The Impact of Tort Reforms on the Neurosurgical Malpractice Environment: A Systematic Review of Literature.

BACKGROUND: Neurosurgeons, especially spine surgeons, have the highest risk of facing a malpractice claim. Average verdicts in spine surgery litigation has been shown to be over USD $1 million/case. This systematic review aimed to clarify the impact of tort reforms on neurosurgical health care environments across the United States, including patient outcomes, practice of defensive medicine, and physician supply aims. METHODS: A systematic literature search was performed using PubMed, Embase, Cochrane, and Web of Science databases until May 13, 2022. Study quality was assessed using the quality assessment tool for studies reporting prevalence data. RESULTS: Five studies (all rated as good quality) were included. Two studies found that in higher-risk state malpractice environments, risk of postoperative complications was higher and odds of nonhome discharge were larger (odds ratio 1.1169, 95% confidence interval 1.139-1.200). One study found that neurosurgeons reported practice of defensive medicine by ordering more imaging in a higher-risk environment, while this was not shown in a study examining imaging rates in different medicolegal environments. One study observed that noneconomic damage caps were associated with a 3.9% increase of physician supply in high-risk specialties. CONCLUSIONS: There was a suggestive association between tort reforms and less practice of defensive medicine among neurosurgeons, improvement in postoperative outcomes in spinal fusion patients, and increase in physician supply. More elaborate studies on the medicolegal environment in neurosurgical practice are needed to give more insight on the current size of the problem that litigation presents in the United States and the effects tort reforms have on neurosurgical health care environments.

A Review on Recent Development of Novel Heterocycles as Acetylcholinesterase Inhibitor for the Treatment of Alzheimer's Disease.

Alzheimer's Disease (AD), affecting a large population worldwide, is characterized by the old population's loss of memory and learning ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed to treat AD, including naturallyderived inhibitors, synthetic analogs, and hybrids. Acetylcholinesterase (AChE) has obtained a renewed interest as a therapeutic target in Alzheimer's disease (AD) due to increased neural cells' function by increasing the concentration of acetylcholine. In this review, we reported the recent development of novel heterocyclic compounds such as coumarin-benzotriazole hybrids, carbazole derivatives, tacrine conjugates, N-benzyl-piperidine-aryl-acyl hydrazones hybrid, spiropyrazoline derivatives, coumarin-dithiocarbamate hybrids, etc., as AChE inhibitors for the treatment of Alzheimer disease. All the bioactive compounds show an effect on different cells and interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE with a narrow range of IC50 values from 0.4 nm to 88.21 µm using Ellman's in vitro AChE assay method and show high BBB permeability in vitro. In addition, the in vitro fluorescence assay study using Amplex Red assay kits revealed that all the compounds could inhibit self-induced ß-amyloid (Aß) aggregation with the highest inhibition range from 31.4 to 82%. Furthermore, most of the compounds show a low toxicity profile during in vivo studies. The results suggest that all the compounds constitute promising leads for the AChE targeted approach for Alzheimer's disease.

Recent Update on the Development of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors: A Promising Target for the Treatment of Parkinson's Disease.

Parkinson's disease is a relatively common neurological disorder with incidence increasing with age. Since current medications only relieve the symptoms and do not change the course of the disease, therefore, finding disease-modifying therapies is a critical unmet medical need. However, significant progress in understanding how genetics underpins Parkinson's disease (PD) has opened up new opportunities for understanding disease pathogenesis and identifying possible therapeutic targets. One such target is leucine-rich repeat kinase 2 (LRRK2), an elusive enzyme implicated in both familial and idiopathic PD risk. As a result, both academia and industry have promoted the development of potent and selective inhibitors of LRRK2. In this review, we have summarized recent progress in the discovery and development of LRKK2 inhibitors as well as the bioactivity of several small-molecule LRRK2 inhibitors that have been used to inhibit LRRK2 kinase activity in vitro or in vivo.