Association of Frailty With Clinical and Financial Outcomes Following Liver Transplantation.

Introduction: Frailty, a measure of physiological aging and reserve, has been validated as a prognostic indicator of mortality in patients with cirrhosis. However, large-scale analyses of the independent association of frailty with clinical and financial outcomes following liver transplantation (LT) are lacking.

Methods: Adults (≥18 years) undergoing LT were identified in the 2016-2020 National Readmissions Database.

Failure to rescue following emergency general surgery: A national analysis.

Background: Failure to rescue (FTR) is increasingly recognized as a quality metric but remains understudied in emergency general surgery (EGS). We sought to identify patient and operative factors associated with FTR to better inform standardized metrics to mitigate this potentially preventable event.

Methods: All adult (≥18 years) non-elective hospitalizations for large bowel resection, small bowel resection, repair of perforated ulcer, laparotomy and lysis of adhesions were identified in the 2016-2020 National Readmissions Database.

Timing of Noncardiac Surgery Following Transcatheter Aortic Valve Replacement: A National Analysis.

Background: The optimal timing of noncardiac surgery (NCS) following transcatheter aortic valve replacement (TAVR) for aortic stenosis has not been elucidated by current national guidelines.

Objectives: The aim of this study was to evaluate the effect of the time interval between TAVR and NCS (Δt) on the perioperative risk of major adverse events (MAEs).

Methods: All adult admissions for isolated TAVR for aortic stenosis were identified in the 2016 to 2020 Nationwide Readmissions Database.

Association of hospital volume and operative approach with clinical and financial outcomes of elective esophagectomy in the United States.

Introduction: Literature regarding the impact of esophagectomy approach on hospitalizations costs and short-term outcomes is limited. Moreover, few have examined how institutional MIS experience affects costs. We thus examined utilization trends, costs, and short-term outcomes of open and minimally invasive (MIS) esophagectomy as well as assessing the relationship between institutional MIS volume and hospitalization costs.

Demystifying the association of center-level operative trauma volume and outcomes of emergency general surgery.

Background: Recent studies have demonstrated a positive volume-outcome relationship in emergency general surgery. Some have advocated for the sub-specialization of emergency general surgery independent from trauma. We hypothesized inferior clinical outcomes of emergency general surgery with increasing center-level operative trauma volume, potentially attributable to overall hospital quality.

Impact of Safety-Net Hospital Status on Immediate Reconstruction Following Mastectomy: A Contemporary National Analysis.

Introduction: Immediate breast reconstruction (IBR) following mastectomy has been shown to improve quality of life and partially mitigate the adverse psychological impacts associated with the procedure. The present study examined hospital-based and patient-level disparities in utilization and outcomes of IBR following mastectomy.

Methods: All female adult hospitalizations with a diagnosis of breast cancer undergoing mastectomy were identified in the 2016 to 2020 National Inpatient Sample.

Machine learning based predictive modeling of readmissions following extracorporeal membrane oxygenation hospitalizations.

Background: Despite increasing utilization and survival benefit over the last decade, extracorporeal membrane oxygenation (ECMO) remains resource-intensive with significant complications and rehospitalization risk. We thus utilized machine learning (ML) to develop prediction models for 90-day nonelective readmission following ECMO.

Methods: All adult patients receiving ECMO who survived index hospitalization were tabulated from the 2016-2020 Nationwide Readmissions Database.

Association of Interhospital Transfer With Outcomes of Extracorporeal Membrane Oxygenation: A Contemporary Analysis.

Background: Extracorporeal membrane oxygenation (ECMO) has emerged as a life-sustaining measure for individuals with end-stage cardiopulmonary derangements. An estimated one-third of patients must be transferred to a specialized center to receive this intervention. Therefore, the present study sought to characterize the impact of interhospital transfer (IHT) status on outcomes following ECMO.

Interhospital Transfer for Emergency General Surgery: A Contemporary National Analysis.

Background: Patients undergoing emergency general surgery (EGS) often require complex management and transfer to higher acuity facilities, especially given increasing national efforts aimed at centralizing care. We sought to characterize factors and evaluate outcomes associated with interhospital transfer using a contemporary national cohort.

Methods: All adult hospitalizations for EGS (appendectomy, cholecystectomy, laparotomy, lysis of adhesions, small/large bowel resection, and perforated ulcer repair) ≤2 days of admission were identified in the 2016-2020 National Inpatient Sample.

Roadmap to risk evaluation and mitigation strategies (REMS) success.

Medical safety-related risk management is a rapidly evolving and increasingly important aspect of drug approval and market longevity. To effectively meet the challenges of this new era, we describe a risk management roadmap that proactively yet practically anticipates risk-management requirements, provides the foundation for enduring yet appropriately flexible risk-management practices, and leverages these techniques to efficiently and effectively utilize risk evaluation and mitigation strategies (REMS)/risk minimization programs as market access enablers. This fully integrated risk-management paradigm creates exciting opportunities for newer tools, techniques, and approaches to more successfully optimize product development, approval, and commercialization, with patients as the ultimate beneficiaries.

In vivo drug-drug interaction studies--a survey of all new molecular entities approved from 1987 to 1997.

Ninety-eight new molecular entities applications approved between 1987 to 1991 (period I) and 193 applications for new molecular entities between 1992 to 1997 (period II) were surveyed for drug-drug interaction studies. In period I (used as a comparator), 32 applications contained drug-drug interaction studies for a total of 117 studies. In period II, 106 applications reported drug-drug interaction studies, and the number of studies per new molecular entity ranged from 0 to 15.

Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam.

This review was conducted to identify the current data on drug interactions with alprazolam, midazolam, and triazolam to guide practitioners in the use of these drugs. The Medline electronic database from 1966 through 1998 was used to identify clinical studies of the pharmacokinetic effect of drugs on these three benzodiazepines. Of a total of 491 literature reports identified, 59 prospective studies met our selection criteria.

In vitro metabolic interaction studies: experience of the Food and Drug Administration.

A total of 194 new molecular entities approved by the Food and Drug Administration between 1992 and 1997 were surveyed to determine the role of in vitro metabolic interactions in the conduct of drug-drug interaction studies and to examine the methods used in these studies. Approximately 30% of the submissions were found to have in vitro metabolism-based interaction studies, most of which were inhibitory in nature. Chemical inhibition was the most commonly used approach in studying drug interactions in vitro.

The pharmacokinetic principles behind scaling from preclinical results to phase I protocols.

Extrapolation of animal data to assess pharmacokinetic parameters in humans is an important tool in drug development. Allometric scaling has many proponents, and many different approaches and techniques have been proposed to optimise the prediction of pharmacokinetic parameters from animals to humans. The allometric approach is based on the power function Y = aWb, where the bodyweight of the species is plotted against the pharmacokinetic parameter of interest on a log-log scale.

Interspecies scaling: predicting clearance of drugs in humans. Three different approaches.

1. The interspecies scaling approach to predict clearance in humans from animal data was tested for a wide variety of drugs. 2.

Determination of CYP2C19 phenotype in black Americans with omeprazole: correlation with genotype.

Background: Our objective was to study omeprazole as a single-dose oral probe in the determination of CYP2C19 phenotype in black subjects and to determine the correlation between phenotype and genotype.

Methods: This single-dose, open-label outpatient study was conducted at a community-based, university-affiliated teaching hospital outpatient clinic. Study subjects were 100 healthy, unrelated black adults (age range, 18 to 50 years) who were receiving no medications.

Interspecies scaling: predicting pharmacokinetic parameters of antiepileptic drugs in humans from animals with special emphasis on clearance.

The objective of this study was to test the interspecies-scaling approach in a series of antiepileptic drugs. Clearance, volume of distribution, and elimination half-life were scaled up from animal data obtained from literature. Four different methods were utilized to generate plots to scale up the clearance values: (i) clearance vs body weight (simple allometric equation); (ii) the product of clearance and maximum life-span potential (MLP) vs body weight (an approach recommended in literature); (iii) the two-term power equation which incorporates both body weight and brain weight suggested by Boxenbaum; and (iv) the product of clearance and brain weight vs body weight (a new approach being introduced in this study).

Interspecies scaling: a comparative study for the prediction of clearance and volume using two or more than two species.

The prediction of pharmacokinetic parameters in humans from data obtained in lower animals can be of considerable importance in the process of drug development. Successful extrapolation will facilitate drug dosing transitions from animals to man and accelerate the drug testing process. Existing literature indicates that for the prediction of pharmacokinetic parameters, data from at least three animal species are used.