Four-Factor Prothrombin Complex Concentrate for the Reversal of Direct Oral Anticoagulants.

BACKGROUND: The prevalence of direct oral anticoagulants (DOACs) has increased with continued evidence of their efficacy and ease of use. However, the rise in their utilization also surfaced a concern regarding their reversal in patients actively bleeding and/or those requiring invasive procedures. Up until 2018, there were several reversal options available including 4-factor prothrombin complex concentrate (4-factor PCC), activated charcoal, desmopressin, and tranexamic acid. Then, in 2018, andexanet alpha, a recombinant factor Xa, was approved for the reversal of apixaban and rivaroxaban in patients with life-threatening or uncontrolled bleeding. Nonetheless, because 4-factor PCC is more easily attainable and cost-effective, it continues to be the more favorable option for many health-care professionals. METHODS: This retrospective chart review was conducted at NYU Winthrop Hospital in patients who received 4-factor PCC for the reversal of DOACs from January 2018 to July 2018. Patient charts were reviewed and relevant data was collected (admitting diagnosis, dose of 4-factor PCC utilized, etc). RESULTS: Fifty-three patients were evaluated with 85% experiencing a positive response and complete recovery following the administration of 4-factor PCC; 8 (15%) patients died after receiving 4-factor PCC, none as a result of its administration; 3 patients died secondary to other underlying comorbidities, 4 patients died due to an intracranial hemorrhage, and 1 died due to hematoma of the tongue. CONCLUSION: Based on the results thus far, the use of 4-factor PCC may be a good treatment option in patients requiring DOAC reversal.

Narcolepsy, depression, and severe flushing in an obese man.

Hypogonadism as a cause of depression, daytime sleepiness, and flushing is often missed in young males. Our case report highlights the importance of screening for hypogonadotropic hypogonadism and its treatment in symptomatic men with severe obesity, especially if they have depression, excessive sleepiness, and narcolepsy.

Acquired Hemophilia A: A Case Report.

Hemophilia A, also known as factor VIII deficiency, is a rare disorder caused by an insufficient level of factor VIII, an essential clotting protein. Hemophilia A can be inherited or acquired. Inherited hemophilia A is caused by a mutation to the factor VIII gene on the X chromosome, which is commonly passed down from parents to children. However, in about one-third of cases, the cause is a spontaneous mutation in that gene. Acquired hemophilia A is due to an autoantibody to factor VIII, which is termed an inhibitor. This rare disorder can cause life-threatening bleeding complications. Management relies on a rapid and accurate diagnosis, control of bleeding episodes, and eradication of the inhibitor by immunosuppression therapy. Most treatment strategies are centered around anecdotal reports or small case series. This case report summarizes the successful treatment of a patient with acquired hemophilia A and major bleeding following a surgical procedure, with the use of desmopressin, recombinant factor VIIa, repeated doses of recombinant factor VIII, rituximab, and prednisone.

A System for Developing and Projecting PM2.5 Spatial Fields to Correspond to Just Meeting National Ambient Air Quality Standards.

PM2.5 concentration fields that correspond to just meeting national ambient air quality standards (NAAQS) are useful for characterizing exposure in regulatory assessments. Computationally efficient methods that incorporate predictions from photochemical grid models (PGM) are needed to realistically project baseline concentration fields for these assessments. Thorough cross validation (CV) of hybrid spatial prediction models is also needed to better assess their predictive capability in sparsely monitored areas. In this study, a system for generating, evaluating, and projecting PM2.5 spatial fields to correspond with just meeting the PM2.5 NAAQS is developed and demonstrated. Results of ten-fold CV based on standard and spatial cluster withholding approaches indicate that performance of three spatial prediction models improves with decreasing distance to the nearest neighboring monitor, improved PGM performance, and increasing distance from sources of PM2.5 heterogeneity (e.g., complex terrain and fire). An air quality projection tool developed here is demonstrated to be effective for quickly projecting PM2.5 spatial fields to just meet NAAQS using realistic spatial response patterns based on air quality modeling. PM2.5 tends to be most responsive to primary PM2.5 emissions in urban areas, whereas response patterns are relatively smooth for NOx and SO2 emission changes. On average, PM2.5 is more responsive to changes in anthropogenic primary PM2.5 emissions than NOx and SO2 emissions in the contiguous U.S.

Amiodarone-Induced Syndrome of Inappropriate Antidiuretic Hormone: A Case Report and Review of the Literature.

Amiodarone (Cordarone®, Pfizer Inc) is an antiarrhythmic medication with a well-known toxicity profile, including rare cases of hyponatremia as a result of syndrome of inappropriate antidiuretic hormone (SIADH). We report on such a case in which a patient was found to be hyponatremic after evaluation. An 88-year-old male who presented to the emergency department was found to be hyponatremic secondary to amiodarone-induced SIADH following a fall, with possible seizure and traumatic brain injury. He had a history of hypertension, paroxysmal atrial fibrillation, emphysema, myocardial infarction, benign prostatic hyperplasia, chronic kidney disease, Meniere's disease, anemia, and gastroesophageal reflux. Upon admission, his urine sodium level was elevated, and his serum sodium, urine osmolality, and anion gap were below normal. In the setting of hyponatremia, the patient's amiodarone was held: he had been taking amiodarone 200 mg once daily for nine months prior to admission. He was treated with intravenous (IV) normal saline over four days. He was fluid-restricted and his sodium levels were closely monitored every two hours. Within 19 hours, his serum sodium levels had improved. Amiodarone was restarted approximately three days later. Upon follow-up after discharge, the patient remained on amiodarone for the next two months. His serum sodium level ranged from 126 mEq/L to 131 mEq/L over a two-week period. He was supplemented with sodium chloride tablets and has been otherwise stable. Amiodarone may cause acute or chronic SIADH, with a wide range of symptoms. Seizures have not been reported in the literature but our patient had a witnessed seizure, although his electroencephalogram (EEG) was negative. Syndrome of inappropriate antidiuretic hormone can occur with any formulation of amiodarone in a dose-dependent fashion. Our patient's sodium levels stabilized within two weeks after amiodarone was resumed. The mechanism of amiodarone-induced SIADH remains unclear.

Droxidopa for Hypotension of Different Etiologies: Two Case Reports.

Orthostatic hypotension is defined as a decrease in systolic blood pressure of at least 20 mmHg or a decrease in diastolic blood pressure of at least 10 mmHg (or both), within three minutes of moving from a supine to an upright or standing position. Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, subsequently providing alpha and beta-agonist effects to increase blood pressure. It is indicated in the treatment of neurogenic orthostatic hypotension caused by primary autonomic failure that is associated with Parkinson disease, multi-system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, and/or non-diabetic autonomic neuropathy. In addition, it has been studied in other disease states, such as diabetic autonomic neuropathy-associated orthostatic hypotension and supine hypotension. We report on two cases of off-label droxidopa use. The first case was for diabetic autonomic neuropathy-associated orthostatic hypotension, and the second case was for hypotension due to autonomic dysfunction associated with rheumatoid arthritis. Although the outcomes differed in each case, this article contributes to the literature demonstrating that droxidopa may have varying effects in treating orthostatic hypotension of non-neurogenic etiology.

Prevalence and Overtesting of True Heparin-Induced Thrombocytopenia in a 591-Bed Tertiary Care, Teaching Hospital.

Heparin-induced thrombocytopenia type II (HIT) is a rare but potentially fatal antibody-mediated reaction to all forms of heparin (unfractionated heparin, low-molecular weight heparin, heparin flushes, and heparin-coated catheters), which can lead to HIT with thrombosis. Two tests commonly used to screen for HIT include the enzyme-linked immunosorbent assay (ELISA) and serotonin release assay (SRA). This is a retrospective chart review study conducted from January 1, 2013, through December 31, 2014, to estimate the rate of true HIT in critical care patients at Winthrop-University Hospital, located in Mineola, New York. Patients are classified as positive for HIT if both ELISA and SRA immunoassays are positive. We reviewed 507 heparin immunoassays, excluding 64 who had an inappropriate ELISA test sent due to no administration of heparin, enoxaparin, or heparin lock flush at this or previous hospital stays at Winthrop. Of the 443 heparin immunoassays, ELISA results were positive for 66 patients (15.1%), and only 11 (2.5%) patients had true cases of HIT with a 95% confidence interval of 1.3% to 4.4%. The 4T score for those with true HIT (median: 5.0) was statistically higher compared to those without true HIT (median: 2.0; P < .001). Despite guidelines in place, overtesting for HIT is still a prevalent issue.

Health benefit assessment of PM2.5 reduction in Pearl River Delta region of China using a model-monitor data fusion approach.

The Pearl River Delta (PRD), one of the most polluted and populous regions of China, experienced a 28% reduction in fine particulate matter (PM2.5) concentration between 2013 (47 µg/m3) and 2015 (34 µg/m3) under a stringent national policy known as the Air Pollution Prevention and Control Action Plan (hereafter Action Plan). In this study, the health and economic benefits associated with PM2.5 reductions in PRD during 2013-2015 were estimated using the Environmental Benefits Mapping and Analysis Program-Community Edition (BenMAP-CE) software. To create reliable gridded PM2.5 surfaces for BenMAP-CE calculations, a data fusion tool which incorporates the accuracy of monitoring data and the spatial coverage of predictions from the Community Multiscale Air Quality (CMAQ) model has been developed. The population-weighted average PM2.5 concentration over PRD was predicted to decline by 24%. PM2.5-related mortality was estimated to decrease by more than 3800 due to decreases in stroke (48%), ischemic heart disease (IHD) (35%), chronic obstructive pulmonary disease (COPD) (10%), and lung cancer (LC) (7%). A 13% reduction in PM2.5-related premature deaths from these four causes yielded a large economic benefit of about 1300 million US dollars. Our research suggests that the Action Plan played a major role in reducing emissions and additional measures should be implemented to further reduce PM2.5 pollution and protect public health in the future.

Electrokinetic nondestructive in-situ technique for rehabilitation of liners damaged by fuels.

Underground Storage Tanks (UGST) are often used to store hydrocarbon products and fuels. Liners under such tanks are normally formed to prevent leaching or/and overflow to groundwater. Similar protection is required in case of waste fuels, which are discharged to disposal sites (e.g. ponds, landfill). Thus, a successful protection depends on the liner formation, which might undergo destruction due to leaching. This paper presents the results of experimental investigation to examine the serviceability of liner against leachate infiltration. In order to simulate the behavior of sand-bentonite liners affected by alternative fuels (ethanol and biofuel), the leaching column tests were applied and the hydraulic conductivity was used as an indicator of the effectiveness of the rehabilitation process. Furthermore, the silicate grout solution and pretreatment with surfactant under the effect of electrokinetic phenomena to pre-wash the biofuel residuals in liner were investigated. Silica grout formulations were developed and adequate curing periods were established for electro-silicatization process. Results showed that hydraulic conductivity was reduced fourfold for the case of using three-step electro-rehabilitation for alternative fuels under pressure of 40 kPa, and reduced threefold in the case of 100 kPa pressure on liner.

Evaluation of Hydrocortisone Continuous Infusion Versus Intermittent Boluses in Resolution of Septic Shock.

PURPOSE: To compare the effectiveness of continuous infusion of hydrocortisone versus intermittent boluses in the resolution of septic shock. METHODS: A retrospective chart review was performed to investigate the effects of low-dose hydrocortisone continuous infusion (200 mg per day) versus intermittent boluses (50 mg every six hours) in septic shock patients who did not respond to fluid resuscitation and vasopressors. The primary outcome was time to resolution of shock, defined by time from the initiation of hydrocortisone to time of vasopressor withdrawal when mean arterial pressure was greater than 65 mm Hg. Hospital length of stay, intensive care unit (ICU) length of stay, 28-day all-cause in-hospital mortality, and hyperglycemia were secondary outcomes. RESULTS: Of the 51 patients in the study, 33 received intermittent boluses of hydrocortisone. The median time to resolution of shock in the continuous group was three days, compared with a mean time of two days in the bolus group (P = 0.41). Mean hospital length of stay was 18.7 ± 19.4 days in the continuous group versus 18.6 ± 17.4 days in the bolus group (P = 0.77). Mean ICU length of stay was 10.4 ± 12.5 days in the continuous group versus 11.1 ± 9.2 days in the bolus group (P = 0.31). Thirteen patients (72%) in the continuous group died within 28 days, compared with 20 (60%) in the bolus group (P = 0.76). Five patients (28%) had hyperglycemic episodes after being given hydrocortisone in the continuous infusion group, compared with 20 patients (60%) in the bolus group (P = 0.04). CONCLUSION: There was no significant difference in time to resolution of septic shock between continuous infusion (200 mg per day) and intermittent boluses (50 mg every six hours) of hydrocortisone. There were also no statistically significant differences in overall hospital length of stay, ICU length of stay, and 28-day all-cause in-hospital mortality. However, there was a significant difference in the incidence of hyperglycemia between the two groups, with patients in the bolus group experiencing more hyperglycemia than those in the continuous infusion group.

Prevalence of Delirium and Coma In Mechanically Ventilated Patients Sedated With Dexmedetomidine or Propofol.

OBJECTIVE: To assess the prevalence of delirium and coma in mechanically ventilated patients sedated with dexmedetomidine or propofol alone; to evaluate the hospital length of stay for both treatment groups; and to evaluate the level of sedation, adverse effects, and hospital outcomes. METHODS: Medical records were reviewed retrospectively for patients who were admitted to the medical or surgical intensive care units (ICUs) in a 591-bed teaching hospital and who received either dexmedetomidine or propofol alone for 24 hours or more for sedation. RESULTS: A total of 111 patients were included in the study, with 56 patients in the dexmedetomidine group and 55 patients in the propofol group. Results of the analysis showed that the propofol group had a higher prevalence of coma (43.6% versus 12.5%; P < 0.001). Dexmedetomidine patients had a longer median hospital length of stay of 23.5 days (interquartile range [IQR], 11.5-39.5 days) versus 15.0 days (IQR, 7.0-24.0 days; P = 0.01). The rates of delirium were similar in both groups, with 16% in dexmedetomidine-treated patients versus 20% in propofol-treated patients (P = 0.63). CONCLUSION: No difference in the prevalence of delirium was found when comparing the dexmedetomidine- and propofol-treated groups. Propofol was associated with more coma and oversedation; dexmedetomidine was associated with longer time to extubation, longer length of stay in the ICU, and longer hospital length of stay.

Effect of Intravenous Acetaminophen on Postoperative Opioid Use in Bariatric Surgery Patients.

BACKGROUND: The use of opioids to achieve adequate pain relief following surgery is a common clinical practice. Opioids, however, are associated with serious adverse effects, such as respiratory depression, excessive sedation, and prolonged ileus, as well as increased mortality. The administration of intravenous (IV) acetaminophen to control postoperative pain has been effective in reducing opioid consumption in various surgical populations, but no studies have been conducted in bariatric surgery patients. This investigation was performed to determine whether IV acetaminophen reduces opioid requirements after bariatric surgery. METHODS: IV acetaminophen was added to the Winthrop-University Hospital formulary in September 2012. We conducted a retrospective chart-review analysis of bariatric surgery patients who received at least four doses of IV acetaminophen (1 g every six hours) plus opioids from October 2012 to March 2013 (after IV acetaminophen was added to the hospital formulary), compared with bariatric surgery patients who received only opioids for postoperative pain control from January 2012 to June 2012 (before IV acetaminophen was added to the hospital formulary). The study's primary endpoint was the difference between the two groups in opioid consumption, expressed in oral morphine equivalents (OMEs). Secondary endpoints included the reduction in the baseline pain score; the total amount of each opioid used; and the average hospital length of stay (LOS). RESULTS: A total of 96 patients were identified for potential enrollment from January 2012 to March 2013. Eight patients, however, did not qualify for participation because they had received only one dose of IV acetaminophen. The remaining 88 patients comprised two study groups: IV acetaminophen plus opiates (n = 44) and IV opiates alone (n = 44). Paradoxically, the patients in the acetaminophen/opiates group required significantly more opiates (in OMEs) compared with the group that received opiates alone (median, 93.5 mg versus 63.0 mg, respectively; P = 0.017). There were no significant differences between the two treatment groups in terms of the median change from baseline in pain scores (-4 versus -4; P = 0.162) or the median hospital LOS (two days versus two days; P = 0.704). CONCLUSION: IV acetaminophen did not reduce opioid use for postoperative pain management in bariatric surgery patients.

Creating locally-resolved mobile-source emissions inputs for air quality modeling in support of an exposure study in Detroit, Michigan, USA.

This work describes a methodology for modeling the impact of traffic-generated air pollutants in an urban area. This methodology presented here utilizes road network geometry, traffic volume, temporal allocation factors, fleet mixes, and emission factors to provide critical modeling inputs. These inputs, assembled from a variety of sources, are combined with meteorological inputs to generate link-based emissions for use in dispersion modeling to estimate pollutant concentration levels due to traffic. A case study implementing this methodology for a large health study is presented, including a sensitivity analysis of the modeling results reinforcing the importance of model inputs and identify those having greater relative impact, such as fleet mix. In addition, an example use of local measurements of fleet activity to supplement model inputs is described, and its impacts to the model outputs are discussed. We conclude that with detailed model inputs supported by local traffic measurements and meteorology, it is possible to capture the spatial and temporal patterns needed to accurately estimate exposure from traffic-related pollutants.

Cardiovascular outcomes and the physical and chemical properties of metal ions found in particulate matter air pollution: a QICAR study.

BACKGROUND: This paper presents an application of quantitative ion character-activity relationships (QICAR) to estimate associations of human cardiovascular (CV) diseases (CVDs) with a set of metal ion properties commonly observed in ambient air pollutants. QICAR has previously been used to predict ecotoxicity of inorganic metal ions based on ion properties. OBJECTIVES: The objective of this work was to examine potential associations of biological end points with a set of physical and chemical properties describing inorganic metal ions present in exposures using QICAR. METHODS: Chemical and physical properties of 17 metal ions were obtained from peer-reviewed publications. Associations of cardiac arrhythmia, myocardial ischemia, myocardial infarction, stroke, and thrombosis with exposures to metal ions (measured as inference scores) were obtained from the Comparative Toxicogenomics Database (CTD). Robust regressions were applied to estimate the associations of CVDs with ion properties. RESULTS: CVD was statistically significantly associated (Bonferroni-adjusted significance level of 0.003) with many ion properties reflecting ion size, solubility, oxidation potential, and abilities to form covalent and ionic bonds. The properties are relevant for reactive oxygen species (ROS) generation, which has been identified as a possible mechanism leading to CVDs. CONCLUSION: QICAR has the potential to complement existing epidemiologic methods for estimating associations between CVDs and air pollutant exposures by providing clues about the underlying mechanisms that may explain these associations.

Use of dexmedetomidine to facilitate non-invasive ventilation.

Patients with chronic obstructive pulmonary disease and congestive heart failure exacerbations, as well as pneumonia benefit from the use of non-invasive ventilation (NIV), due to increased patient comfort and a reduced incidence of ventilator-associated pneumonia. However, some patients do not tolerate NIV due to anxiety or agitation, and traditionally physicians have withheld sedation from these patients due to concerns of loss of airway protection and respiratory depression. We report our recent experience with a 91-year-old female who received NIV for acute respiratory distress secondary to pneumonia. The duration of NIV was a total time period of 86 h, using the bilevel positive airway pressure mode via a full face mask. The patient was initially agitated with the NIV, but with the addition of the dexmedetomidine, she tolerated it well. The dexmedetomidine was administered without a loading dose, as a continuous infusion ranging from 0.2 to 0.5 mcg/kg/hr, titrated to a Ramsey score of three. This case illustrates the safe use of dexmedetomidine to facilitate NIV, and improve compliance, which may reduce ICU length of stay.

Acute lung injury following the use of granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor with immunostimulatory effects that include the activation and priming of neutrophils. Neutrophils are an important part of the human immune system, yet they have been implicated in the pathogenesis of acute lung injury (ALI). GM-CSF has been found to increase the amount of activated neutrophils recruited to the lung tissue as well as to increase the life span of neutrophils leading to substantial lung tissue injury and the development of ALI. While, there have been few cases reported of ALI following GM-CSF, the experience reported here is the first of ALI subsequent to local administration of GM-CSF in a patient with significant pulmonary comorbidities.

Use of dexmedetomidine for the treatment of alcohol withdrawal syndrome in critically ill patients: a retrospective case series.

Alcohol withdrawal syndrome (AWS) continues to be a challenge to manage in the ICU setting, and the ideal pharmacological treatment continues to evolve. Dexmedetomidine is a newer agent approved for short-term sedation in the ICU, but its use in the treatment of AWS has been limited. We report a retrospective case series of ten patients who were identified as receiving dexmedetomidine for AWS as designated by electronic pharmacy records. All subjects were male, with a mean age of 53.6 years, and a mean ICU length of stay of 9.3 days. They were all diagnosed with AWS by DSM-IV criteria. All the study patients received dexmedetomidine during their hospital course as a treatment for AWS. Studied variables included demographic data, dose and duration of dexmedetomidine, other pharmaceutical agents, and hemodynamics. Dexmedetomidine was safe to use in all patients, although mechanical ventilation was still required in three patients. With dexmedetomidine, the autonomic hyperactivity was blunted, with a mean 12.8% reduction in rate pressure product observed. Consideration should be given to the combined use of dexmedetomidine with benzodiazepines in the treatment of AWS.