Emergency department provider in triage: assessing site-specific rationale, operational feasibility, and financial impact.

Emergency department (ED) crowding is recognized as a critical threat to patient safety, while sub-optimal ED patient flow also contributes to reduced patient satisfaction and efficiency of care. Provider in triage (PIT) programs-which typically involve, at a minimum, a physician or advanced practice provider conducting an initial screening exam and potentially initiating treatment and diagnostic testing at the time of triage-are frequently endorsed as a mechanism to reduce ED length of stay (LOS) and therefore mitigate crowding, improve patient satisfaction, and improve ED operational and financial performance. However, the peer-reviewed evidence regarding the impact of PIT programs on measures including ED LOS, wait times, and costs (as variously defined) is mixed. Mechanistically, PIT programs exert their effects by initiating diagnostic work-ups earlier and, sometimes, by equipping triage providers to directly disposition patients. However, depending on local contextual factors-including the co-existence of other front-end interventions and delays in ED throughput not addressed by PIT-we demonstrate how these features may or may not ultimately translate into reduced ED LOS in different settings. Consequently, site-specific analysis of the root causes of excessive ED LOS, along with mechanistic assessment of potential countermeasures, is essential for appropriate deployment and successful design of PIT programs at individual EDs. Additional motivations for implementing PIT programs may include their potential to enhance patient safety, patient satisfaction, and team dynamics. In this conceptual article, we address a gap in the literature by demonstrating the mechanisms underlying PIT program results and providing a framework for ED decision-makers to assess the local rationale for, operational feasibility of, and financial impact of PIT programs.

Research Impact Core: A Research Impact Initiative at the University of Michigan.

Informationists at the Taubman Health Sciences Library, University of Michigan, formed a research impact consultation and education initiative in early 2017 to increase engagement with the health sciences community around the informed, responsible use of a range of citation and alternative metrics and associated tools. So far, the Research Impact Core has primarily entailed developing training content and cultivating partnerships related to publication metrics and associated best practices. This article reports on progress from the first two years of the Research Impact Core, including a snapshot of information session registrants, and a broader discussion of collaborative partnerships around research impact in the health sciences and library system.

Hopeahainol A binds reversibly at the acetylcholinesterase (AChE) peripheral site and inhibits enzyme activity with a novel higher order concentration dependence.

Natural product inhibitors of AChE are of interest both because they offer promise as inexpensive drugs for symptomatic relief in Alzheimer's disease and because they may provide insights into the structural features of the AChE catalytic site. Hopeahainol A is an uncharged polyphenol AChE inhibitor from the stem bark of Hopea hainanensis with a constrained, partially dearomatized bicyclic core. Molecular modeling indicates that hopeahainol A binds at the entrance of the long but narrow AChE active site gorge because it is too bulky to be accommodated within the gorge without severe distortion of the gorge as depicted in AChE crystal structures. We conducted inhibitor competition experiments in which AChE inhibition was measured with hopeahainol A together with either edrophonium (which binds at the base of the gorge) or thioflavin T (which binds to the peripheral or P-site near the gorge mouth). The results agreed with the molecular modeling and indicated that hopeahainol A at lower concentrations (<200 µM) bound only to the P-site, as hopeahainol A and thioflavin T were unable to form a ternary complex with AChE while hopeahainol A and edrophonium did form a ternary complex with essentially no competition between them. Inhibition increased to a striking extent at higher concentrations of hopeahainol A, with plots analogous to classic Dixon plots showing a dependence on hopeahainol A concentrations to the third- or fourth order. The inhibition at higher hopeahainol A concentrations was completely reversed on dilution and blocked by bound edrophonium. We hypothesize that bound hopeahainol A induces conformational changes in the AChE active site that allow binding of additional hopeahainol A molecules, a phenomenon that would be unprecedented for a reversible inhibitor that apparently forms no covalent bonds with AChE.

Examining care navigation: librarian participation in a team-based approach?

OBJECTIVE: This study investigated responsibilities, skill sets, degrees, and certifications required of health care navigators in order to identify areas of potential overlap with health sciences librarianship. METHOD: The authors conducted a content analysis of health care navigator position announcements and developed and assigned forty-eight category terms to represent the sample's responsibilities and skill sets. RESULTS: Coordination of patient care and a bachelor's degree were the most common responsibility and degree requirements, respectively. Results also suggest that managing and providing health information resources is an area of overlap between health care navigators and health sciences librarians, and that librarians are well suited to serve on navigation teams. CONCLUSION: Such overlap may provide an avenue for collaboration between navigators and health sciences librarians.

Antiparallel ß-Sheet Structure within the C-Terminal Region of 42-Residue Alzheimer's Amyloid-ß Peptides When They Form 150-kDa Oligomers.

Understanding the molecular structures of amyloid-ß (Aß) oligomers and underlying assembly pathways will advance our understanding of Alzheimer's disease (AD) at the molecular level. This understanding could contribute to disease prevention, diagnosis, and treatment strategies, as oligomers play a central role in AD pathology. We have recently presented a procedure for production of 150-kDa oligomeric samples of Aß(1-42) (the 42-residue variant of the Aß peptide) that are compatible with solid-state nuclear magnetic resonance (NMR) analysis, and we have shown that these oligomers and amyloid fibrils differ in intermolecular arrangement of ß-strands. Here we report new solid-state NMR constraints that indicate antiparallel intermolecular alignment of ß-strands within the oligomers. Specifically, 150-kDa Aß(1-42) oligomers with uniform (13)C and (15)N isotopic labels at I32, M35, G37, and V40 exhibit ß-strand secondary chemical shifts in 2-dimensional (2D) finite-pulse radiofrequency-driven recoupling NMR spectra, spatial proximities between I32 and V40 as well as between M35 and G37 in 2D dipolar-assisted rotational resonance spectra, and close proximity between M35 H(α) and G37 H(α) in 2D CHHC spectra. Furthermore, 2D dipolar-assisted rotational resonance analysis of an oligomer sample prepared with 30% labeled peptide indicates that the I32-V40 and M35-G37 contacts are between residues on different molecules. We employ molecular modeling to compare the newly derived experimental constraints with previously proposed geometries for arrangement of Aß molecules into oligomers.

A mass spectrometric approach for characterization of amyloid-ß aggregates and identification of their post-translational modifications.

Endogenous amyloid-ß (Aß) oligomeric aggregates have been proposed as toxic agents in Alzheimer's disease (AD). Knowledge of their structures not only may provide insight into the basis of their neurotoxicities but also may reveal new targets for therapeutic drugs and diagnostic tools. However, the low levels of these Aß oligomers have impeded structural characterization. Evidence suggests that the endogenous oligomers are covalently modified in vivo. In this report, we demonstrate an established mass spectrometry (MS) methodology called precursor ion mapping (PIM) that potentially may be applied to endogenous oligomer characterization. First, we illustrate the use of this PIM technique with a synthetic Aß(1-40) monomer sample that had been cross-linked with transglutaminase (TGase) and digested with pepsin. From PIM analysis of an Aß(4-13) MS/MS fragment, precursor ions were identified that corresponded to peptic fragments of three TGase cross-linked species: Aß(4-19)--(4-19), Aß(4-19)--(20-34), and Aß(1-19)--(20-34). Next, we demonstrate the applicability of the PIM technique to an endogenous Aß sample that had been purified and concentrated by immunoaffinity chromatography. Without pepsin digestion, we successfully identified the full length and C-terminally truncated monomeric Aß species 1-35 to 1-42, along with select methionine-oxidized counterparts. Because PIM focuses only on a subpopulation of ions, namely the related precursor ions, the resulting spectra are of increased specificity and sensitivity. Therefore, this methodology shows great promise for structural analysis and identification of post-translational modification(s) in endogenous Aß oligomers.

A comparison of variability in Papanicolaou and liquid-based cytology inadequacy rates using Shewhart control charts.

OBJECTIVE: To use Shewhart control charts to compare variability in inadequacy rates from Papanicolaou (Pap) and liquid-based cytology (LBC). DESIGN: Retrospective analysis of quality assurance data. SETTING: Eleven Welsh cytology laboratories. METHODS: Shewhart 'p' charts were plotted for proportions of slides reported as inadequate. Charts were compared for statistical control. MAIN OUTCOME MEASURES: Evidence of statistical control in the processes. RESULTS: Control charts allowed easy interpretation of patterns in the data. Variability in inadequacy rates was much lower for LBC than for Pap cytology. CONCLUSION: Monitoring inadequate rates with Shewhart charts provides more information than tabular monitoring reports, assisting in quality improvement. With respect to inadequacy rates, LBC is less variable than Pap cytology.

Delta-NT or NT MoM: which is the most appropriate method for calculating accurate patient-specific risks for trisomy 21 in the first trimester?

OBJECTIVE: To assess whether in screening for trisomy 21 by nuchal translucency (NT) the delta or the multiples of the median (MoM) approach is the most appropriate method for calculating accurate individual patient-specific risks. METHODS: Data on fetal NT and crown-rump length from 128,030 unaffected and 428 trisomy 21 pregnancies, measured by sonographers who had obtained The Fetal Medicine Foundation Certificate of Competence in the 11-14-Week Scan, were used. We examined first, if the distribution of NT MoM and log(10)(NT MoM) was Gaussian; second, if the standard deviation of the distributions did not change with gestation; and third, if the median MoM in the affected population was a constant proportion of the median for unaffected pregnancies. All of these features are required to underpin the MoM approach. NT distributions and those of delta-NT were also analyzed. A non-parametric kernel density method was then used to assess the validity of both methods. Errors in the estimation of individual patient-specific risks using the MoM approach were assessed. RESULTS: In the unaffected pregnancies, the distributions of NT MoM and log(10)(NT MoM) were not Gaussian and the standard deviation of log(10)(NT MoM) decreased with gestation. In the trisomy 21 pregnancies, the median NT MoM decreased significantly with gestation, whereas the median delta-NT did not change with gestation. The non-parametric density approach showed that contours of constant likelihood ratio were parallel to the gestational age-dependent median NT values, thus supporting the delta-NT approach. The NT MoM approach resulted in women being given an overestimate of risk for trisomy at 11 weeks and a considerable underestimate of risk at 13 weeks. CONCLUSION: In the calculation of risk for trisomy 21 by NT the NT MoM approach is inaccurate and inappropriate because the underlying assumptions are not valid. In contrast, the delta-NT approach gives accurate estimates of risks.

The effect of temporal variation in biochemical markers of trisomy 21 across the first and second trimesters of pregnancy on the estimation of individual patient-specific risks and detection rates for Down's syndrome.

BACKGROUND: In a previous study we examined the changes in the median multiple of the median (MoM) with gestation of free beta human chorionic gonadotrophin (F beta-hCG), total human chorionic gonadotrophin (ThCG), alpha-fetoprotein (AFP) and pregnancy-associated plasma protein A (PAPP-A) in a large series of Down's syndrome pregnancies. Results showed that there was a significant temporal variation of the MoM for each marker. In this paper, we assess the impact of this temporal shift on the estimation of patient-specific risks and the detection rates (DRs) for Down's syndrome pregnancies. METHODS: Individual patient-specific risks, DRs and false positive rates were estimated using statistical modelling techniques and computer simulations. The data for these simulations were the regressed mean log(10) analyte MoMs, marker standard deviations (as log(10) MoM) and correlation coefficients derived from the analysis of over 1000 cases of Down's syndrome and 150,000 unaffected pregnancies between 6 and 20 weeks of gestation reported in our previous study. Two models were compared: the classical constant median separation model, which assumes no variation in median shift with gestation (model 1), and a variable median separation model (model 2), which takes account of the changes in median shift with gestation as described in our previous study. RESULTS: When individual patient-specific risks calculated for various MoM values using model 1 were compared with those derived from model 2, considerable differences in risk estimates were observed for all marker combinations, particularly in the first trimester. Using a 1 in 250 cut-off risk, DRs at each gestation in the second trimester for the AFP+F beta-hCG combination were maximized at 14-17 weeks of gestation and were virtually identical at 63-65% for model 1 and model 2. A similar trend was observed for the AFP+ThCG combination, with an optimum gestational range of 15-18 weeks and DRs of 66-68%. In the first trimester, using a 1 in 250 cut-off risk, DRs were more variable with gestation for the prime marker combination of F beta-hCG+PAPP-A, varying from 73% at 8 weeks to 65% at 13 weeks with model 1 and from 75% to 66% with model 2. CONCLUSION: Risk algorithms should take into account temporal variation in marker MoMs in order to produce accurate patient-specific risks. This also helps to maximize DRs, particularly when samples are taken out with the optimal gestational range.

Bias in risk estimation: application to Down's syndrome screening.

In this paper we consider the bias associated with parametric estimation of a univariate or bivariate Gaussian density, and also the induced bias when these Gaussian densities are used to determine a likelihood ratio. Algebraic approximations are derived that accurately predict the relative biases obtained, verification being achieved by a simulation exercise. The expressions confirm that when estimating a univariate Gaussian density there are four Z-scores for which there is zero bias and that relative bias increases rapidly beyond two standard deviations from the mean. The results are then extended to determine approximate confidence intervals for both the true density and the likelihood ratio. A simulation exercise confirms that the derived 95 per cent confidence intervals have coverage that ranges from 94 to 97 per cent. The results are applied to a Down's syndrome screening programme where 95 per cent confidence intervals are established for a woman's posterior odds of carrying a Down's foetus. It is shown that patients with similar posterior odds can give rise to confidence intervals for their true posterior odds that have very different widths, thus emphasizing that not all risks are of equal quality.

Temporal changes in maternal serum biochemical markers of trisomy 21 across the first and second trimester of pregnancy.

BACKGROUND: Many maternal serum markers show concentration changes in Down's syndrome pregnancies but the magnitude of the change in median marker levels varies with gestation. To date these changes have not been accurately specified. METHODS: The trends in marker median levels between 6 and 20 weeks of gestation were examined for alphafetoprotein (AFP), free beta human chorionic gonadotrophin (Fbeta-hCG), total human chorionic gonadotrophin (ThCG) and pregnancy-associated plasma protein A (PAPP-A) by a meta-analysis of data obtained from our collaborative studies and routine screening programmes for Down's syndrome over a 10-year period. Data were available from between 709 and 1082 Down's syndrome pregnancies and from between 14607 and 153909 unaffected pregnancies for each marker. The median multiple of the median (MoM) and mean log10MoM for each marker at each completed week of gestation were estimated and the trend with gestation smoothed using a weighted least squares regression model. RESULTS: The gestational ages at which maximum separation of marker levels occurred, comparing affected and unaffected pregnancies, and the respective regressed median MoMs and mean log10MoMs, were: for AFP at 16 weeks, 0.72 MoM, -0.14288log10MoM; for Fbeta-hCG at 15 weeks, 2-24MoM, 0.35034 log10MoM; for ThCG at 16 weeks, 1.93 MoM, 0.28548 log10MoM, as well as before 8 weeks (<0.65 MoM, -0.18853 log10MoM); and for PAPP-A before 8 weeks, <0.33 MoM, -0.47727 log10MoM. CONCLUSION: There is significant temporal variation in mean log10MoM values for the screening markers investigated. Screening algorithms, modified to take account of this variation, should allow more accurate gestation-specific risks to be calculated in individual pregnancies.

Correlation of marker values in Down's syndrome screening: the effect of dating error.

Central to any screening algorithm for Down's syndrome are the values used for the parameters in the multivariate Gaussian statistical model that is used to describe the joint distribution of the marker values. There has been much discussion about the values of the means and standard deviations which are appropriate but little interest has been shown in the values of the correlation coefficients between markers. There has been some speculation that the range of parameter values quoted in the literature arises from factors such as storage of samples, between-assay effects and differences in assay methodologies. We show that gestational dating error, among other factors, could be responsible for much of the variation that is present in quoted parameter values, though the factors mentioned above clearly have an effect.

Temporary abdominal closure using an i.v. bag silo for severe trauma.

Patients with severe abdominal trauma injuries can have improved outcomes if a priority-oriented approach is taken to surgical intervention. This includes temporary abdominal closure and planned reoperation to complete complex, lengthy procedures when the patient is stabilized. Temporary abdominal closure can be achieved safely and cost-effectively by using a presterilized 3-liter cystoscopy fluid i.v. bag. This article discusses the rationale for temporary abdominal closure and planned reoperation, physiologic considerations in abdominal compartment syndrome (ACS), abdominal injuries or conditions leading to ACS, and manifestations of ACS. It compares and contrasts various materials used for temporary abdominal closure, illustrates bag preparation and silo application and removal, and analyzes complex intraoperative and postoperative nursing activities.

Screening for Down's syndrome: the effect of test date on the detection rate.

Screening tests for Down's syndrome are carried out at different gestational ages. Because of fetal loss, crude estimates of their detection rates cannot be directly compared. We present methods for estimating the true detection rates along with their standard errors. This enables a proper statistical comparison of the true detection rates of tests carried out, for example, in different trimesters.

Detection rates and false positive rates for Down's syndrome screening: how precisely can they be estimated and what factors influence their value?

Down's syndrome screening is currently carried out using a combination of biochemical markers measured in maternal serum samples; these include MSAFP, Total hCG, uE3 and Free beta-hCG. Recently a number of papers have compared the effectiveness of different combinations of these markers. Some recommend MSAFP, Total hCG and uE3 (triple test) while others advocate MSAFP and Free beta-hCG (double test). The cases put forward to support these tests rely on estimated detection and false positive rates for the proposed test. A recent paper by Wright used simulation techniques to estimate the effects of sampling error on such error rates. In prospective studies there are two methods commonly used for estimating these rates. We obtain formulae for the standard deviations of these estimates and show that one of them always gives a smaller standard error than the other. We also show that in such studies the accuracy of estimating detection rates and false positive rates depends not only upon the method of calculation but also on the age distribution of pregnant women and the parameters used to calculate patient specific risk. We show that these effects can result in estimation errors of such magnitude that many observed differences in detection rates could be of questionable significance, a conclusion also reached by Wright.

The effects of gestation dating on the calculation of patient-specific risks in Down's syndrome screening: multivariate case.

When screening for Down's syndrome using biochemical markers, the measurements are adjusted for the gestational age of the fetus because the concentrations of the markers are known to change with gestational age. This adjustment is performed by referring each marker measurement to the population median for that marker for the appropriate estimated gestational age group. The measurement of gestational age is subject to error, whichever method is used, and so the population median used is usually the median of a mixture of distributions for different true gestational ages. Most screening programmes aim for a specific number of weeks and this produces a concentrated distribution of true gestational ages. This fact, combined with dating errors, leads to an asymmetric mixture for each gestational age group and hence to bias in the estimates of the medians. In a previous communication we have shown how the proportions in this mixture distribution can be estimated and how the true medians corresponding to a true gestational age can be estimated. The calculations presented were performed using a single marker, and the details of our method were restricted to this situation. This paper extends the method to the multimarker situation and, as expected, leads to a gain in the detection rate for a specified false positive rate. The true patient-specific risk estimates are again markedly different from the quoted nominal value obtained by ignoring the dating errors. The data set on which the method is illustrated uses two markers, although the technique generalises in an obvious way to more than two.