BackgroundUrinalysis and urine culture are commonly ordered tests in the emergency department (ED). We evaluated the impact of removal of order sets from the ‘frequently ordered test’ in the ...computerised physician order entry system (CPOE) on urine testing practices.MethodsWe conducted a before (1 September to 20 October 2015) and after (21 October to 30 November 2015) study of ED patients. The intervention consisted of retaining ‘urinalysis with reflex to microscopy’ as the only urine test in a highly accessible list of frequently ordered tests in the CPOE system. All other urine tests required use of additional order screens via additional mouse clicks. The frequency of urine testing before and after the intervention was compared, adjusting for temporal trends.ResultsDuring the study period, 6499 (28.2%) of 22 948 ED patients had ≥1 urine test ordered. Urine testing rates for all ED patients decreased in the post intervention period for urinalysis (291.5 pre intervention vs 278.4 per 1000 ED visits post intervention, P=0.03), urine microscopy (196.5vs179.5, P=0.001) and urine culture (54.3vs29.7, P<0.001). When adjusted for temporal trends, the daily culture rate per 1000 ED visits decreased by 46.6% (−46.6%, 95% CI −66.2% to –15.6%), but urinalysis (0.4%, 95% CI −30.1 to 44.4%), microscopy (−6.5%, 95% CI −36.0% to 36.6%) and catheterised urine culture rates (17.9%, 95% CI −16.9 to 67.4) were unchanged.ConclusionsA simple intervention of retaining only ‘urinalysis with reflex to microscopy’ and removing all other urine tests from the ‘frequently ordered’ window of the ED electronic order set decreased urine cultures ordered by 46.6% after accounting for temporal trends. Given the injudicious use of antimicrobial therapy for asymptomatic bacteriuria, findings from our study suggest that proper design of electronic order sets plays a vital role in reducing excessive ordering of urine cultures.
To evaluate the impact of changes to urine testing orderables in computerized physician order entry (CPOE) system on urine culturing practices.
Retrospective before-and-after study.
A 1,250-bed ...academic tertiary-care referral center.
Hospitalized adults who had ≥1 urine culture performed during their stay.
The intervention (implemented in April 2017) consisted of notifications to providers, changes to order sets, and inclusion of the new urine culture reflex tests in commonly used order sets. We compared the urine culture rates before the intervention (January 2015 to April 2016) and after the intervention (May 2016 to August 2017), adjusting for temporal trends.
During the study period, 18,954 inpatients (median age, 62 years; 68.8% white and 52.3% female) had 24,569 urine cultures ordered. Overall, 6,662 urine cultures (27%) were positive. The urine culturing rate decreased significantly in the postintervention period for any specimen type (38.1 per 1,000 patient days preintervention vs 20.9 per 1,000 patient days postintervention; P < .001), clean catch (30.0 vs 18.7; P < .001) and catheterized urine (7.8 vs 1.9; P < .001). Using an interrupted time series model, urine culture rates decreased for all specimen types (P < .05).
Our intervention of changes to order sets and inclusion of the new urine culture reflex tests resulted in a 45% reduction in the urine cultures ordered. CPOE system format plays a vital role in reducing the burden of unnecessary urine cultures and should be implemented in combination with other efforts.
Background
Therapeutic plasma exchange (TPE) utilizes an extracorporeal circuit to remove pathologic proteins causing serious illness. When processing a patient's entire blood volume through an ...extracorporeal circuit, proteins responsible for maintaining hemostatic system homeostasis can reach critically low levels if replacement fluid types and volumes are not carefully titrated, which may increase complications.
Methods
The charts from 27 patients undergoing 46 TPE procedures were reviewed to evaluate the accuracy of our predictive mathematical model, utilizing the following patient information: weight, hematocrit, pre‐ and post‐TPE factor levels (fibrinogen, n = 46, and antithrombin, n = 23), process volume and volumes of fluids (eg, plasma, albumin, and normal saline) administered during TPE and adverse events during and after TPE.
Results
Altogether, 25% of patients experienced minor adverse events that resolved spontaneously or with management. There were no bleeding or thrombotic complications. The mean difference between predicted and measured post‐TPE fibrinogen concentrations was −0.29 mg/dL (SD ±23.0, range −59 to 37), while percent difference between measured and predicted fibrinogen concentration was 0.94% (SD ±10.8, range of −22 to 19). The mean difference between predicted and measured post‐TPE antithrombin concentrations were 0.89% activity (SD ±10.0, range −23 to 14), while mean percent difference between predicted and measured antithrombin concentrations was 3.87% (SD ±14.5, range −25 to 38).
Conclusions
Our model reliably predicts post‐TPE fibrinogen and antithrombin concentrations, and may help optimize patient management and attenuate complications.
While some members of the ubiquitous DExD/H box family of proteins have RNA helicase activity in vitro, their roles in vivo remain virtually unknown. Here, we show that the function of an otherwise ...essential DEAD box protein, Prp28p, can be bypassed by mutations that alter either the protein U1-C or the U1 small nuclear RNA. Further analysis suggests that the conserved L13 residue in the U1-C protein makes specific contact to stabilize the U1 snRNA/5′ splice site duplex in the prespliceosome, and that Prp28p functions to counteract the stabilizing effect of the U1-C protein, thereby promoting the dissociation of the U1 small nuclear ribonucleoprotein particle from the 5′ splice site. Thus, in addition to unwinding RNA, the DExD/H box proteins may affect RNA–RNA rearrangements by antagonizing specific RNA-stabilizing proteins.
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•Information theory directly measures test value as reduction in uncertainty.•Information-theoretic optimization accounts for physician ordering practice.•Optimal diagnostic ...thresholds differ for accuracy- and information-based approaches.•In practice, accuracy-based optimization leads to a noisy, less-informative test.
Clinicians order laboratory tests in an effort to reduce diagnostic or therapeutic uncertainty. Information theory provides the opportunity to quantify the degree to which a test result is expected to reduce diagnostic uncertainty. We sought to apply information theory toward the evaluation and optimization of a diagnostic test threshold and to determine if the results would differ from those of conventional methodologies. We used a heparin/PF4 immunoassay (PF4 ELISA) as a case study.
The laboratory database was queried for PF4 ELISA and serotonin release assay (SRA) results during the study period, with the latter serving as the gold standard for the disease heparin-induced thrombocytopenia (HIT). The optimized diagnostic threshold of the PF4 ELISA test was compared using conventional versus information theoretic approaches under idealized (pretest probability = 50%) and realistic (pretest probability = 2.4%) testing conditions.
Under ideal testing conditions, both analyses yielded a similar optimized optical density (OD) threshold of OD > 0.79. Under realistic testing conditions, information theory suggested a higher threshold, OD > 1.5 versus OD > 0.6. Increasing the diagnostic threshold improved the global information value, the value of a positive test and the noise content with only a minute change in the negative test value.
Our information theoretic approach suggested that the current FDA approved cutoff (OD > 0.4) is overly permissive leading to loss of test value and injection of noise into an already complex diagnostic dilemma. Because our approach is purely statistical and takes as input data that are readily accessible in the clinical laboratory it offers a scalable and data-driven strategy for optimizing test value that may be widely applicable in the domain of laboratory medicine.
Information theory provides more meaningful measures of test value than the widely used accuracy-based metrics.
Vascular access for red blood cell exchange Otrock, Zaher K.; Thibodeaux, Suzanne R.; Jackups, Ronald
Transfusion (Philadelphia, Pa.),
February 2018, 2018-02-00, 20180201, Letnik:
58, Številka:
S1
Journal Article
Recenzirano
Red blood cell exchange is the process of removing red blood cells from a patient and replacing them with donated blood using either automated or manual techniques. Red blood cell exchange is a ...well‐recognized and effective therapy for many red blood cell‐related diseases, especially sickle cell disease. However, decisions regarding the best methods for vascular access are not intuitive and must account for the patient's clinical condition, complication risks, and lifestyle, especially in the context of long‐term vascular access. In this review, we discuss the recognized indications for red blood cell exchange, considerations for the selection of exchange modality and vascular access, and recommendations for the appropriate care and prevention of risks associated with vascular access.
β-Barrel membrane proteins are found in the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts. Little is known about how residues in membrane β-barrels interact preferentially ...with other residues on adjacent strands. We have developed probabilistic models to quantify propensities of residues for different spatial locations and for interstrand pairwise contact interactions involving strong H-bonds, side-chain interactions, and weak H-bonds. Using the reference state of exhaustive permutation of residues within the same β-strand, the propensity values and
p-values measuring statistical significance are calculated exactly by analytical formulae we have developed. Our findings show that there are characteristic preferences of residues for different membrane locations. Contrary to the “positive-inside” rule for helical membrane proteins, β-barrel membrane proteins follow a significant albeit weaker “positive-outside” rule, in that the basic residues Arg and Lys are disproportionately favored in the extracellular cap region and disfavored in the periplasmic cap region. We find that different residue pairs prefer strong backbone H-bonded interstrand pairings (e.g. Gly–aromatic) or non-H-bonded pairings (e.g. aromatic–aromatic). In addition, we find that Tyr and Phe participate in aromatic rescue by shielding Gly from polar environments. We also show that these propensities can be used to predict the registration of strand pairs, an important task for the structure prediction of β-barrel membrane proteins. Our accuracy of 44% is considerably better than random (7%). It also significantly outperforms a comparable registration prediction for soluble β-sheets under similar conditions. Our results imply several experiments that can help to elucidate the mechanisms of
in vitro and
in vivo folding of β-barrel membrane proteins. The propensity scales developed in this study will also be useful for computational structure prediction and for folding simulations.
Abstract
Background
Serum free light chain (sFLC) assays are interpreted using a sFLC-ratio-based reference interval (manufacturer’s interval) that was defined using a cohort of healthy patients. ...However, renal impairment elevates the sFLC-ratio, leading to a high false positive rate when using the manufacturer’s interval. Prior studies have developed renal-specific reference intervals; however, this approach has not been widely adopted due to practical limitations. Thus, there remains a critical need for a renally robust sFLC interpretation method.
Methods
Retrospective data mining was used to define patient cohorts that reflect the spectrum of renal function seen in clinical practice. Two new reference intervals, one based on the sFLC-ratio and one based on a novel principal component analysis (PCA)-based metric, were developed for the FREELITE assay (Binding Site) on the Roche Cobas c501 instrument (Roche).
Results
Compared to the manufacturer’s reference interval, both new methods exhibited significantly lower false positive rates and greater robustness to renal function while maintaining equivalent sensitivity for monoclonal gammopathy (MG) diagnosis. While not significantly different, the point estimate for sensitivity was highest for the PCA-based approach.
Conclusion
Renally robust sFLC interpretation using a single reference interval is possible given a reference cohort that reflects the variation in renal function observed in practice. Further studies are needed to achieve sufficient power and determine if the novel PCA-based metric offers superior sensitivity for MG diagnosis. These new methods offer the practical advantages of not requiring an estimated glomerular filtration rate result or multiple reference intervals, thereby lowering practical barriers to implementation.
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