Citations

AbstractBackground: Accrediting organizations require laboratories to establish analytic performance criteria that ensure their tests provide results of the high quality required for patient care. However, the procedures for instituting performance criteria that are directly linked to the needs of medical practice are not well established, and therefore alternative strategies often are used to create and implement surrogate performance standards.Content: We reviewed 6 approaches for establishing outcome-related analytic performance goals: (a) limits defined by regulations and external assessment programs, (b) limits based on biologic variation, (c) limits based on surveys of clinicians about their needs, (d) limits based on effects on guideline driven medical decisions, (e) limits based on analysis of patterns for ordering follow-up clinical tests, and (f) limits based on formal medical decision models. Performance criteria were tabulated for 12 common chemistry analytes and 4 routine hematology tests.Conclusions: There is no consensus currently about the preferred methods for establishing medically necessary analytic performance limits. The various methods reviewed give considerably different performance limits. The analytic performance limits claimed by a laboratory should correspond to those limits that can be reliably maintained based on validated QC monitoring systems. These limits generally are larger than the observed CVs and bias parameters collected for assay validation. There is a major need for increased communication among laboratorians and clinicians on this topic, especially when the analytic performance limits that can be consistently maintained by a laboratory are inconsistent with the expectations of health care providers.

Chemotaxis signals between hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC) maintain hepatic vascular homeostasis and integrity and also regulate changes in sinusoidal structure in response to liver injury. Our prior studies have demonstrated that the bidirectional chemotactic signaling molecules EphrinB2 and EphB4 are expressed in HSC. The aim of our present study was to explore whether and how the EphrinB2/EphB4 system in HSC could promote SEC recruitment, which is essential for sinusoidal structure and remodeling. Stimulation of human HSC (hHSC) with chimeric agonists (2 μg/ml) of either EphrinB2 or EphB4 (EphrinB2 Fc or EphB4 Fc, respectively) significantly increased VEGF mRNA levels in hHSC as assessed by quantitative PCR, with respective small interfering RNAs for EphrinB2 and EphB4 inhibiting this increase ( P < 0.05, n = 3). EphrinB2 agonist-induced increase in VEGF mRNA levels in hHSC was associated with increased phosphorylation of Erk and was significantly blocked by U0126 (20 μM), an inhibitor of MEK, which is a kinase upstream from Erk ( P < 0.05, n = 3). The EphB4 agonist also significantly increased human VEGF promoter activity ( P < 0.05, n = 3) as assessed by promoter reporter luciferase assay in transfected LX2-HSC. This was associated with upregulation of the vasculoprotective transcription factor, Kruppel-like factor 2 (KLF2). In Boyden chamber assays, conditioned media from hHSC stimulated with agonists of EphrinB2 or EphB4 increased SEC chemotaxis in a VEGF-dependent manner, compared with control groups that included basal media with agonists of EphrinB2, EphB4, or HSC-conditioned media from HSC in absence of agonist stimulation ( P < 0.05, n = 3). EphB4 expression was detected in situ within liver sinusoidal vessels of rats after carbon tetrachloride-induced liver injury. In summary, activation of the EphrinB2/EphB4 signaling pathway in HSC promotes chemotaxis of SEC through a pathway that involves Erk, KLF2, and VEGF. These studies identify EphrinB2 or EphB4 as a key intermediary that links HSC signal transduction pathways with angiogenesis and sinusoidal remodeling.

Potential donors with congenital renal anomalies but normal renal function are often overlooked because of a possible increase in technical difficulty and complications associated with the surgery. However, as the waiting list for a deceased donor kidney transplant continues to grow, it is important to consider these kidneys for potential transplant. This paper describes the procurement of a crossed fused ectopic kidney, and subsequent parenchymal transection prior to transplantation as part of a combined simultaneous kidney pancreas transplant. The transplant was uncomplicated, and the graft had immediate function. The patient is now two years from transplant with excellent function.

The allocation of surgeries to operating rooms (ORs) is a challenging combinatorial optimization problem. There is also significant uncertainty in the duration of surgical procedures, which further complicates assignment decisions. In this paper, we present stochastic optimization models for the assignment of surgeries to ORs on a given day of surgery. The objective includes a fixed cost of opening ORs and a variable cost of overtime relative to a fixed length-of-day. We describe two types of models. The first is a two-stage stochastic linear program with binary decisions in the first stage and simple recourse in the second stage. The second is its robust counterpart, in which the objective is to minimize the maximum cost associated with an uncertainty set for surgery durations. We describe the mathematical models, bounds on the optimal solution, and solution methodologies, including an easy-to-implement heuristic. Numerical experiments based on real data from a large health-care provider are used to contrast the results for the two models and illustrate the potential for impact in practice. Based on our numerical experimentation, we find that a fast and easy-to-implement heuristic works fairly well, on average, across many instances. We also find that the robust method performs approximately as well as the heuristic, is much faster than solving the stochastic recourse model, and has the benefit of limiting the worst-case outcome of the recourse problem.

ABSTRACT The SLOMYCO Sensititre panel and the custom JustOne strip (both from TREK Diagnostic Systems, Cleveland, OH) were evaluated for susceptibility testing of Mycobacterium avium complex isolates against clarithromycin. Seventy-one archived and prospectively collected isolates were tested using both the SLOMYCO panel and the JustOne strip, and the results were compared to those obtained using the BACTEC 460 (BD, Sparks, MD) radiometric method and a broth microdilution reference method. Results obtained by the SLOMYCO panel and the JustOne strip agreed with the BACTEC 460 method for 64/71 isolates (90%). Similarly, concordance with the broth microdilution method was 40/43 isolates (93%) for both test systems. The effect of the source medium on inoculum preparation was evaluated, and there were no differences noted in MICs, regardless of whether the inoculum was prepared from isolates grown in Middlebrook 7H9 medium, on Middlebrook 7H10 agar, or in VersaTREK broth culture bottles (Trek Diagnostics). Clarithromycin susceptibility testing of MAC using the SLOMYCO panel and the JustOne strip methods is easy to set up and simple to read and is readily incorporate into the clinical laboratory. These systems offer advantages over the BACTEC 460 system including the lack of a need for radioactive substrates, sharps, or costly instrumentation.

Objective: This study aimed to determine the effects of active workstation designs on speed and error during typing, mouse pointing, and combined type and mouse-use tasks. Background: Office ergonomics has focused on musculoskeletal disorder prevention; however, increasing computer-based work also increases health risks associated with inactivity. Workstations allowing computer users to walk or cycle while performing computer tasks have been shown to demand sufficient energy expenditure to result in significant health benefits. However the performance effects of being active while using a computer have not been documented. Method: Thirty office workers (16 female, 15 touch typists) performed standardized computer tasks in six workstation conditions: sitting, standing, walking at 1.6 km/h and 3.2 km/h, and cycling at 5 and 30 watts. Performance, perceived performance, and heart rate were measured. Results: Computer task performance was lower when walking and slightly lower when cycling, compared with chair sitting. Standing performance was not different from sitting performance. Mouse performance was more affected than typing performance. Performance decrements were equal for females and males and for touch typists and nontouch typists. Conclusion: Performance decrements maybe related to both biomechanical and cognitive processes. Active workstations may be less suitable for mouse-intensive work and susceptible users. Application: Although active workstations may result in some decrement in performance, their ability to increase daily energy expenditure may make them a feasible solution for workplace inactivity.

Abstract Aims Central sleep apnoea (CSA) and increased serum erythropoietin (EPO) concentration have each been associated with adverse prognosis in heart failure (HF) patients. The aim of this study was to examine the relationship between nocturnal hypoxaemia due to CSA and the serum EPO concentration in patients with HF. Methods and results Heart failure subjects (n = 33) and healthy controls (n = 18) underwent polysomnography (PSG) for diagnosis of CSA and identification and quantification of hypoxaemia. Blood collection for measurement of EPO was performed immediately post-PSG. For the analysis, HF subjects were dichotomized into subgroups defined by the presence or absence of CSA and by HF severity. Multivariate analyses were performed to evaluate the relationships of hypoxaemia and advanced HF to EPO concentration. Mean EPO concentration was 62% higher for HF subjects with CSA than for healthy controls (P = 0.004). The magnitude of nocturnal hypoxaemia was significantly and positively related to EPO concentration (r = 0.45, P = 0.02). Advanced HF was also significantly and positively related to EPO concentration (r = 0.43, P = 0.02). On multivariate analysis, the presence of combined nocturnal hypoxaemia and advanced HF yielded greater correlation to EPO concentration than either factor alone (r = 0.57, P = 0.04 and P = 0.05, respectively). Linear regression demonstrated that the combination of New York Heart Association Class and CSA was strongly associated with EPO concentration (P &lt; 0.0001). Conclusion In non-anaemic HF patients, advanced HF and hypoxaemia due to CSA may each be independently associated with increased serum EPO concentration.

Fronto-temporal lobar degeneration (FTLD) is a form of dementia which may manifest through symptoms similar to Alzheimer’s, including language-specific impairment. Linguistic manifestations of the disorder are often described in subjective assessments of the disorder, but not always easily quantifiable using objective tests. This paper investigates a speech characteristic not yet assessed in FTLD patients, that of “temporal cycles” [Henderson et al. (1966); Butterworth and Goldman-Eisler (1979)]. Temporal cycles in the speech of healthy adults consist of alternating and roughly equal periods of fluent and hesitant speech [Roberts and Kirsner (2000)]. A time series analysis of temporal cycles was conducted using spontaneous speech from 45 adults diagnosed with FTLD. Patients’ cognitive functioning was assessed using the language-specific clinical dementia rating (CDR) scale by board-certified neurologists. Periodicity of temporal cycles was quantified using the proportion of the energy in the highest peak to the total energy in the power spectrum. It was found that this measure was correlated with independent CDR assessments. The results of this study indicate that temporal cycles may be used to characterize the effects of neurodegenerative disorders on speech communication. [Work supported by US NIA Grants Nos. R01-AG023195, P50-AG16574, P30-AG19610, and NIH NIA-1R01AG026390, and Univ. of MN Academic Health Center.]

Rapid calculations of the intensity are required for models of the radiation force generated by linear ultrasound phased arrays. To determine the computation times and numerical errors produced by two medical ultrasound simulation packages, namely, FIELD II and FOCUS, comparisons of the calculated pressures and intensities are performed using a simulated Vermon L5 phased array probe with 128 active elements. In these simulations, the array generates a fixed focus 25 mm from the array for a 5-MHz excitation, and the pressure field is computed on a 133 × 133 × 261 rectilinear grid that is centered at the focus. Half wavelength sampling is employed in all three directions. In FIELD II, this calculation takes approximately 4 h on a 64-bit laptop running Linux, and in FOCUS, the same calculation takes less than 4 min on the same computer. The numerical errors are also much smaller with FOCUS. Details of the simulation approaches employed for this transducer model will be presented, including selection of FIELD II and FOCUS simulation parameters and calculations of the reference pressure field for error evaluations. The impact of numerical errors on shear wave calculations will also be discussed.