A Learning Health System Approach to Increasing Human Papillomavirus Immunizations Among Young Adults.

INTRODUCTION Immunization rates against the human papillomavirus (HPV) remain suboptimal in the young adult population. Little is known about the most effective means for encouraging vaccination in this population. METHODS The authors conducted a clinical trial of 3 methods to encourage HPV vaccination in a large Northern California integrated Health Plan. Young adults aged 18-26 with evidence of insufficient HPV vaccination were sent a bulk secure message from the Health Plan (standard outreach); those who did not respond were randomized to no further outreach, a second, personalized secure message from a specific practitioner, or a letter mailed to their home. The primary outcome was receipt of at least 1 HPV vaccine within 3 months following the initial bulk secure message. RESULTS In total, 7718 young adults were randomized. After 3 months, 86 patients (3.5%) who received no additional outreach obtained an immunization, compared with 114 (4.6%) who received the second secure message (p = 0.05) and 126 (5.1%) who received the mailed letter (p = 0.006). DISCUSSION Supplemental mailed or personalized electronic messages increased vaccination beyond no additional intervention, although gains were not clinically meaningful. These findings highlight the need for more successful alternatives to encourage uptake of such preventive health interventions among young adults. The successful conduct of this rapid-cycle, randomized trial showed that such evaluations are feasible, providing actionable data to inform implementation strategies. CONCLUSIONS Further study is needed to identify effective strategies for improving preventive health uptake in this important and underserved population. Rapid-cycle randomized evaluation strategies can provide critical information to focus efforts for achieving this goal.

Docking of endothelial nitric oxide synthase (eNOS) to the mitochondrial outer membrane: a pentabasic amino acid sequence in the autoinhibitory domain of eNOS targets a proteinase K-cleavable peptide on the cytoplasmic face of mitochondria.

Despite growing evidence for a mitochondrial localization of nitric oxide (NO) synthase and a broadening spectrum of NO actions on mitochondrial respiration and apoptosis, the basis for interaction between the enzyme and the organelle remain obscure. Here we investigated mitochondrial localization of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells and human embryonic kidney cells transfected or infected with eNOS expression vectors. Copurification of eNOS with mitochondria was observed in both human umbilical vein endothelial cells and eNOS-expressing human embryonic kidney cells. Immunodetectable eNOS was cleaved from mitochondria by proteinase K treatment, suggesting eNOS association with the outer mitochondrial membrane. Localization of eNOS to a proteinase K-cleavable site on the cytoplasmic face of the outer membrane was confirmed by immunogold labeling of non-permeabilized mitochondria. Markers for mitochondrial subfractions ruled out the possibility of eNOS association with an intramitochondrial site or inverted mitochondrial particles. Denaturation of eNOS did not attenuate association with mitochondria. Mutant eNOS lacking a pentabasic amino acid sequence within the autoinhibitory domain (residues 628-632 of the bovine eNOS) showed dramatically reduced binding to the mitochondrial but not to the plasma membrane, which was associated with increased oxygen consumption. Collectively, these findings argue in favor of eNOS localization to the outer mitochondrial membrane in endothelial cells and identify elements of a novel anchoring mechanism.