Cost–utility analysis of an advanced pressure ulcer management protocol followed by trained wound,ostomy, and continence nurses

The high prevalence of severe pressure ulcers (PUs) is an important issue that requires to be highlighted in Japan. In a previous study, we devised an advanced PU management protocol to enable early detection of and intervention for deep tissue injury and critical colonization. This protocol was effective for preventing more severe PUs. The present study aimed to compare the cost‐effectiveness of the care provided using an advanced PU management protocol, from a medical provider's perspective, implemented by trained wound, ostomy, and continence nurses (WOCNs), with that of conventional care provided by a control group of WOCNs. A Markov model was constructed for a 1‐year time horizon to determine the incremental cost‐effectiveness ratio of advanced PU management compared with conventional care. The number of quality‐adjusted life‐years gained, and the cost in Japanese yen (¥) ($US1 = ¥120; 2015) was used as the outcome. Model inputs for clinical probabilities and related costs were based on our previous clinical trial results. Univariate sensitivity analyses were performed. Furthermore, a Bayesian multivariate probability sensitivity analysis was performed using Monte Carlo simulations with advanced PU management. Two different models were created for initial cohort distribution. For both models, the expected effectiveness for the intervention group using advanced PU management techniques was high, with a low expected cost value. The sensitivity analyses suggested that the results were robust. Intervention by WOCNs using advanced PU management techniques was more effective and cost‐effective than conventional care.     

Target-induced death by apoptosis in human lymphokine-activated natural killer cells

Activated human natural killer (NK) cells undergo rapid apoptotic cell death after ligand binding to the Fc receptor (CD16). We examined whether human NK cells die after engagement in cytolytic functions. Peripheral blood NK cells, with and without prior activation in vitro with interleukin-2 (IL-2), were tested for the occurrence of cell death after incubation with K562, the prototype NK-sensitive target cell. A proportion (15.2%) of NK cells that were stimulated for 3 days with IL- 2 and then incubated for 4 hours with K562 cells showed rapid cell death, but NK cells not stimulated with IL-2 did not. This cell death was found to involve nuclear condensation and fragmentation and DNA cleavage, all of which are characteristic of apoptosis. These data indicate that a proportion of activated human NK cells undergo apoptosis as they engage in target cell lysis. Target-induced NK cell death may represent an important mechanism for regulation of inflammatory processes involving NK cells.     

Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia

Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation.     

Optimal Timing of Implantable Cardioverter‐Defibrillator Implantation After Myocardial Infarction: A Decision Analysis

ICD Implant Timing . Background: The optimal timing of implantable cardioverter defibrillator (ICD) placement for the primary prevention of sudden cardiac death after myocardial infarction (MI) remains unknown. Methods and Results: We developed a Markov model to investigate the optimal timing of ICD implantation after MI (no ICD, ICD at 60 days, 6 months, and 1 year) in patients who meet current guidelines. Estimates of arrhythmic death (baseline risk 6%, range 1–20% per year), nonarrhythmic death, and ICD efficacy were based upon MADIT‐II and other contemporary post‐MI clinical trials. We used both deterministic and stochastic modeling processes in our analysis. After 10 years follow‐up, the baseline probability of survival was higher in those treated with ICD implantation versus not (42% vs 30%, P < 0.001). Survival was highest with ICD implantation at 60 days versus 6 months versus 1 year: 42.4%, 42.3%, and 42.0% (P = 0.0028). ICD implantation at 60 days provided a mean incremental survival of 0.28 months and 0.84 months per patient (compared with implantation at 6 months and 1 year). In sensitivity analyses, patients’ competing risk for nonarrhythmic death was the primary determinant of benefit from ICD implantation. Overall, ICD implantation at 60 days resulted in the greatest life expectancy over a wide range of plausible nonarrhythmic and arrhythmic death rates. Conclusions: The benefits of early ICD implantation are modest when compared with delayed implantation at 6 months/1 year. Our results suggest that making sure a patient receives an ICD, when appropriate, may be more important than the timing of the implantation procedure. (J Cardiovasc Electrophysiol, Vol. pp. 791‐798, July 2010)     

Viscoelastic properties of bovine articular cartilage attached to subchondral bone at high frequencies

Background  

Articular cartilage is a viscoelastic material, but its exact behaviour under the full range of physiological loading frequencies is unknown. The objective of this study was to measure the viscoelastic properties of bovine articular cartilage at loading frequencies of up to 92 Hz.     

PFXYD序列参与phospholemman对L型钙通道的调节作用

目的探讨PFXYD序列在phospholemman（PLM）调节L型钙通道中的作用。方法用丙氨酸（Ala／,A）替换组成PFXYD序列的5个氨基酸,得到突变型PLM—ALL5。用磷酸钙沉淀法将编码L型钙通道的cDNA分别与编码载体质粒（empUvector,EV）、野生型PLM（wildtype,wT）、突变型PLM（ALL5）的cDNA转染到HEK293细胞中,待其表达相应蛋白后,用全细胞膜片钳方法记录L型钙电流（ICa（L））并分析其动力学特性。结果在除极化电位为一20mV和一10mV时,ALL5较wT更加明显地减慢了ICa（L）激活速度,而在相同电位下ALLJ5使ICa（L）失活速度也明显减慢;与WT相反,ALL5没有减慢ICa（L）灭活速度,反使其加快了;以上ALL5所致的ICa（L）改变与电流大小无关。结论PFXYD序列理化性质的改变可以引起PLM对L型钙通道调节作用的改变,提示PFXYD序列在PLM调节L型钙通道的过程中发挥重要作用。     

When "no" might not quite mean "no"; the importance of informed and meaningful non-consent: results from a survey of individuals refusing participation in a health-related research project

Background  

Low participation rates can lead to sampling bias, delays in completion and increased costs. Strategies to improve participation rates should address reasons for non-participation. However, most empirical research has focused on participants' motives rather than the reasons why non-participants refuse to take part. In this study we investigated the reasons why older people choose not to participate in a research project.     

EFFECTS OF ALPROSTADIL AND PRAZOSIN ON MOTILITY, VIABILITY AND MEMBRANE INTEGRITY OF HUMAN SPERM

Purpose

We evaluated the effects of alprostadil, prazosin hydrochloride, and alprostadil/prazosin hydrochloride, agents used in the clinical treatment of male erectile dysfunction, on the motility, viability and membrane integrity of human sperm.

Materials and Methods

Ten healthy volunteers provided semen samples that were incubated with 0.4 mg./ml. alprostadil, 0.1 and 0.2 mg./ml. prazosin hydrochloride and 0.4 mg./ml. alprostadil plus 0.1 mg./ml. prazosin hydrochloride for 2 hours. Control incubations included polyethylene glycol 1450, the formulation vehicle for the clinical use of alprostadil and prazosin, and Ham's F-10 buffer. Serial evaluations of percent sperm motility, percent viability, membrane function (by hypo-osmotic swelling test) and several computer generated measurements of sperm motion, including straight line velocity, curvilinear velocity, linearity and amplitude of lateral head displacement, were made.

Results

None of the agents had a significant impact on the percentage of motile or viable sperm or on sperm membrane function. Incubation with 0.2 mg./ml. prazosin reduced straight line velocity and curvilinear velocity significantly compared with the other agents. These changes were most likely a direct result of the viscosity of the 0.2 mg./ml. prazosin solution and not a cellular or metabolic effect on the sperm.

Conclusions

Alprostadil and prazosin hydrochloride at doses used in transurethral therapy for erectile dysfunction have no effect on the motility, viability and membrane integrity of human sperm.     

Reactions and Crossreactions of a Rabbit Anti-H2 Antigen Serum

A rabbit antiserum raised against highly purified, papain-solubilized H-2d antigens contained two sets of non-crossreacting antibodies directed against each one of the two H-2 antigen subunits. The antiserum recognized only 12,000 and 47,000 dalton polypeptide chains when splenocyte membrane glycoproteins were analysed. Among the molecules precipitated with the rabbit antiserum all H-2K and D antigens were present. In addition to regular H-2K and D antigens minor amounts of material with the typical H-2 antigen subnit structure, but lacking alloantigenic determinants, were precipitated by the antiserum. These 'non-H-2 antigens' were produced in relatively greater amounts by T-cells than by B-cells. Both sets of antibodies in the rabbit antiserum reacted with the TL antigens demonstrating that there is an immunological crossreactivity between the classical alloantigenic H-2 antigen chain and the alloantigenic TL antigen chain. The F9 cell line, believed to represent cells at the morula stage, display H-2 antigen-like structures as revealed by the rabbit antiserum.