BACKGROUND
To test whether trazodone, one of the most commonly prescribed medications for treatment of insomnia, improves subjective and/or objective sleep among methadone-maintained persons with sleep complaints, we performed a randomized, double-blind, placebo-controlled trial with six month follow-up.
METHODS
From eight methadone maintenance programs in the northeastern United States, we recruited 137 persons receiving methadone for at least one month who reported a Pittsburgh Sleep Quality Index (PSQI) score of six or higher. Two-night home polysomnography (PSG) was completed at baseline and one month later, with morning surveys and urine drug toxicologies. Interviews assessed sleep over the past 30 days at baseline and 1-, 3-, and 6- month follow-ups.
RESULTS
Participants averaged 38 years of age, were 47% male, and had a mean PSQI total score of 12.9 (± 3.1). At baseline, intervention groups did not significantly differ on 10 PSG-derived objective sleep measures and 11 self-reported measures. Over 88% (n = 121) of participants completed the PSG at 1-month. Without adjusting p-values for multiple comparisons, only 1 of 21 sleep measure comparisons was statistically significant (p<.05). The effect of trazodone on mean PSQI scores during the six-month follow-up was not statistically significant (p = .10). Trazodone neither significantly increased nor decreased illicit drug use relative to placebo.
CONCLUSIONS
Trazodone did not improve subjective or objective sleep in methadone-maintained persons with sleep disturbance. Other pharmacologic and non-pharmacologic treatments should be investigated for this population with high rates of insomnia.
doi:10.1016/j.drugalcdep.2011.06.026
PMCID: PMC3214692
PMID: 21798674
Trazodone; Methadone; Opiate dependence; Sleep
Introduction and background
At the time of incarceration, women have a high prevalence of sexually transmitted infections (STI). In the months following community release, women remain at high risk for new infections. This study assessed the rates and predictors of incident Chlamydia, Gonorrhea, and Trichomoniasis in a sample of hazardously-drinking women following incarceration.
Methods
Self-reported behavioral data were collected from 245 incarcerated women. Vaginal swabs were collected at baseline, 3-, and 6-month time-points and tested for Chlamydia, Gonorrhea, and Trichomoniasis. Treatment was provided for all positive tests.
Results
Participants’ mean age was 34.1 years of age, 175 (71.4%) (n=175) were Caucasian, 47 (19.2%) were African-American, 17 (6.9%) were Hispanic and 6 (2.4%) were of other ethnic origins. The STI incidence rate was estimated to be 30.5 (95%CI 21.3 – 43.5) new infections per 100 person-years. Number of male sex partners reported during follow-up was a significant (z = 2.16, p = .03) predictor of STI; each additional male sex partner increased the estimated hazard of STI by 1.26.
Conclusions and discussion
Incarcerated women who are hazardous drinkers are at high risk for sexually transmitted infection in the months following their return to the community. In addition to testing and treatment during incarceration, post-release rescreening, education, partner treatment, and follow-up are recommended.
doi:10.1016/j.whi.2011.05.005
PMCID: PMC3217105
PMID: 21835632
Incidence; Sexually transmitted infections; incarceration; women
Pain
2011;152(11):2640-2644.
Pain is common among opioid dependent patients, yet pharmacologic strategies are limited. The aim of this study was to explore whether escitalopram, a selective serotonin reuptake inhibitor, was associated with reductions in pain. The study used longitudinal data from a randomized, controlled trial that evaluated the effects of escitalopram on treatment retention in patients with depressive symptoms who were initiating buprenorphine/naloxone for treatment of opioid dependence. Participants were randomized to take escitalopram 10mg or placebo daily. Changes in pain severity, pain interference and depression were assessed at 1, 2 and 3 months visits using the Visual Analog Scale, Brief Pain Inventory and the Beck Depression Inventory II, respectively. Fixed-effects estimator for panel regression models were used to assess the effects of intervention on changes in outcomes over time. Additional models were estimated to explore whether the intervention effect was mediated by within-person changes in depression. In this sample of 147 adults, we found that participants randomized to escitalopram had significantly larger reductions on both pain severity (b = −14.34, t = −2.66, p < .01) and pain interference (b = −1.20, t = −2.23, p < .05) between baseline and follow-up. After adjusting for within-subject changes in depression, the estimated effects of escitalopram on pain severity and pain interference were virtually identical to the unadjusted effects. In summary, this study of opioid-dependent patients with depressive symptoms found that treatment with escitalopram was associated with clinically meaningful reductions in pain severity and pain interference during the first three months of therapy.
doi:10.1016/j.pain.2011.08.011
PMCID: PMC3235744
PMID: 21924552
Pain; opioid dependence; anti-depressant; escitalopram
We created a model conceptualizing sexual risk as a series of discrete event-specific behavioral decisions and tested the hypothesis that marijuana use was associated with increased sexual risk-taking. Three hundred eight marijuana-using women aged 18–24 completed a 90-day time-line-follow-back to assess sexual behaviors and marijuana use. A sequential logit model estimated the effect of marijuana use on the likelihood of being sexually active, partner type when sexually active, and condom nonuse conditional on partner type. Participants had a mean age of 20.4 years, with 67% Caucasian. Marijuana use was associated with an increased likelihood of being sexually active (OR 1.6; 95% CI 1.33, 1.93) and with condom nonuse when sexually active with casual partners (OR 2.58; 95% CI 1.1, 6.09). This behavioral decision model identified where marijuana use affected sexual risk, and suggests where interventions designed to reduce risk may have an impact.
doi:10.1007/s10461-010-9694-z
PMCID: PMC2916938
PMID: 20358274
Sexual risk; Condom use; Marijuana; Alcohol; Sequential-logit model
This study tests the acquired preparedness model (APM) to explain associations among trait impulsivity, social learning principles, and marijuana use outcomes in a community sample of female marijuana users. The APM states that individuals with high-risk dispositions are more likely to acquire certain types of learning that, in turn, instigate problematic substance use behaviors. In this study, three domains of psychosocial learning were tested: positive and negative marijuana use expectancies, and marijuana refusal self-efficacy. Participants were 332 community-recruited women aged 18-24 enrolled in a study of motivational interviewing for marijuana use reduction. The present analysis is based on participant self-reports of their impulsivity, marijuana use expectancies, marijuana refusal self-efficacy, marijuana use frequency, marijuana use-related problems, and marijuana dependence. In this sample, impulsivity was significantly associated with marijuana use frequency, marijuana-related problems, and marijuana dependence. Results also indicate that the effect of impulsivity on all three marijuana outcomes was fully mediated by the three principles of psychosocial learning tested in the model, namely, positive and negative marijuana expectancies, and marijuana refusal self-efficacy. These findings lend support to the APM as it relates to marijuana use. In particular, they extend the applicability of the theory to include marijuana refusal self-efficacy, suggesting that, among high-impulsives, those who lack appropriate strategies to resist the temptation to use marijuana are more likely to exhibit more frequent marijuana use and use-related negative consequences.
doi:10.1016/j.addbeh.2010.12.018
PMCID: PMC3039452
PMID: 21216536
marijuana; acquired preparedness; impulsivity; social learning
It is unknown if infection with hepatitis C virus (HCV) is a risk factor for pain among persons who have used injection drugs (IDU). Multivariate regression was used to determine whether HCV was associated with greater likelihood of reporting significant chronic pain and discomfort intolerance in a cohort of 97 opioid dependent IDU. Study results suggest that participants with HCV may be more likely to suffer chronic pain (aOR=1.98; 95% CI: 0.76 to 5.12, p=0.16). Furthermore, HCV was found to be associated with a higher discomfort intolerance scale score, reflecting intolerance to physical discomfort (β=2.34; 95% CI: 0.06 to 4.62, p=0.04). Infection with HCV may be an overlooked cause for chronic pain and discomfort intolerance among opioid dependent IDU.
doi:10.1080/10550887.2011.554775
PMCID: PMC3089758
PMID: 21491290
Hepatitis C virus; injection drug use; chronic pain; pain hypersensitivity
Objectives
Comparisons of subjective and objective sleep measures have shown discrepancies between reported sleep and polysomnography (PSG) in non-drug dependent individuals with and without insomnia. Sleep may affect behavioral and physiologic aspects of drug abuse and dependence; patients in methadone maintenance therapy (MMT) for opioid dependence frequently report sleep problems. Whether subjective sleep reflects objective sleep in MMT patients is unknown. We undertook these analyses to establish the correlations among subjective and objective sleep measures in MMT patients.
Methods
We compared one week of daily sleep diaries, one night of home PSG, a questionnaire completed the morning after PSG, and the Pittsburgh Sleep Quality Inventory (PSQI) as well as demographics and drug use measures in 62 MMT patients with disturbed sleep (PSQI score > 5).
Results
Subjective and objective sleep durations were similar in this sample; average sleep times for the diary, morning questionnaire, and PSG were 340, 323, and 332 minutes, respectively. Average diary sleep time, subjective ratings of feeling rested, and PSG sleep efficiency were correlated significantly with PSQI score. Age was inversely correlated with PSG sleep time. Participants whose urine toxicology showed benzodiazapine use reported significantly longer sleep times on the morning questionnaire.
Conclusions
Objective sleep measures confirm subjective measures in MMT patients with disturbed sleep. The high prevalence of sleep complaints in this population likely reflects pathology rather than sleep misperception. Both objective and subjective measures are useful in research and clinical settings for assessing sleep in opioid-dependent patients.
doi:10.1016/j.drugalcdep.2010.08.007
PMCID: PMC3025068
PMID: 20850231
methadone; opioid dependence; sleep; polysomnography; PSQI; sleep diaries
This study determined the frequency of reporting being introduced to opioids by a physician among opioid dependent patients. Cross-sectional analyses were performed using baseline data from a cohort of opioid addicts seeking treatment with buprenorphine. The primary outcome was response to the question: “Who introduced you to opiates?” Covariates included sociodemographics, depression, pain, current and prior substance use. Of 140 participants, 29% reported that they had been introduced to opioids by a physician. Of those who were introduced to opioids by a physician, all indicated that they had initially used opioids for pain, versus only 11% of those who did not report being introduced to opioids by a physician (p<0.01). There was no difference in current pain (78% vs. 85%, p=0.29), however participants who were introduced to opioids by a physician were more likely to have chronic pain (63% vs. 43%, p=0.04). A substantial proportion of individuals with opioid dependence seeking treatment may have been introduced to opioids by a physician.
doi:10.1016/j.jsat.2010.06.012
PMCID: PMC3129653
PMID: 20727704
This study examined associations between the endorsement of drug use expectancies and the frequency and severity of marijuana use in a community sample of 332 women aged 18–24 years who were not explicitly seeking treatment for their marijuana use. Participants were enrolled in a larger intervention study of motivational interviewing for various health behaviors and provided self-reports of their current and past marijuana use, marijuana abuse/dependence symptoms, and marijuana use expectancies. Marijuana use expectancies were measured using the six subscales of the Marijuana Effects Expectancy Questionnaire (MEEQ). Use frequency was defined as the number of use days in the past month, severity as the total number of DSM-IV marijuana abuse or dependence symptom criteria met. Replicating and extending prior research, expectations regarding Relaxation and Tension Reduction emerged as a robust belief in this cohort, predicting not only frequency (p<.01) but also severity (p<.01) of marijuana use in multivariate analyses. Severity of marijuana use was further predicted by expectations regarding loss of control, affective changes following marijuana use, and other aspects of emotion dysregulation (Global Negative Effects, p<.01). These findings document meaningful associations between substance related cognitions and use behavior and suggest that marijuana users who hold certain beliefs regarding marijuana use may be particularly susceptible to clinically significant problems associated with their substance use. As such, marijuana use expectancies may represent a clinical target that could be incorporated into future interventions.
doi:10.1016/j.addbeh.2010.06.017
PMCID: PMC2919625
PMID: 20621423
marijuana; drug use expectancies
Glasner, Jeremy D. | Yang, Ching-Hong | Reverchon, Sylvie | Hugouvieux-Cotte-Pattat, Nicole | Condemine, Guy | Bohin, Jean-Pierre | Van Gijsegem, Frédérique | Yang, Shihui | Franza, Thierry | Expert, Dominique | Plunkett, Guy | San Francisco, Michael J. | Charkowski, Amy O. | Py, Béatrice | Bell, Kenneth | Rauscher, Lise | Rodriguez-Palenzuela, Pablo | Toussaint, Ariane | Holeva, Maria C. | He, Sheng Yang | Douet, Vanessa | Boccara, Martine | Blanco, Carlos | Toth, Ian | Anderson, Bradley D. | Biehl, Bryan S. | Mau, Bob | Flynn, Sarah M. | Barras, Frédéric | Lindeberg, Magdalen | Birch, Paul R. J. | Tsuyumu, Shinji | Shi, Xiangyang | Hibbing, Michael | Yap, Mee-Ngan | Carpentier, Mathilde | Dassa, Elie | Umehara, Masahiro | Kim, Jihyun F. | Rusch, Michael | Soni, Pritin | Mayhew, George F. | Fouts, Derrick E. | Gill, Steven R. | Blattner, Frederick R. | Keen, Noel T. | Perna, Nicole T.
Dickeya dadantii is a plant-pathogenic enterobacterium responsible for the soft rot disease of many plants of economic importance. We present here the sequence of strain 3937, a strain widely used as a model system for research on the molecular biology and pathogenicity of this group of bacteria.
doi:10.1128/JB.01513-10
PMCID: PMC3133054
PMID: 21217001
Our goal was to determine whether treatment of depressive symptoms with escitalopram during buprenorphine treatment for opioid dependence, would improve treatment retention compared to placebo in a 12-week, randomized, double-blind trial. Treatment drop-out was defined as missing seven consecutive buprenorphine dosing days. Participants were 76% male, 80% non-Hispanic Caucasian, and 64% heroin users. At baseline, the mean Beck Depression Inventory-II (BDI-II) score was 28.4 (±9.7). Sixty-one percent of participants completed the 12 week buprenorphine protocol. Dropout rates were 33.3% and 44.0% among those randomized to escitalopram or placebo respectively (p=.19). Relative to baseline, mean BDI-II scores were significantly lower at all follow-up assessments, but the treatment by time interaction effect was not statistically significant (p = .18). Participants randomized to escitalopram also did not have a significantly lower likelihood of testing positive for either opiates or other drugs during follow-up. Depressive symptoms often resolved with buprenorphine treatment and the immediate initiation of escitalopram does not improve treatment retention, depression outcomes, or illicit drug use. Clinicians should determine the need for antidepressant treatment later in buprenorphine care.
doi:10.1016/j.jsat.2010.05.014
PMCID: PMC2910850
PMID: 20598836
Depression; Buprenorphine; Retention; Antidepressant; Opiate
Abstract
Background
The current study tested the hypothesis that tension reduction expectancies mediate the relationship between anxiety symptoms and marijuana use.
Methods
Interview data for 332 young adult females from Southern New England were collected from 2004 to 2009.
Results
In structural equation modeling, anxiety symptoms had a significant direct effect (byx = 0.227, 95% confidence interval [CI] 0.086-0.369, p < 0.05) on tension reduction expectancies and a significant indirect effect (byx = 0.026, 95% CI 0.010-0.046, p < 0.05) on marijuana use.
Conclusions
The effect of anxiety symptoms on marijuana use was fully mediated by tension reduction expectancies. Implications for tension reduction as a possible component of treatment interventions are discussed.
doi:10.1089/jwh.2010.1973
PMCID: PMC2965700
PMID: 20718677
Objective
This study sought to empirically derive marijuana user subtypes based on DSM abuse and dependence criteria and examine demographic and substance abuse distinctions of derived classes.
Method
A community sample of 308 female marijuana users between the ages of 18-24 were recruited in the Southern New England region. Latent class analysis was used to derive subgroups based on DSM criteria. The use and demographic characteristics of classes were further analyzed using ANOVA and chi-square tests.
Results
Based on fit criteria, a three class solution was selected. Class I (37%), an “unaffected/mild” group was characterized by very low endorsement rates of abuse and dependence criteria. This class was also found to have significantly lower rates of other substance use problems. Class II (41.6%) “moderate problem users” showed moderate endorsement rates of abuse and dependence criteria. Class III (21.4%) - “severe problem users” showed the greatest levels of abuse and dependence with 90% meeting DSM criteria for abuse and 100% meeting diagnostic criteria for marijuana dependence. Class III also showed the greatest levels of other substance use problems.
Conclusion
Three distinct marijuana abuse and dependence subtypes were derived using LCA. Findings may have implications for the development of more targeted treatment and prevention interventions for young women struggling with varying degrees of marijuana abuse and dependence.
doi:10.1016/j.whi.2010.02.001
PMCID: PMC2992809
PMID: 20457408
Marijuana; Cannabis; Latent Class Analysis; Females; Young Adults; Substance Use
Objectives
Opioid-dependent patients treated with methadone have subjective sleep complaints and disrupted sleep on polysomnography (PSG). Previous studies of sleep-disordered breathing (SDB) in this population have focused on central sleep apnea (CSA). Our objectives were to: (1) characterize obstructive sleep apnea (OSA) and CSA in patients in methadone maintenance treatment (MMT) for opioid dependence; (2) examine factors associated with SDB in this population; and (3) investigate whether SDB was related to severity of subjective sleep complaints in MMT patients with subjective sleep disturbances.
Methods
We analyzed OSA and CSA from one night of home PSG in 71 patients who were in MMT for at least 3 months and had a Pittsburgh Sleep Quality Inventory (PSQI) score > 5.
Results
OSA (defined as obstructive apnea-hypoponea index (OAHI) ≥ 5) was observed in 35.2% of our sample. OSA was associated with higher body mass index, longer duration in MMT, and non-Caucasian race. CSA (defined as central apnea index (CAI) ≥ 5) was observed in 14.1% of the sample. CSA was not associated with methadone dose or concomitant drug use. Subjective sleep disturbance measured with the PSQI was not related to OSA or CSA.
Conclusions
SDB was common in this sample of MMT patients and OSA was more common than CSA. Given the lack of association between presence of SDB and severity of subjective sleep difficulties, factors other than sleep apnea must account for complaints of disturbed sleep in this population.
doi:10.1016/j.drugalcdep.2009.11.019
PMCID: PMC2859844
PMID: 20079978
methadone; opiate dependence; sleep; sleep apnea; central sleep apnea; obstructive sleep apnea; sleep-disordered breathing
Objective
To test the hypothesis that among hazardously drinking incarcerated women who are returning to the community, a brief alcohol intervention will result in less alcohol use at follow-up relative to standard of care.
Methods
Eligible participants endorsed hazardous alcohol consumption--four or more drinks at a time on at least three separate days in the previous three months or a score of 8 or above on the AUDIT. Participants were randomized to either an assessment-only condition or to two brief motivationally-focused sessions, the first delivered during incarceration, the second one month later after community re-entry. Participants recalled drinking behaviors at three and six months after the baseline interview using a 90-day Timeline Followback method.
Results
The 245 female participants averaged 34 years of age, and were 71% Caucasian. Participants were abstinent only 47% of days in the three months prior to incarceration. On most days (85%) that they drank, women consumed four or more drinks. Intervention effects on abstinent days were statistically significant at 3-months (OR = 1.96, 95% CI 1.17, 3.30); the percent of days abstinent was 68% for those randomized to intervention and 57% for controls. At 6-months the effect of the intervention was attenuated and no longer statistically significant.
Conclusions
Among incarcerated women who reported hazardous drinking, a two-session brief alcohol intervention increased abstinent days at three-months, but this effect decayed by six months. Study participants continued to drink heavily after return to the community. More intensive intervention pre-release and after re-entry may benefit hazardously-drinking incarcerated women.
doi:10.1111/j.1360-0443.2009.02813.x
PMCID: PMC2858363
PMID: 20402990
Alcohol; Incarceration; Women
Bacteriophages are increasingly being utilized and considered for various practical applications, ranging from decontaminating foods and inanimate surfaces to human therapy; therefore, it is important to determine their concentrations quickly and reliably. Traditional plaque assay (PA) is the current “gold standard” for quantitating phage titers. However, it requires at least 18 h before results are obtained, and they may be significantly influenced by various factors. Therefore, two alternative assays based on the quantitative real-time polymerase chain reaction (QPCR) and NanoSight Limited (NS) technologies were recently proposed for enumerating phage particles. The present study compared the three approaches' abilities to quantitate Listeria monocytogenes-, Escherichia coli O157:H7- and Yersinia pestis-specific lytic phages quickly and reproducibly. The average coefficient of variation (CVS) of the PA method including all three phages was 0.15. The reproducibility of the PA method decreased dramatically when multiple investigators performed the assays, and mean differences of as much as 0.33 log were observed. The QPC R method required costly equipment and the synthesis of phage-specific oligonucleotide primers, but it determined phage concentrations faster (within about 4 h) and more precisely than did PA (CVS = 0.13). NS technology required costly equipment, was less precise (CVS = 0.28) than the PA and QPCR methods, and only worked when the phages were suspended in clear medium. However, it provided results within 5 min. After the overall correlation is established with the PA method, either of the two assays may be useful for quickly and reproducibly determining phage concentrations.
doi:10.4161/bact.1.2.15456
PMCID: PMC3278645
PMID: 22334864
bacteriophage; phage; plaque assays; phage titer
We randomized 332 women, 18–24 years old who were not explicitly seeking treatment for their marijuana use, to either a two-session motivationally-focused intervention or an assessment only condition. Assessed by time-line follow-back methodology, participants reported using marijuana 57 % of days in the three months prior to study entry. Intervention effects on the likelihood of marijuana use were not statistically significant at 1-month (OR = 0.77, p = .17), significant at 3-months (OR = 0.53, p=.01), and no longer significant at 6-months (OR = .74; p = .20). Among the 61% of participants endorsing any desire to quit using marijuana at baseline, significant intervention effects on the likelihood of marijuana use days were observed at 1- (OR = 0.42, p = .03), 3- (OR = 0.31, p = .02), and 6-months (OR = 0.35, p = .03). A two-session brief motivational intervention reduced marijuana use among young women not seeking treatment. Women with a desire to quit showed a greater and more durable response.
doi:10.1016/j.jsat.2007.07.004
PMCID: PMC2996851
PMID: 17869051
marijuana; motivational interviewing; women; motivation to change; clinical trial
To test if a four-session motivational intervention would reduce hepatitis C virus (HCV) seroincidence among injection and non-injection drug users compared to an assessment-only condition, we performed a randomized 24-month clinical trial. At baseline 277 participants reported using heroin or cocaine at least three times weekly were HCV antibody negative, 65% male and 46% and 39% reported having injected drugs. Among the fifteen persons (5.4%) who seroconverted, all reported injecting drugs either at baseline or during follow-up. Seroconversion rates did not differ significantly by treatment assignment (p=.79). The annual HCV incident rate for injectors was 8.20 (95% CI 4.76-14.13) and for non-injectors was 0.74 (95% CI 0.19-2.98) per 100 person years. Significantly fewer participants in the intervention group initiated injection drug use behaviors (p = .009). This intervention was no more effective at reducing HCV seroconversion than assessment alone, but did decrease injection initiation.
doi:10.1080/10550880903183034
PMCID: PMC2822987
PMID: 20155608
Hepatitis C incidence; motivational intervention; injection drug use; noninjection drug use; prevention
The purpose of this work was to study the effect of pH on the liposomal encapsulation of a model camptothecin anti-tumor agent, DB-67, by considering the state of ionization and bilayer membrane/water partitioning of the drug as a function of pH. A novel fluorescence method was developed to monitor intravesicular pH in liposomal formulations containing entrapped DB-67 by using the drug itself as a pH indicator. Fluorescence spectra were recorded in aqueous buffers and liposomes and used to estimate the ionization constant of the A-ring phenol of DB-67 (pKa2) and shifts in ionization constants (pKa1 and pKa2) due to membrane binding. Bilayer/water partitioning studies by equilibrium dialysis were employed to show that DB-67 is highly membrane bound over the entire pH range examined though binding decreases with an increase in pH. The observed ionization constants of membrane-bound DB-67 obtained from the equilibrium dialysis experiments were consistent with observations from fluorescence measurements and previous permeability results. The pH dependence of DB-67 loading using a passive loading technique was found to reflect the pH dependence of membrane binding of the drug. This results in poor encapsulation efficiency of DB-67 at high pH, necessitating further development of formulation strategies to improve loading efficiency.
doi:10.1016/j.ijpharm.2007.10.003
PMCID: PMC2277365
PMID: 18065174
Liposomes; nanoparticles; intraliposomal pH; membrane binding; lipid bilayers; camptothecins; tumor drug delivery; fluorescence; drug encapsulation
The α-amino acid ester prodrugs of the antitumor agent camptothecin and a more potent, lipophilic silatecan analog, DB-67, have been shown by NMR spectroscopy and quantitative kinetic analyses to undergo quantitative conversion to their pharmacologically active lactones via a non-enzymatic mechanism that at pH 7.4 is favored over direct hydrolysis. The alternate pathway involves the reversible intramolecular nucleophilic amine attack at the camptothecin E-ring carbonyl to generate a lactam (I) followed by a second intramolecular reaction to produce a bicyclic hemiorthoester (I′). The intermediates were isolated and shown to exist in an apparent equilibrium dominated by the hemiorthoester in DMSO using NMR spectroscopy. The conversion of prodrugs of camptothecin or DB-67 containing either α-NH2 or α-NHCH3 and their corresponding hemiorthoesters were monitored versus time in aqueous buffer (pH 3.0 and 7.4) at 37°C and the kinetic data were fit to a model based on the proposed mechanism. The results indicated that while the prodrugs are relatively stable at pH 3, facile lactone release occurs from both the prodrugs and their corresponding hemiorthoester intermediates under physiological conditions (pH 7.4). The glycinate esters and their hemiorthoesters were found to be more cytotoxic than the N-methylglycinates or their corresponding hemiorthoester intermediates in vitro using a human breast cancer cell line (MDA-MB-435S), consistent with their more rapid conversion to active lactone. The pH dependence of the non-enzymatic pathway for conversion of these α-amino acid ester prodrugs suggests that they may be useful for tumor-targeting via liposomes, as they can be stabilized in an acidic environment in the core of liposomes and readily convert to the active lactone following their intratumoral release.
doi:10.1021/jm060016l
PMCID: PMC2516925
PMID: 16821794
The objective of this study was to determine how injection drug users’ (IDUs) HIV-risk behavior differs with primary and other sex partners. Interviews were conducted with injection drug users from a needle exchange program (n = 243). Those with one sexual partner were more likely to report never using condoms with primary partners than were those with more than one partner (74% vs. 54%, p < 0.001). Those with more than one partner differed, between primary and other sexual partners, in their disclosure of HIV and IDU status, condom use, and drug use in combination with sex. Primary sexual partners of IDUs are placed at risk from IDUs’ risk behavior with other sexual partners. Those planning HIV-risk reduction interventions for IDUs should consider risk behavior with primary partners separately from behavior with other partners. Evaluation of intervention effects should use partner-specific assessments of risk behavior.
doi:10.1081/ADA-120037375
PMCID: PMC1351211
PMID: 15230073
Injection drug user; HIV; Partner—specific; Drugs; Needle exchange
Glasner, Jeremy D. | Plunkett, Guy | Anderson, Bradley D. | Baumler, David J. | Biehl, Bryan S. | Burland, Valerie | Cabot, Eric L. | Darling, Aaron E. | Mau, Bob | Neeno-Eckwall, Eric C. | Pot, David | Qiu, Yu | Rissman, Anna I. | Worzella, Sara | Zaremba, Sam | Fedorko, Joel | Hampton, Tom | Liss, Paul | Rusch, Michael | Shaker, Matthew | Shaull, Lorie | Shetty, Panna | Thotakura, Silpa | Whitmore, Jon | Blattner, Frederick R. | Greene, John M. | Perna, Nicole T.
ERIC, the Enteropathogen Resource Integration Center (www.ericbrc.org), is a new web portal serving as a rich source of information about enterobacteria on the NIAID established list of Select Agents related to biodefense—diarrheagenic Escherichia coli, Shigella spp., Salmonella spp., Yersinia enterocolitica and Yersinia pestis. More than 30 genomes have been completely sequenced, many more exist in draft form and additional projects are underway. These organisms are increasingly the focus of studies using high-throughput experimental technologies and computational approaches. This wealth of data provides unprecedented opportunities for understanding the workings of basic biological systems and discovery of novel targets for development of vaccines, diagnostics and therapeutics. ERIC brings information together from disparate sources and supports data comparison across different organisms, analysis of varying data types and visualization of analyses in human and computer-readable formats.
doi:10.1093/nar/gkm973
PMCID: PMC2238966
PMID: 17999997
AIM
To determine the association between daily smoking and use of nicotine replacement therapy (NRT), and to determine predictors of greater NRT use among methadone-maintained smokers.
INTERVENTION
Assignment to free nicotine patch (8 to 12 weeks) plus either (1) a baseline-tailored brief motivational intervention, a quit date behavioral skills counseling session, and a relapse prevention follow-up session (max), or (2) brief advice using NCI's 4 A's model (min).
SETTING
Five methadone maintenance treatment centers.
PARTICIPANTS
Of the 383 methadone-maintained smokers enrolled, 309 (80.6%) set a specific quit date (received NRT) and were located for assessments. Participants were 51.8% male, 78.6% Caucasian, and smoked 26.6 (SD = 12.2) cigarettes/day.
OUTCOME
Use of NRT and smoking behaviors during the 180-day follow-up period assessed by the Timeline follow-back method.
FINDINGS
On the day following their quit day, 86.4% of participants used NRT. The percentage of participants using NRT was 52.3%, 27.1%, and 10.4% on day 30, day 60, and day 90, respectively. Participants used NRT on 44.1% of the days through the 90 days of the treatment protocol. The estimated odds of smoking abstinence was 7.1 (P < 0.001) times higher on days when NRT was used than on days when NRT was not used, and cigarettes/day was also significantly lower on NRT days (14.93 vs 4.65; P < 0.001).
CONCLUSION
Nicotine replacement therapy use was inconsistent following an initial quit attempt among methadone-maintained smokers. On days when NRT was used, individuals were likely to smoke at reduced levels or not at all.
doi:10.1111/j.1525-1497.2006.00504.x
PMCID: PMC1924690
PMID: 16808777
methadone maintenance; clinical trial; nicotine replacement; adherence
Introduction
Many smokers reduce their cigarette consumption during failed attempts to quit. We report the impact of changes in consumption on smoking-related respiratory symptom severity (SRRSS).
Methods
Between February 2002 and May 2004 we recruited 383 smokers from 5 methadone maintenance programs for a randomized trial of nicotine replacement plus behavioral treatment versus nicotine replacement alone for smoking cessation. Cigarette use in the 28 days prior to the interview, and severity of SRRSS using a 7-item respiratory index, were assessed at baseline and at 3-month follow-up.
Outcome
Baseline minus 3-month assessment difference in SRRSS score.
Results
Follow-up of 319 participants (83.3%), mean age 40.4 years, 51.4% male, who smoked 26.4 cigarettes per day, demonstrated a mean reduction of 16.7 cigarettes per day. A reduction in cigarette use was positively and significantly (b=0.29, t=5.16, P<.001) associated with a reduction in smoking-related symptom severity after adjusting for age, gender, race, years of regular smoking, baseline nicotine dependence, and history of treatment for asthma or emphysema. A 1 standard deviation reduction in average daily smoking (about 14.1 cigarettes) was associated with a 0.28 standard deviation decrease in smoking-related symptom severity.
Conclusion
Reduction in symptom severity increases as absolute reduction in daily smoking increases. This is the first study to demonstrate an association between subjective short-term health changes and reduction in smoking.
doi:10.1111/j.1525-1497.2005.0190.x
PMCID: PMC1490242
PMID: 16191133
cigarettes; symptoms; methadone; nicotine; quality of life
Pirraglia, Paul A | Bishop, Duane | Herman, Debra S | Trisvan, Elizabeth | Lopez, Rosalie A | Torgersen, Christopher S | Van Hof, Ann Marie | Anderson, Bradley J | Miller, Ivan | Stein, Michael D
BACKGROUND
Few studies have examined the factors associated with depression in informal caregivers of HIV-infected persons.
OBJECTIVE
To investigate the relationship between depression and caregiver burden among informal caregivers of HIV-infected individuals.
DESIGN
Cross-sectional study using baseline data from an ongoing randomized trial of a supportive telephone intervention.
PARTICIPANTS
One hundred seventy-six dyads of HIV patients and their informal caregiver.
MEASUREMENTS
Depression was defined as a Beck Depression Inventory >10. A Caregiver Strain Index >6 identified informal caregivers with a high caregiver burden. We used logistic regression to identify characteristics that were associated with depression in the informal caregiver.
RESULTS
Informal caregivers were 42 years old (SD, 13), 53% female, 59% nonwhite, and 30% had education beyond high school. Forty-seven percent of informal caregivers were the patient's partner, 18% a friend, and 35% a family member. Twenty-seven percent of informal caregivers had a high caregiver burden, and 50% were depressed. We found significantly greater odds of informal caregiver depression with high caregiver burden (OR, 6.08; 95% CI, 2.40 to 15.4), informal caregiver medical comorbidity besides HIV (OR, 2.32; 95% CI, 1.09 to 4.92), spending all day together (OR, 3.92; 95% CI, 1.59 to 9.69), having to help others besides the HIV patient (OR, 2.55; 95% CI, 1.14 to 5.74), and duration of the HIV patient's diagnosis (OR, 1.01 per month; 95% CI, 1.00 to 1.01).
CONCLUSIONS
High caregiver burden was strongly associated with depression among HIV-infected individuals' informal caregivers, who themselves had difficult life circumstances. Informal caregivers of HIV patients may be in need of both mental health services and assistance in caregiving.
doi:10.1111/j.1525-1497.2005.0073.x
PMCID: PMC1490132
PMID: 15987325
caregivers; depression; HIV