County-level factors underlying opioid mortality in the United States.

BACKGROUND: Mortality from overdoses involving opioids in the United States (U.S.) has reached epidemic proportions. More research is needed to examine the underlying factors contributing to opioid-related mortality regionally. This study's objective was to identify and examine the county-level factors most closely associated with opioid-related overdose deaths across all counties in the U.S.Methods: Using a national cross-sectional ecological study design, we analyzed the relationships between 17 county-level characteristics in four categories (i.e. socio-economic, availability of medical care, health-related concerns, and demographics) with opioid mortality. Data were extracted from the Robert Wood Johnson County Health Rankings aggregate database and Centers for Disease Control and Prevention (CDC)'s Wide-ranging Online Data for Epidemiological Research (WONDER) system.Results: There were 1058 counties (33.67% of 3142 nationally) with reported opioid-related fatalities. Median opioid-related mortality was 15.61 per 100,000 persons. Multivariate regression results indicate that counties with the highest opioid-related mortality had increased rates of tobacco use, HIV, Non-Hispanic Caucasians, and females and were rural areas, but lower rates of food insecurity and uninsured adults. The rates of tobacco use and HIV had the strongest association with mortality. Availability of either mental health or primary care providers were not significantly associated with mortality. Severe housing problems, high school graduation rate, obesity, violent crime, and median household income also did not contribute to county-level differences in overdose mortality.Conclusions: Future health policies should fund further investigations and ultimately address the most influential and significant underlying county-level factors associated with opioid-related mortality.

Feasibility and outcomes from an integrated bridge treatment program for opioid use disorder.

OBJECTIVE: With a significant proportion of individuals with opioid use disorder not currently receiving treatment, it is critical to find novel ways to engage and retain patients in treatment. Our objective is to describe the feasibility and preliminary outcomes of a program that used emergency physicians to initiate a bridge treatment, followed by peer support services, behavioral counseling, and ongoing treatment and follow-up. METHODS: We developed a program called the Houston Emergency Opioid Engagement System (HEROES) that provides rapid access to board-certified emergency physicians for initiation of buprenorphine, plus at least 1 behavioral counseling session and 4 weekly peer support sessions over the course of 30 days. Follow-ups were conducted by phone and in person to obtain patient-reported outcomes. Primary outcomes included percentage of patients who completed the 30-day program and the percentage for successful linkage to more permanent ongoing treatment after the initial program. RESULTS: There were 324 participants who initiated treatment on buprenorphine from April 2018 to July 2019, with an average age of 36 (±9.6 years) and 52% of participants were males. At 30 days, 293/324 (90.43%) completed the program, and 203 of these (63%) were successfully connected to a subsequent community addiction medicine physician. There was a significant improvement (36%) in health-related quality of life. CONCLUSION: Lack of insurance is a predictor for treatment failure. Implementation of a multipronged treatment program is feasible and was associated with positive patient-reported outcomes. This approach holds promise as a strategy for engaging and retaining patients in treatment.

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.

Prevalence and charges of opioid-related visits to U.S. emergency departments.

OBJECTIVE: An overwhelming responsibility for responding to the opioid epidemic falls on hospital emergency departments (ED). We sought to examine the overall prevalence rate and associated charges of opioid-related diagnoses and overdoses. Although charge data do not necessarily represent cost, they are proxy indicators of resource utilization and burden. METHODS: We conducted a retrospective study of the National Emergency Department Sample (NEDS) dataset, the largest all-payer ED database in the United States. We queried using specific relevant ICD-10 codes to estimate the number of adult ED visits for both opioid poisonings and other opioid-related diagnoses during 2016 and 2017, which was the most recent publicly available data. Prevalence rates and financial charges were calculated by year and odds ratios were used to examine differences. RESULTS: Of approximately 234 million adult visits to EDs across 2016 and 2017, 2.88 million (1.23%) were related to opioids, with overdoses comprising nearly 27.5% and visits for other opioid-related diagnoses totaling 72.5%. As the primary diagnosis, opioids were responsible for 37% of all ED visits across both years. Total opioid-related visits for the two years accounted for $9.57 billion in ED charges, or $4.78 billion annually, with Medicaid and Medicare responsible for 66% of all charges. CONCLUSION AND RELEVANCE: Approximately one of every 80 visits to the ED were opioid-related, leading to financial charges approaching $5 billion per year. Since both prevalence and the economic burden of opioid-related visits are high, targeted interventions to address this epidemic's impact on healthcare systems should be a national priority.

Impact of Hurricane Harvey on Healthcare Utilization and Emergency Department Operations.

INTRODUCTION: Hurricanes have increased in severity over the past 35 years, and climate change has led to an increased frequency of catastrophic flooding. The impact of floods on emergency department (ED) operations and patient health has not been well studied. We sought to detail challenges and lessons learned from the severe weather event caused by Hurricane Harvey in Houston, Texas, in August 2017. METHODS: This report combines narrative data from interviews with retrospective data on patient volumes, mode of arrival, and ED lengths of stay (LOS). We compared the five-week peri-storm period for the 2017 hurricane to similar periods in 2015 and 2016. RESULTS: For five days, flooding limited access to the hospital, with a consequent negative impact on provider staffing availability, disposition and transfer processes, and resource consumption. Interruption of patient transfer capabilities threatened patient safety, but flexibility of operations prevented poor outcomes. The total ED patient census for the study period decreased in 2017 (7062 patients) compared to 2015 (7665 patients) and 2016 (7770) patients). Over the five-week study period, the arrival-by-ambulance rate was 12.45% in 2017 compared to 10.1% in 2016 (p < 0.0001) and 13.7% in 2015 (p < 0.0001). The median ED length of stay (LOS) in minutes for admitted patients was 976 minutes in 2015 (p < 0.0001) compared to 723 minutes in 2016 and 591 in 2017 (p < 0.0001). For discharged patients, median ED LOS was 336 minutes in 2016 compared to 356 in 2015 (p < 0.0001) and 261 in 2017 (p < 0.0001). Median boarding time for admitted ED patients was 284 minutes in 2016 compared to 470 in 2015 (p < 0.0001) and 234.5 in 2017 (p < 0.001). Water damage resulted in a loss of 133 of 179 inpatient beds (74%). Rapid and dynamic ED process changes were made to share ED beds with admitted patients and to maximize transfers post-flooding to decrease ED boarding times. CONCLUSION: A number of pre-storm preparations could have allowed for smoother and safer ride-out functioning for both hospital personnel and patients. These measures include surplus provisioning of staff and supplies to account for limited facility access. During a disaster, innovative flexibility of both ED and hospital operations may be critical when disposition and transfer capibilities or bedding capacity are compromised.

The ventilatory effect of high velocity nasal insufflation compared to non-invasive positive-pressure ventilation in the treatment of hypercapneic respiratory failure: A subgroup analysis.

PURPOSE: Oxygen delivery by high flow nasal cannula (HFNC) is effective in providing respiratory support. HFNC has utility in clearing the extra-thoracic dead space, making it potentially beneficial in the treatment of hypercapnic respiratory failure. This study compares high velocity nasal insufflation (HVNI), a form of HFNC, to non-invasive positive pressure ventilation (NIPPV) in their abilities to provide ventilatory support for patients with hypercapnic respiratory failure. METHODS: This is a pre-defined subgroup analysis from a larger randomized clinical trial of Emergency Department (ED) patients with respiratory failure requiring NIPPV support. Patients were randomized to HVNI or NIPPV. Subgroup selection was done for patients with discharge diagnoses of acute hypercapnic respiratory failure or acute exacerbation of chronic obstructive pulmonary disease. The primary outcomes were change in pCO2 and pH over time. Secondary outcomes were treatment failure and intubation rate. RESULTS: 65 patients with hypercapnic respiratory failure were compared. 34 were randomized to HVNI and 31 to NIPPV. The therapeutic impact on PCO2 and pH over time was similar in each group. The intubation rate was 5.9% in the HVNI group and 16.1% in the NIPPV group (p = 0.244). The rate of treatment failure was 23.5% in the HVNI group and 25.8% in the NIPPV group (p = 1.0). CONCLUSION: HVNI may provide ventilatory support similar to NIPPV in patients presenting with acute hypercapnic respiratory failure, but further study is needed to corroborate these findings.

Outreach to people who survive opioid overdose: Linkage and retention in treatment.

Cognitive motivation theories contend that individuals have greater readiness for behavioral change during critical periods or life events, and a non-fatal overdose could represent such an event. The objective of this study was to examine if the use of a specialized mobile response team (assertive outreach) could help identify, engage, and retain people who have survived an overdose into a comprehensive treatment program. We developed an intervention, consisting of mobile outreach followed by medication and behavioral treatment, in Houston Texas between April and December 2018. Our primary outcome variables were the level of willingness to engage in treatment, and percent who retained in treatment after 30 and 90 day endpoints. We screened 103 individuals for eligibility, and 34 (33%) elected to engage in the treatment program, while two-thirds chose not to engage in treatment, primarily due to low readiness levels. The average age was 38.2 ± 12 years, 56% were male, 79% had no health insurance, and the majority (77%) reported being homeless or in temporary housing. There were 30 (88%) participants still active in the treatment program after 30 days, and 19 (56%) after 90 days. Given the high rates of relapse using conventional models, which wait for patients to present to treatment, our preliminary results suggest that assertive outreach could be a promising strategy to motivate people to enter and remain in long-term treatment.

Disparities Between US Opioid Overdose Deaths and Treatment Capacity: A Geospatial and Descriptive Analysis.

INTRODUCTION: With opioid-related deaths reaching epidemic levels, gaining a better understanding of access to treatment for opioid use disorder (OUD) is critical. Most studies have focused on 1 side of the equation-either provider capacity or patients' need for care, as measured by overdose deaths. This study examines the overlay between treatment program availability and opioid mortality, comparing accessibility by region. METHODS: Geospatial and statistical analyses were used to model OUD treatment programs relative to population density and opioid overdose death incidence at the state and county level. We computed a ratio between program capacity and mortality called the programs-per-death (PPD) ratio. RESULTS: There were 40 274 opioid deaths in 2016 and 12 572 treatment programs across the contiguous 48 states, yielding a ratio of 1 program for every 3.2 deaths. Texas had the lowest number of treatment programs per 100 000 persons (1.4) and Maine the highest (13.2). West Virginia ranked highest in opioid deaths (39.09 per 100 000). Ohio, the District of Columbia, and West Virginia had the greatest mismatch between providers and deaths, with an average of 1 program for every 8.5 deaths. Over 32% of US counties had no treatment programs and among those with >10 deaths, nearly 2.5% had no programs. Over 19% of all counties had a ratio ≤1 provider facility per 10 deaths. CONCLUSION: Assessing the overlay between treatment capacity and need demonstrated that regional imbalances exist. These data can aid in strategic planning to correct the mismatch and potentially reduce mortality in the most challenged geographic regions.

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.

Randomized Controlled Double-blind Trial Comparing Haloperidol Combined With Conventional Therapy to Conventional Therapy Alone in Patients With Symptomatic Gastroparesis.

OBJECTIVE: Gastroparesis is a debilitating condition that causes nausea, vomiting, and abdominal pain. Management includes analgesics and antiemetics, but symptoms are often refractory. Haloperidol has been utilized in the palliative care setting for similar symptoms. The study objective was to determine whether haloperidol as an adjunct to conventional therapy would improve symptoms in gastroparesis patients presenting to the emergency department (ED). STUDY DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled trial of adult ED patients with acute exacerbation of previously diagnosed gastroparesis. The treatment group received 5 mg of haloperidol plus conventional therapy (determined by the treating physician). The control group received a placebo plus conventional therapy. The severity of each subject's abdominal pain and nausea were assessed before intervention and every 15 minutes thereafter for 1 hour using a 10-point scale for pain and a 5-point scale for nausea. Primary outcomes were decreased pain and nausea 1 hour after treatment. RESULTS: Of the 33 study patients, 15 were randomized to receive haloperidol. Before treatment, the mean intensity of pain was 8.5 in the haloperidol group and 8.28 in the placebo group; mean pretreatment nausea scores were 4.53 and 4.11, respectively. One hour after therapy, the mean pain and nausea scores in the haloperidol group were 3.13 and 1.83 compared to 7.17 and 3.39 in the placebo group. The reduction in mean pain intensity therapy was 5.37 in the haloperidol group (p ≤ 0.001) compared to 1.11 in the placebo group (p = 0.11). The reduction in mean nausea score was 2.70 in the haloperidol group (p ≤ 0.001) and 0.72 in the placebo group (p = 0.05). Therefore, the reductions in symptom scores were statistically significant in the haloperidol group but not in the placebo group. No adverse events were reported. CONCLUSIONS: Haloperidol as an adjunctive therapy is superior to placebo for acute gastroparesis symptoms.

Improved Accuracy and Quality of Information During Emergency Department Care Transitions.

INTRODUCTION: Suboptimal communication during emergency department (ED) care transitions has been shown to contribute to medical errors, sometimes resulting in patient injury and litigation. The study objective was to determine whether a standardized checkout process would decrease the number of relevant missed clinical items (MCI). METHODS: In this prospective pre- and post-intervention study conducted in an urban academic ED, we collected data on omitted or inaccurately conveyed medical information before and after the initiation of a standardized checkout process. The intervention included group checkout in an optimal location, review of electronic medical records, case discussion and assigned roles. MCI were considered relevant if they resulted in a delay or alteration in disposition or treatment plan. The primary outcome was the change in the number of MCI. Secondary outcomes were duration of checkout and physician satisfaction with the intervention. RESULTS: Pre-intervention, there were 94 relevant MCI during 164 care transitions. Post-intervention, there were 36 MCI in 157 transitions. The mean MCI per transition decreased by 58% from 0.57 (95% confidence interval [CI] [0.41, 0.73]) to 0.23 (95% CI [0.11-0.35]). Instituting the intervention did not lengthen checkout duration, which was 15 minutes (95% CI [13.81-16.19]) pre-intervention and 14 minutes (95% CI [12.99-15.01]) post-intervention. The majority of participants (73.4%) felt that the process decreased MCI, and 89.5% reported that the new process had a positive or neutral effect on their satisfaction with care transitions. CONCLUSION: The adoption of a standardized care transition process markedly decreased clinically relevant communication errors without lengthening checkout duration.

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.

A unique lysophospholipid acyltransferase (LPAT) antagonist, CI-976, affects secretory and endocytic membrane trafficking pathways.

Previous studies have shown that inhibition of a Golgi-complex-associated lysophospholipid acyltransferase (LPAT) activity by the drug CI-976 stimulates Golgi tubule formation and subsequent redistribution of resident Golgi proteins to the endoplasmic reticulum (ER). Here, we show that CI-976 stimulates tubule formation from all subcompartments of the Golgi complex, and often these tubules formed independently, i.e. individual tubules usually did not contain markers from different subcompartments. Whereas the cis, medial and trans Golgi membranes redistributed to the ER, the trans Golgi network (TGN) collapsed back to a compact juxtanuclear position similar to that seen with brefeldin A (BFA) treatment. Also similar to BFA, CI-976 induced the formation of endosome tubules, but unlike BFA, these tubules did not fuse with TGN tubules. Finally, CI-976 produced an apparently irreversible block in the endocytic recycling pathway of transferrin (Tf) and Tf receptors (TfRs) but had no direct effect on Tf uptake from the cell surface. Tf and TfRs accumulated in centrally located, Rab11-positive vesicles indicating that CI-976 inhibits export of cargo from the central endocytic recycling compartment. These results, together with previous studies, demonstrate that CI-976 inhibits multiple membrane trafficking steps, including ones found in the endocytic and secretory pathways, and imply a wider role for lysophospholipid acyltransferases in membrane trafficking.

Postpartum blindness: two cases.

We present 2 cases, one eclamptic patient and one noneclamptic patient, of headache, cortical blindness, and seizures. Both patients demonstrated findings consistent with posterior leukoencephalopathy syndrome. Posterior leukoencephalopathy syndrome is a rapidly evolving neurologic condition that is characterized by headache, nausea and vomiting, seizures, visual disturbances, altered sensorium, and occasionally focal neurologic deficits. Posterior leukoencephalopathy syndrome can be triggered by numerous conditions, including preeclampsia-eclampsia, and can be seen in the postpartum period. It is characterized predominately by white matter vasogenic edema of the occipital and posterior parietal lobes. This condition can be difficult to differentiate clinically from cerebral ischemia, and magnetic resonance imaging with diffusion-weighted imaging and apparent diffusion coefficient are needed to do so. In most cases of posterior leukoencephalopathy syndrome, the prognosis is excellent, with full resolution of symptoms.

Characterization of a novel CI-976-sensitive lysophospholipid acyltransferase that is associated with the Golgi complex.

Recent studies have identified a novel lysophospholipid acyltransferase (LPAT) that is associated with the Golgi complex and that is sensitive to the previously characterized acyl-CoA cholesterol acyltransferase inhibitor, 2,2-methyl-N-(2,4,6-trimethoxyphenyl)dodecanamide (CI-976). Here we show that besides acting on exogenous lysophospholipid (LPL) substrates, the CI-976-sensitive LPAT is also capable of reacylating endogenous Golgi LPL substrates, preferentially lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). Moreover, using exogenous substrates, we find that the CI-976-sensitive LPAT is capable of using a variety of fatty acyl-CoA donors ranging in chain length from 10 to 20 carbons. Additional characterization demonstrates that the CI-976-sensitive LPAT is ubiquitously expressed in rat tissues, is tightly associated with Golgi membranes, and has a pH optimum between pH 7.0 and 8.0. These studies further define a unique LPC/LPE-specific LPAT from Golgi membranes that likely has a novel function in membrane trafficking.

Inhibition of a Golgi complex lysophospholipid acyltransferase induces membrane tubule formation and retrograde trafficking.

Recent studies have suggested that formation of Golgi membrane tubules involves the generation of membrane-associated lysophospholipids by a cytoplasmic Ca2+-independent phospholipase A2 (PLA2). Herein, we provide additional support for this idea by showing that inhibition of lysophospholipid reacylation by a novel Golgi-associated lysophosphatidylcholine acyltransferase (LPAT) induces the rapid tubulation of Golgi membranes, leading in their retrograde movement to the endoplasmic reticulum. Inhibition of the Golgi LPAT was achieved by 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide (CI-976), a previously characterized antagonist of acyl-CoA cholesterol acyltransferase. The effect of CI-976 was similar to that of brefeldin A, except that the coatomer subunit beta-COP remained on Golgi-derived membrane tubules. CI-976 also enhanced the cytosol-dependent formation of tubules from Golgi complexes in vitro and increased the levels of lysophosphatidylcholine in Golgi membranes. Moreover, preincubation of cells with PLA2 antagonists inhibited the ability of CI-976 to induce tubules. These results suggest that Golgi membrane tubule formation can result from increasing the content of lysophospholipids in membranes, either by stimulation of a PLA2 or by inhibition of an LPAT. These two opposing enzyme activities may help to coordinately regulate Golgi membrane shape and tubule formation.

Phospholipase A2 (PLA2) enzymes in membrane trafficking: mediators of membrane shape and function.

Since the mid-1990s, there have been tremendous advances in our understanding of the roles that lipid-modifying enzymes play in various intracellular membrane trafficking events. Phospholipases represent the largest group of lipid-modifying enzymes and accordingly display a wide range of functions. The largest class of phospholipases are the phospholipase A(2) (PLA2) enzymes, and these have been most extensively studied for their roles in the generation lipid signaling molecules, e.g. arachidonic acid. In recent years, however, cytoplasmic PLA2 enzymes have also become increasingly associated with various intracellular trafficking events, such as the formation of membrane tubules from the Golgi complex and endosomes, and membrane fusion events in the secretory and endocytic pathways. Moreover, the ability of cytoplasmic PLA2 enzymes to directly affect the structure and function of membranes by altering membrane curvature suggests novel functional roles for these enzymes. This review will focus on the role of cytoplasmic PLA2 enzymes in intracellular membrane trafficking and the mechanisms by which they influence membrane structure and function.

A comparison trial for stratifying intermediate-risk chest pain: benefits of emergency department observation centers.

Chest pain of uncertain etiology (intermediate-risk chest pain [IR-CP]) constitutes a majority of acute chest pain presentations to emergency departments (EDs). A before- and-after trial of 2197 IR-CP patients transferred from the hospital's ED to one of three units-ED-based observation center (ED-OC), inpatient observation center (IN-OC), and inpatient units-compared mean cost, length of stay, and safety over a 2-year period. The mean per patient cost for management of IR-CP was lower in the ED-OC ($1642) than the IN-OC ($1910) or the inpatient units ($2785). The mean length of stay was shorter in the ED-OC (0.75 days) than in the IN-OC (1.18 days) or the inpatient units (2.16 days). Return rates were lower in the ED-OC at 7 days (0%) and at 6 months (0.45%) than the IN-OC (0% and 1.22%) or the inpatient units (0.77% and 3.67%). Overall hospital costs for managing IR-CP dropped significantly (12.5%) after the ED-OC was opened. ED-OCs provide a safe and cost-effective alternative to admission of IR-CP patients.