Publications

PURPOSE

Increasing evidence of a link between erectile dysfunction and cardiovascular disease suggests a shared vascular etiology with endothelial dysfunction as a plausible underlying biological mechanism. To our knowledge whether this association is different for large arterial endothelium compared to microvascular endothelium has not yet been established. We investigated the association of erectile dysfunction with macrovascular and microvascular endothelial function.

MATERIALS AND METHODS

A sample of 390 men with a mean age of 55.5 years was recruited from the BACH survey, a population based survey of urological symptoms. Erectile dysfunction was assessed using IIEF-5. The percent of brachial artery flow mediated dilatation, a measure of macrovascular function, and hyperemic flow velocity in cm per second, a measure of microvascular function, were assessed by ultrasound. Linear regression was used to assess the association of erectile dysfunction and endothelial function, and adjust for potential confounders.

RESULTS

Reactive hyperemia was lower in men with vs without erectile dysfunction (mean ± SE 97.1 ± 2.5 vs 106.0 ± 1.6 cm per second, p = 0.003). However, the difference in flow mediated dilatation between men with vs without erectile dysfunction was statistically nonsignificant (mean 6.6% ± 0.33% vs 7.2% ± 0.24%, p = 0.147). The association of erectile dysfunction with reactive hyperemia was attenuated but it remained statistically significant in men with moderate to severe erectile dysfunction (IIEF-5 less than 12) after adjusting for traditional cardiovascular risk factors (p = 0.038).

CONCLUSIONS

These results provide evidence of greater microvascular than macrovascular endothelial dysfunction as a potential contributor to erectile dysfunction and an underlying mechanism linking erectile dysfunction and cardiovascular disease.

Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only vaccine currently used against tuberculosis, is an attenuated derivative of M. bovis that has been propagated in vitro for more than 40 years. We have previously reported that the experimentally-verified human T cell epitopes of the M. tuberculosis complex (MTBC) are the most conserved elements of the genome; whether immune recognition is the force driving the conservation of epitopes in the MTBC is unknown. Therefore, we sequenced the genomes of 12 BCG strains to determine whether T cell epitopes were under selection pressure during BCG in vitro evolution. We constructed a genome-wide phylogeny and refined the previously-determined BCG phylogeny. Notably, we identified a new cluster between BCG Japan and BCG Russia, and repositioned the relationships of several strains within the lineage. We also compared the sequence diversity of 1530 experimentally verified human T cell epitopes in the BCG vaccines with those in the MTBC. We found 23% of the known T cell epitopes are absent, and that the majority (82%) of the absent epitopes in BCG are contained in 6 proteins encoded in 2 regions of difference (RD) unique to BCG strains. We also found that T cell epitope sequences in BCG are more conserved than non-epitope sequences in the same gene. Finally, we find evidence that epitope sequence variation in BCG potentially affects human T cell recognition. These findings provide new insight into sequence variation in a slow-growing bacterium closely related to the MTBC that has been subjected to prolonged passage outside of a mammalian host, and indicate little difference in the extent of variation in vivo and in vitro.

BACKGROUND

Quality care for patients with cancer often requires access to specialty providers, but little is known about barriers to referring cancer patients for specialized care. Referral barriers may also lessen physician career satisfaction. The study was aimed at determining what factors are associated with these barriers and whether greater barriers are associated with low career satisfaction.

METHODS

This cross-sectional study examined 1562 primary care physicians (PCPs) and 2144 specialists responding to the multiregional Cancer Care Outcomes Research and Surveillance Consortium physician survey. The prevalence of physician-reported barriers to referring cancer patients for more specialized care (restricted provider networks, preauthorization requirements, patient inability to pay, lack of surgical subspecialists, and excessive patient travel time) was assessed. The 5 items were averaged to calculate a barrier score. A multivariate linear regression was used to determine physician and practice setting characteristics associated with the barrier score, and a multivariate logistic regression was used to analyze the association of the barrier score with physician career satisfaction.

RESULTS

Three in 5 physicians reported always, usually, or sometimes encountering any barrier to cancer patient specialty referrals. In adjusted analyses of PCPs and specialists, international medical graduates, physicians practicing in solo or government-owned practices, and physicians with <90% of their patients in managed care plans had higher barrier scores than others (P < .05). High barrier scores were associated with lower physician career satisfaction among PCPs and specialists (P < .05).

CONCLUSIONS

Many physicians experience barriers to specialty referral for cancer patients. Uniform systems for providing and tracking timely referrals may enhance care and promote physician career satisfaction.