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Jane Topolovec-Vranic Marlene Santos Andrew J Baker Orla M Smith Karen EA Burns 《Canadian respiratory journal》2014,21(5):293-296
INTRODUCTION:
Alterations from first-party and surrogate decision-maker consent can enhance the feasibility of research involving critically ill patients.OBJECTIVE:
To describe the use of a deferred-consent model to enable participation of critically ill patients in a minimal-risk biomarker study.METHODS:
A prospective observational study was conducted in which serum biomarker samples were collected three times daily over the first 14 days following aneurysmal subarachnoid hemorrhage. Sample collection was initiated on intensive care unit admission and consent was obtained when research personnel could approach the patient or the patient’s surrogate decision maker.RESULTS:
Twenty-seven patients were eligible for the study, of whom only five were capable of providing informed consent. Full consent was obtained for 21 (78%) patients through self- (n=4) and surrogate (n=17) consent. Partial consent or refusal (only permitting the collection of blood samples as a part of routine care or use of data) occurred in three patients. Among the 22 consents sought from surrogates, three (11%) refused participation. The refusals included the sickest patients in the cohort. Once consent was provided, no patient or surrogate withdrew consent before study completion.DISCUSSION:
Use of a deferred consent model enabled participation of critically ill patients in a minimal-risk biomarker study with no withdrawals.CONCLUSIONS:
Further research and enhanced awareness of the potential utility of hybrid models, including deferred consent in addition to patient or surrogate consent, in the conduct of low-risk and minimally interventional time-sensitive studies of critically ill patients are required. 相似文献34.
PJ Hurley L Marchionni BW Simons AE Ross SB Peskoe RM Miller N Erho IA Vergara M Ghadessi Z Huang B Gurel BH Park E Davicioni RB Jenkins EA Platz DM Berman EM Schaeffer 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(37):14977-14982
Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene, Sparcl1, a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence. 相似文献
35.
36.
Purpose
To evaluate the association between statin drug use and peripheral blood leukocyte telomere length in a U.S. nationally representative sample of adults.Methods
We conducted a cross-sectional analysis of data from National Health and Nutrition Examination Survey 1999–2002, representative of the noninstitutionalized U.S. population. The analytic study population included 3496 men and women aged 40–84 years without a history of cancer and who had information of telomere length and statin use.Results
Compared with nonusers, statin users were more likely to be former smokers, older, white, male, and had more comorbidities. Statin users did not have longer telomeres than nonusers after age (coefficient ?0.013, p = .30) and multivariable (0.0003, p = .98) adjustment. After multivariable adjustment, log-transformed telomere length nonstatistically significantly increased with increasing duration of use (0.003, p-trend = .11), which did not differ by number of comorbidities (p-interaction = 0.18). Compared with nonuse, more than 5 years of use had an odds ratio of telomere length above the 75th percentile of 1.62 (95% confidence interval 0.90–2.92; p-trend = .10).Conclusions
Although telomere length appeared to be longer with longer duration of use of a statin, this association was not statistically significant, and we could not rule out bias as the explanation. 相似文献37.
38.
Acute dilatation of the colon with signs of systemic toxicity developed in an elderly man with malignant lymphoma. Although barium contrast X-rays taken previously were interpreted as consistent with granulomatous colitis, rectal biopsy had revealed features characteristic of malignant lymphoma, poorly differentiated lymphocytic type. Bone marrow and lymph nodes were also involved. The onset of dilatation was temporally related to therapy with opiates and anticholinergics, and the acute episode was resolved with nasogastric suction, intravenous fluids, albumin, and antibiotics. 相似文献
39.
Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans 总被引:3,自引:0,他引:3
Granowitz EV; Porat R; Mier JW; Orencole SF; Callahan MV; Cannon JG; Lynch EA; Ye K; Poutsiaka DD; Vannier E 《Blood》1993,82(10):2985-2990
Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra. 相似文献
40.
The balance of tissue-type plasminogen activator (t-PA) production and degradation determines its concentration in blood and tissues. Disturbance of this balance may result in either increased or decreased proteolysis. In the present study, we identified the receptor systems involved in the degradation of t-PA by human monocytes/macrophages in culture. Monocytes were cultured and became macrophages within 2 days. At 4 degrees C, 125I-t-PA bound to macrophages with high (apparent dissociation constant [kd], 1 to 5 nmol/L) and low affinity (kd > 350 nmol/L). At 37 degrees C, the cells internalized and degraded t-PA via the high affinity binding sites, which were partially inhibited by mannan. The low affinity binding sites were 6-aminohexanoic acid- inhibitable and not involved in t-PA degradation. Degradation of t-PA was upregulated during differentiation of monocytes to macrophages. Dexamethasone further upregulated the mannan-inhibitable t-PA degradation. Lipopolysaccharide downregulated both mannan-inhibitable and non-mannan-inhibitable t-PA degradation. Non-mannan-inhibitable degradation was completely blocked by recombinant 39-kD receptor- associated protein (RAP, inhibitor of lipoprotein receptor-related protein [LRP]), whereas mannan-inhibitable degradation was blocked by the addition of a monoclonal antibody against the mannose receptor. No differences between the degradation of t-PA and functionally inactivated t-PA were observed. We conclude that human monocyte-derived macrophages are able to bind, internalize, and degrade t-PA. Degradation of t-PA does not require complex formation with plasminogen activator inhibitors. The macrophages use two independently regulated receptors, namely, the mannose receptor and LRP, for the uptake and degradation of t-PA. 相似文献