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* Context.--Convenience, avoidance of doctor's appointments, curiosity, and the desire to take control of one's health are driving interest toward direct-to-consumer (DTC) testing. DTC is laboratory testing that is initiated by the consumer without a physician order. The results are reported back directly to the consumer. DTC testing is an exciting addition to the traditional healthcare model for consumers who want knowledge of their health status and disease risk, ancestry, and their body's expected response to certain medications based on their genotype. Objectives.--To discuss the perceived and potential benefits and risks involved in DTC testing. Data Sources.--Recent published literature on DTC testing. Conclusions.--The benefits of DTC testing are enticing and are driving the DTC testing market. Consumers must weigh the perceived benefits with the potential risks, including privacy concerns, the possibility of receiving confusing health information, and/or information that could generate unexpected emotions, misdiagnosis, and over-testing., The traditional model of laboratory testing in healthcare starts with the patient recognizing the need to see a physician (Figure 1). In nonemergent cases, the patient must make an appointment [...]

Point-of-care (POC) urine drug screening (UDS) assays provide immediate information for patient management. However, POC UDS assays can produce false-positive results, which may not be recognized until confirmatory testing is completed several days later. To minimize the potential for patient harm, it is critical to identify sources of interference. Here, we applied an approach based on statistical analysis of electronic health record (EHR) data to identify medications that may cause false positives on POC UDS assays. From our institution's EHR data, we extracted 120,670 POC UDS and confirmation results, covering 12 classes of target drugs, along with each individual's prior medication exposures. Our approach is based on the idea that exposure to an interfering medication will increase the odds of a false-positive UDS result. For a given assay–medication pair, we quantified the association between medication exposures and UDS results as an odds ratio from logistic regression. We evaluated interference experimentally by spiking compounds into drug-free urine and testing the spiked samples on the POC device. Our dataset included 446 false-positive UDS results (presumptive positive screen followed by negative confirmation). We quantified the odds ratio of false positives for 528 assay–medication pairs. Of the six assay–medication pairs we evaluated experimentally, two showed interference capable of producing a presumptive positive: labetalol on the 3,4-methylenedioxymethamphetamine (MDMA) assay (at 200 μg/mL) and ranitidine on the methamphetamine assay (at 50 μg/mL). Ranitidine also produced a presumptive positive for opiates at 1,600 μg/mL and for propoxyphene at 800 μg/mL. These findings highlight the generalizability and the limits of our approach to use EHR data to identify medications that interfere with clinical immunoassays. [ABSTRACT FROM AUTHOR]

Urine drug screening (UDS) assays can rapidly and sensitively detect drugs of abuse but can also produce spurious results due to interfering substances. We previously developed an approach to identify interfering medications using electronic health record (EHR) data, but the approach was limited to UDS assays for which presumptive positives were confirmed using more specific methods. Here we adapted the approach to search for medications that cause false positives on UDS assays lacking confirmation data. From our institution's EHR data, we used our previous dataset of 698,651 UDS and confirmation results. We also collected 211,108 UDS results for acetaminophen, ethanol and salicylates. Both datasets included individuals' prior medication exposures. We hypothesized that the odds of a presumptive positive would increase following exposure to an interfering medication independently of exposure to the assay's target drug(s). For a given assay–medication pair, we quantified potential interference as an odds ratio from logistic regression. We evaluated interference of selected compounds in spiking experiments. Compared to the approach requiring confirmation data, our adapted approach showed only modestly diminished ability to detect interfering medications. Applying our approach to the new data, we discovered and validated multiple compounds that can cause presumptive positives on the UDS assay for acetaminophen. Our approach can reveal interfering medications using EHR data from institutions at which UDS results are not routinely confirmed. [ABSTRACT FROM AUTHOR]

Objectives: Despite extensive research on procalcitonin (PCT)-guided therapy in lower respiratory tract infections, the association between PCT and bacterial pneumonia remains unclear.Methods: We evaluated retrospectively the performance of PCT in patients presenting with lower respiratory tract infection symptoms and grouped by seven diagnoses. All patients had microbial testing, chest imaging, and CBC counts within 1 day of PCT testing.Results: Median PCT level in patients diagnosed with bacterial pneumonia was significantly higher than in patients diagnosed with other sources of infections or those not diagnosed with infections. Median PCT levels were not different among patients grouped by type or quantity of pathogen detected. They were significantly higher in patients with higher pathogenicity scores for isolated bacteria, those with abnormal WBC count, and those with chest imaging consistent with bacterial pneumonia. A diagnostic workup that included imaging, WBC count, and Gram stain had an area under the receiver operating characteristic curve of 0.748, and the addition of PCT increased it to 0.778.Conclusions: PCT was higher in patients diagnosed with bacterial pneumonia. Less clear is its diagnostic ability to detect bacterial pneumonia over and above imaging and laboratory data routinely available to clinicians. [ABSTRACT FROM AUTHOR]

Background: The anion gap is primarily used in the diagnosis of acid-base disorders. We conducted a study to determine the anion gap reference interval in our patient population, investigated the workup of abnormal vs normal anion gaps, and examined the anion gap variation upon repeated testing. Methods: A retrospective review was performed on 17137 adult and pediatric patients who presented to Yale- New Haven Hospital outpatient clinics, emergency department, or intensive care units between 2012 and 2017. Results: We derived a new reference interval of 7 to 18 mmol/L with a median of 13 mmol/L in healthy adults with no significant differences owing to partitioning by sex or age. Based on the new reference interval, 5%, 23%, and 18% of healthy, emergency department, and intensive care unit adult patients, respectively, were misclassified as having high values with the previous interval of 6 to 16 mmol/L. However, there were no significant differences in the number of tests ordered in patients with anion gaps above and below the upper limit of the previous reference interval. The majority of increased anion gaps that were repeated normalized by 12 h. In a subgroup of healthy adult patients with annual testing, the median percent change in each patient's anion gap from 2015 to 2016 was approximately 13%. Conclusions: The anion gap should be used with an appropriate reference interval to avoid misclassification. There may be a moderate degree of individuality that argues for comparing the anion gap with its baseline value in the same patient pending further studies that formally derive its biological variation. [ABSTRACT FROM AUTHOR]

Rat perivascular adipose tissue ( PVAT) stores, takes up, and releases norepinephrine ( NE; Ayala-Lopez et al. (2014) Pharmacol Res Perspect 2, e00041). We hypothesized that 3T3-L1 adipocytes would exhibit similar behaviors and, thus, could serve as a model for PVAT adipocytes. However, basal levels of NE were not detected in 3T3-L1 adipocytes. While incubation of 3T3-L1 adipocytes with exogenous NE increased their cellular NE content, the mRNA expression of several NE transporters [e.g., norepinephrine transporter ( NET)] were not detected in these cells. Similarly, we observed expression of the vesicular monoamine transporter 1 ( VMAT1) in 3T3-L1 adipocytes by qRT- PCR and immunostaining, but stimulation of the cells with tyramine (100 μ m) did not cause a significant release of NE. These studies support that 3T3-L1 adipocytes are not an adequate model of perivascular adipocytes for studying NE handling. [ABSTRACT FROM AUTHOR]

Perivascular Tissue (PVAT) is a recent focus of studies for its regulation of blood vessel tone. Contraction to norepinephrine (NE) is reduced by PVAT through mechanisms not entirely clear. Loss of this anti-contractile function of PVAT occurs in obesity-related hypertension. We hypothesized that PVAT can remove NE from the blood vessel environment through transporters and reduce NE induced contraction in health. RT-PCR of mesenteric PVAT was positive for norepinephrine transporter (NET; Ct=33.2±1.4) and serotonin transporter (SERT; Ct=31.9±0.9) relative to beta-2-microglobulin. To study NE uptake in the healthy state, mesenteric and aortic PVAT from the male Sprague Dawley rat was incubated with 10 μM NE after pre-incubation with an inhibitor of transport (10 μM desipramine to inhibit NET and SERT, 100 μM corticosterone to inhibit organic cation transporter 3) or vehicle and quantified by HPLC for NE. Desipramine plus corticosterone inhibited NE uptake in mesenteric PVAT (figure) but desipramine (410.5±80.8 ng/g vs. 414.4±67.0 ng/g NE only; n=8) or corticosterone (225.0±26.1 ng/g vs. 319.2±35.9 ng/g NE only; n=5) alone did not, indicating a robust uptake capacity. In aortic PVAT, NE uptake was not inhibited by desipramine plus corticosterone (figure), desipramine (1763.5±460.8 ng/g vs. 1702.7±298.4 ng/g NE only; n=6), or corticosterone (1085.8±205.3 ng/g vs. 2245.8±506.8 ng/g NE only; n=4). Protein staining revealed bands positive for NET in mesenteric PVAT by Western blot. Taken together, we found that PVAT is a reservoir of NE that can remove NE from the blood vessel environment, an important finding to understand vasculature-PVAT interactions in health and disease. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system is undeniably important to blood pressure control. With the discovery of an adrenergic system in perivascular adipose tissue (PVAT) around both the aorta and mesenteric artery, we hypothesized that this system could promote contraction of the vessel around which it lives. Using isolated tissue bath and HPLC techniques, we examined the mechanism of contraction to the indirect sympathomimetic tyramine. Tyramine (100 nM - 1 mM) caused a concentration dependent contraction that was dependent on the presence of PVAT in normal rat thoracic aorta (figure, maximum tyramine contraction as a % initial phenylephrine contraction + PVAT = 47+/2, -PVAT = 11+/2), superior mesenteric artery (+ PVAT =64+/15 , -PVAT = 6+/2), and mesenteric resistance artery (+ PVAT =83+/17 , -PVAT = 3+/1). Tyramine stimulated release of NE, dopamine (DA) and serotonin (5-HT) from PVAT isolated from the superior mesenteric artery. In the thoracic aorta, tyramine induced contraction (Max = 61+/-13%) was rightward shifted and maximum contraction inhibited by the norepinephrine transporter inhibitor nisoxetine (1 uM =25+/-9%), vesicular monoamine transporter tetrabenazine (10 uM; 43+/-10%) and abolished by the alpha adrenergic receptor antagonist prazosin (100 nM). Removal of the celiac ganglion as a neuronal source of NE reduced PVAT content by ~38% and reduced maximum tyramine contraction by only ~22%. These data suggest that PVAT components that are independent of the formal SNS can release NE in a tyramine-sensitive manner. One of these components may be the adipocyte itself, a novel finding that has implications for control of vascular tone and local metabolic control. [ABSTRACT FROM AUTHOR]