Publications

Pathologic features of idiopathic pulmonary fibrosis (IPF) include genetic predisposition, activation of the unfolded protein response, telomere attrition, and cellular senescence. The mechanisms leading to alveolar epithelial cell (AEC) senescence are poorly understood. MicroRNAs (miRNAs) have been reported as regulators of cellular senescence. Senescence markers including p16, p21, p53, and senescence-associated β-galactosidase (SA-βgal) activity were measured in type II AECs from IPF lungs and unused donor lungs. miRNAs were quantified in type II AECs using gene expression arrays and quantitative RT-PCR. Molecular markers of senescence (p16, p21, and p53) were elevated in IPF type II AECs. SA-βgal activity was detected in a greater percentage in type II AECs isolated from IPF patients (23.1%) compared to patients with other interstitial lung diseases (1.2%) or normal controls (0.8%). The relative levels of senescence-associated miRNAs miR-34a, miR-34b, and miR-34c, but not miR-20a, miR-29c, or miR-let-7f were significantly higher in type II AECs from IPF patients. Overexpression of miR-34a, miR-34b, or miR-34c in lung epithelial cells was associated with higher SA-βgal activity (27.8%, 35.1%, and 38.2%, respectively) relative to control treated cells (8.8%). Targets of miR-34 miRNAs, including E2F1, c-Myc, and cyclin E2, were lower in IPF type II AECs. These results show that markers of senescence are uniquely elevated in IPF type II AECs and suggest that the miR-34 family of miRNAs regulate senescence in IPF type II AECs.

Prevalence and reasons for using electronic cigarettes (e-cigarettes) was examined among patients enrolled in 24 substance abuse treatment centers in the United States (N=1113). Prevalence of e-cigarette use was assessed for the full sample. Bivariate analyses and multivariate logistic regression were used to identify characteristics associated with e-cigarette use among current cigarette smokers (the majority of e-cigarette users). Overall 55.5% of the sample reported lifetime use of e-cigarettes, and 30.5% reported using e-cigarettes in the past 30days (current users). The main reasons for using e-cigarettes were (a) at times/places when smoking was prohibited (53.5%), and (b) as a way to quit/reduce cigarette smoking (50.3%). Daily vs non-daily e-cigarette users were more likely to use e-cigarettes both as a way to reduce health risks, and as a way to quit/reduce cigarette smoking. A majority of e-cigarette users (87.1%) reported dual use of e-cigarettes and tobacco cigarettes during the past month. Among current cigarette smokers, those that also used e-cigarettes smoked more cigarettes per day, were more likely to have made a past year cigarette quit attempt, and to have tried nicotine replacement therapy compared to cigarette only smokers. There was a high rate of dual e-cigarette and cigarette use by persons enrolled in addiction treatment. E-cigarette users may be heavier cigarette smokers trying to quit or reduce their cigarette smoking. However, e-cigarettes were also used at times when individuals could not smoke cigarettes. Substance abuse treatment centers developing tobacco policies need to consider these potentially conflicting reasons for using e-cigarettes.

BACKGROUND

Unintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States.

OBJECTIVE

To evaluate the feasibility and effect of implementing naloxone prescription to patients prescribed opioids for chronic pain.

DESIGN

2-year nonrandomized intervention study.

SETTING

6 safety-net primary care clinics in San Francisco, California.

PARTICIPANTS

1985 adults receiving long-term opioid therapy for pain.

INTERVENTION

Providers and clinic staff were trained and supported in naloxone prescribing.

MEASUREMENTS

Outcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review.

RESULTS

38.2% of 1985 patients receiving long-term opioids were prescribed naloxone. Patients prescribed higher doses of opioids and with an opioid-related ED visit in the past 12 months were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month in the 6 months after receipt of the prescription (incidence rate ratio [IRR], 0.53 [95% CI, 0.34 to 0.83]; P = 0.005) and 63% fewer visits after 1 year (IRR, 0.37 [CI, 0.22 to 0.64]; P < 0.001) compared with patients who did not receive naloxone. There was no net change over time in opioid dose among those who received naloxone and those who did not (IRR, 1.03 [CI, 0.91 to 1.27]; P = 0.61).

LIMITATION

Results are observational and may not be generalizable beyond safety-net settings.

CONCLUSION

Naloxone can be coprescribed to primary care patients prescribed opioids for pain. When advised to offer naloxone to all patients receiving opioids, providers may prioritize those with established risk factors. Providing naloxone in primary care settings may have ancillary benefits, such as reducing opioid-related adverse events.

PRIMARY FUNDING SOURCE

National Institutes of Health.