 0.39 and 0.26). Significant disparities between what surgeons identified as ideal, actual current practice and RHSCIR data were demonstrated. A great majority of surgeons (93.0%) believed surgery under 24 h was ideal for cervical AIS A/B injuries and 91.0% for thoracic AIS A/B/C/D injuries. Definitive surgical management within 24 h was actually accomplished in 39.0% of cervical and 45.0% of thoracic cases. CONCLUSION: Ideal surgical timing for traumatic spinal cord injury (tSCI) within 24 h of injury was identified, but not accomplished. Discrepancies between the opinions on the optimal and actual timing of surgery in tSCI patients suggest the need for strategies for knowledge translation and reduction of administrative barriers to early surgery.

Evaluation of a pilot Pressure Ulcer Prevention Initiative (PUPI) for patients with traumatic spinal cord injury.

OBJECTIVE: The purpose of this study was to determine whether implementation of a Pressure Ulcer Prevention Initiative (PUPI) changed the assessment and treatment of patients with a traumatic spinal cord injury (SCI) in an acute care setting, and improved patient outcomes. METHOD: The success of implementation was evaluated by examining the percentage of patients with completed occupational therapist (OT) skin care assessments and prescriptions for therapeutic support surfaces (TSS; i.e., mattresses) before implementation (historical, cohort 1) and after implementation (experimental, cohort 2). Patient outcomes were evaluated by examining changes in PU incidence, severity, timing and recurrence, as well as PU prevalence and satisfaction with life in the community. RESULTS: Final analysis included 70 patients in cohort 1 and 73 in cohort 2. OT skin care assessment documentation (31% to 60%; p<0.001) and TSS prescriptions (31% to 60%; p=0.02) significantly increased following the implementation. The PU incidence based on patient charts (both nursing and OT assessments) did not increase significantly (26% to 36%; p=0.2). However, documented PU incidence according to OT assessments showed a substantial increase (14% to 33%; p=0.002). No effect of the PUPI was seen on immediate or long-term patient outcomes during the study period. CONCLUSION: PUPI was successful in changing clinical practice in PU prevention but no statistically significant improvements in PU-related patient outcomes were demonstrated. Results from this study identified facilitators and barriers to implementation and highlighted the complexity and difficulty of instituting effective preventative or therapeutic interventions for this population in an acute care setting. This information will assist with refinements of the PUPI and inform similar future initiatives.

The economic burden of traumatic spinal cord injury in Canada.

INTRODUCTION: The purpose of this study is to estimate the current lifetime economic burden of traumatic spinal cord injury (tSCI) in Canada from a societal perspective, including both direct and indirect costs, using an incidence-based approach. METHODS: Available resource use and cost information for complete/incomplete tetraplegia and paraplegia was applied to the estimated annual incidence of tSCI, by severity, in Canada. RESULTS: The estimated lifetime economic burden per individual with tSCI ranges from $1.5 million for incomplete paraplegia to $3.0 million for complete tetraplegia. The annual economic burden associated with 1389 new persons with tSCI surviving their initial hospitalization is estimated at $2.67 billion. CONCLUSION: While the number of injuries per year in Canada is relatively small, the annual economic burden is substantial.

TITLE: Fardeau économique lié aux traumatismes de la moelle épinière au Canada. INTRODUCTION: Cette étude vise à mesurer, au moyen d'une approche fondée sur l'incidence, le fardeau économique à vie lié aux traumatismes de la moelle épinière (TME) au Canada du point de vue social, en incluant les coûts directs et indirects. MÉTHODOLOGIE: Les ressources disponibles et l'information sur les coûts liés aux cas de tétraplégie et de paraplégie complètes et incomplètes ont été appliquées à l'incidence annuelle estimative des TME au Canada en fonction de leur gravité. RÉSULTATS: Le fardeau économique à vie d'une personne atteinte d'un TME varie de 1,5 million de dollars pour une paraplégie incomplète à 3 millions de dollars pour une tétraplégie complète. Le fardeau économique annuel lié aux 1 389 nouveaux cas de TME où le patient a survécu à son hospitalisation est estimé à 2,67 milliards de dollars. CONCLUSION: Malgré leur fréquence annuelle relativement faible au Canada, ces blessures entraînent un fardeau économique annuel important.

The influence of depression on physical complications in spinal cord injury: behavioral mechanisms and health-care implications.

STUDY DESIGN: This study is a literature review and a proposed conceptual model. OBJECTIVES: The objective of this study is to develop a conceptual model to explore the relationship between the presence of depressive symptoms and secondary physical complications such as pressure ulcers, urinary tract infections and autonomic dysreflexia in spinal cord injury (SCI). SETTING: Community setting for individuals with SCI. METHODS: A conceptual model explaining the mechanism underlying the relationship between depression and secondary physical SCI complications was developed based on the International Classification of Functioning, Disability and Health (ICF). A literature review was conducted to develop the model and to identify potential mechanisms responsible for the association. RESULTS: A conceptual model based on ICF was created, informed by the literature discussing the link between depression and secondary physical SCI complications. Evidence in the literature was located that supports both a causal connection between depression and increased physical complications and/or the potential mechanisms mediating that connection. CONCLUSION: The proposed model can be utilized to encourage further research on the influence of depression on SCI outcomes and the importance of prompt and effective identification and treatment of depressive symptoms. Additional research is needed to assess the relationship between depression and secondary physical SCI complications, and to test the validity of the model.

Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations.

Oncogenic mutations in PIK3CA, which encodes the phosphoinositide-3-kinase (PI3K) catalytic subunit p110α, occur in ∼25% of human breast cancers. In this study, we report the development of a knock-in mouse model for breast cancer where the endogenous Pik3ca allele was modified to allow tissue-specific conditional expression of a frequently found Pik3ca(H1047R) (Pik3ca(e20H1047R)) mutant allele. We found that activation of the latent Pik3ca(H1047R) allele resulted in breast tumors with multiple histological types. Whole-exome analysis of the Pik3ca(H1047R)-driven mammary tumors identified multiple mutations, including Trp53 mutations that appeared spontaneously during the development of adenocarinoma and spindle cell tumors. Further, we used this model to test the efficacy of GDC-0941, a PI3K inhibitor, in clinical development, and showed that the tumors respond to PI3K inhibition.

A grid overlay framework for analysis of medical images and its application to the measurement of stroke lesions.

OBJECTIVES: To create and evaluate an interactive software tool for measuring imaging data in situations where hand-drawn region-of-interest measurements are unfeasible, for example, when the structure of interest is patchy with ill-defined boundaries. METHODS: An interactive grid overlay software tool was implemented that enabled coding of voxels dependent on their imaging appearance with a series of user-defined classes. The Grid Analysis Tool (GAT) was designed to automatically extract quantitative imaging data, grouping the results by tissue class. Inter- and intra-observer reproducibility was evaluated by six observers of various backgrounds in a study of acute stroke patients. RESULTS: The software tool enabled a more detailed classification of the stroke lesion than would be possible with a region-of-interest approach. However, inter-observer coefficients of variation (CVs) were relatively high, reaching 70% in "possibly abnormal" tissue and around 15-20% in normal appearing tissues, while intra-observer CVs were no more than 13% in "possibly abnormal" tissue and generally less than 1% in normal-appearing tissues. CONCLUSIONS: The grid-overlay method overcomes some of the limitations of conventional Region Of Interest (ROI) approaches, providing a viable alternative for segmenting patchy lesions with ill-defined boundaries, but care is required to ensure acceptable reproducibility if the method is applied by multiple observers. KEY POINTS: Computer software developed to overcome limitations of conventional regions of interest measurements • This software is suitable for patchy lesions with ill-defined borders • Allows a more detailed assessment of imaging data.

MR diffusion-weighted imaging and outcome prediction after ischemic stroke.

BACKGROUND: MR diffusion-weighted imaging (DWI) shows acute ischemic lesions early after stroke so it might improve outcome prediction and reduce sample sizes in stroke treatment trials. Previous studies of DWI and outcome produced conflicting results. OBJECTIVE: To determine whether DWI lesion characteristics independently predict outcome in a broad range of patients with acute stroke. METHODS: The authors recruited hospital-admitted patients with all severities of suspected stroke, assessed stroke severity on the NIH Stroke Scale (NIHSS), performed early brain DWI, and assessed outcome at 3 months (modified Rankin Scale). Clinical data and DWI lesion parameters were evaluated in a logistic regression model to identify independent predictors of outcome at 3 months and a previously described "Three-Item Scale" (including DWI) was tested for outcome prediction. RESULTS: Among 82 patients (mean NIHSS 7.1 [+/-6.3 SD]), the only independent outcome predictors were age and stroke severity. Neither DWI lesion volume nor apparent diffusion coefficient nor the previously described Three-Item Scale predicted outcome independently. Comparison with previous studies suggested that DWI may predict outcome only in patients with more severe cortical ischemic strokes. CONCLUSIONS: Across a broad range of stroke severities, diffusion-weighted imaging (DWI) did not predict outcome beyond that of key clinical variables. Thus, DWI is unlikely to reduce sample sizes in acute stroke trials assessing functional outcome, especially where estimated treatment effects are modest.

Do acute diffusion- and perfusion-weighted MRI lesions identify final infarct volume in ischemic stroke?

BACKGROUND AND PURPOSE: An acute mismatch on diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) may represent the "tissue-at-risk." It is unclear which "semiquantitative" perfusion parameter most closely identifies final infarct volume. METHODS: Acute stroke patients underwent DWI and PWI (dynamic-susceptibility contrast imaging) on admission (baseline), and T2-weighted imaging (T2WI) at 1 or 3 months after stroke. "Semiquantitative" mean transit time (MTTsq=first moment of concentration/time curve), cerebral blood volume (CBVsq=area under concentration/time curve), and cerebral blood flow (CBFsq=CBVsq/MTTsq) were calculated. DWI and PWI lesions were measured at baseline and final infarct volume on T2WI acquired > or =1 month after stroke. Baseline DWI, CBFsq, and MTTsq lesion volumes were compared with final T2WI lesion volume. RESULTS: Among 46 patients, baseline DWI and CBFsq lesions were not significantly different from final T2WI lesion volume, but baseline MTTsq lesions were significantly larger. The correlation with final T2WI lesion volume was strongest for DWI (Spearman rank correlation coefficient rho=0.68), intermediate for CBFsq (rho=0.55), and weakest for MTTsq (rho=0.49) baseline lesion volumes. Neither DWI/CBFsq nor DWI/MTTsq mismatch predicted lesion growth; lesion growth was equally common in those with and without mismatch. CONCLUSIONS: Of the 2 PWI parameters, CBFsq lesions most closely identifies, and MTTsq overestimates, final T2WI lesion volume. "DWI/PWI mismatch" does not identify lesion growth. Patients without "DWI/PWI mismatch" are equally likely to have lesion growth as those with mismatch and should not be excluded from acute stroke treatment.

Cognitive correlates of cerebral white matter lesions and water diffusion tensor parameters in community-dwelling older people.

BACKGROUND: The biological basis of cognitive ageing is unknown. One underlying process might be disruption of white matter tracts connecting cortical regions. White matter lesions (WML) seen on structural MRI may disrupt cortical connections, but diffusion tensor MRI (DT-MRI) parameters - mean diffusivity () and fractional anisotropy (FA) - may reflect more subtle changes in white matter integrity. Here the relationships between WML load, DT-MRI parameters and cognition in a large cohort of elderly subjects with a very narrow age range were investigated. METHODS: 105 community-dwelling volunteers underwent MRI and neuropsychological assessment. Seventy-two (68.6%) were female, and their mean age was 78.4 (SD 1.5) years. Scans were rated for WML load. and FA were measured from regions of interest in normal-appearing frontal and occipital white matter, and centrum semiovale. RESULTS: and FA differed significantly among the three brain regions studied (p << 0.01). increased with age (r = 0.22 to 0.35, p < 0.03), and was negatively correlated with FA (r = -0.20 to -0.51, p < 0.05) in all three regions. There was a trend towards increased WML load correlating with poorer cognitive function, and this was statistically significant for the Mini-Mental State Examination (rho = -0.23, p = 0.02). was generally negatively correlated with cognitive test score, and FA was positively correlated. This pattern was more consistent for than for FA, and particularly for verbal fluency (: r = -0.22 to -0.27, p < 0.03), which measures executive function. CONCLUSIONS: DT-MRI parameters, in particular , are sensitive to early ultrastructural changes underlying cognitive ageing. Executive function may be the cognitive domain most sensitive to age-related decline in white matter tract integrity.

Temporal evolution of water diffusion parameters is different in grey and white matter in human ischaemic stroke.

OBJECTIVES: Our purpose was to investigate whether differences exist in the values and temporal evolution of mean diffusivity () and fractional anisotropy (FA) of grey and white matter after human ischaemic stroke. METHODS: Thirty two patients with lesions affecting both grey and white matter underwent serial diffusion tensor magnetic resonance imaging (DT-MRI) within 24 hours, and at 4-7 days, 10-14 days, 1 month, and 3 months after stroke. Multiple small circular regions of interest (ROI) were placed in the grey and white matter within the lesion and in the contralateral hemisphere. Values of [grey], [white], FA[grey] and FA[white] were measured in these ROI at each time point and the ratios of ischaemic to normal contralateral values (R and FAR) calculated. RESULTS: and FA showed different patterns of evolution after stroke. After an initial decline, the rate of increase of [grey] was faster than [white] from 4-7 to 10-14 days. FA[white] decreased more rapidly than FA[grey] during the first week, thereafter for both tissue types the FA decreased gradually. However, FA[white] was still higher than FA[grey] at three months indicating that some organised axonal structure remained. This effect was more marked in some patients than in others. R[grey] was significantly higher than R[white] within 24 hours and at 10-14 days (p<0.05), and FAR[white] was significantly more reduced than FAR[grey] at all time points (p<0.001). CONCLUSIONS: The values and temporal evolution of and FA are different for grey and white matter after human ischaemic stroke. The observation that there is patient-to-patient variability in the degree of white matter structure remaining within the infarct at three months may have implications for predicting patient outcome.