Stage 1 acute kidney injury is independently associated with infection following cardiac surgery

ObjectivesSevere acute kidney injury (AKI) is a known risk factor for infection and mortality. However, whether stage 1 AKI is a risk factor for infection has not been evaluated in adults. We hypothesized that stage 1 AKI following cardiac surgery would independently associate with infection and mortality.MethodsIn this retrospective propensity score–matched study, we evaluated 1620 adult patients who underwent nonemergent cardiac surgery at the University of Colorado Hospital from 2011 to 2017. Patients who developed stage 1 AKI by Kidney Disease Improving Global Outcomes creatinine criteria within 72 hours of surgery were matched to patients who did not develop AKI. The primary outcome was an infection, defined as a new surgical-site infection, positive blood or urine culture, or development of pneumonia. Secondary outcomes included in-hospital mortality, stroke, and intensive care unit (ICU) and hospital length of stay (LOS).ResultsStage 1 AKI occurred in 293 patients (18.3%). Infection occurred in 20.9% of patients with stage 1 AKI compared with 8.1% in the no-AKI group (P < .001). In propensity-score matched analysis, stage 1 AKI independently associated with increased infection (odds ratio [OR]; 2.24, 95% confidence interval [CI], 1.37-3.17), ICU LOS (OR, 2.38; 95% CI, 1.71–3.31), and hospital LOS (OR, 1.30; 95% CI, 1.17-1.45).ConclusionsStage 1 AKI is independently associated with postoperative infection, ICU LOS, and hospital LOS. Treatment strategies focused on prevention, early recognition, and optimal medical management of AKI may decrease significant postoperative morbidity.     

重视医学信用伦理的研究与开发

医疗行业市场化是必然趋势。在医疗行业市场化进程中，医学伦理道德除了道德价值之外，还含有积极的经济内涵。医学伦理道德也是重要的医疗资源，通过参与医疗市场资源的配制和运作，也可以产生经济效益，转化为医疗资本。医疗行业要重视医学伦理道德资源的开发。信用伦理是在市场经济条件下形成的，这是医学伦理学所面临的新课题。笔者认为，不说谎、不期诈，兑现承诺，保证医疗质量，发扬医学人道主义，是医学信用伦理的四项基本标准。     

Facilitation of discrimination transfers under amphetamine: the relative control by S+ and S− and general transfer effects

Rats were trained in a Y-maze on a two-choice simultaneous black-white discrimination with either black or white as S⁺. Animals were then transferred to one of three discrimination tasks. In task 1 (New S^–), a new stimulus, either vertical or horizontal stripes, was substituted for the original S^–. In task 2 (New S⁺), a new stimulus, either vertical or horizontal stripes as in task 1, was substituted for the original S⁺. In task 3 (New S⁺/S^–) animals were trained on horizontal-vertical discrimination. The pre-trial administration of 1 mg/kg d-amphetamine facilitated the acquisition of the original black-white discrimination with both black as S⁺ and white as S⁺. Likewise, the drug improved performance in all three transfer conditions. However, the course of learning in the three transfer tasks was different in the placebo- and amphetamine-treated animals. Amphetamine-treated animals were disrupted more by a change in S⁺ than by a change in S^–, whereas the opposite pattern was evident in the placebo controls. When both discriminative stimuli were changed, placebo animals exhibited pronounced decrement in performance, whereas amphetamine animals exhibited excellent learning. The implications of these findings for the effects of amphetamine on discrimination learning are discussed.     

Simultaneous non-parametric confidence intervals for survival probabilities from censored data

In medical studies with censored data Kaplan and Meier's product limit estimator has frequent use as the estimate of the survival function. Simultaneous confidence intervals for the survival function at various time points constitute a useful addition to the analysis. This study compares several such methods. We consider in a simulation investigation two whole curve confidence bands and four methods based on the Bonferroni inequality. The results show that three Bonferroni-type methods are essentially equivalent, all being better than the other methods when the number of time points is small (3 or 5).     

Simultaneous versus sequential optimal design for pharmacokinetic-pharmacodynamic models with FO and FOCE considerations

We consider nested multiple response models which are used extensively in the area of pharmacometrics. Given the conditional nature of such models, differences in predicted responses are a consequence of different assumptions about how the models interact. As such, sequential versus simultaneous and First Order (FO) versus First Order Conditional Estimation (FOCE) techniques have been explored in the literature where it was found that the sequential and FO approaches can produce biased results. It is therefore of interest to determine any design consequences between the various methods and approximations. As optimal design for nonlinear mixed effects models is dependent upon initial parameter estimates and an approximation to the expected Fisher information matrix, it is necessary to incorporate any influence of nonlinearity (or parameter-effects curvature) into our exploration. Hence, sequential versus simultaneous design with FO and FOCE considerations are compared under low, typical and high degrees of nonlinearity. Additionally, predicted standard errors of parameters are also compared to empirical estimates formed via a simulation/estimation study in NONMEM. Initially, design theory for nested multiple response models is developed and approaches mentioned above are investigated by considering a pharmacokinetic–pharmacodynamic model found in the literature. We consider design for situations where all responses are continuous and extend this methodology to the case where a response may be a discrete random variable. In particular, for a binary response pharmacodynamic model, it is conjectured that such responses will offer little information about all parameters and hence a sequential optimization, in the form of product design optimality, may yield near optimal designs.     

Video-EEG Analysis of Drop Seizures in Myoclonic Astatic Epilepsy of Early Childhood (Doose Syndrome)

We studied 36 drop seizures in 5 patients with myoclonic astatic epilepsy of early childhood (MAEE) with simultaneous split-screen video recording and polygraph. Sixteen were falling attacks and 20 were either less severe attacks exhibiting only deep head nodding or seizures equivalent to drop attacks in terms of ictal pattern but recorded in the supine position. All seizures except those that occurred in patients in the supine position showed sudden momentary head dropping or collapse of the whole body downward. Recovery to the preictal position was observed in 0.3-1 s. As a result of carefully repeated observations, the 36 seizures were classified as myoclonic flexor type in 9, myoclonic atonic type in 2, and atonic type, with and without transient preceding symptoms in the remaining 25. The MF seizure was characterized by sudden forward flexion of the head and trunk as well as both arms, which caused the patient to fall. In the myoclonic atonic seizure, patients showed brief myoclonic flexor spasms, immediately followed by atonic falling. The AT seizure showed abrupt atonic falling, with and without transient preceding facial expression change and/or twitching of extremities. The ictal EEGs of all 36 seizures exhibited generalized bilaterally synchronous single or multiple spike(s) and wave discharges. Atonic drop attacks appear to be a common cause of ictal epileptic falling in MAEE.     

Evaluation of hypothesis testing for comparing two populations using NONMEM analysis

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i)the ratio of mean clearance and (ii)the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.Partial support from the Upjohn Company, NIH-BRSG SO RR 07066, and the Burroughs Wellcome Foundation.     

A simple model describes large individual differences in simultaneous colour contrast

We report experimental evidence for substantial individual differences in the susceptibility to simultaneous colour contrast. Interestingly, we found that not only the general amount of colour induction varies across observers, but also the general shape of the curves describing asymmetric matching data. A simple model based on von Kries adaptation and crispening describes the data rather well when we regard its free parameters as observer specific. We argue that the von Kries component reflects the action of a temporal adaptation mechanism, while the crispening component describes the action of the instantaneous, purely spatial mechanism most appropriately labeled simultaneous colour contrast. An interesting consequence of this view is that traditional ideas about the general characteristics of simultaneous contrast must be considered as misleading. According to Kirschmann’s 4th law, for instance, the simultaneous contrast effect should increase with increasing saturation of the surround, but crispening predicts the converse. Based on this reasoning, we offer a plausible explanation for the mixed evidence on the validity of Kirschmann’s 4th law. We also argue that simultaneous contrast, the crispening effect, Meyer’s effect and the gamut expansion effect are just different names for the same basic phenomenon.