Xtra Meter Research Articles

Integrative Tumor Profiling Following a Ketogenic Diet Offers a Window into the Interplay between Metabolic Vulnerabilities and Radiation Sensitization in Glioblastoma.

Glioblastoma (GBM) continues to be an invariably fatal malignancy with limited treatment options. Although considerable progress has been made in understanding molecular alterations in these tumors, this level of knowledge has not translated to clinical improvements. Metabolic reprogramming represents a hallmark of cancer and may serve as a therapeutic target. A ketogenic diet (KD) is a clinical strategy designed to target tumor metabolism and represents an active area of research. Although both preclinical and clinical data demonstrating efficacy has been mixed, a recent report suggests an unprecedented potential of a KD to enhance radiation response (RT) in an orthotopic model using an established mouse GBM cell line. In this study, we sought to validate these findings by determining the capacity of a KD to enhance RT in an aggressive, patient-derived GBM stem cell model and perform an integrative analysis on tissue to both define metabolic changes related to a KD and provide a mechanistic framework of activity. Immune deficient mice (nu/nu) were injected orthotopically with patient derived mesenchymal GBM tumor stem cells and randomized to four treatment arms (n=8/arm). Mice were fed ad libitum standard diet (SD) or KD (Bio-Serve; 1:4) alone or in combination with hypofractionated RT (hfRT; 6 Gy x 3). LC/GC-MS will be used to perform global metabolomic and proteomic profiling of tumor, serum, and normal brain of treated mice. Blood glucose and ketones were measured using the Abbott Precision Xtra meter kit. A KD demonstrated improved survival in GBM tumor bearing mice when compared to SD (mOS 22d vs. 17d; p=0.001) and equivalent survival when compared to SD mice treated with hfRT (mOS 24d; p= 0.57). The combination of KD and hfRT led to marked improvement in overall survival (mOS not reached; p<0.001). Although studies remain ongoing, at Day 29, 7/8 mice treated with KD+hfRT remained alive, while all 8 mice treated with SD+hfRT required euthanization due to neurologic progression. Surprisingly, alterations in blood ketone levels or glucose were not observed in mice treated with a KD. Global metabolomic and proteomic profiling of tumor, serum, and normal brain are ongoing. The anti-tumor activity and potent radiation sensitization of a KD was validated in an aggressive patient-derived GBM model. Ongoing integrative profiling of tumor and serum in mice treated with a KD will be presented to provide a previously undescribed insight into mechanisms of anti-tumor activity. As a KD is challenging to implement clinically, these mechanistic-based studies will provide a unique opportunity to learn how metabolism may be therapeutically exploited to provide a framework for the identification of novel mechanisms of radiation sensitization.

Evaluation of the Precision Xtra meter for monitoring blood β-hydroxybutyrate concentrations in late-gestation ewes.

Blood samples were collected from late-gestation ewes to determine the agreement of a point-of-care (POC) Precision Xtra meter and a standard laboratory test for β-hydroxybutyrate (BHBA). Fresh whole blood samples were immediately tested with the POC instrument, and serum samples were analyzed with a standard commercial biochemical analyzer. Ewes were classified as having ketonemia if their BHBA concentrations were ≥800 µmol/L. Scatter plots, paired t-tests, Bland-Altman limits of agreement, and Gwet AC1 tests were used to compare results. The 2 tests had very good agreement. The values between instruments were not statistically different based on paired t-tests ( p = 0.312). The intercept and slope of a linear mixed model, containing the standard test results as an outcome and the POC meter results as a predictor, were 0.02 (95% CI: 0.00, 0.04) and 0.98 (95% CI: 0.96, 1.01), respectively. When the samples were classified into ketonemic classes (non-ketonemic and ketonemic) based on BHBA concentrations obtained from each test, the Gwet AC1 statistic was 0.94 (95% CI: 0.91, 0.97; p < 0.001). The ketosis classification agreed in 95% of samples. Based on the Bland-Altman plot and limits of agreement, the optimal cutoff to diagnose ketonemia with the POC meter was 1,000 µmol/L, which is 200 µmol/L higher than the laboratory BHBA medical decision limit. The Precision Xtra meter provided excellent correlation and substantial agreement with the standard laboratory technique for measuring blood BHBA in late-gestation ewes.

Technical note: Evaluation of the diagnostic accuracy of 2 point-of-care β-hydroxybutyrate devices in stored bovine plasma at room temperature and at 37°C

The use of point-of-care (POC) devices to measure blood metabolites, such as β-hydroxybutyrate (BHB), on farm have become an important diagnostic and screening tool in the modern dairy industry. The POC devices allow for immediate decision making and are often more economical than the use of laboratory-based methods; however, precision and accuracy may be lower when measurements are performed in an uncontrolled environment. Ideally, the advantages of the POC devices and the standardized laboratory environment could be combined when measuring samples that do not require an immediate result-for example, in research applications or when immediate intervention is not the goal. The objective of this study was to compare the capability of 2 POC devices (TaiDoc, Pharmadoc, Lübeck, Germany; Precision Xtra, Abbott Diabetes Care, Abingdon, UK) to measure BHB concentrations either at room temperature (RT; 20-22°C) or at 37°C compared with the gold standard test in stored plasma samples. Whole blood from multiparous Holstein dairy cows (n = 113) was sampled from the coccygeal vessels between 28 d before expected calving and 42 DIM. Whole-blood BHB concentrations were determined cow-side using the TaiDoc POC device. Plasma was separated within 1 h of collection and stored until analysis. A subset of stored plasma samples (n = 100) consisting of 1 sample per animal was chosen retrospectively based on the BHB concentrations in whole blood within the range of 0.2 to 4.0 mmol/L. The samples were analyzed for BHB plasma concentration using an automated chemistry analyzer (Hitachi 917, Hitachi, Tokyo, Japan), which was considered the gold standard. On the same day, the samples were also measured with the 2 POC devices, with samples either at RT or heated up to 37°C. Our study showed high Spearman correlation coefficients (>0.99) using either device and with samples at both temperatures compared with the gold standard. Passing-Bablok regression revealed a very strong correlation (>0.99), indicating good agreement between both POC devices and the gold standard method. For hyperketonemia detection, defined as BHB concentration ≥1.2 mmol/L, the sensitivity for both POC devices at RT and 37°C was equally high at 100%. Specificity was lowest (67.4%) for the TaiDoc used with plasma at RT and was highest (86.5%) when plasma was measured at 37°C with the Precision Xtra meter. Bland-Altman plots revealed a mean bias of 0.25 and 0.4 mmol/L for the Precision Xtra meter and TaiDoc, respectively, when tested on plasma at 37°C. Our data showed that both POC devices are suitable for measuring BHB concentration in stored bovine plasma, and accuracy was highest when samples were heated to 37°C compared with RT.

Predicting blood β-hydroxybutyrate using milk Fourier transform infrared spectrum, milk composition, and producer-reported variables with multiple linear regression, partial least squares regression, and artificial neural network

Prediction of postpartum hyperketonemia (HYK) using Fourier transform infrared (FTIR) spectrometry analysis could be a practical diagnostic option for farms because these data are now available from routine milk analysis during Dairy Herd Improvement testing. The objectives of this study were to (1) develop and evaluate blood β-hydroxybutyrate (BHB) prediction models using multivariate linear regression (MLR), partial least squares regression (PLS), and artificial neural network (ANN) methods and (2) evaluate whether milk FTIR spectrum (mFTIR)-based models are improved with the inclusion of test-day variables (mTest; milk composition and producer-reported data). Paired blood and milk samples were collected from multiparous cows 5 to 18 d postpartum at 3 Wisconsin farms (3,629 observations from 1,013 cows). Blood BHB concentration was determined by a Precision Xtra meter (Abbot Diabetes Care, Alameda, CA), and milk samples were analyzed by a privately owned laboratory (AgSource, Menomonie, WI) for components and FTIR spectrum absorbance. Producer-recorded variables were extracted from farm management software. A blood BHB ≥1.2 mmol/L was considered HYK. The data set was divided into a training set (n = 3,020) and an external testing set (n = 609). Model fitting was implemented with JMP 12 (SAS Institute, Cary, NC). A 5-fold cross-validation was performed on the training data set for the MLR, PLS, and ANN prediction methods, with square root of blood BHB as the dependent variable. Each method was fitted using 3 combinations of variables: mFTIR, mTest, or mTest + mFTIR variables. Models were evaluated based on coefficient of determination, root mean squared error, and area under the receiver operating characteristic curve. Four models (PLS-mTest + mFTIR, ANN-mFTIR, ANN-mTest, and ANN-mTest + mFTIR) were chosen for further evaluation in the testing set after fitting to the full training set. In the cross-validation analysis, model fit was greatest for ANN, followed by PLS and MLR. Diagnostic strength after cross-validation was poorest for MLR and was similar for ANN and PLS. Models that used mTest + mFTIR variables performed marginally better than models that used only mFTIR or mTest variables. These results suggest that blood BHB prediction models that use mFTIR + mTest variables may be useful additions to existing HYK diagnostic and management programs.

Technical note: Validation of the BHBCheck blood β-hydroxybutyrate meter as a diagnostic tool for hyperketonemia in dairy cows

Accurate cow-side blood β-hydroxybutyrate (BHB) detection meters are valuable tools for rapid diagnosis of hyperketonemia. The main objective of this study was to compare the blood BHB measured in whole blood by the BHBCheck meter (PortaCheck, Moorestown, NJ) to a previously validated meter, Precision Xtra meter (Abbott Laboratories, Abbott Park, IL) and a colorimetric laboratory assay. Samples (n = 426) were collected from postpartum primiparous and multiparous Holstein cows (n = 79 cows) enrolled in 1 of 2 experiments (Exp) with different sampling schedules (Exp 1: n = 39 cows, 58 samples; Exp 2: n = 40 cows, 368 samples). In both Exp, whole-blood samples were collected from the coccygeal vessels after morning milking, before morning feeding. Blood samples were used immediately for BHB quantification via the BHBCheck meter and the Precision Xtra meter. Blood was also collected into evacuated tubes containing no additive (Exp 1) or potassium oxalate/sodium fluoride (Exp 2), which were centrifuged for serum or plasma separation and stored at -20°C for subsequent analysis. Laboratory quantification of BHB concentration was done by the BHB LiquiColor Assay (EKF Diagnostics-Stanbio, Boerne, TX; certified for serum and plasma). Data were analyzed by UNIVARIATE, CORR, FREQ, REG, and LOGISTIC procedures of SAS 9.4 (SAS Institute Inc., Cary, NC). Within this sample set, average parity was 3.3 lactations and DIM was 14 d. The proportion of samples classified as hyperketonemia (BHB ≥1.2 mmol/L) was 25, 28, and 31% as determined by the colorimetric assay, BHBCheck meter, and Precision Xtra meter, respectively. The correlation for BHBCheck meter BHB concentration compared with the colorimetric assay concentrations was r = 0.96, with a sensitivity of 91% and specificity of 93%. Correlation, sensitivity, and specificity of the Precision Xtra meter concentrations were 0.97, 98%, and 92%, respectively. Bland-Altman plots demonstrated minimal bias for both meters. Area under the receiver operator characteristic curve suggests adequate diagnostic accuracy of both meters. Overall, accuracy, sensitivity, and specificity of the BHBCheck meter was similar to the Precision Xtra meter and laboratory assay, indicating the BHBCheck meter is appropriate for use as a cow-side diagnostic test for hyperketonemia in dairy cows.

Technical note: Comparison of 4 electronic handheld meters for diagnosing hyperketonemia in dairy cows

The objective of this study was to evaluate 4 handheld ketone meters for use in on-farm β-hydroxybutyrate (BHB) monitoring of hyperketonemia in transition dairy cows. Blood samples taken from 250 Holstein cows between 262d pregnant and 15d in milk were evaluated on 4 different handheld ketone meters: Precision Xtra (Abbott Laboratories, Abbott Park, IL), TaiDoc (Pharmadoc, Lüdersdorf, Germany), Nova Max (Nova Biomedical, Billerica, MA), and Nova Vet (Nova Biomedical). Samples were screened using the Precision Xtra and tested on the remaining 3 m if the sample BHB concentration fell into predetermined ranges. A total of 89 samples were used for analysis. Performance of each meter was compared with the average of 2 plasma BHB concentrations both determined by a gold standard spectrophotometric Randox assay performed at 2 independent laboratories. Agreement between the 2 laboratories was very strong (Pearson correlation=0.998). All meters had Pearson correlation coefficients greater than 0.95. The Precision Xtra and TaiDoc meters were 100.0% sensitive and 73.5% specific at a BHB concentration cut point of 1.2mmol/L. The Nova Vet and Nova Max meters had sensitivities of 94.9 and 74.4% and specificities of 91.8 and 100.0%, respectively, at the same cut point. Agreement between the gold standard and the handheld meter was the best for the Nova Vet meter when evaluated using a Bland Altman graph with a mean BHB difference of 0.08mmol/L. Trends in bias were noted with the Precision Xtra and Nova Max meters resulting in increasing average discrepancy between the gold standard and the meter for both at higher plasma BHB concentrations and mean BHB differences of -0.34 and 0.26mmol/L, respectively. The coefficient of variation was <10% for the Precision Xtra, TaiDoc, and Nova Vet meters, and <15% for the Nova Max meter. We conclude that the TaiDoc and Nova Vet meters, similar to the already validated Precision Xtra meter, are acceptable for use in on-farm testing for monitoring and treatment of hyperketonemia.

Effects of sample temperature on the concentrations of glucose and β-OH butyrate measured by the Precision Xtra meter in plasma from periparturient dairy cattle

Early and accurate diagnosis of hypoglycemia and hyperketonemia is helpful in the diagnosis and treatment of ketosis in periparturient dairy cattle. The results of a preliminary study recently indicated that the glucose concentration [glue] and β-OH butyrate concentration [BHB] measured by the Precision Xtra meter was impacted by sample temperature when temperature &lt;89.6° (&lt; 32°C). The objective of this study was to fully characterize the effects of sample temperature on the accuracy of the Precision Xtra® for measuring [glue] and [BHB].

Definition of prepartum hyperketonemia in dairy goats

A prospective cohort study was conducted on 1,081 dairy goats from 10 commercial herds in Québec (Canada) to define prepartum hyperketonemia based on optimal blood β-hydroxybutyrate acid threshold values for the early prediction of pregnancy toxemia (PT) and mortality in late-gestation dairy goats. All pregnant goats had blood sampled weekly during the last 5wk of pregnancy. The blood was analyzed directly on the farm for β-hydroxybutyrate acid quantification using a Precision Xtra meter (Abbott Diabetes Care, Saint-Laurent, QC, Canada). Body condition scores on the lumbar region and sternum were noted. Each goat was classified as being at low (n=973) or high risk (n=108) of having PT by producers based on a standardized definition. The optimal threshold for predicting a PT diagnosis or mortality for each week before kidding was determined based on the highest sum of sensitivity and specificity. The association between hyperketonemia and subsequent PT was tested using a multivariable logistic regression model considering hyperketonemia at wk 4 prepartum, litter size, and body condition score at wk 4 prepartum as covariates, and herd and parturition cohort as random effects. The association between mortality and hyperketonemia was also tested using a logistic regression model accounting for the presence or absence of treatment during the last month of pregnancy. The hyperketonemia definition based on PT varied between ≥0.4 and ≥0.9mmol/L during the last 5wk prepartum. Goats affected by hyperketonemia at wk 4 prepartum and with a large litter size (≥3 fetuses) had 2.1 and 40.5 times the odds, respectively, of subsequent PT than other goats. Hyperketonemia definitions based on mortality varied between ≥0.6 and ≥1.4mmol/L during the last 4wk prepartum, and was ≥1.7mmol/L during the first week postpartum. Goats affected by hyperketonemia and treated by producers had 3.4 and 11.8 times the odds, respectively, of subsequent mortality than did other goats. These results showed that prepartum hyperketonemia could be defined in dairy goats using subsequent risks of PT or mortality during the last month of pregnancy.

Dry period and parturient predictors of early lactation hyperketonemia in dairy cattle

The purpose was to determine important dry and calving period predictors of (1) a cow developing hyperketonemia at any time between 3 and 16d in milk (DIM) and (2) a cow having hyperketonemia at her first β-hydroxybutyrate (BHBA) test after calving (between 3 and 5 DIM). Cows from 4 freestall dairy herds [2 in New York (NY) and 2 in Wisconsin] were enrolled at 266d carried calf. Precalving data included body condition score, locomotion score, and blood nonesterified fatty acids (NEFA) concentration; calving-associated data included previous days carried calf, calving ease, calf sex, twins, stillbirth, and parity. Cows were each tested 6 times for hyperketonemia from 3 to 16 DIM on Mondays, Wednesdays, and Fridays using the Precision Xtra meter (Abbott Laboratories, Abbott Park, IL). Hyperketonemia was defined as a blood BHBA concentration of ≥1.2mmol/L. Multivariable fixed-effects Poisson regression models were developed to predict the probability of a cow developing hyperketonemia between either 3 and 16 DIM or at her first BHBA test. As only the NY herds had precalving NEFA data, each prediction model was developed twice: once with data from all 4 herds (n=1,672) and once with data from only the NY herds (n=544). For the models with data from all 4 herds, increased body condition score group and an interaction between advanced parity and herd were important predictors of hyperketonemia development at any time from 3 to 16 DIM; calf sex (male), herd, and an advanced parity by increased body condition score group interaction were important predictors of hyperketonemia development between 3 and 5 DIM. The 4-herd models had a 64 and 78% predictive concordance for hyperketonemia between 3 and 16 DIM and at first BHBA test, respectively. For the models with data from the NY herds only, increased NEFA, calf sex (male), advanced parity, and herd were found to be important predictors of hyperketonemia development at any time from 3 to 16 DIM; increased NEFA, calf sex (male), decreased calving ease, stillbirth, and advanced parity were important predictors of having hyperketonemia at first BHBA test. The NY models had a 69 and 87% predictive concordance, respectively. These results may help identify at-risk animals and improve dry-cow management strategies before hyperketonemia develops.

Epidemiology of subclinical ketosis in early lactation dairy cattle

The purpose of this study was to describe the epidemiology of subclinical ketosis (SCK) in dairy cows in early lactation and determine the association of (1) days in milk (DIM) at onset of SCK, and (2) blood β-hydroxybutyrate (BHBA) concentration at onset of SCK with development of displaced abomasum (DA) and removal from herd in the first 30 DIM, conception to first service, days to conception within 150 DIM, and early lactation milk yield. Cows from 4 freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 DIM using the Precision Xtra meter (Abbott Laboratories, Abbott Park, IL). Subclinical ketosis was defined as a BHBA concentration of 1.2 to 2.9mmol/L. Mixed-effects multivariable Poisson regression was used to assess DA, removal from herd, and conception to first service. Semiparametric proportional hazards models were used to evaluate days to conception, and repeated-measures ANOVA was used to evaluate milk yield in the first 30 DIM. A total of 741 of 1,717 (43.2%) eligible cows had a least one BHBA test of 1.2 to 2.9mmol/L. Peak incidence of SCK occurred at 5 DIM, when 22.3% of cows had their first SCK-positive test. Peak prevalence of SCK occurred at 5 DIM, when 28.9% of cows had a SCK-positive test. Median time from first positive SCK test until BHBA test <1.2mmol/L was 5d. Cows first testing SCK positive from 3 to 5 DIM were 6.1 times more likely [95% confidence interval (CI) = 2.3 to 16.0] to develop a DA than cows first testing SCK positive at 6 DIM or later. Cows first testing SCK positive from 3 to 7 DIM were 4.5 times more likely (95% CI = 1.7 to 11.7) to be removed from the herd, were 0.7 times as likely (95% CI = 0.6 to 0.8) to conceive to first service, and produced 2.2kg less milk per day for the first 30 DIM than cows first testing positive at 8 DIM or later. Each 0.1mmol/L increase in BHBA at first SCK-positive test increased the risk of developing a DA by a factor of 1.1 (95% CI = 1.0 to 1.2), increased the risk of removal from herd by a factor of 1.4 (95% CI = 1.1 to 1.8), and was associated with a decrease in milk production by 0.5kg/d for the first 30DIM. These results show that time of onset and BHBA concentration of first SCK-positive test are important indicators of individual cow performance.

A field trial on the effect of propylene glycol on displaced abomasum, removal from herd, and reproduction in fresh cows diagnosed with subclinical ketosis

The purpose was to determine the effect of oral propylene glycol (PG) administration in fresh cows diagnosed with subclinical ketosis (SCK). Measured outcomes were development of displaced abomasum (DA) and removal from herd in the first 30 d in milk (DIM), conception to first service, and time to conception within 150 DIM. Cows from 4 freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 DIM on Mondays, Wednesdays, and Fridays using the Precision Xtra meter (Abbott Laboratories, Abbott Park, IL). Subclinical ketosis was defined as a blood β-hydroxybutyrate concentration of 1.2 to 2.9mmol/L. Cows with SCK were randomized to treatment group (oral PG) or untreated control group (no PG); treatment cows were orally drenched with 300mL of PG once daily from the day they tested 1.2 to 2.9mmol/L until the day they tested <1.2mmol/L. Mixed effects multivariable Poisson regression was used to assess the effect of PG on DA, removal from herd, and conception to first service; a semiparametric proportional hazards model was used to evaluate the days-to-conception outcome. A total of 741 of 1,717 (43.2%) eligible enrolled cows had at least 1 β-hydroxybutyrate test of 1.2 to 2.9mmol/L. Of these, 372 were assigned to the PG treatment group and 369 to the control group. Thirty-nine cows (5.3%) developed a DA after testing positive for SCK and 30 cows (4.0%) died or were sold within the first 30 DIM. Based on risk ratios, control cows were 1.6 times more likely [95% confidence interval (CI)=1.3 to 2.0] to develop a DA and 2.1 times more likely (95% CI=1.2 to 3.6) to die or be sold than cows treated with PG. In addition, PG-treated cows were 1.3 times more likely (risk ratio 95% CI=1.1 to 1.5) to conceive at first insemination than control cows in 3 of the herds. No difference was observed in days to conception within 150 DIM between treatment groups (hazard ratio for PG cows=1.1, 95% CI=0.8 to 1.4), with a median time to conception of 100 d (95% CI=93 to 111) and 104 d (95% CI=95 to 114) for PG-treated and control cows, respectively. These results show that intensive detection of SCK, followed by treatment of positive cows with oral PG decreased the risk of developing a DA or leaving the herd within the first 30 DIM and increased the risk of conception to first service.

Field Trial on the Effect of Propylene Glycol on Milk Yield and Resolution of Ketosis in Fresh Cows Diagnosed with Subclinical Ketosis

Subclinical ketosis (SCK), a metabolic disorder that can affect more than half the cows in a herd, occurs in early lactation when dairy cows are unable to adapt to the changing energy requirements necessary for substantial milk production. While propylene glycol (PG) has long been used to treat clinical ketosis, its effect on SCK has not been studied, due in part to the monitoring necessary to diagnose the disorder. The recent identification and validation of the Precision Xtra meter (Abbott Laboratories, Abbott Park, IL), a rapid, accurate, and relatively inexpensive cow-side test for SCK, eases many of the previous difficulties associated with intensive monitoring programs. The purpose of this study was to determine the effect of oral PG administration on resolution of SCK, prevention of clinical ketosis, and milk yield in cows diagnosed with SCK.

Bedside Monitoring of Blood β-Hydroxybutyrate Levels in the Management of Diabetic Ketoacidosis in Children

Diabetic ketoacidosis (DKA) affects many children with type 1 diabetes. Insulin treatment of DKA is traditionally guided by changes in the blood glucose levels and blood gases, whereas beta-hydroxybutyrate (beta-OHB)--the main ketoacid causing acidosis--is rarely measured. The purpose of this study was to evaluate if bedside monitoring of blood beta-OHB levels can simplify management of DKA through elimination of superfluous laboratory monitoring. Our emergency department treated 68 children with DKA using a standard protocol with monitoring of venous pH, partial pressure of CO(2) (pCO(2)), bicarbonate, glucose, blood urea nitrogen, and electrolytes (two to 10 time points per patient). Venous beta-OHB levels were measured using the Precision Xtra meter (MediSense/Abbott Diabetes Care, Abbott Park, IL) and, on duplicate batched serum samples, using a reference laboratory method (Cobas Mira Plus; Roche Diagnostics, Indianapolis, IN). Correlations between bedside meter beta-OHB and other parameters were evaluated in a series of general linear models with a time series covariance structure fit using spatial power law. The bedside meter beta-OHB levels were significantly correlated with pH (r = -0.63; P <0.0001), bicarbonate (r = -0.74; P <0.0001), and pCO(2) (r = -0.55; P <0.0001) at all points of measurement during the treatment (unadjusted Pearson correlations). The pH, bicarbonate, and pCO(2) were entered into separate time series analysis models with treatment duration as a measure of time. The results confirmed that bedside levels of beta-OHB correlated very closely with time-dependent levels of venous pH, bicarbonate, and pCO(2). Good agreement between the two methods of beta-OHB measurement (r = 0.92; P <0.0001) was confirmed using the Bland-Altman plot analysis. The Precision Xtra accurately measures blood beta-OHB levels, particularly at lower levels. While the initial measurement of pH and/or bicarbonates is warranted, real-time beta-OHB levels may replace repeat laboratory measurement of these parameters in the management of DKA. Future studies should evaluate safety and cost-effectiveness of such simplified DKA treatment protocol.

Point‐of‐care Test Identifies Diabetic Ketoacidosis at Triage

Diabetic ketoacidosis (DKA) is a common, life-threatening complication of diabetes. The diagnosis of DKA relies on signs and symptoms, plus laboratory findings of blood glucose (BG) of > 250 mg/dL, an anion gap (AG) of > or = 15 mmol/L, and carbon dioxide (CO2) of < or = 18 mmol/L when other causes of acidosis are excluded. To compare the results of a point-of-care test for the ketone beta-hydroxybutyrate (beta-OHB) with standard measures for accuracy in predicting DKA. After providing informed consent, 160 patients who presented with BG of > 250 mg/dL underwent testing for beta-OHB with the Precision Xtra meter (Abbott Laboratories, North Chicago, IL) at triage in a large urban hospital emergency department. The diagnosis of DKA was made by clinicians by using standard clinical criteria without knowledge of the beta-OHB test. A diagnosis of DKA was made in 57 of 160 subjects. The beta-OHB values correlated strongly with AG (r = 0.66, p < 0.001) and with CO2 (r = -0.69, p < 0.001), as well as with glucose (r = 0.31, p < 0.001). Cross-classification of DKA vs. beta-OHB yielded sensitivity of 98% (95% CI = 91% to 100%), specificity of 85% (95% CI = 78% to 91%), with a positive likelihood ratio of 6.7 (95% CI = 4.22 to 10.78), and negative likelihood ratio of 0.021 (95% CI = 0.003 to 0.144) at the manufacturer-suggested beta-OHB level of 1.5. The point-of-care test for beta-OHB was as sensitive as more established indicators of DKA. It is more useful than glucose alone for the diagnosis of DKA and offers immediate diagnosis of patients at triage.

New Point-of-Care test identifies diabetic ketoacidosis in triage

Study objectives: Diabetic ketoacidosis (DKA) is a common, life-threatening complication of diabetes. Immediate treatment is necessary to avoid rapid clinical deterioration and the need for higher levels of care. Patients presenting with elevated blood glucose levels have become so common in the emergency department (ED) that clinical suspicion of DKA may not be sufficient to discriminate the true metabolic emergency from less serious hyperglycemic conditions. Treatment delays are common because of nonclassic presentation and the need for laboratory test results to make the diagnosis of DKA. The diagnosis of DKA relies on signs and symptoms plus laboratory findings of blood glucose level greater than 250 mg/dL, an anion gap greater than 15 mmol/L, and carbon dioxide (CO 2 ) level less than 20 mmol/L, excluding other, less common causes of anion gap acidosis. We compared the results of a point-of-care test for the ketone β-hydroxybutyrate (β-OHB) with standard measures for accuracy in predicting the diagnosis of DKA. Methods: After providing informed consent, 101 patients who presented with blood glucose greater than 250 mg/dL or clinical signs of DKA underwent testing for β-OHB at Barnes-Jewish Hospital ED triage using the Precision Xtra meter (Abbott Laboratories, North Chicago, IL). Additional diagnostic evaluation followed clinical guidelines but included a measured glucose and electrolyte panel in all cases. The diagnosis of DKA was made by experienced clinicians using standard clinical criteria. Logistic regression was used to identify clinical indicators of DKA, and χ 2 analysis was used to evaluate binary decision rules. Results: Demographics of the study group include mean age 46.4±16.3 years (range 20 to 83 years); 45.1% female patients; 83.3% black patients, and 16.6% white patients (including 1 Asian and 1 Hispanic patient). The mean blood glucose level was 511±265 mg/dL (range 76 to 1,340 mg/dL); creatinine level 1.76±1.56 mg/dL (range 0.5 to 9.8 mg/dL); and anion gap level 15.7±8.7 mmol/L. A clinical diagnosis of DKA was made in 37 patients. Values of β-OHB ranged between 0 and 6 mmol/L (mean 1.86±2.12 mmol/L). The β-OHB values correlated with anion gap (0.614 mmol/L, P 2 (–0.603 mmol/L, P P 1.5 mmol/L, patient at high risk for DKA; β-OHB from 0.6 to 1.5 mmol/L with blood glucose >250 mg/dL, patient at intermediate risk of DKA). This decision rule was significantly related to DKA status (χ 2 =38.176, P 2 ), implied a complex decision rule with sensitivity of .949 and specificity of .919. Additional logistic regression analysis, using only information available at triage (β-OHB and BG), showed that blood glucose level added little to classification of patients. Therefore, an alternate decision rule using only β-OHB was tested, in which β-OHB greater than 1.1 mmol/L was used as an indicator of DKA status. This decision rule left diagnostic sensitivity at .949, reduced specificity to .806, and provided an overall correct classification rate of .861 (χ 2 =54.66, P Conclusion: The point-of-care test for β-OHB was as sensitive as more established clinical indicators of DKA and offers immediate preliminary diagnosis of patients so that timely, critical interventions can be initiated.