Publications

IMPORTANCE

The association between industry payments to physicians and prescribing rates of the brand-name medications that are being promoted is controversial. In the United States, industry payment data and Medicare prescribing records recently became publicly available.

OBJECTIVE

To study the association between physicians' receipt of industry-sponsored meals, which account for roughly 80% of the total number of industry payments, and rates of prescribing the promoted drug to Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS

Cross-sectional analysis of industry payment data from the federal Open Payments Program for August 1 through December 31, 2013, and prescribing data for individual physicians from Medicare Part D, for all of 2013. Participants were physicians who wrote Medicare prescriptions in any of 4 drug classes: statins, cardioselective β-blockers, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ACE inhibitors and ARBs), and selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs). We identified physicians who received industry-sponsored meals promoting the most-prescribed brand-name drug in each class (rosuvastatin, nebivolol, olmesartan, and desvenlafaxine, respectively). Data analysis was performed from August 20, 2015, to December 15, 2015.

EXPOSURES

Receipt of an industry-sponsored meal promoting the drug of interest.

MAIN OUTCOMES AND MEASURES

Prescribing rates of promoted drugs compared with alternatives in the same class, after adjustment for physician prescribing volume, demographic characteristics, specialty, and practice setting.

RESULTS

A total of 279 669 physicians received 63 524 payments associated with the 4 target drugs. Ninety-five percent of payments were meals, with a mean value of less than $20. Rosuvastatin represented 8.8% (SD, 9.9%) of statin prescriptions; nebivolol represented 3.3% (7.4%) of cardioselective β-blocker prescriptions; olmesartan represented 1.6% (3.9%) of ACE inhibitor and ARB prescriptions; and desvenlafaxine represented 0.6% (2.6%) of SSRI and SNRI prescriptions. Physicians who received a single meal promoting the drug of interest had higher rates of prescribing rosuvastatin over other statins (odds ratio [OR], 1.18; 95% CI, 1.17-1.18), nebivolol over other β-blockers (OR, 1.70; 95% CI, 1.69-1.72), olmesartan over other ACE inhibitors and ARBs (OR, 1.52; 95% CI, 1.51-1.53), and desvenlafaxine over other SSRIs and SNRIs (OR, 2.18; 95% CI, 2.13-2.23). Receipt of additional meals and receipt of meals costing more than $20 were associated with higher relative prescribing rates.

CONCLUSIONS AND RELEVANCE

Receipt of industry-sponsored meals was associated with an increased rate of prescribing the brand-name medication that was being promoted. The findings represent an association, not a cause-and-effect relationship.

INTRODUCTION

Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease. Patients with severe AD often require assistance with daily functioning and have a substantially higher probability of admission to nursing homes compared to the general population.

AREAS COVERED

Medications approved by the US Food and Drug Administration for the treatment of severe AD include the cholinesterase inhibitors (ChEIs), donepezil (10 and 23 mg/day) and rivastigmine (transdermal patch, 13.3 mg/24 hours), and the N-methyl-D-aspartate receptor antagonist memantine (immediate- and extended-release formulations). This article will review the efficacy, safety, and tolerability data of these agents in the treatment of severe AD. Issues related to combination therapy, neuropsychiatric symptoms, and treatment discontinuation are also discussed.

EXPERT OPINION

AD therapeutics provide benefits on measures of cognition, functioning, behavior, and global status even in the severe stages of AD. Combination therapy with memantine and ChEIs may provide additive benefits compared with ChEI monotherapy. Decisions regarding discontinuation of these medications should be made on a case-by-case basis, with some evidence suggesting that discontinuation may worsen cognition and functional impairment. It is recommended that patients entering the terminal stages of AD discontinue all medications not necessary for comfort.

KRAS is the most frequently mutated oncogene in human cancer. In addition to holding this distinction, unsuccessful attempts to target this protein have led to the characterization of RAS as 'undruggable'. However, recent advances in technology and novel approaches to drug discovery have renewed hope that a direct KRAS inhibitor may be on the horizon. In this Review, we provide an in-depth analysis of the structure, dynamics, mutational activation and inactivation, and signalling mechanisms of RAS. From this perspective, we then consider potential mechanisms of action for effective RAS inhibitors. Finally, we examine each of the many recent reports of direct RAS inhibitors and discuss promising avenues for further development.

Programmed cell death is an essential aspect of animal development. Mutations in vertebrate genes that mediate apoptosis only mildly perturb development, suggesting that other cell death modes likely have important roles. Linker cell-type death (LCD) is a morphologically conserved cell death form operating during the development of Caenorhabditis elegans and vertebrates. We recently described a molecular network governing LCD in C. elegans, delineating a key role for the transcription factor heat-shock factor 1 (HSF-1). Although HSF-1 functions to protect cells from stress in many settings by inducing expression of protein folding chaperones, it promotes LCD by inducing expression of the conserved E2 ubiquitin-conjugating enzyme LET-70/UBE2D2, which is not induced by stress. Following whole-genome RNA interference and candidate gene screens, we identified and characterized four conserved regulators required for LCD. Here we show that two of these, NOB-1/Hox and EOR-1/PLZF, act upstream of HSF-1, in the context of Wnt signaling. A third protein, NHR-67/TLX/NR2E1, also functions upstream of HSF-1, and has a separate activity that prevents precocious expression of HSF-1 transcriptional targets. We demonstrate that the SET-16/mixed lineage leukemia 3/4 (MLL3/4) chromatin regulation complex functions at the same step or downstream of HSF-1 to control LET-70/UBE2D2 expression. Our results identify conserved proteins governing LCD, and demonstrate that transcriptional regulators influence this process at multiple levels.