Rising Drug Costs for Neurologic Diseases.

The cost of prescription drugs in the United States is rising like never before and has led to an inflection point where clinicians must consider the potential financial damage to the patient and to society related to the more expensive drugs available. Many of the highest-priced drugs are approved as orphan drugs, a legally defined status providing additional benefits to pharmaceutical companies that is intended to incentivize therapeutic development for rare diseases. The Orphan Drug Act has been a great success since it was enacted in 1983, resulting in the development of many innovative, life-changing, and even lifesaving drugs; however, high drug prices place patients at risk for personal bankruptcy, prescription abandonment, and higher rates of hospitalization.

A crisis in US drug pricing: Consequences for patients with neuromuscular diseases, physicians, and society, part 2.

Escalating drug costs place patients at risk for financial toxicity and demand that physicians understand and act on the ethical and economic principles related to drug pricing. This manuscript reviews these principles and provides clinicians with a framework to think about the value of the drugs prescribed for patients with neuromuscular diseases. A key component of addressing the drug pricing crisis will be establishing a value based (benefit/cost) drug pricing framework.

A crisis in US drug pricing: Consequences for patients with neuromuscular diseases, physicians and society, part 1.

Drug prices in the United States have reached astounding heights, negatively impacting patients and society. The vast majority of prescription drug spending is on brand name drugs, which are protected from typical market pressures by FDA exclusivity and intellectual property patents. Drugs to treat "orphan" diseases, of particular relevance to neuromuscular clinicians, are some of the most expensive in all of medicine.

Awake Testing during Deep Brain Stimulation Surgery Predicts Postoperative Stimulation Side Effect Thresholds.

Despite substantial experience with deep brain stimulation for movement disorders and recent interest in electrode targeting under general anesthesia, little is known about whether awake macrostimulation during electrode targeting predicts postoperative side effects from stimulation. We hypothesized that intraoperative awake macrostimulation with the newly implanted DBS lead predicts dose-limiting side effects during device activation in clinic. We reviewed 384 electrode implants for movement disorders, characterized the presence or absence of stimulus amplitude thresholds for dose-limiting DBS side effects during surgery, and measured their predictive value for side effects during device activation in clinic with odds ratios ±95% confidence intervals.

Surgery for Dystonia and Tremor.

Surgical procedures for dystonia and tremor have evolved over the past few decades, and our understanding of risk, benefit, and predictive factors has increased substantially in that time. Deep brain stimulation (DBS) is the most utilized surgical treatment for dystonia and tremor, though lesioning remains an effective option in appropriate patients. Dystonic syndromes that have shown a substantial reduction in severity secondary to DBS are isolated dystonia, including generalized, cervical, and segmental, as well as acquired dystonia such as tardive dystonia.

Synthesis and X-ray structure determination of highly active Pd(II), Pd(I), and Pd(0) complexes of di(tert-butyl)neopentylphosphine (DTBNpP) in the arylation of amines and ketones.

The air-stable complex Pd(η(3)-allyl)(DTBNpP)Cl (DTBNpP = di(tert-butyl)neopentylphosphine) serves as a highly efficient precatalyst for the arylation of amines and enolates using aryl bromides and chlorides under mild conditions with yields ranging from 74% to 98%. Amination reactions of aryl bromides were carried out using 1-2 mol % Pd(η(3)-allyl)(DTBNpP)Cl at 23-50 °C without the need to exclude oxygen or moisture. The C-N coupling of the aryl chlorides occurred at relatively lower temperature (80-100 °C) and catalyst loading (1 mol %) using the Pd(η(3)-allyl)(DTBNpP)Cl precatalyst than the catalyst generated in situ from DTBNpP and Pd(2)(dba)(3) (100-140 °C, 2-5 mol % Pd).