Navigating Federal and State Laws Regarding the Prescription of Opioids.

Since 2000, the opioid epidemic has claimed the lives of more than 500,000 people and policies regarding the prescription of opioids for chronic pain have undergone drastic changes. While neurologists account for a small number of overall opioid prescriptions, they may treat patients on opioids, prescribed by other physicians or obtained illicitly, and need to be aware of the latest practice guidelines and the legal regime regulating opioid prescriptions.

Fatal Case of Exercise Collapse Associated with Sickle Cell Trait with Novel Underlying LAMA2 Mutation.

Sickle cell trait is typically thought to be an asymptomatic carrier state, but it is rarely associated with exertional rhabdomyolysis in cases termed Exercise Collapse Associated with Sickle Cell Trait (ECAST). In a subset of these cases, underlying disease contributes to the development and/or severity of the ensuing medical complications. We describe the first ever case of ECAST reported in a previously asymptomatic, multiply deployed, highly physically active service member with an underlying heterozygous LAMA2 mutation.

3D reconstruction of skin and spatial mapping of immune cell density, vascular distance and effects of sun exposure and aging.

Mapping the human body at single cell resolution in three dimensions (3D) is important for understanding cellular interactions in context of tissue and organ organization. 2D spatial cell analysis in a single tissue section may be limited by cell numbers and histology. Here we show a workflow for 3D reconstruction of multiplexed sequential tissue sections: MATRICS-A (Multiplexed Image Three-D Reconstruction and Integrated Cell Spatial - Analysis).

False Claims Act and Anti-Kickback Statute: Avoiding Legal Landmines.

Health care entities doing business with the federal government may run afoul of the False Claims Act and Anti-Kickback Statute not only when they directly submit fraudulent claims for government reimbursement but also when they create schemes that manipulate others into submitting (whether knowingly or unknowingly) illegal claims. In recent years, the Department of Justice is deploying these statutes to ensure that electronic health records are built and maintained with appropriate cybersecurity protections.

Protecting Privacy: Health Insurance Portability and Accountability Act of 1996, Twenty-First Century Cures Act, and Social Media.

Advances in electronic health record technology, the ever-expanding use of social media, and cybersecurity sabotage threaten patient privacy and render physicians and health care organizations liable for violating federal and state laws. Violating a patient's privacy is both an ethical and legal breach with potentially serious legal and reputational consequences. Even an unintentional Health Insurance Portability and Accountability Act of 1996 (HIPAA) violation can result in financial penalties and reputational harm.

Physiologically-based pharmacokinetic modeling to predict drug-drug interaction of enzalutamide with combined P-gp and CYP3A substrates.

Enzalutamide is known to strongly induce cytochrome P450 3A4 (CYP3A4). Furthermore, enzalutamide showed induction and inhibition of P-glycoprotein (P-gp) in in vitro studies. A clinical drug-drug interaction (DDI) study between enzalutamide and digoxin, a typical P-gp substrate, suggested enzalutamide has weak inhibitory effect on P-gp substrates.

Learn-confirm in model-informed drug development: Assessing an immunogenicity quantitative systems pharmacology platform.

Immunogenicity against therapeutic proteins frequently causes attrition owing to its potential impact on pharmacokinetics, pharmacodynamics, efficacy, and safety. Predicting immunogenicity is complex because of its multifactorial drivers, including compound properties, subject characteristics, and treatment parameters. To integrate these, the Immunogenicity Simulator was developed using published, predominantly late-stage trial data from 15 therapeutic proteins.

Application of physiologically based pharmacokinetic models for therapeutic proteins and other novel modalities.

The past two decades have seen diversification of drug development pipelines and approvals from traditional small molecule therapies to alternative modalities including monoclonal antibodies, engineered proteins, antibody drug conjugates (ADCs), oligonucleotides and gene therapies. At the same time, physiologically based pharmacokinetic (PBPK) models for small molecules have seen increased industry and regulatory acceptance.This review focusses on the current status of the application of PBPK models to these newer modalities and give a perspective on the successes, challenges and future directions of this field.

A quantitative systems pharmacology model for simulating OFF-Time in augmentation trials for Parkinson's disease: application to preladenant.

The clinical impact of therapeutic interventions in Parkinson's disease is often measured as a reduction in OFF-time when the beneficial effects of the standard-of-care L-DOPA formulations wanes off. We investigated the pharmacodynamic interactions of augmentation therapy to standard-of-care using a quantitative systems pharmacology (QSP) model of the basal ganglia motor circuit, essentially a computer model of neuronal firing in the different subregions with anatomically informed connectivity, cell-specific expression of 17 different G-protein coupled receptors and corresponding coupling to voltage-gated ion channel effector proteins based on experimentally observed intracellular signaling. The calculated beta/gamma (b/g) power spectrum of the local field potentials in the subthalamic nucleus was previously calibrated on the clinically relevant Unified Parkinson's Disease Rating Scale (UPDRS).

COVID-19 nightmare response and stress: A new Mexico sample based survey.

Studies conducted during the COVID-19 Pandemic have reported increased rates of mental illnesses including depression, anxiety, and post-traumatic stress disorder (PTSD) [1]. A common symptom of mental illness is change in Rapid Eye Movement (REM) sleep, the phase of sleep associated with dreaming and nightmares. The COVID-19 pandemic offers a unique opportunity to evaluate the effects of systemic stress on nightmares.

The Medicolegal and Ethical Dimensions of Physician Prescription Reluctance.

This article addresses the potential legal ramifications for neurologists caring for patients with Alzheimer disease (AD) who elect neither to prescribe aducanumab nor to refer patients with AD for treatment with aducanumab. To prevail against a neurologist for failing to prescribe aducanumab or refer for aducanumab treatment, the plaintiff would have to establish that the neurologist's failure to prescribe the medication or refer for treatment was a breach of the standard of care. The standard of care is conceptualized as the generally accepted approach to diagnosing or treating a condition.

Legal and Ethical Challenges in the Care of the Pregnant Patient After Brain Death.

Using two scenarios based on real-life cases reported in the media, this article examines the ethical and legal controversies that arise when a pregnant woman dies based on neurologic criteria while her fetus remains alive. In the first scenario, all parties agreed to maintain physiologic support until a safe delivery could be achieved, whereas in the second scenario the woman's family sought a legal remedy to stop the hospital from continuing to provide physiologic support for the patient and her neurologically devastated fetus.

Interprofessional Internet Consultations: The Potential Benefits and Perils of eConsults.

This article addresses the question of whether neurologists performing interprofessional internet consultations, known as eConsults, face the same malpractice liability as for face-to-face patient care. Because the physician-patient relationship is usually unambiguous, determining the scope of legal liability arising from these relatively new approaches to patient care requires understanding the types of interactions courts have found to establish a patient-physician relationship.

False Claims Act Overview and Implications for Neurologists.

The US Department of Health and Human Services Office of the Inspector General identifies the five most important federal fraud and abuse laws that are most applicable to physicians: the False Claims Act, the Anti-Kickback Statute, the Physician Self-Referral Law (Stark Law), the Exclusion Authorities, and the Civil Monetary Penalties LawThe False Claims Act is the US government's primary tool for combating fraud perpetrated through the filing of false claims for federal government reimbursement. Neurologists and companies serving the needs of neurologic patients have not been immune from False Claims Act-related legal action. This article provides an overview of the False Claims Act, uses real-life neurologic cases to illustrate the range of False Claims Act violations and recoveries, and offers some practical compliance suggestions.

The use of PBPK/PD to establish clinically relevant dissolution specifications for zolpidem immediate release tablets.

Background: Zolpidem is a non-benzodiazepine hypnotic agent which has been shown to be effective in inducing and maintaining sleep in adults and is one of the most frequently prescribed hypnotics in the world. For drugs that are used to treat sleeping disorders, the time to reach the maximum concentration (T) of the drug in plasma is important to achieving a fast onset of action and this must be maintained when switching from one product to another.

Objectives: The main objective of the present work was to create a PBPK/PD model for zolpidem and establish a clinically relevant "safe space" for dissolution of zolpidem from the commercial immediate release (IR) formulation.

Criminal Culpability for Acts Committed During a Possible Episode of REM Sleep Behavior Disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) may result in a patient injuring a bed partner while acting out a dream. This article examines the complexities associated with RBD as a criminal defense strategy as well as the legal implications for physicians and their duty to patients and their families to mitigate risks associated with possible injuries related to RBD.

Legal Liability Associated With rtPA Administration and Surrogate Decision Makers.

Stroke is one of the most common conditions neurologists treat in emergency situations. This article examines the issues of surrogate decision makers and the physician's potential legal liability in the context of the administration or nonadministration of recombinant tissue plasminogen activator (rtPA) in a common emergency department scenario.

Liability and Failure to Warn a Patient.

This medicolegal article examines a physician's liability when he or she has knowledge of adverse effects associated with a prescription medication and suggests ways to mitigate that liability risk. The article also discusses the circumstances under which pharmaceutical companies face liability for side effects such as tardive dyskinesia.

Driving and Epilepsy: Ethical, Legal, and Health Care Policy Challenges.

Although the principle of autonomy allows patients to refuse interventions their physicians recommend, patients are not free to ignore legally mandated restrictions on driving, and physicians are ethically justified in constraining their patients' driving rights in compliance with state law. Furthermore, the standard of care for treatment of patients with epilepsy includes counseling about lifestyle modifications that promote patient safety and compliance with the law. Neurologists should not only counsel their patients with epilepsy about legally mandated driving restrictions but also document this counseling in the medical record.

Prescribing Antipsychotic Medications to Patients With Dementia: Boxed Warnings and Mitigation of Legal Liability.

Clinicians caring for patients with dementia are often at a loss when trying to manage dementia-related behavioral disturbances pharmacologically because no drugs have been proven effective for this indication. Antipsychotics are commonly prescribed for these patients despite a US Food and Drug Administration (FDA)-mandated boxed warning about the heightened risk of death in patients with dementia treated with antipsychotic drugs. This boxed warning does not prevent clinicians from prescribing antipsychotics to patients with dementia.

Legal and Ethical Considerations of Disclosing Human Immunodeficiency Virus Seropositivity to a Surrogate Decision Maker.

Ethical and legal issues arise when a patient who is human immunodeficiency virus (HIV) positive lacks decision-making capacity and the HIV status must be disclosed to a surrogate decision maker to allow for informed medical decision making. This article discusses the special exceptions to confidentiality built into the Health Insurance Portability and Accountability Act privacy protections, the limitations on claims of common-law marriage, and public health laws that often require informing individuals who are either sex partners or needle-sharing partners of newly diagnosed HIV-infected individuals that they have been exposed to HIV infection.

Common Legal Considerations When Moving to a New Medical Practice.

This article presents a hypothetical case of the legal issues a physician must consider when moving to a new medical practice, such as the enforceability of a noncompete clause, malpractice insurance, communicating this change in practice to existing patients, and custody of medical records.

Incorporation of the Time-Varying Postprandial Increase in Splanchnic Blood Flow into a PBPK Model to Predict the Effect of Food on the Pharmacokinetics of Orally Administered High-Extraction Drugs.

Following a meal, a transient increase in splanchnic blood flow occurs that can result in increased exposure to orally administered high-extraction drugs. Typically, physiologically based pharmacokinetic (PBPK) models have incorporated this increase in blood flow as a time-invariant fed/fasted ratio, but this approach is unable to explain the extent of increased drug exposure. A model for the time-varying increase in splanchnic blood flow following a moderate- to high-calorie meal (TV-Q ) was developed to describe the observed data for healthy individuals.