Economics of implementing an early deterioration detection solution for general care patients at a US hospital.

Aim: This study estimates the costs and outcomes pre- versus post-implementation of an early deterioration detection solution (EDDS), which assists in identifying patients at risk of clinical decline. Materials & methods: A retrospective database analysis was conducted to assess average costs per discharge, length of stay (LOS), complications, in-hospital mortality and 30-day all-cause re-admissions pre- versus post-implementation of an EDDS. Results: Average costs per discharge were significantly reduced by 18% (US$16,201 vs $13,304; p = 0.007). Average LOS was also significantly reduced (6 vs 5 days; p = 0.033), driven by a reduction in general care LOS of 1 day (p = 0.042). Complications, in-hospital mortality and 30-day all-cause re-admissions were similar. Conclusion: Costs and LOS were lower after implementation of an EDDS for general care patients.

Early deterioration detection solutions (EDDS) assist in identifying patients at risk of clinical decline to enable a timely response. This study estimates the costs and outcomes before and after implementation of an EDDS at a US hospital for general care patients. Results show average costs per discharge and average length of stay were significantly reduced after implementation. Complications, in-hospital mortality and 30-day all-cause re-admissions were similar in the two time periods.

Methamphetamine-Associated Heart Failure Hospitalizations Across the United States: Geographic and Social Disparities.

Background Although methamphetamine abuse is associated with the development of heart failure (HF), nationwide data on methamphetamine-associated HF (MethHF) hospitalizations are limited. This study evaluates nationwide HF hospitalizations associated with substance abuse to better understand MethHF prevalence trends and the clinical characteristics of those patients. Methods and Results This cross-sectional period-prevalence study used hospital discharge data from the National Inpatient Sample to identify adult primary HF hospitalizations with a secondary diagnosis of abuse of methamphetamines, cocaine, or alcohol in the United States from 2002 to 2014. All 2014 MethHF admissions were separated by regional census division to evaluate geographical distribution. Demographics, payer information, and clinical characteristics of MethHF hospitalizations were compared with all other HF hospitalizations. Total nationwide MethHF hospitalizations increased from 547 in 2002 to 6625 in 2014 with a predominance on the West Coast. Methamphetamine abuse was slightly more common among primary HF hospitalizations compared with all-cause hospitalizations (7.4 versus 6.4 per 1000; Cohen h=0.012; P<0.001). Among HF hospitalizations, patients with MethHF were younger (mean age, 48.9 versus 72.4 years; Cohen d=1.93; P<0.001), more likely to be on Medicaid (59.4% versus 8.8%; Cohen h=1.16; P<0.001) or uninsured (12.0% versus 2.6%; Cohen h=0.36; P<0.001), and more likely to present to urban hospitals (43.8% versus 28.3%; Cohen h=0.32; P<0.001) than patients with non-methamphetamine associated HF. Patients with MethHF had higher rates of psychiatric comorbidities and were more likely to leave the hospital against medical advice. Conclusions MethHF hospitalizations have significantly increased in the United States, particularly on the West Coast. Coordinated public health policies and systems of care are needed to address this rising epidemic.

Clinical and echocardiographic outcomes in heart failure associated with methamphetamine use and cessation.

OBJECTIVE: Methamphetamine use is associated with systolic dysfunction, pulmonary arterial hypertension and may also be associated with diastolic dysfunction. The impact of methamphetamine cessation on methamphetamine-associated heart failure (MethHF) remains poorly characterised. We aimed to longitudinally characterise methamphetamine-associated heart failure patients with reduced (METHrEF) and preserved (METHpEF) left ventricular ejection fraction (EF), and evaluate the relationship between methamphetamine cessation and clinical outcomes. METHODS: We performed a retrospective cohort study, and reviewed medical records of patients with METHrEF, METHpEF and heart failure controls without methamphetamine use. Echocardiographic variables were recorded for up to 12 months, with clinical follow-up extending to 24 months. RESULTS: Among METHrEF patients (n=28, mean age 51±9 years, 82.1% male), cessation was associated with improvement in EF (+10.6±13.1%, p=0.009) and fewer heart failure admissions per year compared with continued use (median 0.0, IQR 0.0-1.0 vs median 2.0, IQR 1.0-3.0, p=0.039). METHpEF patients (n=28, mean age 50±8 years, 60.7% male) had higher baseline right ventricular systolic pressure (median 53.44, IQR 43.70-84.00 vs median 36.64, IQR 29.44-45.95, p=0.011), and lower lateral E/E' ratio (8.1±3.6 vs 11.2±4., p<0.01) compared with controls (n=32). Significant improvements in echocardiographic parameters and clinical outcomes were not observed following cessation in this group. CONCLUSIONS: METHrEF patients who cease methamphetamine use have significant improvement in left ventricular systolic function and fewer heart failure admissions, suggesting that METHrEF may be reversible. Echocardiographic parameters suggest that some patients with METHpEF may have pulmonary hypertension in the absence of overt signs of left ventricular diastolic dysfunction, but additional study is needed to characterise this patient cohort.

Clinical Characteristics and Outcomes of Patients With Heart Failure and Methamphetamine Abuse.

BACKGROUND: Despite a global epidemic of methamphetamine abuse, methamphetamine-associated heart failure (MethHF) remains poorly understood. We sought to evaluate characteristics and outcomes for patients with MethHF. METHODS: We reviewed the electronic health records of the University of California, San Diego, from 2005 to 2016. We compared characteristics and outcomes between 896 patients with MethHF and 20,576 patients with heart failure (HF) identified using diagnosis codes, urine toxicology, and natriuretic peptides. RESULTS: Compared with HF, patients with MethHF were younger (50±10 vs 67±16 years), predominantly male (72% vs 54%), and had more psychiatric and substance use comorbidities, including mood/anxiety disorders (29% vs 16%) and opioid use (44% vs 7%). MethHF had a higher 5-year HF readmission rate (64±4% vs 45±1%; hazard ratio [HR] 1.53, P < .001) and a lower 10-year total mortality rate (25±3% vs 28±1%; HR 0.85, P = .09). Predictors of poor outcomes included mood/anxiety disorders (HF readmission HR 1.41, P = .04) and opioid abuse (mortality HR 1.52, P = .04). CONCLUSIONS: Patients with MethHF are frequently encumbered by psychiatric and substance abuse comorbidities, and carry a substantial risk of HF readmission and mortality. Comprehensive efforts are needed to stem this emerging epidemic.

The Impact of Substance Abuse on Heart Failure Hospitalizations.

BACKGROUND: The burden of substance abuse among patients with heart failure and its association with subsequent emergency department visits and hospital admissions are poorly characterized. METHODS: We evaluated the medical records of patients with a diagnosis of heart failure treated at the University of California-San Diego from 2005 to 2016. We identified substance abuse via diagnosis codes or urine drug screens. We used Poisson regression to evaluate the incidence rate ratios (IRR) of substance abuse for emergency department visits or hospitalizations with a primary diagnosis of heart failure, adjusted for age, sex, race, medical insurance status, and medical diagnoses. RESULTS: We identified 11,268 patients with heart failure and 15,909 hospital encounters for heart failure over 49,712 person-years of follow-up. Substance abuse was diagnosed in 15.2% of patients. Disorders such as methamphetamine abuse (prevalence 5.2%, IRR 1.96, 95% confidence interval [CI] 1.85-2.07), opioid use and abuse (8.2%, IRR 1.54, 95% CI 1.47-1.61), and alcohol abuse (4.5%, IRR 1.51, 95% CI 1.42-1.60) were associated with a greater number of hospital encounters for heart failure, with associations that were comparable to diagnoses such as atrial fibrillation (37%, IRR 1.78, 95% CI 1.73-1.84), ischemic heart disease (24%, IRR 1.67, 95% CI 1.62-1.73), and chronic kidney disease (26%, IRR 1.57, 95% CI 1.51-1.62). CONCLUSIONS: Although less prevalent than common medical comorbidities in patients with heart failure, substance-abuse disorders are significant sources of morbidity that are independently associated with emergency department visits and hospitalizations for heart failure. Greater recognition and treatment of substance abuse may improve outcomes among patients with heart failure.

Regression of inflammation in atherosclerosis by the LXR agonist R211945: a noninvasive assessment and comparison with atorvastatin.

OBJECTIVES: The aim of this study was to noninvasively detect the anti-inflammatory properties of the novel liver X receptor agonist R211945. BACKGROUND: R211945 induces reversal cholesterol transport and modulates inflammation in atherosclerotic plaques. We aimed to characterize with (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced cardiac magnetic resonance (DCE-CMR) inflammation and neovascularization, respectively, in atherosclerotic plaques with R211945 treatment compared with atorvastatin treatment and a control. METHODS: Twenty-one atherosclerotic New Zealand white rabbits were divided into 3 groups (control, R211945 [3 mg/kg orally], and atorvastatin [3 mg/kg orally] groups). All groups underwent (18)F-FDG-PET/CT and DCE-CMR at baseline and at 1 and 3 months after treatment initiation. Concomitantly, serum metabolic parameters and histology were assessed. For statistical analysis, continuous DCE-CMR and PET/CT outcomes were modeled as linear functions of time by using a linear mixed model, whereas the histological data, animal characteristics data, and nonlinear regression imaging data were analyzed with a 2-tailed Student t test. RESULTS: (18)F-FDG-PET/CT detected a decrease in mean and maximum standard uptake values (SUV) over time in the R211945 group (both p = 0.001), indicating inflammation regression. The atorvastatin group displayed no significant change (p = 0.371 and p = 0.600, respectively), indicating no progression or regression. The control group demonstrated an increase in SUV (p = 0.01 and p = 0.04, respectively), indicating progression. There was a significant interaction between time and group for mean and maximum SUV (p = 0.0003 and p = 0.0016, respectively) . DCE-CMR detected a trend toward difference (p = 0.06) in the area under the curve in the atorvastatin group, suggesting a decrease in neovascularization. There was no significant interaction between time and group (p = 0.6350 and p = 0.8011, respectively). Macrophage and apolipoprotein B immunoreactivity decreased in the R211945 and atorvastatin groups (p < 0.0001 and p = 0.0004, respectively), and R211945 decreased oxidized phospholipid immunoreactivity (p = 0.02). CONCLUSIONS: Noninvasive imaging with (18)F-FDG-PET/CT and DCE-CMR and histological analysis demonstrated significant anti-inflammatory effects of the LXR agonist R211945 compared with atorvastatin. The results suggest a possible role for LXR agonists in the treatment of atherosclerosis.

In vivo detection of oxidation-specific epitopes in atherosclerotic lesions using biocompatible manganese molecular magnetic imaging probes.

OBJECTIVES: This study sought to evaluate the in vivo magnetic resonance imaging (MRI) efficacy of manganese [Mn(II)] molecular imaging probes targeted to oxidation-specific epitopes (OSE). BACKGROUND: OSE are critical in the initiation, progression, and destabilization of atherosclerotic plaques. Gadolinium [Gd(III)]-based MRI agents can be associated with systemic toxicity. Mn is an endogenous, biocompatible, paramagnetic metal ion that has poor MR efficacy when chelated, but strong efficacy when released within cells. METHODS: Multimodal Mn micelles were generated to contain rhodamine for confocal microscopy and conjugated with either the murine monoclonal IgG antibody MDA2 targeted to malondialdehyde (MDA)-lysine epitopes or the human single-chain Fv antibody fragment IK17 targeted to MDA-like epitopes ("targeted micelles"). Micelle formulations were characterized in vitro and in vivo, and their MR efficacy (9.4-T) evaluated in apolipoprotein-deficient (apoE(-/-)) and low-density lipoprotein receptor negative (LDLR(-/-)) mice (0.05 mmol Mn/kg dose) (total of 120 mice for all experiments). In vivo competitive inhibition studies were performed to evaluate target specificity. Untargeted, MDA2-Gd, and IK17-Gd micelles (0.075 mmol Gd/kg) were included as controls. RESULTS: In vitro studies demonstrated that targeted Mn micelles accumulate in macrophages when pre-exposed to MDA-LDL with ∼10× increase in longitudinal relativity. Following intravenous injection, strong MR signal enhancement was observed 48 to 72 h after administration of targeted Mn micelles, with colocalization within intraplaque macrophages. Co-injection of free MDA2 with the MDA2-Mn micelles resulted in full suppression of MR signal in the arterial wall, confirming target specificity. Similar MR efficacy was noted in apoE(-/-) and LDLR(-/-) mice with aortic atherosclerosis. No significant differences in MR efficacy were noted between targeted Mn and Gd micelles. CONCLUSIONS: This study demonstrates that biocompatible multimodal Mn-based molecular imaging probes detect OSE within atherosclerotic plaques and may facilitate clinical translation of noninvasive imaging of human atherosclerosis.

Pioglitazone modulates vascular inflammation in atherosclerotic rabbits noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging.

OBJECTIVES: We sought to determine the antiatherosclerotic properties of pioglitazone using multimethod noninvasive imaging techniques. BACKGROUND: Inflammation is an essential component of vulnerable or high-risk atheromas. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, possesses potent anti-inflammatory properties. We aimed to quantify noninvasively the anti-inflammatory effects of pioglitazone on atheroma using (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). METHODS: Atherosclerotic plaques were induced in the aorta of 15 New Zealand white rabbits by a combination of a hyperlipidemic diet and 2 balloon endothelial denudations. Nine rabbits continued the same diet, whereas 6 rabbits received pioglitazone (10 mg/kg orally) in addition to the diet. Twelve animals underwent (18)F-FDG-PET/CT, and 15 animals underwent DCE-MRI at baseline, 1 month, and 3 months after treatment initiation. Concomitantly, serum metabolic parameters were monitored. After imaging was completed, aortic histologic analysis and correlation analysis were performed. RESULTS: The (18)F-FDG-PET/CT imaging detected an increase in average standardized uptake value in the control group (p < 0.01), indicating progressive inflammation, whereas stable standardized uptake values were observed in the treatment group, indicating no progression. The DCE-MRI analysis detected a significant decrease in the area under the curve for the pioglitazone group (p < 0.01). Immunohistologic examination of the aortas demonstrated a significant decrease in macrophage and oxidized phospholipid immunoreactivity in the pioglitazone group (p = 0.04 and p = 0.01, respectively) with respect to control animals, underlining the imaging results. Serum metabolic parameters showed no difference between groups. Strong positive correlations between standardized uptake value and macrophage density and between area under the curve and neovessels were detected (r(2) = 0.86 and p < 0.0001, and r(2) = 0.66 and p = 0.004, respectively). CONCLUSIONS: Both (18)F-FDG-PET/CT and DCE-MRI demonstrate noninvasively the anti-inflammatory effects of pioglitazone on atheroma. Both imaging methods seem suited to monitor inflammation in atherosclerosis.

Targeted iron oxide particles for in vivo magnetic resonance detection of atherosclerotic lesions with antibodies directed to oxidation-specific epitopes.

OBJECTIVES: The aim of this study was to determine whether iron oxide particles targeted to oxidation-specific epitopes image atherosclerotic lesions. BACKGROUND: Oxidized low-density lipoprotein plays a major role in atherosclerotic plaque progression and destabilization. Prior studies indicate that gadolinium micelles labeled with oxidation-specific antibodies allow for in vivo detection of vulnerable plaques with magnetic resonance imaging (MRI). However, issues related to biotransformation/retention of gadolinium might limit clinical translation. Iron oxides are recognized as safe and effective contrast agents for MRI. Because the efficacy of passively targeted iron particles remains variable, it was hypothesized that iron particles targeted to oxidation-specific epitopes might increase the utility of this platform. METHODS: Lipid-coated ultra-small superparamagnetic iron particles (LUSPIOs) (<20 nm) and superparamagnetic iron particles (<40 nm) were conjugated with antibodies targeted to either malondialdehyde-lysine or oxidized phospholipid epitopes. All formulations were characterized, and their in vivo efficacy evaluated in apolipoprotein E deficient mice 24 h after bolus administration of a 3.9-mg Fe/kg dose with MRI. In vivo imaging data were correlated with the presence of oxidation-specific epitopes with immunohistochemistry. RESULTS: MRI of atherosclerotic lesions, as manifested by signal loss, was observed after administration of targeted LUSPIOs. Immunohistochemistry confirmed the presence of malondialdehyde-epitopes and iron particles. Limited signal attenuation was observed for untargeted LUSPIOs. Additionally, no significant arterial wall uptake was observed for targeted or untargeted lipid-coated superparamagnetic iron oxide particles, due to their limited ability to penetrate the vessel wall. CONCLUSIONS: This study demonstrates that LUSPIOs targeted to oxidation-specific epitopes image atherosclerotic lesions and suggests a clinically translatable platform for the detection of atherosclerotic plaque.

Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis.

Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. (18)F-Fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of noninvasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy.

Longitudinal tracking of human dendritic cells in murine models using magnetic resonance imaging.

Ex vivo generated dendritic cells are currently used to induce therapeutic immunity in solid tumors. Effective immune response requires dendritic cells to home and remain in lymphoid organs to allow for adequate interaction with T lymphocytes. The aim of the current study was to detect and track Feridex labeled human dendritic cells in murine models using magnetic resonance imaging. Human dendritic cells were incubated with Feridex and the effect of labeling on dendritic cells immune function was evaluated. Ex vivo dendritic cell phantoms were used to estimate sensitivity of the magnetic resonance methods and in vivo homing was evaluated after intravenous or subcutaneous injection. R2*-maps of liver, spleen, and draining lymph nodes were obtained and inductively coupled plasma mass spectrometry or relaxometry methods were used to quantify the Feridex tissue concentrations. Correlations between in vivo R2* values and iron content were then determined. Feridex labeling did not affect dendritic cell maturation or function. Phantom results indicated that it was possible to detect 125 dendritic cells within a given slice. Strong correlation between in vivo R2* values and iron deposition was observed. Importantly, Feridex-labeled dendritic cells were detected in the spleen for up to 2 weeks postintravenous injection. This study suggests that magnetic resonance imaging may be used to longitudinally track Feridex-labeled human dendritic cells for up to 2 weeks after injection.

Iron oxide core oil-in-water emulsions as a multifunctional nanoparticle platform for tumor targeting and imaging.

Nanoemulsions are increasingly investigated for the delivery of hydrophobic drugs to improve their bioavailability or make their administration possible. In the current study, oil-in-water emulsions with three different mean diameters (30, 60, and 95 nm) were developed as a new multimodality nanoparticle platform for tumor targeting and imaging. To that aim, hydrophobically coated iron oxide particles were included in the soybean oil core of the nanoemulsions to enable their detection with magnetic resonance imaging (MRI), while the conjugation of a near infrared fluorophore allowed optical imaging. The accumulation of this novel nanocomposite in subcutaneous human tumors in nude mice was demonstrated with MRI and fluorescence imaging in vivo, and with Perl's staining of histological tumor sections ex vivo.

An investigation of nebulized bronchodilator delivery using a pediatric lung model of spontaneous breathing.

BACKGROUND: The literature lacks comparative data on nebulizer aerosol delivered via mask versus T-piece, to spontaneously breathing pediatric subjects. PURPOSE: To compare total inhaled drug mass delivered via standard pediatric aerosol mask versus via T-piece, with increasing distance. METHODS: We used a sample of 5 nebulizers, operated under manufacturers' conditions, with a standard pediatric aerosol mask and with a T-piece capped at one end, at 0 cm, 1 cm, and 2 cm from an inhalation filter placed at the inlet of a pediatric test lung. Inhaled drug mass was analyzed with spectrophotometry. Aerosol particle size was measured separately from the breathing simulations, using a laser particle sizer to determine fine-particle mass (particles < 4.7 mum) and fine-particle fraction as percent of total mass. The fine-particle fraction was used to estimate the fine-particle mass. RESULTS: The mean + SD values for inhaled drug mass as a percentage of nominal dose, at 0 cm, 1 cm, and 2 cm, with the mask were 2.88 + 0.79%, 1.61 + 0.65%, and 1.3 + 0.42%, respectively, and with the T-piece were 4.14 + 1.37%, 3.77 + 1.04%, and 3.47 + 0.64%, respectively. There was a statistically greater inhaled drug mass with T-piece than with mask, overall (p < 0.01), and a significant decrease with mask or T-piece as distance increased (p < 0.01). The difference between mask and T-piece for inhaled drug mass at 2 cm was statistically significant (p < 0.018). The mean + SD values for fine-particle mass estimated as a percentage of total drug mass at 0, 1, and 2 cm, with the mask were 1.39 + 0.36%, 0.78 + 0.29%, and 0.64 + 0.20%, respectively, and with the T-piece were 2.1 + 0.63%, 1.84 + 0.45%, and 1.71 + 0.27%, respectively. CONCLUSION: Inhaled drug mass was greater with T-piece than with a standard pediatric aerosol mask under the conditions studied.

Managing coastal erosion hazards in Maine

Natural processes cause hazards when shoreline recession or flooding threatens coastal development. Change of the coastline itself is not hazardous until something of value is threatened. The major causes of coastal hazards are storm surge, sea-level rise, erosion, and inlet migration. In recent decades human activity has become a major cause of coastal erosion. Coastal Maine sea levels can become elevated one meter (three feet) under a storm's center and may persist for the duration of the storm. This elevation is superimposed on and is independent of the tides. The threat of coastal flooding and erosion is greatest when a storm surge is superimposed on spring or perigean high tides. The recognition of coastal hazards from erosion and flooding is useful in directing public policy that may reduce the loss of property and life. Erosion rates could be used to determine a setback line in coastal sand dunes. New development could be concentrated landward of one or more setback lines in order to reduce future losses