Changes in fecal elastase-1 following initiation of CFTR modulator therapy in pediatric patients with cystic fibrosis.

BACKGROUND: Improvement in exocrine pancreatic function in persons with CF (pwCF) on cystic fibrosis transmembrane conductance regulator (CFTR) modulators has been documented in clinical trials using fecal pancreatic elastase-1 (FE-1). Our group endeavored to evaluate real-world data on FE-1 in children on CFTR modulator therapy at three pediatric cystic fibrosis (CF) centers. METHODS: Pediatric pwCF were offered FE-1 testing if they were on pancreatic enzyme replacement therapy (PERT) and on CFTR modulator therapy according to their center's guideline. FE-1 data were collected retrospectively. The primary outcome was absolute change in FE-1. RESULTS: 70 pwCF were included for analysis. 53 had baseline and post-modulator FE-1 values. There was a significant increase in FE-1 from median 25 mcg/g (IQR 25-60) at baseline to 57 mcg/g (IQR 20-228) post-modulator (p<0.001 by Wilcoxon matched pairs), with an absolute change in FE-1 of median 28 mcg/g (IQR -5-161) and mean 93.5 ± 146.8 mcg/g. Age was negatively correlated with change in FE-1 (Spearman r=-0.48, p<0.001). 15 pwCF (21%) had post-modulator FE-1 values ≥200 mcg/g, consistent with pancreatic sufficiency (PS). The PS group was significant for younger age at initiation of first CFTR modulator and a higher baseline FE-1. CONCLUSIONS: Most pwCF experienced an increase in FE-1 while receiving CFTR modulator treatment and a small percentage demonstrated values reflective of PS. These data suggest that PS may be attained in those that initiated modulator therapy at a younger age or had a higher baseline FE-1. FE-1 testing is suggested for children on any CFTR modulator therapy.

E-Cigarettes for Immediate Smoking Substitution in Women Diagnosed with Cervical Dysplasia and Associated Disorders.

The aim of this study was to determine if 31 women with cervical dysplasia and associated conditions exacerbated by smoking would be successful substituting cigarettes with their choice of either nicotine replacement therapy (NRT) or electronic cigarettes (EC). Women received motivational interviewing and tried both NRT and ECs, choosing one method to use during a six-week intervention period. Daily cigarette consumption was measured at baseline, six, and 12 weeks, with differences analyzed by the Wilcoxon signed-rank test. Study analysis consisted only of women choosing to use ECs (29/31), as only two chose NRT. At the 12-week follow-up, the seven day point prevalence abstinence from smoking was 28.6%, and the median number of cigarettes smoked daily decreased from 18.5 to 5.5 (p < 0.0001). The median number of e-cigarette cartridges used dropped from 21 at the six-week follow-up to 12.5 at the 12-week follow-up. After initiating EC use, women at risk for cervical cancer were able to either quit smoking or reduce the number of cigarettes smoked per day. Although a controlled trial with a larger sample size is needed to confirm these initial results, this study suggests that using ECs during quit attempts may reduce cigarette consumption.

Which nicotine products are gateways to regular use? First-tried tobacco and current use in college students.

BACKGROUND: The potential for emerging tobacco products (ETPs) to be gateway products for further tobacco use among youth is of significant concern. PURPOSE: To examine use of various nicotine-containing products on a tobacco-free college campus and whether the first product tried predicts subsequent tobacco use. METHODS: Undergraduate students (N=1,304) at a large university completed an online survey of past/current use of cigarettes; smokeless tobacco (SLT); hookah; ETPs (dissolvables, snus, and electronic cigarettes); and nicotine replacement therapy (NRT). Data were collected from September 2012 to May 2013 and analyses were conducted from June to September 2013. Students were classified as single, dual, or poly tobacco users. RESULTS: The sample consisted of 79.5% non-users, 13.8% single, 4.4% dual, and 1.5% poly users. Overall, 49.4% of participants reported trying a tobacco product. Hookah was the most tried product (38%), but cigarettes were most often the first product ever tried (51%). First product tried did not predict current tobacco use and non-use, but individuals who first tried SLT or cigarettes (rather than hookah or ETPs) were more likely to be poly tobacco users. Current tobacco users who first tried ETPs or hookah were largely non-daily users of hookah; current tobacco users who first tried cigarettes or SLT were largely non-daily or daily users of cigarettes/SLT. CONCLUSIONS: Hookah and ETPs are increasingly becoming the first tobacco product ever tried by youth; however, uptake of ETPs is poor, unlike cigarettes and SLT, and does not appear to lead to significant daily/non-daily use of cigarettes and SLT.

Sulpiride, but not SCH23390, modifies cocaine-induced conditioned place preference and expression of tyrosine hydroxylase and elongation factor 1α in zebrafish.

Finding genetic polymorphisms and mutations linked to addictive behavior can provide important targets for pharmaceutical and therapeutic interventions. Forward genetic approaches in model organisms such as zebrafish provide a potentially powerful avenue for finding new target genes. In order to validate this use of zebrafish, the molecular nature of its reward system must be characterized. We have previously reported the use of cocaine-induced conditioned place preference (CPP) as a reliable method for screening mutagenized fish for defects in the reward pathway. Here we test if CPP in zebrafish involves the dopaminergic system by co-treating fish with cocaine and dopaminergic antagonists. Sulpiride, a potent D2 receptor (DR2) antagonist, blocked cocaine-induced CPP, while the D1 receptor (DR1) antagonist SCH23390 had no effect. Acute cocaine exposure also induced a rise in the expression of tyrosine hydroxylase (TH), an important enzyme in dopamine synthesis, and a significant decrease in the expression of elongation factor 1α (EF1α), a housekeeping gene that regulates protein synthesis. Cocaine selectively increased the ratio of TH/EF1α in the telencephalon, but not in other brain regions. The cocaine-induced change in TH/EF1α was blocked by co-treatment with sulpiride, but not SCH23390, correlating closely with the action of these drugs on the CPP behavioral response. Immunohistochemical analysis revealed that the drop in EF1α was selective for the dorsal nucleus of the ventral telencephalic area (Vd), a region believed to be the teleost equivalent of the striatum. Examination of TH mRNA and EF1α transcripts suggests that regulation of expression is post-transcriptional, but this requires further examination. These results highlight important similarities and differences between zebrafish and more traditional mammalian model organisms.