Machine Learning ADME Models in Practice: Four Guidelines from a Successful Lead Optimization Case Study.

Optimization of the ADME properties and pharmacokinetic (PK) profile of compounds is one of the critical activities in any medicinal chemistry campaign to discover a future clinical candidate. Finding ways to expedite the process to address ADME/PK shortcomings and reduce the number of compounds to synthesize is highly valuable. This article provides practical guidelines and a case study on the use of ML ADME models to guide compound design in small molecule lead optimization.

Anesthetic Choice for Percutaneous Transcatheter Closure of the Left Atrial Appendage: A National Anesthesia Clinical Outcomes Registry Analysis.

Context: Left atrial appendage closure (LAAC) was developed as a novel stroke prevention alternative for patients with atrial fibrillation, particularly for those not suitable for long-term oral anticoagulant therapy. Traditionally, general anesthesia (GA) has been more commonly used primarily due to the necessity of transesophageal echocardiography.

Aims: Compare trends of monitored anesthesia care (MAC) versus GA for percutaneous transcatheter LAAC with endocardial implant and assess for independent variables associated with primary anesthetic choice.

Traumatic spinal cord injury in West Virginia: Impact on long-term outcomes by insurance status and discharge disposition.

Objectives: Specialized rehabilitation is important for people with traumatic spinal cord injuries (SCIs) to optimize function, independence and mitigate complications, and access to this service varies by the payor. In West Virginia, admission to acute rehabilitation facilities is a "non-covered entity," impeding access to this care for patients with SCI and Medicaid. Our previous work examined the discharge disposition from an acute care hospital of patients with and without Medicaid and found that Medicaid patients were almost twice as likely to be discharged home or to a nursing home, despite similar injury severity and younger age compared to non-Medicaid patients.

Efficacy of tranexamic acid (TXA) for post-tonsillectomy hemorrhage.

Purpose: To determine if tranexamic acid (TXA) reduces the need for operative re-cauterization in the setting of a post-tonsillectomy hemorrhage (PTH).

Methods: A retrospective chart review was performed on 1428 adult and pediatric patients who underwent tonsillectomy over a two-year period at a tertiary care hospital with continuous otolaryngologic coverage. Collected data of PTH patients included age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, length of stay (LOS), the requirement of a blood transfusion, day of PTH, TXA usage and route, complications from TXA administration, and TXA failure requiring operative intervention.

Systematic bias in real-world tonometry readings based on laterality?

Aims: In research settings, the first eye examined tends to have a higher intraocular pressure (IOP) than the second. We sought to verify whether clinicians in Yorkshire, UK, measure IOP in right eyes before left and whether such behavioural factors affect IOP readings at the population level.

Methods: We observed 128 IOP measurements taken by 28 ophthalmologists using Goldmann applanation tonometry (GAT) over a 4-month period in 2018, recording which eye was examined first.