Quantifying the impact of novel metastatic cancer therapies on health inequalities in survival outcomes.

Background: Novel therapies in metastatic cancers have contributed to improvements in survival outcomes, yet real-world data suggest that improvements may be mainly driven by those patient groups who already had the highest survival outcomes. This study aimed to develop and apply a framework for quantifying the impact of novel metastatic cancer therapies on health inequalities in survival outcomes based on published aggregate data. Methods: Nine (N = 9) novel therapies for metastatic breast cancer (mBC), metastatic colorectal cancer (mCRC), and metastatic non-small cell lung cancer (mNSCLC) were identified, 3 for each cancer type. Individual patient data (IPD) for overall survival (OS) and progression-free survival (PFS) were replicated from published Kaplan-Meier (KM) curves. For each cancer type, data were pooled for the novel therapies and comparators separately and weighted based on sample size to ensure equal contribution of each therapy in the analyses. Parametric (mixture) distributions were fitted to the weighted data to model and extrapolate survival. The inequality in survival was defined by the absolute difference between groups with the highest and lowest survival for 2 stratifications: one for which survival was stratified into 2 groups and one using 5 groups. Additionally, a linear regression model was fitted to survival estimates for the 5 groups, with the regression coefficient or slope considered as the inequality gradient (IG). The impact of the pooled novel therapies was subsequently defined as the change in survival inequality relative to the pooled comparator therapies. A probabilistic analysis was performed to quantify parameter uncertainty. Results: The analyses found that novel therapies were associated with significant increases in inequalities in survival outcomes relative to their comparators, except in terms of OS for mNSCLC. For mBC, the inequalities in OS increased by 13.9 (95% CI: 1.4; 26.6) months, or 25.0%, if OS was stratified in 5 groups. The IG for mBC increased by 3.2 (0.3; 6.1) months, or 24.7%. For mCRC, inequalities increased by 6.7 (3.0; 10.5) months, or 40.4%, for stratification based on 5 groups; the IG increased by 1.6 (0.7; 2.4) months, or 40.2%. For mNSCLC, inequalities decreased by 14.9 (-84.5; 19.0) months, or 12.2%, for the 5-group stratification; the IG decreased by 2.0 (-16.1; 5.1) months, or 5.5%. Results for the stratification based on 2 groups demonstrated significant increases in OS inequality for all cancer types. In terms of PFS, the increases in survival inequalities were larger in a relative sense compared with OS. For mBC, PFS inequalities increased by 8.7 (5.9; 11.6) months, or 71.7%, for stratification based on 5 groups; the IG increased by 2.0 (1.3; 2.6) months, or 67.6%. For mCRC, PFS inequalities increased by 5.4 (4.2; 6.6) months, or 147.6%, for the same stratification. The IG increased by 1.3 (1.1; 1.6) months, or 172.7%. For mNSCLC, inequalities increased by 18.2 (12.5; 24.4) months, or 93.8%, for the 5-group stratification; the IG increased by 4.0 (2.8; 5.4) months, or 88.1%. Results from the stratification based on 2 groups were similar. Conclusion: Novel therapies for mBC, mCRC, and mNSCLC are generally associated with significant increases in survival inequalities relative to their comparators in randomized controlled trials, though inequalities in OS for mNSCLC decreased nonsignificantly when stratified based on 5 groups. Although further research using real-world IPD is warranted to assess how, for example, social determinants of health affect the impact of therapies on health inequalities among patient groups, the proposed framework can provide important insights in the absence of such data.

Diagnosis and Treatment of Gordonia Species Infection in a Peach-Faced Lovebird (Agapornis roseicollis).

Respiratory distress is a common presentation for avian species. A 9-week-old peach-faced lovebird (Agapornis roseicollis) was presented with a 2-week history of progressive dyspnea. Computed tomographic (CT) images were suggestive of splenomegaly and bilateral granulomatous pulmonary disease. Polymerase chain reaction testing of samples from the choana, cloaca, and distal tracheal/syringeal area were positive for Mycobacterium species hsp65. A comparison search of the 400 base pair sequence in the NCBI/BLAST/blastn database revealed a best match of 93% similarity to Gordonia species and 91% similarity to Gordonia bronchialis. Gordonia is a genus in the phylum Actinomycetota, the same lineage that includes Mycobacterium species. Gordonia species can be mistaken for Mycobacterium species unless more definitive diagnostic testing is pursued. Infection caused by Gordonia species is rare in humans. Reports commonly cite infection of immunocompromised patients, and to our knowledge, no reports of treatment have been published in the veterinary literature. After the test results were obtained, the patient was treated with azithromycin and pradofloxacin for 3 months. The lovebird was presented for reexamination when the antibiotic treatment was complete. When reexamined, and a second series of CT images evaluated, it was determined that the treatment achieved clinical resolution of signs and lesions.

Liposarcoma of Probable Medullary Bone Origin in a Lovebird (Agapornis roseicollis).

A 15-year-old female peach-faced lovebird (Agapornis roseicollis) was presented to the hospital for a possible left wing injury and an inability to fly after falling in its cage. On physical examination the left elbow was swollen and painful. Radiographic images revealed left wing soft tissue swelling surrounding the elbow and lysis of the distal humerus with extensive cortical thinning. Subsequent high-definition volumetric-imaging 3-dimensional computed tomography (HDVI 3D CT) revealed a pathological fracture, cortical lysis, periosteal reaction, and abnormal intraosseous soft tissue of the left humerus with associated soft tissue swelling, suggestive of neoplasia. No evidence of metastatic disease was identified. Surgical amputation of the left wing was elected. A liposarcoma and pathologic fracture of the humerus were diagnosed histologically and by oil red O staining for lipids in the neoplastic cells. The morphologic features of the tumor suggested that it developed within the adipocyte component of the medullary bone. The incision at the amputation site healed without complication. A follow-up HDVI 3D CT performed 4 months postsurgery showed no evidence of metastatic disease. To the authors' knowledge, this is the first report of a primary liposarcoma of medullary bone origin in an avian species.

An Automated Risk Index for Diabetic Ketoacidosis in Pediatric Patients With Type 1 Diabetes: The RI-DKA.

Identifying patients at high risk for diabetic ketoacidosis (DKA) is crucial for informing efforts at preventive intervention. This study sought to develop and validate an electronic medical record (EMR)-based tool for predicting DKA risk in pediatric patients with type 1 diabetes. Based on analysis of data from 1,864 patients with type 1 diabetes, three factors emerged as significant predictors of DKA: most recent A1C, type of health insurance (public vs. private), and prior DKA. A prediction model was developed based on these factors and tested to identify and categorize patients at low, moderate, and high risk for experiencing DKA within the next year. This work demonstrates that risk for DKA can be predicted using a simple model that can be automatically derived from variables in the EMR.

A Comprehensive System for Identifying Patients With Type 1 Diabetes at Increased Risk for Diabetic Ketoacidosis at Texas Children's Hospital.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a project at Texas Children's Hospital aimed at improving identification of patients with type 1 diabetes at high risk for diabetic ketoacidosis.

The Clinical Respiratory Score: investigating the reliability of an asthma scoring tool across a multidisciplinary team.

BACKGROUND: Asthma scoring tools are used by emergency department (ED) teams to communicate severity of illness. Although most have been validated, none has been found to be sufficiently valid to allow for use across a multidisciplinary team managing pediatric asthma exacerbations. OBJECTIVE: We sought to evaluate the inter-rater reliability of the Clinical Respiratory Score (CRS) among all members of an ED care team. DESIGN/METHODS: We conducted a retrospective study of children aged 2 to 18 years presenting with an acute asthma exacerbation to an urban pediatric ED over a 2-year period. We determined reliability using two CRS measurements independently documented by two separate providers, 15 min apart. An inter-class correlation coefficient (ICC) was calculated to determine overall reliability among users. Subgroup analysis was conducted to determine reliability between types of providers and the six components of the CRS. RESULTS: A total of 9,749 patient encounters were identified and 1,562 (16%) met our inclusion criteria. The majority of score pairings (n = 1096, 70.2%) were documented by a registered nurse followed by a respiratory therapist. The overall reliability of the CRS, when documented by two providers, was acceptable with an ICC of 0.76 (95% CI: 0.74-0.78, p < 0.001). Removing CRS components with the lowest agreement did not affect the overall ICC when re-calculated. CONCLUSION(S): The CRS is a reliable asthma severity scoring tool for pediatric patients presenting with an acute asthma exacerbation when utilized across care team members. Simplifying the CRS by removing the color and mental status components did not affect its reliability.

Does crowding influence emergency department treatment time and disposition?

OBJECTIVE: The objective of this study was to determine whether crowding influences treatment times and disposition decisions for emergency department (ED) patients. METHODS: We conducted a retrospective cohort study at 2 hospitals from January 1, 2014, to July 1, 2014. Adult ED visits with dispositions of discharge, admission, or transfer were included. Treatment times were modeled by linear regression with log-transformation; disposition decisions (admission or transfer vs discharge) were modeled by logistic regression. Both models adjusted for chief complaint, Emergency Severity Index (ESI), and 4 crowding metrics in quartiles: waiting count, treatment count, boarding count, and National Emergency Department Overcrowding Scale. RESULTS: We included 21,382 visits at site A (12.9% excluded) and 29,193 at site B (15.0% excluded). Respective quartiles of treatment count increased treatment times by 7.1%, 10.5%, and 13.3% at site A (P < 0.001) and by 4.0%, 6.5%, and 10.2% at site B (P < 0.001). The fourth quartile of treatment count increased estimates of treatment time for patients with chest pain and ESI level 2 from 2.5 to 2.9 hours at site A (20 minutes) and from 3.0 to 3.3 hours at site B (18 minutes). Treatment times decreased with quartiles of waiting count by 5.6%, 7.2%, and 7.3% at site B (P < 0.001). Odds of admission or transfer increased with quartiles of waiting count by 8.7%, 9.6%, and 20.3% at site A (P = 0.011) and for the third (11.7%) and fourth quartiles (27.3%) at site B (P < 0.001). CONCLUSIONS: Local crowding influenced ED treatment times and disposition decisions at 2 hospitals after adjusting for chief complaint and ESI.

Impact of a Pediatric-Focused Communication Course on Patient/Caregiver-Perceived Physician Communication Skills in a Pediatric Emergency Department.

OBJECTIVES: To evaluate the impact of a pediatric-focused, relationship-centered communication course on patient/caregiver assessment of emergency department (ED) physician communication skills. METHODS: This was a prospective study; a previously validated assessment tool (Pediatric Physician Interpersonal Communication Skills Assessment [P-PICSA]) was used to collect pediatric patient/caregiver evaluation of ED physician communication skills. Emergency department physicians were required to attend a 5.5-hour communication course. Differences in precourse/postcourse P-PICSA and top-box scores were analyzed to determine course impact on ED physician communication skills. RESULTS: From July 2016 to August 2017, 49 pediatric ED physicians participated in the course, and 24 physicians (49%) had 6-month precourse/postcourse P-PICSA data. Postcourse scores were higher for all 13 items, with 3 items achieving statistical significance: (1) the doctor used words I could understand; (2) the way the doctor involved me in making decisions about my child's care in the ED; (3) how the doctor discussed next steps and/or follow-up plans for my child's care after we leave the ED (P < 0.05). Additionally, postcourse, top-box score percentages were higher for 12 items, with 1 item achieving statistical significance (P = 0.0386). CONCLUSIONS: An organization-wide, pediatric-focused, relationship-centered communication course improved patient/caregiver-perceived ED physician communication. Further research is necessary to assess long-term sustainability.

PATHOLOGY AND DISCRETE TYPING UNIT ASSOCIATIONS OF TRYPANOSOMA CRUZI INFECTION IN COYOTES (CANIS LATRANS) AND RACCOONS (PROCYON LOTOR) OF TEXAS, USA.

Trypanosoma cruzi is a vector-borne, protozoal parasite of mammals. Infected humans, dogs (Canis lupus familiaris), and nonhuman primates may remain asymptomatic or may develop Chagas disease, most commonly characterized by lymphoplasmacytic myocarditis with myocardial degeneration and fibrosis, ultimately resulting in heart failure. Although wildlife species have important roles as sylvatic reservoirs, investigations into the pathology of T. cruzi in wildlife are limited to a few studies documenting histologic lesions in opossums (Didelphis spp.) and raccoons (Procyon lotor). Pathology in coyotes (Canis latrans) has not, to our knowledge, been described, despite their recognition as a reservoir and close genetic relationship to domestic dogs. Our objectives were to perform a detailed, comparative cardiac pathology study of sympatric, naturally infected coyotes and raccoons, to characterize the overall T. cruzi infection prevalence in the heart and blood of each species via PCR, and to identify infecting discrete typing units (DTUs). We sampled hunter-harvested coyotes (n=120) and raccoons (n=24) in a 28 county region of central and south Texas, US. Raccoons were significantly more likely to have positive PCR results (P<0.001) with a prevalence of 62% (15/24), comprising DTU TcIV exclusively, with mild to no evidence of cardiac pathology. In contrast, coyotes had a lower infection prevalence (8%, 10/120), comprising DTU TcI exclusively, with lymphoplasmacytic myocarditis observed in four of the six PCR-positive animals. Many raccoons had PCR-positive blood and heart tissue simultaneously, supporting previous reports that raccoons maintain parasitemia into chronic stages of infection; in contrast, none of the PCR-positive coyotes were positive in both heart and blood. Our findings demonstrate marked differences in T. cruzi infection dynamics between coyotes and raccoons, with important implications for reservoir potential and their role in transmission cycles.

Communication Course for Pediatric Providers Improves Self-efficacy.

BACKGROUND: Communication is essential to building a trusting, clinician-patient relationship. Multiple studies have demonstrated the effects of experiential communication training on patient experience and provider well-being and resiliency. To date, no studies have described an organization-wide communication training program for pediatric clinicians. The objective of this study was to evaluate the impact of a pediatric-focused communication course on provider satisfaction, self-efficacy, and burnout. METHODS: Texas Children's Hospital, in collaboration with the Academy on Communication in Healthcare, designed and implemented a pediatric focused communication course entitled Breakthrough Communication. Pre, immediate-post, and 3-month postcourse completion online surveys were sent to participants 1 day before, 1 day after, and 3 months after course completion. Participant demographic information, self-assessment of communication skills, the Maslach Burnout Inventory Human Services Survey, and postcourse satisfaction data were collected. RESULTS: Participants reported high course satisfaction and improved self-efficacy in all measured skill sets both following and 3 months after course completion. Trends indicating a reduction in provider burnout improved in 2 of the 3 Maslach Burnout Inventory domains; however, statistical significance was not achieved. CONCLUSIONS: A pediatric-focused communication course was well received by multi-specialty clinicians within a large, academic health care organization. This course enhanced clinician self-efficacy with newly learned pediatric encounter specific communication skills.

The Incidence and Outcome Differences in Severe Sepsis with and without Lactic Acidosis.

INTRODUCTION: To compare the incidence, characteristics, and outcomes of lactate expressors and nonexpressors in patients with severe sepsis and septic shock. METHODS: This is a retrospective cohort study of patients with severe sepsis and septic shock who presented over a 40-month period to an academic tertiary care center. Primary outcome of interest was in-hospital mortality. Secondary outcomes were hospital length of stay (LOS), Intensive Care Unit (ICU) LOS, and escalation of care. RESULTS: Three hundred and thirty-eight patients met inclusion criteria and were divided into a lactate expressor group (n = 197; initial lactate ≥2.5 mmol/L) and a nonexpressor group (n = 141; lactate <2.5 mmol/L). The mortality rate was 46.2% for lactate expressors and 24.8% for nonexpressors. There were no significant differences in hospital or ICU LOS. The escalation-of-care rate in the severe sepsis nonexpressor group was more than double that found in the expressor group: 16.5% versus 6.2% (P = 0.040). The two groups had baseline differences: expressor group had a higher median Acute Physiology and Chronic Health Evaluation II (APACHE II) illness severity score, and nonexpressors had an increased prevalence of comorbid conditions. APACHE II score (odds ratio [OR] 1.10 (1.07-1.14), P < 0.001) and being in the expressor group (OR 1.72 [1.03-2.89], P = 0.039) increased the odds of mortality. CONCLUSIONS: In patients with severe sepsis and septic shock, lactate nonexpressors are common. Although the mortality in this cohort is less than its counterparts who present with lactate elevation, it is still significant which warrants vigilance in their care.

Outcomes of severe sepsis and septic shock patients after stratification by initial lactate value.

BACKGROUND: In the setting of severe sepsis and septic shock, mortality increases when lactate levels are ≥ 4 mmol/L. However, the consequences of lower lactate levels in this population are not well understood. The study aimed to determine the in-hospital mortality associated with severe sepsis and septic shock when initial lactate levels are < 4 mmol/L. METHODS: This is a retrospective cohort study of septic patients admitted over a 40-month period. Totally 338 patients were divided into three groups based on initial lactate values. Group 1 had lactate levels < 2 mmol/L; group 2: 2-4 mmol/L; and group 3: ≥ 4 mmol/L. The primary outcome was in-hospital mortality. RESULTS: There were 111 patients in group 1, 96 patients in group 2, and 131 in group 3. The mortality rates were 21.6%, 35.4%, and 51.9% respectively. Univariate analysis revealed the mortality differences to be statistically significant. Multivariate logistic regression demonstrated higher odds of death with higher lactate tier group, however the findings did not reach statistical significance. CONCLUSION: This study found that only assignment to group 3, initial lactic acid level of ≥ 4 mmol/L, was independently associated with increased mortality after correcting for underlying severity of illness and organ dysfunction. However, rising lactate levels in the other two groups were associated with increased severity of illness and were inversely proportional to prognosis.

Does the National Resident Match Program Rank List Predict Success in Emergency Medicine Residency Programs?

BACKGROUND: Emergency medicine (EM) residency programs use nonstandardized criteria to create applicant rank lists. One implicit assumption is that predictive associations exist between an applicant's rank and their future performance as a resident. To date, these associations have not been sufficiently demonstrated. OBJECTIVES: We hypothesized that a strong positive correlation exists between the National Resident Match Program (NRMP) match-list applicant rank, the United States Medical Licensing Examination (USMLE) Step 1 and In-Training Examination (ITE) scores, and the graduating resident rank. METHODS: A total of 286 residents from five EM programs over a 5-year period were studied. The applicant rank (AR) was derived from the applicant's relative rank list position on each programs' submitted NRMP rank list. The graduation rank (GR) was determined by a faculty consensus committee. GR was then correlated to AR using a Spearman's partial rank correlation. Additional correlations were sought with a ranking of the USMLE Step Score (UR) and the ITE Score (IR). RESULTS: Combining data for all five programs, weak positive correlations existed between GR and AR, UR, and IR. The majority of correlations ranged between. When comparing GR and AR, there was a weak correlation of 0.13 (p = 0.03). CONCLUSION: Our study found only weak correlations between GR and AR, UR, and IR, suggesting that those variables may not be strong predictors of resident performance. This has important implications for EM programs considering the resources devoted to applicant evaluation and ranking.

Development and usage of wiki-based software for point-of-care emergency medical information.

OBJECTIVE: To describe the creation and evaluate the usage of the first medical wiki linked to dedicated mobile applications. METHODS: With the support of multiple current and past contributors, we developed an emergency medicine wiki linked to offline mobile applications (WikEM) in 2009. First deployment was at the Harbor-UCLA Medical Center emergency medicine residency program, with the wiki later opened to public use. To evaluate the project, we performed a post hoc analysis of system use and surveyed 8 years of current and past residents. Outcomes included website and application analytics, as well as survey analysis by composite response categories. RESULTS: Over the 6-year period of this project, the wiki grew to over 7250 pages and 45 500 edits. The website receives more than 85 000 user sessions per month, with over 150 million page views to date. There have been over 200 000 installs of the mobile applications, progressing to produce over 5000 mobile sessions daily. Of potential survey respondents, 87.7% (107) completed the Internet-based survey. Among those who contributed to the wiki, 74.6% reported that it benefited their understanding of core emergency medicine content. Of program graduates, the vast majority reported use of the wiki as a resource after residency (93.8%) along with improvement in clinical efficiency (89.7%). Residents reported higher use and a more favorable opinion of wiki usefulness compared to graduates (P < .001). CONCLUSIONS: A wiki paired with mobile applications is beneficial for resident education and useful in post-residency clinical practice.

Genetic and toxinological characterization of North Atlantic strains of the dinoflagellate Ostreopsis and allelopathic interactions with toxic and non-toxic species from the genera Prorocentrum, Coolia and Gambierdiscus.

The genus Ostreopsis includes several toxic species that can develop blooms in benthic ecosystems, with potential harmful consequences for human health and marine invertebrates. Despite of this, little is known about the allelopathic interactions between these organisms and other co-occurring microalgae that exploit similar spatial and nutrient resources in benthic ecosystems. The aim of this study was to follow these interactions in cultures of two Ostreopsis ribotypes with different toxin profiles (O. cf. ovata contained ovatoxins-a, b, c and e, while only ovatoxin-d was found in O .sp. "Lanzarote-type"), mixed with species of three benthic dinoflagellate genera (Coolia, Prorocentrum and Gambierdiscus), isolated from the same area (North East Atlantic, Canary Islands). In a first experiment, the potential allelopathic effects on growth rates were followed, in mixed cultures of Coolia monotis (a non toxic species) exposed to the clarified medium and to cells of O. sp."Lanzarote-type" and O. cf. ovata. Growth delayed in C. monotis was observed specially in clarified medium, while the O. sp. "Lanzarote-type" strain attained much lower densities in mixed cultures. In a second experiment, we examined the potential effects of clarified media from O. sp."Lanzarote-type" and O. cf. ovata on the adherence capacity in two toxic species (Prorocentrum hoffmannianum and Gambierdiscus excentricus). Contrasting effects were found: a significant increase of adherence capacity in P. hoffmannianum vs attachment decline in G. excentricus, that experienced also severe deleterious effects (cell lysis). Our results suggest the existence of weak to moderate allelopathic interactions between the studied organisms, although the outcome is dependent on the species involved.

Effect of Therapeutic Hypothermia on Survival to Hospital Discharge in Out-of-hospital Cardiac Arrest Secondary to Nonshockable Rhythms.

OBJECTIVES: Therapeutic hypothermia has been shown to improve neurologic outcome and survival in out-of-hospital cardiac arrest (OHCA) following return of spontaneous circulation (ROSC), and current guidelines recommend therapeutic hypothermia for all comatose survivors of OHCA. However, recommendations for nonshockable rhythms are not as strongly supported. Our study aims to provide further evidence on the use of therapeutic hypothermia in nonshockable rhythms. METHODS: A multivariate analysis with propensity score matching was performed using a cardiac arrest registry maintained by the Houston Fire Department. The analysis was limited to adult patients achieving ROSC following OHCA secondary to nonshockable rhythm in Houston from 2007 to 2012 with definitive information regarding the implementation of therapeutic hypothermia. The primary outcome was survival to hospital discharge. RESULTS: Of 9,479 records identified for analysis, 7,839 had an initial nonshockable rhythm. Of these, 2,609 (33.3%) had sustained ROSC and 1,768 (22.6%) were admitted to the hospital. Data on therapeutic hypothermia use were available for 696 patients, with 335 (48.1%) receiving therapeutic hypothermia. Propensity score matching yielded 260 case/control pairs. The odds of survival to hospital discharge was an odds ratio of 1.07 (95% confidence interval = 0.71 to 1.60) for those in the therapeutic hypothermia group versus the nontherapeutic hypothermia group (p = 0.79). CONCLUSIONS: Based on this retrospective study, therapeutic hypothermia is not associated with improved survival in patients with OHCA secondary to nonshockable rhythms. Given the limitations of our study, further prospective trials to assess the effect of therapeutic hypothermia for OHCA with nonshockable rhythms are warranted.

Synchronous Fibrolamellar Hepatocellular Carcinoma and Auricular Myxoma.

Synchronic occurrence of benign and malignant tumors is extremely rare. Fibrolamellar hepatocellular carcinoma represents 1% to 2% of all hepatocarcinomas, while myxomas represent about half of all the cases of primary tumors of the heart. We present the case of a 53-year-old woman with a left atrial myxoma that was surgically removed. Several weeks later, the patient returned to the hospital with abdominal pain. CT scan showed a mass in the left lobe of the liver that was resected and diagnosed as fibrolamellar hepatocellular carcinoma. As of this writing, the patient is healthy.

Prospective randomized trial of insulin glargine in acute management of diabetic ketoacidosis in the emergency department: a pilot study.

OBJECTIVES: The objective was to determine the efficacy of coadministration of subcutaneous (SQ) insulin glargine in combination with intravenous (IV) insulin for treating diabetic ketoacidosis (DKA). METHODS: This was a prospective, randomized, controlled trial comparing coadministration of insulin glargine and IV insulin (experimental) with IV insulin (standard care control). The setting was emergency departments (EDs) in two hospitals in Houston, Texas. Patients presenting with blood sugar ≥ 200 mg/dL, pH ≤ 7.3, bicarbonate (HCO3 ) ≤ 18 mg/dL, ketonemia or ketonuria, and anion gap ≥ 16 between November 2012 and April 2013 were enrolled. All patients received IV insulin. Additionally, the experimental group was given SQ insulin glargine within 2 hours of diagnosis. Upon closure of anion gap, patients in the control group were subsequently transitioned to long-acting insulin. In the study group, IV insulin was discontinued and long-acting SQ insulin was reinstituted 24 hours after initial introduction. The primary outcome of time to closure of anion gap (TCAG) was compared between groups using a general linear model (GLM), adjusting for initial anion gap, etiology, and presence of comorbidities. Similarly, the secondary outcome hospital length of stay (LOS) was adjusted for age, etiology, and hospital site in the GLM. Rate of hypoglycemia and intensive care unit (ICU) admission was compared using Fisher's exact test while ICU LOS was compared using Wilcoxon's two-sample test. RESULTS: A total of 40 patients were enrolled in this pilot trial. The estimated mean TCAG was 10.2 hours (SE ± 6.8 hours) in the experimental group and 11.6 hours (SE ± 6.4 hours) in the control group (p = 0.63). The estimated mean hospital LOS was 3.9 days (SE ± 3.4 days) in the experimental group and 4.8 days (SE ± 3.6 days) in the control group (p = 0.66). Incidents of hypoglycemia, rates of ICU admission, and ICU LOS were similar between the groups. CONCLUSIONS: Coadministration of glargine in combination with an insulin infusion in the acute management of DKA is feasible. Further study is needed to determine the true efficacy in terms of TCAG and hospital LOS.

Iodinated contrast prior to thrombolysis was not associated with worse intracranial hemorrhage.

OBJECTIVES: The objective was to assess relative incidence of clinical adverse effects between patients receiving, and not receiving, iodinated contrast prior to thrombolysis. METHODS: This was a retrospective registry review of patients presenting to the emergency department treated with recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke between 2004 and 2012. The authors compared the occurrence of all grades of intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH), and in-hospital deaths between patients undergoing computed tomographic angiography (CTA) prior to thrombolysis and those who did not. RESULTS: A total of 1,014 patients were available for analysis meeting inclusion criteria. A total of 473 patients underwent CTA prior to rt-PA administration. Baseline characteristics were generally similar across groups, excepting fewer signs of acute infarct and old stroke in the CTA group (28.8% vs. 8.5% and 9.9% vs. 3.7%, respectively) and creatinine. Adverse event outcomes were not consistently distributed across the groups. Patients in the CTA group had a similar incidence of any ICH (11.0% vs. 8.1%, p = 0.120), but fewer type II parenchymal hemorrhages (2.1% vs. 4.6%, p = 0.025) and fewer in-hospital deaths (7.2% vs. 12.6%, p = 0.005). CONCLUSIONS: No consistent harms were observed in association with intravenous iodinated contrast prior to rt-PA administration. It is reasonable to continue CTA prior to thrombolysis as clinically indicated.

Outcomes of Patients Requiring Blood Pressure Control Before Thrombolysis with tPA for Acute Ischemic Stroke.

INTRODUCTION: The purpose of this study was to assess safety and efficacy of thrombolysis in the setting of aggressive blood pressure (BP) control as it compares to standard BP control or no BP control prior to thrombolysis. METHODS: We performed a retrospective review of patients treated with tissue plasminogen activator (tPA) for acute ischemic stroke (AIS) between 2004-2011. We compared the outcomes of patients treated with tPA for AIS who required aggressive BP control prior to thrombolysis to those requiring standard or no BP control prior to thrombolysis. The primary outcome of interest was safety, defined by all grades of hemorrhagic transformation and neurologic deterioration. The secondary outcome was efficacy, determined by functional status at discharge, and in-hospital deaths. RESULTS: Of 427 patients included in the analysis, 89 received aggressive BP control prior to thrombolysis, 65 received standard BP control, and 273 required no BP control prior to thrombolysis. Patients requiring BP control had more severe strokes, with median arrival National Institutes of Health Stroke Scale of 10 (IQR [6-17]) in patients not requiring BP control versus 11 (IQR [5-16]) and 13 (IQR [7-20]) in patients requiring standard and aggressive BP lowering therapies, respectively (p=0.048). In a multiple logistic regression model adjusting for baseline differences, there were no statistically significant differences in adverse events between the three groups (P>0.10). CONCLUSION: We observed no association between BP control and adverse outcomes in ischemic stroke patients undergoing thrombolysis. However, additional study is necessary to confirm or refute the safety of aggressive BP control prior to thrombolysis.