Feasibility assessment of using the MiToS staging system for conducting economic evaluation in amyotrophic lateral sclerosis.

OBJECTIVES: This study assessed the feasibility of using the Milano-Torino staging (MiToS) system for conducting economic evaluation to measure health outcomes in amyotrophic lateral sclerosis (ALS). METHODS: A Markov model was developed using the MiToS system and evaluated with a hypothetical treatment versus standard of care. Health utilities and transition probabilities were derived from the literature. Four-time horizons (1, 5, 10, and 20 years) were examined. Treatment effects of 20-35% relative risk reduction (RRR) of progressing to the next MiToS stage were assessed. Three patient distribution scenarios were tested: (1) all patients began in stage 0; (2) patient distribution based on real-world TONiC study; (3) distribution based on the PRO-ACT database. Health outcomes (quality-adjusted life-years [QALYs], life-years [LYs]) were reported with a 3% discount rate. RESULTS: A time horizon of 10 years fully captured treatment benefits: incremental QALYs were 0.28-0.60, 0.21-0.45, and 0.26-0.55 for scenarios 1-3, respectively; incremental LYs were 0.56-1.17, 0.46-0.97, and 0.53-1.11, respectively. CONCLUSION: MiToS-based staging can be used for conducting economic analyses in ALS. Estimated incremental QALY and LY gains were meaningful within the context of ALS, for hypothetical treatments with RRR of 20-35%.

Assessment of pain-related behaviors in HIV-1 transgenic rats as a model of HIV-associated chronic pain.

Human immunodeficiency virus-1 (HIV)-associated chronic pain is a debilitating comorbid condition that affects 25-85% of people with HIV. The use of opioids to alleviate pain has given rise to opioid dependency in this cohort. Therefore, there is an urgent need to understand mechanisms and identify novel therapeutics for HIV-associated chronic pain. Several animal models have been developed to study HIV-related comorbidities. HIV-1 transgenic (Tg) rats have been shown to serve as a reliable model that mimic the deficits observed in people with HIV, such as neurological and immune system alterations. However, pain-related behavior in these animals has not been extensively evaluated. In this study, we measured evoked and spontaneous behavior in HIV-1Tg male and female rats. The results indicated that HIV-1Tg rats exhibit similar behavior to those with HIV-1-related neuropathy, specifically, cold sensitivity. Consequently, HIV-1Tg rats can serve as a model of neuropathy to study pain-related mechanisms and therapeutics targeted toward individuals living with HIV-1.

Temporal Trends, Predictors, and Outcomes of Acute Ischemic Stroke in Acute Myocardial Infarction in the United States.

Background There are limited contemporary data prevalence and outcomes of acute ischemic stroke (AIS) complicating acute myocardial infarction (AMI). Methods and Results Adult (>18 years) AMI admissions using the National Inpatient Sample database (2000-2017) were evaluated for in-hospital AIS. Outcomes of interest included in-hospital mortality, hospitalization costs, length of stay, discharge disposition, and use of tracheostomy and percutaneous endoscopic gastrostomy. The discharge destination was used to classify survivors into good and poor outcomes. Of a total 11 622 528 AMI admissions, 183 896 (1.6%) had concomitant AIS. As compared with 2000, in 2017, AIS rates increased slightly among ST-segment-elevation AMI (adjusted odds ratio, 1.10 [95% CI, 1.04-1.15]) and decreased in non-ST-segment-elevation AMI (adjusted odds ratio, 0.47 [95% CI, 0.46-0.49]) admissions (P<0.001). Compared with those without, the AIS cohort was on average older, female, of non-White race, with greater comorbidities, and higher rates of arrhythmias. The AMI-AIS admissions received less frequent coronary angiography (46.9% versus 63.8%) and percutaneous coronary intervention (22.7% versus 41.8%) (P<0.001). The AIS cohort had higher in-hospital mortality (16.4% versus 6.0%; adjusted odds ratio, 1.75 [95% CI, 1.72-1.78]; P<0.001), longer hospital length of stay, higher hospitalization costs, greater use of tracheostomy and percutaneous endoscopic gastrostomy, and less frequent discharges to home (all P<0.001). Among AMI-AIS survivors (N=153 318), 57.3% had a poor functional outcome at discharge with relatively stable temporal trends. Conclusions AIS is associated with significantly higher in-hospital mortality and poor functional outcomes in AMI admissions.

Increased return of spontaneous circulation at the expense of neurologic outcomes: Is prehospital epinephrine for out-of-hospital cardiac arrest really worth it?

INTRODUCTION: Current guidelines for the management of out-of-hospital cardiac arrest (OHCA) recommend the use of prehospital epinephrine by initial responders. This recommendation was initially based on data from animal models of cardiac arrest and minimal human data, but since its inception, more human data regarding prehospital epinephrine in this setting are now available. Although out-of-hospital return of spontaneous circulation (ROSC) may be higher with the use of epinephrine, worse neurologic outcomes may be associated with its use. METHODS: A systematic review of the literature was conducted by search of databases including PubMed, Embase, and OVID to identify studies comparing patients with OHCA who had received epinephrine before arrival to the hospital with those who had not. Studies were assessed for quality and bias, and data were abstracted from studies deemed appropriate for inclusion. A meta-analysis was conducted using a Mantel-Haenszel model for dichotomous outcomes. Outcomes studied were prehospital ROSC, survival at 1 month, survival to discharge, and positive neurologic outcome. RESULTS: A total of 14 studies with 655853 patients were included for the meta-analysis. The use of epinephrine for OHCA before arrival to the hospital was associated with a significant increase in ROSC (odds ratio, 2.86; P<.001) and a significant increase in the risk of poor neurologic outcome at the time of discharge (odds ratio 0.51, P=.008). There was no significant difference in survival at 1 month or survival to discharge. CONCLUSION: Use of epinephrine before arrival to the hospital for OHCA does not increase survival to discharge but does make it more likely for those who are discharged to have poor neurologic outcome. There is a need for additional randomized controlled trials.

Rates of and factors associated with infection in 200 909 Medicare implantable cardioverter-defibrillator implants: results from the National Cardiovascular Data Registry.

BACKGROUND: The rate of implantable cardioverter-defibrillator (ICD) infections has been increasing faster than that of implantation. We sought to determine the rate and predictors of ICD infection in a large cohort of Medicare patients. METHODS AND RESULTS: Cases submitted to the ICD Registry from 2006 to 2009 were matched to Medicare fee-for-service claims data using indirect patient identifiers. ICD infections occurring within 6 months of hospital discharge after implantation were identified by ICD-9 codes. Logistic regression was used to examine factors associated with risk of ICD infection. Of 200 909 implants, 3390 patients (1.7%) developed an ICD infection. The infection rate was 1.4%, 1.5%, and 2.0% for single, dual, and biventricular ICDs, respectively (P<0.001). Generator replacement had a higher rate compared with initial implant (1.9% versus 1.6%, P<0.001). The factors associated with infection were adverse event during implant requiring reintervention (odds ratio [OR], 2.692; 95% confidence interval [CI], 2.304-3.145), previous valvular surgery (OR, 1.525; 95% CI, 1.375-1.692), reimplantation for device upgrade, malfunction, or manufacturer advisory (OR, 1.354; 95% CI, 1.196-1.533), renal failure on dialysis (OR, 1.342; 95% CI, 1.123-1.604), chronic lung disease (OR, 1.215; 95% CI, 1.125-1.312), cerebrovascular disease (OR, 1.172; 95% CI, 1.076-1.276), and warfarin (OR, 1.155; 95% CI, 1.060-1.257). CONCLUSIONS: Patients who developed an ICD infection were more likely to have had peri-ICD implant complications requiring early reintervention, previous valve surgery, device replacement for reasons other than battery depletion, and increased comorbidity burden. Efforts should be made to carefully consider when to reenter the pocket at any time other than battery replacement.

Assessment of biological half life using in silico QSPkR approach: a self organizing molecular field analysis (SOMFA) on a series of antimicrobial quinolone drugs.

The quinolones belong to a family of synthetic potent broad-spectrum antibiotics and particularly active against gram-negative organisms, especially Pseudomonas aeruginosa. A 3D-QSPkR approach has been used to obtain the quantitative structure pharmacokinetic relationship for a series of quinolone drugs using SOMFA. The series consisting of 28 molecules have been investigated for their pharmacokinetic performance using biological half life (t(1/2)). A statistically validated robust model for a diverse group of quinolone drugs having flexibility in structure and pharmacokinetic profile (t(1/2)) obtained using SOMFA having good cross-validated correlation coefficient r(cv)(2) (0.6847), non cross-validated correlation coefficient r(2) values (0.7310) and high F-test value (33.9663). Analysis of 3D-QSPkR models through electrostatic and shape grids provide useful information about the shape and electrostatic potential contributions on t(1/2). The analysis of SOMFA results provide an insight for the generation of novel molecular architecture of quinolones with optimal half life and improved biological profile.

What's fueling the biotech engine--2008.

Despite the global economic slowdown, biologics managed single-digit growth in 2008, driven mainly by continued high growth in sales of antibodies and insulins. Novel biologics in development look promising, but crowding, pricing and reimbursement are emerging as longer-term concerns.