ABSTRACT
BACKGROUND: Angiotensin receptor-neprilysin inhibitor (ARNI) prescription in the United States remains suboptimal despite strong evidence for efficacy and value in heart failure with reduced ejection fraction. Factors responsible for under prescription are not completely understood. Economic limitations may play a disproportionate role in reduced access for some patients. METHODS: This is an analysis of the Get With The Guidelines-Heart Failure registry, supplemented with data from the Distressed Community Index. Data were fit to a mixed-effects regression model to investigate clinical and socioeconomic factors associated with ARNI prescription at hospital discharge. Missing data were handled by multilevel multiple imputation. RESULTS: Of the 136 144 patients included in analysis, 12.6% were prescribed an ARNI at discharge. The dominant determinants of ARNI prescription were ARNI use while inpatient (odds ratio [OR], 72 [95% CI, 58-89]; P<0.001) and taking an ARNI before hospitalization (OR 9 [95% CI, 7-13]; P<0.001). Having an ACE (angiotensin-converting enzyme) inhibitor/angiotensin receptor blocker (ARB)/ARNI contraindication was associated with lower likelihood of ARNI prescription at discharge (OR, 0.11 [95% CI, 0.10-0.12]; P<0.001). Socioeconomic factors associated with lower likelihood of ARNI prescription included having no insurance (OR, 0.60 [95% CI, 0.50-0.72]; P<0.001) and living in a ZIP Code identified as distressed (OR, 0.81 [95% CI, 0.70-0.93]; P=0.010). The rate of ARNI prescription is increasing with time (OR, 2 [95% CI, 1.8-2.3]; P<0.001 for patients discharged in 2020 as opposed to 2017), but the disparity in prescription rates between distressed and prosperous communities appears to be increasing. CONCLUSIONS: Multiple medical and socioeconomic factors contribute to low rates of ARNI prescription at hospital discharge. Potential targets for improving ARNI prescription rates include initiating ARNIs during hospitalization and aggressively addressing patients' access barriers with the support of inpatient social services and pharmacists.
Subject(s)
Heart Failure , Neprilysin , Humans , United States , Heart Failure/diagnosis , Heart Failure/drug therapy , Stroke Volume , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin Receptor Antagonists/pharmacology , Patient Discharge , Receptors, Angiotensin , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Socioeconomic Factors , Antihypertensive Agents/pharmacology , Prescriptions , HospitalsABSTRACT
BACKGROUND: Continuous outpatient inotrope infusion therapy (COIIT) can be used as palliative or interim treatment in patients with advanced heart failure (AHF). Despite widespread use, there is a relative lack of data informing best practices. This study aimed to examine whether patterns of COIIT use differed by region and to explore whether observed differences influenced clinical outcomes. METHODS: Retrospective study of AHF patients receiving COIIT from May 2009 through June 2016. The primary outcome was regional difference, the secondary outcome was persistence (duration) on therapy. Cox proportional hazards model was used to calculate hazard ratios for treatment regimens. RESULTS: There were 3,286 patients, mean (SD) age 61.9 (14.4) years and 74.0% (2,433) male. Inotrope selection and beta blocker use varied by region by chi square (χ2 (21) = 166.9, p < 0.001). Persistence was greater on milrinone compared to dobutamine (HR (for discontinuation) 0.54, CI 0.41-0.70, p < 0.001). Concurrent beta-blocker was associated with greater persistence for patients receiving milrinone (HR 0.13, CI 0.08-0.20, p < 0.001) and dobutamine (HR 0.36, CI 0.18-0.71, p < 0.001). CONCLUSIONS: Patterns of COIIT use varied by region, and variations in use were associated with differences in clinical outcomes.
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PURPOSE: Neuroretinitis (NR) is an inflammatory disorder that presents with painless vision loss due to optic disc edema, peripapillary detachment, and macular lipid exudation. We report the first two documented cases of co-infections of pediatric NR due to Bartonella henselae with HSV and Toxocara cati, respectively. OBSERVATIONS: A 10-year-old female with acute right-sided facial droop, right eye pain, and acute visual loss of the right eye is diagnosed with co-infection of Bartonella and HSV retinitis and is successfully treated with acyclovir, rifampin, and doxycycline. A 13-year-old female with progressive visual loss of the left eye is diagnosed with co-infection of Bartonella and ocular toxocariasis and is successfully treated with doxycycline, rifampin, prednisolone, and albendazole. CONCLUSIONS AND IMPORTANCE: Early recognition and multi-modal treatment is necessary to prevent delayed diagnosis and treat the underlying NR causes for optimal visual recovery.
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AIMS: Sacubitril/valsartan combines renin-angiotensin-aldosterone system inhibition with amplification of natriuretic peptides. In addition to well-described effects, natriuretic peptides exert direct effects on pulmonary vasculature. The effect of sacubitril/valsartan on pulmonary artery pressure (PAP) has not been fully defined. METHODS AND RESULTS: This was a retrospective case-series of PAP changes following transition from angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) to sacubitril/valsartan in patients with heart failure reduced ejection fraction and a previously implanted CardioMEMS™ sensor. Pre-sacubitril/valsartan and post-sacubitril/valsartan PAPs were compared for each patient by examining averaged consecutive daily pressure readings from 1 to 5 days before and after sacubitril/valsartan exposure. PAP changes were also compared between patients based on elevated trans-pulmonary gradients (trans-pulmonary gradient ≥ 12 mmHg) at time of CardioMEMS™ sensor implantation. The cohort included 18 patients, 72% male, mean age 60.1 ± 13.6 years. There was a significant decrease in PAPs associated with transition from ACEI/ARB to sacubitril/valsartan. The median (interquartile range) pre-treatment and post-treatment change in mean, systolic and diastolic PAPs were -3.6 (-9.8, -0.7) mmHg (P < 0.001), -6.5 (-15.0, -2.0) mmHg (P = 0.001), and -2.5 (-5.7, -0.7) (P = 0.001), respectively. The decrease in PAPs was independent of trans-pulmonary gradient (F(1,16) = 0.49, P = 0.49). CONCLUSIONS: In this retrospective case series, transition from ACEI/ARB to sacubitril/valsartan was associated with an early and significant decrease in PAPs.
Subject(s)
Angiotensin Receptor Antagonists , Heart Failure , Aged , Aminobutyrates , Angiotensin-Converting Enzyme Inhibitors , Biphenyl Compounds , Drug Combinations , Female , Heart Failure/drug therapy , Humans , Male , Middle Aged , Neprilysin , Retrospective Studies , Stroke Volume , ValsartanSubject(s)
Histiocytosis, Langerhans-Cell/diagnostic imaging , Orbital Diseases/diagnostic imaging , Paranasal Sinus Diseases/diagnostic imaging , Sphenoid Sinus/pathology , Biopsy , Child, Preschool , Female , Histiocytosis, Langerhans-Cell/drug therapy , Humans , Magnetic Resonance Imaging , Orbital Diseases/drug therapy , Paranasal Sinus Diseases/drug therapy , Positron-Emission Tomography , Sphenoid Sinus/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Hemodynamic-guided therapy using the CardioMEMS™ system has been shown to reduce heart failure hospitalization (HFH) in both clinical trials and real-world settings. However, the CardioMEMS system requires input from multiple independent elements to achieve its effect, and no studies have been done to investigate those elements. Consistent patient participation and health care provider participation are two of those key elements, and this study sought to assess how they affect HFHs. METHODS: This was a single-center, retrospective cohort study of patients with the CardioMEMS sensor. The primary outcome was the number of HFH days patients experienced in the 1 year following CardioMEMS sensor implant. The primary independent variables were the average number of days between patient transmissions of data and the average number of days between health care provider reviews of those data. Covariates included patient demographics, medical comorbidities, history of HFHs, and initial pressure response to hemodynamic-guided therapy at 28 days after implant. Data were fit to a zero-inflated negative binomial regression. RESULTS: Seventy-eight patients were included in the study. The mean age was 64 ± 15 years, 52 (67%) were male, and 58 (76%) had heart failure with reduced ejection fraction. During the study period, there were 538 cumulative HFH patient-days. Based on the regression model, there was an exponential relationship between HFH days and the mean number of days between patient transmissions (IRR = 1.74, 95% CI: 1.09-2.75, p=0.019). There was also an exponential relationship between HFH days and the mean number of days between health care provider reviews (IRR = 1.03, 95% CI: 1.01-1.05, p=0.013). CONCLUSIONS: This single-center study suggests that more frequent patient transmissions and health care provider reviews of the CardioMEMS system are associated with a decreased number of HFH days, but larger multicentered studies are required. Further systems-based analyses of the CardioMEMS system may be a useful approach to guiding effective use of the CardioMEMS device.
Subject(s)
Abnormalities, Multiple , Imaging, Three-Dimensional , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus/abnormalities , Salivary Gland Diseases/diagnosis , Salivary Glands/abnormalities , Tomography, X-Ray Computed/methods , Adult , Diagnosis, Differential , Humans , Lacrimal Apparatus/diagnostic imaging , Lacrimal Apparatus Diseases/congenital , Male , Salivary Gland Diseases/congenital , Salivary Glands/diagnostic imagingABSTRACT
We describe the clinical course of a 64-year-old woman with stage IVa lung adenocarcinoma who presented with over 1 month of fatigue, unintentional weight loss and emesis. She initiated treatment with nivolumab immunotherapy 1 year prior and had been tolerating the treatment well. A comprehensive workup revealed multiple endocrinological abnormalities consistent with hypophysitis leading to hypopituitarism in the form of central adrenal insufficiency and hypogonadism as well as a partially empty sella on imaging. This case demonstrates that while receiving novel forms of treatment such as immunotherapy, patients should be monitored closely for a wide range of adverse effects.
Subject(s)
Carcinoma, Non-Small-Cell Lung/complications , Hypophysitis/chemically induced , Nivolumab/adverse effects , Adenocarcinoma of Lung/pathology , Adrenal Insufficiency/complications , Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Empty Sella Syndrome/diagnostic imaging , Empty Sella Syndrome/etiology , Female , Humans , Hydrocortisone/administration & dosage , Hydrocortisone/therapeutic use , Hypophysitis/complications , Hypopituitarism/drug therapy , Hypopituitarism/etiology , Lung Neoplasms/pathology , Middle Aged , Nivolumab/therapeutic use , Treatment OutcomeABSTRACT
Purpose: The photopic negative response (PhNR) is a slow negative component of a flash photopic full-field ERG that has been shown to be specific for retinal ganglion cell (RGC) activity. Direct evaluation of RGC function is desirable in patients with Leber's hereditary optic neuropathy (LHON) in which the loss of central acuity can make it difficult to monitor patients with standard metrics. The purpose of this study was to evaluate the use of PhNR as an objective noninvasive clinical metric in LHON. Methods: Full-field photopic ERG recordings were collected in subjects with the mt.11778G>A/ND4 LHON mutation using a red on blue stimulus. The PhNR was identified using a computer-based automated detection system, and data were manually examined to remove movement artifacts. Results: The PhNR amplitude was compared between controls (n = 13), carriers (n = 17), and affected (n = 6). Mean PhNR amplitude decreased significantly across groups (P < 0.0001). Post hoc Tukey's test revealed a significant decrease in PhNR amplitude between carriers and controls (P < 0.05) and between carriers and affected (P < 0.01). Conclusions: We are able to demonstrate that the PhNR amplitude is significantly decreased in patients affected by LHON compared to carriers in a well-described pedigree. Surprisingly, there was also a decrease in PhNR in carriers, suggesting potential subclinical RGC dysfunction in some carriers. This is important in patients affected with LHON who typically have a dense central scotoma. The PhNR may be a useful objective outcome measure for future clinical trials.
Subject(s)
Color Vision/physiology , Optic Atrophy, Hereditary, Leber/physiopathology , Retinal Ganglion Cells/physiology , Adult , DNA Mutational Analysis , DNA, Mitochondrial/genetics , Electroretinography , Female , Heterozygote , Humans , Male , Middle Aged , Nerve Fibers/pathology , Optic Atrophy, Hereditary, Leber/genetics , Photic Stimulation , Visual Acuity/physiology , Visual Fields/physiologyABSTRACT
Purpose: To compare the efficacy of microneedle-delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con1 versus vehicle controls on choroidal neovascularization (CNV) growth in a pig model. Methods: Forty-one pigs were injected on the day of CNV induction (hI-con1 on postinduction day 14) with either 2.5 mg Ivit bevacizumab (n = 9), 1 mg Ivit pazopanib (n = 9), 300 Ivit µg hI-con1 (n = 4), or 1 mg SC pazopanib (n = 9), vs. 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at week 2 (11), 3 (8), 4 (11), and 8 (11), and eyes were fixed for histology. The size of the CNV was determined from histology, and CNV height was the primary outcome measure. Immunostaining for cytotoxic T-cells was performed in the hI-con1 study. Results: In 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost during dissection. One animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller mean height measurements (90 ± 20 µm) versus controls (180 ± 20 µm; P = 0.009), and Ivit pazopanib had smaller maximum CNV height (173 ± 43 µm) compared to SC pazopanib (478 ± 105 µm; P = 0.018). The mean lesion size in hI-con1-treated animals trended smaller than in controls (P = 0.11). Immunostaining did not detect cytotoxic T-cells. Conclusions: Intravitreal pazopanib and to a lesser extent hI-con1 reduced the size of CNV lesions. The pig model has nearly a 100% rate of type 2 CNV induction and is a reliable preclinical model with pharmacodynamics similar to humans.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Bevacizumab/pharmacology , Choroidal Neovascularization/drug therapy , Disease Models, Animal , Immunoconjugates/pharmacology , Pyrimidines/pharmacology , Sulfonamides/pharmacology , Animals , Choroidal Neovascularization/pathology , Fluorescein Angiography , Indazoles , Intravitreal Injections , Swine , T-Lymphocytes, Cytotoxic/immunology , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
PURPOSE: To illustrate the natural history of Leber's hereditary optic neuropathy (LHON). DESIGN: Prospective observational case series. PARTICIPANTS: The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation. METHODS: A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged. MAIN OUTCOME MEASURES: The main outcome measures were visual acuity, HVF MD, and RNFL thickness. RESULTS: Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes. CONCLUSIONS: Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau.
Subject(s)
Nerve Fibers/pathology , Optic Atrophy, Hereditary, Leber/diagnosis , Retinal Ganglion Cells/pathology , Vision Disorders/diagnosis , Visual Fields/physiology , Adolescent , Adult , DNA, Mitochondrial/genetics , Female , Humans , Male , Middle Aged , Optic Atrophy, Hereditary, Leber/genetics , Pedigree , Prospective Studies , Tomography, Optical Coherence , Vision Disorders/physiopathology , Visual Acuity/physiology , Visual Field Tests , Young AdultABSTRACT
This study aims to determine the course of vision loss after Baerveldt aqueous tube shunt placement and identify risk factors associated with unexplained severe long-term vision loss, or snuff-out. We retrospectively reviewed 247 eyes of 222 patients who underwent Baerveldt implantations at one of two academic institutions. Postoperative vision loss at 6 months following surgery was categorized as mild-to-moderate versus severe and long-term versus transient. Long-term vision loss, defined as 3 or more lines of Snellen visual acuity (VA) loss compared with preoperative VA, occurred in 63 of 247 eyes (25.5%), and 39 had mild-to-moderate and 24 had severe loss. Of these 63 eyes, 18 had no identifiable cause of vision loss. On multivariate analysis, poorer Snellen VA on postoperative day 1 (POD1) was found to be a significant risk factor for long-term vision loss (p = 0.005). In addition, the negative change in preoperative versus POD1 Snellen VA (p = 0.021) and the presence of split fixation involving the inferonasal quadrant on preoperative Humphrey visual field (p = 0.044) were significant risk factors for snuff-out. Transient vision loss occurred in 76 of 242 eyes (30.8%). In conclusion, vision loss is not uncommon after Baerveldt surgery, with snuff-out occurring in 2.4% of cases in this study.
ABSTRACT
In this paper, the authors describe an online tool with which to convert and thus quantify count finger measurements of visual acuity into Snellen equivalents. It is hoped that this tool allows for the re-interpretation of retrospectively collected data that provide visual acuity in terms of qualitative count finger measurements.
Subject(s)
Ophthalmology/trends , Practice Patterns, Physicians' , Retina , Specialization/trends , Adult , Aged , Female , Humans , Male , Middle Aged , Self Report , Societies, Medical , Surveys and Questionnaires , United StatesABSTRACT
Patients with Bipolar disorder smoke more than the general population. Smoking negatively impacts mortality and clinical course in Bipolar disorder patients. Prior studies have shown contradictory results regarding the impact of psychosis on smoking behavior in Bipolar disorder. We analyzed a large sample of Bipolar disorder and Schizoaffective disorder, Bipolar Type patients and predicted those with a history of psychosis would be more likely to be nicotine dependent. Data from subjects and controls were collected from the Genomic Psychiatry Cohort (GPC). Subjects were diagnosed with Bipolar disorder without psychosis (N = 610), Bipolar disorder with psychosis (N = 1544). Participants were classified with or without nicotine dependence. Diagnostic groups were compared to controls (N = 10065) using logistic regression. Among smokers (N = 6157), those with Bipolar disorder had an increased risk of nicotine dependence (OR = 2.5; P < 0.0001). Patients with Bipolar disorder with psychosis were more likely to be dependent than Bipolar disorder patients without psychosis (OR = 1.3; P = 0.03). Schizoaffective disorder, Bipolar Type patients had more risk of nicotine dependence when compared to Bipolar disorder patients with or without psychosis (OR = 1.2; P = 0.02). Bipolar disorder patients experiencing more severity of psychosis have more risk of nicotine dependence. © 2015 Wiley Periodicals, Inc.
Subject(s)
Bipolar Disorder/epidemiology , Bipolar Disorder/psychology , Tobacco Use Disorder/epidemiology , Tobacco Use Disorder/psychology , Adult , Female , Humans , Logistic Models , MaleABSTRACT
BACKGROUND: Ninety percent of emergency incidents occur in developing countries, and this is only expected to get worse as these nations develop. As a result, governments in developing countries are establishing emergency care systems. However, there is currently no widely-usable, objective method to monitor or research the rapid growth of emergency care in the developing world. METHODS: Analysis of current quantitative methods to assess emergency care in developing countries, and the proposal of a more appropriate method. RESULTS: Currently accepted methods to quantitatively assess the efficacy of emergency care systems cannot be performed in most developing countries due to weak record-keeping infrastructure and the inappropriateness of applying Western derived coefficients to developing country conditions. As a result, although emergency care in the developing world is rapidly growing, researchers and clinicians are unable to objectively measure its progress or determine which policies work best in their respective countries. We propose the TEWS methodology, a simple analytical tool that can be handled by low-resource, developing countries. CONCLUSIONS: By relying on the most basic universal parameters, simplest calculations and straightforward protocol, the TEWS methodology allows for widespread analysis of emergency care in the developing world. This could become essential in the establishment and growth of new emergency care systems worldwide.