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1.  Examining Vulnerability to Smokeless Tobacco Use Among Adolescents and Adults Meeting Diagnostic Criteria for Major Depressive Disorder 
Smoking prevalence is unevenly distributed in the U.S. population, with those with mental illness, other substance use disorders, and lower socioeconomic status being especially vulnerable. Less research has been conducted on the association between these same vulnerabilities and smokeless tobacco (ST) use. The present study examined cigarette and ST use among adolescents and adults who met diagnostic criteria for major depressive disorder in the National Survey on Drug Use and Health (NSDUH).
Utilizing the most recent (2011) NSDUH, we compared odds for current cigarette smoking and ST use among adolescents and adults meeting criteria for past-year major depressive disorder to the general population, after adjusting for potential confounding influences of sociodemographic and other substance use characteristics. Analyses were conducted to examine sex as a moderator of the relation between major depressive disorder and tobacco use.
Odds for current cigarette smoking among those classified with major depressive disorder were increased among adolescents (OR with 95% CI = 1.33 [1.05, 1.69], p = 0.021) and adults (OR = 1.70 [1.47, 1.97], p < .0005), while odds for current ST use did not differ among adolescents (OR = 0.90 [0.54, 1.49], p = 0.678) and were lower among adults (OR = 0.68 [0.51, 0.91], p = 0.010). Sex was not a significant moderator in adolescents or adults.
Major depressive disorder is associated with increased risk for smoking but not ST use among adolescents and adults further demonstrating heterogeneity in predictors of vulnerability to use of different tobacco products.
PMCID: PMC4124457  PMID: 24978349
smokeless tobacco; cigarette smoking; epidemiology; major depression; NSDUH
2.  State-by-State Variations in Cardiac Rehabilitation Participation Are Associated With Educational Attainment, Income, and Program Availability 
Wide geographic variations in cardiac rehabilitation (CR) participation in the United States have been demonstrated but are not well understood. Socioeconomic factors such as educational attainment are robust predictors of many health-related behaviors, including smoking, obesity, physical activity, substance abuse, and cardiovascular disease. We investigated potential associations between state-level differences in educational attainment, other socioeconomic factors, CR program availability, and variations in CR participation.
A retrospective database analysis was conducted using data from the US Census Bureau, the Centers for Disease Control and Prevention, and the 1997 Medicare database. The outcome of interest was CR participation rates by state, and predictors included state-level high school (HS) graduation rates (in 2001 and 1970), median household income, smoking rates, density of CR program (programs per square mile and per state population), sex and race ratios, and median age.
The relationship between HS graduation rates and CR participation by state was significant for both 2001 and 1970 (r = 0.64 and 0.44, respectively, P < .01). Adding the density of CR programs (per population) and income contributed significantly with a cumulative r value of 0.74 and 0.71 for the models using 2001 and 1970, respectively (Ps < .01). The amount of variance accounted for by each of the 3 variables differed between the 2000 and 1970 graduation rates, but both models were unaltered by including additional variables.
State-level HS graduation rates, CR programs expressed as programs per population, and median income were strongly associated with geographic variations in CR participation rates.
PMCID: PMC4098712  PMID: 24820451
education; income; program availability; state cardiac rehabilitation participation
4.  Maternal Body Mass Index Moderates the Influence of Smoking Cessation on Breast Feeding 
Nicotine & Tobacco Research  2013;16(5):527-535.
Smoking cessation is associated with greater breast feeding in newly postpartum women, while being overweight or obese is associated with lower rates of breast feeding. The purpose of this study is to examine whether the increases in breast feeding associated with smoking cessation are moderated by maternal body mass index (BMI). To our knowledge, the interaction of maternal smoking status and overweight/obesity on breast feeding has not been previously reported.
Participants (N = 370) were current or recent smokers at the start of prenatal care who participated in controlled trials on smoking cessation or relapse prevention during/after pregnancy. Study participants were followed from the start of prenatal care through 24 weeks postpartum. Smoking status was biochemically verified, and maternal reports of breast feeding were collected at 2-, 4-, 8-, 12-, and 24-week postpartum assessments.
Women who reported postpartum smoking abstinence or had a normal/underweight prepregnancy BMI (<25) were more likely to be breast feeding at the time that smoking status was ascertained (odds ratio [OR] = 3.02, confidence interval [CI] = 2.09–4.36, and OR = 2.07, CI = 1.37–3.12, respectively). However, smoking status and BMI interacted such that (a) normal/underweight women showed a stronger association between smoking abstinence and breast feeding (OR = 4.58, CI = 2.73–7.66) than overweight/obese women (OR = 1.89, CI = 1.11–3.23), and (b) abstainers showed an association between normal/underweight BMI and breast feeding (OR = 3.53, CI = 1.96–6.37), but smokers did not (OR = 1.46, CI = 0.88–2.44).
Overweight/obesity attenuates the positive relationship between smoking abstinence and greater breast feeding among newly postpartum women.
PMCID: PMC3977482  PMID: 24203932
Addiction (Abingdon, England)  2015;110(4):690-692.
PMCID: PMC4412735  PMID: 25771694
Contingency management; financial incentives; pregnancy; smoking cessation; vouchers
6.  Does Impulsiveness Moderate Response to Financial Incentives for Smoking Cessation Among Pregnant and Newly Postpartum Women? 
We examined whether impulsiveness moderates response to financial incentives for cessation among pregnant smokers. All participants were randomized to either a condition wherein financial incentives were delivered contingent on smoking abstinence or to a control condition wherein incentives were delivered independent of smoking status. The study was conducted in two steps: First, we examined associations between baseline impulsiveness scores and abstinence at late pregnancy and 24-weeks postpartum as part of a planned prospective study of this topic using data from a recently completed, randomized controlled clinical trial (N = 118). Next, to increase statistical power, we conducted a second analysis collapsing results across that recent trial and two prior trials involving the same contingent incentive and control conditions (N = 236). Impulsivity was assessed using a delay discounting (DD) of hypothetical monetary rewards task in all three trials and Barratt Impulsiveness Scale (BIS) in the most recent trial. Neither DD nor BIS predicted antepartum or postpartum smoking status in the single or combined trials. Receiving abstinence-contingent incentives, lower baseline smoking rate (cigs/day), and a history of quit attempts pre-pregnancy predicted greater odds of antepartum abstinence across the single and combined trials. No variable predicted postpartum abstinence across the single and combined trials, although a history of antepartum quit attempts and receiving abstinence-contingent incentives predicted in the single and combined trials, respectively. Overall, this study provides no evidence that impulsiveness as assessed by DD or BIS moderates response to this treatment approach while underscoring a substantial association of smoking rate and prior quit attempts with abstinence across the contingent incentives and control treatment conditions.
PMCID: PMC4388785  PMID: 25730417
Pregnant smokers; Contingency management; Financial Incentives; Impulsivity; Impulsiveness; Smoking Cessation
7.  Behavior change, health, and health disparities: An introduction 
Preventive medicine  2014;68:1-4.
This Special Issue of Preventive Medicine (PM) focuses on behavior change, health, and health disparities, topics of fundamental importance to improving population health in the U.S. and other industrialized countries. While the U.S. health care system and those of other industrialized countries were developed to manage infectious disease and acute illnesses, it is chronic health conditions that most need to be understood and managed in the 21st century. The evidence is clear that personal behavior patterns like cigarette smoking and physical inactivity/obesity are critically important proximal causes of chronic disease (cardiovascular disease, site-specific cancers, type-2 diabetes) and as such behavior change will need to be a key component of their management. As the outstanding contributions to this Special Issue illustrate, substantial headway is being made in advancing knowledge including developing effective prevention and treatment strategies, with cigarette smoking being an excellent example that change is possible. That said, cigarette smoking continues to be responsible for approximately 480,000 premature deaths annually in the U.S. alone and 5 million globally. So more needs to be done, especially in economically disadvantaged populations. The same certainly applies to the challenges of the obesity epidemic, which of course is a more recent problem and understandably efforts to curtail it are in earlier stages of development.
PMCID: PMC4338024  PMID: 25456804
8.  Characterizing and Improving HIV and Hepatitis Knowledge Among Primary Prescription Opioid Abusers 
Drug and alcohol dependence  2013;133(2):10.1016/j.drugalcdep.2013.08.007.
The high rates of HIV and Hepatitis C (HCV) infection among opioid abusers is a serious public health problem, and efforts to enhance knowledge regarding risks for HIV/hepatitis infection in this population are important. Abuse of prescription opioids (PO), in particular, has increased substantially in the past decade and is associated with increasing rates of injection drug use and HCV infection.
This study describes the effects of a brief HIV/HCV educational intervention delivered in the context of a larger randomized, double-blind clinical trial evaluating the relative efficacy of 1-, 2-, and 4-week outpatient buprenorphine tapers and subsequent oral naltrexone maintenance for treating PO dependence. HIV- and HCV-related knowledge and risk behaviors were characterized pre- and post-intervention in 54 primary PO abusers.
The educational intervention was associated with significant improvements in HIV (p<.001) and HCV (p<.001) knowledge. Significant improvements (p<.001) were observed on all three domains of the HIV questionnaire (i.e., general knowledge, sexual risk behaviors, drug risk behaviors) and on 21 and 11 individual items on the HIV and HCV questionnaires, respectively. Self-reported likelihood of using a condom also increased significantly (p<.05) from pre- to post-intervention. No additional changes in self-reported risk behaviors were observed.
These results suggest that a brief, easy-to-administer intervention is associated with substantial gains in HIV and HCV knowledge among PO abusers and represents the necessary first step towards the dissemination of a structured prevention HIV and HCV intervention for PO abusers.
PMCID: PMC3824383  PMID: 24051063
HIV; hepatitis C; noninjection; injection; education; intervention; opioids; prescription opioids; treatment; buprenorphine
9.  Examining Educational Attainment, Pre-Pregnancy Smoking Rate, and Delay Discounting as Predictors of Spontaneous Quitting Among Pregnant Smokers 
We investigated three potential predictors (educational attainment, pre-pregnancy smoking rate, and delay discounting [DD]) of spontaneous quitting among pregnant smokers. These predictors were examined alone and in combination with other potential predictors using study-intake assessments from controlled clinical trials examining the efficacy of financial incentives for smoking cessation and relapse prevention. Data from 349 pregnant women (231 continuing smokers and 118 spontaneous quitters) recruited from the greater Burlington, Vermont area contributed to this secondary analysis, including psychiatric/sociodemographic characteristics, smoking characteristics, and performance on a computerized DD task. Educational attainment, smoking rate, and DD values were each significant predictors of spontaneous quitting in univariate analyses. A model examining those three predictors together retained educational attainment as a main effect and revealed a significant interaction of DD and smoking rate (i.e., DD was a significant predictor at lower but not higher smoking rates). A final model considering all potential predictors included education, the interaction of DD and smoking rate, and five additional predictors (i.e., stress ratings, the belief that smoking during pregnancy will “greatly harm my baby,” age of smoking initiation, marital status, and prior quit attempts during pregnancy. The present study contributes new knowledge on predictors of spontaneous quitting among pregnant smokers with substantive practical implications for reducing smoking during pregnancy.
PMCID: PMC4180793  PMID: 25069014
delay discounting; pregnancy; cigarette smoking; health disparities; spontaneous quitting
10.  A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers 
JAMA psychiatry  2013;70(12):1347-1354.
Although abuse of prescription opioids (POs) is a significant public health problem, few experimental studies have investigated the treatment needs of this growing population.
To evaluate, following brief stabilization with a combination of buprenorphine hydrochloride and naloxone hydrochloride dihydrate, the relative efficacy of 1-, 2-, and 4-week buprenorphine tapering regimens and subsequent naltrexone hydrochloride therapy in PO-dependent outpatients.
A double-blind, 12-week randomized clinical trial was conducted in an outpatient research clinic. Following a brief period of buprenorphine stabilization, 70 PO-dependent adults were randomized to receive 1-, 2-, or 4-week tapers followed by naltrexone therapy.
During phase 1 (weeks 1–5 after randomization), participants visited the clinic daily; during phase 2 (weeks 6–12), visits were reduced to thrice weekly. Participants received behavioral therapy and urine toxicology testing throughout the trial.
The percentage of participants negative for illicit opioid use, retention, naltrexone ingestion, and favorable treatment response (ie, retained in treatment, opioid abstinent, and receiving naltrexone at the end of the study).
Opioid abstinence at the end of phase 1 was greater in the 4-week compared with the 2- and 1-week taper conditions (P = .02), with 63% (n = 14), 29% (n = 7), and 29% (n = 7) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. Abstinence at the end of phase 2 was also greater in the 4-week compared with the 2- and 1-week conditions (P = .03), with 50% (n = 11), 16% (n = 4), and 20% (n = 5) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. There were more treatment responders in the 4-week condition (P = .03), with 50% (n = 11), 17% (n = 4), and 21% (n = 5) of participants in the 4-, 2-, and 1-week groups considered responders at the end of treatment, respectively. Retention and naltrexone ingestion also were superior in the 4-week vs briefer tapers (both P = .04). Experimental condition (ie, taper duration) was the strongest predictor of treatment response, followed by buprenorphine stabilization dose.
This study represents a rigorous experimental evaluation of outpatient buprenorphine stabilization, brief taper, and naltrexone maintenance for treatment of PO dependence. Results suggest that a meaningful subset of PO-dependent outpatients may respond positively to a 4-week taper plus naltrexone maintenance intervention.
PMCID: PMC4131728  PMID: 24153411
11.  Examining the effects of initial smoking abstinence on response to smoking-related stimuli and response inhibition in a human laboratory model 
Psychopharmacology  2013;231(10):2145-2158.
Research is needed on initial smoking abstinence and relapse risk.
This study aims to investigate the effects of different durations of initial abstinence on sensitivity to smoking-related stimuli and response inhibition in the context of a larger battery of outcome measures.
Smokers were randomly assigned to receive payment contingent on smoking abstinence across all 15 study days (15C) or just the final 2 days (2C). Smoking status and subject ratings were assessed daily. Participants completed fMRI sessions at baseline and day 14 during which they completed craving ratings after exposure to smoking-related and neutral stimuli and performed a response inhibition task. On day 15, participants completed a smoking preference session involving 20 exclusive choices between smoking and money.
The payment contingencies were effective in producing greater smoking abstinence in the 15C vs. 2C conditions. Ratings of withdrawal decreased, while ratings of ease and confidence in abstaining increased in the 15C vs. 2C conditions across the 15-day study. 15C participants were less likely to choose the smoking option in the preference session. 15C participants reported greater reductions in craving compared to the 2C participants in the presence of smoking-related and neutral stimuli (i.e., decreases in generalized craving), but no differences were noted in cue reactivity per se or in response inhibition.
Results systematically replicate prior observations that a period 2 weeks of initial abstinence decreases the relative reinforcing effects of smoking and improves other outcomes associated with relapse risk compared to the initial day or two of a cessation effort, and extends them by underscoring the importance of generalized rather than cue-induced craving in relation to relapse risk during the initial weeks of smoking cessation.
PMCID: PMC4123458  PMID: 24337077
Cigarette smoking; Abstinence; Reinforcement; Nicotine withdrawal; Craving; Contingency management; Financial incentives; Cue reactivity; Response inhibition
12.  Incentives and health: An introduction 
Preventive medicine  2012;55(0):S2-S6.
PMCID: PMC4107351  PMID: 22554884
13.  Improving Medicaid Health Incentives Programs: Lessons from Substance Abuse Treatment Research 
Preventive medicine  2014;63:87-89.
This commentary addresses the efforts of Medicaid programs in several US states to employ financial incentives to increase healthy behavior among their beneficiaries. While these Medicaid incentives programs have been successful at boosting rates of less effortful behaviors, like semiannual dental visits, they have fallen short in promoting more complex behaviors, like smoking cessation, drug abstinence, and weight management. Incentives have been extensively studied as a treatment for substance use disorders for over 20 years, with good success. We identify two variables shown by meta-analysis to moderate the efficacy of incentives interventions in substance abuse treatment, the immediacy of incentive delivery and size (or magnitude) of the incentive, that are lacking in current Medicaid incentives program. We also offer some guidance on how these moderating variables could be addressed within Medicaid programs. This is a critical time for such analysis, as more than 10 states are employing incentives in their Medicaid programs, and some are currently reevaluating their incentives strategies.
PMCID: PMC4043298  PMID: 24613792
14.  Characterizing and Improving HIV/AIDS Knowledge Among Cocaine-Dependent Outpatients Using Modified Materials* 
Drug and alcohol dependence  2012;127(0):220-225.
Only 56% of outpatient substance abuse treatment programs in the U.S. provide HIV/AIDS education, likely due to the time required to complete existing educational interventions. This report describes results of a third study in a series to develop a brief educational intervention to increase HIV/AIDS knowledge among cocaine-dependent outpatients.
Participants (N=90) were randomized to experimental or control conditions and completed two HIV/AIDS knowledge pre-tests with response formats modified to “true-false-don’t know.” Pre-test results were later compared to historical controls that completed pre-tests in their original “true-false” format. Next, participants in the experimental condition completed an HIV/AIDS educational intervention while participants in the control condition completed a sham intervention. Participants in both conditions then completed knowledge tests a second time. Participants in both conditions were subsequently crossed over, and then completed knowledge tests a third time. Post-intervention analyses were conducted using test data from all participants who completed the educational intervention (N=56). A subset of these participants (N=40) completed follow-up tests approximately 9 weeks after completing the educational intervention.
Scores on both pre-tests were lower than those observed in historical controls (p < .001). Scores on knowledge tests increased from baseline after participants completed the educational intervention (p < .001), but not after the sham intervention (p >.05). Scores at follow-up remained higher than baseline scores (p < .001).
Modifying response formats to include a “don’t know” option likely increases identification of baseline knowledge deficits. This brief intervention is effective at increasing HIV/AIDS knowledge among cocaine-dependent outpatients.
PMCID: PMC4026286  PMID: 22889696
HIV/AIDS education; HIV/AIDS drug users; HIV/AIDS knowledge
15.  Illicit Drug Use Among Pregnant Women Enrolled in Treatment for Cigarette Smoking Cessation 
Nicotine & Tobacco Research  2012;15(5):987-991.
Smoking during pregnancy is the leading preventable cause of poor pregnancy outcomes in the United States. In population studies and nationwide surveys, pregnant smokers report more illicit drug use than pregnant nonsmokers. The purpose of this study was to examine the prevalence of illicit drug use among pregnant women enrolled in clinical trials for smoking cessation.
Urine specimens from 115 pregnant women were tested for illicit drug use during a study intake visit (~10th week of pregnancy) and during the final antepartum (FAP) smoking-status assessment (~28th week of pregnancy). Participants smoked about 18 cigarettes/day prepregnancy, were generally young (<25 years), Caucasian, with a high school education and without private insurance.
About 34% of specimens from the intake visit and 25% of those from the FAP assessment tested positive for an illicit drug. The most common drug detected was marijuana (90% of positive specimens), followed by opioids (18%), cocaine (5%), benzodiazepines (3%), and methadone (3%). None tested positive for amphetamines. The majority of women (53%) who tested positive for an illicit substance at intake also tested positive at the FAP assessment.
Approximately a quarter to a third of pregnant women enrolled in these smoking-cessation trials were determined to be using illicit drugs, with marijuana use being the most prevalent. Those providing smoking-cessation services to pregnant women may want to be prepared to assist with obtaining services for other drug use as well.
PMCID: PMC3621582  PMID: 23072871
16.  SERPINE1: A Molecular Switch in the Proliferation-Migration Dichotomy in Wound-“Activated” Keratinocytes 
Advances in Wound Care  2014;3(3):281-290.
Significance: A highly interactive serine protease/plasmin/matrix metalloproteinase axis regulates stromal remodeling in the wound microenvironment. Current findings highlight the importance of stringent controls on protease expression and their topographic activities in cell proliferation, migration, and tissue homeostasis. Targeting elements in this cascading network may lead to novel therapeutic approaches for fibrotic diseases and chronic wounds.
Recent Advances: Matrix-active proteases and their inhibitors orchestrate wound site tissue remodeling, cell migration, and proliferation. Indeed, the serine proteases urokinase plasminogen activator and tissue-type plasminogen activator (uPA/tPA) and their major phsyiological inhibitor, plasminogen activator inhibitor-1 (PAI-1; serine protease inhibitor clade E member 1 [SERPINE1]), are upregulated in several cell types during injury repair. Coordinate expression of proteolytic enzymes and their inhibitors in the wound bed provides a mechanism for fine control of focal proteolysis to facilitate matrix restructuring and cell motility in complex environments.
Critical Issues: Cosmetic and tissue functional consequences of wound repair anomalies affect the quality of life of millions of patients in the United States alone. The development of novel therapeutics to manage individuals most affected by healing anomalies will likely derive from the identification of critical, translationally accessible, control elements in the wound site microenvironment.
Future Directions: Activation of the PAI-1 gene early after wounding, its prominence in the repair transcriptome and varied functions suggest a key role in the global cutaneous injury response program. Targeting PAI-1 gene expression and/or PAI-1 function with molecular genetic constructs, neutralizing antibodies or small molecule inhibitors may provide a novel, therapeutically relevant approach, to manage the pathophysiology of wound healing disorders associated with deficient or excessive PAI-1 levels.
PMCID: PMC3955966  PMID: 24669362
In this study we examined the association between social discounting and smoking status in a cohort of pregnant cigarette smokers (n=91), quitters (n=27), or never-smokers (n=30). The smokers and quitters were participants in clinical trials on smoking cessation and relapse prevention, while the never-smokers were controls in a study on nicotine withdrawal during pregnancy. Social discounting was assessed using a paper and pencil task that assesses the amount of hypothetical money a person is willing to forgo in order to share with individuals in their social network ranging from the person who is emotionally closest to them to a mere acquaintance. The amount that women were willing to forgo in order to share decreased hyperbolically as a function of social distance, with smokers exhibiting steeper discounting functions (i.e., less generosity) than quitters or never-smokers; discounting functions of quitters and never-smokers did not differ significantly. In multivariate analyses controlling for potential sociodemographic and other confounds, social discounting remained a significant predictor of smoking status among smokers versus quitters. Overall, these results suggest that individual differences in social discounting may be a factor influencing the choices that women make about quitting smoking upon learning of a pregnancy.
PMCID: PMC3496264  PMID: 23162211
18.  Financial Incentives for Smoking Cessation Among Pregnant and Newly Postpartum Women 
Preventive medicine  2011;55(Suppl):S33-S40.
Smoking during pregnancy is the leading preventable cause of poor pregnancy outcomes in the U.S., causing serious immediate and longer-term adverse effects for mothers and offspring. In this report we provide a narrative review of research on the use of financial incentives to promote abstinence from cigarette smoking during pregnancy, an intervention wherein women earn vouchers exchangeable for retail items contingent on biochemically-verified abstinence from recent smoking.
Published reports based on controlled trials are reviewed. All of the reviewed research was conducted by one of two research groups who have investigated this treatment approach.
Results from six controlled trials with economically disadvantaged pregnant smokers support the efficacy of financial incentives for increasing smoking abstinence rates antepartum and early postpartum. Results from three trials provide evidence that the intervention improves sonographically estimated fetal growth, mean birth weight, percent of low-birth-weight deliveries, and breastfeeding duration.
The systematic use of financial incentives has promise as an efficacious intervention for promoting smoking cessation among economically disadvantaged pregnant and recently postpartum women and improving birth outcomes. Additional trials in larger and more diverse samples are warranted to further evaluate the merits of this treatment approach.
PMCID: PMC3399924  PMID: 22227223
financial incentives; contingency management; vouchers; pregnancy; cigarette smoking; birth outcomes
19.  Infant Pupillary Response to Methadone Administration During Treatment for Neonatal Abstinence Syndrome: A Feasibility Study 
Drug and alcohol dependence  2012;126(1-2):268-271.
Pupil diameter is a frequently assessed objective index of the pharmacodynamic effects of opioids in adults, but to our knowledge has never been examined in infants. Such a measure could improve assessment and treatment of neonates exposed to opioids in utero. The present study examined changes in pupil diameter after opioid administration in opioid-exposed infants who required pharmacological treatment for neonatal abstinence syndrome (NAS) to test the feasibility of using pupil diameter as a measure of opioid effects in these infants.
Ten infants (2–7 days old) receiving methadone (0.4–0.5 mg every 12 hours) for the treatment of NAS participated. A picture of one of each infant's eyes was taken under controlled illumination conditions with a standard digital camera just prior to dosing and 0–1, 2–4, 5–7, and 8–10 hours after dosing. The diameters of the pupil and iris were measured and relative pupil diameter (pupil diameter expressed as a percentage of iris diameter) was analyzed.
Mean (±SE) relative pupil diameter decreased significantly after dosing from 41±2% to 29±2%. After dosing, a significant increasing linear trend was observed over time, with values of 29±2%, 33±3%, 38±3%, and 41±3% at 0–1, 2–4, 5–7, and 8–10 hours after dosing.
Infant pupils respond to opioid administration in the same sensitive, orderly manner as is commonly observed in adults. Pupil diameter appears to be an objective, sensitive measure of neonatal response to opioids that may be a useful complement to, or perhaps at times a replacement for, observer-rated scale scores.
PMCID: PMC3467317  PMID: 22682657
Opioids; methadone; pupil diameter; neonatal abstinence syndrome
20.  The use of palliative care services amongst end-stage kidney disease patients in an Irish tertiary referral centre 
Clinical Kidney Journal  2013;6(6):604-608.
Although patients with end-stage kidney disease (ESKD) have a shortened life expectancy, their end-of-life (EOL) care is suboptimal. The aim of this study was to review the utilization of specialist palliative care (SPC) in patients with ESKD in Dublin, Ireland.
We conducted a retrospective chart review of prevalent patients with ESKD who died between January 2005 and December 2009 at a tertiary referral centre. We recorded SPC referrals, modality of renal replacement therapy, age and place of death.
Of 131 included patients, 88 (67.2%) were male, mean age at death was 63.2 ± 15.1 years and 102 (77.9%) were treated with haemodialysis. Forty-eight patients (36.7%) were referred to SPC, who were involved in the patients' management for a median of 12 days (range 0–907) before death. A total 104 patients (79.4%) died in an acute hospital, 19 (14.5%) died at home, 3 (2.3%) died in an inpatient hospice and the place of death was unknown for 5 patients (3.8%). Dialysis was withdrawn prior to death in 50 patients (38.1%), with a median time to death after withdrawal of dialysis of 6 days (0–105 days). A discussion regarding the withdrawal of dialysis was more frequently held with family member(s) rather than the patient.
SPC was involved in the antemortem care of ∼1/3 of the patients with the majority of referrals placed at a late stage. Given the short timeframe until death once dialysis is withdrawn, it is imperative that appropriate EOL care is instituted. This study identifies an underutilization of SPC and improved integration of palliative care and nephrology services may optimize EOL care for patients with ESKD.
PMCID: PMC4438365  PMID: 26069830
dialysis; end-of-life care; end-stage kidney disease; palliative care; withdrawal of dialysis
21.  PAI-1 Mediates the TGF-β1+EGF-Induced “Scatter” Response in Transformed Human Keratinocytes 
Cooperative interactions between growth factor signaling pathways are important elements in carcinoma progression. A model system combining transforming growth factor-β1 (TGF-β1) and EGF was developed to investigate mechanisms underlying induced epithelial-to-mesenchymal transition (EMT) in ras-transformed human (HaCaT II-4) keratinocytes. Dual stimulation with TGF-β1+EGF resulted in keratinocyte “plasticity” and pronounced colony dispersal. The most highly expressed transcript, identified by mRNA profiling, encoded plasminogen activator inhibitor-1 (PAI-1; SERPINE1). PAI-1 negatively regulates plasmin-dependent matrix degradation, preserving a stromal scaffold permissive for keratinocyte motility. Mitogen-activated extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK) and p38 signaling were required for maximal PAI-1 upregulation and TGF-β1+EGF-stimulated cell locomotion, as pharmacologic disruption of MEK/p38 activity ablated both responses. Moreover, PAI-1 knockdown alone effectively inhibited TGF-β1+EGF-dependent cell scattering, indicating a functional role for this SERPIN in the dual-growth factor model of induced motility. Moreover, EGFR signaling blockade or EGFR knockdown attenuated TGF-β1-induced PAI-1 expression, implicating EGFR transactivation in TGF-β1-stimulated PAI-1 expression, and reduced colony dispersal in TGF-β1+EGF-treated cultures. Identification of such cooperative signaling networks and their effect on specific invasion-promoting target genes, such as PAI-1, may lead to the development of pathway-specific therapeutics that affect late-stage events in human tumor progression.
PMCID: PMC3774605  PMID: 20428185
22.  A Contingency-Management Intervention to Promote Initial Smoking Cessation Among Opioid-Maintained Patients 
Prevalence of cigarette smoking among opioid-maintained patients is more than threefold that of the general population and associated with increased morbidity and mortality. Relatively few studies have evaluated smoking interventions in this population. The purpose of the present study was to examine the efficacy of contingency management for promoting initial smoking abstinence. Forty methadone- or buprenorphine-maintained cigarette smokers were randomly assigned to a contingent (n = 20) or noncontingent (n = 20) experimental group and visited the clinic for 14 consecutive days. Contingent participants received vouchers based on breath carbon monoxide levels during Study Days 1 to 5 and urinary cotinine levels during Days 6 to 14. Voucher earnings began at $9.00 and increased by $1.50 with each subsequent negative sample for maximum possible of $362.50. Noncontingent participants earned vouchers independent of smoking status. Although not a primary focus, participants who were interested and medically eligible could also receive bupropion (Zyban). Contingent participants achieved significantly more initial smoking abstinence, as evidenced by a greater percentage of smoking-negative samples (55% vs. 17%) and longer duration of continuous abstinence (7.7 vs. 2.4 days) during the 2 week quit attempt than noncontingent participants, respectively. Bupropion did not significantly influence abstinence outcomes. Results from this randomized clinical trial support the efficacy of contingency management interventions in promoting initial smoking abstinence in this challenging population.
PMCID: PMC3605744  PMID: 20158293
contingency management; smoking cessation; methadone; buprenorphine; bupropion
23.  TGF-β1 → SMAD/p53/USF2 → PAI-1 transcriptional axis in ureteral obstruction-induced renal fibrosis 
Cell and tissue research  2011;347(1):117-128.
Chronic kidney disease constitutes an increasing medical burden affecting 26 million people in the United States alone. Diabetes, hypertension, ischemia, acute injury, and urological obstruction contribute to renal fibrosis, a common pathological hallmark of chronic kidney disease. Regardless of etiology, elevated TGF-β1 levels are causatively linked to the activation of profibrotic signaling pathways initiated by angiotensin, glucose, and oxidative stress. Unilateral ureteral obstruction (UUO) is a useful and accessible model to identify mechanisms underlying the progression of renal fibrosis. Plasminogen activator inhibitor-1 (PAI-1), a major effector and downstream target of TGF-β1 in the progression of several clinically important fibrotic disorders, is highly up-regulated in UUO and causatively linked to disease severity. SMAD and non-SMAD pathways (pp60c-src, epidermal growth factor receptor [EGFR], mitogen-activated protein kinase, p53) are required for PAI-1 induction by TGF-β1. SMAD2/3, pp60c-src, EGFR, and p53 activation are each increased in the obstructed kidney. This review summarizes the molecular basis and translational significance of TGF-β1-stimulated PAI-1 expression in the progression of kidney disease induced by ureteral obstruction. Mechanisms discussed here appear to be operative in other renal fibrotic disorders and are relevant to the global issue of tissue fibrosis, regardless of organ site.
PMCID: PMC3188682  PMID: 21638209
Fibrosis; PAI-1; TGF-β1; p53; Transcription
25.  Using NicAlert Strips to Validate Smoking Status Among Pregnant Cigarette Smokers 
Drug and alcohol dependence  2011;119(1-2):130-133.
Decreasing smoking during pregnancy is an important public health priority. An important step towards decreasing smoking during pregnancy is wider dissemination of evidence-based smoking cessation interventions. One such intervention is contingency management wherein mothers earn vouchers exchangeable for retail items contingent on biochemically-verified smoking abstinence. Wider dissemination may be possible by using smoking verification methods that require minimal training and equipment. One possibility is to use a cotinine-sensitive dipstick (NicAlert) rather than a bench-top cotinine analyzer, which is expensive and requires relatively extensive technician expertise, or breath carbon monoxide analysis, which is relatively nonspecific. The present study was conducted to begin examining the utility of cotinine-sensitive dipsticks for this purpose.
Fifty urine samples from pregnant women enrolled in a smoking cessation program were analyzed to compare three different methods for verifying smoking status: NicAlert strips, a bench-top enzyme multiplied immunoassay technique (EMIT) analyzer, and gas chromatography (GC), the current gold standard for determining cotinine levels in urine.
Agreement between GC and NicAlert results were high (96%) and comparable to agreement between GC and EMIT results (94%). Semi-quantitative measurements using NicAlert were low with only 30% of samples in agreement between GC and specific ranges given on the strips.
NicAlert strips appear to be a valid measure of determining smoking status among pregnant smokers although not of absolute cotinine concentration. With minimal training and equipment required, NicAlert strips provide a potentially practical method for using urine cotinine to verify smoking status in community treatment settings.
PMCID: PMC3205243  PMID: 21652155
NicAlert; urine cotinine; pregnant smokers; gas chromatography; smoking status; biochemical verification; contingency management

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