Publications

CONTEXT

Medical devices are common in clinical practice and have important effects on morbidity and mortality, yet there has not been a systematic examination of evidence used by the US Food and Drug Administration (FDA) for device approval.

OBJECTIVES

To study premarket approval (PMA)--the most stringent FDA review process--of cardiovascular devices and to characterize the type and strength of evidence on which it is based.

DATA SOURCES AND STUDY SELECTION

Systematic review of 78 summaries of safety and effectiveness data for 78 PMAs for high risk cardiovascular devices that received PMA between January 2000 and December 2007 [corrected].

DATA EXTRACTION

Examination of the methodological characteristics considered essential to minimize confounding and bias, as well as the primary end points of the 123 studies supporting the PMAs.

RESULTS

Thirty-three of 123 studies (27%) used to support recent FDA approval of cardiovascular devices were randomized and 17 of 123 (14%) were blinded. Fifty-one of 78 PMAs (65%) were based on a single study. One hundred eleven of 213 primary end points (52%) were compared with controls and 34 of 111 controls (31%) were retrospective. One hundred eighty-seven of 213 primary end points (88%) were surrogate measures and 122 of 157 (78%) had a discrepancy between the number of patients enrolled in the study and the number analyzed.

CONCLUSION

Premarket approval of cardiovascular devices by the FDA is often based on studies that lack adequate strength and may be prone to bias.

Pulmonary alveolar type I cells (TI cell) are very large (approximately 5400 microm(2) in surface area) squamous cells that cover more than 98% of the internal surface area of rodent lungs. In the past, TI cells were believed to serve only passive barrier functions, with no active functional properties in the lung. The fairly recent development of methods to isolate TI cells has permitted investigation of functions of this cell type for the first time. Resolvable by electron microscopy, TI cells contain microvilli and organelles typically associated with metabolic functions, such as mitochondria, abundant smooth and rough endoplasmic reticulum and Golgi apparatus. TI cells contain the molecular machinery necessary for ion transport and take up Na(+), K(+), and Cl(-), from which one can infer that it is likely that they play a role in ion and fluid transport in vivo. Because the abundance/microm(2) of highly selective Na(+) channels (HSC channels, consisting of all three ENaC subunits) is the same in TI and TII cells and because TI cells cover the majority of the lung internal surface, TI cells may play the major role in bulk transport of Na(+). In vitro, TI cells can proliferate and exhibit phenotypic plasticity, raising the question of whether this cell type may play a role in development and lung repair after injury. From gene expression analysis of TI cells, one can infer a variety of other possible functions for TI cells. The development of techniques to administer transgenes specifically to TI cells will permit direct study of this cell type in vivo.

Whether genetic factors account for differences in early kidney disease among blacks in a young healthy population is not well known. We evaluated the association of self-reported race and genetic African ancestry with elevated creatinine (> or =1.3 mg/dl for men, > or =1.1 mg/dl for women) among 3,113 black and white participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, ages 38-50 years. We estimated individual African ancestry using 42 ancestry informative markers. Blacks were more likely to have elevated creatinine than whites, and this effect was more pronounced in men: adjusted odds ratio (AOR) for black versus white men = 7.03, 4.15-11.91; AOR for women = 2.40, 1.15-5.02. Higher African ancestry was independently associated with elevated creatinine among black men (AOR = 1.53,1.08-2.16 per SD increase in African ancestry), but not women. A graded increase in odds of elevated creatinine by African Ancestry was observed among black men compared with white men: AOR = 4.27 (2.26-10.06) for black men with 40-70% African ancestry; AOR = 8.09 (4.19-15.61) for black men with 70-80% African ancestry; AOR = 9.05 (4.81-17.02) for black men with >80% African ancestry. Genetic factors common to African ancestry may be associated with increased risk of early kidney dysfunction in a young, healthy population, particularly among black men.

BACKGROUND

Limited data exist on the risk of Chlamydia trachomatis and Neisseria gonorrhoeae transmission from oropharynx to urethra. We examined urethral C. trachomatis and N. gonorrhoeae positivity among men who have sex with men (MSM) seen at San Francisco City Clinic (San Francisco, CA) during 2007.

METHODS

All patients who sought care at the San Francisco City Clinic (the only municipal sexually transmitted disease clinic in San Francisco) received a standardized interview conducted by clinicians. We estimated urethral C. trachomatis and N. gonorrhoeae positivity for 2 groups of visits by MSM who visited during 2007: (1) men who reported their only urethral exposure was receiving fellatio in the previous 3 months and (2) men who reported unprotected insertive anal sex in the previous 3 months. Additionally, urethral C. trachomatis and N. gonorrhoeae positivity was estimated, stratified by human immunodeficiency virus infection status, urogenital symptom history, and whether the patient had been a contact to a sex partner with either chlamydia or gonorrhea.

RESULTS

Among MSM who reported only receiving fellatio, urethral C. trachomatis and N. gonorrhoeae positivity were 4.8% and 4.1%, respectively. These positivity estimates were similar to positivity found among MSM who reported unprotected insertive anal sex.

CONCLUSIONS

A more complete understanding of the risks of transmission of C. trachomatis and N. gonorrhoeae from oropharynx to urethra will help inform prevention and screening programs.