CLUE: a randomized comparative effectiveness trial of IV nicardipine versus labetalol use in the emergency department

Abstract Introduction Our purpose was to compare the safety and efficacy of food and drug administration (FDA) recommended dosing of IV nicardipine versus IV labetalol for the management of acute hypertension. Methods Multicenter randomized clinical trial. Eligible patients had 2 systolic blood pressure (SBP) measures ≥180 mmHg and no contraindications to nicardipine or labetalol. Before randomization, the physician specified a target SBP ± 20 mmHg (the target range: TR). The primary endpoint was the percent of subjects meeting TR during the initial 30 minutes of treatment. Results Of 226 randomized patients, 110 received nicardipine and 116 labetalol. End organ damage preceded treatment in 143 (63.3%); 71 nicardipine and 72 labetalol patients. Median initial SBP was 212.5 (IQR 197, 230) and 212 mmHg (IQR 200,225) for nicardipine and labetalol patients (P = 0.68), respectively. Within 30 minutes, nicardipine patients more often reached TR than labetalol (91.7 vs. 82.5%, P = 0.039). Of 6 BP measures (taken every 5 minutes) during the study period, nicardipine patients had higher rates of five and six instances within TR than labetalol (47.3% vs. 32.8%, P = 0.026). Rescue medication need did not differ between nicardipine and labetalol (15.5 vs. 22.4%, P = 0.183). Labetalol patients had slower heart rates at all time points (P \u3c 0.01). Multivariable modeling showed nicardipine patients were more likely in TR than labetalol patients at 30 minutes (OR 2.73, P = 0.028; C stat for model = 0.72) Conclusions Patients treated with nicardipine are more likely to reach the physician-specified SBP target range within 30 minutes than those treated with labetalol. Trial registration ClinicalTrials.gov: NCT0076564

Rapid Discharge After Interfacility Transfer for Mild Traumatic Intracranial Hemorrhage: Frequency and Associated Factors

Introduction: Traumatic intracranial hemorrhage (TIH), brain injury with radiographic hemorrhage, is a common emergency department (ED) presentation, and encompasses a wide range of clinical syndromes. Patients with moderate and severe neurotrauma (Glasgow Coma Scale [GCS] < 13) with intracranial hemorrhage require care at a trauma center with neurosurgical capabilities. However, many patients with mild traumatic intracranial hemorrhage (mTIH), defined as radiographic bleeding and GCS ≥ 13, do not require operative intervention or intensive care unit monitoring, but are still routinely transferred to tertiary care centers. We hypothesized that a significant proportion of patients are managed non-operatively and are discharged within 24 hours of admission. Methods: This was a retrospective, observational study of consecutive patients age ≥ 16 years, GCS ≥ 13 who were transferred to an urban, medical school-affiliated, 100,000 annual visit ED over a seven-year period with blunt isolated mTIH. The primary outcome was discharge within 24 hours of admission. We measured rates of neurosurgical intervention, computed tomography hemorrhage progression, and neurologic deterioration as well as other demographic and clinical variables. Results: There were 1079 transferred patients with isolated mTIH. Of these, 92.4% were treated non-operatively and 35.8% were discharged within 24 hours of presentation to the tertiary ED. Patient characteristics associated with rapid discharge after transfer include a GCS of 15 (odds ratio [OR] 2.9, 95% confidence interval [CI], 1.9 – 4.4), subdural hematoma ≤ 6mm (OR 3.1, 95% CI, 2.2 – 4.5) or the presence of an isolated subarachnoid hemorrhage (OR 1.7, 95% CI, 1.3 – 2.4). Of patients with length of stay < 24 hours, 79.8% were discharged directly from the ED or ED observation unit. Conclusion: Patients transferred to tertiary care centers are frequently discharged after brief observation without intervention. Risk can be predicted by clinical and radiographic data. Further prospective research is required to determine a safe cohort of patients who could be managed at community sites

Rapid Discharge After Interfacility Transfer for Mild Traumatic Intracranial Hemorrhage: Frequency and Associated Factors

Introduction: Traumatic intracranial hemorrhage (TIH), brain injury with radiographic hemorrhage, is a common emergency department (ED) presentation, and encompasses a wide range of clinical syndromes. Patients with moderate and severe neurotrauma (Glasgow Coma Scale [GCS] &lt; 13) with intracranial hemorrhage require care at a trauma center with neurosurgical capabilities. However, many patients with mild traumatic intracranial hemorrhage (mTIH), defined as radiographic bleeding and GCS ≥ 13, do not require operative intervention or intensive care unit monitoring, but are still routinely transferred to tertiary care centers. We hypothesized that a significant proportion of patients are managed non-operatively and are discharged within 24 hours of admission. Methods: This was a retrospective, observational study of consecutive patients age ≥ 16 years, GCS ≥ 13 who were transferred to an urban, medical school-affiliated, 100,000 annual visit ED over a seven-year period with blunt isolated mTIH. The primary outcome was discharge within 24 hours of admission. We measured rates of neurosurgical intervention, computed tomography hemorrhage progression, and neurologic deterioration as well as other demographic and clinical variables. Results: There were 1079 transferred patients with isolated mTIH. Of these, 92.4% were treated non-operatively and 35.8% were discharged within 24 hours of presentation to the tertiary ED. Patient characteristics associated with rapid discharge after transfer include a GCS of 15 (odds ratio [OR] 2.9, 95% confidence interval [CI], 1.9 – 4.4), subdural hematoma ≤ 6mm (OR 3.1, 95% CI, 2.2 – 4.5) or the presence of an isolated subarachnoid hemorrhage (OR 1.7, 95% CI, 1.3 – 2.4). Of patients with length of stay &lt; 24 hours, 79.8% were discharged directly from the ED or ED observation unit.  Conclusion: Patients transferred to tertiary care centers are frequently discharged after brief observation without intervention. Risk can be predicted by clinical and radiographic data. Further prospective research is required to determine a safe cohort of patients who could be managed at community sites

Can tablet video‐based telehealth assessment of the abdomen safely determine the need for abdominal imaging? A pilot study

Abstract Objective There is limited evidence on the reliability of video‐based physical examinations. We aimed to evaluate the safety of a remote physician‐directed abdominal examination using tablet‐based video. Methods This was a prospective observational pilot study of patients >19 years old presenting with abdominal pain to an academic emergency department July 9, 2021–December 21, 2021. In addition to usual care, patients had a tablet video‐based telehealth history and examination by an emergency physician who was otherwise not involved in the visit. Both telehealth and in‐person clinicians were asked about the patient's need for abdominal imaging (yes/no). Thirty‐day chart review searched for subsequent ED visits, hospitalizations, and procedures. Our primary outcome was agreement between telehealth and in‐person clinicians on imaging need. Our secondary outcome was potentially missed imaging by the telehealth physicians leading to morbidity or mortality. We used descriptive and bivariate analyses to examine characteristics associated with disagreement on imaging needs. Results Fifty‐six patients were enrolled; the median age was 43 years (interquartile range: 27–59), 31 (55%) were female. The telehealth and in‐person clinicians agreed on the need for imaging in 42 (75%) of the patients (95% confidence interval [CI]: 62%–86%), with moderate agreement with Cohen's kappa ((k = 0.41, 95% CI: 0.15–0.67). For study patients who had a procedure within 24 hours of ED arrival (n = 3, 5.4%, 95% CI: 1.1%–14.9%) or within 30 days (n = 7, 12.5%, 95% CI: 5.2%–24.1%), neither telehealth physicians nor in‐person clinicians missed timely imaging. Conclusion In this pilot study, telehealth physicians and in‐person clinicians agreed on the need for imaging for the majority of patients with abdominal pain. Importantly, telehealth physicians did not miss the identification of imaging needs for patients requiring urgent or emergent surgery

Early-Stage Lung Adenocarcinoma MDM2 Genomic Amplification Predicts Clinical Outcome and Response to Targeted Therapy

Lung cancer is the most common cause of cancer-related deaths in both men and women, accounting for one-quarter of total cancer-related mortality globally. Lung adenocarcinoma is the major subtype of non-small cell lung cancer (NSCLC) and accounts for around 40% of lung cancer cases. Lung adenocarcinoma is a highly heterogeneous disease and patients often display variable histopathological morphology, genetic alterations, and genomic aberrations. Recent advances in transcriptomic and genetic profiling of lung adenocarcinoma by investigators, including our group, has provided better stratification of this heterogeneous disease, which can facilitate devising better treatment strategies suitable for targeted patient cohorts. In a recent study we have shown gene expression profiling identified novel clustering of early stage LUAD patients and correlated with tumor invasiveness and patient survival. In this study, we focused on copy number alterations in LUAD patients. SNP array data identified amplification at chromosome 12q15 on MDM2 locus and protein overexpression in a subclass of LUAD patients with an invasive subtype of the disease. High copy number amplification and protein expression in this subclass correlated with poor overall survival. We hypothesized that MDM2 copy number and overexpression predict response to MDM2-targeted therapy. In vitro functional data on a panel of LUAD cells showed that MDM2-targeted therapy effectively suppresses cell proliferation, migration, and invasion in cells with MDM2 amplification/overexpression but not in cells without MDM2 amplification, independent of p53 status. To determine the key signaling mechanisms, we used RNA sequencing (RNA seq) to examine the response to therapy in MDM2-amplified/overexpressing p53 mutant and wild-type LUAD cells. RNA seq data shows that in MDM2-amplified/overexpression with p53 wild-type condition, the E2F → PEG10 → MMPs pathway is operative, while in p53 mutant genetic background, MDM2-targeted therapy abrogates tumor progression in LUAD cells by suppressing epithelial to mesenchymal transition (EMT) signaling. Our study provides a potentially clinically relevant strategy of selecting LUAD patients for MDM2-targeted therapy that may provide for increased response rates and, thus, better survival

Characteristics of Patients That Do Not Initially Respond to Intravenous Antihypertensives in the Emergency Department: Subanalysis of the CLUE Trial

Introduction: Hypertensive emergency has a high mortality risk and the treatment goal is to quicklylower blood pressure with intravenous (IV) medications. Characteristics that are associated withnon-response to IV antihypertensives have not been identified. The objective is to identify patientcharacteristics associated with resistance to IV antihypertensives.Methods: This was a subanalysis of patients enrolled in the previously described comparativeeffectiveness trial of IV nicardipine vs. labetalol use in the emergency department (CLUE) study, arandomized trial of nicardipine vs. labetalol. Non-responders were defined as those patients whodid not achieve target systolic blood pressure (SBP), as set by the treating physician, within thirtyminutes of IV antihypertensive medication, +/- 20mmHg. Stepwise logistic regression was used toidentify covariates associated with the measurement outcomes.Results: CLUE enrolled 226 patients, 52.7% female, 76.4% black, mean age of 52.6±14.6 years,of whom 110 were treated with nicardipine and 116 with labetalol. The median (IQR) initial systolicblood pressure was 211mmHg (198, 226), 210 (200, 230), and 211mmHg (198,226), for the total,non-responder, and responder cohorts, respectively (p-value=0.65, 95% CI [-5.8-11.3]). Twentyninewere non-responders, 9 in the nicardipine and 20 in the labetalol group. In univariate analysis,several symptoms suggestive of end organ damage were associated with non-response. Aftermultiple variable logistic regression (AUC = 0.72), treatment with labetalol (OR 2.7, 95% CI [1.1-6.7]), history of stroke (OR 5.4, 95% CI [1.6-18.5]), and being male (OR 3.3, 95% CI [1.4-8.1]) wereassociated with failure to achieve target blood pressure.Conclusion: Male gender and history of previous stroke are associated with difficult to controlblood pressure. [West J Emerg Med. 2015;16(2):276–283.

Characteristics of Patients That Do Not Initially Respond to Intravenous Antihypertensives in the Emergency Department: Subanalysis of the CLUE Trial

Introduction: Hypertensive emergency has a high mortality risk and the treatment goal is to quicklylower blood pressure with intravenous (IV) medications. Characteristics that are associated withnon-response to IV antihypertensives have not been identified. The objective is to identify patientcharacteristics associated with resistance to IV antihypertensives.Methods: This was a subanalysis of patients enrolled in the previously described comparativeeffectiveness trial of IV nicardipine vs. labetalol use in the emergency department (CLUE) study, arandomized trial of nicardipine vs. labetalol. Non-responders were defined as those patients whodid not achieve target systolic blood pressure (SBP), as set by the treating physician, within thirtyminutes of IV antihypertensive medication, +/- 20mmHg. Stepwise logistic regression was used toidentify covariates associated with the measurement outcomes.Results: CLUE enrolled 226 patients, 52.7% female, 76.4% black, mean age of 52.6±14.6 years,of whom 110 were treated with nicardipine and 116 with labetalol. The median (IQR) initial systolicblood pressure was 211mmHg (198, 226), 210 (200, 230), and 211mmHg (198,226), for the total,non-responder, and responder cohorts, respectively (p-value=0.65, 95% CI [-5.8-11.3]). Twentyninewere non-responders, 9 in the nicardipine and 20 in the labetalol group. In univariate analysis,several symptoms suggestive of end organ damage were associated with non-response. Aftermultiple variable logistic regression (AUC = 0.72), treatment with labetalol (OR 2.7, 95% CI [1.1-6.7]), history of stroke (OR 5.4, 95% CI [1.6-18.5]), and being male (OR 3.3, 95% CI [1.4-8.1]) wereassociated with failure to achieve target blood pressure.Conclusion: Male gender and history of previous stroke are associated with difficult to controlblood pressure. [West J Emerg Med. 2015;16(2):276–283.