Sampling Patients Within and Across Health Care Providers: Multi-Stage Non-Nested Samples in Health Services Research

In order to better inform study design decisions when sampling patients within and across health care providers we develop a simulation-based approach for designing complex multi-stage samples. The approach explores the tradeoff between competing design goals such as precision of estimates, coverage of the target population and cost.We elicit a number of sensible candidate designs, evaluate these designs with respect to multiple sampling goals, investigate their tradeoffs, and identify the design that is the best compromise among all goals. This approach recognizes that, in the practice of sampling, precision of the estimates is not the only important goal, and that there are tradeoffs with coverage and cost that should be explicitly considered. One can easily add other goals. We construct a sample frame with all phase III clinical cancer treatment trials that are conducted by cooperative oncology groups of the National Cancer Institute from October 1, 1998 through December 31, 1999. Simulation results for our study suggest sampling a different number of trials and institutions than initially considered.Simulations of different study designs can uncover efficiency gains both in terms of improved precision of the estimates and in terms of improved coverage of the target population. Simulations enable us to explore the tradeoffs between competing sampling goals and to quantify these efficiency gains. This is true even for complex designs where the stages are not strictly nested in one another.     

Grasp synthesis for upper-extremity FNS

Functional neuromuscular stimulation (FNS) has been used in upper extremity neuroprostheses to provide grasp and release for quadriplegic individuals. The goal of this project was to determine the electrode/muscle input/output characteristics with the greatest influence on the grasp output. This was evaluated by simulating the grasp synthesis procedure, using a model of the electrode/muscle output as a function of stimulus level and joint angle. The parameters of this model were determined from experimental data from 112 electrodes. The grasp output for 500 different modelled pairs of electrodes were analysed, with each pair consisting of a thumb flexor and a thumb extensor. The simulation results indicate that the most influential electrode input/output characteristics are the output stiffness, defined as the change in force output for a unit change in joint angle at a constant level of stimulation, and the length dependency mean-squared error. Recruitment gain was found to be of secondary influence on the grasp output, and the threshold, force direction and non-linearity of the stimulus level to force relationship were found to have little influence on the grasp output. These results establish criteria for electrode selection and implantation for use in upper extremity FNS.     

The membrane attack complex of complement induces interleukin-8 and monocyte chemoattractant protein-1 secretion from human umbilical vein endothelial cells.

Cell surface assembly of the membrane attack complex (MAC) of complement occurs in a variety of pathophysiological settings. Depending upon the density and size distribution of pores formed by the MAC and the functional integrity of membrane regulators of complement activation, the MAC can either cause direct cell lysis or transduce cell activation. We have examined the functional capacity of sublytic concentrations of MAC to induce the secretion of specific alpha- and beta-chemokines from human umbilical vein endothelial cells (HUVECs). Endothelial cell activation by the MAC has particular relevance to complement-dependent inflammatory processes including ischemia-reperfusion injury and acute lung injury. Assembly of sublytic concentrations of the MAC on HUVECs resulted in the sequential secretion of both neutrophil and monocyte chemotactic activities. Analysis of conditioned medium from MAC-bearing HUVECs revealed that the neutrophil chemotactic activity was largely attributable to interleukin (IL)-8, whereas the monocyte chemotactic activity, which was detected later (peak at 8 hours versus 4 hours), was largely attributable to MCP-1. This temporal pattern of MAC-induced secretion of IL-8 and MCP-1 was confirmed using IL-8- and MCP-1-specific enzyme-linked immunosorbent assays. Northern hybridization analysis of HUVECs revealed that MAC deposition was accompanied by an increase in IL-8 and MCP-1 mRNA levels. These data indicate that assembly of sublytic concentrations of the MAC on HUVECs can induce the sequential secretion of both neutrophil and monocyte chemotactic activities and that the former is largely attributable to IL-8 whereas the latter is largely attributable to MCP-1.     

Situational factors associated with AIDS risk behavior lapses and coping strategies used by gay men who successfully avoid lapses

While most gay men have reduced behavior practices at high risk for HIV infection, there is growing evidence that many also lapse to unsafe sex. This study examined situational factors related to risk behavior lapses as well as coping strategies used by men who successfully resist lapse urges. A convenience sample of 470 men patronizing gay bars or attending social organization meetings in four cities was surveyed. Forty-five percent of men were classified as "lapsers" (those who had had unprotected anal intercourse in the previous 6 months) and 24% were classified as "resisters" (those who successfully resisted urges to engage in this behavior). All provided information concerning the importance of factors related to the most recent occurrence of either unsafe sex or resisting unsafe urges. Most episodes of unsafe sex occurred outside monogamous relationships and with partners of unknown HIV serostatus, although simply inquiring about partner serostatus was relatively common. Lapsers rated affectionate feelings and wishing to please a partner as well as spontaneity of unsafe sex as the most important situational factors surrounding high-risk behavior. Resisters of unsafe sex urges reported active cognitive self-guidance, experience in safe sex, and recall of both AIDS fears and safety benefits as their most important coping strategies. Gay men who continue high-risk behavior may be overrelying on partner reports of negative serostatus. Lapse prevention approaches tailored to situations that create increased risk vulnerability must be developed. Teaching skills already used by men who successfully resist unsafe sex urges might be one approach.     

Participation of patients 65 years of age or older in cancer clinical trials.

PURPOSE: Although 61% of new cases of cancer occur among the elderly, recent studies indicate that the elderly comprise only 25% of participants in cancer clinical trials. Further investigation into the reasons for low elderly participation is warranted. Our objective was to evaluate the participation of the elderly in clinical trials sponsored by the National Cancer Institute (NCI) and assess the impact of protocol exclusion criteria on elderly participation. PATIENTS AND METHODS: We conducted a retrospective analysis using NCI data, analyzing patient and trial characteristics for 59,300 patients enrolled onto 495 NCI-sponsored, cooperative group trials, active from 1997 through 2000. Our main outcome measure was the proportion of elderly patients enrolled onto cancer clinical trials compared with the proportion of incident cancer patients who are elderly. RESULTS: Overall, 32% of participants in phase II and III clinical trials were elderly, compared with 61% of patients with incident cancers in the United States who are elderly. The degree of underrepresentation was more pronounced in trials for early-stage cancers than in trials for late-stage cancers (P <.001). Furthermore, protocol exclusion criteria on the basis of organ-system abnormalities and functional status limitations were associated with lower elderly participation. We estimate that if protocol exclusions were relaxed, elderly participation in cancer trials would be 60%. CONCLUSION: The elderly are underrepresented in cancer clinical trials relative to their disease burden. Older patients are more likely to have medical histories that make them ineligible for clinical trials because of protocol exclusions. Insurance coverage for clinical trials is one step toward improvement of elderly access to clinical trials. Without a change in study design or requirements, this step may not be sufficient.     

不同地区婴幼儿轮状病毒感染性腹泻的流行病学研究

目的 分析比较不同地区婴幼儿轮状病毒(RV)感染性腹泻的流行病学特征。方法 于2001年9月至2003年9月在江苏省苏州市和安徽省马鞍山市各选择一所医院建立临床监测哨点,以临床就诊的<5岁腹泻患儿为研究对象,用酶联免疫吸附试验检测RV抗原,同时采用逆转录聚合酶链反应对RV毒株进行血清型与基因型的鉴定。结果 (1)两地区RV感染均呈现明显的秋冬季节性,但季节高峰有所不同,高峰季节的感染率可达50％～80％;(2)两地区腹泻患儿RV感染率差异具有统计学意义,住院腹泻患儿的平均感染率分别为47.28％和30.38％,门诊腹泻患儿平均感染率分别为28.39％和14.77％;(3)两地区RV的感染率均表现出年龄分布的不同,以6～35月龄组较高,无性别差异;(4)苏州市的两个流行高峰均以G3型为主,其次是G1型;马鞍山市第一个流行高峰以G1型为主,第二个高峰则以G3型为主;两地区流行株的G/P组合型与国内外有所不同。结论 婴幼儿RV腹泻在地区、时间以及病毒流行株分布等方面各有不同,提示RV感染的监测工作对其疫苗的研制和应用具有重要的指导作用。     

Cefotetan versus cefoxitin as prophylaxis in hysterectomy

Seventy hospitalized women were entered into an open, randomized, parallel study of antimicrobial prophylaxis for abdominal and vaginal hysterectomy with the use of either cefotetan, a new long-acting cephalosporin, or cefoxitin. Ninety-four percent of cefotetan recipients and 83% of cefoxitin recipients did not develop clinical signs or symptoms of infection. The satisfactory bacteriologic response rates were significantly different: 91% satisfactory (43 of 47 patients) for cefotetan and 74% satisfactory (17 of 23 patients) for cefoxitin. The two treatment groups demonstrated no significant differences in postoperative temperature changes, duration of hospitalization, or grading of surgical wounds. Neither drug was associated with significant side effects.