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Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels, and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis. Few channel blockers have been tested in preclinical models of OA, with varying results. Finally, we discuss some examples of G-protein coupled receptors, which may offer attractive therapeutic strategies for OA pain, including receptors for bradykinin, calcitonin gene-related peptide, and chemokines. Since many of the pathways described above can be selectively and potently targeted, they offer an exciting opportunity for pain management in OA, either systemically or locally. 相似文献
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Anderson Spickard III Toufeeq Ahmed Kimberly Lomis Kevin Johnson Bonnie Miller 《Teaching and learning in medicine》2016,28(1):80-87
Problem: Many medical schools are modifying curricula to reflect the rapidly evolving health care environment, but schools struggle to provide the educational informatics technology (IT) support to make the necessary changes. Often a medical school's IT support for the education mission derives from isolated work units employing separate technologies that are not interoperable. Intervention: We launched a redesigned, tightly integrated, and novel IT infrastructure to support a completely revamped curriculum at the Vanderbilt School of Medicine. This system uses coordinated and interoperable technologies to support new instructional methods, capture students' effort, and manage feedback, allowing the monitoring of students' progress toward specific competency goals across settings and programs. Context: The new undergraduate medical education program at Vanderbilt, entitled Curriculum 2.0, is a competency-based curriculum in which the ultimate goal is medical student advancement based on performance outcomes and personal goals rather than a time-based sequence of courses. IT support was essential in the creation of Curriculum 2.0. In addition to typical learning and curriculum management functions, IT was needed to capture data in the learning workflow for analysis, as well as for informing individual and programmatic success. We aligned people, processes, and technology to provide the IT infrastructure for the organizational transformation. Outcomes: Educational IT personnel were successfully realigned to create the new IT system. The IT infrastructure enabled monitoring of student performance within each competency domain across settings and time via personal student electronic portfolios. Students use aggregated performance data, derived in real time from the portfolio, for mentor-guided performance assessment, and for creation of individual learning goals and plans. Poorly performing students were identified earlier through online communication systems that alert the appropriate instructor or coach of low quiz grades or missed learning goals. Graphical and narrative displays of a student's competency performance across courses and clinical experiences informed high-stake decisions made about student progress by the promotions committee. Similarly, graphical display of aggregate student outcomes provided education leaders with information needed to adjust and improve the curriculum. Lessons Learned: With the alignment of people, processes, and technology, educational IT can facilitate transformational steps in the training of medical students. 相似文献
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This study aimed at analysing first-time hospitalisations for traumatic brain injury (TBI) and spinal cord injury (SCI) in Western Australia (WA), in terms of socio-demographic profile, cause of injury, relative risks and survival, using tabular and regression analyses of linked hospital discharge and mortality census files and comparing results with published standardised mortality rates (SMRs) for TBI. Participants were all 9,114 first hospital admissions for TBI or SCI from 7/2003 to 6/2008, linked to mortality census data through 12/2008, and the main outcome measures were number of cases by cause, SMRs in hospital and post-discharge by year through year 5. Road crashes accounted for 34 % of hospitalised TBI and 52 % of hospitalised SCI. 8,460 live TBI discharges experienced 580 deaths during 24,494 person-years of follow-up. The life-table expectation of deaths in the cohort was 164. Post-discharge SMRs were 7.66 in year 1, 3.86 in year 2 and averaged 2.31 in years 3 through 5. 317 live SCI discharges experienced 18 deaths during 929 years of follow-up. Post-discharge SMRs were 7.36 in year 1 and a fluctuating average of 2.13 in years 2 through 5. Use of data from model systems does not appear to yield biased SMRs. Similarly no systematic variation was observed between all-age studies and the more numerous studies that focused on those aged 14 to 16 and older. Based on two studies, SMRs for TBI, however, may be higher in year 2 post-discharge in Australia than elsewhere. That possibility and its cause warrant exploration. Expanding public TBI/SCI compensation in WA from road crash to all causes might triple TBI compensation and double SCI compensation. 相似文献
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