Early Point-of-Care Testing at Triage Reduces Care Time in Stable Adult Emergency Department Patients.

BACKGROUND: Core laboratory testing may increase length of stay and delay care. OBJECTIVES: We compared length of emergency department (ED) care in patients receiving point-of-care testing (POCT) at triage vs. traditional core laboratory testing. METHODS: We conducted a prospective, case-controlled trial of adult patients with prespecified conditions requiring laboratory testing and had POCT performed by a nurse after triage for: a basic metabolic panel, troponin I, lactate, INR (i-STAT System), urinalysis (Beckman Coulter Icon), or urine pregnancy test. Study patients were matched with controls based on clinical condition, gender, age, and time to be seen. Groups were compared with Wilcoxon rank-sum or Fisher's exact tests. RESULTS: We matched 52 POCT study patients with 52 controls. Groups were similar in age, gender, clinical condition, time to be seen by a physician (3.3 h, 95% confidence interval [CI] 2.2-4.4, vs. 3.1 h, 95% CI 2.2-4.5 h, in POCT and control patients, respectively; p = 0.84), use of imaging, and disposition. Of 52 study patients, 3 (5.8%, 95% CI 2.0-15.9) were immediately transferred to the critical care area to be urgently seen by an emergency physician. POCT patients had a significantly shorter median (interquartile range [IQR]) ED care time than matched controls (7.6, 95% CI 5.1-9.5 vs. 8.5, 6.2-11.3 h, respectively; p = 0.015). Median [IQR] ED length of stay was similar in study patients and controls (9.6, 95% CI 7.9-14.5 vs. 12.5, 8.2-21.2 h, respectively; p = 0.15). CONCLUSIONS: Among stable adult patients presenting to the ED with one of the prespecified conditions, early POCT at triage, compared with traditional core laboratory testing after evaluation by an ED provider, reduced ED care time by approximately 1 h.

Diagnostic characteristics of a clinical screening tool in combination with measuring bedside lactate level in emergency department patients with suspected sepsis.

BACKGROUND: Early identification of sepsis and initiation of aggressive treatment saves lives. However, the diagnosis of sepsis may be delayed in patients without overt deterioration. Clinical screening tools and lactate levels may help identify sepsis patients at risk for adverse outcomes. OBJECTIVES: The objective was to determine the diagnostic characteristics of a clinical screening tool in combination with measuring early bedside point-of-care (POC) lactate levels in emergency department (ED) patients with suspected sepsis. METHODS: This was a prospective, observational study set at a suburban academic ED with an annual census of 90,000. A convenience sample of adult ED patients with suspected infection were screened with a sepsis screening tool for the presence of at least one of the following: temperature greater than 38°C or less than 36°C, heart rate greater than 90 beats/min, respiratory rate greater than 20 breaths/min, or altered mental status. Patients meeting criteria had bedside POC lactate testing following triage, which was immediately reported to the treating physician if ≥2.0 mmol/L. Demographic and clinical information, including lactate levels, ED interventions, and final diagnosis, were recorded. Outcomes included presence or absence of sepsis using the American College of Chest Physicians/Society of Critical Care Medicine consensus conference definitions and intensive care unit (ICU) admissions, use of vasopressors, and mortality. Diagnostic test characteristics were calculated using 2-by-2 tables with their 95% confidence intervals (CIs). The association between bedside lactate and ICU admissions, use of vasopressors, and mortality was determined using logistic regression. RESULTS: A total of 258 patients were screened for sepsis. Their mean (± standard deviation [SD]) age was 64 (±19) years; 46% were female, and 82% were white. Lactate levels were 2.0 mmol/L or greater in 80 (31%) patients. Patients were confirmed to meet sepsis criteria in 208 patients (81%). The diagnostic characteristics for sepsis of the combined clinical screening tool and bedside lactates were sensitivity 34% (95% CI = 28% to 41%), specificity 82% (95% CI = 69% to 90%), positive predictive value 89% (95% CI = 80% to 94%), and negative predictive value 23% (95% CI = 17% to 30%). Bedside lactate levels were associated with sepsis severity (p < 0.001), ICU admission (odds ratio [OR] = 2.01; 95% CI = 1.53 to 2.63), and need for vasopressors (OR = 1.54; 95% CI = 1.13 to 2.12). CONCLUSIONS: Use of a clinical screening tool in combination with early bedside POC lactates has moderate to good specificity but low sensitivity in adult ED patients with suspected sepsis. Elevated bedside lactate levels are associated with poor outcomes.

Bone-targeted Src kinase inhibitors: novel pyrrolo- and pyrazolopyrimidine analogues.

Src tyrosine kinase is a therapeutic target for bone diseases that has been validated by gene knockout studies. Furthermore, in vitro cellular studies implicate that Src has a positive regulatory role in osteoclasts and a negative regulatory role in osteoblasts. The potential use of Src inhibitors for osteoporosis therapy has been previously shown by novel bone-targeted ligands of the Src SH2 (e.g., AP22408) and non-bone-targeted, ATP-based inhibitors of Src kinase. Significant to this study, compounds 2-12 exemplify novel analogues of known pyrrolopyrimidine and pyrazolopyrimidine template-based Src kinase inhibitors that incorporate bone-targeting group modifications designed to provide tissue (bone) selectivity and diminished side effects. Accordingly, we report here the structure-based design, synthetic chemistry and biological testing of these compounds and proof-of-concept studies thereof.