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991.
Sewitch MJ Stein D Joseph L Bitton A Hilsden RJ Rabeneck L Paszat L Tinmouth J Cooper MA 《Journal canadien de gastroenterologie》2010,24(11):656-660
BACKGROUND
Determining whether a colonoscopy is performed for screening or nonscreening purposes can facilitate clinical practice and research. However, there is no simple method to determine the colonoscopy indication using patient medical files or health administrative databases.OBJECTIVE
To determine patient-endoscopist agreement on the colonoscopy indication.METHODS
A cross-sectional study was conducted among staff endoscopists and their patients at seven university-affiliated hospitals in Montreal, Quebec. The study participants were 50 to 75 years of age, they were able to understand English or French, and were about to undergo colonoscopy. Self- (endoscopist) and interviewer-administered (patient) questionnaires ascertained information that permitted classification of the colonoscopy indication. Patient colonoscopy indication was defined as the following: perceived screening (routine screening, family history, age); perceived nonscreening (follow-up); medical history that implied nonscreening; and a combination of the three preceding indications. Agreement between patient and endoscopist indications was measured using concordance and Kappa statistic.RESULTS
In total, 702 patients and 38 endoscopists participated. The three most common reasons for undergoing colonoscopy were routine screening/regular check-up (33.8%), follow-up to a previous problem (30.2%) and other problem (24.6%). Concordance (range 0.79 to 0.85) and Kappa (range 0.58 to 0.70) were highest for perceived nonscreening colonoscopy. Recent large bowel symptoms accounted for 120 occurrences of disagreement in which the patient perceived a nonscreening colonoscopy while the endoscopist perceived a screening colonoscopy.CONCLUSIONS
Patient self-report may be an acceptable means for rapidly assessing whether a colonoscopy is performed for screening or nonscreening purposes. Delivery of patient-centred care may help patients and endoscopists reach a shared understanding of the reason for colonoscopy. 相似文献992.
Youth with type 1 diabetes are at high risk for psychosocial morbidities. These include depression, disturbed eating behavior,
family conflict, poor health-related quality of life, low self-efficacy, and difficulty with medical adherence and metabolic
control. A number of prevention interventions have been studied in this group, with the overall goal of improving adaptation
and coping skills. This paper reviews the current research aimed at preventing poor outcomes in youth with type 1 diabetes
and recommends simple interventions that can be added to clinical encounters. Recommendations for future psychosocial prevention
studies are also discussed. 相似文献
993.
Roberto Pisoni Jill Barker-Finkel Michael Allo 《Clinical journal of the American Society of Nephrology》2010,5(8):1447-1450
Background and objectives: Neointimal hyperplasia is the major cause of vascular access failure in hemodialysis patients. Statins reduce neointimal hyperplasia in experimental models, which may reduce access failure. The study presented here evaluated whether vascular access outcomes are superior in patients receiving statin therapy than in those not on statins.Design, setting, participants, & measurements: A prospective computerized vascular access database was retrospectively queried to determine the access outcomes of 601 patients receiving an upper-arm fistula or graft at a single large dialysis center.Results: Primary fistula failure was observed in 37% of patients on statin therapy versus 38% not on statin therapy. Primary graft failure occurred in 20% of patients on statin therapy versus 14% not on statin therapy. A multiple variable logistic regression analysis including statin use, diabetes, coronary artery disease, peripheral artery disease, sex, and age found that only sex predicted primary fistula failure and graft failure. After excluding primary failures, cumulative fistula survival was similar for patients with or without statin therapy (hazard ratio [HR] 1.26; 95% confidence interval [CI] 0.76 to 2.16). Likewise, cumulative graft survival was similar for statin therapy versus no statin therapy (HR 0.88; 95% CI 0.59 to 1.32). Using a multivariable survival analysis model to predict cumulative fistula survival, only age predicted fistula failure (HR 1.21 per decade; 95% CI 1.02 to 1.44). None of the variables in this model predicted cumulative graft survival.Conclusions: Statin therapy is not associated with improved fistula or graft outcomes in patients with chronic kidney disease.Hemodialysis vascular access complications are common in hemodialysis patients, accounting for approximately 20% of all hospitalizations (1–3). Arteriovenous (AV) fistulas have a much higher suitability failure (primary failure) than do AV grafts. However, once suitability for dialysis has been achieved, fistulas have a better cumulative survival as compared with AV grafts (4,5). The main cause of fistula and graft failure is aggressive neointimal hyperplasia that results in stenosis and subsequent thrombosis, most commonly in the perianastomotic region for fistulas or at the venous anastomosis for grafts (6,7).The pathogenetic mechanisms of neointimal hyperplasia are complex and not fully understood, but inflammation plays a central role in the cascade of events leading to access stenosis (8,9). Thus, targeting neointimal hyperplasia and inflammation may be critical in improving vascular access survival. Although several drugs have been shown to inhibit neointimal hyperplasia in experimental models, current treatments to prevent or treat vascular access dysfunction in dialysis patients are minimally effective (10–14). The published literature provides conflicting evidence regarding the potential protective effects of statins on vascular access outcomes (15,16).The aim of the study presented here was to evaluate whether fistula or graft outcomes are superior in chronic kidney disease (CKD) patients receiving statins. We assessed this research question by comparing the primary failure rate and cumulative survival of new vascular accesses in CKD patients treated or not treated with statin therapy. 相似文献
994.
White EA Horne A Runciman J Orazem ME Navidi WC Roper CS Bunge AL 《Toxicology in vitro》2011,25(8):2095-2104
The objective of this study was to quantitatively compare measurements of tritiated water permeability with impedance determined at either 100 or 1000 Hz using an LCR databridge on the same pieces of skin. A previously published expression based on a simple circuit of a parallel resistor and constant phase element (CPE) was used to relate (RPARA) measured at different frequencies to the DC resistance (RskinA) and the steady-state skin permeability of tritiated water (kp). Using this analysis, kp and (RPARA) data from three laboratories were shown to be consistent with each other, and kp and (RskinA) estimated from (RPARA) were linearly correlated. Compared with urea and mannitol, which are known to permeate skin through a polar pathway, the value of kp for water was found to be about two times larger than expected for transport through only the polar pathway, suggesting an approximately equal contribution from the lipophilic pathway. Equations relating kp to (RPARA) and (RskinA) were used to compare on a consistent basis proposed tests for identifying and excluding damaged skin from chemical absorption studies. The criterion of 20 kΩ cm2 for (RskinA) corresponds to a tritiated water permeability of 3.2 × 10−3 cm/h, which should exclude damaged skin without screening undamaged but higher permeability skin samples from study. 相似文献
995.
Discoveries in the pre-clinical neurosciences have set the stage for bringing new therapies to patients affected by neurological disorders. The National lnstitute of Neurological Disorders and Stroke (NINDS) is dedicated to promoting the development of new therapies through its funding programs that range from basic neuroscience to translational research and finally clinical research to test the most promising new therapies in patients. In an effort to accelerate the translation of new discoveries to clinical practice, NINDS is piloting novel organizational strategies. In translational research, NINDS is taking the lead on the establishment of a ‘virtual pharma'' structure, through which researchers will partner with the NIH to accelerate the progress of drug development from early hit discovery through phase 1 clinical trials. In clinical research, the new Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) aims to promote the efficient implementation of scientifically sound, biomarker-informed phase 2 clinical trials that can be initiated by academic or industry investigators.Disorders affecting the nervous system create an enormous burden in lost life, disability, and suffering. In recent decades, neuroscientists—many funded by the NIH—have made huge strides in understanding their causes and developing new ideas for treatment. The molecular and cellular mechanisms underlying many nervous system diseases are emerging, along with potential therapeutic targets. High-throughput screening facilities, such as those created through NIH Molecular Libraries Roadmap initiatives, are allowing scientists to identify small-molecule compounds that could eventually become new drugs (Austin et al, 2004). The development of new disease models offers increasing opportunities to assess the promise of novel candidate therapeutics.Despite the opportunities, there is often no clear path for translating these research discoveries into new treatments for patients (Collins, 2011). Industry is increasingly averse to supporting early stages of therapeutics development, particularly for nervous system disorders, where both cost and failure rates are high relative to other therapeutic areas. Although industry efforts in early development continue to shrink, NIH-funded researchers have been slow to move into the gap. Very few academic labs have the resources to conduct industry-scale optimization of therapeutic leads or the studies required by the FDA to test a new intervention in patients. And for the hundreds of nervous system disorders that have no treatment, developing the capacity to conduct meaningful clinical trials can be nearly as challenging as developing interventions to test. With the inherent difficulties of developing an effective treatment for any disorder, these factors conspire to produce an especially bleak picture for translation of neurotherapeutics.To close the gap between discovery and drugs, the National Institute of Neurological Disorders and Stroke (NINDS) has launched two new programs designed to ‘de-risk'' promising therapeutic candidates to the point where they can attract industry investment for subsequent development and commercialization. Through the NIH Blueprint Neurotherapeutics Network and NeuroNEXT, NINDS offers the research community access to the infrastructure and the expertise necessary to develop and test new drugs. Importantly, these programs are designed to allow neuroscientists to pursue their most exciting ideas for new drugs without having to invest substantial time and resources in retooling and retraining. In addition, these preclinical and clinical networks enable NINDS to take advantage of economies of scale, making the most efficient use of limited research dollars. 相似文献
996.
997.
998.
Coltman R Spain A Tsenkina Y Fowler JH Smith J Scullion G Allerhand M Scott F Kalaria RN Ihara M Daumas S Deary IJ Wood E McCulloch J Horsburgh K 《Neurobiology of aging》2011,32(12):203-2324.12
The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing parallel pathology and behavior in the same mice. 相似文献
999.
Morphological changes in the anterior cingulate cortex are found in subjects with schizophrenia, attention deficit hyperactivity disorder, and obsessive-compulsive disorder. These changes are hypothesized to underlie the impairments these individuals show on tasks that require cognitive control. The anterior cingulate cortex has previously been shown to be active in situations involving high conflict, presentation of salient, distracting stimuli, and error processing, that is, situations that occur when a shift in attention or responding is required. However, there is some uncertainty as to what specific role the anterior cingulate cortex plays in these situations. The current study used converging evidence from two behavioral paradigms to determine the effects of excitotoxic lesions in the anterior cingulate cortex on executive control. The first assay tests reversal learning, attentional set formation and shifting. The second assesses sustained attention with and without distractors. Animals with anterior cingulate cortex lesions were impaired during reinforcement reversals, discriminations that required subjects to disregard previously relevant stimulus attributes and showed a more rapid decline in attentional ability than Sham-Lesioned subjects when maintaining sustained attention for extended periods of time. These results are consistent with the hypothesis that the anterior cingulate cortex is involved in attending to stimulus attributes that currently predict reinforcement in the presence of previously relevant, salient distractors and maintaining sustained attention over prolonged time on task. 相似文献
1000.
Schweighofer N Lee JY Goh HT Choi Y Kim SS Stewart JC Lewthwaite R Winstein CJ 《Journal of neurophysiology》2011,106(5):2632-2641
Although intermixing different motor learning tasks via random schedules enhances long-term retention compared with "blocked" schedules, the mechanism underlying this contextual interference effect has been unclear. Furthermore, previous studies have reported inconclusive results in individuals poststroke. We instructed participants to learn to produce three grip force patterns in either random or blocked schedules and measured the contextual interference effect by long-term forgetting: the change in performance between immediate and 24-h posttests. Nondisabled participants exhibited the contextual interference effect: no forgetting in the random condition but forgetting in the blocked condition. Participants at least 3 mo poststroke exhibited no forgetting in the random condition but marginal forgetting in the blocked condition. However, in participants poststroke, the integrity of visuospatial working memory modulated long-term retention after blocked schedule training: participants with poor visuospatial working memory exhibited little forgetting at 24 h. These counterintuitive results were predicted by a computational model of motor memory that contains a common fast process and multiple slow processes, which are competitively updated by motor errors. In blocked schedules, the fast process quickly improved performance, therefore reducing error-driven update of the slow processes and thus poor long-term retention. In random schedules, interferences in the fast process led to slower change in performance, therefore increasing error-driven update of slow processes and thus good long-term retention. Increased forgetting rates in the fast process, as would be expected in individuals with visuospatial working memory deficits, led to small updates of the fast process during blocked schedules and thus better long-term retention. 相似文献