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1.  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
2.  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
3.  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
4.  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
5.  Incentives and health: An introduction 
Preventive medicine  2012;55(0):S2-S6.
PMCID: PMC4107351  PMID: 22554884
6.  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
7.  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
8.  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
9.  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
11.  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
12.  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
13.  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
14.  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
15.  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
17.  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
18.  The Association between Outpatient Buprenorphine Detoxification Duration and Clinical Treatment Outcomes: A Review 
Drug and alcohol dependence  2011;119(1-2):1-9.
The association between buprenorphine taper duration and treatment outcomes is not well understood. This review evaluated whether duration of outpatient buprenorphine taper is significantly associated with treatment outcomes.
Studies that were published in peer-reviewed journals, administered buprenorphine as an outpatient taper to opioid-dependent participants, and provided data on at least one of three primary treatment outcome measures (opioid abstinence, retention, peak withdrawal severity) were reviewed. Primary treatment outcomes were evaluated as a function of taper duration using hierarchical linear regressions using pre-taper maintenance as a cofactor.
Twenty-eight studies were reviewed. Taper duration significantly predicted percent of opioid-negative samples provided during treatment, however pre-taper maintenance period predicted percent participants abstinent on the final day of treatment. High rates of relapse were reported. No significant association between taper duration and retention in treatment or peak withdrawal severity was observed.
The data reviewed here suggest taper duration is associated with opioid abstinence achieved during detoxification but not with other markers of treatment outcome. The reviewed studies varied widely on several parameters (e.g., frequency of urinalysis testing, provision of ancillary medications) that may influence treatment outcome and thus could have interfered with the ability to identify relationships between taper duration and outcomes. Future studies evaluating opioid detoxification should utilize rigorous experimental methods and report a wider range of outcome measures in order to help advance our understanding of the association between taper duration and treatment outcomes.
PMCID: PMC3205338  PMID: 21741781
opioid; buprenorphine; taper; detoxification; withdrawal; outpatient
19.  Delay Discounting is Associated with Treatment Response among Cocaine-Dependent Outpatients 
Delay discounting (DD) describes the rate at which reinforcers lose value as the temporal delay to their receipt increases. Steeper discounting has been positively associated with vulnerability to substance use disorders, including cocaine use disorders.
In the present study, we examined whether DD of hypothetical monetary reinforcers is associated with the duration of cocaine abstinence achieved among cocaine-dependent outpatients.
Participants were 36 adults who were participating in a randomized controlled trial examining the efficacy of voucher-based contingency management (CM) using low-magnitude (N = 18) or high-magnitude (N = 18) voucher monetary values.
DD was associated with the number of continuous weeks of cocaine abstinence achieved, even after adjusting for treatment condition during the initial 12-week (t(33) = 2.48, p = .045) and entire recommended 24-week of treatment (t(33) = 2.40, p = .022). Participants who exhibited steeper discounting functions achieved shorter periods of abstinence in the Low-magnitude voucher condition (12-week: t(16) = 2.48, p = .025; 24-week: t(16) = 2.68, p = .017), but not in the High-magnitude voucher condition (12-week: t(16) = 0.51, p = .618; 24-week: t(16) = 1.08, p = .298), although the interaction between DD and treatment condition was not significant (12-week: t(32) = −1.12, p = .271; 24-week: t(32) = −0.37, p = .712).
These results provide further evidence on associations between DD and treatment response and extend those observations to a new clinical population (i.e., cocaine-dependent outpatients), while also suggesting that a more intensive intervention like the High-magnitude CM condition may diminish this negative relationship between DD and treatment response.
PMCID: PMC3476946  PMID: 21517195
Temporal discounting; delay discounting; cocaine dependence; contingency management; vouchers; treatment response
20.  Examining Maternal Weight Gain During Contingency-Management Treatment for Smoking Cessation Among Pregnant Women 
Drug and alcohol dependence  2010;114(1):73-76.
Excessive maternal weight gain during pregnancy can result in serious adverse maternal and neonatal health consequences making it an important outcome to monitor in developing smoking-cessation interventions for pregnant women. Maternal weight gain was investigated in the present study with 154 pregnant participants in controlled trials investigating the efficacy of contingency management (CM) for smoking cessation. Women were assigned to either an abstinence-contingent condition wherein they earned vouchers exchangeable for retail items by abstaining from smoking or to a control condition where they received comparable vouchers independent of smoking status. Mean percent of negative smoking status tests throughout antepartum was greater in the incentive than control condition (45.2±4.6 vs. 15.5±2.4, p < .001) as was late-pregnancy point-prevalence abstinence (36% vs. 8%, p < .001) but maternal weight gain did not differ significantly between treatment conditions (15.0 ± 0.8 kg vs. 15.0 ± 0.9 kg, p = .97). In a comparison of women classified by smoking status rather than treatment condition, a greater percent of negative smoking status tests predicted significantly more weight gain (0.34 kg per 10% increase in negative tests), an effect that appeared to be attributable to women with greater abstinence having larger infants. This study shows no evidence of excessive maternal weight gain among pregnant women receiving a CM intervention for smoking cessation.
PMCID: PMC3027838  PMID: 20870365
Maternal weight gain; smoking cessation; pregnancy; contingency management; vouchers
21.  Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades 
Spatial and temporal regulation of the pericellular proteolytic environment by local growth factors, such as EGF and TGF-β, initiates a wide repertoire of cellular responses coupled to a plasmin/matrix metalloproteinase (MMP) dependent stromal-remodeling axis. Cell motility and invasion, tumor metastasis, wound healing, and organ fibrosis, for example, represent diverse events controlled by expression of a subset of genes that encode various classes of tissue remodeling proteins. These include members of the serine protease and MMP families that functionally constitute a complex system of interacting protease cascades and titrated by their respective inhibitors. Several structural components of the extracellular matrix are upregulated by TGF-β as are matrix-active proteases (e.g., urokinase (uPA), plasmin, MMP-1, -3, -9, -10, -11, -13, -14). Stringent controls on serine protease/MMP expression and their topographic activity are essential for maintaining tissue homeostasis. Targeting individual elements in this highly interactive network may lead to novel therapeutic approaches for the treatment of cancer, fibrotic diseases, and chronic wounds.
PMCID: PMC3290807  PMID: 22454771
22.  Effects of Smoking Cessation with Voucher-Based Contingency Management on Birth Outcomes 
Addiction (Abingdon, England)  2010;105(11):2023-2030.
This study combined data from three controlled trials to examine whether smoking cessation using voucher-based contingency management (CM) improves birth outcomes.
Participants (N = 166) were pregnant women who participated in trials examining the efficacy of voucher-based CM for smoking cessation. Women were assigned to either a contingent condition wherein they earned vouchers exchangeable for retail items by abstaining from smoking or to a noncontingent condition where they received vouchers independent of smoking status. Birth outcomes were determined by review of hospital delivery records.
Antepartum abstinence was greater in the contingent than noncontingent condition, with late-pregnancy abstinence being 34.1% vs. 7.4% (p < .001). Mean birth weight of infants born to mothers treated in the contingent condition was greater than infants born to mothers treated in the noncontingent condition (3295.6 ± 63.8 g vs. 3093.6 ± 67.0 g, p = .03) and the percent of low birth weight (< 2500g) deliveries was less (5.9% vs. 18.5%, p = .02). No significant treatment effects were observed across three other outcomes investigated although each was in the direction of improved outcomes in the contingent vs. the noncontingent condition: mean gestational age (39.1 ± 0.2 weeks vs. 38.5 ± 0.3 weeks, p = .06), percent of preterm deliveries (5.9 vs. 13.6, p = .09), and percent admissions to the Neonatal Intensive Care Unit (4.7% vs. 13.8%, p = .06).
These results provide evidence that smoking-cessation treatment with voucher-based CM may improve important birth outcomes.
PMCID: PMC2970671  PMID: 20840188
vouchers; contingency management; birth outcomes; gestational age; preterm birth; birth weight; low birth weight; cigarette smoking; smoking cessation
23.  Comments on Contingency Management and Conditional Cash Transfers 
Health economics  2010;19(10):1255-1258.
This essay discusses research on incentive-based interventions to promote healthy behavior change, contingency management (CM) and conditional cash transfers (CCT). The overarching point of the essay is that CM and CCT are often treated as distinct areas of inquiry when at their core they represent a common approach. Some potential bi-directional benefits of recognizing this commonality are discussed. Distinct intellectual traditions probably account for the separate paths of CM and CCT to date, with the former being rooted in behavioral psychology and the latter in microeconomics. It is concluded that the emerging field of behavioral economics, which is informed by and integrates principles of each of those disciplines, may provide the proper conceptual framework for integrating CM and CCT.
PMCID: PMC2891912  PMID: 19670269
contingency management; conditional cash transfers; incentive-based interventions
24.  PAI-1 Expression Is Required for HDACi-Induced Proliferative Arrest in ras-Transformed Renal Epithelial Cells 
Malignant transformation of mammalian cells with ras family oncogenes results in dramatic changes in cellular architecture and growth traits. The generation of flat revertants of v-K-ras-transformed renal cells by exposure to the histone deacetylase inhibitor sodium butyrate (NaB) was previously found to be dependent on transcriptional activation of the PAI-1 (SERPINE1) gene (encoding the type-1 inhibitor of urokinase and tissue-type plasminogen activators). NaB-initiated PAI-1 expression preceded induced cell spreading and entry into G1 arrest. To assess the relevance of PAI-1 induction to growth arrest in this cell system more critically, two complementary approaches were used. The addition of a stable, long half-life, recombinant PAI-1 mutant to PAI-1-deficient v-K-ras-/c-Ha-ras-transformants or to PAI-1 functionally null, NaB-resistant, 4HH cells (engineered by antisense knockdown of PAI-1 mRNA transcripts) resulted in marked cytostasis in the absence of NaB. The transfection of ras-transformed cells with the Rc/CMVPAI expression construct, moreover, significantly elevated constitutive PAI-1 synthesis (10- to 20-fold) with a concomitant reduction in proliferative rate. These data suggest that high-level PAI-1 expression suppresses growth of chronic ras-oncogene transformed cells and is likely a major cytostatic effector of NaB exposure.
PMCID: PMC3168268  PMID: 21912547
25.  PAI-1: An Integrator of Cell Signaling and Migration 
Cellular migration, over simple surfaces or through complex stromal barriers, requires coordination between detachment/re-adhesion cycles, involving structural components of the extracellular matrix and their surface-binding elements (integrins), and the precise regulation of the pericellular proteolytic microenvironment. It is now apparent that several proteases and protease inhibitors, most notably urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1), also interact with several cell surface receptors transducing intracellular signals that significantly affect both motile and proliferative programs. These events appear distinct from the original function of uPA/PAI-1 as modulators of the plasmin-based proteolytic cascade. The multifaceted interactions of PAI-1 with specific matrix components (i.e., vitronectin), the low-density lipoprotein receptor-related protein-1 (LRP1), and the uPA/uPA receptor complex have dramatic consequences on the migratory phenotype and may underlie the pathophysiologic sequalae of PAI-1 deficiency and overexpression. This paper focuses on the increasingly intricate role of PAI-1 as a major mechanistic determinant of the cellular migratory phenotype.
PMCID: PMC3151495  PMID: 21837240

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