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991.
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Assessing impact of organised breast screening across small residential areas—development and internal validation of a prediction model 下载免费PDF全文
G. Farshid MBBS MD FRCPA FFSc G. Gill MBBS MD FRACS J. Kollias FRACS MD B. Koczwara BM BS FRACP MBioethics C. Karapetis MBBS FRACP MMedSc J. Adams MBBS PhD FRACP MRCP R. Joshi MBBS MD FRACP D. Keefe PSM MBBS MD FRACP FRCP T. Niyonsenga MSC PhD K. Powell BABus K. Fusco BHlth Sci DipBiomedSc M. Eckert MPH DNurs MN DipAppSc K. Beckmann PhD MPH BSc D. Roder DDSc MPH BDS 《European journal of cancer care》2017,26(4)
Monitoring screening mammography effects in small areas is often limited by small numbers of deaths and delayed effects. We developed a risk score for breast cancer death to circumvent these limitations. Screening, if effective, would increase post‐diagnostic survivals through lead‐time and related effects, as well as mortality reductions. Linked cancer and BreastScreen data at four hospitals (n = 2,039) were used to investigate whether screened cases had higher recorded survivals in 13 small areas, using breast cancer deaths as the outcome (M1), and a risk of death score derived from TNM stage, grade, histology type, hormone receptor status, and related variables (M2). M1 indicated lower risk of death in screened cases in 12 of the 13 areas, achieving statistical significance (p < .05) in 5. M2 indicated lower risk scores in screened cases in all 13 areas, achieving statistical significance in 12. For cases recently screened at diagnosis (<6 months), statistically significant reductions applied in 8 areas (M1) and all 13 areas (M2). Screening effects are more detectable in small areas using these risk scores than death itself as the outcome variable. An added advantage is the application of risk scores for providing a marker of screening effect soon after diagnosis. 相似文献
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Optimizing the analysis strategy for the CANVAS Program: A prespecified plan for the integrated analyses of the CANVAS and CANVAS‐R trials 下载免费PDF全文
Bruce Neal MB ChB PhD Vlado Perkovic MBBS PhD Kenneth W. Mahaffey MD Greg Fulcher MD Ngozi Erondu MD PhD Mehul Desai MD Wayne Shaw DSL Gordon Law PhD Marc K. Walton MD PhD Norm Rosenthal MD Dick de Zeeuw MD PhD David R. Matthews DPhil BM BCh 《Diabetes, obesity & metabolism》2017,19(7):926-935
Two large cardiovascular outcome trials of canagliflozin, comprising the CANVAS Program, will complete in early 2017: the CANagliflozin cardioVascular Assessment Study (CANVAS) and the CANagliflozin cardioVascular Assessment Study–Renal (CANVAS‐R). Accruing data for the sodium glucose co‐transporter 2 (SGLT2) inhibitor class has identified questions and opportunities that were not apparent when the trials were designed. Accordingly, a series of modifications have been made to the planned analyses. These updates will ensure that the data from the CANVAS Program will maximize advances in scientific knowledge and patient care. The specification of the analysis strategy prior to knowledge of the trial results, their design by the independent scientific trial Steering Committee, the detailed a priori definition of the analysis plans, and the external review provided by the US Food and Drug Administration all provide maximally efficient and robust utilization of the data. The CANVAS Program should significantly advance our understanding of the effects of canagliflozin, and the broader SGLT2 inhibitor class, on a range of important efficacy and safety outcomes. 相似文献
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The effect of activation rate on left atrial bipolar voltage in patients with paroxysmal atrial fibrillation 下载免费PDF全文
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Kinetics of the Immune Response Profile in Guinea Pigs after Vaccination with Mycobacterium bovis BCG and Infection with Mycobacterium tuberculosis 下载免费PDF全文
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Leonardo BM Resstel Rodrigo F Tavares Sabrina FS Lisboa Samia RL Joca Fernando MA Corrêa Francisco S Guimar?es 《British journal of pharmacology》2009,156(1):181-188
Background and purpose
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa which induces anxiolytic- and antipsychotic-like effects in rodents. These effects could be mediated by facilitation of the endocannabinoid system or by the activation of 5-HT1A receptors. As either of these mechanisms could promote adaptation to inescapable stress, the aim of the present work was to test the hypothesis that CBD would attenuate the autonomic and behavioural consequences of restraint stress (RS). We also investigated if the responses to CBD depended on activation of 5-HT1A receptors.Experimental approach
Male Wistar rats received i.p. injections of vehicle or CBD (1, 10 or 20 mg kg−1) and 30 min later were submitted to 60 min of restraint where their cardiovascular responses were recorded. The protocol of the second experiment was similar to the first one except that animals received i.p. injections of the 5-HT1A receptor antagonist WAY100635 (0.1 mg kg−1) before CBD treatment and exposure to restraint. 24 h later they were also tested in the elevated plus-maze (EPM), an animal model of anxiety.Key results
Exposure to RS increased blood pressure and heart rate and induced an anxiogenic response in the EPM 24 h later. These effects were attenuated by CBD. WAY100635 by itself did not change the cardiovascular and anxiogenic response to RS, but blocked the effects of CBD.Conclusion and implications
The results suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT1A receptor-mediated neurotransmission. 相似文献997.
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Kruithof E De Rycke L Vandooren B De Keyser F FitzGerald O McInnes I Tak PP Bresnihan B Veys EM Baeten D;OMERACT Special Interest Group on Synovial Analysis in Clinical Trials 《Arthritis and rheumatism》2006,54(6):1795-1804
OBJECTIVE: To identify biomarkers for effective treatment in early-phase clinical trials of spondylarthritis (SpA), by analyzing which synovial features can be reliably identified in patients with SpA. METHODS: Synovial biopsies were performed at weeks 0 and 12 in 20 SpA patients treated with infliximab, 20 treated with etanercept, and 12 who were not treated. Primary clinical outcome measures were patient and physician global assessment of disease activity. Extensive histologic evaluation included assessment of lining layer hyperplasia, vascularity, markers of cellular infiltration, and metalloproteinases (MMPs) in the lining and sublining layers. RESULTS: Changes in levels of CD163 (resident tissue macrophages) in the lining, and CD163, MMP-3, and myeloid-related protein 14 (MRP-14; infiltrating myeloid cells) in the sublining correlated significantly with changes in the primary clinical outcomes. Comparison between responders (n = 35) and nonresponders (n = 17) showed differences in the degree of change in the levels of CD163 in the lining and CD163, MMP-3, and CD3 in the sublining, whereas trends in change in the levels of MRP-8 and MRP-14 in the lining and sublining were similar in the 2 groups. Accordingly, the highest differences in standardized response means (SRMs) between the 2 groups were found for CD163 in the lining, MMP-3, CD163, CD3, and MRP-8 in the sublining, and the level of polymorphonuclear cells (PMNs). When comparing treated and untreated patients, high differences in SRMs were again found for CD163 in the lining, MMP-3, CD163, and MRP-8 in the sublining, and PMNs. These parameters performed prognostically as well as the erythrocyte sedimentation rate and better than the C-reactive protein level. Class prediction analysis yielded a 90% correct prediction using 8 synovial parameters, as follows: lining and sublining CD163, MRP-8, and MRP-14, sublining MMP-3, and PMNs. In validation analyses with independent samples, effective treatment was correctly predicted in 24 of 30 SpA patients and in 2 of 2 placebo-treated patients. CONCLUSION: Changes in synovial macrophage subsets, PMN levels, and MMP-3 expression reflect response to treatment in SpA. The ability of these parameters to correctly identify effective therapy makes them interesting biomarkers for use in early-phase clinical trials in SpA. 相似文献
1000.
Guy Laureys Ralph Clinckers Sarah Gerlo Anneleen Spooren Nadine Wilczak Ron Kooijman Ilse Smolders Yvette Michotte Jacques De Keyser 《Progress in neurobiology》2010
Evidence accumulates for a key role of the β2-adrenergic receptors in the many homeostatic and neuroprotective functions of astrocytes, including glycogen metabolism, regulation of immune responses, release of neurotrophic factors, and the astrogliosis that occurs in response to neuronal injury. A dysregulation of the astrocytic β2-adrenergic-pathway is suspected to contribute to the physiopathology of a number of prevalent and devastating neurological conditions such as multiple sclerosis, Alzheimer's disease, human immunodeficiency virus encephalitis, stroke and hepatic encephalopathy. In this review we focus on the physiological functions of astrocytic β2-adrenergic receptors, and their possible impact in disease states. 相似文献