用计算机模拟选择丙泊酚的药代动力学参数

目的 用Marsh、Shuttler和Kirkpatrick(以下简称M、S、K参数)报道的药代学参数模拟单次静注丙泊酚血浆浓度以选择适合中国人的参数。方法 90例患者分为青年组、中年组和老年组,测定和模拟静注丙油酚后1～5 min和10 min血浆浓度。计算样本加权残差(WR)和绝对值加权残差(absWR)、个体内中位数加权残差(MDWR)和中位数绝对值加权残差(MDAWR)、预测和实测浓度的目标函数。结果 三种参数预测和实测浓度均显著相关(P<0.05)。老年组M和S参数WR、absWR、MDWR、MDAWR无差异,但与K参数差异显著(P<0.05);中、青年组S参数预测和实测浓度拟合最好。老、中和青年组Marsh参数目标函数分别是-286.9、-332.2和-480.5,S参数分别是-290.6、-334.6和-393.5,K参数分别是-454.7、-350.2和-386.6。结论 M和S药代学参数适用于老年人单次静注丙泊酚浓度预测,中青年选用S参数为好。     

Sensitization to amphetamine,but not PCP,impairs attentional set shifting: reversal by a D<Subscript>1</Subscript> receptor agonist injected into the medial prefrontal cortex

Rationale Repeated exposure to psychomotor stimulants can lead to sensitization to their effects, and sensitization has been implicated in the pathophysiology of schizophrenia and drug abuse. These disorders are characterized by cognitive deficits, particularly in prefrontally mediated executive function.Objective The present experiments were conducted to investigate the effects of sensitizing regimens of amphetamine and phencyclidine (PCP) on attentional set shifting.Methods Rats received injections of amphetamine, PCP or saline three times per week for 5 weeks. Four weeks later, rats were trained to dig for food in one of two bowls, each bowl having an odour and a texture. Only one dimension (odour or texture) correctly predicted which bowl was baited. Rats were then tested on a series of discriminations including those requiring an intra-dimensional shift (IDS), an extra-dimensional shift (EDS) or a reversal of previously relevant and irrelevant stimuli.Results Rats sensitized to amphetamine performed normally on the IDS, but were impaired on the EDS, as well as on reversal discriminations. PCP-sensitized rats were unaffected on any of the discriminations. In amphetamine-sensitized rats the deficit at the EDS stage was reversed by infusion of the D₁ receptor agonist SKF38393 into the medial prefrontal cortex (mPFC).Conclusions Results show that the amphetamine-sensitized state impairs prefrontally mediated attentional set shifting. This is consistent with cognitive deficits in schizophrenia and addiction, and with the evidence that amphetamine sensitization is accompanied by functional changes in the mPFC. These results further add to a growing literature showing that activating D₁ receptors in the mPFC improves aspects of cognition.     

The quality of the quality indicator of pain derived from the minimum data set

OBJECTIVE: To examine facility variation in data quality of the level of pain documented in the minimum data set (MDS) as a function of level of hospice enrollment in nursing homes (NHs). DATA SOURCE: Clinical assessments on 3,469 nonhospice residents from 178 NHs were merged with On-line Survey Certification and Reporting data of 2000, Medicare Claims data of 2000 and the MDS of 2000-2002. STUDY DESIGN: Using the same assessment protocol, NH staff and study nurses independently assessed 3,469 nonhospice residents. Study nurses' assessments being gold standard, we quantified and compared quality of NH staff's pain rating across NHs with high, medium, or low hospice use. Multilevel models were built to assess the effect of NH hospice use levels on the occurrence of false positive (FP) and false negative (FN) errors in NH-rated "severe pain." PRINCIPAL FINDINGS: Of 178 NHs, 25 had medium and 41 high hospice use. NHs with higher hospice use had lower sensitivities. In multilevel analysis, we found a significant facility-level variation in the probability of FP and FN errors in facility-rated "severe pain." Resident characteristics only explained 4 and 0 percent of the facility variation in FP and FN, respectively; characteristics and locations (state) of NHs further explained 53 and 52 percent of the variance. After controlling for resident and NH characteristics, staff in NHs with medium or high hospice use were less likely to have FP or FN errors in their MDS documentation of pain than were staff in NHs with low or no hospice use. CONCLUSIONS: The examination of data quality of pooled MDS data from multiple NHs is insufficient. Multilevel analysis is needed to elucidate sources of heterogeneity in the quality of MDS data across NHs. Facility characteristics, e.g., hospice use or NH location, are systematically associated with overrated/underrated pain and may bias pain quality indicator (QI) comparisons. To ensure the integrity of QI comparison in the NH setting, the government may need to institute regular audits of MDS data quality.     

Performance characteristics of 10 home mechanical ventilators in pressure-support mode: a comparative bench study

OBJECTIVE: Inspiratory pressure (Pi) support delivered by a bilevel device has become the technique of choice for noninvasive home ventilation. Considerable progress has been made in the performance and functionality of these devices. The present bench study was designed to compare the various characteristics of 10 recently developed bilevel Pi devices under different conditions of respiratory mechanics. DESIGN: Bench model study. SETTING: Research laboratory, university hospital. MEASUREMENTS: Ventilators were connected to a lung model, the mechanics of which were set to normal, restrictive, and obstructive, that was driven by an ICU ventilator to mimic patient effort. Pressure support levels of 10 and 15 cm H(2)O, and maximum were tested, with "patient" inspiratory efforts of 5, 10, 15, 20, and 25 cm H(2)O. Tests were conducted in the absence and presence of leaks in the system. Trigger delay, trigger-associated inspiratory workload, pressurization capabilities, and cycling were analyzed. RESULTS: All devices had very short trigger delays and triggering workload. Pressurization capability varied widely among the machines, with some bilevel devices lagging behind when faced with a high inspiratory demand. Cycling was usually not synchronous with patient inspiratory time when the default settings were used, but was considerably improved by modifying cycling settings, when that option was available. CONCLUSIONS: A better knowledge of the technical performance of bilevel devices (ie, pressurization capabilities and cycling profile) may prove to be useful in choosing the machine that is best suited for a patient's respiratory mechanics and inspiratory demand. Clinical algorithms to help set cycling criteria for improving patient-ventilator synchrony and patient comfort should now be developed.     

Advance preparation and stimulus-induced interference in cued task switching: further insights from BOLD fMRI

To switch from one cognitive task to another is thought to rely on additional control effort being indicated by performance costs relative to repeating the same task. This switch cost can be reduced by advance task preparation. In the present experiment the nature of advance preparation was investigated by comparing a situation where an explicit task cue was presented 2000 ms in advance of the target stimulus (CTI-2000) with a situation where cue and target were presented in close succession (CTI-100). We mapped the blood-oxygenation-level-dependent (BOLD) activation correlates of switch-related control effort and advance task preparation to test alternative explanations why advance preparation is reducing switch costs. A previously reported control-related cortical network of frontal and parietal brain areas emerged that was more strongly activated for switching between tasks. However, this was true exclusively for CTI-100 where no advance task preparation was possible. At CTI-2000 these same brain areas were equally engaged in both switch and repeat trials. For some of these areas, this common activation was time-locked to the presentation of both the cue as well as the target. Other areas were exclusively associated with target processing. The overall pattern of results suggests that advance task preparation is a common process of pre-activating (cue-locked activation) the currently relevant task set which does not face interference from a persisting N - 1 task set. During target processing the same brain areas are re-engaged (subsequent target-locked activation) to apply the pre-activated task set. Though being common to repeat and switch trials, advance preparation has a differential benefit for switch trials. This is because the instructed task set has time to settle into a stable state, thus becoming resistant against disruption from the previous task set, which is retrieved by the current target stimulus.     

Validity of the minimum data set in identifying urinary tract infections in residents of long-term care facilities

OBJECTIVES: To determine the validity of the Minimum Data Set (MDS) to detect cases of urinary tract infection (UTI) that meet specific evidence-based criteria. DESIGN: Prospective surveillance. SETTING: Sixteen long-term care facilities (LTCFs) in Idaho. PARTICIPANTS: Residents of participating LTCFs for whom an MDS form was completed. MEASUREMENTS: Prospective surveillance of all types of infection, including UTI, and data collection on clinical manifestation, microbiology, and treatment; MDS data on identification of UTI. RESULTS: A stratified analysis demonstrated that the validity of MDS was 14% when using the evidence-based criteria for UTIs as the criterion standard. The estimated sensitivity and specificity of MDS entries were 57.9% and 86.5%, respectively. The estimated positive and negative predictive values for the study population were 13.9% and 98.2%, respectively. CONCLUSION: MDS has the potential to be an important measure of quality in the long-term care setting. When used to detect residents with UTIs, it appears to greatly overestimate the number of cases while adequately screening out residents without UTIs. These problems may be overcome by providing more-explicit definitions for UTIs to be used by providers when completing MDS information on individual residents.     

Automated classification of short echo time in in vivo 1H brain tumor spectra: a multicenter study.

Automated pattern recognition techniques are needed to help radiologists categorize MRS data of brain tumors according to histological type and grade. A major question is whether a computer program "trained" on spectra from one hospital will be able to classify those from another, particularly if the acquisition protocol is different. A subset of 144 histopathologically validated brain tumor spectra in the INTERPRET database, obtained from three of the collaborating centers, was grouped into meningiomas, low-grade astrocytomas, and "aggressive tumors" (glioblastomas and metastases). Spectra from two centers formed the training set (94 spectra) while the third acted as the test set (50 spectra). Linear discriminant analysis successfully classified 48/50 in the test set; the remaining two were atypical cases. When the training and test sets were combined, 133 of the 144 spectra were correctly classified using the leave-one-out procedure. These spectra had been obtained using different sequences (STEAM and PRESS), different echo times (20, 30, 31, and 32 ms), different repetition times (1600 and 2000 ms), and different manufacturers' instruments (GE and Philips). Pattern recognition algorithms are less sensitive to acquisition parameters than had been expected.     

铜绿假单胞菌大鼠肺部感染模型的建立

目的 评价铜绿假单胞菌接种至大鼠肺部感染模型的建立。方法 Sprague-Dawley大鼠200只分为2组：铜绿假单胞菌感染组与对照组;应用锐孔喷射装置制成铜绿假单胞菌藻酸盐包裹体凝胶小珠,接种至大鼠肺部,接种后3、7、14、28 d观察变化。结果 细菌学：感染组大鼠肺组织匀浆菌落计数在感染后3、7 d均〉10^5CFU/g,在感染后14、28 d均〉10^3CFU/g;病理学：接种后37、d,感染动物肺组织均有脓肿、实变、水肿,镜下可见中性粒细胞聚集在藻酸盐包被体周围形成脓肿,接种后14、28 d,以纤维增生、肉芽肿形成为主要表现。结论 使用锐孔喷射装置制成铜绿假单胞菌藻酸盐包裹体凝胶小珠,接种至大鼠肺部,可成功建立大鼠肺部感染模型。     

留置针联合微调输液器在缩宫素引产中的应用

目的:分析留置针与微调输液器联合运用于缩宫素引产中的应用价值.方法:选取2017年4月~2019年4月本院接收的需要进行宫缩引产的104例产妇作为研究对象,将其按照奇偶顺序平均分为对照组和观察组,对照组产妇52例采用一般输液器进行输液,观察组产妇52例采用留置针与微调输液器联合进行输液,观察两组产妇引产过程中的输液意外情况以及出现规律宫缩的时间.结果:观察组产妇在引产过程中没有出现输液意外情况发生,对照组产妇在引产过程中有3例发生针头脱落、3例发生针头堵塞、8例发生液体外渗,总输液意外情况发生率为26.92%(14/52),两组之间差异具有统计学意义(P<0.05);观察组产妇出现规律宫缩时间为(2.48±0.61)h,明显低于对照组产妇的(3.23±0.64)h,差异具有统计学意义(P<0.05).结论:对于需要进行宫缩素引产的产妇联合应用留置针与微调输液器,有助于防止输液意外情况发生,缩短规律宫缩出现时间,更有助于控制缩宫素的滴数.     

On the utility of gene set methods in genomewide association studies of quantitative traits

In genomewide genetic association studies, prior biological knowledge may help distinguish variation that is truly associated with a quantitative trait from the vast majority of unassociated variation that may be significant in hypothesis testing due to chance. However, formal methods for integrating prior biological knowledge into association studies have only been proposed recently, and their potential utility has not been thoroughly evaluated. Herein, gene set methods from genomewide analysis of gene expression data are adapted for application to genomewide genetic analysis of quantitative traits. The proposed gene set method was tested in simulations with gene sets that included up to 500 total variants, among which up to 20 collectively explained 5% of the variance. In a population of 1,000 individuals, the gene set method was largely more efficient at detecting truly associated variants in these gene sets than a comparably calibrated conventional approach relying on P-values alone. While extremely strong associations remain best identified by conventional methods, the gene set approach may provide a complementary mode of analysis for revealing the full spectrum of genes that influence a quantitative trait.