Publications

Although the transient receptor potential vanilloid 4 (TRPV4) has been implicated in the process of osmomechanical transduction, it appears to make little contribution to the normal somatosensory detection of mechanical stimuli. However, evidence suggests that it may play an important role in mechanical hyperalgesia. In the present study, we examined the common requirement for TRPV4 in mechanical hyperalgesia associated with diverse pain models and investigated whether the very close association observed between TRPV4 and mechanical hyperalgesia, regardless of etiology, reflects a close functional connection of TRPV4 with other molecules implicated in mechanical transduction. In models of painful peripheral neuropathy associated with vincristine chemotherapy, alcoholism, diabetes, and human immunodeficiency virus/acquired immune deficiency syndrome therapy, mechanical hyperalgesia was markedly reduced by spinal intrathecal administration of oligodeoxynucleotides antisense to TRPV4. Similarly, mechanical hyperalgesia induced by paclitaxel, vincristine, or diabetes was strongly reduced in TRPV4 knock-out mice. We also show that alpha2beta1 integrin and Src tyrosine kinase, which have been implicated in mechanical transduction, are important for the development of mechanical hyperalgesia, and that their contribution requires TRPV4. Furthermore, we establish a direct interaction between TRPV4, alpha2 integrin, and the Src tyrosine kinase Lyn in sensory neurons. We suggest that TRPV4 plays a role in mechanotransduction, as a component of a molecular complex that functions only in the setting of inflammation or nerve injury.

BACKGROUND

Infection with multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus (MRSA) has been reported but seems to be isolated.

OBJECTIVE

To determine the incidence of a multidrug-resistant MRSA clone (USA300) in San Francisco, and to determine risk factors for the infection.

DESIGN

Population-based survey and cross-sectional study using chart review.

SETTING

9 hospitals in San Francisco (population-based survey) and 2 outpatient clinics in San Francisco and Boston (cross-sectional study).

PATIENTS

Persons with culture-proven MRSA infections in 2004 to 2006.

MEASUREMENTS

Annual incidence, spatial clustering, and risk factors for multidrug-resistant USA300 infection. Pulsed-field gel electrophoresis, polymerase chain reaction assays, and DNA sequencing were used to characterize MRSA isolates.

RESULTS

The overall incidence of multidrug-resistant USA300 infection in San Francisco was 26 cases per 100,000 persons (95% CI, 16 to 36 cases per 100,000 persons); the incidence was higher in 8 contiguous ZIP codes with a higher proportion of male same-sex couples. Male-male sex was a risk factor for multidrug-resistant USA300 infection (relative risk, 13.2 [CI, 1.7 to 101.6]; P < 0.001) independent of past MRSA infection (relative risk, 2.1 [CI, 1.2 to 3.7]; P = 0.007) or clindamycin use (relative risk, 2.1 [1.2 to 3.6]; P = 0.007). The risk seemed to be independent of HIV infection. In San Francisco, multidrug-resistant USA300 manifested most often as infection of the buttocks, genitals, or perineum. In Boston, the infection was recovered exclusively from men who had sex with men.

LIMITATIONS

The study was retrospective, and sexual risk behavior was not assessed.

CONCLUSION

Infection with multidrug-resistant USA300 MRSA is common among men who have sex with men, and multidrug-resistant MRSA infection might be sexually transmitted in this population. Further research is needed to determine whether existing efforts to control epidemics of other sexually transmitted infections can control spread of community-associated, multidrug-resistant MRSA.

BACKGROUND

There is a paucity of data on the adequacy of the resources and tools used by the Centers for Medicaid and Medicare Services (CMS) in making national coverage determinations about services for beneficiaries. The objective of this study was to determine the extent to which clinical trials relied on by the CMS are applicable to Medicare beneficiaries.

METHODS

We performed a meta-analysis of data on 40 009 individuals from all 141 trials included in the technology assessments for the 6 cardiovascular disease meetings of the CMS advisory panel and compared them with the demographics of the Medicare population.

RESULTS

Medicare beneficiaries differ significantly from the cardiovascular clinical trial participants used to inform Medicare coverage decisions. Clinical trial participants, compared with beneficiaries, are more likely to be younger (60.1 vs 74.7 years), male (75.4% vs 41.8%), and non-US residents (60% vs 0%). The clinical trials, moreover, rarely included outcome stratification by age, sex, and race.

CONCLUSIONS

Participants in cardiovascular studies relied on by the CMS for coverage determinations differ substantially from the Medicare population. Data frequently are not available on relevant subgroup populations. Suggestions are made that address the need for data more relevant to Medicare beneficiaries by increasing enrollment of, and reporting on, women and elderly individuals in clinical trials and use of relevant data for coverage decisions.