Kimberly W. Hart

Testing the Prognostic Accuracy of the Updated Pediatric Sepsis Biomarker Risk Model

Background We previously derived and validated a risk model to estimate mortality probability in children with septic shock (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl). PERSEVERE uses five biomarkers and age to estimate mortality probability. After the initial derivation and validation of PERSEVERE, we combined the derivation and validation cohorts (n = 355) and updated PERSEVERE. An important step in the development of updated risk models is to test their accuracy using an independent test cohort. Objective To test the prognostic accuracy of the updated version PERSEVERE in an independent test cohort. Methods Study subjects were recruited from multiple pediatric intensive care units in the United States. Biomarkers were measured in 182 pediatric subjects with septic shock using serum samples obtained during the first 24 hours of presentation. The accuracy of PERSEVERE 28-day mortality risk estimate was tested using diagnostic test statistics, and the net reclassification improvement (NRI) was used to test whether PERSEVERE adds information to a physiology-based scoring system. Results Mortality in the test cohort was 13.2%. Using a risk cut-off of 2.5%, the sensitivity of PERSEVERE for mortality was 83% (95% CI 62–95), specificity was 75% (68–82), positive predictive value was 34% (22–47), and negative predictive value was 97% (91–99). The area under the receiver operating characteristic curve was 0.81 (0.70–0.92). The false positive subjects had a greater degree of organ failure burden and longer intensive care unit length of stay, compared to the true negative subjects. When adding PERSEVERE to a physiology-based scoring system, the net reclassification improvement was 0.91 (0.47–1.35; p<0.001). Conclusions The updated version of PERSEVERE estimates mortality probability reliably in a heterogeneous test cohort of children with septic shock and provides information over and above a physiology-based scoring system.

The incidence of seizures in patients undergoing therapeutic hypothermia after resuscitation from cardiac arrest

STUDY OBJECTIVE Non-convulsive seizures/status epilepticus occur in approximately 20% of comatose, non-cardiac arrest intensive care unit (ICU) patients, and are associated with increased mortality. The prevalence and clinical significance of seizures in comatose survivors of cardiac arrest undergoing therapeutic hypothermia is not well described. METHODS At this urban level I trauma center, every patient undergoing therapeutic hypothermia is monitored with continuous video encephalography (cvEEG). We abstracted medical records for all cardiac arrest patients treated with therapeutic hypothermia during 2010. Clinical data were extracted in duplicate. cvEEGs were independently reviewed for seizures by two board-certified epileptologists. RESULTS There were 33 patients treated with therapeutic hypothermia after cardiac arrest in 2010 who met inclusion criteria for this study. Median age was 58 (range 28-86 years), 63% were white, 55% were male, and 9% had a history of seizures or epilepsy. During cooling, seizures occurred in 5/33 patients (15%, 95%CI 6%-33%). 11/33 patients (33%, 95% CI 19%-52%) had seizures at some time during hospitalization. 13/33 (39%) survived to discharge and of these, 7/13 (54%) survived to 30 days. 9/11 patients with seizures died during hospitalization, compared with 11/22 patients without seizures (82% vs. 50%; difference 32%, CI 951%-63%). No patient with seizures was alive at 30 days. CONCLUSIONS Seizures are common in comatose patients treated with therapeutic hypothermia after cardiac arrest. All patients with seizures were deceased within 30 days of discharge. Routine use of EEG monitoring could assist in early detection of seizures in this patient population, providing an opportunity for intervention to potentially improve outcomes.

Randomized comparison of universal and targeted HIV screening in the emergency department.

Objective:Universal HIV screening is recommended but challenging to implement. Selectively targeting those at risk is thought to miss cases, but previous studies are limited by narrow risk criteria, incomplete implementation, and absence of direct comparisons. We hypothesized that targeted HIV screening, when fully implemented and using maximally broad risk criteria, could detect nearly as many cases as universal screening with many fewer tests. Methods:This single-center cluster-randomized trial compared universal and targeted patient selection for HIV screening in a lower prevalence urban emergency department. Patients were excluded for age (<18 and >64 years), known HIV infection, or previous approach for HIV testing that day. Targeted screening was offered for any risk indicator identified from charts, staff referral, or self-disclosure. Universal screening was offered regardless of risk. Baseline seroprevalence was estimated from consecutive deidentified blood samples. Results:There were 9572 eligible visits during which the patient was approached. For universal screening, 40.8% (1915/4692) consented with 6 being newly diagnosed [0.31%, 95% confidence interval (CI): 0.13% to 0.65%]. For targeted screening, 37% (1813/4880) had no testing indication. Of the 3067 remaining, 47.4% (1454) consented with 3 being newly diagnosed (0.22%, 95% CI: 0.06% to 0.55%). Estimated seroprevalence was 0.36% (95% CI: 0.16% to 0.70%). Targeted screening had a higher proportion consenting (47.4% vs. 40.8%, P < 0.002), but a lower proportion of ED encounters with testing (29.7% vs. 40.7%, P < 0.002). Conclusions:Targeted screening, even when fully implemented with maximally permissive selection, offered no important increase in positivity rate or decrease in tests performed. Universal screening diagnosed more cases, because more were tested, despite a modestly lower consent rate.

Galectin 3 complements BNP in risk stratification in acute heart failure

Background: Galectin 3 (G3) is a mediator of fibrosis and remodeling in heart failure. Methods: Patients diagnosed with and treated for Acute Heart Failure Syndromes were prospectively enrolled in the Decision Making in Acute Decompensated Heart Failure multicenter trial. Results: Patients with a higher G3 had a history of renal disease, a lower heart rate and acute kidney injury. They also tended to have a history of HF and 30-day adverse events compared with B-type natriuretic peptide. Conclusion: In Acute Heart Failure Syndromes, G3 levels do not provide prognostic value, but when used complementary to B-type natriuretic peptide, G3 is associated with renal dysfunction and may predict 30-day events.

Elevated urinary neutrophil gelatinase-associated lipocalcin after acute heart failure treatment is associated with worsening renal function and adverse events

Reliable detectors of worsening renal function (WRF) in Emergency Department (ED) patients with acute heart failure (AHF) are limited. We hypothesized that initial urinary neutrophil gelatinase‐associated lipocalcin (NGAL) levels, and changes in urinary NGAL levels after initial ED AHF therapy, would be associated with WRF and adverse events.

Interleukin 27 as a sepsis diagnostic biomarker in critically ill adults.

ABSTRACT Purpose: We previously identified interleukin 27 (IL-27) as a sepsis diagnostic biomarker in critically ill children. The current study tested the performance of IL-27 alone and in combination with procalcitonin (PCT) for diagnosing sepsis in critically ill adults. Methods: Serum samples were made available from a prior prospective study of sepsis biomarkers in critically ill adults. The primary analysis used receiver operating characteristic curves to evaluate the performance of IL-27 and PCT. Secondary analysis explored IL-27 performance in subgroups of patients with sepsis secondary to lung and nonlung sources of infection. The net reclassification improvement was used to estimate the incremental predictive ability of IL-27 compared with PCT alone. Classification and regression tree analysis was used to generate an IL-27- and PCT-based decision tree. Results: There were 145 patients with sepsis and 125 without sepsis. The receiver operating characteristic curve for IL-27 was inferior (area under the curve [AUC], 0.68; 95% confidence interval [CI], 0.62–0.75) to that of PCT (AUC, 0.84; 95% CI, 0.79–0.89). Similar findings were observed when comparing patients with a lung source of infection and those without sepsis. For sepsis patients with a nonlung source of infection, adding IL-27 to PCT improved discrimination (net reclassification improvement = 0.685; P < 0.001). The AUC for the classification and regression tree–derived decision tree was 0.92 (95% CI, 0.88–0.96) and was significantly greater than that of PCT alone. Conclusions: When used in combination with PCT, IL-27 may improve classification of critically ill adults with sepsis secondary to a nonlung source of infection.

Intermittent androgen deprivation for patients with recurrent/metastatic prostate cancer.

This study was designed to assess the duration of response to intermittent androgen deprivation therapy (IAD) in patients with recurrent and/or metastatic prostate cancer. Between January 1993 and March 2000, 74 patients with recurrent and/or metastatic prostate cancer had IAD with either luteinizing hormone-releasing hormone agonist (LHRH) or an LHRH with an oral antiandrogen. Forty-one patients were treated for an increasing prostate-specific antigen (PSA) level after primary local treatment. Of the remaining 33 patients, 17 patients were treated for metastases (9 for bone metastases, 8 for lymph nodes metastases, and 16 for local recurrence). Patients who had undergone IAD completed between 1 and 6 cycles. A cycle was defined as the period during which the patient was actively taking the hormone medication. Seventy-four patients completed the first cycle, 49 completed the second cycle, and 23 completed the third cycle. The pattern of PSA changes with each cycle, the length of each cycle, and the time interval between successive cycles were studied. The time to progression (defined as an increasing PSA level on two consecutive measurements or radiologic evidence of progression of disease while the patient was on androgen deprivation) was also studied. The median PSA before the IAD was 11.4 ng/mL (range 0.12–378). The median PSA nadir at the end of each cycle increased progressively (0.1 ng/mL after the first cycle to 3.3 ng/mL after the fifth cycle). The time interval between the cycles progressively decreased from 9.5 months between the first and second cycles to 6 months between the third and fourth cycles. The 4-year actuarial androgen-independent free survival was 71%. For the subgroups of patients treated for biochemical failure, locoregional recurrence, and bone metastases, the 4-year actuarial progression-free survival rates were 80%, 67%, and 45% respectively (P = 0.018). The median time of 18 months to progression in patients with bone metastases is similar to that reported with continuous hormonal therapy. In patients with biochemical failure, the median time to progression (more than 5 years) suggests that the IAD approach may be a viable option for this group of patients.

Ground Emergency Medical Services Requests for Helicopter Transfer of ST-segment Elevation Myocardial Infarction Patients Decrease Medical Contact to Balloon Times in Rural and Suburban Settings

OBJECTIVES   ST-segment elevation myocardial infarction (STEMI) care is time-dependent. Many STEMI patients require interhospital helicopter transfer for percutaneous coronary intervention (PCI) if ground emergency medical services (EMS) initially transport the patient to a non-PCI center. This investigation models potential time savings of ground EMS requests for helicopter EMS (HEMS) transport of a STEMI patient directly to a PCI center, rather than usual transport to a local hospital with subsequent transfer. METHODS   Data from a multicenter retrospective chart review of STEMI patients transferred for primary PCI by a single HEMS agency over 12 months were used to model medical contact to balloon times (MCTB) for two scenarios: a direct-to-scene HEMS response and hospital rendezvous after ground EMS initiation of transfer. RESULTS   Actual MCTB median time for 36 hospital-initiated transfers was 160 minutes (range = 116 to 321 minutes). Scene response MCTB median time was estimated as 112 minutes (range = 69 to 187 minutes). The difference in medians was 48 minutes (95% confidence interval [CI] = 33 to 62 minutes). Hospital rendezvous MCTB median time was estimated as 113 minutes (range = 74 to 187 minutes). The difference in medians was 47 minutes (95% CI = 32 to 62 minutes). No patient had an actual MCTB time of less than 90 minutes; in the scene response and hospital rendezvous scenarios, 2 of 36 (6%) and 3 of 36 (8%), respectively, would have had MCTB times under 90 minutes. CONCLUSIONS   In this setting, ground EMS initiation of HEMS transfers for STEMI patients has the potential to reduce MCTB time, but most patients will still not achieve MCTB time of less than 90 minutes.

Transient and Sustained Changes in Operational Performance, Patient Evaluation, and Medication Administration During Electronic Health Record Implementation in the Emergency Department

STUDY OBJECTIVE Little is known about the transient and sustained operational effects of electronic health records on emergency department (ED) performance. We quantify how the implementation of a comprehensive electronic health record was associated with metrics of operational performance, test ordering, and medication administration at a single-center ED. METHODS We performed a longitudinal analysis of electronic data from a single, suburban, academic ED during 28 weeks between May 2011 and November 2011. We assessed length of stay, use of diagnostic testing, medication administration, radiologic imaging, and patient satisfaction during a 4-week baseline measurement period and then tracked changes in these variables during the 24 weeks after implementation of the electronic health record. RESULTS Median length of stay increased and patient satisfaction was reduced transiently, returning to baseline after 4 to 8 weeks. Rates of laboratory testing, medication administration, overall radiologic imaging, radiographs, computed tomography scans, and ECG ordering all showed sustained increases throughout the 24 weeks after electronic health record implementation. CONCLUSION Electronic health record implementation in this single-center study was associated with both transient and sustained changes in metrics of ED performance, as well as laboratory and medication ordering. Understanding ways in which an ED can be affected by electronic health record implementation is critical to providing insight about ways to mitigate transient disruption and to maximize potential benefits of the technology.

Dog bite prevention: an assessment of child knowledge

OBJECTIVES To determine what children know about preventing dog bites and to identify parental desires for dog bite prevention education. STUDY DESIGN This cross-sectional study sampled 5- to 15-year-olds and their parents/guardians presenting to a pediatric emergency department with nonurgent complaints or dog bites. The parent/guardian-child pairs completed surveys and knowledge-based simulated scenario tests developed on the basis of American Academy of Pediatrics and Centers for Disease Control and Prevention dog bite prevention recommendations. Regression analyses modeled knowledge test scores and probability of passing; a passing score was ≥11 of 14 questions. RESULTS Of 300 parent/guardian-child pairs, 43% of children failed the knowledge test. Older children had higher odds of passing the knowledge test than younger children, as did children with white parents vs those with nonwhite parents. No associations were found between knowledge scores and other sociodemographic or experiential factors. More than 70% of children had never received dog bite prevention education, although 88% of parents desired it. CONCLUSIONS Dog bites are preventable injures that disproportionately affect children. Dog bite prevention knowledge in our sample was poor, particularly among younger children and children with nonwhite parents. Formal dog bite prevention education is warranted and welcomed by a majority of parents.