Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction and arterial stiffening with aging. Supplementation with sodium nitrite, a precursor of NO, ameliorates age-related vascular endothelial dysfunction and arterial stiffness in mice, but effects on humans, including the metabolic pathways altered, are unknown. The purpose of this study was to determine the safety, feasibility, and efficacy of oral sodium nitrite supplementation for improving vascular function in middle-aged and older adults and to identify related circulating metabolites. Ten weeks of sodium nitrite (80 or 160 mg/day, capsules, TheraVasc; randomized, placebo control, double blind) increased plasma nitrite acutely (5- to 15-fold, P < 0.001 vs. placebo) and chronically (P < 0.10) and was well tolerated without symptomatic hypotension or clinically relevant elevations in blood methemoglobin. Endothelial function, measured by brachial artery flow-mediated dilation, increased 45-60% vs. baseline (P < 0.10) without changes in body mass or blood lipids. Measures of carotid artery elasticity (ultrasound and applanation tonometry) improved (decreased β-stiffness index, increased cross-sectional compliance, P < 0.05) without changes in brachial or carotid artery blood pressure. Aortic pulse wave velocity was unchanged. Nitrite-induced changes in vascular measures were significantly related to 11 plasma metabolites identified by untargeted analysis. Baseline abundance of multiple metabolites, including glycerophospholipids and fatty acyls, predicted vascular changes with nitrite. This study provides evidence that sodium nitrite supplementation is well tolerated, increases plasma nitrite concentrations, improves endothelial function, and lessens carotid artery stiffening in middle-aged and older adults, perhaps by altering multiple metabolic pathways, thereby warranting a larger clinical trial.

Geosocial-networking smartphone applications (“apps”) are widely used by gay, bisexual, and other men who have sex with men (MSM) and facilitate connections between users based on proximity and attraction. MSM have sexual encounters and relationships of varying degrees of emotional and physical intimacy with app-met individuals, potentially placing them at risk for intimate partner violence (IPV). The purpose of the current study was to utilize a geosocial-networking application to investigate relationships between experiences of IPV victimization as it relates to substance use and sexual risk behaviors in a sample of MSM. Participants ( n = 175) were recruited by means of broadcast advertisements on an application widely used by MSM (Grindr) to seek sexual partners. Multivariable regression models were fit to examine associations between IPV, substance abuse, and sexual risk behaviors. Lifetime experiences of IPV victimization were common, where 37.7% of respondents reported having experienced at least one form of IPV. While a marginally significant positive association between IPV and substance abuse was detected in multivariable models ( p = .095), individual forms of IPV were strongly associated with substance abuse. For example, sexual IPV victimization was associated with an increase in substance abuse in the preceding month ( p = .004). Experiences of IPV victimization were associated with higher numbers of partners for both condomless receptive and insertive anal intercourse ( p < .05). Given the relatively high prevalence of IPV victimization and its associations with substance abuse and sexual risk behaviors, these findings suggest that IPV screening and prevention programs may reduce substance abuse and sexual risk behaviors in this population.

Advancing age is associated with reductions in nitric oxide bioavailability and changes in metabolic activity, which are implicated in declines in motor and cognitive function. In preclinical models, sodium nitrite supplementation (SN) increases plasma nitrite and improves motor function, whereas other nitric oxide-boosting agents improve cognitive function. This pilot study was designed to translate these findings to middle-aged and older (MA/O) humans to provide proof-of-concept support for larger trials. SN (10 weeks, 80 or 160 mg/day capsules, TheraVasc, Inc.) acutely and chronically increased plasma nitrite and improved performance on measures of motor and cognitive outcomes (all p<0.05 or better) in healthy MA/O adults (62 ± 7 years). Untargeted metabolomics analysis revealed that SN significantly altered 33 (160 mg/day) to 45 (80 mg/day) different metabolites, 13 of which were related to changes in functional outcomes; baseline concentrations of 99 different metabolites predicted functional improvements with SN. This pilot study provides the first evidence that SN improves aspects of motor and cognitive function in healthy MA/O adults, and that these improvements are associated with, and predicted by, the plasma metabolome. Our findings provide the necessary support for larger clinical trials on this promising pharmacological strategy for preserving physiological function with aging.

The number of new HIV infections continues to be on the rise in many high-income countries, most notably among men who have sex with men (MSM). Despite recent attention to the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) among MSM, considerably less research has been devoted to examining the awareness and use of post-exposure prophylaxis (PEP). Based on a convenience sample of 179 self-reported HIV-uninfected MSM using a geosocial-networking smartphone application, this study is among the first to examine the awareness and use of PEP and their demographic and behavioral correlates among MSM in London. Most respondents (88.3%) had heard of PEP, where 27.4% reported having used it. In multivariable models, the disclosure of one’s sexual orientation to their general practitioner (Prevalence ratio [PR]: 3.49; 95% confidence interval (CI): 1.14, 10.70; p = .029) and reporting one’s HIV status as negative (rather than unknown) (PR: 11.49; 95% CI: 1.68, 76.92; p = .013) were associated with having heard of PEP; while the recent use of club drugs (PR: 3.02; 95% CI: 1.42, 6.43; p = .004) was associated with having ever used PEP. High awareness and use in this sample suggest that PEP is a valuable risk-reduction strategy that should be capitalized on, be it in addition to or in the absence of PrEP.

Physical medicine and rehabilitation physicians routinely care for patients with serious illness and injury who could benefit from an integrated palliative care approach due to the propensity for high or complex symptom burden. Despite this, it has been unknown whether and how physical medicine and rehabilitation residency programs are equipping residents with a foundational palliative care skillset. We report national survey results characterizing the current status of palliative care education within US physical medicine and rehabilitation residency programs. Programs vary widely in the type and amount of palliative care education provided, with nearly a third of responding programs reporting no palliative care education at all. These findings suggest the need for nationally unifying palliative care education standards for physical medicine and rehabilitation residency programs to ensure that all physical medicine and rehabilitation residents have the opportunity to develop a robust palliative lens that can be applied across rehabilitation practice settings. An articulated set of standards could both facilitate achievement of palliative care-specific objectives and support achievement of foundational physical medicine and rehabilitation residency program objectives.