Dataset of test volume and tests repeated for complete blood count and electrolyte panels from hospitals in a Canadian province in 2018.

All laboratory tests performed within the province of Alberta in Canada are captured by three Laboratory Information Systems (LIS; Millennium, Sunquest and Meditech), which comprise the provincial Consolidated Laboratory Data Repository (CLDR). The following secondary laboratory data for electrolyte panel (EP) and complete blood count (CBC) test panels performed in emergency room (ER) and inpatient settings were collected from January 1 - December 31, 2018: total test panel volume, total number of test panels repeated, number of test panels repeated within the 24 hour period, test result, date of testing, time of test, and patient Provincial Health Number (PHN). Patient PHN were used as a linking variable to match subsequent tests performed on the same patient. The first time a test was recorded per patient was defined as the "index test". If the same test panel was performed within a 24-h period following the index test for the patient, data for the repeated test panel was also collected. The index test was defined as "normal" or "abnormal" according to established laboratory normal values and laboratory test reference ranges. For CBCs, we considered the panel to be abnormal if any of the hematocrit (Hct), hemoglobin (Hgb), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), platelet (PLT), red blood cell (RBC), red cell distribution width (RDW) or white blood cell (WBC) values were outside the normal laboratory reference range. For electrolyte panels, we considered the panel to be abnormal if any of the chloride (Cl), potassium (K), and sodium (Na) were outside of the normal laboratory reference range. All EP results were from clinical chemistry analyzers only. The reuse potential of this dataset can allow other jurisdictions in Canada to compare their redundant repeat testing in their hospital settings with this dataset as a benchmark. This article was submitted via another Elsevier journal as a co-submission ("Inappropriate repeat testing of complete blood count (CBC) and electrolytes in inpatients from Alberta, Canada" [1]), and readers should refer to the co-submission article for interpretation of the results.

Inappropriate repeat testing of complete blood count (CBC) and electrolyte panels in inpatients from Alberta, Canada.

INTRODUCTION: The avoidance of repeat chemistry testing such as Complete Blood Count (CBC) and Electrolyte Panel (EP) on clinically stable patients was identified as important utilization goals by Choosing Wisely Canada. The purpose of this study was to assess the volume of overutilization of CBC and EP in an inpatient setting in Alberta, Canada, and provide an estimated cost assessment of unnecessary testing. METHODS: The total laboratory testing volumes of two common test panels were collected retrospectively for one-year from January to December 2018. Data was collected on test panels performed in an emergency room (ER) and inpatient setting from three separate Laboratory Information Systems covering the provincial population in Alberta, Canada. Total initial test panel instances, total repeated panels, repeated panels that were previously normal or abnormal, and estimated costs were examined. Cost assessment was completed based on Reference Median Cost (RMC) analysis for each of these two common test panels. RESULTS: During the study period, 2,020,467 (CBC) and 1,455,983 (EP) initial test panel instances were recorded, of which 67.7% and 73.5% were repeated for the CBC and EP, respectively. There was a higher proportion of EP repeated inappropriately (previously normal; 35.6%) compared to CBCs (5.4%). The cost to the province for inappropriately repeating CBC and EP were estimated to be RMC $0.52 million and RMC $1.90 million CAD, respectively. CONCLUSION: Results from this study can assist policy makers in implementing utilization management initiatives and update clinical practice guidelines to reduce costs to healthcare without compromising patient care.

Implementation of an educational province-wide intervention to reduce redundant vitamin B12 testing: A cross-sectional study.

INTRODUCTION: We describe the implementation of an Alberta-wide intervention aimed at educating clinicians about redundant vitamin B12 testing. We hypothesized that the introduction of an educational comment outlining recommended vitamin B12 test intervals would reduce the annual number of vitamin B12 tests performed. MATERIALS AND METHODS: We performed a cross-sectional observational study that included all vitamin B12 tests ordered in Alberta between May 1, 2017 and April 30, 2018. An educational comment was appended to all vitamin B12 test results in Alberta beginning May 2, 2017. Using a simple seasonal model, we compared predicted versus observed vitamin B12 test volumes for the 12-month period following the introduction of the educational comment. The sole outcome measured was the monthly change in volume of vitamin B12 testing. A cost-analysis of the effects of the intervention on test volumes was also performed. RESULTS: Over the sum of the first 12 months of the intervention, 18,000 more vitamin B12 tests were ordered compared to the predicted value in Alberta. With an estimated cost of $7 per test, this resulted in a $126,000 increase in costs for vitamin B12 testing provincially. CONCLUSIONS: An educational intervention aimed at limiting inappropriate vitamin B12 testing in Alberta did not alter testing as desired. Multiple utilization management strategies and a longer observation period may be needed to reduce redundant vitamin B12 testing.

Vitamin B12 test volume data before and after the implementation of an educational province-wide intervention to reduce redundant testing in Alberta.

The data presented in this article is the provincial vitamin B12 test volume data for Alberta, Canada per month between April 1, 2015 and April 30, 2018. This data set was collected from the three different Alberta Public Laboratories Laboratory Information Systems: Cerner Millennium for Calgary, Sunquest for Edmonton, and MediTech for the remaining rural zones of Alberta (Bonnyville, Grand Prairie, Camrose, Red Deer, and Medicine Hat). An educational province-wide intervention aimed at reducing redundant testing was implemented on April 11, 2017 in Calgary, Alberta and Edmonton, Alberta and on May 2, 2017 in rural Alberta sites. All vitamin B12 test results in Alberta were appended with the educational comment "A normal test result indicates adequate stores and should not be repeated. However, if specific clinical situations require re-testing, the interval should not be sooner than 1 year." Provincial monthly test volumes prior to this intervention ranged from 54,182 to 73,522 tests per month and after this intervention ranged from 59,116 to 74,006 tests per month. The total number of vitamin B12 tests ordered over the 37 months in Alberta was 2,444,724; 690,448 tests were ordered in Calgary, 1,029,315 tests were ordered in Edmonton, and 724,961 tests were ordered in rural sites. This data article was submitted as a companion paper to the related research article, "Implementation of an educational province-wide intervention to reduce redundant vitamin B12 testing: a cross-sectional study"[1].

Test volume data for 51 most commonly ordered laboratory tests in Calgary, Alberta, Canada.

Data presented in this article include the top 51 ordered laboratory tests in Calgary and surrounding area, Alberta, from January to December 2017. This data set was collected from Calgary Laboratory Service's Laboratory Information System, and included top 51 tests ordered from community (n = 11, 224, 330), inpatient (n = 2,340,594) and emergency (n = 1,670,062) settings. Test order mnemonic that were not true laboratory tests (eg: "extra PST tube", "extra tube", etc.) were excluded in the analysis. The top test ordered in all 3 test encounters was the complete blood count test (community encounter, n = 921, 873; inpatient setting, n = 357, 375; and emergency setting, n = 276, 954). This data article was submitted as a companion paper to the related research article, "Estimated costs of 51 commonly ordered laboratory tests in Canada" [1].

Estimated costs of 51 commonly ordered laboratory tests in Canada.

INTRODUCTION: Test cost display has been shown to reduce inappropriate laboratory test ordering practices in the United States. Unfortunately, such a system is limited in the Canadian publically funded healthcare environment. Many Canadian physicians inaccurately estimate the cost of laboratory tests, which may contribute to mis-utilization. Here, we provide an estimated cost of over 50 commonly ordered laboratory tests in Canada as an educational tool for physicians. METHODS: Test volume data was collected from Calgary Laboratory Services' Laboratory Information System in order to determine which laboratory and diagnostic tests are most commonly ordered in Calgary and its surrounding area. Reference median cost (RMC) of fifty one commonly ordered test was calculated by determining the price list of all-inclusive indirect costs from six different clinical laboratories across Canada. RESULTS: Of the 51 laboratory tests included, the minimum RMC was $5 CAD (eg: albumin, calcium, urea), and the maximum RMC was $300 (surgical pathology report). CONCLUSIONS: A caveat to the provided list of test costs is that it is only an estimate and may differ from what each individual clinical laboratories charges to third parties or for research purposes. However, this list can serve as an educational tool and raise awareness for Canadian physicians on the relative costs of laboratory tests.

Canadian family physician knowledge and attitudes toward laboratory utilization management.

OBJECTIVES: Mitigation of unnecessary and redundant laboratory testing is an important quality assurance priority for laboratories and represents an opportunity for cost savings in the health care system. Family physicians represent the largest utilizers of laboratory testing by a large margin. Engagement of family physicians is therefore key to any laboratory utilization management initiatives. Despite this, family physicians have been largely excluded from the planning and implementation of such initiatives. Our purposes were to (1) assess the importance of lab management issues to family physicians, and (2) attempt to define the types of initiatives most acceptable to family physicians. DESIGN AND METHODS: We invited all Alberta family practice residents and practicing physicians to participate in a self-administered online electronic survey. Survey questions addressed the perceived importance of lab misutilization, prevalence of various types of misutilization, acceptability of specific approaches to quality control, and responsibility of various parties to address this issue. RESULTS: Of 162 respondents, 95% considered lab misutilization to be either important or very important. Many physicians placed the responsibility for addressing lab misutilization issues on multiple parties, including patients, but most commonly the ordering physician (97%). Acceptability for common strategies for quality improvement in lab misutilization showed a wide range (35%-98%). CONCLUSIONS: These responses could serve as a framework for laboratories to begin discussions on this important topic with primary care groups.

Bacterial ferrous iron transport: the Feo system.

To maintain iron homeostasis within the cell, bacteria have evolved various types of iron acquisition systems. Ferric iron (Fe(3+)) is the dominant species in an oxygenated environment, while ferrous iron (Fe(2+)) is more abundant under anaerobic conditions or at low pH. For organisms that must combat oxygen limitation for their everyday survival, pathways for the uptake of ferrous iron are essential. Several bacterial ferrous iron transport systems have been described; however, only the Feo system appears to be widely distributed and is exclusively dedicated to the transport of iron. In recent years, many studies have explored the role of the FeoB and FeoA proteins in ferrous iron transport and their contribution toward bacterial virulence. The three-dimensional structures for the Feo proteins have recently been determined and provide insight into the molecular details of the transport system. A highly select group of bacteria also express the FeoC protein from the same operon. This review will provide a comprehensive look at the structural and functional aspects of the Feo system. In addition, bioinformatics analyses of the feo operon and the Feo proteins have been performed to complement our understanding of this ubiquitous bacterial uptake system, providing a new outlook for future studies.

A population study of fasting time and serum prostate-specific antigen (PSA) level.

Prostate cancer is one of the most common cancers in men. Traditional screening and diagnostic methods include digital rectal examinations (DREs), biopsies and serum prostate-specific antigen (PSA) tests, with the latter being the more popular. PSA is a biomarker for prostate cancer; however, it is highly sensitive to external factors as well as other prostate diseases. As such, the reliability of of the serum PSA level as a sole screening and diagnostic tool for prostate cancer is controversial. Recently, it has been shown that fasting extremes can affect concentrations of serum chemistry analytes, thus raising the question of whether or not fasting has an effect on the highly sensitive PSA biomarker. Patients testing for serum PSA levels are often concomitantly submitting to other tests that require fasting, subjecting certain patients to a fasting PSA level while others not. The objective of this study was to investigate whether this discrepancy in fasting state translates into an effect on serum PSA levels. Serum PSA levels and fasting time records for 157 276 men who underwent testing at Calgary Laboratory Services (CLS; Calgary, Alberta, Canada) between 01 January 2010 and 31 March 2013 were accessed. Linear regression models of mean PSA levels and fasting times revealed a statistically important relationship at certain fasting times. Applying a dynamic mathematical model to explore the clinical effect of fasting suggests minimal impact on serum PSA result interpretation. Thus, patients can be tested for serum PSA levels regardless of their fasting state.

Mechanism of action of puroindoline derived tryptophan-rich antimicrobial peptides.

A tryptophan (Trp)-rich region in the wheat endosperm protein, puroindoline A, was previously shown to possess potent antimicrobial activity against Gram-positive and Gram-negative bacteria and this was attributed to the peptide inducing membrane instability. In the present work, the antimicrobial activity of the corresponding Trp-rich region in the puroindoline B isoform was examined and its antimicrobial activity was characterized. Unexpectedly, the puroindoline B Trp-rich peptide (PuroB) was relatively inactive compared to the related puroindoline A peptide (PuroA), despite strong sequence similarity. Using the sequence of PuroA as a template, a series of PuroB variants were synthesized and the antimicrobial activity was restored. Interestingly, all of these PuroB peptides preferentially interacted with negatively charged phospholipids, but unlike PuroA, they did not disrupt the integrity of lipid bilayers. This suggests that the primary mode of action of the PuroB peptides involves an antimicrobial target other than the bacterial membrane. Further tests revealed that all of the puroindoline derived peptides bind deoxyribonucleic acid (DNA) and block macromolecular synthesis in vivo. Based on these results, it appears that the interaction between puroindoline derived peptides and membranes is only an initial step in the mode of action and that binding to intracellular targets, such as DNA and ribonucleic acid (RNA), contributes significantly to their antimicrobial mode of action.

Solution structure of Escherichia coli FeoA and its potential role in bacterial ferrous iron transport.

Iron is an indispensable nutrient for most organisms. Ferric iron (Fe(3+)) predominates under aerobic conditions, while during oxygen limitation ferrous (Fe(2+)) iron is usually present. The Feo system is a bacterial ferrous iron transport system first discovered in Escherichia coli K-12. It consists of three genes, feoA, feoB, and feoC (yhgG). FeoB is thought to be the main transmembrane transporter while FeoC is considered to be a transcriptional regulator. Using multidimensional nuclear magnetic resonance (NMR) spectroscopy, we have determined the solution structure of E. coli FeoA. The structure of FeoA reveals a Src-homology 3 (SH3)-like fold. The structure is composed of a ß-barrel with two α-helices where one helix is positioned over the barrel. In comparison to the standard eukaryotic SH3 fold, FeoA has two additional α-helices. FeoA was further characterized by heteronuclear NMR dynamics measurements, which suggest that it is a monomeric, stable globular protein. Model-free analysis of the NMR relaxation results indicates that a slow conformational dynamic process is occurring in ß-strand 4 that may be important for function. (31)P NMR-based GTPase activity measurements with the N-terminal domain of FeoB (NFeoB) indicate a higher GTP hydrolysis rate in the presence of potassium than with sodium. Further enzymatic assays with NFeoB suggest that FeoA may not act as a GTPase-activating protein as previously proposed. These findings, together with bioinformatics and structural analyses, suggest that FeoA may have a different role, possibly interacting with the cytoplasmic domain of the highly conserved core portion of the FeoB transmembrane region.

NMR solution structure and biophysical characterization of Vibrio harveyi acyl carrier protein A75H: effects of divalent metal ions.

Bacterial acyl carrier protein (ACP) is a highly anionic, 9 kDa protein that functions as a cofactor protein in fatty acid biosynthesis. Escherichia coli ACP is folded at neutral pH and in the absence of divalent cations, while Vibrio harveyi ACP, which is very similar at 86% sequence identity, is unfolded under the same conditions. V. harveyi ACP adopts a folded conformation upon the addition of divalent cations such as Ca(2+) and Mg(2+) and a mutant, A75H, was previously identified that restores the folded conformation at pH 7 in the absence of divalent cations. In this study we sought to understand the unique folding behavior of V. harveyi ACP using NMR spectroscopy and biophysical methods. The NMR solution structure of V. harveyi ACP A75H displays the canonical ACP structure with four helices surrounding a hydrophobic core, with a narrow pocket closed off from the solvent to house the acyl chain. His-75, which is charged at neutral pH, participates in a stacking interaction with Tyr-71 in the far C-terminal end of helix IV. pH titrations and the electrostatic profile of ACP suggest that V. harveyi ACP is destabilized by anionic charge repulsion around helix II that can be partially neutralized by His-75 and is further reduced by divalent cation binding. This is supported by differential scanning calorimetry data which indicate that calcium binding further increases the melting temperature of V. harveyi ACP A75H by ∼20 °C. Divalent cation binding does not alter ACP dynamics on the ps-ns timescale as determined by (15)N NMR relaxation experiments, however, it clearly stabilizes the protein fold as observed by hydrogen-deuterium exchange studies. Finally, we demonstrate that the E. coli ACP H75A mutant is similarly unfolded as wild-type V. harveyi ACP, further stressing the importance of this particular residue for proper protein folding.

Siderophore uptake in bacteria and the battle for iron with the host; a bird's eye view.

Siderophores are biosynthetically produced and secreted by many bacteria, yeasts, fungi and plants, to scavenge for ferric iron (Fe(3+)). They are selective iron-chelators that have an extremely high affinity for binding this trivalent metal ion. The ferric ion is poorly soluble but it is the form of iron that is predominantly found in oxygenated environments. Siderophore uptake in bacteria has been extensively studied and over the last decade, detailed structural information for many of the proteins that are involved in their transport has become available. Specifically, numerous crystal structures for outer membrane siderophore transporters, as well as for soluble periplasmic siderophore-binding proteins, have been reported. Moreover, unique siderophore-binding proteins have recently been serendipitously discovered in humans, and the structures of some of their siderophore-complexes have been characterized. The binding pockets for different ferric-siderophores in these proteins have been described in great molecular detail. In addition to highlighting this structural information, in this review paper we will also briefly discuss the relevant chemical properties of iron, and provide a perspective on our current understanding of the human and bacterial iron uptake pathways. Potential clinical uses of siderophores will also be discussed. The emerging overall picture is that iron metabolism plays an extremely important role during bacterial infections. Because levels of free ferric iron in biological systems are always extremely low, there is serious competition for iron and for ferric-siderophores between pathogenic bacteria and the human or animal host.