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1

Diversion of methadone and buprenorphine from opioid substitution treatment: a staff perspective.  

PubMed

Abstract Opioid substitution treatment (OST) is still controversial, despite positive results. The issue of diversion to the illicit drug market is a cornerstone in the criticism typically voiced against the treatment. Little research is available concerning how professionals who work in OST view the issue of diversion. In this article, we discuss existing ideas and attitudes toward diversion of methadone and buprenorphine among OST staff in Sweden. The article is based on semi-structured interviews with 25 professionals working in eight OST-programs in southern Sweden. Diversion was seen as a deleterious phenomenon by the interviewees. Three problematic aspects were highlighted: medical risks in the form of overdose fatalities and the recruitment of new opiate/opioid users; negative consequences for the legitimacy of OST; and moral objections, since diversion means that the patients remain in a criminal environment. However, positive aspects were also highlighted. Illicit methadone or buprenorphine is perceived as safer than heroin. In this way, diversion can fulfill a positive function; for instance, if there is a shortage of access to regular treatment. Patients who share their medication with opioid-dependent friends are seen as less culpable than those who sell to anyone for money. PMID:25364995

Johnson, Björn; Richert, Torkel

2014-01-01

2

Buprenorphine Treatment of Opioid Dependence: A Review  

Microsoft Academic Search

Buprenorphine, a partial mu-agonist opioid, is a promising pharmacotherapy for the treatment of opioid dependence. One hundred and eight papers are organized according to 3 components essential to buprenorphine's use as a pharmacotherapy for opioid dependence: inducting patients onto buprenorphine, maintaining patients on buprenorphine, and discontinuing patients from buprenorphine treatment. The research suggests that inducting patients onto buprenorphine should lead

Warren K. Bickel; Leslie Amass

1995-01-01

3

Clinical profile of responders to buprenorphine as a substitution treatment in heroin addicts: results of a multicenter study of 73 patients  

Microsoft Academic Search

In France, high-dosage buprenorphine (HDB) is the main substitution treatment for narcotic addiction. Few data have been published concerning clinical factors predicting a good response to this treatment in a daily practice. A hospital-based multicenter clinical research program (PHRC) was undertaken in heroin-addicted patients, diagnosed according to DSM-III-R, to detect clinical criteria susceptible of predicting a good response to HDB

Marie-France Poirier; Xavier Laqueille; Valérie Jalfre; Dominique Willard; Marie Chantal Bourdel; Jacques Fermanian; Jean Pierre Olié

2004-01-01

4

Prior buprenorphine experience is associated with office-based buprenorphine treatment outcomes  

PubMed Central

Objectives As buprenorphine treatment and illicit buprenorphine use increase, many patients seeking buprenorphine treatment will have had prior experience with buprenorphine. Little evidence is available to guide optimal treatment strategies for patients with prior buprenorphine experience. We examined whether prior buprenorphine experience was associated with treatment retention and opioid use. We also explored whether type of prior buprenorphine use (prescribed or illicit use) was associated with these treatment outcomes. Methods We analyzed interview and medical record data from a longitudinal cohort study of 87 individuals who initiated office-based buprenorphine treatment. We examined associations between prior buprenorphine experience and 6-month treatment retention using logistic regression models, and prior buprenorphine experience and any self-reported opioid use at 1, 3, and 6 months using non-linear mixed models. Results Most (57.4%) participants reported prior buprenorphine experience; of these, 40% used prescribed buprenorphine and 60% illicit buprenorphine only. Compared to buprenorphine-naïve participants, those with prior buprenorphine experience had better treatment retention (AOR=2.65, 95% CI=1.05–6.70). Similar associations that did not reach significance were found when exploring prescribed and illicit buprenorphine use. There was no difference in opioid use when comparing participants with prior buprenorphine experience to those who were buprenorphine-naive (AOR=1.33, 95% CI=0.38–4.65). Although not significant, qualitatively different results were found when exploring opioid use by type of prior buprenorphine use (prescribed buprenorphine vs. buprenorphine-naïve, AOR=2.20, 95% CI=0.58–8.26; illicit buprenorphine vs. buprenorphine-naïve, AOR=0.47, 95% CI=0.07–3.46). Conclusions Prior buprenorphine experience was common and associated with better retention. Understanding how prior buprenorphine experience affects treatment outcomes has important clinical and public health implications. PMID:23722632

Cunningham, Chinazo O.; Roose, Robert J.; Starrels, Joanna L.; Giovanniello, Angela; Sohler, Nancy L.

2013-01-01

5

Buprenorphine substitution treatment in France: drug users' views of the doctor-user relationship  

PubMed Central

The French system for drug substitution, or maintenance treatment, established in 1996, differs from the often strict conditions attached to methadone clinics in other countries. Because of the predominant role of general practitioners and the flexible prescription rules for Subutex® in France, the relationship between the physician and the drug user becomes a central element in the treatment. This article deals with the expectations that these users have of the physician, and their perception of his or her attitude towards them. In order to identify possible reasons for the absence of treatment compliance and of Subutex® misuse, it focuses on the users’ assessment of the physician’s response to the problems they report. This study, based on a diversified sample of 28 persons in treatment, showed 4 patterns of relationships between physicians and users, which differed in their focus: a) dosage, b) compliance, c) the person and d) obtaining a prescription. In all four case types, users had difficulty reporting other drug use or intravenous Subutex® injection within this relationship in which the stigma attached to drug dependence seems to reappear. Moreover, the lack of clarity about the treatment objectives and time frame limits the users’ ability to integrate the treatment into their lives and to commit themselves to it. The heterogeneity and fragility of the users’ situations are elements related to dependence that, during contact with the physician, require regular assessment of the individual’s situation and of the treatment objectives. This constant reappraisal of the situation with the physician should help to optimize the treatment and avoid the hiatus that can generate or continue “misuse.” PMID:17442473

Guichard, Anne; Lert, France; Brodeur, Jean-Marc; Richard, Lucie

2007-01-01

6

Clinical profile of responders to buprenorphine as a substitution treatment in heroin addicts: results of a multicenter study of 73 patients.  

PubMed

In France, high-dosage buprenorphine (HDB) is the main substitution treatment for narcotic addiction. Few data have been published concerning clinical factors predicting a good response to this treatment in a daily practice. A hospital-based multicenter clinical research program (PHRC) was undertaken in heroin-addicted patients, diagnosed according to DSM-III-R, to detect clinical criteria susceptible of predicting a good response to HDB administered during a 3-month treatment period. At the inclusion time in the study, a diagnostic structured interview (DIGS) was performed, and the Addiction Severity Index (ASI), Zuckerman scale, depression scale from Jouvent, and CGI were scored. MMPI was also administered. Good response was defined as an ongoing participation in the study, with absence of opiate detected in 75% of urine collected during the last month of treatment. Only subjects treated for at least 1 month were eligible for analyses. One hundred fifteen patients were recruited and 73 were analyzed. Patients received 8.5+/-2.6 mg (m+/-S.D.) of buprenorphine for 1 to 3 months. A forward stepwise logistic regression showed that six clinical parameters may predict a good response to treatment: probability to respond to buprenorphine was higher in subjects having a high psychopathology (ASI) subscore, low disinhibition and boredom susceptibility factor scores (Zuckerman scale), no alcohol dependence, no family history of addiction or mood disorder, and duration of opiate dependence less than 10 years. Only the MMPI D subscale was a psychological pattern correlated to a good response to substitution treatment. These findings are important to consider when making the decision to prescribe HDB substitution treatment in opiate addiction. PMID:14751421

Poirier, Marie-France; Laqueille, Xavier; Jalfre, Valérie; Willard, Dominique; Bourdel, Marie Chantal; Fermanian, Jacques; Olié, Jean Pierre

2004-03-01

7

Illicit buprenorphine use, interest in and access to buprenorphine treatment among syringe exchange participants.  

PubMed

Poor access to buprenorphine maintenance treatment (BMT) may contribute to illicit buprenorphine use. This study investigated illicit buprenorphine use and barriers to BMT among syringe exchange participants. Computer-based interviews conducted at a New York City harm reduction agency determined: prior buprenorphine use; barriers to BMT; and interest in BMT. Of 102 opioid users, 57 had used illicit buprenorphine and 32 had used prescribed buprenorphine. When illicit buprenorphine users were compared to non-users: barriers to BMT ("did not know where to get treatment") were more common (64 vs. 36%, p<0.01); mean levels of interest in BMT were greater (3.37±1.29 vs. 2.80±1.34, p=0.03); and more participants reported themselves likely to initiate treatment (82 vs. 50%, p<0.01). Illicit buprenorphine users were interested in BMT but did not know where to go for treatment. Addressing barriers to BMT could reduce illicit buprenorphine use. PMID:25205666

Fox, Aaron D; Chamberlain, Adam; Sohler, Nancy L; Frost, Taeko; Cunningham, Chinazo O

2015-01-01

8

Comparison of Buprenorphine Treatment for Opioid Dependence in Three Settings  

PubMed Central

Although use of buprenorphine in the treatment of opioid dependence is expected to continue to increase, little is known about the optimal setting for providing the medical and psychosocial care required with buprenorphine pharmacotherapy. OBJECTIVE This study compared buprenorphine therapy delivered in three distinct treatment settings: an opioid-treatment program (OTP) offering individual counseling; a group counseling program utilizing the manualized Matrix Model (MMM) of cognitive-behavioral treatment; and a private clinic setting mirroring standard medical management for buprenorphine treatment provided specifically at a psychiatrist’s private practice (PCS). METHOD Participants were inducted on buprenorphine and provided with treatment over a 52-week study duration. All participants were scheduled for weekly treatment visits for the first 6 study weeks, and two sites reduced treatment to monthly visits for dispensing of medication and psychosocial counseling. Outcomes include opioid use, participant retention in treatment, and treatment participation. RESULTS Participants presenting for treatment at the sites differed only by race/ethnicity, and opioid use did not differ by site. Retention differed by treatment site, with the number of participants who stayed in the study until the end of 20 weeks significantly associated with treatment site. The mean number of minutes spent in each individual counseling session also differed by site. Although no difference in opioid use by treatment site was found, results document a significant association between opioid use and buprenorphine dose. DISCUSSION These results show some differences by treatment site, although the similarity and relative ease in which the sites were able to recruit participants for treatment with buprenorphine, and minor implementation problems reported suggests the feasibility of treatment with buprenorphine across various treatment settings. CONCLUSION Similar rates of continued opioid use across study sites and few qualitative reports of problems indicates that treatment with buprenorphine and associated psychosocial counseling are safe and relatively easy to implement in a variety of treatment settings. PMID:22105061

Hillhouse, Maureen; Donovick, Roger; Cunningham-Rathner, Jerry; Charuvastra, Charlie; Torrington, Matthew; Esagoff, Asher E.; Ling, Walter

2011-01-01

9

Integrating Buprenorphine Treatment into a Public Healthcare System: The San Francisco Department of Public Health's Office-Based Buprenorphine Pilot Program  

Microsoft Academic Search

Despite well-documented efficacy, US physicians have been relatively slow to embrace the use of buprenorphine for the treatment of opioid dependence. In order to introduce and support the use of buprenorphine across the San Francisco Department of Public Health system of care, the Buprenorphine Pilot Program was initiated in 2003. Program treatment sites included a centralized buprenorphine induction clinic and

David Hersh; Sherri L. Little; Alice Gleghorn

2011-01-01

10

Buprenorphine diffusion: the attitudes of substance abuse treatment counselors  

Microsoft Academic Search

In October 2002, the Food and Drug Administration approved buprenorphine for use in the treatment of opioid dependence. Successful diffusion, adoption, and implementation of this medication within the treatment field depend in part on substance abuse counselors. Using questionnaire data obtained from 2,298 counselors in community-based treatment programs in the private and public sectors between June 2002 and July 2004,

Hannah K. Knudsen; Lori J. Ducharme; Paul M. Roman; Tanja Link

2005-01-01

11

A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the Treatment of Opioid Dependence during Pregnancy: Maternal and Neonatal Outcomes  

PubMed Central

Given that buprenorphine + naloxone is prescribed for opioid-dependent pregnant women, it is important to examine the extent to which it differs from buprenorphine alone, methadone, or methadone-assisted withdrawal on neonatal and maternal outcomes. Summary statistics on maternal and neonatal outcomes were collected from 7 previously published studies examining treatment for opioid-dependent pregnant women that represented a range of research methodologies. Outcomes from these studies were compared to the same outcomes for 10 women treated with the combined buprenorphine + naloxone product. There were no significant differences in maternal outcomes for buprenorphine + naloxone compared to buprenorphine, methadone, or methadone-assisted withdrawal. Preliminary findings suggest no significant adverse maternal or neonatal outcomes related to the use of buprenorphine + naloxone for the treatment of opioid dependence during pregnancy. However, further research should examine possible differences between buprenorphine + naloxone and buprenorphine alone or methadone in fetal physical development. PMID:23531704

Lund, Ingunn O.; Fischer, Gabriele; Welle-Strand, Gabrielle K.; O’Grady, Kevin E.; Debelak, Kimber; Morrone, William R.; Jones, Hendrée E.

2013-01-01

12

Comparison of Behavioral Treatment Conditions in Buprenorphine Maintenance  

PubMed Central

Background and aims The Controlled Substances Act requires physicians in the United States to provide or refer to behavioral treatment when treating opioid-dependent individuals with buprenorphine; however no research has examined the combination of buprenorphine with different types of behavioral treatments. This randomized controlled trial compared the effectiveness of 4 behavioral treatment conditions provided with buprenorphine and medical management (MM) for the treatment of opioid dependence. Design After a 2-week buprenorphine induction/stabilization phase, participants were randomized to 1 of 4 behavioral treatment conditions provided for 16 weeks: Cognitive Behavioral Therapy (CBT=53); Contingency Management (CM=49); both CBT and CM (CBT+CM=49); and no additional behavioral treatment (NT=51). Setting Study activities occurred at an outpatient clinical research center in Los Angeles, California, USA. Participants Included were 202 male and female opioid-dependent participants. Measurements Primary outcome was opioid use, measured as a proportion of opioid-negative urine results over the number of tests possible. Secondary outcomes include retention, withdrawal symptoms, craving, other drug use, and adverse events. Findings No group differences in opioid use were found for the behavioral treatment phase (Chi-square=1.25, p=0.75), for a second medication-only treatment phase, or at weeks 40 and 52 follow-ups. Analyses revealed no differences across groups for any secondary outcome. Conclusion There remains no clear evidence that cognitive behavioural therapy and contingency management reduce opiate use when added to buprenorphine and medical management in opiates users seeking treatment. PMID:23734858

Ling, Walter; Hillhouse, Maureen; Ang, Alfonso; Jenkins, Jessica; Fahey, Jacqueline

2013-01-01

13

Intrathecal Buprenorphine in the Treatment of Phantom Limb Pain  

Microsoft Academic Search

hantom limb pain is a chronic pain perceived in an absent part of the body. It can totally con- sume a patient's life. Suggested treatments for this complaint are many, but none have proved to have lasting efficacy. We have treated two patients suffering from phan- tom limb pain. Intrathecal buprenorphine provided not only immediate and long-lasting pain relief, but

Keiichi Omote; Hideya Ohmori; Mikito Kawamata; Maki Matsumoto; Akiyoshi Namiki

1995-01-01

14

Patterns of non-compliant buprenorphine, levomethadone, and methadone use among opioid dependent persons in treatment  

PubMed Central

Background The non-compliant use of opioid substitution treatment (OST) medicines is widespread and well-documented. However, less is known about characteristics of non-compliant OST medicine use and the factors that predict it. The two main goals of this study are to compare characteristics of non-compliant levomethadone, methadone, and buprenorphine use and to explore factors that may differentially predict it among opioid dependent persons in treatment. Methods Data from 595 opioid dependent patients with non-compliant OST medicine use were analyzed. Characteristics of use between substances were compared using chi-squared tests and predictive factors were explored through multinomial logistic regressions. Results Non-compliant levomethadone and methadone use was characterized by more frequent parallel consumption of other psychoactive substances and intravenous use, whereas buprenorphine was more often procured without a prescription. Regarding predictive factors, methadone was perceived to relieve withdrawal symptoms better than buprenorphine and levomethadone was perceived as being better at modulating the effects of other substances and worst at enhancing mood. Conclusions Patterns of non-compliant use differ according to OST medicine. These patterns are considered with the reduction of non-compliant use and the improvement of treatment in mind. PMID:24885218

2014-01-01

15

Buprenorphine versus methadone in the treatment of opioid-dependent cocaine users  

Microsoft Academic Search

This study compared the efficacy of buprenorphine to methadone for decreasing cocaine use in patients with combined opioid and cocaine use. Participants (n=51) were enrolled in a 26-week treatment program and randomly assigned to either buprenorphine or methadone. Dosing was double-blind and double-dummy. Patients were stabilized on either 8 mg sublingual buprenorphine or 50 mg oral methadone, with dose increases

Eric C. Strain; Maxine L. Stitzer; Ira A. Liebson; George E. Bigelow

1994-01-01

16

Bringing Buprenorphine-Naloxone Detoxification to Community Treatment Providers: The NIDA Clinical Trials Network Field Experience  

PubMed Central

In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone®) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women were randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16mg buprenorphine-4 mg naloxone in three days. Medication compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence. PMID:15204675

Amass, Leslie; Ling, Walter; Freese, Thomas E.; Reiber, Chris; Annon, Jeffrey J.; Cohen, Allan J.; M.F.T.; McCarty, Dennis; Reid, Malcolm S.; Brown, Lawrence S.; Clark, Cynthia; Ziedonis, Douglas M.; Krejci, Jonathan; Stine, Susan; Winhusen, Theresa; Brigham, Greg; Babcock, Dean; L.C.S.W.; Muir, Joan A.; Buchan, Betty J.; Horton, Terry

2005-01-01

17

Inquiries about and initiation of buprenorphine treatment in an inner-city clinic.  

PubMed

Despite increases in opioid dependence, availability of buprenorphine treatment remains limited. Reasons may include health center concerns about becoming overwhelmed or attracting patients who differ from the local community. This study documents inquiries about and initiation of buprenorphine treatment in an inner-city health center. From 2006-2008, we collected demographic information and subsequent treatment data for everyone who inquired about treatment. Of the 324 people who inquired, 55.6% initiated treatment. The number of inquiries increased gradually over time, and most came from local community residents (80.4%). These results may allay health center concerns, and can help planning for buprenorphine treatment. PMID:19591064

Cunningham, Chinazo O; Giovanniello, Angela; Sacajiu, Galit; Li, Xuan; Brisbane, Mia; Sohler, Nancy L

2009-01-01

18

Methadone versus buprenorphine maintenance for the treatment of heroin-dependent outpatients.  

PubMed

The aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks. Subjects were randomized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment. The 164 subjects included 41 patients in 1-mg, 41 patients in 3-mg, and 41 patients in 8-mg dosage group of buprenorphine, and also 41 patients in the 30-mg dosage group of methadone. The mean age was 31.4 years for total buprenorphine group and 33.7 years for methadone group (the mean age differences in 4 groups were not statistically significant). Subjects received buprenorphine at a dose of 1, 3, or 8 mg per day or methadone at a dose of 30 mg per day and were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Days retained in treatment were measured. Completion rates by buprenorphine dosage group were 29.3% for the 1-mg dose group, 46.3% for the 3-mg dose group, 68.3% for the 8-mg dose group, and 61% for the 30-mg methadone dose group. Retention in the 8-mg dose group was significantly better than in the 1-mg dose group (p=.00041) and in the 3-mg dose group (p=.045); other comparison (1 mg dose with 3 mg dose) was not significant. Methadone group was significantly better than 1mg buprenorphine dose group (p=.004), but was not significantly different from 3 mg buprenorphine dose group (p=.18) or 8 mg buprenorphine dose group (p=.49). The results support the efficacy of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (8 mg) of buprenorphine was the best of the three doses of buprenorphine, and also support the superiority of 30 mg of methadone compared to 1 mg dose of buprenorphine for Iranian heroin-dependent patients to increase their retention in treatment. PMID:12810142

Ahmadi, Jamshid

2003-04-01

19

Buprenorphine Treatment Outcomes among Opioid-Dependent Cocaine Users and Non-users  

PubMed Central

Background and Objectives National treatment guidelines state that polysubstance users, including cocaine users, may not be appropriate candidates for office-based buprenorphine treatment. However, data to support this recommendation are sparse and conflicting, and the implications of this recommendation may include limiting the usefulness of buprenorphine treatment, as cocaine use is common among opioid-dependent individuals seeking buprenorphine treatment. We compared buprenorphine treatment outcomes (6-month treatment retention and self-reported opioid use over 6 months) in opioid-dependent cocaine users versus non-users who initiated buprenorphine treatment at an urban community health center. Methods We followed 87 participants over 6 months, collecting interview and medical record data. We used logistic regression models to test whether baseline cocaine use was associated with treatment retention and mixed effects non-linear models to test whether baseline cocaine use was associated with self-reported opioid use. Results At baseline, 39.1% reported cocaine use. In all participants, self-reported opioid use decreased from 89.7% to 27.4% over 6 months, and 6-month treatment retention was 54.5%. We found no significant difference in 6-month treatment retention (AOR=1.56, 95%CI=0.58–4.17, p=0.38) or self-reported opioid use (AOR=0.89, 95%CI=0.26–3.07, p=0.85) between cocaine users and non-users. Conclusions and Scientific Significance This study demonstrates that buprenorphine treatment retention is not worse in cocaine users than non-users, with clinically meaningful improvements in self-reported opioid use. These findings suggest that opioid-dependent cocaine users attain considerable benefits from office-based buprenorphine treatment and argue for the inclusion of these patients in office-based buprenorphine treatment programs. PMID:23795874

Cunningham, Chinazo O.; Giovanniello, Angela; Kunins, Hillary V.; Roose, Robert J.; Fox, Aaron D.; Sohler, Nancy L.

2013-01-01

20

Top Manager Effects on Buprenorphine Adoption in Outpatient Substance Abuse Treatment Programs  

PubMed Central

To examine the influence of top managers’ characteristics on the adoption of buprenorphine for opioid dependence among U.S. outpatient substance abuse treatment units, this investigation analyzed a cross-sectional national study of 547 such units in the 2004–2005 wave of the Drug Abuse Treatment System Survey. Administrators reported their demographics, training, and treatment orientation, as well as features of the unit and its pattern of use of buprenorphine. Nationally, 15.8% of programs offered any buprenorphine services. Greater adoption of buprenorphine correlated with directors’ younger age, longer tenure, male gender, and weaker endorsement of abstinence as the most important treatment goal. Availability of naltrexone and medical services also correlated positively with buprenorphine adoption. The authors conclude that leaders’ characteristics are related to the adoption of innovative practices in addiction treatment programs. Future work should examine whether leadership development for community addiction programs might speed up the diffusion of buprenorphine and other innovative, evidence-based practices. PMID:19296223

Friedmann, Peter D.; Jiang, Lan; Alexander, Jeffrey A.

2013-01-01

21

Adoption of evidence-based clinical innovations: the case of buprenorphine use by opioid treatment programs.  

PubMed

This article examines changes from 2005 to 2011 in the use of an evidence-based clinical innovation, buprenorphine use, among a nationally representative sample of opioid treatment programs and identifies characteristics associated with its adoption. We apply a model of the adoption of clinical innovations that focuses on the work needs and characteristics of staff; organizations' technical and social support for the innovation; local market dynamics and competition; and state policies governing the innovation. Results indicate that buprenorphine use increased 24% for detoxification and 47% for maintenance therapy between 2005 and 2011. Buprenorphine use was positively related to reliance on private insurance and availability of state subsidies to cover its cost and inversely related to the percentage of clients who injected opiates, county size, and local availability of methadone. The results indicate that financial incentives and market factors play important roles in opioid treatment programs' decisions to adopt evidence-based clinical innovations such as buprenorphine use. PMID:24051897

Andrews, Christina M; D'Aunno, Thomas A; Pollack, Harold A; Friedmann, Peter D

2014-02-01

22

Facts about Buprenorphine for Treatment of Opioid Addiction  

MedlinePLUS

... stop taking them, you will feel sick. This sickness is called withdrawal . Dependence is not the same ... people. Side effects are feelings of discomfort or sickness that come with taking medicine. Buprenorphine has a ...

23

Buprenorphine/naloxone treatment in primary care is associated with decreased human immunodeficiency virus risk behaviors.  

PubMed

Methadone treatment reduces human immunodeficiency virus (HIV) risk, but the effects of primary-care-based buprenorphine/naloxone on HIV risk are unknown. The purpose of this study was to determine whether primary-care-based buprenorphine/naloxone was associated with decreased HIV risk behavior. We conducted a longitudinal analysis of 166 opioid-dependent persons (129 men and 37 women) receiving buprenorphine/naloxone treatment in a primary care clinic. We compared baseline and 12- and 24-week overall, drug-related, and sex-related HIV risk behaviors using the AIDS/HIV Risk Inventory (ARI). Buprenorphine/naloxone treatment was associated with significant reductions in overall and drug-related ARI scores from baseline to 12 and 24 weeks. Intravenous drug use in the past 3 months was endorsed by 37%, 12%, and 7% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Sex while you or your partner were "high" was endorsed by 64%, 13%, and 15% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Inconsistent condom use during sex with a steady partner was high at baseline and did not change over time. We conclude that primary-care-based buprenorphine/naloxone treatment is associated with decreased drug-related HIV risk, but additional efforts may be needed to address sex-related HIV risk when present. PMID:17933486

Sullivan, Lynn E; Moore, Brent A; Chawarski, Marek C; Pantalon, Michael V; Barry, Declan; O'Connor, Patrick G; Schottenfeld, Richard S; Fiellin, David A

2008-07-01

24

Predictors of Outcome in LAAM, Buprenorphine, and Methadone Treatment for Opioid Dependence  

Microsoft Academic Search

This study examined (1) predictors of treatment outcome for opioid-dependent participants in a single-site controlled trial comparing methadone, buprenorphine, and LAAM treatments and (2) the extent to which various subpopulations of patients may have more successful outcomes with each medication. The relationships between patient demographics, drug use history, and psychological status and outcome measures of treatment retention, opiate use, and

Lisa A. Marsch; Mary Ann Chutuape Stephens; Timothy Mudric; Eric C. Strain; George E. Bigelow; Rolley E. Johnson

2005-01-01

25

A qualitative study of the adoption of buprenorphine for opioid addiction treatment.  

PubMed

Qualified physicians may prescribe buprenorphine to treat opioid dependence, but medication use remains controversial. We examined adoption of buprenorphine in two not-for-profit integrated health plans, over time, completing 101 semi-structured interviews with clinicians and clinician-administrators from primary and specialty care. Transcripts were reviewed, coded, and analyzed. A strong leader championing the new treatment was critical for adoption in both health plans. Once clinicians began using buprenorphine, patients' and other clinicians' experiences affected decisions more than did the champion. With experience, protocols developed to manage unsuccessful patients and changed to support maintenance rather than detoxification. Diffusion outside addiction and mental health settings was nonexistent; primary care clinicians cited scope-of-practice issues and referred patients to specialty care. With greater diffusion came questions about long-term use and safety. Recognizing how implementation processes develop may suggest where, when, and how to best expend resources to increase adoption of such treatments. PMID:24268947

Green, Carla A; McCarty, Dennis; Mertens, Jennifer; Lynch, Frances L; Hilde, Anadam; Firemark, Alison; Weisner, Constance M; Pating, David; Anderson, Bradley M

2014-03-01

26

Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes".  

PubMed

In a recent article, Lund et al sought to compare maternal and neonatal outcomes of various treatment regimens for opioid dependence during pregnancy.1 In their background, discussion the authors state that "In the United States buprenorphine plus naloxone [Suboxone(®)] … has been the preferred form of prescribed buprenorphine due to its reduced abuse liability relative to buprenorphine alone [Subutex(®)]." This claim is certainly consistent with the view of the firm that has manufactured and sold both products, Reckitt Benckiser. In September of 2011, the company announced that it was "… discontinuing distribution and sale of Subutex(®) tablets as we believe that mono product (product containing buprenorphine alone with no naloxone) creates a greater risk of misuse, abuse and diversion …".2 Supporting evidence for the alleged "reduced abuse liability" appears to be lacking, however, and evidence cannot be located in the two references cited by Dr. Lund and his co-authors, which in fact are silent on the subject of abuse potential.3,4 In contrast, it has been reported that the transition to buprenorphine/naloxone from the mono formulation has been associated with "… no reduction in injection risk behaviors among IDUs."5. PMID:23772177

Newman, Robert G; Gevertz, Susan G

2013-01-01

27

Clinical Differences Between Opioid Abuse Classes Ameliorated After One Year of Buprenorphine-Medication Assisted Treatment  

Microsoft Academic Search

This study compared clinical and demographic profiles of three opioid dependent user groups, while also measuring their response to one year of buprenorphine-medication assisted treatment (B-MAT). Opioid prescription, street, and combination (street + prescription) users completed the Addiction Severity Index (ASI) multiple times over the course of one treatment year. Although groups differed on all measured demographics (p's < .05),

Joseph Tkacz; Jamie Severt; Cheryl Kassed; Charles Ruetsch

2012-01-01

28

A Comparison of Attitudes Toward Opioid Agonist Treatment among Short-Term Buprenorphine Patients  

PubMed Central

Background Obtaining data on attitudes toward buprenorphine and methadone of opioid-dependent individuals in the United States may help fashion approaches to increase treatment entry and improve patient outcomes. Objectives This secondary analysis study compared attitudes toward methadone and buprenorphine of opioid-dependent adults entering short-term buprenorphine treatment (BT) with opioid-dependent adults who are either entering methadone maintenance treatment or not entering treatment. Methods The 417 participants included 132 individuals entering short-term BT, 191 individuals entering methadone maintenance, and 94 individuals not seeking treatment. Participants were administered an Attitudes toward Methadone scale and its companion Attitudes toward Buprenorphine scale. Demographic characteristics for the three groups were compared using ?2 tests of independence and one-way analysis of variance. A repeated-measures multivariate analysis of variance with planned contrasts was used to compare mean attitude scores among the groups. Results Participants entering BT had significantly more positive attitudes toward buprenorphine than toward methadone (p < .001) and more positive attitudes toward BT than methadone-treatment (MT) participants and out-of-treatment (OT) participants (p < .001). In addition, BT participants had less positive attitudes toward methadone than participants entering MT (p < .001). Conclusions Participants had a clear preference for a particular medication. Offering a choice of medications to OT individuals might enhance their likelihood of entering treatment. Treatment programs should offer a choice of medications when possible to new patients, and future comparative effectiveness research should incorporate patient preferences into clinical trials. Scientific Significance These data contribute to our understanding of why people seek or do not seek effective pharmacotherapy for opioid addiction. PMID:22242643

Kelly, Sharon M.; Brown, Barry S.; Katz, Elizabeth C.; O'Grady, Kevin E.; Mitchell, Shannon Gwin; King, Stuart; Schwartz, Robert P.

2014-01-01

29

Sublingual Buprenorphine for Treatment of Neonatal Abstinence Syndrome: A Randomized Trial  

Microsoft Academic Search

ABSTRACT OBJECTIVE.In utero exposure,to drugs of abuse can lead to neonatal,abstinence syn- drome, a condition that is associated with prolonged hospitalization. Buprenorphine is a partial,-opioid agonist used for treatment,of adult detoxification and mainte-

Walter K. Kraft; Eric Gibson; Kevin Dysart; Vidula S. Damle; Jennifer L. Larusso; Jay S. Greenspan; David E. Moody; Karol Kaltenbach; Michelle E. Ehrlich

30

Developing and Implementing a New Prison-Based Buprenorphine Treatment Program  

ERIC Educational Resources Information Center

Research suggests that buprenorphine treatment may be a promising intervention for incarcerated individuals with heroin addiction histories. However, its implementation varies from corrections-based methadone because of unique challenges regarding dosing, administration, and regulation. Describing the first randomized clinical trial of…

Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.

2010-01-01

31

Cost-Effectiveness of Buprenorphine and Naltrexone Treatments for Heroin Dependence in Malaysia  

PubMed Central

Aims To aid public health policymaking, we studied the cost-effectiveness of buprenorphine, naltrexone, and placebo interventions for heroin dependence in Malaysia. Design We estimated the cost-effectiveness ratios of three treatments for heroin dependence. We used a microcosting methodology to determine fixed, variable, and societal costs of each intervention. Cost data were collected from investigators, staff, and project records on the number and type of resources used and unit costs; societal costs for participants’ time were estimated using Malaysia’s minimum wage. Costs were estimated from a provider and societal perspective and reported in 2004 US dollars. Setting Muar, Malaysia. Participants 126 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial in Malaysia (2003–2005) receiving counseling and buprenorphine, naltrexone, or placebo for treatment of heroin dependence. Measurements Primary outcome measures included days in treatment, maximum consecutive days of heroin abstinence, days to first heroin use, and days to heroin relapse. Secondary outcome measures included treatment retention, injection drug use, illicit opiate use, AIDS Risk Inventory total score, and drug risk and sex risk subscores. Findings Buprenorphine was more effective and more costly than naltrexone for all primary and most secondary outcomes. Incremental cost-effectiveness ratios were below $50 for primary outcomes, mostly below $350 for secondary outcomes. Naltrexone was dominated by placebo for all secondary outcomes at almost all endpoints. Incremental treatment costs were driven mainly by medication costs, especially the price of buprenorphine. Conclusions Buprenorphine appears to be a cost-effective alternative to naltrexone that might enhance economic productivity and reduce drug use over a longer term. PMID:23226534

Ruger, Jennifer Prah; Chawarski, Marek; Mazlan, Mahmud; Ng, Nora; Schottenfeld, Richard

2012-01-01

32

Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40  

ERIC Educational Resources Information Center

This Treatment Improvement Protocol (TIP) addresses the clinical use of buprenorphine in the treatment of opioid addiction. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts…

Boone, Margaret; Brown, Nancy J.; Moon, Mary A.; Schuman, Deborah J.; Thomas, Josephine; Wright, Denise L.

2004-01-01

33

Buprenorphine and nor-buprenorphine levels in head hair samples from former heroin users under Suboxone® treatment.  

PubMed

In the current study, buprenorphine (BUP) and its major metabolite, nor-buprenorphine (NBUP), were determined in hair samples from former heroin users following Suboxone® treatment. Hair samples from 36 subjects were analyzed. The drugs of interest were isolated from hair by solid-liquid extraction with methanol and were determined by liquid chromatography-mass spectrometry, using an electrospray ionization interface. The analytical parameters of the method (such as linearity, limits of quantification, recovery, accuracy, and precision) were determined. The inter-quartile range of BUP levels was from 11.4 to 37.4?pg/mg (mean value 56.6?pg/mg) for the proximal hair segment, from 5.8 to 43.3?pg/mg for the middle hair segment (mean value 25.3?pg/mg), while a range from 4.3 to 33.9?pg/mg (mean value 105.2?pg/mg) for the distant to the root hair segment was determined. For NBUP the corresponding inter-quartile range was from 27.0 to 147.6 for the proximal segment (mean value 95.4?pg/mg), from 21.5 to 164.7?pg/mg for the middle segment (mean value 102.0?pg/mg) and from 20.4 to 103.6?pg/mg for the distant segment (mean value 156.8?pg/mg). The mean BUP/NBUP concentration ratio was 0.5. The daily dose of Suboxone® correlated significantly with BUP and NBUP levels in hair (p?=?0.001 and p?=?0.023) as well as with the BUP/NBUP ratio (p?=?0.010). No significant correlation was found between the levels of BUP and NBUP and the duration of Suboxone® administration. The developed and validated method was successfully used for the determination of BUP and NBUP in hair samples collected from former heroin users under Suboxone® treatment. PMID:24817054

Belivanis, Stamatis; Tzatzarakis, Manolis N; Vakonaki, Elena; Kovatsi, Leda; Mantsi, Mary; Alegakis, Athanasios; Kavvalakis, Matthaios P; Vynias, Dionisios; Tsatsakis, Aristidis M

2014-06-01

34

Buprenorphine-Mediated Transition from Opioid Agonist to Antagonist Treatment: State of the Art and New Perspectives  

PubMed Central

Constant refinement of opioid dependence (OD) therapies is a condition to promote treatment access and delivery. Among other applications, the partial opioid agonist buprenorphine has been studied to improve evidence-based interventions for the transfer of patients from opioid agonist to antagonist medications. This paper summarizes PubMed-searched clinical investigations and conference papers on the transition from methadone maintenance to buprenorphine and from buprenorphine to naltrexone, discussing challenges and advances. The majority of the 26 studies we examined were uncontrolled investigations. Many small clinical trials have demonstrated the feasibility of in- or outpatient transfer to buprenorphine from low to moderate methadone doses (up to 60–70 mg). Results on the conversion from higher methadone doses, on the other hand, indicate significant withdrawal discomfort, and need for ancillary medications and inpatient treatment. Tapering high methadone doses before the transfer to buprenorphine is not without discomfort and the risk of relapse. The transition buprenorphine-naltrexone has been explored in several pilot studies, and a number of treatment methods to reduce withdrawal intensity warrant further investigation, including the co-administration of buprenorphine and naltrexone. Outpatient transfer protocols using buprenorphine, and direct comparisons with other modalities of transitioning from opioid agonist to antagonist medications are limited. Given its potential salience, the information gathered should be used in larger clinical trials on short and long-term outcomes of opioid agonist-antagonist transition treatments. Future studies should also test new pharmacological mechanisms to help reduce physical dependence, and identify individualized approaches, including the use of pharmacogenetics and long-acting opioid agonist and antagonist formulations. PMID:22280332

Mannelli, Paolo; Peindl, Kathleen S.; Lee, Tong; Bhatia, Kamal S.; Wu, Li-Tzy

2012-01-01

35

Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence  

PubMed Central

Background Buprenorphine is a partial ?-opiate agonist and ?-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. Methods Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. Results The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P = .0135 for 8 mg and P < .001 for 16 mg) or benzoylecgonine concentrations (P = .0277 for 8 mg and P = .006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events. Conclusions A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use. PMID:14749690

Montoya, Ivan D.; Gorelick, David A.; Preston, Kenzie L.; Schroeder, Jennifer R.; Umbricht, Annie; Cheskin, Lawrence J.; Lange, W. Robert; Contoreggi, Carlo; Johnson, Rolley E.; Fudala, Paul J.

2008-01-01

36

Suboxone® (Buprenorphine\\/Naloxone) as an Agonist Opioid Treatment in Spain: A Budgetary Impact Analysis  

Microsoft Academic Search

Objective: To evaluate the economic impact of buprenorphine\\/naloxone (B\\/N) as an agonist opioid treatment for opiate dependence. Methods: A budgetary impact analysis model was designed to calculate the annual costs (drugs and associated costs) to the Spanish National Healthcare System of methadone versus B\\/N. Data for the model were obtained from official databases and expert panel opinion. Results: It was

José Martínez-Raga; Francisco González Saiz; César Pascual; Miguel A. Casado; Francisco J. Sabater Torres

2010-01-01

37

Time to Initiation of Treatment for Neonatal Abstinence Syndrome in Neonates exposed in utero to Buprenorphine or Methadone  

PubMed Central

Background The recommended standard of care calls for treating opioid-dependent pregnant women with methadone and observing neonates exposed in utero for five to seven postnatal days to see if treatment for neonatal abstinence syndrome (NAS) is needed. Data from a large multisite randomized clinical trial comparing buprenorphine vs. methadone for the treatment of opioid dependence during pregnancy suggest buprenorphine-exposed neonates had less severe NAS, but may require pharmacologic treatment for NAS later than methadone-exposed neonates. The present study examined whether time to pharmacologic treatment initiation differed in a relatively large non-blinded clinical sample of buprenorphine- vs. methadone-exposed neonates treated for NAS. Methods Medical records for 75 neonates exposed to buprenorphine (n = 47) or methadone (n = 28) in utero who required treatment for NAS were examined. Time elapsed between birth and initiation of pharmacologic treatment was calculated for each neonate and time to treatment initiation compared between groups. Results Median time to treatment initiation (hours:minutes, IQR) was significantly later in buprenorphine- vs. methadone-exposed neonates (71:02, 44:21-96:27 vs. 34:12, 21:00-55:41, respectively, p<.001). Estimates of mean time to treatment initiation from parametric analyses that adjusted for maternal and neonatal characteristics were very similar (73:10 (95% CI: 61:00 to 87:18) vs. 42:36 (95% CI: 33:06 to 53:30), respectively, p = .0005). This difference was not dependent on maternal age or neonatal sex, gestational age, or birth weight. Conclusions These findings confirm results from randomized clinical trials, adding generality to the observation that buprenorphine-exposed neonates require treatment significantly later than methadone-exposed neonates. PMID:23845658

Gaalema, Diann E.; Heil, Sarah H.; Badger, Gary J.; Metayer, Jerilyn S.; Johnston, Anne M.

2013-01-01

38

Effects of buprenorphine versus buprenorphine\\/naloxone tablets in non-dependent opioid abusers  

Microsoft Academic Search

Rationale: Buprenorphine is an opioid agonist-antagonist under development in the United States as a sublingual medication for treatment\\u000a of opioid dependence. Buprenorphine may be abused; therefore, tablets combining buprenorphine with naloxone have been developed\\u000a with the intent of reducing the abuse risk in people physically dependent upon opioids. The characteristics and abuse potential\\u000a of buprenorphine and buprenorphine\\/naloxone tablets in non-dependent

Eric C. Strain; Kenneth Stoller; Sharon L. Walsh; George E. Bigelow

2000-01-01

39

The effects of buprenorphine in buprenorphine-maintained volunteers  

Microsoft Academic Search

Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid\\u000a dependence. The purpose of this study was to determine the abuse liability of parenteral buprenorphine in volunteers maintained\\u000a on daily sublingual (SL) buprenorphine (8?mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges\\u000a two times per week. Medication challenges were

Eric C. Strain; Sharon L. Walsh; Kenzie L. Preston; Ira A. Liebson; George E. Bigelow

1997-01-01

40

Initiation of buprenorphine during incarceration and retention in treatment upon release.  

PubMed

We report here on a feasibility study of initiating buprenorphine/naloxone prior to release from incarceration and linking participants to community treatment providers upon release. The study consisted of a small number of Rhode Island (RI) prisoners (N = 44) diagnosed with opioid dependence. The study design is a single arm, open-label pilot study with a 6-month follow up interview conducted in the community. However, a natural experiment arose during the study comparing pre-release initiation of buprenorphone/naloxone to initiation post-release. Time to post-release prescriber appointment (mean days) for initiation of treatment outside Rhode Island Department of Corrections (RIDOC) versus inside RIDOC was 8.8 and 3.9, respectively (p = .1). Median post release treatment duration (weeks) for outside RIDOC versus inside RIDOC was 9 and 24, respectively (p = .007). We conclude that initiating buprenorphine/naloxone prior to release from incarceration may increase engagement and retention in community-based treatment. PMID:23541303

Zaller, Nickolas; McKenzie, Michelle; Friedmann, Peter D; Green, Traci C; McGowan, Samuel; Rich, Josiah D

2013-08-01

41

Variation in use of Buprenorphine and Methadone Treatment by Racial, Ethnic and Income Characteristics of Residential Social Areas in New York City  

PubMed Central

National data indicate that patients treated with buprenorphine for opiate use disorders are more likely to be White, highly educated, and to have greater incomes than those receiving methadone, but patterns of buprenorphine dissemination across demographic areas have not been documented in major metropolitan areas where poverty, minority populations and injection heroin use are concentrated. Rates of buprenorphine and methadone treatment are compared among areas of New York City defined by their income and ethnic/racial composition. Residential social areas (hereinafter called social areas) were defined as aggregations of ZIP codes with similar race/ethnicity and income characteristics, and were formed based on clustering techniques. Treatment rates were obtained for each New York City ZIP code: buprenorphine treatment rates were based on the annual number of buprenorphine prescriptions written, and the methadone treatment rate on the number of methadone clinic visits for persons in each ZIP code. Treatment rates were correlated univariately with ethnicity and income characteristics of ZIP codes. Social area treatment rates were compared using individual ANOVA models for each rate. Buprenorphine and methadone treatment rates were significantly correlated with the ethnicity and income characteristics of ZIP codes, and treatment rates differed significantly across the social areas. Buprenorphine treatment rates were highest in the social area with the highest income and lowest percentage of Black and Hispanic residents. Conversely, the methadone treatment rate was highest in the social area with the highest percentage of low income and Hispanic residents. The uneven dissemination of 0pioid maintenance treatment in New York City may be reflective of the limited public health impact of buprenorphine in ethnic minority and low income areas. Specific policy and educational interventions to providers are needed to promote the use of buprenorphine for opiate use disorders in diverse populations. PMID:23702611

Hansen, Helena B.; Siegel, Carole E.; Case, Brady G.; Bertollo, David N.; DiRocco, Danae; Galanter, Marc

2013-01-01

42

In control?: Ukrainian opiate substitution treatment patients strive for a voice in their treatment.  

PubMed

This article explores the burgeoning advocacy movement for methadone and buprenorphine treatment by patients, parents, and doctors in Ukraine, and their efforts to remake a system that infantilizes and controls patients into one where patients have a voice in their treatment. Through a review of gray literature and in-depth interviews with 28 patient-advocates and doctors in five Ukrainian cities between October 2009 and July 2010, this piece chronicles the emergence of opiate substitution treatment in Ukraine, describes successes toward patient-friendly treatment, and explores the institutionalized barriers that have pushed the patients to become advocates for their own treatment. PMID:22428819

Golovanevskaya, Maria; Vlasenko, Leonid; Saucier, Roxanne

2012-04-01

43

Supply of buprenorphine waivered physicians: The influence of state policies.  

PubMed

Buprenorphine, an effective opioid use disorder treatment, can be prescribed only by buprenorphine-waivered physicians. We calculated the number of buprenorphine-waivered physicians/100,000 county residents using 2008-11 Buprenorphine Waiver Notification System data, and used multivariate regression models to predict number of buprenorphine-waivered physicians/100,000 residents in a county as a function of county characteristics, state policies and efforts to promote buprenorphine use. In 2011, 43% of US counties had no buprenorphine-waivered physicians and 7% had 20 or more waivered physicians. Medicaid funding, opioid overdose deaths, and specific state guidance for office-based buprenorphine use were associated with more buprenorphine-waivered physicians, while encouraging methadone programs to promote buprenorphine use had no impact. Our findings provide important empirical information to individuals seeking to identify effective approaches to increase the number of physicians able to prescribe buprenorphine. PMID:25218919

Stein, Bradley D; Gordon, Adam J; Dick, Andrew W; Burns, Rachel M; Pacula, Rosalie Liccardo; Farmer, Carrie M; Leslie, Douglas L; Sorbero, Mark

2015-01-01

44

Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth  

ERIC Educational Resources Information Center

Objective: To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. Method: Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly…

Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

2011-01-01

45

Buprenorphine withdrawal syndrome in a newborn  

Microsoft Academic Search

A pregnant woman who was addicted to heroin rapidly withdrew from illicit drugs after the onset of a 4 mg\\/day buprenorphine treatment. In the newborn's blood, urine, and meconium 20 hours after birth, high concentrations of buprenorphine and its metabolite norbuprenorphine were detected, with a higher buprenorphine\\/norbuprenorphine ratio than in adults, possibly as a consequence of immature hepatic function; no

Pierre Marquet; Jean Chevrel; Pierre Lavignasse; Louis Merle; Gérard Lachâtre

1997-01-01

46

Factors associated with complicated buprenorphine inductions.  

PubMed

Despite data supporting its efficacy, barriers to implementation of buprenorphine for office-based treatment are present. Complications can occur during buprenorphine inductions, yet few published studies have examined this phase of treatment. To examine factors associated with complications during buprenorphine induction, we conducted a retrospective chart review of the first 107 patients receiving buprenorphine treatment in an urban community health center. The primary outcome, defined as complicated induction (precipitated or protracted withdrawal), was observed in 18 (16.8%) patients. Complicated inductions were associated with poorer treatment retention (than routine inductions) and decreased over time. Factors independently associated with complicated inductions included recent use of prescribed methadone, recent benzodiazepine use, no prior experience with buprenorphine, and a low initial dose of buprenorphine/naloxone. Findings from this study and further investigation of patient characteristics and treatment characteristics associated with complicated inductions can help guide buprenorphine treatment strategies. PMID:20682186

Whitley, Susan D; Sohler, Nancy L; Kunins, Hillary V; Giovanniello, Angela; Li, Xuan; Sacajiu, Galit; Cunningham, Chinazo O

2010-07-01

47

Combined abuse of clonidine and amitriptyline in a patient on buprenorphine maintenance treatment.  

PubMed

Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed. PMID:25314340

Seale, J Paul; Dittmer, Trent; Sigman, Erika J; Clemons, Holly; Johnson, J Aaron

2014-01-01

48

Combined Abuse of Clonidine and Amitriptyline in a Patient on Buprenorphine Maintenance Treatment  

PubMed Central

Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed. PMID:25314340

Dittmer, Trent; Sigman, Erika J.; Clemons, Holly; Johnson, J. Aaron

2014-01-01

49

Characteristics of U.S. substance abuse treatment facilities adopting buprenorphine in its initial stage of availability  

Microsoft Academic Search

This study examined the adoption of buprenorphine for the treatment of opiate dependence among U.S. substance abuse treatment facilities and their characteristics at the time of the initial availability of the medication. Data come from a 2003 national survey of all substance abuse treatment facilities in the U.S. Out of our sample of 13,060 facilities, 5.5% of facilities reported they

Alison L. Koch; Cynthia L. Arfken; Charles R. Schuster

2006-01-01

50

Opioid Addiction and Abuse in Primary Care Practice: A Comparison of Methadone and Buprenorphine as Treatment Options  

PubMed Central

Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200 000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care. PMID:23092049

Bonhomme, Jean; Shim, Ruth S.; Gooden, Richard; Tyus, Dawn; Rust, George

2014-01-01

51

Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome  

Microsoft Academic Search

This study was designed to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. This randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care. Participants were opioid-dependent pregnant

E. Jonesa; Rolley E. Johnsona; Donald R. Jasinskib; Kevin E. O'Gradyc; Christian A. Chisholmd; Robin E. Choof; Michael Crocettie; Robert Dudase; Cheryl Harrowe; Marilyn A. Huestisf; Lauren M. Janssone; Michael Lantzd; Barry M. Lesterg; Lorraine Miliod

52

Effects of buprenorphine and methadone in methadone-maintained subjects  

Microsoft Academic Search

Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study

S. L. Walsh; H. L. June; K. J. Schuh; K. L. Preston; G. E. Bigelow; M. L. Stitzer

1995-01-01

53

Retention on Buprenorphine Treatment Reduces Emergency Department Utilization, But Not Hospitalization Among Treatment-Seeking Patients With Opioid Dependence  

PubMed Central

Drug users are marginalized from typical primary care, often resulting in emergency department (ED) usage and hospitalization due to late-stage disease. Though data suggest methadone decreases such fragmented healthcare utilization (HCU), the impact of buprenorphine maintenance treatment (BMT) on HCU is unknown. Chart review was conducted on opioid dependent patients seeking BMT, comparing individuals (N=59) who left BMT ? 3 days with those retained on BMT (N=150), for ED use and hospitalization. Using negative binomial regressions, including comparison of time before BMT induction, ED utilization and hospitalization was assessed. Overall, ED utilization was 0.93 events per person year and was significantly reduced by BMT, with increasing time (retention) on BMT. BMT had no significant effect on hospitalizations or average length of stay. PMID:22534003

Schwarz, Ryan; Zelenev, Alexei; Bruce, R. Douglas; Altice, Frederick L.

2012-01-01

54

Improved Quality of Life for Opioid Dependent Patients Receiving Buprenorphine Treatment in HIV Clinics  

PubMed Central

Background Opioid dependence and HIV infection are associated with poor health-related quality of life (HRQOL). Buprenorphine/naloxone (bup/nx) provided in HIV care settings may improve HRQOL. Methods We surveyed 289 HIV-infected opioid-dependent persons treated with clinic-based bup/nx about HRQOL using the Short Form Health Survey (SF-12) administered at baseline, 3, 6, 9, and 12 months. We used normalized SF-12 scores which correspond to a mean HRQOL of 50 for the general U.S. population (SD 10, possible range 0–100). We compared mean normalized mental and physical composite and component scores in quarters 1, 2, 3, and 4 with baseline scores using GEE models. We assessed the effect of clinic-based bup/nx prescription on HRQOL composite scores using mixed effects regression with site as random effect and time as repeated effect. Results Baseline normalized SF-12 scores were lower than the general U.S. population for all HRQOL domains. Average composite mental HRQOL improved from 38.3 (SE 12.5) to 43.4 (SE 13.2) (? 1.13 [95% CI 0.72, 1.54]) and composite physical HRQOL remained unchanged (? 0.21 [95% CI ?0.16, 0.57]) over 12 months follow-up. Continued bup/nx treatment across all four quarters was associated with improvements in both physical (? 2.38 [95% CI 0.63, 4.12]) and mental (? 2.51 [95% CI 0.42, 4.60]) HRQOL after adjusting for other contributors to HRQOL. Conclusions Clinic-based bup/nx maintenance therapy is potentially effective in ameliorating some of the adverse effects of opioid dependence on HRQOL for HIV-infected populations. PMID:21317593

Korthuis, P. Todd; Tozzi, Mary Jo; Nandi, Vijay; Fiellin, David A.; Weiss, Linda; Egan, James E.; Botsko, Michael; Acosta, Angela; Gourevitch, Marc N.; Hersh, David; Hsu, Jeffrey; Boverman, Joshua; Altice, Frederick L.

2011-01-01

55

Use of conventional, complementary, and alternative treatments for pain among individuals seeking primary care treatment with buprenorphine-naloxone  

PubMed Central

Previous studies have not examined patterns of pain treatment use among patients seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence. Objectives To examine, among individuals with pain seeking BNT for opioid dependence, the use of pain treatment modalities, perceived efficacy of prior pain treatment, and interest in pursuing pain treatment while in BNT. Methods 244 patients seeking office-based BNT for opioid dependence completed measures of demographics, pain status (i.e. “chronic pain (CP)” [pain lasting at least 3 months] vs. “some pain (SP)” [pain in the past week not meeting the duration criteria for chronic pain]), pain treatment use, perceived efficacy of prior pain treatment, and interest in receiving pain treatment while in BNT. Results In comparison to the SP group (N = 87), the CP group (N = 88) was more likely to report past-week medical use of opioid medication (AOR 3.2, 95% CI 1.2–8.4), lifetime medical use of non-opioid prescribed medication (AOR 2.2, 95% CI 1.1–4.7), and lifetime use of prayer (AOR 2.8, 95% CI 1.2–6.5), and was less likely to report lifetime use of yoga (AOR 0.2, 95% CI 0.1–0.7) to treat pain. While the two pain groups did not differ on levels of perceived efficacy of prior lifetime pain treatments, in comparison to the SP group, the CP group was more likely to report interest in receiving pain treatment while in BNT (P < 0.001). Conclusions Individuals with pain seeking BNT for opioid dependence report a wide range of conventional, complementary, and alternative pain-related treatments and are interested (especially those with CP) in receiving pain management services along with BNT. PMID:23041680

Barry, Declan T.; Savant, Jonathan D.; Beitel, Mark; Cutter, Christopher J.; Moore, Brent A.; Schottenfeld, Richard S.; Fiellin, David A.

2012-01-01

56

[The transdermal 7-day buprenorphine patch--an effective and safe treatment option, if tramadol or tilidate/naloxone is insufficient. Results of a non-interventional study].  

PubMed

The transdermal 7-day buprenorphine matrix patch provides a constant and user-friendly pain management when chronic musculoskeletal pain requires opioids. This analysis of clinical routine data evaluated the benefit of this treatment for patients previously receiving oral long-term treatment with weak opioids alone. Data of 310 patients previously treated with tramadol or tildate/naloxone and part of a multicentre observational study with 3295 patients were analyzed. In 89.7% of the 310 patients oral treatment with weak opioids was replaced by the 7-day buprenorphine patch due to insufficient analgesia. During treatment with the 7-day buprenorphine patch there was a clinically significant decrease of the mean pain intensity at rest during the day from 5.7 to 2.9, on physical effort during the day from 7.3 to 3.8 and at night from 5.2 to 2.3 (11-point NRS scale, p < or = 0.001). In addition, quality of life aspects such as mobility, self-reliance and quality of sleep improved, which are relevant for individual patient satisfaction with pain management. For patients with previous long-term tramadol or tilidate/naloxone treatment the switch to the 7-day buprenorphine matrix patch proved to be effective and safe for the management of chronic pain. The user-friendly 7-day application interval contributes to improving compliance and a reducing exposure to tablets. PMID:21591321

Schutter, U; Ritzdorf, I; Heckes, B

2010-07-01

57

Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain  

PubMed Central

Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient’s self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient’s medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1–110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75–100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain. PMID:25170278

Skaer, Tracy L

2014-01-01

58

Barriers to Primary Care Physicians Prescribing Buprenorphine  

PubMed Central

PURPOSE Despite the efficacy of buprenorphine-naloxone for the treatment of opioid use disorders, few physicians in Washington State use this clinical tool. To address the acute need for this service, a Rural Opioid Addiction Management Project trained 120 Washington physicians in 2010–2011 to use buprenorphine. We conducted this study to determine what proportion of those trained physicians began prescribing this treatment and identify barriers to incorporating this approach into outpatient practice. METHODS We interviewed 92 of 120 physicians (77%), obtaining demographic information, current prescribing status, clinic characteristics, and barriers to prescribing buprenorphine. Residents and 7 physicians who were prescribing buprenorphine at the time of the course were excluded from the study. We analyzed the responses of the 78 remaining respondents. RESULTS Almost all respondents reported positive attitudes toward buprenorphine, but only 22 (28%) reported prescribing buprenorphine. Most (95%, n = 21) new prescribers were family physicians. Physicians who prescribed buprenorphine were more likely to have partners who had received a waiver to prescribe buprenorphine. A lack of institutional support was associated with not prescribing the medication (P = .04). A lack of mental health and psychosocial support was the most frequently cited barrier by both those who prescribe and who do not prescribe buprenorphine. CONCLUSION Interventions before and after training are needed to increase the number of physicians who offer buprenorphine for treatment of addiction. Targeting physicians in clinics that agree in advance to institute services, coupled with technical assistance after they have completed their training, their clinical teams, and their administrations is likely to help more physicians become active providers of this highly effective outpatient treatment. PMID:24615308

Hutchinson, Eliza; Catlin, Mary; Andrilla, C. Holly A.; Baldwin, Laura-Mae; Rosenblatt, Roger A.

2014-01-01

59

Participant Characteristics and Buprenorphine Dose  

PubMed Central

Background Clinical parameters for determining buprenorphine dose have not been adequately examined in treatment outcome research. Objectives The current study is a secondary analysis of data collected in a recently completed comparison of buprenorphine taper schedules conducted as part of the National Institute on Drug Abuse’s (NIDA) Clinical Trials Network (CTN) to assess whether participant baseline characteristics are associated with buprenorphine dose. Methods After 3 weeks of flexible dosing, 516 participants were categorized by dose provided in the final dosing week (9.3% received a final week dose of 8mg buprenorphine, 27.3% received 16mg, and 63.4% received 24mg). Results Findings show that final week dose groups differed in baseline demographic and drug use characteristics including education, heroin use, route of drug administration, withdrawal symptoms, and craving. These groups also differed in opioid use during the four dosing weeks, with the lowest use in the 8mg group and highest use in the 24mg group (p < 0.0001). Additional analyses address withdrawal symptoms, and craving. Conclusions and Scientific Significance Final week dose groups differed in demographic and drug use characteristics, and the group receiving the largest final week dose had the highest rate of continued opioid use. These findings may contribute to the development of clinical guidelines regarding buprenorphine dose in the treatment of opioid dependence, however further investigations that include random assignment to dose by baseline characteristics are needed. PMID:21854290

Hillhouse, Maureen; Canamar, Catherine; Doraimani, Geetha; Thomas, Christie; Hasson, Al; Ling, Walter

2012-01-01

60

Buprenorphine in the Treatment of Opiate Dependence: Its Pharmacology and Social Context of Use in the U.S  

Microsoft Academic Search

Buprenorphine's physiological effects are produced when it attaches to specific opiate receptors that are designated mu, kappa, or delta. Buprenorphine, a partial agonist at the mu receptor and an antagonist at the kappa receptor, produces typical morphine-like effects at low doses. At higher doses, it produces opiate effects that are less than those of full opiate agonists. Knowledge of the

Donald R. Wesson

2004-01-01

61

Buprenorphine use in pregnant opioid users: a critical review.  

PubMed

Pregnancy in opioid users poses a number of problems to treating physicians. Most guidelines recommend maintenance treatment to manage opioid addiction in pregnancy, with methadone being the gold standard. More recently, buprenorphine has been discussed as an alternate medication. The use and efficacy of buprenorphine in pregnancy is still controversial. This article reviews the current database on the basis of a detailed and critical literature search performed in MEDLINE (206 counts). Most of the relevant studies (randomised clinical trials and one national cohort sample) were published in the last 2 years and mainly compared buprenorphine with methadone. Some studies are related to maternal outcomes, others to foetal, neonatal or older child outcomes. With respect to maternal outcomes, most studies suggest that buprenorphine has similar effects to methadone. Very few data from small studies discuss an effect of buprenorphine on neurodevelopment of the foetus. Neonatal abstinence syndrome is common in infants of both buprenorphine- and methadone-maintained mothers. As regards neonatal outcomes, buprenorphine has the same clinical outcome as methadone, although some newer studies suggest that it causes fewer withdrawal symptoms. Since hardly any studies have investigated the combination of buprenorphine with naloxone (which has been suggested to possibly have teratogenic effects) in pregnant women, a switch to buprenorphine monotherapy is recommended in women who become pregnant while receiving the combination product. These novel findings indicate that buprenorphine is emerging as a first-line treatment for pregnant opioid users. PMID:23775478

Soyka, Michael

2013-08-01

62

Buprenorphine-Naloxone Maintenance Following Release from Jail  

Microsoft Academic Search

Primary care is understudied as a reentry drug and alcohol treatment setting. This study compared treatment retention and opioid misuse among opioid-dependent adults seeking buprenorphine\\/naloxone maintenance in an urban primary care clinic following release from jail versus community referrals. Postrelease patients were either (a) induced to buprenorphine in-jail as part of a clinical trial, or (b) seeking buprenorphine induction post

Joshua D. Lee; Ellie Grossman; Andrea Truncali; John Rotrosen; Andrew Rosenblum; Stephen Magura; Marc N. Gourevitch

2012-01-01

63

Buprenorphine for Human Immunodeficiency Virus/Hepatitis C Virus-coinfected Patients  

PubMed Central

Objectives Buprenorphine is associated with enhanced human immunodeficiency virus (HIV) treatment outcomes including increased antiretroviral therapy initiation rates, adherence, and CD4+ cell counts among HIV-infected opioid-dependent individuals. Buprenorphine facilitates hepatitis C virus (HCV) treatment in opioid-dependent patients with HCV monoinfection. Less is known about buprenorphine’s role in HIV/HCV coinfection. Methods We conducted a retrospective chart review to evaluate HCV care for HIV-infected buprenorphine patients in the first 4 years of buprenorphine’s integration into a Rhode Island HIV clinic. Results Sixty-one patients initiated buprenorphine. All had HCV antibody testing; 57 (93%) were antibody-positive. All antibody-positive patients underwent HCV RNA testing; 48 (84%) were RNA-positive. Of these, 15 (31%) were not referred to HCV care. Among chronically infected patients, 3 received HCV treatment after buprenorphine; all had cirrhosis and none achieved viral eradication. At buprenorphine induction, most patients had inadequately controlled HIV infection, with detectable HIV RNA (59%) or CD4+ cell count less than or equal to 350/µL (38%). Conclusions Buprenorphine has shown limited success to date as a bridge to HCV treatment within an HIV clinic. Buprenorphine’s stabilization of opioid dependence and HIV disease may permit the use of HCV therapy over time. PMID:22614935

Taylor, Lynn E.; Maynard, Michaela A.; Friedmann, Peter D.; MacLeod, Cynthia J.; Rich, Josiah D.; Flanigan, Timothy P.; Sylvestre, Diana L.

2014-01-01

64

Comparative effects of vasectomy surgery and buprenorphine treatment on faecal corticosterone concentrations and behaviour assessed by manual and automated analysis methods in C57 and C3H mice.  

PubMed

Establishing effective cage-side pain assessment methods is essential if post-surgical pain is to be controlled effectively in laboratory animals. Changes to overall activity levels are the most common methods of assessment, but may not be the most appropriate for establishing the analgesic properties of drugs, especially in mice, due their high activity levels. Use of drugs that can affect activity (e.g. opioids) is also a problem. The relative merits of both manual and automated behaviour data collection methods was determined in two inbred mouse strains undergoing vasectomy following treatment with one of 2 buprenorphine dose rates. Body weights and the effects of surgery and buprenorphine on faecal corticosterone were also measured. Surgery caused abnormal behaviour and reduced activity levels, but high dose buprenorphine caused such large-scale increases in activity in controls that we could not establish analgesic effects in surgery groups. Only pain-specific behaviour scoring using the manual approach was effective in showing 0.05 mg/kg buprenorphine alleviated post-vasectomy pain. The C57 mice also responded better to buprenorphine than C3H mice, indicating they were either less painful, or more responsive to its analgesic effects. C3H mice were more susceptible to the confounding effects of buprenorphine irrespective of whether data were collected manually or via the automated approach. Faecal corticosterone levels, although variable, were higher in untreated surgery mice than in control groups, also indicating the presence of pain or distress. Pain-specific scoring was superior to activity monitoring for assessing the analgesic properties of buprenorphine in vasectomised mice. Buprenorphine (0.01 mg/kg), in these strains of male mice, for this procedure, provided inadequate analgesia and although 0.05 mg/kg was more effective, not completely so. The findings support the recommendation that analgesic dose rates should be adjusted in relation to the potential severity of the surgical procedure, the mouse strain, and the individual animals' response. PMID:24098748

Wright-Williams, Sian; Flecknell, Paul A; Roughan, Johnny V

2013-01-01

65

Comparative Effects of Vasectomy Surgery and Buprenorphine Treatment on Faecal Corticosterone Concentrations and Behaviour Assessed by Manual and Automated Analysis Methods in C57 and C3H Mice  

PubMed Central

Establishing effective cage-side pain assessment methods is essential if post-surgical pain is to be controlled effectively in laboratory animals. Changes to overall activity levels are the most common methods of assessment, but may not be the most appropriate for establishing the analgesic properties of drugs, especially in mice, due their high activity levels. Use of drugs that can affect activity (e.g. opioids) is also a problem. The relative merits of both manual and automated behaviour data collection methods was determined in two inbred mouse strains undergoing vasectomy following treatment with one of 2 buprenorphine dose rates. Body weights and the effects of surgery and buprenorphine on faecal corticosterone were also measured. Surgery caused abnormal behaviour and reduced activity levels, but high dose buprenorphine caused such large-scale increases in activity in controls that we could not establish analgesic effects in surgery groups. Only pain-specific behaviour scoring using the manual approach was effective in showing 0.05 mg/kg buprenorphine alleviated post-vasectomy pain. The C57 mice also responded better to buprenorphine than C3H mice, indicating they were either less painful, or more responsive to its analgesic effects. C3H mice were more susceptible to the confounding effects of buprenorphine irrespective of whether data were collected manually or via the automated approach. Faecal corticosterone levels, although variable, were higher in untreated surgery mice than in control groups, also indicating the presence of pain or distress. Pain-specific scoring was superior to activity monitoring for assessing the analgesic properties of buprenorphine in vasectomised mice. Buprenorphine (0.01 mg/kg), in these strains of male mice, for this procedure, provided inadequate analgesia and although 0.05 mg/kg was more effective, not completely so. The findings support the recommendation that analgesic dose rates should be adjusted in relation to the potential severity of the surgical procedure, the mouse strain, and the individual animals' response. PMID:24098748

Wright-Williams, Sian; Flecknell, Paul A.; Roughan, Johnny V.

2013-01-01

66

Nurse practitioner and physician assistant interest in prescribing buprenorphine  

Microsoft Academic Search

Office-based buprenorphine places health care providers in a unique position to combine HIV and drug treatment in the primary care setting. However, federal legislation restricts nurse practitioners (NPs) and physician assistants (PAs) from prescribing buprenorphine, which may limit its potential for uptake and inhibit the role of these nonphysician providers in delivering drug addiction treatment to patients with HIV. This

Robert J. Roose; Hillary V. Kunins; Nancy L. Sohler; Rashiah T. Elam; Chinazo O. Cunningham

2008-01-01

67

Socio-demographic Profile and Help-seeking Behaviour of Buprenorphine Abusers in Singapore  

Microsoft Academic Search

Introduction: The US Food and Drug Administration (FDA) approved buprenorphine or Subutex for the treatment of opiate dependence in October 2002. Buprenorphine is a partial agonist of the mu-opioid receptor; although initial animal research suggested a low abuse potential for buprenorphine, it was subsequently shown to have an abuse potential similar to that of morphine or hydromorphone. The objectives of

Munidasa Winslow; Wei-Ling Ng; Subramaniam Mythily

68

Buprenorphine-naloxone maintenance following release from jail.  

PubMed

Primary care is understudied as a reentry drug and alcohol treatment setting. This study compared treatment retention and opioid misuse among opioid-dependent adults seeking buprenorphine/naloxone maintenance in an urban primary care clinic following release from jail versus community referrals. Postrelease patients were either (a) induced to buprenorphine in-jail as part of a clinical trial, or (b) seeking buprenorphine induction post release. From 2007 to 2008, N = 142 patients were new to primary care buprenorphine: n = 32 postrelease; n = 110 induced after community referral and without recent incarceration. Jail-released patients were more likely African American or Hispanic and uninsured. Treatment retention rates for postrelease (37%) versus community (30%) referrals were similar at 48 weeks. Rates of opioid positive urines and self-reported opioid misuse were also similar between groups. Postrelease patients in primary care buprenorphine treatment had equal treatment retention and rates of opioid abstinence versus community-referred patients. PMID:22263712

Lee, Joshua D; Grossman, Ellie; Truncali, Andrea; Rotrosen, John; Rosenblum, Andrew; Magura, Stephen; Gourevitch, Marc N

2012-01-01

69

Agonist substitution--a treatment alternative for high-dose benzodiazepine-dependent patients?  

PubMed

There is vast evidence for the superiority of agonist treatments (methadone, buprenorphine) over a withdrawal approach in opioid-dependent populations. Little research, however, has been conducted on the same approach for the treatment of high-dose benzodiazepine (BZD) dependence. Even large-scale reviews and meta-analyses discussing treatment strategies for benzodiazepine-dependent patients focus solely upon approaches that aim at achieving abstinence, namely on complete BZD withdrawal. While the types of interventions differ (e.g. gradual benzodiazepine taper with a long or a short half-life benzodiazepine, switching to non-benzodiazepine anxiolytics or prescribing adjunctive medications such as antidepressants or anticonvulsants on an in- or out-patient basis), the common aim of treatment still is total abstinence from benzodiazepines. However, the majority of patients suffering from high-dose BZD dependence do not succeed with long-term abstinence, irrespective of the procedure, and clinicians have been using BZD 'substitution' treatment in such cases for decades. Therefore, we suggest the evaluation of a substitution approach in this group, consisting of maintenance treatment with a slow-onset, long-acting BZD. Advantages of such a procedure may be improved health, less craving, fewer withdrawal complications, reduced anxiety, increased treatment retention, improvements in social functioning and less illegal activity. Cognitive impairments, the most problematic side effects of substitution treatment with benzodiazepines, could possibly be minimized by using an optimal agonist. PMID:20456294

Liebrenz, Michael; Boesch, Lukas; Stohler, Rudolf; Caflisch, Carlo

2010-11-01

70

The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol  

PubMed Central

Background Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. Methods/Design The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). Discussion Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. Systematic review registration PROSPERO CRD42013006507. PMID:25239213

2014-01-01

71

Disaccharides in urine samples as markers of intravenous abuse of methadone and buprenorphine.  

PubMed

Methadone and buprenorphine are commonly used as oral substitutes in opiate maintenance programs to treat persons who are dependent on heroin. During these programs, patients are not allowed to continue using illicit drugs. Abstinence can easily be monitored by urine tests with immunochemical methods. It is well known that the intravenous abuse of heroin substitutes like methadone or buprenorphine has become common as well. The methadone-prescribing physician has no opportunity to check whether the opiate maintenance treatment patient takes his substitution medicines orally as intended or continues with his intravenous misuse now substituting the methadone instead of injecting heroin. In Germany, substitutes are available as liquids and tablets that contain carbohydrates as adjuvants. Sucrose is used to increase viscosity in liquids, while lactose is needed for pressing tablets (e.g., Methaddict® and Subutex®). In case of oral ingestion, disaccharides are broken down into monosaccharides by disaccharidases in the small intestine. These monosaccharides are absorbed into the blood stream by special monosaccharide transporters. Disaccharidases do not exist in blood, thus sucrose and lactose are not split if substitute medicines are injected intravenously. Our assumption, therefore, was that they are excreted unchanged in urine. We investigated a method for the detection of disaccharides in urine as markers of intravenous abuse of substitutes. Urine samples of 26 intravenous substitute abusers showed all positive results for lactose (76.9%) and/or sucrose (73.1%). The method is assumed to be useful to detect intravenous abuse of substitutes. PMID:24099717

Jungen, Hilke; Andresen-Streichert, Hilke; Müller, Alexander; Iwersen-Bergmann, Stefanie

2013-01-01

72

Pain and Associated Substance Use among Opioid Dependent Individuals Seeking Office-Based Treatment with Buprenorphine-Naloxone: A Needs Assessment Study  

PubMed Central

Background and Objectives A paucity of studies has examined the pain experiences of opioid dependent individuals seeking office-based buprenorphine-naloxone treatment (BNT). We set out to examine, among those seeking BNT: (a) the prevalence of pain types (i.e., recent pain, chronic pain), (b) the characteristics of pain (intensity, frequency, duration, interference, location, and genesis), and (c) substance use to alleviate pain. Methods We surveyed 244 consecutive individuals seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence about physical pain and associated substance use. Results Thirty-six percent of respondents reported chronic pain (CP) (i.e., pain lasting at least 3 months) and 36% reported “some pain” (SP) (i.e., past week pain not meeting the threshold for CP). In comparison to SP respondents, those with CP were, on average, older; reported greater current pain intensity, pain frequency, typical pain duration, typical pain intensity, and typical pain interference; were more likely to report shoulder or pelvis and less likely to report stomach or arms as their most bothersome pain location; and were more likely to report accident or nerve damage and less likely to report opioid withdrawal as the genesis of their pain. Both pain subgroups reported similarly high rates of past-week substance use to alleviate pain. Conclusions and Scientific Significance The high rates of pain and self-reported substance use to manage pain suggest the importance of assessing and addressing pain in BNT patients. PMID:23617861

Barry, Declan T.; Savant, Jonathan D.; Beitel, Mark; Cutter, Christopher J.; Moore, Brent A.; Schottenfeld, Richard S.; Fiellin, David A.

2012-01-01

73

Buprenorphine/Naloxone and Methadone Maintenance Treatment Outcomes for Opioid Analgesic, Heroin, and Combined Users: Findings From Starting Treatment With Agonist Replacement Therapies (START)  

PubMed Central

Objective: The objective of this secondary analysis was to explore differences in baseline clinical characteristics and opioid replacement therapy treatment outcomes by type (heroin, opioid analgesic [OA], or combined [heroin and OA]) and route (injector or non-injector) of opioid use. Method: A total of 1,269 participants (32.2% female) were randomized to receive one of two study medications (methadone or buprenorphine/naloxone [BUP]). Of these, 731 participants completed the 24-week active medication phase. Treatment outcomes were opioid use during the final 30 days of treatment (among treatment completers) and treatment attrition. Results: Non-opioid substance dependence diagnoses and injecting differentiated heroin and combined users from OA users. Non-opioid substance dependence diagnoses and greater heroin use differentiated injectors from non-injectors. Further, injectors were more likely to be using at end of treatment compared with non-injectors. OA users were more likely to complete treatment compared with heroin users and combined users. Non-injectors were more likely than injectors to complete treatment. There were no interactions between type of opioid used or injection status and treatment assignment (methadone or BUP) on either opioid use or treatment attrition. Conclusions: Findings indicate that substance use severity differentiates heroin users from OA users and injectors from non-injectors. Irrespective of medication, heroin use and injecting are associated with treatment attrition and opioid misuse during treatment. These results have particular clinical interest, as there is no evidence of superiority of BUP over methadone for treating OA users versus heroin users. PMID:23739025

Potter, Jennifer S.; Marino, Elise N.; Hillhouse, Maureen P.; Nielsen, Suzanne; Wiest, Katharina; Canamar, Catherine P.; Martin, Judith A.; Ang, Alfonso; Baker, Rachael; Saxon, Andrew J.; Ling, Walter

2013-01-01

74

A retrospective evaluation of patients switched from buprenorphine (subutex) to the buprenorphine/naloxone combination (suboxone)  

PubMed Central

Background In Finland, buprenorphine (Subutex) is the most abused opioid. In order to curb this problem, many treatment centres transferred ("forced transfer") their buprenorphine patients to the buprenorphine plus naloxone (Suboxone) combination product in late 2003. Methods Data from a retrospective study involving five different treatment centers, examining the effects of switching patients to Suboxone, were gathered from 64 opioid-dependent patients who had undergone the medication transfer. Results Most patients (90.6%) switched to Suboxone at the same dose of buprenorphine that they had been receiving as Subutex (average 22 mg). The majority of these patients (71.9%) were maintained at the same dose of Suboxone throughout the 4-week study period. During the first 4 weeks, 50% of the patients reported adverse events and at the four month time point, 26.6% reported adverse events. However, due to adverse events one patient only discontinued treatment with Suboxone during the 4-week study period, and five during the four month follow-up period. Of the 26 patients in the follow-up period, Suboxone was misused intravenously once each by 4 patients and twice by 1 patient. These 5 patients all reported that injecting Suboxone was like injecting "nothing" with any euphoria, or that it was a bad experience. Conclusion We conclude that when patients are transferred from high doses (> 22 mg) of buprenorphine to the combination product, dose adjustments may be necessary especially in the later phase of the treatment. We recommend that a transfer from Subutex to Suboxone should be carefully discussed and planned in advance with the patients and after the transfer adverse events should be regularly monitored. With regard of buprenorphine IV abuse, the combination product seems to have a less abuse potential than buprenorphine alone. PMID:18559110

Simojoki, Kaarlo; Vorma, Helena; Alho, Hannu

2008-01-01

75

Rewarding or aversive effects of buprenorphine/naloxone combination (Suboxone) depend on conditioning trial duration.  

PubMed

Buprenorphine is used as a sublingual medication in the treatment of opioid dependence. However, its misuse by i.v. injection may limit its acceptability and dissemination. A buprenorphine/naloxone (ratio 4:1) combination has been developed to reduce diversion and abuse. So far, the relevance of this combination has not been investigated in the animal models traditionally used to study the reinforcing effects of drugs of abuse. The aim of this study was to compare the rewarding effects, assessed by conditioned place preference (CPP), of buprenorphine and buprenorphine/naloxone combination following i.v. administration in mice. Animals were treated with different doses of buprenorphine or buprenorphine/naloxone combination (ratio 4:1), and CPP conditioning trial duration was 5 or 30 min. At the longest trial duration, a bell-shaped dose-response curve was obtained with buprenorphine, which was shifted significantly to the right with naloxone combination. At the shortest trial duration, an aversive effect was observed with the buprenorphine/naloxone combination in animals, involving opioid receptor-like 1 (ORL1). These findings may explain the discrepancies reported in the literature as some authors have shown a reduced buprenorphine/naloxone misuse compared to buprenorphine in opioid abusers, while others have not. PMID:24606726

Canestrelli, Corinne; Marie, Nicolas; Noble, Florence

2014-09-01

76

Buprenorphine and methadone maintenance in jail and post-release: a randomized clinical trial.  

PubMed

Buprenorphine has rarely been administered as an opioid agonist maintenance therapy in a correctional setting. This study introduced buprenorphine maintenance in a large urban jail, Rikers Island in New York City. Heroin-dependent men not enrolled in community methadone treatment and sentenced to 10-90 days in jail (N=116) were voluntarily randomly assigned either to buprenorphine or methadone maintenance, the latter being the standard of care for eligible inmates at Rikers. Buprenorphine and methadone maintenance completion rates in jail were equally high, but the buprenorphine group reported for their designated post-release treatment in the community significantly more often than did the methadone group (48% vs. 14%, p<.001). Consistent with this result, prior to release from Rikers, buprenorphine patients stated an intention to continue treatment after release more often than did methadone patients (93% vs. 44%, p<.001). Buprenorphine patients were also less likely than methadone patients to withdraw voluntarily from medication while in jail (3% vs. 16%, p<.05). There were no post-release differences between the buprenorphine and methadone groups in self-reported relapse to illicit opioid use, self-reported re-arrests, self-reported severity of crime or re-incarceration in jail. After initiating opioid agonist treatment in jail, continuing buprenorphine maintenance in the community appears to be more acceptable to offenders than continuing methadone maintenance. PMID:18930603

Magura, Stephen; Lee, Joshua D; Hershberger, Jason; Joseph, Herman; Marsch, Lisa; Shropshire, Carol; Rosenblum, Andrew

2009-01-01

77

Correlations of Maternal Buprenorphine Dose, Buprenorphine, and Metabolite Concentrations in Meconium With Neonatal Outcomes  

Microsoft Academic Search

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal

SL Kacinko; HE Jones; RE Johnson; RE Choo; MA Huestis

2008-01-01

78

Unobserved versus observed office buprenorphine\\/naloxone induction: A pilot randomized clinical trial  

Microsoft Academic Search

Physician adoption of buprenorphine treatment of opioid dependence may be limited in part by concerns regarding the induction process. Although national guidelines recommend observed induction, some physicians utilize unobserved induction outside the office. The aim of this pilot randomized clinical trial was to assess preliminary safety and effectiveness of unobserved versus observed office buprenorphine\\/naloxone induction among patients entering a 12-week

Erik W. Gunderson; Xin-Qun Wang; David A. Fiellin; Benjamin Bryan; Frances R. Levin

2010-01-01

79

Transfer of Buprenorphine Into Breast Milk and Calculation of Infant Drug Dose  

Microsoft Academic Search

Little is known about the safety of buprenorphine (BUP) in breastfeeding. The aim of this work was to investigate the transfer of buprenorphine and its main active metabolite, norbuprenorphine (n-BUP), into human milk and to determine the drug dose and effects in exposed infants. Seven lactating women, who were maintained on BUP treatment because of previous opiate addiction, were studied

Synnove Lindemalm; Per Nydert; Jan-Olov Svensson; Lars Stahle; Ihsan Sarman

2009-01-01

80

HIV Treatment Outcomes Among HIV-Infected, Opioid-Dependent Patients Receiving Buprenorphine/Naloxone Treatment within HIV Clinical Care Settings: Results From a Multisite Study  

PubMed Central

Background Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes. Methods HIV-infected, opioid-dependent subjects (N = 295) recruited from 10 clinical sites initiated buprenorphine/naloxone (BUP/NX) and were assessed at baseline and quarterly for 12 months. Primary outcomes included receiving antiretroviral therapy (ART), HIV-1 RNA suppression, and mean changes in CD4 lymphocyte count. Analyses were stratified for the 119 subjects not on ART at baseline. Generalized estimating equations were deployed to examine time-dependent correlates for each outcome. Results At baseline, subjects on ART (N = 176) were more likely than those not on ART (N = 119) to be older, heterosexual, have lower alcohol addiction severity scores, and lower HIV-1 RNA levels; they were less likely to be homeless and report sexual risk behaviors. Subjects initiating BUP/NX (N = 295) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline; however, these improvements were not significantly improved by longer retention on BUP/NX. Retention on BUP/NX for three or more quarters was, however, significantly associated with increased likelihood of initiating ART (? = 1.34 [1.18, 1.53]) and achieve viral suppression (? = 1.25 [1.10, 1.42]) for the 64 of 119 (54%) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX. In longitudinal analyses, being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores (? = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (? = 0.55 [0.35, 0.97]), homeless (? = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (? = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (? = 10.27 [5.79, 18.23]). Female gender (? = 1.91 [1.07, 3.41]), Hispanic ethnicity (? = 2.82 [1.44, 5.49]), and increased general health quality of life (? = 1.02 [1.00,1.04]) were also independently correlated with viral suppression. Improvements in CD4 lymphocyte count were significantly associated with being on ART and increased over time. Conclusions Initiating BUP/NX in HIV clinical care settings is feasible and correlated with initiation of ART and improved CD4 lymphocyte counts. Longer retention on BPN/NX was not associated with improved prescription of ART, viral suppression, or CD4 lymphocyte counts for the overall sample in which the majority was already prescribed ART at baseline. Among those retained on BUP/NX, HIV treatment outcomes did not worsen and were sustained. Increasing time on BUP/NX, however, was especially important for improving HIV treatment outcomes for those not on ART at baseline, the group at highest risk for clinical deterioration. Retaining subjects on BUP/NX is an important goal for sustaining HIV treatment outcomes for those on ART and improving them for those who are not. Comorbid substance use disorders (especially alcohol), mental health problems, and quality–of-life indicators independently contributed to HIV treatment outcomes among HIV-infected persons with opioid dependence, suggesting the need for multidisciplinary treatment strategies for this population. PMID:21317590

Altice, Frederick L.; Bruce, R. Douglas; Lucas, Gregory M.; Lum, Paula J.; Korthuis, P. Todd; Flanigan, Timothy P.; Cunningham, Chinazo O.; Sullivan, Lynn E.; Vergara-Rodriguez, Pamela; Fiellin, David A.; Cajina, Adan; Botsko, Michael; Nandi, Vijay; Gourevitch, Marc N.; Finkelstein, Ruth

2012-01-01

81

Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans.  

PubMed

This study assessed the blockade of hydromorphone challenge effects (cumulative s.c. doses of 0, 6 and 18 mg) during chronic buprenorphine treatment of opioid dependent subjects. Buprenorphine was administered daily via the sublingual route in ascending doses of 2, 4, 8 and 16 mg. Hydromorphone challenges were conducted after 10 to 14 days of chronic administration of each buprenorphine dose and 24 h after the last buprenorphrine dose. Buprenorphrine itself only produced dose-related effects in respiration rate. While subjects were maintained on 2 mg of buprenorphine, the hydromorphone challenge produced dose-related changes in physiological and self-report measures. As the dose of buprenorphine was increased, hydromorphone effects on self-report measures were attenuated to a greater extent than was noted for pupil diameter. The results of this study confirm previous reports of buprenorphine blockade of opioid agonist effects in humans and extent those findings by demonstrating both a buprenorphine dose-effect function and a dissociation between the potency of buprenorphine's opioid blockade for self-report vs. physiological measures. PMID:2459370

Bickel, W K; Stitzer, M L; Bigelow, G E; Liebson, I A; Jasinski, D R; Johnson, R E

1988-10-01

82

Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?  

PubMed Central

Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that to date this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the specific brain regions responsible for relapse prevention. PMID:21948099

Blum, Kenneth; Chen, Thomas JH; Bailey, John; Bowirrat, Abdulla; Femino, John; Chen, Amanda LC; Simpatico, Thomas; Morse, Siobhan; Giordano, John; Damle, Uma; Kerner, Mallory; Braverman, Eric R.; Fornari, Frank; Downs, B.William; Rector, Cynthia; Barh, Debmayla; Oscar-Berman, Marlene

2013-01-01

83

A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts.  

PubMed

The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts. Forty-five patients were randomized to receive either sublingual buprenorphine or oral methadone under double-dummy and double-blind conditions to study the pharmacology of buprenorphine in a 90-day detoxification protocol. The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by 4 weeks of dose reductions and 6 weeks of placebo medication. No significant between-group differences were seen on measures of treatment retention, drug use, or symptom report. During the hydromorphone challenge, methadone attenuated opioid effects to a greater extent than did buprenorphine on both physiologic (pupil constriction) and self-report measures. However, this did not result in greater abuse of illicit opioid drugs by subjects taking buprenorphine. The results of this clinical trial indicated that buprenorphine was acceptable to patients and as effective as methadone in the detoxification treatment of heroin addicts. PMID:3275523

Bickel, W K; Stitzer, M L; Bigelow, G E; Liebson, I A; Jasinski, D R; Johnson, R E

1988-01-01

84

Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering  

ERIC Educational Resources Information Center

A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…

Greenwald, Mark K.

2008-01-01

85

Open-label trial of an injection depot formulation of buprenorphine in opioid detoxification  

Microsoft Academic Search

Buprenorphine, a partial mu-opioid agonist, has been shown effective for treatment of opioid dependence but also has some abuse potential. A novel formulation of buprenorphine, using a polymer microcapsule depot sustained-release technology, has been developed which may offer effective treatment of opioid dependence while also minimizing risks of patient noncompliance and illicit diversion. This open-label, first-in-human study evaluated the safety

Bai-Fang X. Sobel; Stacey C. Sigmon; Sharon L. Walsh; Rolley E. Johnson; Ira A. Liebson; Elie S. Nuwayser; James H. Kerrigan; George E. Bigelow

2004-01-01

86

Urine specimen detection of concurrent nonprescribed medicinal and illicit drug use in patients prescribed buprenorphine.  

PubMed

Patients being treated with buprenorphine usually have a history of opioid dependence and may be predisposed to misuse of drugs. Concurrent drug misuse increases the risk of life-threatening drug interactions. This retrospective data analysis observed which nonprescribed and illicit drugs were most commonly detected in the urine of patients from pain management clinics taking buprenorphine with or without a prescription. GC, LC/MS and LC-MS-MS were used to quantify 20,929 urine specimens. The most prevalent illicit drug used in both the groups (prescribed and nonprescribed buprenorphine) was marijuana, followed by cocaine. The most prevalent nonprescribed medications abused by both the groups were benzodiazepines, followed by oxycodone and hydrocodone. The overall prevalence of illicit and nonprescribed drug use was significantly higher in subjects who used buprenorphine without a prescription versus prescribed use. Of the concurrent use of marijuana and cocaine with buprenorphine, cocaine is most concerning since it decreases exposure to buprenorphine (lower area under the concentration-time curve and maximum concentration). The concurrent use of nonprescribed benzodiazepines with buprenorphine can cause excess sedation leading to respiratory depression and even death. These findings highlight the importance of educating patients about these potential toxicities. Furthermore, pain providers should consider expanding the spectrum of drugs that they monitor in patients under treatment. PMID:24080973

Guo, Alexander Y; Ma, Joseph D; Best, Brookie M; Atayee, Rabia S

2013-01-01

87

Effect of Incarceration History on Outcomes of Primary Care Office-based Buprenorphine/Naloxone  

PubMed Central

Background Behaviors associated with opioid dependence often involve criminal activity, which can lead to incarceration. The impact of a history of incarceration on outcomes in primary care office-based buprenorphine/naloxone is not known. Objective The purpose of this study is to determine whether having a history of incarceration affects response to primary care office-based buprenorphine/naloxone treatment. Design In this post hoc secondary analysis of a randomized clinical trial, we compared demographic, clinical characteristics, and treatment outcomes among 166 participants receiving primary care office-based buprenorphine/naloxone treatment stratifying on history of incarceration. Main Results Participants with a history of incarceration have similar treatment outcomes with primary care office-based buprenorphine/naloxone than those without a history of incarceration (consecutive weeks of opioid-negative urine samples, 6.2 vs. 5.9, p?=?0.43; treatment retention, 38% vs. 46%, p?=?0.28). Conclusions Prior history of incarceration does not appear to impact primary care office-based treatment of opioid dependence with buprenorphine/naloxone. Community health care providers can be reassured that initiating buprenorphine/naloxone in opioid dependent individuals with a history of incarceration will have similar outcomes as those without this history. PMID:20213205

Moore, Brent A.; Sullivan, Lynn E.; Fiellin, David A.

2010-01-01

88

A randomized trial of buprenorphine maintenance for heroin dependence in a primary care clinic for substance users versus a methadone clinic  

Microsoft Academic Search

PURPOSE: Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis. Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use.SUBJECTS AND METHODS: Opioid-dependent patients were randomly

PatrickG O’Connor; AlisonH Oliveto; JuliaM Shi; ElisaG Triffleman; KathleenM Carroll; ThomasR Kosten; BruceJ Rounsaville; JulianaA Pakes; RichardS Schottenfeld

1998-01-01

89

Buprenorphine prescribing practices and exposures reported to a poison center--Utah, 2002-2011.  

PubMed

Buprenorphine is an effective medication for the treatment of opioid dependence. Its use has increased in the United States as a result of the Drug Addiction Treatment Act of 2000, which allowed physicians to prescribe certain medications as part of office-based treatment for opioid addiction. In France, widespread use of medication-assisted therapy, primarily buprenorphine treatment, was associated with an 80% decrease in overdose deaths from heroin or cocaine from 465 in 1996 to 89 in 2003. With the expanded use of buprenorphine, an increase in exposures among children and adults has been reported in the United States. These exposures (including unintentional and intentional, therapeutic and nontherapeutic) have resulted in adverse effects and, in a small number of cases, death. To assess statewide increases in buprenorphine use and the number of reported exposures, the Utah Department of Health analyzed data from the Utah Controlled Substance Database (CSD) and the Utah Poison Control Center (PCC). The results of that analysis indicated a statewide increase in the annual number of patients prescribed buprenorphine from 22 in 2002 to 9,793 in 2011, and a concurrent increase in the annual number of prescribers writing buprenorphine prescriptions from 16 to 1,088. Over the same period, the number of exposures to buprenorphine reported annually to the PCC increased from six to 81. However, comparison of the ratios of buprenorphine exposures to patients and prescribers in 2002 with data for 2011 indicated substantial decreases from 6/22 for patients and 6/16 for prescribers in 2002 to 81/9,793 for patients and 81/1,088 for prescribers in 2011. Three of the total 462 buprenorphine exposures reported during 2002-2011 in Utah, in a teen and two adults, were associated with fatal outcomes. Increased buprenorphine prescribing in Utah during 2002-2011 likely represents expanded access to critically needed opioid addiction treatment; however, safeguards should be in place to prevent adverse effects. Prescribers and pharmacists are encouraged to counsel patients carefully regarding the safe use, storage, and disposal of buprenorphine. PMID:23235296

2012-12-14

90

The cost-effectiveness of buprenorphine maintenance therapy for opiate addiction in the United States  

Microsoft Academic Search

Aims. To determine the cost-effectiveness of buprenorphine maintenance therapy for opiate addiction in the United States, particularly its effect on the HIV epidemic. Design. We developed a dynamic model to capture the effects of adding buprenorphine maintenance to the current opiate dependence treatment system. We evaluated incremental costs, including all health-care costs, and incremental effectiveness, measured as quality-adjusted life years

Paul G. Barnett; Gregory S. Zaric; Margaret L. Brandeau

2001-01-01

91

The history of the development of buprenorphine as an addiction therapeutic.  

PubMed

This paper traces the early 21st century success of the agonist-antagonist buprenorphine and the combination drug buprenorphine with naloxone within the broader quest to develop addiction therapeutics that began in the 1920s as the search for a nonaddictive analgesic. Drawing on archival research, document analysis, and interviews with contemporary actors, this paper situates the social organization of laboratory-based and clinical research within the domestic and international confluence of several issues, including research ethics, drug regulation, public attitudes, tensions around definitions of drug addiction, and the evolving roles of the pharmaceutical industry. The fervor that drove the champions of buprenorphine must be understood in relation to (1) the material work of research and pharmaceutical manufacturing; (2) the symbolic role of buprenorphine as a solution to numerous problems with addiction treatment evident by the mid-1970s; the destigmatization and individualization of addicts as patients; and (3) the complex configurations of public and private partnerships. PMID:22256949

Campbell, Nancy D; Lovell, Anne M

2012-02-01

92

Oral buprenorphine and aspirin analgesia in rats undergoing liver transplantation  

Microsoft Academic Search

Summary The objective of this study was to establish effective postoperative analgesia for Dark Agouti rats undergoing liver transplantation with minimal additional stress due to handling and no adverse effect on transplant outcome. Oral administration of buprenorphine (0.5 mg =kg=dose) or aspirin (100 mg =kg=dose) in raspberry-¯ avoured gelatine were compared to controls receivingno treatment or plain gelatine. The drugs

P. Jablonski; B. O. Howden

2002-01-01

93

Oligodendrocyte responses to buprenorphine uncover novel and opposing roles of ?-opioid- and nociceptin/orphanin FQ receptors in cell development: implications for drug addiction treatment during pregnancy.  

PubMed

Although the classical function of myelin is the facilitation of saltatory conduction, this membrane and the oligodendrocytes, the cells that make myelin in the central nervous system (CNS), are now recognized as important regulators of plasticity and remodeling in the developing brain. As such, oligodendrocyte maturation and myelination are among the most vulnerable processes along CNS development. We have shown previously that rat brain myelination is significantly altered by buprenorphine, an opioid analogue currently used in clinical trials for managing pregnant opioid addicts. Perinatal exposure to low levels of this drug induced accelerated and increased expression of myelin basic proteins (MBPs), cellular and myelin components that are markers of mature oligodendrocytes. In contrast, supra-therapeutic drug doses delayed MBP brain expression and resulted in a decreased number of myelinated axons. We have now found that this biphasic-dose response to buprenorphine can be attributed to the participation of both the ?-opioid receptor (MOR) and the nociceptin/orphanin FQ receptor (NOP receptor) in the oligodendrocytes. This is particularly intriguing because the NOP receptor/nociceptin system has been primarily linked to behavior and pain regulation, but a role in CNS development or myelination has not been described before. Our findings suggest that balance between signaling mediated by (a) MOR activation and (b) a novel, yet unidentified pathway that includes the NOP receptor, plays a crucial role in the timing of oligodendrocyte maturation and myelin synthesis. Moreover, exposure to opioids could disrupt the normal interplay between these two systems altering the developmental pattern of brain myelination. PMID:22002899

Eschenroeder, Andrew C; Vestal-Laborde, Allison A; Sanchez, Emilse S; Robinson, Susan E; Sato-Bigbee, Carmen

2012-01-01

94

Transdermal delivery of buprenorphine through cadaver skin.  

PubMed

The skin permeation of buprenorphine base and HCl salt through cadaver skin was investigated. The octanol-water partition coefficient and solubilities of both buprenorphine free base and HCl salt were determined at 32 degrees C. As expected, buprenorphine free base was more lipophilic than its HCl salt and was practically insoluble in aqueous buffer at pH 8.7. The drug solubility decreased exponentially as the pH of the solution increased, whereas the permeability coefficient increased as the donor solution pH decreased. The skin flux of buprenorphine.HCl was significantly higher than that of the free base from propylene glycol/lauric acid vehicle mixtures. Buprenorphine base permeation through tape-stripped epidermis suggested that in addition to stratum corneum, viable epidermis presented a significant diffusion barrier because of the very low aqueous solubility of the free base observed. The mean steady-state skin fluxes of buprenorphine.HCl were 20.3 and 29.7 micrograms/cm2/h from propylene glycol:lauryl alcohol: ethanol (80:15:5) and propylene glycol: propylene glycol monolaurate: water (80:15:5) vehicle mixtures, respectively. The skin flux of buprenorphine.HCl from various monolithic matrix patches was also evaluated. When capric acid, lauric acid, and lauryl alcohol were separately incorporated into an adhesive matrix, the skin flux of buprenorphine.HCl was enhanced by a factor of 2 to 3.5. Finally, based on the total body clearance and minimum effective concentration of buprenorphine, a transdermal delivery rate of 2.5 micrograms/cm2/h from a 20-cm2 patch was estimated. The in vitro skin permeation data clearly suggest that transdermal delivery of buprenorphine is feasible to achieve a desired systemic analgesic effect. PMID:8169777

Roy, S D; Roos, E; Sharma, K

1994-02-01

95

Adverse effects on growth rates in rats caused by buprenorphine administration.  

PubMed

As a routine postoperative treatment, a single dose of buprenorphine was given to rats at a dose of 0.05 mg/kg subcutaneously. However, some rats developed abnormal secretions around the nose and mouth and some animals died 3-5 days after surgery and analgesic treatment. At autopsy a yellow fibrous mass was found in the stomach and intestines. Observations of animals given buprenorphine revealed an abnormal ingestion of bedding material. This caused a disturbance to normal digestion, with gastric distension, weight loss or decreased growth rate, constipation and occasionally death. In this study rats were monitored for 6 days following surgery and analgesic treatment. A comparison of growth rates was made between rats given saline and buprenorphine or nalbuphine and between animals kept on bedding or grid floors for the first 24h after treatment. Of the animals held on bedding, the buprenorphine-treated animals did not lose weight as the other animals did, but had on the other hand a decreased growth rate during the measuring period of 6 days after surgery. When denied access to bedding for the first 24 h after surgery, rats given saline or nalbuphine had a reduced weight gain over the first 24 h, similar to the groups held on bedding. Rats held on grid floors and given buprenorphine continued to gain weight for the first 24 h. From day 3, there was no significant difference between the groups, which all gained weight. PMID:10817460

Jacobson, C

2000-04-01

96

The Baltimore Buprenorphine Initiative: understanding the role of buprenorphine in addressing heroin addiction in an urban-based community.  

PubMed

Adequate drug treatment for substance users continues to be a challenge for most U.S. cities. To address heroin addiction in Baltimore, the Baltimore Buprenorphine Initiative was implemented as a joint project to promote individualized, patient-centered buprenorphine therapy in conjunction with behavioral treatment to accelerate recovery from opioid addiction. The purpose of this analysis was to explore differences in recovery trajectories predicting length of stay and use this information to predict characteristics that influence an individual's ability to remain in the Baltimore Buprenorphine Initiative program. The sample consisted of 1,039 subjects enrolled in the program between January 2008 and June 2009. The regression modeling determined that age, income, employment, and higher level of treatment were significant predictors of length of stay in the recovery program. The findings of this study have practical implications for the design and implementation of heroin addiction programs. The research indicates that focusing on these specific predictive variables early in the program design phase could increase recovery success rates as measured by length of stay. PMID:24613946

Murphy, Lyn Stankiewicz; Oros, Marla T; Dorsey, Susan G

2014-01-01

97

A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine.  

PubMed

Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical ?-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation. PMID:24227768

Tompkins, D Andrew; Smith, Michael T; Mintzer, Miriam Z; Campbell, Claudia M; Strain, Eric C

2014-02-01

98

Well-being, psychosocial factors, and side-effects among heroin-dependent inpatients after detoxification using buprenorphine versus clonidine  

Microsoft Academic Search

Previous studies comparing buprenorphine and clonidine provided little information about subjective factors associated with the effective management of opioid withdrawal. This study sought to compare detoxification programs using these medications with regard to side-effects and related distress, general well-being, perceived self-efficacy and social support. A total of 200 treatment-seeking heroin-dependent patients, aged 18–50, were randomly assigned to buprenorphine or clonidine

Alexander M. Ponizovsky; Alexander Grinshpoon; Anatoly Margolis; Rami Cohen; Paula Rosca

2006-01-01

99

Buprenorphine Misuse among Heroin and Amphetamine Users in Malmo, Sweden: Purpose of Misuse and Route of Administration  

Microsoft Academic Search

Buprenorphine misuse by injecting drug users was assessed in a survey of 350 needle exchangers, either amphetamine (57%) or heroin users (42%). 89% of heroin users and 24% of amphetamine users reported using buprenorphine at some time during the previous year. Most users reported illicit acquisition. Among illicit users, 87% of heroin users reported intake for withdrawal treatment or self-detoxification,

A. Hakansson; A. Medvedeo; M. Andersson; M. Berglund

2007-01-01

100

Management of opioid addiction with buprenorphine: French history and current management.  

PubMed

The way in which opioid addiction is managed in France is unique, as it is based on the prescription of buprenorphine by general practitioners and is dispensed by retail pharmacies. This policy has had a direct, positive impact on the number of deaths caused by heroin overdose, which was reduced by four-fifths between 1994 and 2002. In addition, certain associated comorbidities, such as infection with the human immunodeficiency virus, have also been reduced; the incidence of acquired immune deficiency syndrome in intravenous drug users fell from 25% in the mid-1990s to 6% in 2010. Since the implementation of this French model of opioid management, major scientific progress has been made, leading to a better understanding of the pathophysiologic mechanisms of addiction and of the management modalities required for its treatment. However, despite notable advances in scientific knowledge and in the implementation of devices, opioid addiction remains a major public health care issue in France, with 275,000-360,000 "problem drug users" being reported in 2011. The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users. In France, the direct involvement of general practitioners in the management of opioid addiction is indisputable. Nevertheless, management could be optimized through better understanding of the pathophysiologic mechanisms of the disease, better knowledge of the pharmacology of opioid substitution treatments, and clear definition of short-, medium- and long-term treatment objectives. Data related to the management of opioid addiction by general practitioners in France have been published in 2005. Since then, the context has changed, other drugs were launched on the market such as generics of buprenorphine, methadone capsule, and Suboxone. Thus, an update seems necessary. This paper provides a description of opioid addiction management objectives and treatment modalities for general practitioners, based on currently available knowledge. PMID:24623988

Poloméni, Pierre; Schwan, Raymund

2014-01-01

101

Buprenorphine/Naloxone Reduces the Reinforcing and Subjective Effects of Heroin in Heroin-Dependent Volunteers  

PubMed Central

Rationale Although buprenorphine is effective in treating opioid dependence, optimal maintenance doses of buprenorphine or the buprenorphine/naloxone combination have not yet been established. Objective The present study was designed to evaluate the effects of buprenorphine/naloxone maintenance (2/0.5, 8/2, 32/8 mg sublingual) on the reinforcing and subjective effects of heroin (0, 12.5, 25, 50, and 100 mg intranasal) in heroin-dependent individuals. Methods During test weeks, participants (N=7) first sampled a dose of heroin and $20. During subsequent choice sessions, participants could choose to self administer heroin and/or money. Participants responded under a modified progressive-ratio schedule (PR 50, …, 2800) during a 10-trial self-administration task. Results Heroin break point values and subjective responses were significantly lower under 8/2 and 32/8 mg buprenorphine/naloxone compared to 2/0.5 mg. The self-administration and subjective effects data for heroin in the presence of buprenorphine/naloxone were compared to a separate control group of recently detoxified participants (N=8) in order to obtain estimates for the apparent in vivo dissociation constant (KA), the efficacy estimate (tau), and the estimated fraction of receptors remaining after buprenorphine/naloxone treatment (q). The apparent in vivo dissociation constant for heroin ranged from 50–126 mg (KA) and the efficacy estimate ranged from 13–20 (tau). In addition, 2/0.5, 8/2 and 32/8 mg buprenorphine/naloxone dose-dependently reduced the receptor population by 74%, 83%, and 91%, respectively. Conclusions These data demonstrate that both 8/2 and 32/8 mg buprenorphine/naloxone were well tolerated and effective in reducing the reinforcing and subjective effects of heroin, relative to the 2/0.5 mg dose. The data also show for the first time in humans that it is possible to quantify the efficacy and affinity of heroin for mu opioid receptors and that 80–90% of mu receptors need to be inactivated in order to obtain significant reductions in heroin-induced effects. These results have important implications for future studies in which it will be possible to obtain estimates of relative affinity and efficacy of different agonists at mu opioid receptors. PMID:16025322

Comer, Sandra D.; Walker, Ellen A.; Collins, Eric D.

2013-01-01

102

Effects of regulation on methadone and buprenorphine provision in the wake of hurricane sandy.  

PubMed

Hurricane Sandy led to the closing of many major New York City public hospitals including their substance abuse clinics and methadone programs, and the displacement or relocation of thousands of opioid-dependent patients from treatment. The disaster provided a natural experiment that revealed the relative strengths and weaknesses of methadone treatment in comparison to physician office-based buprenorphine treatment for opioid dependence, two modalities of opioid maintenance with markedly different regulatory requirements and institutional procedures. To assess these two modalities of treatment under emergency conditions, semi-structured interviews about barriers to and facilitators of continuity of care for methadone and buprenorphine patients were conducted with 50 providers of opioid maintenance treatment. Major findings included that methadone programs presented more regulatory barriers for providers, difficulty with dose verification due to impaired communication, and an over reliance on emergency room dosing leading to unsafe or suboptimal dosing. Buprenorphine treatment presented fewer regulatory barriers, but buprenorphine providers had little to no cross-coverage options compared to methadone providers, who could refer to alternate methadone programs. The findings point to the need for well-defined emergency procedures with flexibility around regulations, the need for a central registry with patient dose information, as well as stronger professional networks and cross-coverage procedures. These interventions would improve day-to-day services for opioid-maintained patients as well as services under emergency conditions. PMID:25163931

McClure, Bridget; Mendoza, Sonia; Duncan, Laura; Rotrosen, John; Hansen, Helena

2014-10-01

103

Randomized, Placebo-Controlled Pilot Trial of Gabapentin During an Outpatient, Buprenorphine-Assisted Detoxification Procedure1  

PubMed Central

This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-wk, double blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during week 1, were randomized and inducted onto gabapentin or placebo during week 2, underwent a 10-day buprenorphine taper during weeks 3–4 and then were tapered off gabapentin/placebo during week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male, 17 Caucasian, 3 African American, 4 Latino, mean age 29.7 yrs) participated in the detoxification portion of the study (gabapentin, N=11; placebo, N=13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a drug x time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during weeks 3–4 (OR=0.73, p=0.004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure. PMID:23855333

Sanders, Nichole C.; Mancino, Michael J.; Gentry, W. Brooks; Guise, J. Benjamin; Bickel, Warren K.; Thostenson, Jeff; Oliveto, Alison H.

2014-01-01

104

Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro.  

PubMed

Buprenorphine is a thebaine derivative used in the treatment of heroin and other opiate addictions. In this study, the selective probe reactions for each of the major hepatic cytochromes P450 (P450s) were used to evaluate the effect of buprenorphine and its main metabolite norbuprenorphine on the activity of these P450s. The index reactions used were CYP1A2 (phenacetin O-deethylation), CYP2A6 (coumarin 7-hydroxylation), CYP2C9 (diclofenac 4'-hydroxylation), CYP2C19 (omeprazole 5-hydrxoylation), CYP2D6 (dextromethorphan O-demethylation), CYP2B6 (7-ethoxy-4-trifluoromethyl-coumarin 7-deethylation), CYP2E1 (chlorzoxazone 6-hydroxylation), and CYP3A4 (omeprazole sulfoxidation). Buprenorphine exhibited potent, competitive inhibition of CYP2D6 (Ki 10 +/- 2 microM and 1.8 +/- 0.2 microM) and CYP3A4 (Ki 40 +/- 1.6 microM and 19 +/- 1.2 microM) in microsomes from human liver and cDNA-expressing lymphoblasts, respectively. Compared with buprenorphine, norbuprenorphine demonstrated a lower inhibitory potency with CYP2D6 (22.4% inhibition at 20 microM norbuprenorphine) and CYP3A4 (13.6% inhibition at 20 microM) in microsomes from human cDNA-expressing lymphoblast cells. Furthermore, buprenorphine was shown to be a substrate of CYP2D6 (Km = 600 microM; Vmax = 0.40 nmol/min/mg protein) and CYP3A4 (Km = 36 microM; Vmax = 0.19 nmol/min/mg protein). The present in vitro study suggests that buprenorphine and its major metabolite norbuprenorphine are inhibitors of CYP2D6 and CYP3A4; however, at therapeutic concentrations they are not predicted to cause potentially clinically important drug interactions with other drugs metabolized by major hepatic P450s. PMID:12756210

Zhang, Wenjiang; Ramamoorthy, Yamini; Tyndale, Rachel F; Sellers, Edward M

2003-06-01

105

The reinforcing and subjective effects of intravenous and intranasal buprenorphine in heroin users.  

PubMed

Abuse of buprenorphine (BUP) by the intravenous (IV) route has been documented in several studies, and reports of intranasal (IN) abuse are increasing. However, no studies have directly compared the effects of BUP when it is administered intranasally and intravenously. The present secondary analysis used data from two separate studies to compare the reinforcing and subjective effects of IV and IN buprenorphine. One study evaluated IV buprenorphine (N=13) and the other evaluated IN buprenorphine (N=12). Participants were maintained on 2 mg sublingual (SL) BUP and tested with each intranasal or intravenous buprenorphine test dose (0 mg, 2 mg, 4 mg, 8 mg, and 16 mg). During morning laboratory sessions, participants received money (US $20) and sample doses of IN or IV BUP, and then completed subjective effects questionnaires. Later that day, they completed a self-administration task to receive 10% portions of the drug and/or money they previously sampled. In general, positive subjective ratings for both IV and IN BUP were significantly greater than placebo, with IV BUP having a greater effect than IN BUP. All active BUP doses (IV and IN) maintained significantly higher progressive ratio breakpoint values than placebo, but breakpoint values for IV BUP were greater than for IN BUP. Buprenorphine is an effective maintenance treatment for opioid dependence, valued for its ability to reduce the positive subjective effects of other opioids. Nevertheless, the present data demonstrate that in participants maintained on a low dose of SL BUP, the medication itself has abuse liability when used intravenously or intranasally. PMID:24793093

Jones, Jermaine D; Madera, Gabriela; Comer, Sandra D

2014-07-01

106

Postcastration analgesia in ponies using buprenorphine hydrochloride.  

PubMed

Buprenorphine has recently obtained UK Marketing Authorisation for horses. The analgesic effects are long lasting, and have considerable potential for postoperative pain relief. This observer blinded, randomised study aimed to evaluate postsurgical analgesia in ponies premedicated with buprenorphine prior to castration under intravenous anaesthesia. Ponies received either 0.01 mg/kg bodyweight (BW) buprenorphine (group B) or an equivalent volume of 5 per cent glucose (group C) given intravenously before induction of anaesthesia. Pain was assessed and recorded using dynamic interactive visual analogue scores (DIVAS 0-100) and a Simple Descriptive Scale (SDS 0-3) (high scores=most pain) before and 1, 3, 6, 9, 12 and 24 hours after anaesthesia. Rescue analgesia was given if DIVAS>40 mm. Data were analysed using the Mann-Whitney U test at P<0.05. Median (range) areas under the curve for DIVAS were 63 (0-383) mm hour in group B and 209 (0-391) mm hour in group C (P=0.0348). The SDS was lower in group B than in group C (P=0.038). Three group B and five group C animals required rescue analgesia. Buprenorphine did not produce any serious adverse effects. Buprenorphine at 0.01 mg/kg BW intravenously administered before anaesthesia provided near-comprehensive postoperative analgesia after surgical castration in ponies. PMID:23736517

Love, E J; Taylor, P M; Whay, H R; Murrell, J

2013-06-15

107

A review of buprenorphine diversion and misuse: the current evidence base and experiences from around the world.  

PubMed

Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy has rapidly expanded in the United States and abroad, and, with this increase in medication availability, there have been increasing concerns about its diversion, misuse, and related harms. This narrative review defines the behaviors of diversion and misuse, examines how the pharmacology of buprenorphine alone and in combination with naloxone influence its abuse liability, and describes the epidemiological data on buprenorphine diversion and intravenous misuse, risk factors for its intravenous misuse, and the unintended consequences of misuse and diversion. Physician practices to prevent, screen for, and therapeutically respond to these behaviors, which are a form of medication nonadherence, are discussed, and gaps in knowledge are identified. Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy experiences from other countries that have varied health care systems, public policies, and access to addiction treatment are shared to make clear that diversion and misuse occur across the world in various contexts, for many different reasons, and are not limited to buprenorphine. Comparisons are made with other opioids with known abuse liability and medications with no known abuse. The objective was to facilitate understanding of diversion and misuse so that all factors influencing their expression (patient and provider characteristics and public policy) can be appreciated within a framework that also recognizes the benefits of addiction treatment. With this comprehensive perspective, further careful work can help determine how to minimize these behaviors without eroding the current benefits realized through improved addiction treatment access and expansion. PMID:25221984

Lofwall, Michelle R; Walsh, Sharon L

2014-01-01

108

Messages about methadone and buprenorphine in reality television: a content analysis of celebrity rehab with Dr. Drew.  

PubMed

Medication-assisted treatment for opioid dependence is safe and effective, yet negative perceptions about methadone and buprenorphine may discourage patients from entering treatment. One source of information that may influence viewers' perceptions is television. We performed a content analysis of a popular reality television program on addiction treatment. Although many patients had histories of opioid use, there were no positive messages about methadone or buprenorphine. The two main messages were that they (1) are primarily drugs of abuse, and (2) not acceptable treatment options. These messages reinforce negative stereotypes and may perpetuate stigma. There were multiple missed opportunities to provide evidence-based information. PMID:22587811

Roose, Robert; Fuentes, Liza; Cheema, Mandeep

2012-08-01

109

Pharmacologic treatments for opioid dependence: detoxification and maintenance options  

PubMed Central

While opioid dependence has more treatment agents available than other abused drugs, none are curative. They can, however, markedly diminish withdrawal symptoms and craving, and block opioid effects due to lapses. The most effective withdrawal method is substituting and tapering methadone or buprenorphine, ?-2 Adrenergic agents can ameliorate untreated symptoms or substitute for agonists if not available. Shortening withdrawal by precipitating it with narcotic antagonists has been studied, but the methods are plagued by safety issues or persisting symptoms. Neither the withdrawal agents nor the methods are associated with better long-term outcome, which appears mostly related to post-detoxification treatment. Excluding those with short-term habits, the best outcome occurs with long-term maintenance on methadone or buprenorphine accompanied by appropriate psychosocial interventions. Those with strong external motivation may do well on the antagonist naltrexone. Currently, optimum duration of maintenance on either is unclear. Better agents are needed to impact the brain changes related to addiction. PMID:18286804

Kleber, Herbert D.

2007-01-01

110

A comparison of buprenorphine taper outcomes between prescription opioid and heroin users  

PubMed Central

Objectives Dependence on prescription opioids (PO) is a growing problem. Although most research with buprenorphine has focused on heroin dependent populations, we hypothesize that individuals dependent on prescription opioids (PO) display characteristics that may predict different outcomes in treatment, particularly in short-term taper procedures in which comorbidities such as pain conditions may complicate taper. Methods This secondary data analysis examined differences in outcomes between PO users (n = 90) and heroin users (n = 426) following a buprenorphine taper. Data were collected in a multisite randomized clinical trial conducted by the National Drug Abuse Treatment Clinical Trials Network at 11 study sites across the United States. After a 4-week buprenorphine induction/stabilization phase, 516 opioid-dependent individuals were randomized into one of two taper lengths (7 vs. 28 days) to assess the association between taper length and outcome. The primary outcome was measured by urine drug test for opioids at the end of the taper period. Craving, withdrawal, and buprenorphine dose were also examined. Results After controlling for baseline demographic and drug use differences between the opioid use groups, results indicate that a higher percentage of the PO group (49%) provided an opioid free urine drug specimen at the end of taper compared to the heroin group (36%; ?2 (1) = 6.592, p < .010). Conclusion Short term taper is not recommended as a stand-alone treatment, however patients may taper from buprenorphine as part of a treatment plan. Despite greater co-morbidity, PO users appear to have favorable taper outcomes compared to heroin users. Further studies are required to examine longer term treatment outcomes. PMID:23222095

Nielsen, S; Hillhouse, M; Thomas, C; Hasson, A; Ling, W

2012-01-01

111

Comparison of the Efficacy of Buprenorphine and Clonidine in Detoxification of Opioid-Dependents  

PubMed Central

Background Since the number of drug users is increasing, applying a method of detoxification with fewer side effects during withdrawal from opioids and greater reliability seems to be necessary. In addition, without maintenance treatment, there will be limited success of treatment. This study aimed to compare success rates of detoxification with sublingual buprenorphine and clonidine and to evaluate addiction relapse in patients using naltrexone in a six-month follow-up. Methods This double-blind trial was carried out on opioid dependent patients in a psychiatric hospital in Kerman (Iran) during 2007-09. The subjects were randomly selected from individuals who had referred for detoxification. They were allocated to two groups to receive either clonidine (n = 21) or buprenorphine (n = 14). The success rates of the two methods were assessed at the end of the course and patients were discharged while prescribed with 25 mg daily use of naltrexone. They were followed up for six months and the continuous use of naltrexone and relapse of substance abuse were evaluated. Findings A total number of 35 patients entered the study. Success of detoxification with naltrexone was confirmed in all cases. One person (8.4%) in the clonidine group and no patient in the buprenorphine group had a clinical opiate withdrawal scale (COWS) score of more than 12 (P > 0.05). The mean levels of objective signs and subjective symptoms of withdrawal and the desire for drug abuse had significant reductions during detoxification period in both groups (P < 0.001). However, the difference in these variables between the two groups was not statistically significant (P > 0.05). Naltrexone was used for an average of one month in 43% and 64% of subjects in the clonidine and buprenorphine groups, respectively. In addition, 62% of patients in the clonidine group and 92.8% of subjects in the buprenorphine group received maintenance treatment. Nevertheless, the mean number of days staying in treatment was not significantly difference between the two groups (P > 0.05). Conclusion Buprenorphine is as effective as clonidine in controlling withdrawal symptoms. A greater percentage of patients detoxified by buprenorphine received maintenance treatment, but there was not a significant difference in relapse rates between the two methods. PMID:24494140

Ziaaddini, Hassan; Nasirian, Mansooreh; Nakhaee, Nouzar

2012-01-01

112

Benzodiazepines increase the reward effects of buprenorphine in a conditioned place preference test in the mouse.  

PubMed

Buprenorphine (BPN) is widely used as a substitution treatment for opioid addiction. Some cases of abuse and misuse, especially associated with various benzodiazepines (BZDs), have been described, and a previous study has shown that BZDs increase the sedative effect of BPN and decrease its anxiogenic properties. To investigate the reward effect that may lead to the abusive combination of BPN and BZD, we studied the influence of different doses of three BZDs extensively used with BPN by drug addicts on conditioned place preference behavior in mice. BPN (0.3, 1, 3 mg/kg) was injected subcutaneously into male mice alone or in combination with a BZD administered intraperitoneally: dipotassium clorazepate (CRZ; 1, 4, 16 mg/kg), diazepam (DAZ; 0.5, 1, 5 mg/kg), or bromazepam (BMZ; 0.5, 1, 3 mg/kg). Amphetamine (8 mg/kg) was used as a reference drug. Reward effects of BPN alone or in combination were measured in a conditioned place preference paradigm using an unbiased procedure. Our results showed that groups treated with BPN associated with different doses of diazepam and clorazepate, but not bromazepam, spent significantly more time in the drug-paired compartment compared to the group treated with BPN alone. Our study shows that joint consumption of diazepam and clorazepate, but not bromazepam, can increase the reward properties of BPN alone in mice. These results could help to explain the use of this type of drug combination in the drug addict population. PMID:24617653

Ma, Lin-Lin; Freret, Thomas; Lange, Mathilde; Bourgine, Joanna; Coquerel, Antoine; Lelong-Boulouard, Véronique

2014-12-01

113

Opioid detoxification using high doses of buprenorphine in 24 hours: A randomized, double blind, controlled clinical trial  

Microsoft Academic Search

In recent years, interest in shortening of opioid detoxification has increased with the rising demands to find more cost-effective approaches for treatment of opioid dependence. This study was designed to evaluate the efficacy of administration of high doses of buprenorphine during 24 h in the management of acute opioid withdrawal. A total of 40 treatment-seeking opioid dependents were admitted and

Seyed Mohammad Assadi; Mohsen Hafezi; Azarakhsh Mokri; Emran Mohammad Razzaghi; Padideh Ghaeli

2004-01-01

114

Effects of multimodal analgesia with LowDose buprenorphine and meloxicam on fecal glucocorticoid metabolites after surgery in New Zealand white rabbits (Oryctolagus cuniculus).  

PubMed

Despite the increasing use of rabbits as companion animals and models for biomedical research, rabbits have not been extensively studied to identify an efficacious postsurgical analgesic that does not cause systemic complications. The synergy of NSAID and systemic opioids is well-documented, and their combined use reduces the amount of either drug required for adequate analgesia. We measured fecal corticosterone metabolites (FCM) in rabbits after a minimally invasive vascular cut-down procedure. Rabbits received buprenorphine (0.03 mg/kg SC every 12 h for 3 d), meloxicam (0.2 mg/kg SC every 24 h for 3 d), buprenorphine-meloxicam (0.01 mg/kg-0.1 mg/kg SC every 24 h for 3 d), or a single dose of 0.5% bupivacaine (0.5 mL) infused locally at the incision site. By day 3 after surgery, buprenorphine, meloxicam, and bupivacaine groups showed elevated FCM levels, which continued to rise until day 7 and then gradually returned to baseline by day 28. In the buprenorphine-meloxicam group, FCM was relatively unchanged until day 3, when treatment was discontinued, and then began to rise. Rabbits in the buprenorphine-meloxicam group gained more weight over the 28-d study than did those in the other 3 treatment groups. This study shows that in rabbits low-dose buprenorphine administered with meloxicam effectively mitigates the FCM response that develops after surgery without the adverse effects associated with higher doses. PMID:24041213

Goldschlager, Gregg B; Gillespie, Virginia L; Palme, Rupert; Baxter, Mark G

2013-09-01

115

Effects of Multimodal Analgesia with Low-Dose Buprenorphine and Meloxicam on Fecal Glucocorticoid Metabolites after Surgery in New Zealand White Rabbits (Oryctolagus cuniculus)  

PubMed Central

Despite the increasing use of rabbits as companion animals and models for biomedical research, rabbits have not been extensively studied to identify an efficacious postsurgical analgesic that does not cause systemic complications. The synergy of NSAID and systemic opioids is well-documented, and their combined use reduces the amount of either drug required for adequate analgesia. We measured fecal corticosterone metabolites (FCM) in rabbits after a minimally invasive vascular cut-down procedure. Rabbits received buprenorphine (0.03 mg/kg SC every 12 h for 3 d), meloxicam (0.2 mg/kg SC every 24 h for 3 d), buprenorphine–meloxicam (0.01 mg/kg–0.1 mg/kg SC every 24 h for 3 d), or a single dose of 0.5% bupivacaine (0.5 mL) infused locally at the incision site. By day 3 after surgery, buprenorphine, meloxicam, and bupivacaine groups showed elevated FCM levels, which continued to rise until day 7 and then gradually returned to baseline by day 28. In the buprenorphine–meloxicam group, FCM was relatively unchanged until day 3, when treatment was discontinued, and then began to rise. Rabbits in the buprenorphine–meloxicam group gained more weight over the 28-d study than did those in the other 3 treatment groups. This study shows that in rabbits low-dose buprenorphine administered with meloxicam effectively mitigates the FCM response that develops after surgery without the adverse effects associated with higher doses. PMID:24041213

Goldschlager, Gregg B; Gillespie, Virginia L; Palme, Rupert; Baxter, Mark G

2013-01-01

116

Buprenorphine rescue from naltrexone-induced opioid withdrawal during relatively rapid detoxification from high-dose methadone: a novel approach.  

PubMed

This small series of case reports illustrates a significantly faster and well tolerated method for a relatively rapid detoxification from high-dose methadone as compared to traditional methadone detoxification regimens. After inducing a withdrawal state using oral naltrexone, the patients were quickly "rescued" with buprenorphine (a combination of buprenorphine/naloxone). By administering a medication that attenuates withdrawal symptoms, patients immediately began to feel better and were better able to invest themselves in the overall treatment. The patients were then able to taper off opioids in a matter of days with minimal discomfort. The average length of stay was seven days, and no patients left before completing the program. PMID:19727311

Urban, Vanessa; Sullivan, Rolly

2008-04-01

117

A non-rewarding, non-aversive buprenorphine/naltrexone combination attenuates drug-primed reinstatement to cocaine and morphine in rats in a conditioned place preference paradigm.  

PubMed

Concurrent use of cocaine and heroin is a major public health issue with no effective relapse prevention treatment currently available. To this purpose, a combination of buprenorphine and naltrexone, a mixed very-low efficacy mu-opioid receptor agonist/kappa-opioid receptor antagonist/nociceptin receptor agonist, was investigated. The tail-withdrawal and the conditioned place preference (CPP) assays in adult Sprague Dawley rats were used to show that naltrexone dose-dependently blocked the mu-opioid receptor agonism of buprenorphine. Furthermore, in the CPP assay, a combination of 0.3?mg/kg buprenorphine and 3.0?mg/kg naltrexone was aversive. A combination of 0.3?mg/kg buprenorphine and 1.0?mg/kg naltrexone was neither rewarding nor aversive, but still possessed mu-opioid receptor antagonist properties. In the CPP extinction and reinstatement method, a combination of 0.3?mg/kg buprenorphine and 1.0?mg/kg naltrexone completely blocked drug-primed reinstatement in cocaine-conditioned rats (conditioned with 3?mg/kg cocaine, drug prime was 3?mg/kg cocaine) and attenuated drug-primed reinstatement in morphine-conditioned rats (conditioned with 5?mg/kg morphine, drug prime was 1.25?mg/kg morphine). These data add to the growing evidence that a buprenorphine/naltrexone combination may be protective against relapse in a polydrug abuse situation. PMID:23240906

Cordery, Sarah F; Taverner, Alistair; Ridzwan, Irna E; Guy, Richard H; Delgado-Charro, M Begoña; Husbands, Stephen M; Bailey, Christopher P

2014-07-01

118

The eŒect of substitution patterns on phonological treatment outcomes  

Microsoft Academic Search

It has been suggested that phonological learning in children with articulation disorders is inuenced by the variability or consistency of substitutes used for sounds that are excluded from the inventory. This proposal was based on a post- hoc analysis of children's pre-treatment inventories and substitution patterns, as well as their generalization patterns at the termination of phonological interven- tion. In

KAREN FORREST; MARY ELBERT; DANIEL A. DINNSEN

119

[Severe distal ischemic syndrome after buprenorphine volunteer intra-arterial injection].  

PubMed

High dosage buprenorphine (HDB) is a sublingual maintenance treatment of opioid dependence which have proved its substantial Public Health results, but it is also known to be frequently abused and diverted, in particular for intravenous injection, with deleterious consequences. Intra-arterial use is more rarely reported with this substance, just like its complications, mainly ischemic, potentially necrotic, phenomena. We report here such a case, with a 30 years-old man suffering from severe ischemia of the thumb, the forefinger and the middle finger few hours after direct injection of a suspension of buprenorphine crushed tablets in right radial arteria. A treatment combining surgery (video-thoracoscopic thoracic sympathectomy) and medicines (heparin, iloprost and piribedil mesilate), permitted a semi-complete digital rehabilitation (only forefinger pulp necrosis persisted and required a distal amputation), and the patient was discharged after 2 weeks. PMID:22186079

Glaizal, Mathieu; Lucciardi, Joseph; Tichadou, Lucia; Spadari, Michel; Hayek-Lanthois, Maryvonne; Micallef, Joëlle; de Haro, Luc

2011-01-01

120

Comparison of Buprenorphine and Butorphanol Analgesia in the Eastern Red-Spotted Newt (Notophthalmus viridescens)  

PubMed Central

The experimental use of amphibian models in biomedical research increases yearly, but there is a paucity of reports concerning analgesic use in many of these species. In this study, buprenorphine given by intracoelomic injection and butorphanol added to the tank water were compared for analgesic effect in the eastern red-spotted newt after bilateral forelimb amputations. Newts undergoing anesthesia but not surgery and newts having surgery but not given analgesia postoperatively were used as control groups. Animals were tested for food consumption, spontaneous movement, response to tapping on the tank, response to being touched, and body posture. Both buprenorphine by intracoelomic injection and butorphanol in tank water significantly promoted resumption of normal behavior after bilateral surgical amputation of the forelimbs. The difference between analgesic treatment and no analgesic treatment was maintained until 72 h after surgery. PMID:19383214

2009-01-01

121

CASE REPORT OF SUBSTANCE DEPENDENCE WITH BUPRENORPHINE AND MEPHENTERMINE  

PubMed Central

Here is reported an unusual case of substance dependence with buprenorphine, mephentermine, & promethazine. This combination taken through intramuscular route produced a relatively mild & delayed abstinence syndrome with features viz. increased sleep and appetite in the patients. The neurophysiological basis for use of this rare form of additive (mephentermine) with buprenorphine is speculated. PMID:21455380

Mendhekar, D.N.; Sharma, Himanshu; Dali, J.S.

1999-01-01

122

Cocaine Use Reduction with Buprenorphine (CURB): Rationale, design, and methodology?  

PubMed Central

Background Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. Methods This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. Conclusions This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP. PMID:23159524

Mooney, Larissa J.; Nielsen, Suzanne; Saxon, Andrew; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Stablein, Don; McCormack, Jennifer; Lindblad, Robert; Ling, Walter

2013-01-01

123

Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?  

PubMed Central

Background The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months. Methods Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. Results No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. Conclusions Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too. PMID:21569624

2011-01-01

124

Change in symptoms of erectile dysfunction in depressed men initiating buprenorphine therapy?  

PubMed Central

Aims The aim of this study is to describe the change in erectile dysfunction (ED) symptoms in the first 12 weeks of outpatient buprenorphine therapy. Background Erectile dysfunction is highly prevalent in men who use illicit opioids when compared with the general population. To date, no study has examined ED symptoms over time in men initiating buprenorphine therapy for opioid dependence. Methods A randomized, double blind, placebo-controlled trial was conducted to determine whether escitalopram treatment of depressive symptoms begun 1 week prior to buprenorphine induction would improve treatment retention. Male patients completed the International Index of Erectile Function scale at baseline prior to induction and monthly thereafter. A score of 25 or less on the erectile function domain (range 1–30) is considered indicative of erectile dysfunction. Findings A total of 111 male subjects enrolled: mean age 38.5 (± 9.7) years, 80.1% non-Hispanic Caucasian; 67.3% reported heroin as their opioid of choice. Mean IIEF at baseline was 20.4 (± 10.5). At baseline, 44.1% of the entire cohort had erectile dysfunction; among those who identified as sexually active at baseline, 26.1% had ED. Baseline erectile function was inversely and significantly correlated with age (r = ?.27, p = .006), but was not associated significantly with race, heroin use, years of opioid use, smoking, or hazardous use of alcohol. Compared to baseline, mean erectile function was significantly improved (p = .001) at 3 months, and sexual desire (p = .002) improved significantly at both 2- and 3-month assessments. Conclusion Erectile dysfunction is highly prevalent in depressed males using illicit opioids. Men who remain in buprenorphine treatment for 3 months show improvement in erectile function and sexual desire. PMID:23891461

Cioe, Patricia A.; Anderson, Bradley J.; Stein, Michael D.

2014-01-01

125

A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers  

PubMed Central

IMPORTANCE Although abuse of prescription opioids (POs) is a significant public health problem, few experimental studies have investigated the treatment needs of this growing population. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTION 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. MAIN OUTCOMES AND MEASURES 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). RESULTS 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. CONCLUSIONS AND RELEVANCE 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. PMID:24153411

Sigmon, Stacey C.; Dunn, Kelly E.; Saulsgiver, Kathryn; Patrick, Mollie E.; Badger, Gary J.; Heil, Sarah H.; Brooklyn, John R.; Higgins, Stephen T.

2014-01-01

126

[Substitution as a possibility for the treatment of opiate dependent patients].  

PubMed

The treatment of patients who are dependent on opiates has definitely been including drug substitution besides withdrawal and weaning in the Swiss urban community ("Kanton") of Basel City since 1980. After a significant increase of treatments in 1987 in connection with the spread of HIV infections, more than 800 patients were presently receiving substitution treatment according to a descentralised schedule. The type of long-term treatment is illustrated by sociodemographic and treatment data of 500 substituted individuals who are mostly being looked after always by the same persons entrusted with caring for them. This represents a flexible, economically feasible and highly individual type of care and treatment that can help to reduce illegal drug consumption and hence the undesirable events associated with it in an urban district such as Basel city. PMID:8146246

von Bardeleben, U; Petitjean, S; Stohler, R; Natsch, C; Ladewig, D

1994-01-01

127

Saliva substitutes for the treatment of radiation-induced xerostomia—a review  

Microsoft Academic Search

Goal  The aim of this review is to summarize the in vitro and in vivo evidence on the performance of contemporary saliva substitutes\\u000a in the treatment of xerostomia and hyposalivation caused by radiation therapy for head and neck malignancies.\\u000a \\u000a \\u000a \\u000a Methods  A literature search was conducted during July to September 2008 in PubMed, using the query terms “saliva substitute”, “saliva\\u000a substitute and xerostomia”,

Sebastian Hahnel; Michael Behr; Gerhard Handel; Ralf Bürgers

2009-01-01

128

Effects of Buprenorphine, Meloxicam, and Flunixin Meglumine as Postoperative Analgesia in Mice  

PubMed Central

C57BL/6NCrl male mice (n = 60; age, 6 to 7 wk) underwent partial hepatectomy or no surgery and were given 1 of 3 analgesics pre- and postoperatively. Food and water consumption, body weight, running wheel activity, locomotor activity, and serum corticosterone concentrations were measured before and after surgery. Mice that were surgically manipulated weighed significantly less on days 1 through 3 after surgery than did mice not manipulated surgically. On the day of surgery, the surgery groups consumed significantly less feed (–1.5 ± 0.35 g) than did nonsurgery groups. There were no differences in water consumption on any day between surgery and nonsurgery groups or among the 3 analgesic groups. For running wheel activity, significant decreases in the surgery groups were seen at day 1 after surgery compared with baseline. Surgery groups that received buprenorphine and meloxicam returned to baseline activity levels on day 2 after surgery. Open-field testing revealed no significant differences in locomotor activity in any groups; however, posttreatment locomotor activity in the buprenorphine nonsurgery group was increased compared with baseline, and posttreatment locomotor activity in the flunixin meglumine surgery group was decreased compared with baseline. Serum corticosterone concentrations were within normal limits regardless of treatment in all groups. Comparison of the overall results indicated that meloxicam and buprenorphine, at the dose given, appear to be suitable postoperative analgesics for partial hepatectomy in mice. Flunixin meglumine at the given dosage (2.5 mg/kg) may not provide adequate analgesia for partial hepatectomy. PMID:21439211

Tubbs, Jacquelyn T; Kissling, Grace E; Travlos, Greg S; Goulding, David R; Clark, James A; King-Herbert, Angela P; Blankenship-Paris, Terry L

2011-01-01

129

Derivatives of C2-substituted indan-1-ol systems for the prophylaxis or treatment of obesity  

US Patent & Trademark Office Database

Derivatives of C2-substituted indan-1-ol compounds of formula I: ##STR1## its physiologically acceptable salts, and its physiologically functional derivatives for the prophylaxis or treatment of obesity are disclosed herein. Compositions comprising the same, methods for preparing the instant compounds, and methods for reducing weight in mammals and for the prophylaxis or treatment of obesity are also described.

2005-07-19

130

Use of oral buprenorphine ('buprenorphine jello') for postoperative analgesia in rats—a clinical trial  

Microsoft Academic Search

Summary Buprenorphine to.l, 0.2, 0.3 or 0.4 mg\\/kg) in a flavoured gelatin base was administered preoperatively to rats undergoing a flank laparotomy. A control group of animals underwent surgery and received only flavoured gelatin. Body weight loss was significantly greater in the group which received no analgesia than in any of the analgesic-treated groups (P < 0.01). Food consumption was

P. A. Flecknell; J. V. Roughan; R. Stewart

1999-01-01

131

The pharmacological treatment of opioid addiction—a clinical perspective  

Microsoft Academic Search

This article reviews the main pharmacotherapies that are currently being used to treat opioid addiction. Treatments include\\u000a detoxification using tapered methadone, buprenorphine, adrenergic agonists such as clonidine and lofexidine, and forms of\\u000a rapid detoxification. In opioid maintenance treatment (OMT), methadone is most widely used. OMT with buprenorphine, buprenorphine-naloxone\\u000a combination, or other opioid agonists is also discussed. The use of the

Philipp Lobmaier; Michael Gossop; Helge Waal; Jorgen Bramness

2010-01-01

132

A clinical trial of buprenorphine: Comparison with methadone in the detoxification of heroin addicts  

Microsoft Academic Search

The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts. Forty-five patients were randomized to receive either sublingual buprenorphine or oral methadone under double-dummy and double-blind conditions to study the pharmacology of buprenorphine in a 90-day detoxification protocol. The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by

Warren K Bickel; Maxine L Stitzer; George E Bigelow; Ira A Liebson; Donald R Jasinski; Rolley E Johnson

1988-01-01

133

ROAD TRAFFIC CRASHES AND PRESCRIBED METHADONE AND BUPRENORPHINE: A FRENCH REGISTRY-BASED CASE-  

E-print Network

ROAD TRAFFIC CRASHES AND PRESCRIBED METHADONE AND BUPRENORPHINE: A FRENCH REGISTRY-BASED CASE among patients under buprenorphine or methadone has not been subject to epidemiological investigation so traffic crash and the use of buprenorphine and methadone. Methods: Data from three French national

Boyer, Edmond

134

Shifts in opioid substitution treatment policy in Denmark from 2000-2011.  

PubMed

This article discusses how opioid substitution treatment policy has developed from 2000 to 2011 in Denmark. Empirically, it takes its point of departure in a stakeholder analysis including 17 qualitative interviews with stakeholders who have played important roles in this field. Analytically, it is inspired by Kingdon's concepts of agenda and policy window. Three major shifts are identified: a shift from psychosocial to medical thinking and practice, from an abstinence driven ideology to health care, and from perceptions of passive clients to user involvement. These shifts are discussed in relation to the legal context of substitute prescribing medicine. PMID:23952511

Frank, Vibeke Asmussen; Bjerge, Bagga; Houborg, Esben

2013-08-01

135

A successful switch from transdermal fentanyl to transdermal buprenorphine in a patient with neuropathic pain: a case report.  

PubMed

Buprenorphine is a frequently used opioid in the treatment of neuropathic pain component that is often present in patients with cancer. A case of a 41-year-old patient was depicted whose pain syndrome was associated with the chondrosarcoma growth originating from the sacral bone and numerous surgical interventions and radiotherapy. Improvement in analgesia and good toleration of therapy were observed after switching from transdermal fentanyl to transdermal buprenorphine while maintaining treatment with antidepressants and anticonvulsants. This case report indicates a possibility of a safe switch of transdermal opioids at home, which may provide benefits in terms of analgesia and adverse effects and in consequence have positive impact on the patients' quality of life. This is also accompanied by constant psychological, social, and spiritual support provided to the patient and family. PMID:23349342

Leppert, Wojciech

2014-02-01

136

Consumer Attitudes about Opioid Addiction Treatment: A focus group study in New York City  

PubMed Central

Objective To develop effective programs for people who are opioid-dependent and to impact the opioid epidemic in New York City, it is crucial that we monitor attitudes about opioid addiction treatments among opioid users who have experienced barriers to engagement and retention in addiction treatment. Design We conducted a qualitative study using focus groups. Methods We conducted six focus groups in three needle exchanges in New York City, which were audio recorded, transcribed, and systematically coded. We report on the main themes related to the study objectives. Participants Participants of each needle exchange who were opioid-dependent and had some knowledge of both methadone and buprenorphine were eligible. Results There were four main findings. Participants felt: (1) buprenorphine is an appropriate option only for those heroin users who are motivated to stop using; (2) they have less control over their addiction treatment with methadone than they would have with buprenorphine; (3) buprenorphine treatment is not accessible to many New York City residents who would benefit from this treatment; and (4) lack of access to buprenorphine treatment is the cause of treatment-related diversion. Conclusions Both methadone maintenance and buprenorphine treatment opportunities are necessary to address the diverse treatment needs of opioid-dependent people in New York City. However, the current medical model of buprenorphine treatment may be too restrictive for some opioid-dependent people, and may be contributing to the use of illicit buprenorphine. New models to deliver buprenorphine treatment may address these problems. PMID:23709320

Weiss, Linda; Egan, James E.; Lopez, Carolina; Favaro, Jamie; Cordero, Robert; Cunningham, Chinazo

2014-01-01

137

Effects of buprenorphine and an alternative nondrug reinforcer, alone and in combination on smoked cocaine self-administration in monkeys  

Microsoft Academic Search

The abuse of smoked cocaine base, also known as ‘crack’, continues to be a major public health problem and to date the success of pharmacological or behavioral interventions has been limited. The purpose of this study was to evaluate the efficacy of a behavioral (alternative reinforcer-saccharin) and pharmacological (0.01 mg\\/kg buprenorphine) treatment alone and in combination. Five adult male rhesus

Joshua S. Rodefer; Adande J. Mattox; Sherry S. Thompson; Marilyn E. Carroll

1997-01-01

138

Effects of d-Amphetamine and Buprenorphine Combinations on Speedball (Cocaine+Heroin) Self-Administration by Rhesus Monkeys  

Microsoft Academic Search

The simultaneous i.v. administration of heroin and cocaine, called a ‘speedball,’ is often reported clinically, and identification of effective pharmacotherapies is a continuing challenge. We hypothesized that treatment with combinations of a monoamine releaser d-amphetamine, and a mu partial agonist, buprenorphine, might reduce speedball self-administration by rhesus monkeys. Speedballs (0.01 mg\\/kg\\/inj cocaine+0.0032 mg\\/kg\\/inj heroin) and food (1 g banana-flavored pellets)

Nancy K Mello; S Stevens Negus

2007-01-01

139

Who prescribes buprenorphine for rural patients? The impact of specialty, location and practice type in Washington State?,??  

PubMed Central

We determined the specialty, geographic location, practice type and treatment capacity of waivered clinicians in Washington State. We utilized the April 2011 Drug Enforcement Agency roster of all waivered buprenorphine prescribers and cross-referenced the data with information from the American Medical Association and online resources. Waivered physicians, as compared to Washington State physicians overall, are more likely to be primary care providers, be older, less likely to be younger than 35years, and more likely to be female. Isolated rural areas have the lowest provider to population ratios. Ten counties lack either a buprenorphine provider or a methadone clinic. In rural areas, waivered physicians work predominately in federally-subsidized safety-net settings, which underscores the need for continued governmental support of primary care and mental health in these settings. PMID:22939650

Kvamme, Erik; Catlin, Mary; Banta-Green, Caleb; Roll, John; Rosenblatt, Roger

2013-01-01

140

Who prescribes buprenorphine for rural patients? The impact of specialty, location and practice type in Washington State.  

PubMed

We determined the specialty, geographic location, practice type and treatment capacity of waivered clinicians in Washington State. We utilized the April 2011 Drug Enforcement Agency roster of all waivered buprenorphine prescribers and cross-referenced the data with information from the American Medical Association and online resources. Waivered physicians, as compared to Washington State physicians overall, are more likely to be primary care providers, be older, less likely to be younger than 35 years, and more likely to be female. Isolated rural areas have the lowest provider to population ratios. Ten counties lack either a buprenorphine provider or a methadone clinic. In rural areas, waivered physicians work predominately in federally-subsidized safety-net settings, which underscores the need for continued governmental support of primary care and mental health in these settings. PMID:22939650

Kvamme, Erik; Catlin, Mary; Banta-Green, Caleb; Roll, John; Rosenblatt, Roger

2013-03-01

141

Buprenorphine Outpatient Outcomes Project: can Suboxone be a viable outpatient option for heroin addiction?  

PubMed Central

Background Opioid dependence treatment traditionally involves methadone clinics, for which dispensing schedules can be cumbersome. Buprenorphine, a partial agonist of the mu receptor and antagonist of the kappa receptor, is a potential outpatient alternative to methadone. Funded by a grant from the State of Maryland's Community Health Resources Commission (CHRC), the Buprenorphine Outpatient Outcomes Project (BOOP) evaluates the outcome of Suboxone (buprenorphine/naloxone) treatment on abstinence from heroin use, rates of emergency room visits and hospitalizations, legal issues, and quality of life. Methods Active heroin users were recruited between June 2007 and June 2010 and induction therapy with Suboxone was instituted during hospitalization. Once discharged, patients were followed as outpatients for maintenance treatment and counseling. Data were collected from electronic medical records, Maryland state legal records, and SF-36® Health Surveys regarding several parameters and patients were categorized according to duration of treatment with Suboxone into one of three groups: <1 month, 1–3 months, and >3 months. Results A total of 220 participants were included in the study. The age range of participants was 18–67 years with most being African American males. Eighty-three (38%) remained in the study for at least 1 month, with 37 of the 83 (45%) remaining in treatment for >3 months. Ten of the 37 (27%) never relapsed after their longest period of abstinence from heroin. During the first year after initiating treatment with Suboxone, hospitalization and emergency room visit rates for all 220 participants decreased by 45 and 23%, respectively, as compared to the year prior to starting treatment. The number of legal charges for drug possession decreased from 70 to 62. Anecdotally, the quality of life seemed to improve in those who were treated with Suboxone for longer periods of time and received regular counseling. Conclusion Overall, Suboxone is an effective treatment method for heroin addiction and is a viable outpatient therapy option. Individualized treatment plans and counseling must be implemented for maximum benefits to be seen. Retention of patients for a long duration of therapy was difficult, but for those who did remain, benefits were seen in overall health, abstinence from heroin use, cognition, and quality of life. PMID:24765257

Sittambalam, Charmian D.; Vij, Radhika; Ferguson, Robert P.

2014-01-01

142

Opiate substitution treatment and HIV transmission in people who inject drugs: systematic review and meta-analysis  

PubMed Central

Objective To quantify the effect of opiate substitution treatment in relation to HIV transmission among people who inject drugs. Design Systematic review and meta-analysis of prospective published and unpublished observational studies. Data sources Search of Medline, Embase, PsychINFO, and the Cochrane Library from the earliest year to 2011 without language restriction. Review methods We selected studies that directly assessed the impact of opiate substitution treatment in relation to incidence of HIV and studies that assessed incidence of HIV in people who inject drugs and that might have collected data regarding exposure to opiate substitution treatment but not have reported it. Authors of these studies were contacted. Data were extracted by two reviewers and pooled in a meta-analysis with a random effects model. Results Twelve published studies that examined the impact of opiate substitution treatment on HIV transmission met criteria for inclusion, and unpublished data were obtained from three additional studies. All included studies examined methadone maintenance treatment. Data from nine of these studies could be pooled, including 819 incident HIV infections over 23?608 person years of follow-up. Opiate substitution treatment was associated with a 54% reduction in risk of HIV infection among people who inject drugs (rate ratio 0.46, 95% confidence interval 0.32 to 0.67; P<0.001). There was evidence of heterogeneity between studies (I2=60%, ?2=20.12, P=0.010), which could not be explained by geographical region, site of recruitment, or the provision of incentives. There was weak evidence for greater benefit associated with longer duration of exposure to opiate substitution treatment. Conclusion Opiate substitution treatment provided as maintenance therapy is associated with a reduction in the risk of HIV infection among people who inject drugs. These findings, however, could reflect comparatively high levels of motivation to change behaviour and reduce injecting risk behaviour among people who inject drugs who are receiving opiate substitution treatment. PMID:23038795

2012-01-01

143

Clinical pharmacology of buprenorphine in healthy, lactating goats.  

PubMed

The pharmacokinetics and the effects of the opioid buprenorphine on behavior, cardiovascular parameters, plasma concentrations of cortisol and vasopressin were studied in the goat. After intravenous injection at a dosage of 0.02 mg/kg bw, the terminal half-life was 73.8+/-19.9 min (mean+/-SD), the apparent volume of distribution 5.22+/-1.01 L/kg, and total body clearance 79.1+/-18.5 mL/min/kg. After intramuscular administration of buprenorphine at the same dosage, bioavailability was complete and clearance was 54.7+/-16.6 mL/min/kg. Heart rate, blood pressure and concentrations of cortisol and vasopressin in plasma increased after drug administration. The goats became agitated and stopped ruminating. The effects were more pronounced the first time the animals received the drug, especially the influence on the hormone levels. The concentrations of cortisol and vasopressin in plasma remained unaffected after the second dose despite a wash-out period of 3-6 weeks. Buprenorphine may be an unsuitable drug in goats because of the profound inhibition of rumination and the agitation it causes. The short half-life of buprenorphine may limit its use if long-term analgesia is required but be advantageous if a short acting drug is desirable. PMID:17472657

Ingvast-Larsson, C; Svartberg, K; Hydbring-Sandberg, E; Bondesson, U; Olsson, K

2007-06-01

144

Treatment of chronic sternal fistulae following cardiac surgery with a bone substitute.  

PubMed

Chronic sternal infection is a relatively rare complication following cardiac surgery that can cause high morbidity and mortality and can require repeated surgical procedures, including sternal resection, to resolve. However, preserving sternal integrity is essential, particularly in children. A variety of conservative treatments for this complication of cardiac surgery have been reported. Here, we report three cases of children in whom a bone substitute containing tricalcium phosphate and hydroxyapatite was used to fill sternal defects. After extensive surgical debridement, this method yielded primary wound closure with good resolution, preventing the recurrence of sternal infection. PMID:24049817

Lamas, M J; Centella, T

2013-06-01

145

Calcium Sulfate as Bone Graft Substitute in the Treatment of Osseous Bone Defects, A Prospective Study  

PubMed Central

Background: Calcium sulfate belongs to synthetic ceramic group of bone graft substitutes having an osteoconductive property. Calcium sulfate is an easily available, economic bone graft substitute. It is a bio-inert material which over a period of weeks get resorbed and fibrovascular tissue takes its place which eventually allows neovascularisation and bone formation within the area. Use of calcium sulfate as a bone graft substitutes avoids the complications and morbidity associated with autograft like infection, second surgery, and finite amount of graft. Material and Methods: A total of 15 patients with benign bone lesions and chronic osteomyelitis were operated and the osseous defects were filled with calcium sulfate which was comprehensively sterilized. Patients were followed with serial radiographs at six week intervals. Calcium sulfate resorption and new bone formation was studied. Results: Thirteen cases out of 15 showed calcium sulphate resorption and new bone incorporation. Calcaium sulphate resorption occurred at an average of 14.5 weeks (range,13-18weeks) whereas new bone incorporation occurred at an average of 6months ( range,5-7months). Thirteen patients out of these 15 cases returned to full activities of daily living. One patient had pathological fracture at the osseous defect postoperatively. One patient with GCT of distal end of tibia had recurrence of tumor and had to undergo second surgery. Conclusion: Although autogenous bone graft is the gold standard for bone grafting, it has limitations like finite amount, additional surgery and donor site morbidity. Calcium sulphate is safe, efficient and easily available bone graft substitute in the treatment of osseous defects. Most common complication encountered was aseptic serous discharge. Functional results were favorable in most of the cases. PMID:24551676

Kumar C, Yashavantha; K B, Nalini; Menon, Jagdish; Patro, Dilip Kumar; B H, Banerji

2013-01-01

146

Barriers to Opioid Substitution Treatment Access, Entry and Retention: A Survey of Opioid Users, Patients in Treatment, and Treating and Non-Treating Physicians  

Microsoft Academic Search

Background\\/Aims: Although the number of patients in opioid substitution treatment (OST) in Germany has increased in recent years, many dependent opioid users remain out of treatment. Project IMPROVE assessed attitudes and beliefs regarding barriers to OST. Methods: Data were collected from opioid-dependent individuals (using self-complete questionnaires) currently in treatment (n = 200) or not in treatment (n = 200), and

Heino Stöver

2011-01-01

147

Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects  

Microsoft Academic Search

Previous reports have demonstrated greater antinociception following administration of a buprenorphine\\/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects

J. L. Hay; S. F. La Vincente; A. A. Somogyi; C. B. Chapleo; J. M. White

2011-01-01

148

A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network  

Microsoft Academic Search

AIMS: The clinical effectiveness of buprenorphine-naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network.\\u000aDESIGN: Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2 : 1 ratio favoring bup-nx,

Walter Ling; Leslie Amass; Steve Shoptaw; Jeffrey J. Annon; Maureen Hillhouse; Dean Babcock; Greg Brigham; Judy Harrer; Malcolm S. Reid; Joan A. Muir; Betty J. Buchan; Debbie Orr; George Woody; Jonathan Krejci; Douglas M. Ziedonis

2005-01-01

149

Interactions between Buprenorphine and Antiretrovirals: Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTI) Didanosine, Lamivudine, and Tenofovir  

PubMed Central

To improve outcomes among injection drug users with HIV and/or chronic hepatitis B, it is important to identify drug interactions between antiretroviral and opiate therapies. We report the results of a study designed to examine the interaction between buprenorphine and the nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine (ddI), lamivudine (3TC), and tenofovir (TDF). Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 27) participated in two 24-hour sessions to determine (1) pharmacokinetics of buprenorphine alone and (2) pharmacokinetics of both buprenorphine and either ddI, 3TC, or TDF. Among buprenorphine/naloxone-maintained study participants, no significant changes in buprenorphine pharmacokinetics were observed following ddI, 3TC, or TDF administration. Buprenorphine had no significant effect on NRTI concentrations. Concomitant use of buprenorphine with ddI, 3TC, or TDF results in neither a significant pharmacokinetic nor pharmacodynamic interaction. PMID:20132118

Baker, Jennifer; Rainey, Petrie M.; Moody, David E.; Morse, Gene D.; Ma, Qing; McCance-Katz, Elinore F.

2013-01-01

150

Clonazepam as Agonist Substitution Treatment for Benzodiazepine Dependence: A Case Report  

PubMed Central

Nowadays, the misuse of benzodiazepines (BZDs) is a cause for a serious concern among pharmacologically inexperienced patients, whether treated or untreated, that could lead to significant complications, including tolerance, dependence, and addiction. We present a case report in which an Italian patient affected by anxiety disorder and treated with BZDs presented a severe case of dependence on BZDs. We treated him according to an agonist substitution approach, switching from the abused BZD to a slow-onset, long-acting, high potency agonist (clonazepam), and looking at the methadone treatment model as paradigm. We decided to use clonazepam for its pharmacokinetic properties. The advantage of choosing a slow-onset, long-lasting BZD for the treatment of our patient was that it led us to a remarkable improvement in the clinical situation, including the cessation of craving, absence of withdrawal symptoms, reduced anxiety, improvements in social functioning, and a better cognition level. PMID:23424702

Maremmani, Angelo Giovanni Icro; Rovai, Luca; Rugani, Fabio; Bacciardi, Silvia; Pacini, Matteo; Dell'Osso, Liliana; Maremmani, Icro

2013-01-01

151

Predictors of Outcome for Short-Term Medically Supervised Opioid Withdrawal during a Randomized, Multi Center Trial of Buprenorphine-Naloxone and Clonidine in the NIDA Clinical Trials Network Drug and Alcohol Dependence  

PubMed Central

Few studies in community settings have evaluated predictors, mediators, and moderators of treatment success for medically supervised opioid withdrawal treatment. This report presents new findings about these factors from a study of 344 opioid dependent men and women prospectively randomized to either buprenorphine-naloxone or clonidine in an open-label 13-day medically-supervised withdrawal study. Subjects were either inpatient or outpatient in community treatment settings; however not randomized by treatment setting. Medication type (buprenorphine-naloxone versus clonidine) was the single best predictor of treatment retention and treatment success, regardless of treatment setting. Compared to the outpatient setting, the inpatient setting was associated with higher abstinence rates but similar retention rates when adjusting for medication type. Early opioid withdrawal severity mediated the relationship between medication type and treatment outcome with buprenorphine-naloxone being superior to clonidine at relieving early withdrawal symptoms. Inpatient subjects on clonidine with lower withdrawal scores at baseline did better than those with higher withdrawal scores; inpatient subjects receiving buprenorphine-naloxone did better with higher withdrawal scores at baseline than those with lower withdrawal scores. No relationship was found between treatment outcome and age, gender, race, education, employment, marital status, legal problems, baseline depression, or length/severity of drug use. Tobacco use was associated with worse opioid treatment outcomes. Severe baseline anxiety symptoms doubled treatment success. Medication type (buprenorphine-naloxone) was the most important predictor of positive outcome; however the paper also considers other clinical and policy implications of other results, including that inpatient setting predicted better outcomes and moderated medication outcomes. PMID:18805656

Ziedonis, Douglas M.; Amass, Leslie; Steinberg, Marc; Woody, George; Krejci, Jonathan; Annon, Jeffrey J.; Cohen, Allan J.; Waite-O’Brien, Nancy; Stine, Susan M.; McCarty, Dennis; Reid, Malcolm S.; Brown, Lawrence S.; Maslansky, Robert; Winhusen, Theresa; Babcock, Dean; Brigham, Greg; Muir, Joan; Orr, Deborah; Buchan, Betty J.; Horton, Terry; Ling, Walter

2009-01-01

152

Depression-Like Effect of Prenatal Buprenorphine Exposure in Rats  

PubMed Central

Studies indicate that perinatal opioid exposure produces a variety of short- and long-term neurobehavioral consequences. However, the precise modes of action are incompletely understood. Buprenorphine, a mixed agonist/antagonist at the opioid receptors, is currently being used in clinical trials for managing pregnant opioid addicts. This study provides evidence of depression-like consequence following prenatal exposure to supra-therapeutic dose of buprenorphine and sheds light on potential mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant Sprague-Dawley rats starting from gestation day 7 and lasting for 14 days. Results showed that pups at postnatal day 21 but not the dams had worse parameters of depression-like neurobehaviors using a forced swimming test and tail suspension test, independent of gender. Neurobehavioral changes were accompanied by elevation of oxidative stress, reduction of plasma levels of brain-derived neurotrophic factor (BDNF) and serotonin, and attenuation of tropomyosin-related kinase receptor type B (TrkB) phosphorylation, extracellular signal-regulated kinase (ERK) phosphorylation, protein kinase A activity, cAMP response element-binding protein (CREB) phosphorylation, and CREB DNA-binding activity. Since BDNF/serotonin and CREB signaling could orchestrate a positive feedback loop, our findings suggest that the induction of oxidative stress, reduction of BDNF and serotonin expression, and attenuation of CREB signaling induced by prenatal exposure to supra-therapeutic dose of buprenorphine provide evidence of potential mechanism for the development of depression-like neurobehavior. PMID:24367510

Hung, Chih-Jen; Wu, Chih-Cheng; Chen, Wen-Ying; Chang, Cheng-Yi; Kuan, Yu-Hsiang; Pan, Hung-Chuan; Liao, Su-Lan; Chen, Chun-Jung

2013-01-01

153

Use of buprenorphine in pregnancy: patient management and effects on the neonate  

Microsoft Academic Search

It is estimated that 55–94% of infants born to opioid-dependent mothers in US will show signs of opioid withdrawal. Buprenorphine has been reported to produce little or no autonomic signs or symptoms of opioid withdrawal following abrupt termination in adults. To date, there have been 21 published reports representing approximately 15 evaluable cohorts of infants exposed to buprenorphine in utero.

Rolley E. Johnson; Hendrée E. Jones; Gabriele Fischer

2003-01-01

154

Novelty seeking as a predictor of treatment retention for heroin dependent cocaine users  

Microsoft Academic Search

This study examined the relationship between novelty seeking between treatment retention and among heroin dependent cocaine users. Participants were treated with buprenorphine maintenance and contingency management. The Tridimensional Personality Questionnaire's (TPQ) Novelty Seeking scale was administered to 68 participants prior to buprenorphine induction. Demographics, mood and anxiety disorders, antisocial personality disorder, and substance use were also assessed. Variables with significant

Todd C Helmus; Karen K Downey; Cynthia L Arfken; Melinda J Henderson; Charles R Schuster

2001-01-01

155

Management of Acute Postpartum Pain in Patients Maintained on Methadone or Buprenorphine During Pregnancy  

PubMed Central

Background Empirical evidence is needed to guide adequate post-partum pain relief of methadone and buprenorphine stabilized patients. Objectives To first determine the adequacy of pain control using non-opioid and opioid medication in participants stabilized on buprenorphine or methadone before a vaginal delivery. Second, to compare the amount of non-opioid and opioid medication needed for adequate pain control for buprenorphine-and methadone-maintained patients during the immediate post-partum period. Methods Pain control adequacy and amount of non-opioid and opioid medication needed in buprenorphine- (n=8) and methadone-maintained (n=10) patients over the first five days post-partum were examined. Results Pain ratings and number of opioid medication doses decreased over time in both medication groups. While the buprenorphine and methadone groups began with similar mean daily ibuprofen (IB) doses, the buprenorphine group decreased its IB use, while the methadone group increased its IB use. Conclusions and Scientific Significance Patients treated daily with either buprenorphine or methadone can have adequate pain control post-partum with opioid medication and IB. Pain control is dependent on the opioid-agonist medication in use at delivery, and must be individualized. PMID:19462298

Jones, Hendree E.; O'Grady, Kevin; Dahne, Jennifer; Johnson, Rolley; Lemoine, Laetitia; Milio, Lorriane; Ordean, Alice; Selby, Peter

2010-01-01

156

Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects.  

PubMed

Previous reports have demonstrated greater antinociception following administration of a buprenorphine/naloxone combination compared to buprenorphine alone among healthy volunteers. The aim of the current investigation was to determine whether buprenorphine antinociception could be enhanced with the addition of ultra-low dose naltrexone, using a range of dose ratios. A repeated-measures, double-blind, cross-over trial was undertaken with 10 healthy participants. The effects of each buprenorphine:naltrexone ratio (100:1, 133:1, 166:1, and 200:1) on cold pressor tolerance time and respiration were compared to the effects of buprenorphine only. The 166:1 ratio was associated with significantly greater tolerance time to cold pressor pain than buprenorphine alone. Minimal respiratory depression and few adverse events were observed in all conditions. These findings suggest that, as previously described with naloxone, the addition of ultra-low dose naltrexone can enhance the antinociceptive effect of buprenorphine in humans. This potentiation is dose-ratio dependent and occurs without a concomitant increase in adverse effects. PMID:20728384

Hay, J L; La Vincente, S F; Somogyi, A A; Chapleo, C B; White, J M

2011-03-01

157

A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids.  

PubMed

We compared the short-term efficacy of a high-dose, 3 day regimen of buprenorphine to a standard 5-day course of clonidine in attenuating the signs and symptoms of the acute opioid abstinence syndrome during rapid detoxification from heroin in 25 men and women admitted to a closed inpatient research ward for this randomized, double-blind, parallel-group trial. Among the 18 completers, there were no significant differences between the buprenorphine and clonidine groups on five subjective and six physiological measures. However, clonidine lowered blood pressure and buprenorphine provided more effective early relief of withdrawal symptoms. PMID:7851278

Cheskin, L J; Fudala, P J; Johnson, R E

1994-10-01

158

Ability to Work and Employability of Patients in Opioid Substitution Treatment Programs in Slovenia  

PubMed Central

Aim To assess the ability to work and employability of individuals taking part in opioid substitution treatment programs (OSTP). Methods The study was composed of two surveys. In the first survey, 237 of 480 patients enrolled in OSTP responded to the questionnaire about their employment status, opinion about employment, and perception of assignments before and during OSTP. In the second survey, 66 of 100 employers responded to the questionnaire on the occurrence, perception, and management of addiction problems in their companies. Results Unemployment rate in individuals enrolled in OSTP was 43.5% and decreased during OSTP by 10.5% (P?=?0.027). Irregular use of OSTP medications was the most important factor for unemployment (odds ratio, 2.44; P?=?0.016). OSTP was highly effective in achieving a positive change in patients’ perception of different kinds of assignments previously perceived as beyond their abilities. Thus, perception of mentally demanding assignments (P?

Bilban, Marjan; Kastelic, Andrej; Zaletel-Kragelj, Lijana

2008-01-01

159

Buprenorphine diversion and misuse in outpatient practice.  

PubMed

: This case is an amalgamation of several real patients in office-based treatment for prescription opioid dependence synthesized into a single theoretical case. The case illustrates the various ways in which medication diversion and misuse may be encountered in clinical practice and therapeutic responses designed to maximize positive treatment outcomes. It is followed by discussions from several expert addiction medicine providers from 3 different countries, giving their perspectives on the salient aspects of this case. This case conference should be of particular interest to clinicians working with opioid-dependent patients in an outpatient setting. PMID:25221985

Lofwall, Michelle R; Martin, Judith; Tierney, Matt; Fatséas, Mélina; Auriacombe, Marc; Lintzeris, Nicholas

2014-01-01

160

Evaluation of the physical properties of water treatment residue for use as a soil substitute compared with decomposed granite soil  

Microsoft Academic Search

To evaluate water treatment residue (WTR) as a soil substitute material, its physical properties were investigated and compared with decomposed granite soil (DGS). For comparison purposes, relative gas diffusivity (D\\/D0), saturated hydraulic conductivity (Ks), water retention curve, porosity and readily available water were measured for both the WTR and the DGS. The measured D\\/D0, Ks, water retention ability and porosity

Seok-Gon Park; Mizue Ohashi; Kiyoshi Kurosawa; Young-Jin Kim; Hisashi Yahata

2010-01-01

161

Hospital morphine preparation for abstinence syndrome in newborns exposed to buprenorphine or methadone  

Microsoft Academic Search

Objective This study was undertaken to evaluate the adequacy of a hospital formulated oral morphine preparation for management of neonatal\\u000a abstinence syndrome (NAS) and to compare clinical features in infants exposed to methadone or buprenorphine in utero. Method Between October 1998 and October 2004 all infants born to mothers treated with buprenorphine or methadone during pregnancy\\u000a were enrolled into this prospective

Nathalie Colombini; Riad Elias; Muriel Busuttil; Myriam Dubuc; Marie-Ange Einaudi; Martine Bues-Charbit

2008-01-01

162

Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs.  

PubMed

The purpose of this study was to compare the pharmacokinetics of two highly protein-bound, lipophilic opioid drugs. Fentanyl (10 ?g/kg) and buprenorphine (20 ?g/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol-water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs. PMID:24684621

KuKanich, B; Allen, P

2014-12-01

163

Illicit Use of Buprenorphine in a Community Sample of Young Adult Non-Medical Users of Pharmaceutical Opioids  

PubMed Central

BACKGROUND There is growing evidence about illicit use of buprenorphine in the U.S. The study aims to: 1) identify prevalence and predictors of illicit buprenorphine use in a community sample of 396 young adult (18-23 years old) non-medical users of pharmaceutical opioids; 2) describe knowledge, attitudes and behaviors linked to illicit buprenorphine use as reported by a qualitative sub-sample (n=51). METHODS Participants were recruited using respondent-driven sampling. Qualitative interview participants were selected from the larger sample. The sample (n=396) was 54% male and 50% white; 7.8% reported lifetime illicit use of buprenorphine. RESULTS Logistic regression analysis results indicate that white ethnicity, intranasal inhalation of pharmaceutical opioids, symptoms of opioid dependence, and a greater number of pharmaceutical opioids used in lifetime were statistically significant predictors of illicit buprenorphine use. Qualitative interviews revealed that buprenorphine was more commonly used by more experienced users who were introduced to it by their “junkie friends.” Those who used buprenorphine to self-medicate withdrawal referred to it as a “miracle pill.” When used to get high, reported experiences ranged from “the best high ever” to “puking for days.” Participants reported using buprenorphine/naloxone orally or by intranasal inhalation. Injection of buprenorphine without naloxone was also reported. CONCLUSION Our findings suggest that illicit buprenorphine use is gaining ground primarily among whites and those who are more advanced in their drug use careers. Continued monitoring is needed to better understand evolving patterns and trends of illicit buprenorphine use. PMID:22036303

Daniulaityte, Raminta; Falck, Russel; Carlson, Robert G.

2011-01-01

164

Improving Adherence to HIV Quality of Care Indicators in Persons With Opioid Dependence: The Role of Buprenorphine  

PubMed Central

Background Opioid-dependent HIV-infected patients are less likely to receive HIV quality of care indicators (QIs) compared with nondependent patients. Buprenorphine/naloxone maintenance therapy (bup/nx) could affect the quality of HIV care for opioid-dependent patients. Methods We abstracted 16 QIs from medical records at nine HIV clinics 12 months before and after initiation of bup/nx versus other treatment for opioid dependence. Summary quality scores (number of QIs received/number eligible × 100) were calculated. We compared change in QIs and summary quality scores in patients receiving bup/nx versus other participants. Results One hundred ninety-four of 268 participants (72%) received bup/nx and 74 (28%) received other treatment. Mean summary quality scores increased over 12 months for participants receiving bup/nx (45.6% to 51.6%, P < 0.001) but not other treatment (48.6% to 47.8%, P = 0.788). Bup/nx participants experienced improvements in six of 16 HIV QIs versus three of 16 QIs in other participants. Improvements were mostly in preventive and monitoring care domains. In multivariable analysis, bup/nx was associated with improved summary quality score (? 8.55; 95% confidence interval, 2.06–15.0). Conclusions In this observational cohort study, HIV-infected patients with opioid dependence received approximately half of HIV QIs at baseline. Buprenorphine treatment was associated with improvement in HIV QIs at 12 months. Integration of bup/nx into HIV clinics may increase receipt of high-quality HIV care. Further research is required to assess the effect of improved quality of HIV care on clinical outcomes. PMID:21317600

Korthuis, P. Todd; Fiellin, David A.; Fu, Rongwei; Lum, Paula J.; Altice, Frederick L.; Sohler, Nancy; Tozzi, Mary J.; Asch, Steven M.; Botsko, Michael; Fishl, Margaret; Flanigan, Timothy P.; Boverman, Joshua; McCarty, Dennis

2011-01-01

165

Effect of low-level laser treatment of tissue-engineered skin substitutes: contraction of collagen lattices  

NASA Astrophysics Data System (ADS)

Fibroblast-populated collagen lattices (FPCL) are widely used in tissue-engineered artificial skin substitutes, but their main drawback is that interaction of fibroblasts and matrix causes contraction of the lattice, reducing it to about 20% of its original area. The effect of low-level laser treatment (LLLT) on the behavior of 3T3 fibroblasts seeded in collagen lattices containing 20% chondroitin-6-sulphate was investigated to determine whether LLLT could control the contraction of FPCL. A He-Ne laser was used at 632.8 nm to deliver a 5-mW continuous wave with fluences from 1 to 4 J/cm2. Laser treatment at 3 J/cm2 increased contraction of collagen lattices in the absence of cells but decreased contraction of cell seeded lattices over a 7-day period. The effect was energy dependent and was not observed at 1, 2, or 4 J/cm2. There was no alteration in fibroblast viability, morphology, or mitochondrial membrane potential after any laser treatments, but the distribution of actin fibers within the cells and collagen fibers in the matrices was disturbed at 3 J/cm2. These effects contribute to the decrease in contraction observed. LLLT may offer a means to control contraction of FPCL used as artificial skin substitutes.

Ho, Gideon; Barbenel, Joseph; Grant, M. Helen

2009-05-01

166

Effect of Rifampin and Nelfinavir on the Metabolism of Methadone and Buprenorphine in Primary Cultures of Human Hepatocytes  

E-print Network

Effect of Rifampin and Nelfinavir on the Metabolism of Methadone and Buprenorphine in Primary that primary cultures of human hepato- cytes could predict potential drug interactions with methadone, or nelfinavir before incubation with methadone or buprenorphine. Culture me- dia (0­60 min) was analyzed

Omiecinski, Curtis

167

Prenatal buprenorphine versus methadone exposure and neonatal outcomes: systematic review and meta-analysis.  

PubMed

Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio=0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio=0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices. PMID:25150272

Brogly, Susan B; Saia, Kelley A; Walley, Alexander Y; Du, Haomo M; Sebastiani, Paola

2014-10-01

168

Clinical efficacy of sustained-release buprenorphine with meloxicam for postoperative analgesia in beagle dogs undergoing ovariohysterectomy.  

PubMed

The goal of the current study was to compare the efficacy, adverse effects, and plasma buprenorphine concentrations of sustained-release buprenorphine (SRB) and buprenorphine after subcutaneous administration in dogs undergoing ovariohysterectomy. In a prospective, randomized, blinded design, 20 healthy adult female Beagle dogs underwent routine ovariohysterectomy and received multimodal analgesia consisting of meloxicam and one of two buprenorphine formulations. Dogs were randomly assigned to receive either SRB (0.2 mg/kg SC, once) or buprenorphine (0.02 mg/kg SC every 12 h for 3 d). Blinded observers assessed all dogs by using sedation scores, pain scores, temperature, HR, RR, and general wellbeing. Dogs were provided rescue analgesia with 0.02 mg/kg buprenorphine SC if the postoperative pain score exceeded a prede- termined threshold. Blood samples were collected, and mass spectrometry was used to determine plasma buprenorphine concentrations. Data were analyzed with a linear mixed model and Tukey-Kramer multiple comparison. Age, body weight, anesthetic duration, surgical duration, sevoflurane concentration, and cardiorespiratory variables did not differ significantly between groups. Dogs in both formulation groups had comparable postoperative sedation and pain scores. One dog from each formulation group had breakthrough pain requiring rescue analgesia. Plasma buprenorphine concentrations remained above a hypothesized therapeutic concentration of 0.6 ng/mL for 136.0 ± 11.3 and 10.67 ± 0.84 h for SRB and buprenorphine, respectively. Based on the results of this study, multimodal analgesic regimens consisting of meloxicam and either buprenorphine or SRB are equally efficacious in managing pain associated with an ovariohysterectomy and show comparable side effects. PMID:25255072

Nunamaker, Elizabeth A; Stolarik, Deanne F; Ma, Junli; Wilsey, Amanda S; Jenkins, Gary J; Medina, Chris L

2014-01-01

169

Sublingual buprenorphine for acute renal colic pain management: a double-blind, randomized controlled trial  

PubMed Central

Background The aim of this study was to compare the efficacy and safety of sublingual buprenorphine with intravenous morphine sulfate for acute renal colic in the emergency department. Methods In this double-dummy, randomized controlled trial, we enrolled patients aged 18 to 55 years who had a clinical diagnosis of acute renal colic. Patients received either 2 mg sublingual buprenorphine with an IV placebo, or 0.1 mg/kg IV morphine sulfate with a sublingual placebo. Subjects graded their pain with a standard 11-point numeric rating scale (NRS) before medication administration and 20 and 40 minutes after that. The need for rescue analgesia and occurrence of side effects were also recorded in the two groups. Results Of 69 patients analyzed, 37 had received buprenorphine, and 32 had taken morphine. Baseline characteristics were similar in both groups. NRS pain scores were reduced across time by administration of both buprenorphine (from 9.8 to 5.22 and then 2.30) and morphine (from 9.78 to 4.25 and then 1.8), significantly (P <0.0001). The two regimens did not differ significantly for pain reduction (P?=?0.260). Dizziness was more frequently reported by the buprenorphine group (62.1% versus 37.5%, P <0.05) but other adverse effects observed within 40 minutes were similar in the two groups. Conclusions Sublingual buprenorphine (2 mg) is as effective as morphine sulfate (0.1 mg/kg) in acute renal colic pain management. PMID:24386894

2014-01-01

170

Illicit use of methadone and buprenorphine among adolescents and young adults in Sweden  

PubMed Central

Background Illicit use of methadone and buprenorphine has been described as a growing problem in Sweden in recent years, and has been associated with an increased drug-related mortality. Critics claim that the substances have become popular among adolescents and that they function as a gateway to heroin use. The aim of this study is to investigate, firstly, the extent to which illicit use of methadone and buprenorphine occurs among adolescents and young adults in Sweden, and secondly, at what stage in a user’s drug career these substances tend to appear. Methods The study is based on surveys and structured interviews on drug use among various populations of young people, in addition to qualitative interviews with 86 informants who, in their professional capacity, encounter adolescents or young adults who are using illicit drugs. Results Illicit use of methadone and buprenorphine is rare among young people in Sweden. According to high school surveys, less than 0.1% have tried these substances. Among young drug users in general, few have tried the substances, and there is nothing to indicate that they act as gateway drugs. Among adolescents and young adults with severe drug problems, however, the illicit use of methadone and buprenorphine is more common (54% in a compulsory care sample). These substances normally enter the drug career late, and few use them as their main drug of choice. Other prescription drugs, like benzodiazepines and tramadol, are used by adolescents to a far greater extent. Diversion and illicit use of methadone and buprenorphine is not seen as a serious problem by the professionals interviewed. A general view is that the substances are mainly used by people with a heroin or polydrug addiction, often for “self-medication” purposes. However, several informants express concern that methadone and buprenorphine may cause fatalities among young drug users without an opioid tolerance. Conclusions Illicit use of methadone and buprenorphine among young drug users is not a widespread problem in Sweden. Harm-reduction measures should target drug users with more severe problems, among whom illicit use of methadone and buprenorphine is more common and pose a medical risk. Illicit use of other prescription drugs, which are less controlled and more widely used by young people, is an important issue for further research. PMID:24139199

2013-01-01

171

The use of buprenorphine as an analgesic after rodent embryo transfer.  

PubMed

Many researchers are reluctant to administer analgesia after rodent embryo transfer, primarily out of concern that analgesia will affect embryo implantation. According to the Animal Welfare Act and the Guide, however, embryo transfer constitutes major survival surgery and is likely to cause pain and distress despite its minimally invasive nature. The authors examined the effects of a single dose of the analgesic buprenorphine on mice that underwent embryo transfer. In mice treated with buprenorphine, the number of viable implanted embryos was typically equal to or greater than that in untreated mice. All mice seemed quiet, alert and active after surgery. PMID:18216800

Krueger, Karen L; Fujiwara, Yuko

2008-02-01

172

Buprederm™, a New Transdermal Delivery System of Buprenorphine: Pharmacokinetic, Efficacy and Skin Irritancy Studies  

Microsoft Academic Search

Purpose  The pharmacokinetics, analgesic efficacy, and irritancy potential of Buprederm™, a new transdermal delivery system of buprenorphine,\\u000a was evaluated.\\u000a \\u000a \\u000a \\u000a Methods  Single and multiple dose pharmacokinetic studies were conducted in mice and rabbits. The analgesic efficacy and skin irritation\\u000a potential were determined by tail flick and writhing tests in mice and by the Draize dermal scoring system in rabbits.\\u000a \\u000a \\u000a \\u000a Results  Fast absorption of buprenorphine

Dongwon Kim; Jindeog Song; Chang Hoon In; Seung-Wei Jeong; Sang Hun Lee; Bumchan Min; Dongho Lee; Sun-Ok Kim

2008-01-01

173

Buprenorphine versus methadone in pregnant opioid-dependent women: a prospective multicenter study  

Microsoft Academic Search

Patients and methods  In order to investigate the effects of exposure to buprenorphine compared with methadone during pregnancy, a prospective multicenter\\u000a study was conducted in collaboration with maternity hospitals, maintenance therapy centers, and general practitioners involved\\u000a in addiction care. Ninety pregnant women exposed to buprenorphine and 45 to metadone were selected for the study.\\u000a \\u000a \\u000a \\u000a \\u000a Results  During pregnancy, some women were exposed to

Isabelle Lacroix; Alain Berrebi; Daniel Garipuy; Laurent Schmitt; Yamina Hammou; Catherine Chaumerliac; Maryse Lapeyre-Mestre; Jean-Louis Montastruc; Christine Damase-Michel

174

Substituting the postproduction treatment for bulk-heterojunction solar cells using chemical additives  

Microsoft Academic Search

Postproduction treatment of poly (3-alkylthiophene) based bulk-heterojunction solar cells is an important and required procedure in order to fabricate organic solar cells with highest power conversion efficiencies. Postproduction treatment, by means of annealing solar cells at elevated temperatures during which an external voltage is simultaneously applied, is not very suitable for large scale production schemes due to the need for

Almantas Pivrikas; Philipp Stadler; Helmut Neugebauer; Niyazi Serdar Sariciftci

2008-01-01

175

Production and validation of model iron-tannate dyed textiles for use as historic textile substitutes in stabilisation treatment studies  

PubMed Central

Background For millennia, iron-tannate dyes have been used to colour ceremonial and domestic objects shades of black, grey, or brown. Surviving iron-tannate dyed objects are part of our cultural heritage but their existence is threatened by the dye itself which can accelerate oxidation and acid hydrolysis of the substrate. This causes many iron-tannate dyed textiles to discolour and decrease in tensile strength and flexibility at a faster rate than equivalent undyed textiles. The current lack of suitable stabilisation treatments means that many historic iron-tannate dyed objects are rapidly crumbling to dust with the knowledge and value they hold being lost forever. This paper describes the production, characterisation, and validation of model iron-tannate dyed textiles as substitutes for historic iron-tannate dyed textiles in the development of stabilisation treatments. Spectrophotometry, surface pH, tensile testing, SEM-EDX, and XRF have been used to characterise the model textiles. Results On application to textiles, the model dyes imparted mid to dark blue-grey colouration, an immediate tensile strength loss of the textiles and an increase in surface acidity. The dyes introduced significant quantities of iron into the textiles which was distributed in the exterior and interior of the cotton, abaca, and silk fibres but only in the exterior of the wool fibres. As seen with historic iron-tannate dyed objects, the dyed cotton, abaca, and silk textiles lost tensile strength faster and more significantly than undyed equivalents during accelerated thermal ageing and all of the dyed model textiles, most notably the cotton, discoloured more than the undyed equivalents on ageing. Conclusions The abaca, cotton, and silk model textiles are judged to be suitable for use as substitutes for cultural heritage materials in the testing of stabilisation treatments. PMID:22616934

2012-01-01

176

Structural barriers in the context of opiate substitution treatment in Germany - a survey among physicians in primary care  

PubMed Central

Background Opiate substitution treatment (OST) is the most widely used treatment for opioid dependence in Germany with substantial long-term benefits for the patient and for society. Due to lessened restrictive admission criteria, the number of registered OST patients in Germany has increased continuously in the recent years, whereas the number of physicians providing OST has remained constant. Previous data already indicated a deteriorating situation in the availability or quality of OST delivered and that structural barriers impede physicians in actively providing OST. The present survey among a sample of primary care physicians in Germany aimed to identify and assess potential structural barriers for the provision of health care in the context of OST. Methods An anonymous written questionnaire was sent out to a sample of 2,332 physicians across Germany providing OST. Physicians contacted were identified through databases of the Federal State Chambers of Physicians and/or of the Federal Associations of Statutory Health Insurance Physicians. Data obtained were analysed descriptively. Results The response rate was 25,5% and the majority of 596 physicians sampled viewed substantial problems in terms of the regulatory framework of OST care in the German context. Furthermore, financial remuneration, insufficient qualification, as well as inadequate interdisciplinary cooperation in the treatment of comorbidities of opiate substituted patients were regarded as problematic. The number of physicians providing OST in Germany is expected to substantially decrease in the near future. Conclusion Despite less restrictive admission criteria for OST in Germany, the legal regulation framework for OST is still a limiting factor through raising concerns on the provider and consumer side to be unable to adhere to the strict rules. To avoid future shortages in the provision of OST care on the system level in Germany, revisions to the legal framework seem to be necessary. In regards to adequate care for drug use-related infectious diseases and psychiatric comorbidities commonly found in opiate substituted patients, efforts are required to improve professional qualifications of physicians providing OST as well as respective interdisciplinary collaboration. PMID:23875627

2013-01-01

177

40 CFR 268.3 - Dilution prohibited as a substitute for treatment.  

...or unless the waste is a D003 reactive cyanide wastewater or nonwastewater. (c...after any bona fide treatment such as cyanide destruction prior to combustion, can...contains hazardous organic constituents or cyanide at levels exceeding the...

2014-07-01

178

Organic Seed-treatment as a Substitute for Chemical Seed-treatment to Control Common Bunt of Wheat  

Microsoft Academic Search

Common bunt of wheat, caused by Tilletia laevis and T. tritici, is a major seed and soil-borne disease in West Asia and North Africa. The use of resistant cultivars and chemical seed-treatments are the current control measures used to combat this disease. The aim of this study was to investigate alternative control measures to chemical seed-treatments that are environmentally friendly

Munzer El-Naimi; Hala Toubia-Rahme; Omar F. Mamluk

2000-01-01

179

Impacts of Substituting Aluminum-Based Coagulants in Drinking Water Treatment  

Microsoft Academic Search

Aluminum-based coagulants in drinking water treatment are widely used across Canada. According to the literature, the presence of aluminum in drinking water poses possible risks to humans. Preliminary studies investigating the use of alterna- tive coagulating agents such as iron-based coagulants, lanthanide salts and organic coagulants have already revealed that their implementation is possible, but require further studies concerning their

Patrick Niquette; Frédéric Monette; Abdelkrim Azzouz; Robert Hausler

2004-01-01

180

Prenatal exposure to methadone and buprenorphine: A review of the potential effects on cognitive development  

Microsoft Academic Search

The amount of opioid users receiving opioid maintenance therapy has increased significantly over the last few years. As a result, an increasing number of children are prenatally exposed to long-lasting opioids such as methadone and buprenorphine. This article reviews the literature on the cognitive development of children born to mothers in opioid maintenance therapy. Topics discussed are the effects of

Carolien Konijnenberg; Annika Melinder

2011-01-01

181

Perioperative Pain Management for Patients on Chronic Buprenorphine: A Case Report  

PubMed Central

Here we present a patient with a Type I Chiari malformation who was receiving buprenorphine for chronic pain who underwent two separate urogynecologic procedures for removal of vaginal mesh with two different pain management regimens. For the first procedure at an outside hospital, the patient’s usual dose of buprenorphine (8 mg sublingual every 8 hours) was continued up through her surgery and then a full opioid receptor agonist was used for postoperative pain management. The patient complained that this resulted in very poor pain control for her in the postoperative period. Prior to her second procedure, which was performed at our institution, buprenorphine was switched to a full opioid agonist (oral hydromorphone 4 mg every 4 to 6 hours, maximum 20 mg per day) for 5 days prior to surgery; postoperative pain was managed with full opioid receptor agonists. The patient again reported suboptimal pain control in spite of substantially increased doses of opioids. This case report highlights the difficulty of perioperative pain management for patients on chronic buprenorphine and emphasizes the need for additional investigation. PMID:24307971

Chern, Sy-Yeu S; Isserman, Rebecca; Chen, Linda; Ashburn, Michael; Liu, Renyu

2013-01-01

182

Managing Treatment Resistant Violent Adolescents: A Step Forward by Substituting Seclusion for Mechanical Restraint?  

Microsoft Academic Search

Despite a growing consensus that seclusion or restraint should never be used with children or adolescents, there are a few\\u000a patients who are resistant to treatment, and are persistently violent. The purpose of this study was to measure the efficacy\\u000a of installing a padded seclusion room to decrease the use of mechanical restraints, a potentially more emotionally traumatic\\u000a and dangerous

Thomas C. Larson; Brian B. Sheitman; John E. Kraus; James Mayo; LuAnn Leidy

2008-01-01

183

The effects of prenatal exposure to buprenorphine or methadone on infant visual evoked potentials.  

PubMed

This study compared the neurological development of 4 month old infants exposed to buprenorphine or methadone during pregnancy to that of a control group of non-exposed infants. Participants were 30 buprenorphine-maintained women, 22 methadone-maintained women and 33 non opioid-dependent controls, and their infants. Women were enrolled during pregnancy as part of an open-label non-randomised flexible-dosing longitudinal study. Groups were matched for maternal age, parity, gravida, and tobacco and alcohol use. Infant neurological development was assessed by measuring latency of pattern reversal visual evoked potentials (VEP). One-way between groups analyses of variance (ANOVA) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns (48' and 69' of retinal arc). Infants prenatally exposed to methadone had significantly prolonged latencies, compared with infants in the control group and infants prenatally exposed to buprenorphine, in response to checks of 48' and 69'. VEP latencies of infants prenatally exposed to buprenorphine did not differ significantly from controls for either check size. After adjustment for covariates, prenatal exposure to methadone remained a significant predictor of VEP response to checks of 48', but not 69'. Maternal self-reported used of marijuana during pregnancy made a significant unique contribution to the variance in P1 latencies for both check sizes. Data from this controlled, non-randomised study suggest that buprenorphine may confer an advantage over methadone as a maintenance drug during pregnancy in terms of infant neural development at 4 months of age. PMID:19751825

Whitham, Justine N; Spurrier, Nicola J; Sawyer, Michael G; Baghurst, Peter A; Taplin, John E; White, Jason M; Gordon, Andrea L

2010-01-01

184

Effects of subcutaneous methadone, morphine, buprenorphine or saline on thermal and pressure thresholds in cats.  

PubMed

This study compared pressure and thermal thresholds after administration of three opioids in eight cats. Pressure stimulation was performed via a bracelet taped around the forearm. Three ball-bearings were advanced against the forearm by inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was tested as previously reported using a heated probe held against the thorax [Dixon et al. (2002) Research in Veterinary Science, 72, 205]. After baseline recordings, each cat received subcutaneous methadone 0.2 mg/kg, morphine 0.2 mg/kg, buprenorphine 0.02 mg/kg or saline 0.3 mL in a four period cross-over study. Measurements were made at 15, 30, 45 min and 1, 2, 3, 4, 8, 12 and 24 h after the injection. Data were analysed by anova (P<0.05). There were no significant changes in thresholds after saline. Thermal threshold increased at 45 min after buprenorphine (maximum 2.8+/-3 degrees C), 1-3 h after methadone (maximum 3.4+/-1.9 degrees C) and 45 min to 1 h (maximum 3.4+/-2 degrees C) after morphine. Pressure threshold increased 30-45 min (maximum 238+/-206 mmHg) after buprenorphine, 45-60 min after methadone (maximum 255+/-232 mmHg) and 45-60 min and 3-6 h (maximum 255+/-232 mmHg) after morphine. Morphine provided the best analgesia, and methadone appears a promising alternative. Buprenorphines limited effect was probably related to the subcutaneous route of administration. Previously, buprenorphine has produced much greater effects when given by other routes. PMID:17083457

Steagall, P V M; Carnicelli, P; Taylor, P M; Luna, S P L; Dixon, M; Ferreira, T H

2006-12-01

185

Longitudinal missing data strategies for substance use clinical trials using generalized estimating equations: an example with a buprenorphine trial  

PubMed Central

Objective A review of substance use clinical trials indicates that sub-optimal methods are the most commonly used procedures to deal with longitudinal missing information. Methods Listwise deletion (i.e., using complete cases only), positive urine analysis (UA) imputation, and multiple imputation (MI) were used to evaluate the effect of baseline substance use and buprenorphine/naloxone tapering schedule (7 or 28 days) on the probability of a positive UA (UA+) across the 4-week treatment period. Results The listwise deletion generalized estimating equations (GEE) model demonstrated that those in the 28-day taper group were less likely to submit a UA+ for opioids during the treatment period (odds ratios (OR) = 0.57, 95% confidence interval (CI): 0.39–0.83), as did the positive UA imputation model (OR = 0.43, CI: 0.34–0.55). The MI model also demonstrated a similar effect of taper group (OR = 0.57, CI: 0.42–0.77), but the effect size was more similar to that of the listwise deletion model. Conclusions Future researchers may find utilization of the MI procedure in conjunction with the common method of GEE analysis as a helpful analytic approach when the missing at random assumption is justifiable. PMID:24014144

McPherson, Sterling; Barbosa-Leiker, Celestina; McDonell, Michael; Howell, Donelle; Roll, John

2013-01-01

186

Evaluation of drug-drug interaction between daclatasvir and methadone or buprenorphine/naloxone  

PubMed Central

Introduction Daclatasvir (DCV) is a potent hepatitis C virus (HCV) NS5A replication complex inhibitor with pangenotypic (1–6) activity in vitro. Methadone (MET) and buprenorphine (BUP) are opioid medications used to treat opioid addiction; patients on HCV therapy may require MET or BUP treatment. The effect of DCV on the pharmacokinetics (PK) of MET or BUP/naloxone (NLX) was assessed in subjects on stable MET or BUP. Materials and Methods An open-label, two-part study assessed the effect of steady-state oral administration of DCV on the PK of MET (Part 1, P1) or BUP/NAL (Part 2, P2). Safety/tolerability and pharmacodynamics (PD, opioid withdrawal scales/overdose assessment) were also assessed. Subjects (P1, N=14; P2, N=11) received daily single-dose oral MET (40–120mg) or BUP/NLX (8/2–24/6mg) based on their prescribed stable dose throughout, in addition to DCV (60mg QD) on Days 2–9. Serial PK sampling occurred predose and postdose till 24 hours on Day 1 (MET/BUP) and Day 10 (MET/BUP/DCV). Noncompartmental PK were derived. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for MET/BUP/norBUP Cmax and AUCTAU were derived from linear mixed effects models. Results Subjects were aged 19–39 years, mostly white (P1, 93%; P2, 100%) and male (P1, 71%; P2, 91%). All subjects completed the study. No clinically meaningful effect was demonstrated as the GMR and 90% CIs fell within the prespecified interval (P1, 0.7–1.4; P2, 0.5–2.0: see Table 1). DCV coadministration was well-tolerated: overall, six (43%) subjects had adverse events (AEs) (all mild and resolved without treatment). DCV had no clinically significant effect on the PD of MET or BUP/NLX. Conclusions Steady-state administration of DCV 60mg QD had no clinically meaningful effect on the PK of MET or BUP/NLX and was generally well-tolerated, suggesting that no dose adjustments will be required. PMID:25394132

Garimella, Tushar; Wang, Reena; Luo, Wen-Lin; Wastall, Philip; Kandoussi, Hamza; Demicco, Michael; Bruce, Douglas; Hwang, Carey; Bertz, Richard; Bifano, Marc

2014-01-01

187

Comparison of the analgesic effects of robenacoxib, buprenorphine and their combination in cats after ovariohysterectomy.  

PubMed

The aim of this study was to compare the postoperative analgesic effects of robenacoxib and buprenorphine alone or in combination, in cats after ovariohysterectomy. Thirty healthy cats were randomly assigned to receive buprenorphine (0.02 mg/kg, n=10; GB), robenacoxib (2mg/kg, n=10; GR) or their combination at the same dosages (n=10; GBR) SC. After 30 min cats were sedated with an IM administration of medetomidine (0.02 mg/kg) and ketamine (5mg/kg). General anaesthesia was induced with propofol and after intubation was maintained with isoflurane. Before premedication and at 1, 2, 3, 4, 6, 8, 12 and 24h after extubation, pain and sedation were assessed using a simple descriptive pain scale, ranging from 0 (no pain/no sedation) to 4 (intense pain/ deep sedation). If the pain score was ? 3, rescue analgesia was provided using buprenorphine (0.02 mg/kg) administered IM. Pain score was higher in GB at 2, 3, 4, 6 and 8h compared to baseline and compared to GBR at the same study times. Moreover, the pain score was also higher in GB compared to GR at 2, 3, 4 and 6h. Pain score was similar at all study times between GR and GBR. Sedation at 1 and 2h was higher than baseline values in all groups. Cats in GB received rescue analgesia more often than cats assigned to GR or GBR. Robenacoxib was an effective analgesic drug in cats up to 24h after ovariohysterectomy. The addition of buprenorphine did not provide any additional analgesic effects compared to robenacoxib alone. PMID:23434263

Staffieri, F; Centonze, P; Gigante, G; De Pietro, L; Crovace, A

2013-08-01

188

Postoperative analgesic effects of dexketoprofen, buprenorphine and tramadol in dogs undergoing ovariohysterectomy.  

PubMed

The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy. PMID:23562407

Morgaz, J; Navarrete, R; Muñoz-Rascón, P; Domínguez, J M; Fernández-Sarmiento, J A; Gómez-Villamandos, R J; Granados, M M

2013-08-01

189

Prospective multicenter observational study of 260 infants born to 259 opiate-dependent mothers on methadone or high-dose buprenophine substitution  

Microsoft Academic Search

Specialized prenatal care and substitution programs improve the perinatal prognoses of pregnant drug-abusers and their infants. Although methadone is well documented, little is known about high-dose buprenorphine (HDB). This prospective, multicenter (n=35) observational study included 259 women on maintenance during pregnancy: 39% on methadone and 61% on HDB. Major findings were: 46% of them received good prenatal care; 62% had

Claude Lejeune; Laurence Simmat-Durand; Laurent Gourarier; Sandrine Aubisson

2006-01-01

190

SURVIVAL OF BURNS INVOLVING 90% OF THE TOTAL BODY SURFACE AREA AFTER TREATMENT WITH AUTOLOGOUS ENGINEERED SKIN SUBSTITUTES  

Microsoft Academic Search

Rapid and effective closure of full-thickness burn wounds remains a limiting factor for survival after burns involving most of the total body surface area (TBSA). Hypothetically, engineered skin substitutes (ESS) consisting of autologous cultured keratinocytes and fibroblasts attached to collagen-based sponges may reduce requirements for donor skin, numbers of grafting procedures, and time of intensive care during hospitalization. To demonstrate

Steven Boyce; Peggy Simpson; Richard Kagan

191

Substitute Solutions.  

ERIC Educational Resources Information Center

In summer 1999, a group of Park City, Utah, school administrators, personnel directors, human-resource specialists, and substitute teacher coordinators brainstormed on improving the recruitment, training, and retention of substitute teachers. Providing effective preservice and on-the-job training and professional recognition are key suggestions.…

Jones, Kevin R.; Hawkins, Amber

2000-01-01

192

Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients  

PubMed Central

AIMS To compare the O- (CYP2D6 mediated) and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone and buprenorphine maintained CYP2D6 extensive metabolizer subjects. METHODS Nine methadone and seven buprenorphine maintained subjects received a single 100 mg dose of tramadol hydrochloride. Blood was collected at 4 h and assayed for tramadol, methadone, buprenorphine and norbuprenorphine (where appropriate) and all urine over 4 h was assayed for tramadol and its M1 and M2 metabolites. RESULTS The urinary metabolic ratio [median (range)] for O-demethylation (M1) was significantly lower (P= 0.0002, probability score 1.0) in the subjects taking methadone [0.071 (0.012–0.103)] compared with those taking buprenorphine [0.192 (0.108–0.392)], but there was no significant difference (P= 0.21, probability score 0.69) in N-demethylation (M2). The percentage of dose [median (range)] recovered as M1 was significantly lower in subjects taking methadone compared with buprenorphine (0.069 (0.044–0.093) and 0.126 (0.069–0.187), respectively, P= 0.04, probability score 0.19), M2 was significantly higher in subjects taking methadone compared with buprenorphine (0.048 (0.033–0.085) and 0.033 (0.014–0.049), respectively, P= 0.04, probability score 0.81). Tramadol was similar (0.901 (0.635–1.30) and 0.685 (0.347–1.04), respectively, P= 0.35, probability score 0.65). CONCLUSIONS Methadone inhibited the CYP2D6-mediated metabolism of tramadol to M1. Hence, as the degree of opioid analgesia is largely dependent on M1 formation, methadone maintenance patients may not receive adequate analgesia from oral tramadol. PMID:22369095

Coller, Janet K; Michalakas, Jennifer R; James, Heather M; Farquharson, Aaron L; Colvill, Joel; White, Jason M; Somogyi, Andrew A

2012-01-01

193

Skin Substitutes  

PubMed Central

In a relatively short timespan, a wealth of new skin substitutes made of synthetic and biologically derived materials have arisen for the purpose of wound healing of various etiologies. This review article focuses on providing an overview of skin substitutes including their indications, contraindications, benefits, and limitations. The result of this overview was an appreciation of the vast array of options available for clinicians, many of which did not exist a short time ago. Yet, despite the rapid expansion this field has undergone, no ideal skin substitute is currently available. More research in the field of skin substitutes and wound healing is required not only for the development of new products made of increasingly complex biomolecular material, but also to compare the existing skin substitutes. PMID:25371771

Howe, Nicole; Cohen, George

2014-01-01

194

Review of calciphylaxis and treatment of a severe case after kidney transplantation with iloprost in combination with hyperbaric oxygen and cultured autologous fibrin-based skin substitutes.  

PubMed

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare complication in patients with end-stage renal disease as well as in patients after renal transplantation. It should be suspected in patients with typical painful violaceous skin lesions on the extremities or on the trunk. Active multidisciplinary management approach, with intensive local wound care, is vital in these patients. Controlling parathyroid hormone, hyperbaric oxygenation, sodium thiosulphate, bisphosphonates, cinacalcet and skin grafting could be effective. In our report, we describe a case of CUA in a 43-year-old patient two years after kidney transplantation. Despite intensive standard treatment, his wounds progressed; therefore, we decided to use iloprost, in combination with hyperbaric oxygenation. The clean wounds were then covered with cultivated autologous skin cells to enhance wound epithelialization. Seven months after finishing iloprost and hyperbaric oxygen treatment and the first application of skin substitute, the wounds healed completely and remained healed during the four-yr follow-up period. We conclude that in patients with severe CUA-induced wounds, the combined treatment with iloprost, hyperbaric oxygen and autologous cultured fibrin-based skin substitutes can be effective. A combination of different treatment modalities is vital in patients with CUA. PMID:19712088

Alikadic, Nadja; Kovac, Damjan; Krasna, Metka; Lindic, Jelka; Sabovic, Miso; Tomazic, Janez; Jeras, Matjaz; Smrke, Dragica

2009-01-01

195

Allergic contact dermatitis from buprenorphine and oral tolerance to other opioid derivatives in three patients.  

PubMed

Transdermal buprenorphine (TDB) is a widely used analgesic for moderate pain. TDB is generally well tolerated, but both irritant and allergic contact dermatitis occur at patch application sites. Oral opioid tolerance in patients with allergic contact dermatitis to TDB remains controversial. Here, we describe 3 patients with allergic contact dermatitis to TDB who subsequently used oral opioid derivatives without adverse reactions. Thus, oral intolerance to opioid derivatives is not a rule in patients with allergic contact dermatitis to TDB, but the possibility should be taken into consideration. PMID:24280659

Huilaja, Laura; Riekki, Riitta; Immonen, Aila; Tasanen, Kaisa

2014-01-01

196

Transdermal buprenorphine for treating nociceptive and neuropathic pain: four case studies.  

PubMed

The use of opioids for treating neuropathic pain is controversial, and some studies have indicated that neuropathic pain may be relatively insensitive to typical mu-opioid analgesics such as morphine. However, it is becoming clear that different opioids produce analgesia by affecting different pain pathways. We present two cases of neuropathic pain and two cases of nociceptive pain with a significant neuropathic component that were treated with transdermal buprenorphine. In each case, sufficient pain relief was obtained and no problems were encountered in switching from prior analgesic therapy with larger doses of other opioids. PMID:15728068

Likar, Rudolf; Sittl, Reinhard

2005-03-01

197

A successful combined treatment with dermal substitutes and products of regenerative medicine in a patient affected by extravasation injury from hypertonic solution.  

PubMed

In neonatal intensive care units, extravasation is one of the most common injuries occurring in infants as a complication of infusion therapy. These very preterm infants have immature skin which is easily damaged. They often require a longer duration of intravenous therapy, and obtaining intravenous access can be difficult. An invasive treatment should be avoided, whenever possible, particularly for very immature infants. In our Special Operative Unit for ulcers and difficult-to-heal wounds, University of Rome, we successfully treated a premature neonate, who experienced extravasation of hypertonic fluid, using dermal substitutes and products of regenerative medicine. PMID:22210728

Onesti, Maria Giuseppina; Carella, Sara; Maruccia, Michele; Marchese, Cinzia; Fino, Pasquale; Scuderi, Nicolò

2012-01-01

198

Combination Interventions to Prevent HCV Transmission Among People Who Inject Drugs: Modeling the Impact of Antiviral Treatment, Needle and Syringe Programs, and Opiate Substitution Therapy  

PubMed Central

Background.?Interventions such as opiate substitution therapy (OST) and high-coverage needle and syringe programs (HCNSP) cannot substantially reduce hepatitis C virus (HCV) prevalence among people who inject drugs (PWID). HCV antiviral treatment may prevent onward transmission. We project the impact of combining OST, HCNSP, and antiviral treatment on HCV prevalence/incidence among PWID. Methods.?An HCV transmission model among PWID was used to project the combinations of OST, HCNSP, and antiviral treatment required to achieve different prevalence and incidence reductions within 10 years for 3 chronic prevalence scenarios and the impact of HCV treatment if only delivered through OST programs. Multivariate and univariate sensitivity analyses were performed. Results.?Large reductions (>45%) in HCV chronic prevalence over 10 years require HCV antiviral treatment. Scaling up OST and HCNSP substantially reduces the treatment rate required to achieve specific HCV prevalence reductions. If OST and HCNSP coverage were increased to 40% each (no coverage at baseline), then annually treating 10, 23, or 42 per 1000 PWID over 10 years would halve prevalence for 20%, 40%, or 60% baseline chronic HCV prevalences, respectively. Approximately 30% fewer treatments are necessary with new direct-acting antivirals. If coverage of OST and HCNSP is 50% at baseline, similar prevalence reductions require higher treatment rates for the same OST and HCNSP coverage. Conclusions.?Combining antiviral treatment with OST with HCNSP is critical for achieving substantial reductions (>50%) in HCV chronic prevalence over 10 years. Empirical studies are required on how best to scale up antiviral treatment and combine treatment with other interventions. PMID:23884064

Martin, Natasha K.; Hickman, Matthew; Hutchinson, Sharon J.; Goldberg, David J.; Vickerman, Peter

2013-01-01

199

Effects of Buprenorphine Maintenance Dose on ?-Opioid Receptor Availability, Plasma Concentrations, and Antagonist Blockade in Heroin-Dependent Volunteers  

Microsoft Academic Search

The clinical effectiveness of opioid maintenance for heroin dependence is believed to result from a medication's ability to decrease ?-opioid receptor (?OR) availability thereby replacing agonist effects, alleviating withdrawal symptoms and attenuating heroin effects. We empirically tested this hypothesis in five heroin-dependent volunteers who were successively maintained on 32, 16, 2, and 0 mg daily buprenorphine (BUP) tablet doses. We

Mark K Greenwald; Chris-Ellyn Johanson; David E Moody; James H Woods; Michael R Kilbourn; Robert A Koeppe; Charles R Schuster; Jon-Kar Zubieta

2003-01-01

200

The Influence of Hyperbaric Oxygen Treatment on the Healing of Experimental Defects Filled with Different Bone Graft Substitutes  

PubMed Central

To assess potential effects of hyperbaric oxygen (HBOT) on artificial bone grafts, ? - Tricalcium phosphate (?-TCP) and calcium phosphate coated bovine bone (CPCBB) substitutes were applied to standard bone defects in rat tibiae. The control defects were left empty. Half of the animals received 60 minutes of 2.4 atmosphere absolute (ATA) of HBOT. Rats were sacrificed at one, two and four weeks. Bone healing was assessed histologically and histomorphometrically using light microscopy. The periosteum over the bone defects was examined ultrastructurally. Cardiac blood was collected to determine the serum osteocalcin levels. The HBOT increased new bone formation in the unfilled controls and ?-TCP groups and significantly decreased cartilage matrix and fibrous tissue formations in all groups. Active osteoblasts and highly organized collagen fibrils were prominent in the periosteum of ?-TCP and control groups. Serum osteocalcin levels also increased with HBOT. The healing of defects filled with CPCBB was similar to the controls and it did not respond to HBOT. These findings suggested that the HBOT had beneficial effects on the healing of unfilled bone defects and those filled with ?-TCP bone substitute but not with CPCBB, indicating a material-specific influence pattern of HBOT. PMID:21326954

Sirin, Yigit; Olgac, Vakur; Dogru-Abbasoglu, Semra; Tapul, Leyla; Aktas, Samil; Soley, Sinan

2011-01-01

201

Understanding Attitudes Toward Use of Medication in Substance Abuse Treatment: A Multilevel Approach  

Microsoft Academic Search

Individual and organizational variables influence attitudes toward use of naltrexone, methadone, and buprenorphine for the treatment of alcohol and drug disorders. Previous research has not considered both sets of influences simultaneously. Hierarchical linear modeling tested the contribution of individual and organizational variables with data from the National Drug Abuse Treatment Clinical Trials Network treatment unit and workforce surveys (n =

John Fitzgerald; Dennis McCarty

2009-01-01

202

Assessing Need for Medication-Assisted Treatment for Opiate-Dependent Prison Inmates  

Microsoft Academic Search

Individuals with a history of heroin dependence are overrepresented in American correctional facilities and 75% of inmates with a drug use disorder do not receive treatment during incarceration or after release. Medication-assisted treatment (MAT) with opiate agonists, such as methadone or buprenorphine, constitute standard of care; to guide planning for an expansion of drug treatment services in correctional facilities, a

Carmen E. Albizu-García; José Noel Caraballo; Glorimar Caraballo-Correa; Adriana Hernández-Viver; Luis Román-Badenas

2011-01-01

203

Assessing Need for Medication-Assisted Treatment for Opiate-Dependent Prison Inmates  

Microsoft Academic Search

Individuals with a history of heroin dependence are overrepresented in American correctional facilities and 75% of inmates with a drug use disorder do not receive treatment during incarceration or after release. Medication-assisted treatment (MAT) with opiate agonists, such as methadone or buprenorphine, constitutes standard of care; to guide planning for an expansion of drug treatment services in correctional facilities, a

Carmen E. Albizu-García; José Noel Caraballo; Glorimar Caraballo-Correa; Adriana Hernández-Viver; Luis Román-Badenas

2012-01-01

204

Respiratory effects of buprenorphine/naloxone alone and in combination with diazepam in naive and tolerant rats.  

PubMed

Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. We investigated the plethysmography effects of BUP/NLX in comparison to BUP/solvent administered by intravenous route in naive and BUP-tolerant Sprague-Dawley rats, and in combination with diazepam (DZP) or its solvent. In naive rats, BUP/NLX in comparison to BUP significantly increased respiratory frequency (f, P<0.05) without altering minute volume (VE). In combination to DZP, BUP/NLX significantly increased expiratory time (P<0.01) and decreased f (P<0.01), tidal volume (VT, P<0.001), and VE (P<0.001) while BUP only decreased VT (P<0.5). In BUP-tolerant rats, no significant differences in respiratory effects were observed between BUP/NLX and BUP. In contrast, in combination to DZP, BUP/NLX did not significantly alter the plethysmography parameters, while BUP increased inspiratory time (P<0.001) and decreased f (P<0.01) and VE (P<0.001). In conclusion, differences in respiratory effects between BUP/NLX and BUP are only significant in combination with DZP, with increased depression in naive rats but reduced depression in BUP-tolerant rats. However, BUP/NLX benefits in humans remain to be determined. PMID:24769261

Cohier, Camille; Chevillard, Lucie; Risède, Patricia; Roussel, Olivier; Mégarbane, Bruno

2014-07-15

205

Combined effects of buprenorphine and a nondrug alternative reinforcer on IV cocaine self-administration in rats maintained under FR schedules  

Microsoft Academic Search

Although previous studies have shown that pharmacological agents, such as buprenorphine, and alternative nondrug reinforcers, such as money or sweetened solutions, reduce cocaine self-administration, few studies have examined the combined effects of these two approaches. The purpose of the present study was to evaluate the effects of the opioid partial agonist buprenorphine (0.1 mg\\/kg) and concurrent access to either water

Sandra D. Comer; Sylvie T. Lac; Cindy L. Wyvell; Marilyn E. Carroll

1996-01-01

206

Monoalphabetic Substitution  

NSDL National Science Digital Library

This applet, created by Kevin O'Bryant of the University of California - San Diego, illustrates the monoalphabetic substitution codebreaking process using a chi-squared process. The author explains how and why this encryption method is used. Overall, it is a wonderful example of how probability and statistics can be applied to real world situations.

O\\'Bryant, Kevin

2009-12-09

207

Buprenorphine detection in urine using liquid chromatography-high-resolution mass spectrometry: comparison with cloned enzyme donor immunoassay (ThermoFisher) and homogeneous enzyme immunoassay (immunalysis).  

PubMed

A sensitive liquid chromatographic-high-resolution mass spectrometric (LC-HR-MS) assay for buprenorphine and its urinary metabolites has been developed that requires minimal sample preparation. The results obtained have been compared with those given by (i) cloned enzyme donor immunoassay (CEDIA) and (ii) homogeneous enzyme immunoassay (HEIA) in the analysis of patient urines submitted for buprenorphine analysis. Centrifuged urine (100 µL) was diluted with internal standard solution (25 µL) + LC eluent (875 µL), and 50 µL of the prepared sample were analyzed (Accucore Phenyl-Hexyl column). MS detection was in alternating positive and negative mode using heated electrospray ionization (ThermoFisher Q Exactive). Intra- and inter-assay accuracy and precision were 104-128 and <11%, respectively, at 5 µg/L. Limits of detection were 1.3 µg/L (buprenorphine, norbuprenorphine and buprenorphine glucuronide) and 2.5 µg/L (norbuprenorphine glucuronide). Immunoassay sensitivity and selectivity were 97 and 100% (HEIA) and 99 and 84% (CEDIA), respectively, compared with LC-HR-MS. In 120 patient urines, norbuprenorphine glucuronide was easily the most abundant analyte except when adulteration with buprenorphine had occurred. The median immunoreactive buprenorphine species present (unhydrolysed urine) were 7.5 and 13% for HEIA and CEDIA, respectively. However, codeine, dihydrocodeine, morphine and morphine-3-glucuronide did not interfere in the HEIA assay. PMID:24925983

Belsey, Sarah L; Couchman, Lewis; Flanagan, Robert J

2014-09-01

208

Experiences from a Community Based Substance Use Treatment Centre in an Urban Resettlement Colony in India  

PubMed Central

Background. There are limited community based treatment services for drug dependence in India. Rural areas and urban resettlement colonies are in particular deficient in such services. Aims. The current study aimed at preliminary assessment of substance use disorder management services at a community based substance use treatment clinic in an urban resettlement colony. Methods. The study was carried out at community based substance use treatment centre in a resettlement colony in India. The records of the centre were chart reviewed. Results. A total of 754 patients were registered at the clinic during the study period. Heroin was the primary drug of abuse for 63% of the patients. The mean duration of follow-up for the patients with opioid and alcohol dependence was 13.47 (SD ± 10.37; range 0–39) months. A total of 220 patients of opioid dependence were prescribed substation or abstinence directed therapy. Buprenorphine (87), slow release oral morphine (SROM) (16), and dextropropoxyphene (98) were used for opioid substitution. Conclusion. It is possible to deliver substance use disorder treatment services in community setting. There is a need to develop area specific community based treatment services for substance abuse in socially disadvantaged populations such as urban resettlement colonies.

Balhara, Yatan Pal Singh; Ranjan, Rajeev; Dhawan, Anju; Yadav, Deepak

2014-01-01

209

Environmental assessment of nutrient recycling from biological pig slurry treatment--impact of fertilizer substitution and field emissions.  

PubMed

Pig slurry treatment is an important means in reducing nitrogen loads applied to farmland. Solid phase separation prior to biological treatment further allows for recovering phosphorus with the solid phase. The organic residues from the pig slurry treatment can be applied as organic fertilizers to farmland replacing mineral fertilizers. The environmental impacts of nutrient recycling from aerobic, biological pig slurry treatment were evaluated applying the life cycle assessment (LCA) methodology. LCA results revealed that direct field emissions from organic fertilizer application and the amount of avoided mineral fertilizers dominated the environmental impacts. A modified plant available nitrogen calculation (PAN) was introduced taking into account calculated nitrogen emissions from organic fertilizer application. Additionally, an equation for calculating the quantity of avoided mineral fertilizers based on the modified PAN calculation was proposed, which accounted for nitrogen emissions from mineral fertilizer application. PMID:24821206

Brockmann, Doris; Hanhoun, Mary; Négri, Ophélie; Hélias, Arnaud

2014-07-01

210

Use of mineralized collagen bone graft substitutes and dorsal locking plate in treatment of elder metaphyseal comminuted distal radius fracture  

NASA Astrophysics Data System (ADS)

Bone graft may be needed to fill bone defect in elderly patients with a metaphyseal comminuted distal radius fracture. In this retrospective, nonrandomized, single-surgeon study, we evaluated the clinical and radiologic outcomes of using both dorsal locking plates with or without augmentation with mineralized collagen (MC) bone graft for elderly patients with dorsally metaphyseal comminuted radius fractures. Patients in group 1 ( n = 12) were treated with dorsal locking plates with MC bone graft application into the metaphyseal bone defect, and those in group 2 ( n = 12) only with dorsal locking plates. Clinical and radiologic parameters were determined at three and 12 months after surgery. At final follow-up, no significant difference was noted between the 2 groups in terms of palmar tilt and radial inclination ( p = 0.80); however, ulnar variance increased significantly in the group 2 treated with dorsal locking plates without augmentation ( p < 0.05). Functionally, there was no significant difference between the groups. Our preliminary study suggests that combination of MC as bone-graft substitutes and dorsal locking plates may be a usefully alternative for elderly patients with metaphyseal comminuted distal radius fracture.

Liu, Ke-Bin; Huang, Kui; Teng, Yu; Qu, Yan-Zheng; Cui, Wei; Huang, Zhen-Fei; Sun, Ting-Fang; Guo, Xiao-Dong

2014-03-01

211

Pilot study of a social network intervention for heroin users in opiate substitution treatment: study protocol for a randomized controlled trial  

PubMed Central

Background Research indicates that 3% of people receiving opiate substitution treatment (OST) in the UK manage to achieve abstinence from all prescribed and illicit drugs within 3 years of commencing treatment, and there is concern that treatment services have become skilled at engaging people but not at helping them to enter a stage of recovery and drug abstinence. The National Treatment Agency for Substance Misuse recommends the involvement of families and wider social networks in supporting drug users’ psychological treatment, and this pilot randomized controlled trial aims to evaluate the impact of a social network-focused intervention for patients receiving OST. Methods and design In this two-site, early phase, randomized controlled trial, a total of 120 patients receiving OST will be recruited and randomized to receive one of three treatments: 1) Brief Social Behavior and Network Therapy (B-SBNT), 2) Personal Goal Setting (PGS) or 3) treatment as usual. Randomization will take place following baseline assessment. Participants allocated to receive B-SBNT or PGS will continue to receive the same treatment that is routinely provided by drug treatment services, plus four additional sessions of either intervention. Outcomes will be assessed at baseline, 3 and 12 months. The primary outcome will be assessment of illicit heroin use, measured by both urinary analysis and self-report. Secondary outcomes involve assessment of dependence, psychological symptoms, social satisfaction, motivation to change, quality of life and therapeutic engagement. Family members (n = 120) of patients involved in the trial will also be assessed to measure the level of symptoms, coping and the impact of the addiction problem on the family member at baseline, 3 and 12 months. Discussion This study will provide experimental data regarding the feasibility and efficacy of implementing a social network intervention within routine drug treatment services in the UK National Health Service. The study will explore the impact of the intervention on both patients receiving drug treatment and their family members. Trial registration Trial Registration Number: ISRCTN22608399 ISRCTN22608399 registration: 27/04/2012 Date of first randomisation: 14/08/2012 PMID:23958332

2013-01-01

212

Sensory Substitution  

NASA Astrophysics Data System (ADS)

The idea that the cutaneous surface may be employed as a substitute for the eyes and ears is by no means a modern notion. Although the sense of touch has long been considered as a surrogate for both the visual and auditory modalities, the focus of this chapter will be on the efforts to develop a tactile substitute for hearing, especially that of human speech. The visual system is our primary means of processing information about environmental space such as orientation, distance, direction and size. It is much less effective in making temporal discriminations. The auditory system is unparalleled in processing information that involves rapid sequences of temporal events, such as speech and music. The tactile sense is capable of processing both spatial and temporal information although not as effective in either domain as the eye or the ear.

Verrillo, Ronald T.

213

Explicit Substitutions  

Microsoft Academic Search

The ##-calculus is a re#nement of the #-calculus where substitutionsare manipulated explicitly. The ##-calculus provides a settingfor studying the theory of substitutions, with pleasant mathematicalproperties. It is also a useful bridge between the classical #-calculusand concrete implementations.#Digital Equipment Corporation, Systems Research Center.yEcole Normale Sup#erieure; part of this work was completed while at Digital EquipmentCorporation, Systems Research Center.z...

Martín Abadi; Luca Cardelli; Pierre-louis Curien; Jean-jacques Lévy

1991-01-01

214

Substitute Teachers  

NSDL National Science Digital Library

Our lives are ones of uncertainty and surprise, yin and yang existences. Some things we can control and others we are powerless to command, even with the best intentions. Teachers are not exempt from emergencies, jury duty, and illness. Luckily, most schools plan for such incidents by having willing substitutes on hand. Teachers need to follow the Scout's motto to "be prepared" and keep the classroom running smoothly and efficiently for students and subs.

Swango, C. J.; Steward, Sally B.

2003-01-01

215

A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network  

PubMed Central

Aims The clinical effectiveness of buprenorphine–naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network. Design Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2:1 ratio favoring bup-nx, to a 13-day detoxification using bup-nx or clonidine. Methods A total of 113 in-patients (77 bup-nx, 36 clonidine) and 231 out-patients (157 bup-nx, 74 clonidine) participated. Supportive interventions included appropriate ancillary medications and standard counseling procedures guided by a self-help handbook. The criterion for treatment success was defined as the proportion of participants in each condition who were both retained in the study for the entire duration and provided an opioid-free urine sample on the last day of clinic attendance. Secondary outcome measures included use of ancillary medications, number of side effects reported and withdrawal and craving ratings. Findings A total of 59 of the 77 (77%) in-patients assigned to the bup-nx condition achieved the treatment success criterion compared to eight of the 36 (22%) assigned to clonidine, whereas 46 of the 157 (29%) out-patients assigned to the bup-nx condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine. Conclusion The benefits of bup-nx for opioid detoxification are supported and illustrate important ways in which clinical research can be conducted in community treatment programs. PMID:16042639

Ling, Walter; Amass, Leslie; Shoptaw, Steve; Annon, Jeffrey J.; Hillhouse, Maureen; Babcock, Dean; Brigham, Greg; Harrer, Judy; Reid, Malcolm; Muir, Joan; Buchan, Betty; Orr, Debbie; Woody, George; Krejci, Jonathan; Ziedonis, Douglas; Group, the Buprenorphine Study Protocol

2005-01-01

216

Differential Involvement of P-Glycoprotein (ABCB1) in Permeability, Tissue Distribution, and Antinociceptive Activity of Methadone, Buprenorphine, and Diprenorphine: In Vitro and In Vivo Evaluation  

PubMed Central

Conclusions based on either in vitro or in vivo approach to evaluate the P-gp affinity status of opioids may be misleading. For example, in vitro studies indicated that fentanyl is a P-gp inhibitor while in vivo studies indicated that it is a P-gp substrate. Quite the opposite was evident for meperidine. The objective of this study was to evaluate the P-gp affinity status of methadone, buprenorphine and diprenorphine to predict P-gp-mediated drug-drug interactions and to determine a better candidate for management of opioid dependence. Two in vitro (P-gp ATPase and monolayer efflux) assays and two in vivo (tissue distribution and antinociceptive evaluation in mdr1a/b (?/?) mice) assays were used. Methadone stimulated the P-gp ATPase activity only at higher concentrations, while verapamil and GF120918 inhibited its efflux (p <0.05). The brain distribution and antinociceptive activity of methadone were enhanced (p <0.05) in P-gp knockout mice. Conversely, buprenorphine and diprenorphine were negative in all assays. P-gp can affect the PK/PD of methadone, but not buprenorphine or diprenorphine. Our report is in favor of buprenorphine over methadone for management of opioid dependence. Buprenorphine most likely is not a P-gp substrate and concerns regarding P-gp-mediated drug-drug interaction are not expected. PMID:19370547

HASSAN, HAZEM E.; MYERS, ALAN L.; COOP, ANDREW; EDDINGTON, NATALIE D.

2012-01-01

217

40 CFR 721.8780 - Substituted pyridine azo substituted phenyl.  

Code of Federal Regulations, 2010 CFR

... Substituted pyridine azo substituted phenyl. 721.8780 Section 721.8780 ...Substituted pyridine azo substituted phenyl. (a) Chemical substance and significant...as substituted pyridine azo substituted phenyl (PMNs P-96-767 and...

2010-07-01

218

Opioid Maintenance Treatment during Pregnancy: Occurrence and Severity of Neonatal Abstinence Syndrome  

Microsoft Academic Search

Background: Opioid maintenance treatment (OMT) is widely used to treat pregnant women with a history of opioid dependence. This study investigated whether maternal methadone\\/buprenorphine dose and nicotine use in pregnancy affects the occurrence and duration of neonatal abstinence syndrome (NAS) in the infant. Methods: Forty-one pregnant women from OMT programmes in Norway who gave birth between January 2005 and January

Brittelise Bakstad; Monica Sarfi; Gabrielle K. Welle-Strand; Edle Ravndal

2009-01-01

219

Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment  

PubMed Central

Background Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects. Method An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naïve to abacavir and non-nucleoside reverse transcriptase inhibitors. Results At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments. Conclusion In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment. PMID:15647105

Keiser, Philip H; Sension, Michael G; DeJesus, Edwin; Rodriguez, Allan; Olliffe, Jeffrey F; Williams, Vanessa C; Wakeford, John H; Snidow, Jerry W; Shachoy-Clark, Anne D; Fleming, Julie W; Pakes, Gary E; Hernandez, Jaime E

2005-01-01

220

Investigation of Cross-Species Translatability of Pharmacological MRI in Awake Nonhuman Primate - A Buprenorphine Challenge Study  

PubMed Central

Background Pharmacological MRI (phMRI) is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biological consequences of drug actions. In most preclinical studies, animals are anesthetized during image acquisition to minimize movement. However, it has been demonstrated anesthesia could attenuate basal neuronal activity, which can confound interpretation of drug-induced brain activation patterns. Significant efforts have been made to establish awake imaging in rodents and nonhuman primates (NHP). Whilst various platforms have been developed for imaging awake NHP, comparison and validation of phMRI data as translational biomarkers across species remain to be explored. Methodology We have established an awake NHP imaging model that encompasses comprehensive acclimation procedures with a dedicated animal restrainer. Using a cerebral blood volume (CBV)-based phMRI approach, we have determined differential responses of brain activation elicited by the systemic administration of buprenorphine (0.03 mg/kg i.v.), a partial µ-opioid receptor agonist, in the same animal under awake and anesthetized conditions. Additionally, region-of-interest analyses were performed to determine regional drug-induced CBV time-course data and corresponding area-under-curve (AUC) values from brain areas with high density of µ-opioid receptors. Principal Findings In awake NHPs, group-level analyses revealed buprenorphine significantly activated brain regions including, thalamus, striatum, frontal and cingulate cortices (paired t-test, versus saline vehicle, p<0.05, n?=?4). This observation is strikingly consistent with µ-opioid receptor distribution depicted by [6-O-[11C]methyl]buprenorphine ([11C]BPN) positron emission tomography imaging study in baboons. Furthermore, our findings are consistent with previous buprenorphine phMRI studies in humans and conscious rats which collectively demonstrate the cross-species translatability of awake imaging. Conversely, no significant change in activated brain regions was found in the same animals imaged under the anesthetized condition. Conclusions Our data highlight the utility and importance of awake NHP imaging as a translational imaging biomarker for drug research. PMID:25337714

Seah, Stephanie; Asad, Abu Bakar Ali; Baumgartner, Richard; Feng, Dai; Williams, Donald S.; Manigbas, Elaine; Beaver, John D.; Reese, Torsten; Henry, Brian; Evelhoch, Jeffrey L.; Chin, Chih-Liang

2014-01-01

221

Yohimbine Increases Opioid-Seeking Behavior in Heroin-Dependent, Buprenorphine-Maintained Individuals  

PubMed Central

Rationale In laboratory animals, the biological stressor yohimbine (?2-noradrenergic autoreceptor antagonist) promotes drug seeking. Human laboratory studies have demonstrated that psychological stressors can increase drug craving but not that stressors alter drug seeking. Objectives This clinical study tested whether yohimbine increases opioid seeking behavior. Methods Ten heroin-dependent, buprenorphine (8-mg/day) stabilized volunteers, sampled two doses of hydromorphone (12 and 24 mg IM in counterbalanced order, labeled Drug A [session 1] and Drug B [session 2]). During each of six later sessions (within-subject, double blind, randomized crossover design), volunteers could respond on a 12-trial choice progressive ratio task to earn units (1 or 2 mg) of the sampled hydromorphone dose (Drug A or B) vs. money ($2) following different oral yohimbine pretreatment doses (0, 16.2 and 32.4 mg). Results Behavioral economic demand intensity and peak responding (Omax) were significantly higher for hydromorphone 2-mg than 1-mg. Relative to placebo, yohimbine significantly increased hydromorphone demand inelasticity, more so for hydromorphone 1-mg units (Pmax = 909, 3647 and 3225 for placebo, 16.2 and 32.4 mg yohimbine doses, respectively) than hydromorphone 2-mg units (Pmax = 2656, 3193 and 3615, respectively). Yohimbine produced significant but clinically modest dose-dependent increases in blood pressure (systolic ?15 and diastolic ?10 mmHg) and opioid withdrawal symptoms, and decreased opioid agonist symptoms and elated mood. Conclusions These findings concur with preclinical data by demonstrating that yohimbine increases drug seeking; in this study, these effects occurred without clinically significant subjective distress or elevated craving, and partly depended on opioid unit dose. PMID:23161001

Greenwald, Mark K.; Lundahl, Leslie H.; Steinmiller, Caren L.

2012-01-01

222

Antinociceptive Effects of Sustained-Release Buprenorphine in a Model of Incisional Pain in Rats (Rattus norvegicus)  

PubMed Central

Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats. PMID:24602547

Chum, Helen H; Jampachairsri, Katechan; McKeon, Gabriel P; Yeomans, David C; Pacharinsak, Cholawat; Felt, Stephen A

2014-01-01

223

Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus).  

PubMed

Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats. PMID:24602547

Chum, Helen H; Jampachairsri, Katechan; McKeon, Gabriel P; Yeomans, David C; Pacharinsak, Cholawat; Felt, Stephen A

2014-03-01

224

Biologic and synthetic skin substitutes: An overview.  

PubMed

The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing. PMID:21321652

Halim, Ahmad Sukari; Khoo, Teng Lye; Mohd Yussof, Shah Jumaat

2010-09-01

225

Novel pharmacotherapeutic strategies for treatment of opioid-induced neonatal abstinence syndrome  

PubMed Central

Summary The non-medical use of prescription drugs, in general, and opioids, in particular, is a national epidemic, resulting in enormous addiction rates, healthcare expenditures, and overdose deaths. Prescription opioids are overly prescribed, illegally trafficked, and frequently abused, all of which have created a new opioid addiction pathway, adding to the number of opioid-dependent newborns requiring treatment for neonatal abstinence syndrome (NAS), and contributing to challenges in effective care in maternal and fetal/neonatal (M-F/N) medicine. The standard of care for illicit or prescription opioid dependence during pregnancy is opioid agonist (methadone or buprenorphine) substitution therapy, which are also frequently abused. The next generation of pharmacotherapies for the treatment of illicit or prescription opioid addiction in the M-F/N interactional dyad must take into consideration the interplay between genetic, epigenetic, and environmental factors. Addiction to illicit drugs during pregnancy presents unique challenges to effectively treat the mother, and the developing fetus and infant after delivery. New pharmacotherapies should be safe to the developing fetus, effective in treating the physical and psychological consequences of addiction in the mother, and reduce the incidence and severity of NAS in the infant after birth. More pharmacotherapeutic options should be available to the physician such that a more individualized rather than a one-drug/strategy-fits-all approach can be used. A myriad of new and exciting pharmacotherapeutic strategies for the treatment of opioid dependence and addiction are on the horizon. This review focuses on such three strategies: (i) pharmacotherapeutic targeting of the serotoninergic system; (ii) mixed opioid immunotherapeutics (vaccines); (iii) pharmacogenomics as a therapeutic strategy to insure personalized care. We review and discuss how these strategies may offer additional treatment modalities for the treatment of M-F/N during pregnancy and the treatment of the infant after birth. PMID:23059064

McLemore, Gabrielle L.; Lewis, Tamorah; Jones, Catherine H.; Gauda, Estelle B.

2014-01-01

226

Fabrication of an ultrasensitive impedimetric buprenorphine hydrochloride biosensor from computational and experimental angles.  

PubMed

For the first time, an ultrasensitive impedimetric buprenorphine hydrochloride (BN) biosensor based on immobilization of bovine serum albumin (BSA) onto multi-walled carbon nanotubes (MWCNTs)/glassy carbon electrode (BSA/MWCNTs/GCE) has been developed using initial characterization by computational methods and complementing them by experimental observations. Computational results showed that the BSA hydrophobically binds to MWCNTs which is energetically favorable and leads to spontaneous formation of the stable BSA/MWCNTs nanobiocomposite (bioconjugate). Computational results also showed that the interaction of BN with BSA is mainly driven by hydrophobic interactions. The interactions of BSA with MWCNTs and BN with BSA were also monitored by fluorescence and UV-vis spectroscopic techniques, and their results were consistent with the computational results. Morphology and electrochemical properties of the fabricated composite electrodes were examined by scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). Besides complementing the computational studies, experimental results showed that the addition of MWCNTs to the surface of the GCE greatly facilitated the electron transfer reactions, and also showed that the presence of BSA inhibits the interfacial electron transfer in some extent due to the non-conductive properties of BSA. On the other hand, the presence of BN may form an electroactive complex with BSA which accelerates the interfacial electron transfer and leads to obvious Faradaic impedance changes. The Faradaic impedance responses were linearly related to BN concentration between 5.0 nM and 72.0 nM and a limit of detection (LOD, 3S(b)/b) of 1.5 nM was achieved. Finally, the proposed biosensor was successfully applied to determination of BN in urine samples of both healthy and addict volunteers. The results were satisfactory and comparable to those obtained by applying the reference method based on high performance liquid chromatography-ultraviolet detection (HPLC-UV). It is expected that the distinctive features of BSA/MWCNTs nanobiocomposite would make it potentially advantageous for a broad range of biosensing, and clinical applications. PMID:24767442

Gholivand, Mohammad-Bagher; Jalalvand, Ali R; Goicoechea, Hector C; Skov, Thomas

2014-06-01

227

Introduction Explicit Substitutions  

E-print Network

for implementing proof assistants and programming languages. F.L.C. de Moura Matching via Explicit Substitutions are to be implemented in the level of the language itself. F.L.C. de Moura Matching via Explicit Substitutions #12 are to be implemented in the level of the language itself. Explicit substitutions provide an adequate framework, closer

Ayala-Rincón, Mauricio

228

Discovery of a new class of bicyclic substituted hydroxyphenylmethanones as 17?-hydroxysteroid dehydrogenase type 2 (17?-HSD2) inhibitors for the treatment of osteoporosis  

Microsoft Academic Search

E2 deficiency in elderly people has directly an effect on the skeleton and can lead to osteoporosis. As 17?-hydroxysteroid dehydrogenase type 2 (17?-HSD2) catalyses the conversion between active 17?-hydroxysteroid estradiol (E2) and testosterone (T) into their less active 17-ketosteroid and has been found in bones, 17?-HSD2 inhibitor may provide a new approach in the onset of osteoporosis. Bicyclic substituted hydroxyphenylmethanone

Marie Wetzel; Emanuele M. Gargano; Stefan Hinsberger; Sandrine Marchais-Oberwinkler; Rolf W. Hartmann

229

Second and ThirdOrder Matching via Explicit Substitutions  

E-print Network

in the language of the ##­calculus of explicit substitutions. This class includes all the problems originatedSecond­ and Third­Order Matching via Explicit Substitutions FL â?? AVIO LEONARDO CAVALCANTI DE MOURA the benefits of using explicit substitutions in the treatment of problems such as unification and matching

Ayala-Rincón, Mauricio

230

Second-and Third-Order Matching via Explicit Substitutions  

E-print Network

in the language of the -calculus of explicit substitutions. This class includes all the problems originatedSecond- and Third-Order Matching via Explicit Substitutions FL´AVIO LEONARDO CAVALCANTI DE MOURA the benefits of using explicit substitutions in the treatment of problems such as unification and matching

Ayala-Rincón, Mauricio

231

The multi-site prescription opioid addiction treatment study: 18-month outcomes.  

PubMed

Despite the high prevalence of prescription opioid dependence in the U.S., little is known about the course of this disorder and long-term response to treatment. We therefore examined 18-month post-randomization outcomes of participants in the Prescription Opioid Addiction Treatment Study, a multi-site, randomized controlled trial examining varying durations of buprenorphine-naloxone treatment and different intensities of counseling for prescription opioid dependence. Thus the current follow-up study provides a unique contribution to the field by reporting longer-term outcomes of a well-characterized population of treatment-seeking prescription opioid dependent patients. Participants from the treatment trial (N=252/653) completed an 18-month follow-up telephone assessment. Multivariable analyses examined associations between participant characteristics and key indicators of month-18 status: opioid abstinence, DSM-IV opioid dependence, and opioid agonist treatment. Overall, participants showed improvement from baseline to month 18: 49.6% were abstinent in the previous 30days, with only 16.3% opioid-dependent. Some participants, however, had initiated past-year heroin use (n=9) or opioid injection (n=17). Most participants (65.9%) engaged in substance use disorder treatment during the past year, most commonly opioid agonist therapy (48.8%). Of particular interest in this population, multivariable analysis showed that greater pain severity at baseline was associated with opioid dependence at 18months. In conclusion, although opioid use outcomes during the treatment trial were poor immediately following a buprenorphine-naloxone taper compared to those during 12weeks of buprenorphine-naloxone stabilization, opioid use outcomes at 18-month follow-up showed substantial improvement over baseline and were comparable to the rate of successful outcomes during buprenorphine-naloxone stabilization in the treatment trial. PMID:25189089

Potter, Jennifer Sharpe; Dreifuss, Jessica A; Marino, Elise N; Provost, Scott E; Dodd, Dorian R; Rice, Lindsay S; Fitzmaurice, Garrett M; Griffin, Margaret L; Weiss, Roger D

2015-01-01

232

Novelty seeking as a predictor of treatment retention for heroin dependent cocaine users.  

PubMed

This study examined the relationship between novelty seeking between treatment retention and among heroin dependent cocaine users. Participants were treated with buprenorphine maintenance and contingency management. The Tridimensional Personality Questionnaire's (TPQ) Novelty Seeking scale was administered to 68 participants prior to buprenorphine induction. Demographics, mood and anxiety disorders, antisocial personality disorder, and substance use were also assessed. Variables with significant relationships with overall retention were entered into a logistic regression analysis. In addition, using a survival analysis, all variables with significant relationships with time to drop-out were entered into a multivariate proportional hazards regression with time dependent covariates. Results demonstrated that although high novelty seekers, in comparison to low novelty seekers, were more likely to drop-out by the end of treatment, they had higher retention rates during the early phases of treatment. It is suggested that buprenorphine and contingency management were viewed by participants as novel treatment components and thus facilitated high novelty seekers' success early in treatment. If replicated, results suggest that inclusion of novel treatment components might facilitate retention among this at-risk group. PMID:11164693

Helmus, T C; Downey, K K; Arfken, C L; Henderson, M J; Schuster, C R

2001-02-01

233

Effect of psychotropic medication on the in vitro metabolism of buprenorphine in human cDNA-expressed cytochrome P450 enzymes  

Microsoft Academic Search

Objective  The aim of the present study was to estimate the drug interaction potential of psychtropic medication on buprenorphine (BUP) N-dealkylation using cDNA-expressed cytochrome P450 (CYP) enzymes.Methods  BUP was incubated with psychotropic drugs and cDNA-expressed CYP 3A4 and CYP 2C8 enzymes. Seven substances were screened for their inhibition potency. To check for a mechanism-based component in inhibition, all substances were tested with

Stephanie Bomsien; Rolf Aderjan; Rainer Mattern; Gisela Skopp

2006-01-01

234

Analgesia after feline ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia with buprenorphine or butorphanol, and carprofen or meloxicam: a prospective, randomised clinical trial  

Microsoft Academic Search

One hundred female cats undergoing routine ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia were included in a blinded, randomised, prospective clinical study to compare postoperative analgesia produced by four analgesic drug combinations given preoperatively (n = 25 per group). A secondary aim was to assess the effects in kittens and pregnant animals. Buprenorphine 180 µg\\/m2 or butorphanol 6 mg\\/m2 were given with either

Sally Polson; Polly M Taylor; David Yates

2012-01-01

235

Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects  

PubMed Central

AIMS To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects. METHODS Ten methadone- and eight buprenorphine-maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine-3- and -6-glucuronides and codeine-6-glucuronide. RESULTS The urinary metabolic ratio for O-demethylation was significantly higher (P = 0.0044) in the subjects taking methadone (mean ± SD, 2.8 ± 3.1) compared with those taking buprenorphine (0.60 ± 0.43), likewise for 6-glucuronide formation (0.31 ± 0.24 vs. 0.053 ± 0.027; P < 0.0002), but there was no significant difference (P = 0.36) in N-demethylation. Similar changes in plasma metabolic ratios were also found. In plasma, compared with those maintained on buprenorphine, the methadone-maintained subjects had increased codeine and norcodeine concentrations (P < 0.004), similar morphine (P = 0.72) and lower morphine-3- and -6- and codeine-6-glucuronide concentrations (P < 0.008). CONCLUSION Methadone is associated with inhibition of CYP2D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6. PMID:22092298

Gelston, Eloise A; Coller, Janet K; Lopatko, Olga V; James, Heather M; Schmidt, Helmut; White, Jason M; Somogyi, Andrew A

2012-01-01

236

Buprenorphine Dose Self-Selection: Effects of an Alternative Reinforcer, Behavioral Economic Analysis of Demand, and Examination of Subjective Drug Effects  

Microsoft Academic Search

Buprenorphine (BUP)-maintained patients were first exposed to various BUP doses and then chose between BUP doses and money. In the choice phase, they had 10 units exchangeable for units of BUP (constant at 3 mg\\/unit) or money (varied from $0.30 to $20\\/unit). They chose BUP exclusively (30 mg) when the money alternative was low. As available money increased, they selected

Nancy M. Petry; Warren K. Bickel

1999-01-01

237

Quantitative treatment of the effect of solvent on the electronic absorption and fluorescence spectra of substituted coumarins: Evaluation of the first excited singlet-state dipole moments.  

PubMed

The electronic absorption and fluorescence spectra of coumarin and 11 substituted coumarins were measured in several solvents (dioxane, ethyl ether, ethyl acetate, ethanol, dimethylformamide, acetonitrile, and dimethyl sulfoxide). Ground-state dipole moments were determined in dioxane at 298 K. The results were used to obtain the first excited singlet-state dipole moments of the coumarins under study by the solvatochromic shift method (Bakhshiev, Kawski-Chamma-Viallet, McRae, and Suppan correlations). Also, the ground- and the first excited singlet-state dipole moments were calculated using a combination of the PPP method (?-contribution) and the vector sum of the ?-bond and group moments (?-contribution). In general, the first excited singlet-state dipole moments of the coumarins are noticeably higher than the corresponding ground-state values, indicating a substantial redistribution of the?-electron densities resulting in a more polar excited state. There is a reasonably good agreement between the calculated and the experimental dipole moments. PMID:24226910

Aaron, J J; Buna, M; Parkanyi, C; Antonious, M S; Tine, A; Cisse, L

1995-12-01

238

A combined liquid three-phase micro-extraction and differential pulse voltammetric method for preconcentration and detection of ultra-trace amounts of buprenorphine using a modified pencil electrode.  

PubMed

A combination of polytetrafluorethylene membrane-based liquid three-phase micro-extraction and voltammetry was used for the micro-separation and determination of buprenorphine. Type of the organic solvent used, pH levels of the donor and acceptor phases, salt concentration, extraction time, stirring rate, and electrochemical parameters as the essential factors affecting the liquid three-phase micro-extraction of buprenorphine were investigated. Differential pulse voltammetry exhibited two linear dynamic ranges of 1.0-109.0 pmol L(-1) and 0.109 nmol L(-1)-0.11 µmol L(-1) of buprenorphine and the detection limit was found to be as low as 0.6 pmol L(-1) of buprenorphine. Also, the effects of a number of common substances potentially interfering with selectivity were studied. The results indicate that the proposed method is highly selective and sensitive for buprenorphine detection in real samples such as human urine and plasma of both drug-addict and non-addict human subjects. PMID:24148523

Ensafi, Ali A; Khoddami, Elaheh; Rezaei, B

2013-11-15

239

Determinants of generic drug substitution in Switzerland  

PubMed Central

Background Since generic drugs have the same therapeutic effect as the original formulation but at generally lower costs, their use should be more heavily promoted. However, a considerable number of barriers to their wider use have been observed in many countries. The present study examines the influence of patients, physicians and certain characteristics of the generics' market on generic substitution in Switzerland. Methods We used reimbursement claims' data submitted to a large health insurer by insured individuals living in one of Switzerland's three linguistic regions during 2003. All dispensed drugs studied here were substitutable. The outcome (use of a generic or not) was modelled by logistic regression, adjusted for patients' characteristics (gender, age, treatment complexity, substitution groups) and with several variables describing reimbursement incentives (deductible, co-payments) and the generics' market (prices, packaging, co-branded original, number of available generics, etc.). Results The overall generics' substitution rate for 173,212 dispensed prescriptions was 31%, though this varied considerably across cantons. Poor health status (older patients, complex treatments) was associated with lower generic use. Higher rates were associated with higher out-of-pocket costs, greater price differences between the original and the generic, and with the number of generics on the market, while reformulation and repackaging were associated with lower rates. The substitution rate was 13% lower among hospital physicians. The adoption of the prescribing practices of the canton with the highest substitution rate would increase substitution in other cantons to as much as 26%. Conclusions Patient health status explained a part of the reluctance to substitute an original formulation by a generic. Economic incentives were efficient, but with a moderate global effect. The huge interregional differences indicated that prescribing behaviours and beliefs are probably the main determinant of generic substitution. PMID:21269426

2011-01-01

240

Client and counselor attitudes toward the use of medications for treatment of opioid dependence.  

PubMed

Attitudes, perceived social norms, and intentions were assessed for 376 counselors and 1,083 clients from outpatient, methadone, and residential drug treatment programs regarding four medications used to treat opiate dependence: methadone, buprenorphine, clonidine, and ibogaine. Attitudes, social norms, and intentions to use varied by treatment modality. Methadone clients and counselors had more positive attitudes toward the use of methadone, whereas their counterparts in residential and outpatient settings had neutral or negative assessments. Across modalities, attitudes, perceived social norms, and intentions toward the use of buprenorphine were relatively neutral. Assessments of clonidine and ibogaine were negative for clients and counselors in all settings. Social normative influences were dominant across settings and medications in determining counselor and client intentions to use medications, suggesting that perceptions about beliefs of peers may play a critical role in use of medications to treat opiate dependence. PMID:17306729

Rieckmann, Traci; Daley, Marilyn; Fuller, Bret E; Thomas, Cindy P; McCarty, Dennis

2007-03-01

241

1,3-Dialkyl-substituted tetrahydropyrimido[1,2-f]purine-2,4-diones as multiple target drugs for the potential treatment of neurodegenerative diseases.  

PubMed

Adenosine receptors and monoamine oxidases are drug targets for neurodegenerative diseases such as Parkinson's and Alzheimer's disease. In the present study we prepared a library of 55 mostly novel tetrahydropyrimido[2,1-f]purinediones with various substituents in the 1- and 3-position (1,3-dimethyl, 1,3-diethyl, 1,3-dipropyl, 1-methyl-3-propargyl) and broad variation in the 9-position. A synthetic strategy to obtain 3-propargyl-substituted tetrahydropyrimido[2,1-f]purinedione derivatives was developed. The new compounds were evaluated for their interaction with all four adenosine receptor subtypes and for their ability to inhibit monoamine oxidases (MAO). Introduction of mono- or di-chloro-substituted phenyl, benzyl or phenethyl residues at N9 of the 1,3-dimethyl series led to the discovery of a novel class of potent MAO-B inhibitors, the most potent compound being 9-(3,4-dichlorobenzyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)-dione (21g, IC(50) human MAO-B: 0.0629 ?M), which displayed high selectivity versus the other investigated targets. Potent dually active A1/A2A adenosine receptor antagonists were identified, for example, 9-benzyl-1-methyl-3-propargyl-6,7,8,9-tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)dione (19f, Ki, human receptors, A1: 0.249 ?M, A2A: 0.253 ?M). Several compounds showed triple-target inhibition, the best compound being 9-(2-methoxybenzyl)-1-methyl-3-(prop-2-ynyl)-6,7,8,9-tetrahydro pyrimido [1,2-f]purine-2,4(1H,3H)-dione (19g, Ki A1: 0.605 ?M, Ki A2A: 0.417 ?M, IC(50) MAO-B: 1.80 ?M). Compounds inhibiting several different targets involved in neurodegeneration may exhibit additive or even synergistic effects in vivo. PMID:24139167

Koch, Pierre; Akkari, Rhalid; Brunschweiger, Andreas; Borrmann, Thomas; Schlenk, Miriam; Küppers, Petra; Köse, Meryem; Radjainia, Hamid; Hockemeyer, Jörg; Drabczy?ska, Anna; Kie?-Kononowicz, Katarzyna; Müller, Christa E

2013-12-01

242

Execution of control among 'non-compliant', imprisoned individuals in opioid maintenance treatment.  

PubMed

Strict control routines of prescribed opiate intake in opioid maintenance treatment, OMT, are used to reduce the risk of diversion and non-prescribed methadone and buprenorphine use. While maintaining a focus on aspects of control, this article explores motivations for and practices of methadone and buprenorphine use, both inside and outside of prison and among imprisoned individuals in OMT. The participants in this qualitative study were subjected to tight external control regimes in their opioid maintenance schemes in prison, as they were prior to imprisonment due to varying degrees of 'non-compliance'. We nevertheless found them to exhibit a considerable amount of self-control, self-regulation and/or self-initiation of external control. Among the participants, a ceaseless surveillance of processes associated with methadone and buprenorphine use throughout diverse situations, relations and contexts was encountered. We conclude that, in opioid maintenance treatment, some individuals might know what particular configurations of internal and external control they need in order to achieve their own treatment goals. The drug users' capacities for execution of control, as well as their delegations of control to others, may be seen as resources throughout the course of treatment. PMID:24594221

Havnes, Ingrid Amalia; Clausen, Thomas; Middelthon, Anne-Lise

2014-05-01

243

40 CFR 721.981 - Substituted naphtholoazo-substituted naphthalenyl-substituted azonaphthol chromium complex.  

Code of Federal Regulations, 2010 CFR

...naphthalenyl-substituted azonaphthol chromium complex. 721.981 Section 721...naphthalenyl-substituted azonaphthol chromium complex. (a) Chemical substance...naphthalenyl-substituted azonaphthol chromium complex (PMN P-93-1631) is...

2010-07-01

244

Determination of buprenorphine by differential pulse voltammetry on carbon paste electrode using SDS as an enhancement factor.  

PubMed

In the present study, a facile electrochemical approach is proposed for the determination of buprenorphine (BPR) in the presence of sodium dodecyl sulfate (SDS). SDS was applied for amplification of oxidation signal. Carbon paste electrode (CPE) used as working electrode and cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) were carried out in phosphate buffer solution (pH3.0). Under optimal experimental conditions, the oxidation current increased with the addition of BPR in the sample and two dynamic ranges obtained from 4.00 nM to 0.126 ?M and from 0.126 to 0.317 ?M by DPV and exhibited a low detection limit (LOD) of 1.33 nM (S/N=3). This offered method has been used for the determination of BPR in the real samples and has validated with the recovery test for BPR spiked urine samples. The result demonstrated that this method is a simple, sensitive, rapid, low-cost, and stable method for BPR detection. PMID:25063147

Behpour, Mohsen; Valipour, Akram; Keshavarz, Mahin

2014-09-01

245

An Attempted Substitute Study of Total Skin Electron Therapy Technique by Using Helical Photon Tomotherapy with Helical Irradiation of the Total Skin Treatment: A Phantom Result  

PubMed Central

An anthropomorphic phantom was used to investigate a treatment technique and analyze the dose distributions for helical irradiation of the total skin (HITS) by helical tomotherapy (HT). Hypothetical bolus of thicknesses of 0, 10, and 15?mm was added around the phantom body to account for the dose homogeneity and setup uncertainty. A central core structure was assigned as a “complete block” to force the dose tangential delivery. HITS technique with prescribed dose (Dp) of 36?Gy in 36 fractions was generated. The radiochromic EBT2 films were used for the dose measurements. The target region with 95.0% of the Dp received by more than 95% of the PTV was obtained. The calculated mean doses for the organs at risk (OARs) were 4.69, 3.10, 3.20, and 2.94?Gy for the lung, heart, liver, and kidneys, respectively. The measurement doses on a phantom surface for a plan with 10?mm hypothetical bolus and bolus thicknesses of 0, 1, 2, and 3?mm are 89.5%, 111.4%, 116.9%, and 117.7% of Dp, respectively. HITS can provide an accurate and uniform treatment dose in the skin with limited doses to OARs and is safe to replace a total skin electron beam regimen. PMID:23984313

Lin, Chi-Ta; Tien, Hui-Ju; Yeh, Hsin-Pei

2013-01-01

246

The substitutability of reinforcers  

PubMed Central

Substitutability is a construct borrowed from microeconomics that describes a continuum of possible interactions among the reinforcers in a given situation. Highly substitutable reinforcers, which occupy one end of the continuum, are readily traded for each other due to their functional similarity. Complementary reinforcers, at the other end of the continuum, tend to be consumed jointly in fairly rigid proportion, and therefore cannot be traded for one another except to achieve that proportion. At the center of the continuum are reinforcers that are independent with respect to each other; consumption of one has no influence on consumption of another. Psychological research and analyses in terms of substitutability employ standard operant conditioning paradigms in which humans and nonhumans choose between alternative reinforcers. The range of reinforcer interactions found in these studies is more readily accommodated and predicted when behavior-analytic models of choice consider issues of substitutability. New insights are gained into such areas as eating and drinking, electrical brain stimulation, temporal separation of choice alternatives, behavior therapy, drug use, and addictions. Moreover, the generalized matching law (Baum, 1974) gains greater explanatory power and comprehensiveness when measures of substitutability are included. PMID:16812696

Green, Leonard; Freed, Debra E.

1993-01-01

247

40 CFR 721.9545 - Substituted phenyl azo substituted sulfocarbopolycle, sodium salt.  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false Substituted phenyl azo substituted sulfocarbopolycle, sodium...Substances § 721.9545 Substituted phenyl azo substituted sulfocarbopolycle, sodium...identified generically as a substituted phenyl azo substituted...

2010-07-01

248

2011 Media Reports of Buprenorphine Diversion and Misuse U n i v e r s i t y o f M a r y l a n d , C o l l e g e P a r k  

E-print Network

/prison, Buprenorphine smuggled into prison & street diversion/trafficking trafficking ("Suboxone Succeeds in Aiding/prison Suboxone smuggled into state prison ("Ex-Caseworker Fined $4,500 for Giving Pills, Porn to Inmate," Portland Press Herald) 6/7/11 PA jail/prison Inmate had Suboxone smuggled into federal prison ("Federal

Milchberg, Howard

249

Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry  

PubMed Central

A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3?-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1–1,000 ng/patch, except EME 5–1,000 ng/patch. Intra-, inter-day and total imprecision were <10.1%CV, analytical recovery 87.2–107.7%, extraction efficiency 35.3– 160.9%, and process efficiency 25.5–91.7%. Ion suppression was detected for EME (?63.3%) and EDDP (?60.4%), and enhancement for NBUP (42.6%). Deuterated internal standards compensated for these effects. No carryover was detected, and all analytes were stable for 24 h at 22 °C, 72 h at 4 °C, and after three freeze/thaw cycles. The method was applied to weekly sweat patches from an opioid-dependent BUP-maintained pregnant woman; 75.0% of sweat patches were positive for BUP, 93.8% for cocaine, 37.5% for opiates, 6.3% for methadone and all for tobacco biomarkers. This method permits a fast and simultaneous quantification of 14 drugs and metabolites in sweat patches, with good selectivity and sensitivity. PMID:21125263

Concheiro, Marta; Shakleya, Diaa M.

2013-01-01

250

Evaluation of tribromoethanol, tribromoethanol-buprenorphine and ketamine-xylazine combinations for anaesthesia in Sprague-Dawley rats undergoing ovariectomy.  

PubMed

Effect of premedication with buprenorphine (BP) on efficacy and safety of tribromoethanol (TBE) - induced anaesthesia was evaluated and compared with anaesthesia induced by ketamine (K) and xylazine (X) combination in rats undergoing ovariectomy. Fifteen Sprague -Dawley rats (mean weight 246.5 ± 13.1g) were randomly divided into three groups. Group (TBE) received tribromoethanol solution (250mg/kg). Group (TBE+BP) was premedicated with BP (0.02mg/kg) and 30 minutes later with TBE (250mg/kg). Group KX was anaesthetized with mixture of K (43.5mg/kg) and X (6.5mg/kg). All injections were administered intraperitoneally. Anaesthetic parameters determined were onset of anaesthesia (OAN), duration of antinociception (DAN), duration of sleep (DSP) and recovery time (RCT). Rectal temperatures (RT) and respiratory rates (RR) were recorded immediately after loss of righting reflex and at ten minute interval up to 90 minute. In addition, rats were monitored for adverse signs up to one week after ovariectomy. Anaesthetic indices were compared using Student's t-test, while RR and RT were compared using analysis of variance (ANOVA). Two rats in TBE group and one rat in TBE+BP group died three days after ovariectomy. Duration of antinociception (DAN) was significantly (P= 0.0015) longer in TBE than in KX anaesthetized rats but not significantly (P= 0.054) different between TBE and TBE-BP anaesthetized rats. Also, DSP was significantly (P=0.001) longer in KX anaesthetized rats than TBE- anaesthetized rats. Similarly, the DSP was significantly (P= 0.013) shorter in TBE group than TBE+ BP anaesthetized rats. Both RR and RT decreased significantly (P< 0.0001) with time following anaesthesia in all groups. It was concluded that KX mixture provided better anaesthesia than TBE and TBE+BP, and addition of BP to TBE did not have any beneficial effect. PMID:23955407

Ajadi, R Adetola; Gazal, N Ayoolamide; Teketay, D Helmie; Gazal, S Oladele

2013-01-01

251

A comparison of buprenorphine induction strategies: patient-centered home-based inductions versus standard-of-care office-based inductions  

PubMed Central

Although novel buprenorphine induction strategies are emerging, they have been inadequately studied. To examine our newly developed patient-centered home-based inductions, we conducted a subgroup analysis of 79 opioid-dependent individuals who had buprenorphine inductions at an urban community health center. Participants chose their induction strategy; standard-of-care office-based inductions were physician-driven, with multiple assessments, and observed, and patient-centered home-based inductions emphasized patient self-management and included a “kit” for induction at home. We conducted interviews and extracted medical records. Using mixed non-linear models, we examined associations between induction strategy and opioid use and any drug use. Compared to those with standard-of-care office-based inductions, participants with patient-centered home-based inductions had no significant differences in opioid use (AOR=0.63, 95%CI=0.13–2.97), but greater reductions in any drug use (AOR=0.05, 95%CI=0.01–0.37). Taking into account the limitations of our observational cohort study design, we conclude that participants with patient-centered home-based inductions had similar reductions in opioid use and greater reductions in any drug use than those with standard-of-care office-based inductions. It is essential that new induction strategies be based on existing models or theories and well-studied. PMID:21310583

Cunningham, Chinazo O.; Giovanniello, Angela; Li, Xuan; Kunins, Hillary V.; Roose, Robert J.; Sohler, Nancy L.

2011-01-01

252

A Convenient Synthesis of Novel N?-tert-Butyl-N?-Substituted Benzoyl-N-(Substituted Phenyl)aminocarbonylhydrazines and Their Derivatives  

Microsoft Academic Search

N-tert-butyl-N-substituted benzoylhydrazines were prepared in two convenient procedures with good yields, subsequent reaction with substituted phenylisocyanates in 1,2-dichloroethane provided a series of novel N?-tert-butyl-N?-substituted benzoyl-N-(substituted phenyl)aminocarbonylhydrazines. Further treatment with oxalyl chloride gave their derivatives in good yields. The title compounds exhibit moderate larvicidal activities and anticancer activities.

Qingmin Wang; Runqiu Huang

2004-01-01

253

EFFICIENT ATTACKS ON HOMOPHONIC SUBSTITUTION CIPHERS  

Microsoft Academic Search

Substitution ciphers are one of the earliest types of ciphers. Examples of classic substitution ciphers include the well-known simple substitution and the less well-known homophonic substitution. Although simple substitution ciphers are indeed simple - both in terms of their use and attacks; the homophonic substitution ciphers are far more challenging to break. Even with modern computing technology, homophonic substitution ciphers

Amrapali Dhavare

2011-01-01

254

Synthetic bone graft substitutes.  

PubMed

Replacement of extensive local bone loss is a significant clinical challenge. There are a variety of techniques available to the surgeon to manage this problem, each with their own advantages and disadvantages. It is well known that there is morbidity associated with harvesting of autogenous bone graft and limitations in the quantity of bone available. Alternatively allografts have been reported to have a significant incidence of postoperative infection and fracture as well as the potential risk of disease transmission. During the past 30 years a variety of synthetic bone graft substitutes has been developed with the aim to minimize these complications. The benefits of synthetic grafts include availability, sterility and reduced morbidity. The present article examines the relevance of synthetic bone graft substitutes, their mechanical properties and clinical application. PMID:11409021

Moore, W R; Graves, S E; Bain, G I

2001-06-01

255

Explicit Substitutions and Programming Languages  

Microsoft Academic Search

The ?-calculus has been much used to study the theory of substitution in logical systems and programming languages. However, with explicit substitutions, it is possible to get finer properties with re- spect to gradual implementations of substitutions as effectively done in runtimes of programming languages. But the theory of explicit substi- tutions has some defects such as non-confluence or the

Jean-jacques Lévy; Luc Maranget

1999-01-01

256

SUBSTITUTION REACTIONS FOR THE DETOXIFICATION OF HAZARDOUS CHEMICALS  

EPA Science Inventory

Chemical Treatment is one of several treatment techniques used for the remediation of toxic and hazardous chemicals. Chemical treatment in this report is defined as substitution of halogens by hydrogens for the conversion of halogenated organic toxicant into its native hydrocarb...

257

Trifluoromethyl-substituted polymers  

NASA Technical Reports Server (NTRS)

Current work sponsored by the grant at Southwest Texas State University is directed toward the synthesis and characterization of: (1) N-alkylated polyamides derived from o-fluorinated diacids; (2) highly fluorinated polyethers; (3) polyesters derived from 2-hydroxy-2-propyl substituted arenes and/or 2,5-difluoroterephthalic acid; and (4) silicon-containing fluoropolymers. Work during the period from 1 July to 31 Dec. 1993 focused primarily on items 3 and 4 and on the development of a phosphorus containing modification of '12F-PEK.'

1993-01-01

258

Polyimides comprising substituted benzidines  

NASA Technical Reports Server (NTRS)

A new class of polyimides and copolyimides made from substituted benzidines and aromatic dianhydrides and other aromatic diamines. The polyimides obtained with said diamines are distinguished by excellent thermal, excellent solubility, excellent electrical properties such as very low dielectric constants, excellent clarity and mechanical properties making the polyimides ideally suited as coating materials for microelectronic apparatii, as membranes for selective molecular or gas separation, as fibers in molecular composites, as high tensile strength, high compression strength fibers, as film castable coatings, or as fabric components.

Harris, Frank W. (Inventor)

1991-01-01

259

Neutron powder diffraction studies of silicon-substituted hydroxyapatite.  

PubMed

The incorporation of a small amount of silicon in the hydroxyapatite (HAp) lattice is known to improve the bioactivity of the material. The effect of silicon substitution was studied by comparing samples of pure and 0.4wt% silicon-substituted HAp prepared by an aqueous precipitation method. High-resolution neutron powder diffraction and Rietveld refinement methods were used to investigate the effect of silicon substitution on the crystal structure parameters of the HAp lattice from room temperature down to 20K. Small structural changes in the lattice constants, interatomic distances, site occupancies and distortion of the phosphate tetrahedron were found. Modifications of the Fourier transform infrared spectra as well as appearance of new modes were observed in the silicon-substituted sample. Heat treatment and silicon substitution also affected the morphology and crystallinity of this bioapatite. PMID:12853251

Leventouri, Th; Bunaciu, C E; Perdikatsis, V

2003-10-01

260

Treatment  

Microsoft Academic Search

Few clinical issues have been more hotly contested than the treatment of ADHD, particularly the relative value of medication\\u000a versus behavioral\\/psychosocial treatments (DuPaul & Power, 2008; Toplak, Connors, Shuster, Knezevic, & Parks, 2008; Wauschbusch\\u000a & Hill, 2003). Treatment decisions are often complicated by biases reflecting media coverage of diagnostic and treatment controversies,\\u000a cultural background, previous experiences or anecdotal stories from

Stephen E. Brock; Shane R. Jimerson; Robin L. Hansen

261

Explicit Substitutions and All That  

NASA Technical Reports Server (NTRS)

Explicit substitution calculi are extensions of the lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda sigma- and lambda S(e)-calculi.

Ayala-Rincon, Mauricio; Munoz, Cesar

2000-01-01

262

Explicit Substitutions and All That  

NASA Technical Reports Server (NTRS)

Explicit substitution calculi are extensions of the Lambda-calculus where the substitution mechanism is internalized into the theory. This feature makes them suitable for implementation and theoretical study of logic-based tools such as strongly typed programming languages and proof assistant systems. In this paper we explore new developments on two of the most successful styles of explicit substitution calculi: the lambda(sigma)- and lambda(s(e))-calculi.

Ayala-Rincon, Mauricio; Munoz, Cesar; Busnell, Dennis M. (Technical Monitor)

2000-01-01

263

Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball’-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine\\/Heroin Polydrug Abusers  

Microsoft Academic Search

The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid\\/cocaine combination (‘speedball’-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg\\/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg\\/day maintenance and double-blind ascending SR-AMP weekly doses of 0,

Mark K Greenwald; Leslie H Lundahl; Caren L Steinmiller

2010-01-01

264

Substituting fossil fuels with biomass  

Microsoft Academic Search

Replacing fossil fuels with sustainably-produced biomass reduces net CO2 emissions. We express the efficiency of this substitution in reduced emissions per unit of used land or biomass. The substitution costs are calculated as the cost difference between a continued use of fossil fuels at current prices and a use of biomass. The biomass technologies are assumed to be implemented when

Leif Gustavsson; Per Svenningsson

1996-01-01

265

A Substitution Operation for Constraints  

Microsoft Academic Search

In order to reduce the search space in finite constraint satisfaction problems, a number of different preprocessing schemes have been proposed. This paper introduces a substitution operation for constraints. This new operation generalizes both the idea of enforcing consistency and the notion of label substitution introduced by Freuder. We show that the constraints in a problem may be replaced by

Peter Jeavons; David A. Cohen; Martin C. Cooper

1994-01-01

266

MICROWAVE PHOTOCHEMISTRY OF SUBSTITUTED PHENOLS  

E-print Network

MICROWAVE PHOTOCHEMISTRY OF SUBSTITUTED PHENOLS V. C�rkva, J. Kurf�rstov�, M. H�jek Institute into the microwave field (MW) has been known for long time [1-3]. The low powered and low-pressure electrodeless of microwave photochemistry of substituted phenols in an original photoche- mical reactor consisting of EDL

Cirkva, Vladimir

267

Displacement, Substitution, Sublimation: A Bibliography.  

ERIC Educational Resources Information Center

Sigmund Freund worked with the mechanisms of displacement, substitution, and sublimation. These mechanisms have many similarities and have been studied diagnostically and therapeutically. Displacement and substitution seem to fit in well with phobias, hysterias, somatiyations, prejudices, and scapegoating. Phobias, prejudices, and scapegoating…

Pedrini, D. T.; Pedrini, Bonnie C.

268

Non-medical use of opioids among HIV-infected opioid dependent individuals on opioid maintenance treatment: the need for a more comprehensive approach  

PubMed Central

Background Opioid maintenance treatment (OMT) has a positive impact on substance use and health outcomes among HIV-infected opioid dependent patients. The present study investigates non-medical use of opioids by HIV-infected opioid-dependent individuals treated with buprenorphine or methadone. Methods The MANIF 2000 study is a longitudinal study that enrolled a cohort of 476 HIV-infected opioid-dependent individuals. Data were collected in outpatient hospital services delivering HIV care in France. The sample comprised all patients receiving OMT (either methadone or buprenorphine) who attended at least one follow-up visit with data on adherence to OMT (N = 235 patients, 1056 visits). Non-medical use of opioids during OMT was defined as having reported use of opioids in a non-medical context, and/or the misuse of the prescribed oral OMT by an inappropriate route of administration (injection or sniffing). After adjusting for the non-random assignment of OMT type, a model based on GEE was then used to identify predictors of non-medical use of opioids. Results Among the 235 patients, 144 (61.3%) and 91 (38.9%) patients were receiving buprenorphine and methadone, respectively, at baseline. Non-medical use of opioids was found in 41.6% of visits for 83% of individual patients. In the multivariate analysis, predictors of non-medical use of opioids were: cocaine, daily cannabis, and benzodiazepine use, experience of opioid withdrawal symptoms, and less time since OMT initiation. Conclusions Non-medical use of opioids was found to be comparable in OMT patients receiving methadone or buprenorphine. The presence of opioid withdrawal symptoms was a determinant of non-medical use of opioids and may serve as a clinical indicator of inadequate dosage, medication, or type of follow-up. Sustainability and continuity of care with adequate monitoring of withdrawal symptoms and polydrug use may contribute to reduced harms from ongoing non-medical use of opioids. PMID:22123176

2011-01-01

269

Biotransformation and Biodegradation of N-Substituted Aromatics in Methanogenic Granular Sludge  

Microsoft Academic Search

N-substituted aromatic compounds are environmental contaminants associated with the production and use of dyes, explosives, pesticides and pharmaceuticals among others. Nitro- and azo-substituted aromatic compounds with strong electron withdrawing groups are poorly biodegradable in aerobic treatment systems. Therefore anaerobic treatment technologies were considered in this research. The toxicity of these compounds to methanogenic bacteria was studied. Batch toxicity assays indicated

E. Razo Flores

1997-01-01

270

40 CFR 721.3063 - Substituted phenyl azo substituted phenyl esters (generic name).  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Substituted phenyl azo substituted phenyl esters (generic name). 721.3063 Section...Chemical Substances § 721.3063 Substituted phenyl azo substituted phenyl esters (generic...

2010-07-01

271

40 CFR 721.3360 - Substituted ethanolamine.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Substituted ethanolamine. 721.3360 Section 721.3360...Substances § 721.3360 Substituted ethanolamine. (a) Chemical substance and significant...identified generically as substituted ethanolamine (PMN P-91-490) is subject...

2010-07-01

272

40 CFR 721.9820 - Substituted triazole.  

Code of Federal Regulations, 2011 CFR

... 2011-07-01 false Substituted triazole. 721.9820 Section 721.9820...Substances § 721.9820 Substituted triazole. (a) Chemical substance and significant...generically identified as a substituted triazole (PMN P-90-1731) is subject...

2011-07-01

273

40 CFR 721.9820 - Substituted triazole.  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false Substituted triazole. 721.9820 Section 721.9820...Substances § 721.9820 Substituted triazole. (a) Chemical substance and significant...generically identified as a substituted triazole (PMN P-90-1731) is subject...

2010-07-01

274

40 CFR 721.4280 - Substituted hydrazine.  

Code of Federal Regulations, 2011 CFR

... 2011-07-01 false Substituted hydrazine. 721.4280 Section 721.4280...Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant...identified generically as substituted hydrazine (PMN P-90-594) is subject...

2011-07-01

275

40 CFR 721.4280 - Substituted hydrazine.  

... 2014-07-01 false Substituted hydrazine. 721.4280 Section 721.4280...Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant...identified generically as substituted hydrazine (PMN P-90-594) is subject...

2014-07-01

276

40 CFR 721.4280 - Substituted hydrazine.  

Code of Federal Regulations, 2012 CFR

... 2012-07-01 false Substituted hydrazine. 721.4280 Section 721.4280...Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant...identified generically as substituted hydrazine (PMN P-90-594) is subject...

2012-07-01

277

40 CFR 721.4280 - Substituted hydrazine.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false Substituted hydrazine. 721.4280 Section 721.4280...Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant...identified generically as substituted hydrazine (PMN P-90-594) is subject...

2013-07-01

278

40 CFR 721.4280 - Substituted hydrazine.  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false Substituted hydrazine. 721.4280 Section 721.4280...Substances § 721.4280 Substituted hydrazine. (a) Chemical substance and significant...identified generically as substituted hydrazine (PMN P-90-594) is subject...

2010-07-01

279

40 CFR 721.9820 - Substituted triazole.  

Code of Federal Regulations, 2012 CFR

... 2012-07-01 false Substituted triazole. 721.9820 Section 721.9820...Substances § 721.9820 Substituted triazole. (a) Chemical substance and significant...generically identified as a substituted triazole (PMN P-90-1731) is subject...

2012-07-01

280

40 CFR 721.9820 - Substituted triazole.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false Substituted triazole. 721.9820 Section 721.9820...Substances § 721.9820 Substituted triazole. (a) Chemical substance and significant...generically identified as a substituted triazole (PMN P-90-1731) is subject...

2013-07-01

281

14 CFR 1260.55 - Reports substitution.  

Code of Federal Regulations, 2011 CFR

... GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of...

2011-01-01

282

14 CFR 1260.55 - Reports substitution.  

... GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of...

2014-01-01

283

14 CFR 1260.55 - Reports substitution.  

Code of Federal Regulations, 2013 CFR

... GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of...

2013-01-01

284

14 CFR 1260.55 - Reports substitution.  

Code of Federal Regulations, 2010 CFR

... GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of...

2010-01-01

285

14 CFR 1260.55 - Reports substitution.  

Code of Federal Regulations, 2012 CFR

... GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.55 Reports substitution. Reports Substitution October 2000 Technical Reports may be substituted for the required Performance Reports. The title page of...

2012-01-01

286

40 CFR 721.10626 - 1,4-Butanediol, polymer with substituted alkane and substituted methylene biscarbomonocycle, 2...  

Code of Federal Regulations, 2013 CFR

...4-Butanediol, polymer with substituted alkane and substituted methylene biscarbomonocycle...4-Butanediol, polymer with substituted alkane and substituted methylene biscarbomonocycle...4-butanediol, polymer with substituted alkane and substituted methylene...

2013-07-01

287

DESIGNING ENVIRONMENTALLY BENIGN SOLVENT SUBSTITUTES  

EPA Science Inventory

Since the signing of 1987 Montreal Protocol, reducing and eliminating the use of harmful solvents has become an internationally imminent environmental protection mission. Solvent substitution is an effective way to achieve this goal. The Program for Assisting the Replacement of...

288

Nucleophilic Substitution by Benzodithioate Anions.  

ERIC Educational Resources Information Center

Describes a two-session experiment designed to provide a good illustration of, and to improve student knowledge of, the Grignard reaction and nucleophilic substitution. Discusses the procedure, experimental considerations, and conclusion of this experiment. (CW)

Bonnans-Plaisance, Chantal; Gressier, Jean-Claude

1988-01-01

289

Synthesis of substituted thienothiazoles  

Microsoft Academic Search

The action of sulfur monochloride on 2-amino-3-carboxy-5-phenylthiophene or 2-amino5-phenylthiophene hydrochloride gave 5-phenylthieno[2,3-d]-2-thioniathiazole chloride, which is converted to the corresponding hydrate on treatment with water. Heating of the thionium salt or its hydrate with carbon disulfide in an aqueous alcohol solution of aklaki gave 2-mercapto-5-phenylthieno[2,3-d]thiazole, which under the influence of dialkyl sulfates or on oxidation with potassium permanganate in alkaline media

P. I. Abramenko; T. K. Ponomareva; G. I. Priklonskikh

1979-01-01

290

Chromane substituted benzimidazole derivatives  

US Patent & Trademark Office Database

This invention relates to compounds of the formula (I): ##STR00001## or a pharmaceutically acceptable salt thereof, wherein: A, B, X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are each as described herein or a pharmaceutically acceptable salt, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by acid pump antagonistic activity such as, but not limited to, as gastrointestinal disease, gastroesophageal disease, gastroesophageal reflux disease (GERD), peptic ulcer, gastric ulcer, duodenal ulcer, NSAID-induced ulcers, gastritis, infection of Helicobacter pylori, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, non-erosive reflux disease (NERD), visceral pain, heartburn, nausea, esophagitis, dysphagia, hypersalivation, airway disorders or asthma.

2010-05-25

291

A pharmaceutical industry perspective on the economics of treatments for alcohol and opioid use disorders.  

PubMed

Individuals with alcohol and/or drug use disorders often fail to receive care, or evidence-based care, yet the literature shows health economic benefits. Comparative effectiveness research is emerging that examines approved approaches in terms of real, total healthcare cost/utilization. Comprehensive retrospective insurance claims analyses are few but tend to be nationally distributed and large. The emerging pattern is that, while treatment in general is cost effective, specific therapeutics can yield different health economic outcomes. Cost/utilization data consistently show greater savings with pharmacotherapies (despite their costs) versus psychosocial treatment alone. All FDA-approved addiction pharmacotherapies (oral naltrexone, extended-release naltrexone, acamprosate, disulfiram, buprenorphine, buprenorphine/naloxone, and methadone) are intended for use in conjunction with psychosocial management, not as stand-alone therapeutics; hence, pharmacotherapy costs must offer benefits in addition to abstinence alone or psychological therapy. Patient persistence is problematic, and (despite its cost) extended-release pharmacotherapy may be associated with lower or no greater total healthcare cost, mostly due to reduced hospitalization. The reviewed studies use rigorous case-mix adjustment to balance treatment cohorts but lack the randomization that clinical trials use to protect against confounding. Unlike trials, however, these studies can offer generalizability to diverse populations, providers, and payment models-and are of particular salience to payers. PMID:25236185

Gastfriend, David R

2014-10-01

292

Functionally Substituted Amides and Esters of 3,4,4-Trichloro-3-butenoic Acid  

Microsoft Academic Search

Substituted amides and esters of 3,4,4-trichloro-3-butenoic acid were prepared by reactions of its chloride with appropriate amines and alcohols. Treatment of 3,4,4-trichloro-3-butenomorpholide and tert-butyl 3,4,4-trichloro-3-butenoate results in nucleophilic substitution of the internal chlorine atom with the morpholine residue, accompanied by prototropic allyl rearrangement.

S. K. Petkevich; E. A. Dikusar; V. I. Potkin; R. V. Kaberdin; K. L. Moiseichuk; A. P. Yuvchenko; P. V. Kurman

2004-01-01

293

Biological background of dermal substitutes.  

PubMed

Dermal substitutes are of major importance in treating full thickness skin defects, both in acute and chronic wounds. In this review we will outline specific requirements of three classes of dermal substitutes: Biological and clinical requirements will be translated to composition, physical structure, immunological properties and cell-matrix interactions of the various materials. Important properties like pore size, cell adhesion sites (e.g. RGD sequences), crosslinking, degradability and the presence of a basement membrane will be discussed for each of the different classes of materials. PMID:19897310

van der Veen, Vincent C; van der Wal, Martijn B A; van Leeuwen, Michiel C E; Ulrich, Magda M W; Middelkoop, Esther

2010-05-01

294

Automated multiple development thin-layer chromatography for separation of opiate alkaloids and derivatives  

Microsoft Academic Search

There are three types of opiate alkaloids. First, the poppy alkaloids: morphine, codeine, thebaine, noscapine and papaverine; then, the semi-synthetic and synthetic derivatives used in therapy as antitussives and analgesics, such as pholcodine, ethylmorphine and dextromethorphan; at last narcotic compounds, diacetylmorphine (heroin) and opiates employed as substitutes in treatment of addiction: buprenorphine and methadone. For classical thin-layer chromatography (TLC) of

Jacques Pothier; Nicole Galand

2005-01-01

295

40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.  

Code of Federal Regulations, 2012 CFR

...substituted benzenediazonium salt. 721.1555 Section 721...substituted benzenediazonium salt. (a) Chemical substance...substituted benzenediazonium salt (PMN P-92-652) is subject...5). (ii) Release to water. Requirements as...

2012-07-01

296

40 CFR 721.1555 - Substituted phenyl azo substituted benzenediazonium salt.  

Code of Federal Regulations, 2011 CFR

...substituted benzenediazonium salt. 721.1555 Section 721...substituted benzenediazonium salt. (a) Chemical substance...substituted benzenediazonium salt (PMN P-92-652) is subject...5). (ii) Release to water. Requirements as...

2011-07-01

297

40 CFR 721.5340 - Substituted benzothiazole-azo-substituted benzoquinoline nickel complex (generic).  

Code of Federal Regulations, 2010 CFR

...benzothiazole-azo-substituted benzoquinoline nickel complex (generic). 721.5340 Section...benzothiazole-azo-substituted benzoquinoline nickel complex (generic). (a) Chemical...benzothiazole-azo-substituted benzoquinoline nickel complex (PMN P-99-897) is...

2010-07-01

298

Solving Substitution Ciphers Sam Hasinoff  

E-print Network

Solving Substitution Ciphers Sam Hasinoff Department of Computer Science, University of Toronto Doyle's short story "The Adventure of the Dancing Men" (1903), the pro- tagonist Sherlock Holmes solves character. Figure 1: Dancing men ciphertext from "The Adventure of the Dancing Men" (1903). Thus, each

Toronto, University of

299

Service Substitution Revisited Dionysis Athanasopoulos  

E-print Network

that the client software is a Permission to make digital or hard copies of all or part of this work for personal issue: the complexity of the substitution process scales up with the number of avail- able services-oriented paradigm fosters the development of software consisting of basic architectural elements (a.k.a ser- vices

Paris-Sud XI, Université de

300

Treatment of Opioid Dependent Pregnant Women: Clinical and Research Issues  

PubMed Central

This paper addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance is provided to aid clinical decision-making, based on both research evidence and the collective clinical experience of the authors which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project. MOTHER is a double-blind, double-dummy, flexible–dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the opioid dependence treatment among pregnant women and their neonates. The paper begins with a discussion of appropriate assessment during pregnancy, and then addresses clinical management stages, including maintenance medication selection, induction and stabilization, opioid agonist medication management before, during and after delivery, pain management, breast-feeding, and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed. PMID:18248941

Jones, H.E.; Martin, P.R.; Heil, S.H.; Stine, S.M.; Kaltenbach, K.; Selby, P.; Coyle, M.G.; O’Grady, K.E.; Arria, A.M.; Fischer, G.

2008-01-01

301

Buprenorphine/naloxone as a promising therapeutic option for opioid abusing patients with chronic pain: Reduction of pain, opioid withdrawal symptoms, and abuse liability of oral oxycodone  

PubMed Central

Aim Few studies have examined abuse of prescription opioids (PO) among individuals with chronic pain under buprenorphine/naloxone (Bup/Nx) maintenance. The current 7-week inpatient study assessed oral oxycodone self-administration by patients with chronic pain who had a history of opioid abuse. Methods Participants (N=25) were transitioned from their pre-admission prescribed opioid to Bup/Nx. All of the participants were tested under each of the sublingual Bup/Nx maintenance doses (2/0.5, 8/2 or 16/4 mg) in random order. During each maintenance period, participants could self-administer oxycodone orally (0, 10, 20, 40 or 60 mg, PO) or receive money during laboratory sessions. Drug choice (percent) was the primary dependent variable. Subjective ratings of clinical pain and withdrawal symptoms also were measured. Mann-Whitney tests compared % drug choice for each active oxycodone dose to placebo. Logistic regression analyses identified correlates of oxycodone preference, defined as 60% or greater choice of oxycodone compared to money. Results Pain was significantly reduced while participants were maintained on Bup/Nx compared to pre-admission ratings. No differences in percent drug choice were observed between the active oxycodone doses and placebo under each Bup/Nx maintenance dose. However, factors associated with oxycodone preference were: lower Bup/Nx maintenance dose, more withdrawal symptoms and more pain. Conclusions These data suggest that Bup/Nx was effective in reducing pain and supplemental oxycodone use. Importantly, adequate management of pain and withdrawal symptoms by Bup/Nx may reduce oxycodone preference in this population. PMID:23707283

Roux, Perrine; Sullivan, Maria A.; Cohen, Julien; Fugon, Lionel; Jones, Jermaine D.; Vosburg, Suzanne K.; Cooper, Ziva D.; Manubay, Jeanne M.; Mogali, Shanthi; Comer, Sandra D.

2013-01-01

302

Development and Clinical Evaluation Synthetic Skin Substitute as a Model of Skin Function.  

National Technical Information Service (NTIS)

Temporary skin substitutes, including human cadaver cutaneous allografts, porcine cutaneous xenografts, and amniotic membranes have become widely used in the treatment of thermally injured patients. The principal use of these biologic dressings is for tem...

N. S. Levine, A. D. Mason, B. A. Pruitt

1983-01-01

303

Effect of nonindependent substitution on phylogenetic accuracy.  

PubMed

All current phylogenetic methods assume that DNA substitutions are independent among sites. However, ample empirical evidence suggests that the process of substitution is not independent but is, in fact, temporally and spatially correlated. The robustness of several commonly used phylogenetic methods to the assumption of independent substitution is examined. A compound Poisson process is used to model DNA substitution. This model assumes that substitution events are Poisson-distributed in time and that the number of substitutions associated with each event is geometrically distributed. The asymptotic properties of phylogenetic methods do not appear to change under a compound Poisson process of DNA substitution. Moreover, the rank order of the performance of different methods does not change. However, all phylogenetic methods become less efficient when substitution follows a compound Poisson process. PMID:12066710

Huelsenbeck, J P; Nielsen, R

1999-06-01

304

Skin Substitutes with Improved Barrier Function.  

National Technical Information Service (NTIS)

The present invention relates to in vitro cultured skin substitutes, and in particular to in vitro cultured skin substitutes that have improved barrier function. In some embodiments, improved barrier function is a result of improved culture conditions, wh...

A. Comer, L. A. Hoffmann, M. Hoffmann

2005-01-01

305

47 CFR 76.130 - Substitutions.  

Code of Federal Regulations, 2012 CFR

...Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) ...Syndicated Exclusivity and Sports Blackout § 76.130 Substitutions...syndicated program exclusivity, or sports blackout rules, a satellite...satellite carrier may, consistent with this Subpart, substitute...

2012-10-01

306

47 CFR 76.130 - Substitutions.  

Code of Federal Regulations, 2013 CFR

...Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) ...Syndicated Exclusivity and Sports Blackout § 76.130 Substitutions...syndicated program exclusivity, or sports blackout rules, a satellite...satellite carrier may, consistent with this Subpart, substitute...

2013-10-01

307

47 CFR 76.130 - Substitutions.  

Code of Federal Regulations, 2011 CFR

...Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) ...Syndicated Exclusivity and Sports Blackout § 76.130 Substitutions...syndicated program exclusivity, or sports blackout rules, a satellite...satellite carrier may, consistent with this Subpart, substitute...

2011-10-01

308

47 CFR 76.130 - Substitutions.  

Code of Federal Regulations, 2010 CFR

...Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) ...Syndicated Exclusivity and Sports Blackout § 76.130 Substitutions...syndicated program exclusivity, or sports blackout rules, a satellite...satellite carrier may, consistent with this Subpart, substitute...

2010-10-01

309

40 CFR 721.1643 - Benzenesulfonic acid, amino substituted phenylazo-.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Benzenesulfonic acid, amino substituted phenylazo-. 721... § 721.1643 Benzenesulfonic acid, amino substituted phenylazo-. ...generically as a benzenesulfonic acid, amino substituted phenylazo-...

2010-07-01

310

Assessment of asbestos insulation substitutes  

SciTech Connect

A state-of-the-art study of asbestos insulation alternatives has been conducted to identify the best substitute material for steam lines in power plants. A survey of utilities across the nation showed that calcium silicate is the most commonly employed material today, followed by mineral wool, fiberglass, and ceramic fibers. However, the calcium silicate was found to be dusty and to become brittle once exposed to elevated temperatures. Although it is asbestos-free, studies on its carcinogenicity are incomplete. Characteristic data on existing substitute materials is compiled and an optimum choice of insulation combination is configured. Potential cost savings of using this combination is evaluated for a major utility. A PC-based computer program is developed to assist utility personnel in selecting the proper insulation materials for steam lines. 31 refs., 8 figs.

Fourroux, J.D.; Frank, R.L. Jr.; Newberry, T.W. Jr. (Tennessee Valley Authority, Chattanooga, TN (USA))

1990-03-01

311

Expectations and Experiences of Substitute Teachers  

ERIC Educational Resources Information Center

This article explores the expectations of support for and the experiences of substitute teachers in an urban school division in Saskatchewan. Data were collected in semistructured interviews with seven substitute teachers. The purpose of the study was to explore how substitute teachers frame their professional experiences and construct their roles…

Duggleby, Patricia; Badali, Sal

2007-01-01

312

A statistical framework for mining substitution rules  

Microsoft Academic Search

In this paper, a new mining capability, called mining of substitution rules, is explored. A substitution refers to the choice made by a customer to replace the purchase of some items with that of others. The mining of substitution rules in a transaction database, the same as that of association rules, will lead to very valuable knowledge in various aspects,

Wei-guang Teng; Ming-jyh Hsieh; Ming-syan Chen

2005-01-01

313

Nucleotide Substitution Rates of HIV1  

Microsoft Academic Search

The molecular evolution of human immunodeficiency virus type 1 (HIV-1) is reviewed from the viewpoint of the rate of nucleotide substitution, which is defined as the number of nucleotide substitutions per site per year. The rate of nucleotide substitution is useful not only for estimating the origin and history of HIV-1 epidemics, but also for detecting natural selection operating at

Yoshiyuki Suzuki; Yumi Yamaguchi-Kabata; Takashi Gojobori

2000-01-01

314

A Comparison of Teachers', Administrators, and Substitute Teachers' Perceptions of Substitute Teachers'  

ERIC Educational Resources Information Center

A five category preference questionnaire was distributed to random samples of substitute teachers, regular teachers, and administrators. The data was analyzed using chi squared statistics. Substitutes rated principals' concern for substitute qualifications lower than did regular teachers and administrators. Substitutes also rated teachers lower in…

Trent, John H.; Ghilotti, Sharon

1972-01-01

315

A randomized trial of transcutaneous electric acupoint stimulation as adjunctive treatment for opioid detoxification.  

PubMed

This pilot study tested the effectiveness of transcutaneous electric acupoint stimulation (TEAS) as an adjunctive treatment for inpatients receiving opioid detoxification with buprenorphine-naloxone at a private psychiatric hospital. Participants (N = 48) were randomly assigned to active or sham TEAS and received three 30-minute treatments daily for 3 to 4 days. In active TEAS, current was set to maximal tolerable intensity (8-15 mA); in sham TEAS, it was set to 1 mA. By 2 weeks postdischarge, participants in active TEAS were less likely to have used any drugs (35% vs. 77%, p < .05). They also reported greater improvements in pain interference (F = 4.52, p < .05) and physical health (F = 4.84, p < .01) over time. TEAS is an acceptable, inexpensive adjunctive treatment that is feasible to implement on an inpatient unit and may be a beneficial adjunct to pharmacological treatments for opioid detoxification. PMID:19574017

Meade, Christina S; Lukas, Scott E; McDonald, Leah J; Fitzmaurice, Garrett M; Eldridge, Jessica A; Merrill, Nancy; Weiss, Roger D

2010-01-01

316

Photocatalytic and Antibacterial Activity of Titanium, Fluorine and Silver Co-Substituted Hydroxyapatite  

NASA Astrophysics Data System (ADS)

Synthetic hydroxyapatite (HA), an analogue of the mineral component of bone tissue has been widely used in medicine as bone replacing material. To impart specific properties, HA can be chemically modified by anionic and cationic substitutions during synthesis. Thus the present study was focused in synthesizing nanocrystalline Ti, Ag and F co-substituted HA by microwave synthesis. The prepared powders were characterized by XRD and FTIR for their crystal size, cystallinity and functional groups respectively. XRD spectra reveal that crystal size of prepared powders was in the range of 21-25 nm in as synthesized condition and 45-51 nm in 900 ?C heat-treated condition. Complete decomposition of HA to tri calcium phosphate was observed for Ti substituted HA powder after heat-treatment. Addition of F improved the thermal stability of Ti substituted HA as indicated by predominant phase of HA after heat-treatment. The photocatalytic activity of co-substituted HA powders was examined by degradation of methylene blue (5 × 10-5 M concentration) under visible light irradiation and the results were compared with pure HA. The degradation efficiency of co-substituted HA with respect to methylene blue was twice as high as that of pure HA. Ti and Ag has improved the visible light photocatalytic activity of HA, further F co-substitution has not affected the photocatalytic activity of substituted HA. The antibacterial effect of prepared powders was observed against 1 × 105 cells/mL of Escherichia coli using spread plate method at 24 h incubation period. Ag co-substituted HA showed complete inhibition of growth of Escherichia coli. Thus, among Ti, Ti-F, Ti-F-Ag substituted HA powders, Ti-F-Ag co-substituted HA with excellent visible light photocatalytic activity and anti-bacterial property is expected to be a potential candidate for biomedical applications.

Sandhyarani, M.; Rameshbabu, N.; Venkateswarlu, K.; Ravisankar, K. V.; Ashok, M.; Anandan, S.

317

[Treatment of hand surgery patients in chronic pain].  

PubMed

The treatment of hand surgery patients suffering from chronic pain requires an interdisciplinary procedure. An imbalance between nociception and antinociception can be seen as a reason for the chronification of pain. The complexity of the problem of chronic pain patients is marked by a wide variety of symptoms. Full diagnostic assessment to detect or to exclude other organic diseases is required. Rehabilitation to improve function and reduce pain intensity has priority. Our therapeutic strategy consists of intensive physiotherapy and analgesic drugs as well as a series of blockades with buprenorphine (Temgesic) of the ganglion stellatum (GLOA). This specific therapy achieved an improvement of the function of the upper extremity and a reduction of pain intensity. The majority of patients were satisfied with the outcome. PMID:12743693

Eiche, J; Krimmer, H; Lanz, U; Müller-Zimmermann, A; Reichl, M

2003-05-01

318

tert-butyl-substituted cyclooctatetraenes  

Microsoft Academic Search

Reaction of cyclooctatetraene (COT) with tert-butyllithium provides a convenient synthesis of tert-butylcyclooctatetraene, 4. As a byproduct of the reaction mixture, 1,4-di-tert-butylcyclooctatriene has been isolated and converted to 1,4-di-tert-butylcyclooctatetraene, 5, by deprotonation with potassium amide and oxidation with iodine. An independent synthesis of 5 was developed from 9-oxabicyclo(6.1.0)octa-2,4,6-triene (cyclooctatetraene oxide), 9. The highly substituted compound 1,3,5,7-tetra-tert-butylcyclooctatetraene (6) has been prepared in

Michael J. Miller; Matthew H. Lyttle; Andrew Streitwieser

1981-01-01

319

Sensory substitution as an artificially acquired synaesthesia.  

PubMed

In this review we explore the relationship between synaesthesia and sensory substitution and argue that sensory substitution does indeed show properties of synaesthesia. Both are associated with atypical perceptual experiences elicited by the processing of a qualitatively different stimulus to that which normally gives rise to that experience. In the most common forms of sensory substitution, perceptual processing of an auditory or tactile signal (which has been converted from a visual signal) is experienced as visual-like in addition to retaining auditory/tactile characteristics. We consider different lines of evidence that support, to varying degrees, the assumption that sensory substitution is associated with visual-like experiences. We then go on to analyse the key similarities and differences between sensory substitution and synaesthesia. Lastly, we propose two testable predictions: firstly that, in an expert user of a sensory substitution device, the substituting modality should not be lost. Secondly that stimulation within the substituting modality, but by means other than a sensory substitution device, should still produce sensation in the normally substituted modality. PMID:22885223

Ward, Jamie; Wright, Thomas

2014-04-01

320

Effectiveness, safety and cost of drug substitution in hypertension  

PubMed Central

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the ‘inactive’ components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended. PMID:20716230

Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

2010-01-01

321

Clinical and radiographic evaluation of the efficacy of platelet-rich plasma combined with hydroxyapatite bone graft substitutes in the treatment of intra-bony defects in maxillofacial region.  

PubMed

Abstract Objective. The aim of this study is to evaluate the efficacy of platelet-rich plasma (PRP) clinically and radiographically when combined with bovine derived hydroxyapatite (HA) bone grafting materials and resorbable collagen membranes for the treatment of intra-bony defects frequently seen at the distal aspect of mandibular second molars following the surgical extraction of fully impacted mandibular wisdom teeth. Study design. Eighteen patients were scheduled for post-operative visits at 1, 3 and 6 months post-operatively, probing depths were measured and digital panoramic radiographs were taken. Results. There were no significant differences on probing depths among two groups. Radiographic assessment also showed no significant difference among groups at 1st and 6th month intervals, while 3 months post-operatively the amount of radiographic density at the PRP side was significantly higher. Conclusion. Combined use of PRP and bovine-derived HA graft materials for the treatment of intra-bony defects might be an appropriate approach when the main goal is providing earlier bone regeneration. PMID:25005628

Durmu?lar, Mustafa Cenk; Alpaslan, Cansu; Alpaslan, Gökhan; Cak?r, Melih

2014-11-01

322

Exfoliation and thermal transformations of Nb-substituted layered titanates  

SciTech Connect

Single-layer Nb-substituted titanate nanosheets of ca. 1 nm thickness were obtained by exfoliating tetrabutylammonium (TBA)-intercalated Nb-substituted titanates in water. AFM images and turbidity measurements reveal that the exfoliated nanosheets crack and corrugate when sonicated. Upon heating, the thermal transformation into anatase and further to rutile is retarded. This suppression of the phase transition upon higher valent substitution may promote technological applications of anatase thin films, hereunder development of films with TCO properties. Depending on the oxygen partial pressure during the transformation, the Nb-substitution into TiO{sub 2} provokes different defect situations and also electronic properties. At reducing conditions, Nb is incorporated as Nb{sup V} and an equivalent amount of Ti{sup IV} is transformed to Ti{sup III} as evidenced by XPS. Magnetic susceptibility data show accordingly paramagnetic behavior. For samples heated in air Ti{sup IV} and Nb{sup V} cations prevail, the latter is compensated by cation vacancies. {sup 93}Nb MAS NMR data prove that Nb is finely dispersed into the transformed (Ti,Nb)O{sub 2} oxide matrices without sign of Nb{sub 2}O{sub 5} (nano)precipitates. The Nb-O-Ti bonds and defects at cation sites are considered key factors for increasing the transformation temperatures for conversion of the nanosheets to anatase and finally into rutile. It is further tempting to link the delay in crystallization to morphology limitations originating from the nanosheets. The present work shows that layered Nb-titanates are appropriate precursors for formation of highly oriented Nb-substituted anatase thin films via delamination, reconstruction and subsequent heat treatment. - Graphical abstract: Layered Nb-titanates are appropriate precursors for formation of highly oriented Nb-substituted anatase thin films via delamination, reconstruction and subsequent heat treatment. Highlights: Black-Right-Pointing-Pointer Single layer Nb-substituted nanosheets were obtained by exfoliation of layered titanates. Black-Right-Pointing-Pointer Nb(V) successfully introduced into anatase and rutile solid solutions. Black-Right-Pointing-Pointer Anatase obtained from reconstructed nanosheets exhibit enhanced thermal stability. Black-Right-Pointing-Pointer Oxygen partial pressure influences the valence of Nb in heat-treated samples. Black-Right-Pointing-Pointer Deposition of oriented thin Ti(Nb)O{sub 2} layers by spray coating was demonstrated.

Song Haiyan; Sjastad, Anja O.; Fjellvag, Helmer; Okamoto, Hiroshi [Department of Chemistry and Centre for Materials Science and Nanotechnology, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo (Norway); Vistad, Ornulv B.; Arstad, Bjornar [SINTEF Materials and Chemistry, P.O. Box 124, Blindern, N-0314 Oslo (Norway); Norby, Poul, E-mail: pnor@risoe.dtu.dk [Department of Chemistry and Centre for Materials Science and Nanotechnology, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo (Norway); Materials Research Division, Riso National Laboratory for Sustainable Energy, Technical University of Denmark, P.O. Box 49, DK-4000 Roskilde (Denmark)

2011-12-15

323

Nucleophilic vinylic substitutions of ? 3-vinyliodanes  

Microsoft Academic Search

Because of the excellent nucleofugality of the ?3-phenyliodanyl group, which shows a leaving group ability about 106 times greater than triflate, ?3-vinyl(phenyl)iodanes serve as highly reactive species in nucleophilic substitutions. This review summarizes the nucleophilic vinylic substitutions of ?3-vinyl(phenyl)iodanes. The reaction rates and mechanism of the nucleophilic vinylic substitutions change depending on the structure of ?3-vinyliodanes; the nature of the

Masahito Ochiai

2000-01-01

324

[Medical mistakes due to generic substitution].  

PubMed

Generic substitution is a major cause of medical mistakes in the general population. Danish legislation obligates pharmacies to substitute prescribed medicine with the cheapest equivalent formulation, despite variations in product name, packaging, shape and colour. Consequently, medical mistakes occur. Scientific evidence on the consequences of generic substitution is sparse. Call upon fellow health workers to report medical mistakes to the national entities and scientific peers, in order to increase awareness and scientific evidence about the problem. PMID:22929573

Rölfing, Jan Hendrik Duedal

2012-08-27

325

Mechanistic studies on iridium catalyzed allylic substitution.  

E-print Network

??Mechanistic studies on iridium catalyzed allylic substitution reactions catalyzed by iridium phosphoramidite complexes revealed that the active catalyst is generated through a base assisted cyclometalation… (more)

Madrahimov, Sherzod

2012-01-01

326

47 CFR 76.110 - Substitutions.  

Code of Federal Regulations, 2010 CFR

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) ...Syndicated Exclusivity and Sports Blackout § 76.110 Substitutions...community unit may, consistent with these rules and the sports blackout rules at §...

2010-10-01

327

47 CFR 76.110 - Substitutions.  

Code of Federal Regulations, 2012 CFR

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) ...Syndicated Exclusivity and Sports Blackout § 76.110 Substitutions...community unit may, consistent with these rules and the sports blackout rules at §...

2012-10-01

328

47 CFR 76.110 - Substitutions.  

Code of Federal Regulations, 2011 CFR

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) ...Syndicated Exclusivity and Sports Blackout § 76.110 Substitutions...community unit may, consistent with these rules and the sports blackout rules at §...

2011-10-01

329

47 CFR 76.110 - Substitutions.  

Code of Federal Regulations, 2013 CFR

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) ...Syndicated Exclusivity and Sports Blackout § 76.110 Substitutions...community unit may, consistent with these rules and the sports blackout rules at §...

2013-10-01

330

Polycyclic Aromatic Triptycenes: Oxygen Substitution Cyclization Strategies  

E-print Network

The cyclization and planarization of polycyclic aromatic hydrocarbons with concomitant oxygen substitution was achieved through acid catalyzed transetherification and oxygen-radical reactions. The triptycene scaffold ...

VanVeller, Brett

331

From thioether substituted porphyrins to sulfur linked porphyrin dimers: an unusual SNAr via thiolate displacement?  

PubMed

Treatment of meso 2-ethylhexyl-3-mercaptopropionate substituted porphyrins with base at room temperature generated a porphyrin thiolate anion which in situ reacted in a nucleophilic aromatic substitution (SNAr) reaction with remaining thioether derivative. This reaction yielded S-linked bisporphyrins in good yields, with mechanistic insight obtained via displacement reactions. Additionally, SNAr of the thioether chain was achieved using S- and organolithium nucleophiles. PMID:24247987

Ryan, Aoife A; Plunkett, Shane; Casey, Aoife; McCabe, Thomas; Senge, Mathias O

2014-01-11

332

[Infusion treatment in shock].  

PubMed

Nowadays, above all dextran, gelatin and starch solutions are available for the infusion theraphy of the various forms of shock. The application of these volume substitutes must be strictly controlled to avoid in particular cardial and pulmonal commplications. Blood transfusion combined with a volume substitute should only be applied in cases of heavy loss of blood. The treatment of metabolic acidose which usually occurs simultaneously is carried out with an alkaline solution. PMID:1344

Esser, H

1975-12-01

333

Treatment of chronic pain in older people: evidence-based choice of strong-acting opioids.  

PubMed

In the treatment of chronic malignant and non-malignant pain, opioids are used as strong analgesics. Frail elderly patients often have multiple co-morbidities and use multiple medicines, leading to an increased risk of clinically relevant drug-drug and drug-disease interactions. Age-related changes and increased frailty may lead to a less predictable drug response, increased drug sensitivity, and potential harmful drug effects. As a result, physicians face a complex task in prescribing medication to elderly patients. In this review, the appropriateness of the strong-acting opioids buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone and tapentadol is determined for use in elderly patients. Evidence-based recommendations for prescribing strong opioids to the frail elderly are presented. A literature search was performed for all individual drugs, using a validated and published set of 23 criteria concerning effectiveness, safety, pharmacokinetics and pharmacodynamics, experience, and convenience in elderly patients. First, information on the criteria was obtained from pharmaceutical reference books and a MEDLINE search. The information obtained on the individual drugs in the class of opioids was compared with the reference drug morphine. Evidence-based recommendations were formulated on the basis of the pros and cons for the frail elderly. Using the set of 23 criteria, no differentiation can be made between the appropriateness of buprenorphine, fentanyl, hydromorphone, morphine and oxycodone for use in elderly patients. Methadone has strong negative considerations in the treatment of chronic pain in the frail elderly. Methadone has a high drug-drug interaction potential and is associated with prolongation of the QT interval and a potential risk of accumulation due to a long elimination half-life. In addition, methadone is difficult to titrate because of its large inter-individual variability in pharmacokinetics, particularly in the frail elderly. Because of a lack of empiric knowledge, the use of tapentadol is not recommended in frail elderly persons. Nevertheless, tapentadol may prove to be a useful analgesic for the treatment of chronic pain in frail elderly persons because of its possible better gastrointestinal tolerability. In the treatment of chronic pain in the frail elderly, the opioids of first choice are buprenorphine, fentanyl, hydromorphone, morphine and oxycodone. In order to improve the convenience for elderly patients, the controlled-release oral dosage forms and transdermal formulations are preferred. PMID:22765848

van Ojik, Annette L; Jansen, Paul A F; Brouwers, Jacobus R B J; van Roon, Eric N

2012-08-01

334

Exfoliation and thermal transformations of Nb-substituted layered titanates  

NASA Astrophysics Data System (ADS)

Single-layer Nb-substituted titanate nanosheets of ca. 1 nm thickness were obtained by exfoliating tetrabutylammonium (TBA)-intercalated Nb-substituted titanates in water. AFM images and turbidity measurements reveal that the exfoliated nanosheets crack and corrugate when sonicated. Upon heating, the thermal transformation into anatase and further to rutile is retarded. This suppression of the phase transition upon higher valent substitution may promote technological applications of anatase thin films, hereunder development of films with TCO properties. Depending on the oxygen partial pressure during the transformation, the Nb-substitution into TiO 2 provokes different defect situations and also electronic properties. At reducing conditions, Nb is incorporated as Nb V and an equivalent amount of Ti IV is transformed to Ti III as evidenced by XPS. Magnetic susceptibility data show accordingly paramagnetic behavior. For samples heated in air Ti IV and Nb V cations prevail, the latter is compensated by cation vacancies. 93Nb MAS NMR data prove that Nb is finely dispersed into the transformed (Ti,Nb)O 2 oxide matrices without sign of Nb 2O 5 (nano)precipitates. The Nb-O-Ti bonds and defects at cation sites are considered key factors for increasing the transformation temperatures for conversion of the nanosheets to anatase and finally into rutile. It is further tempting to link the delay in crystallization to morphology limitations originating from the nanosheets. The present work shows that layered Nb-titanates are appropriate precursors for formation of highly oriented Nb-substituted anatase thin films via delamination, reconstruction and subsequent heat treatment.

Song, Haiyan; Sjåstad, Anja O.; Fjellvåg, Helmer; Okamoto, Hiroshi; Vistad, Ørnulv B.; Arstad, Bjørnar; Norby, Poul

2011-12-01

335

Material substitution and path dependence: empirical evidence on the substitution of copper for aluminum  

Microsoft Academic Search

Adopting an evolutionary perspective, this paper argues that path dependence plays a major role in material use and substitution such that it might delay or even prevent substitution despite the occurrence of significant relative price changes. After elucidating the importance of material substitution from an ecological-economic point of view and after explaining the meaning of path dependence from an evolutionary

Frank Messner

2002-01-01

336

Allogeneic skin substitutes applied to burns patients  

Microsoft Academic Search

Early re-surfacing of burn wounds remains the ideal but is limited by the availability of skin graft donor sites. Cultured grafts overcome these problems and autologous keratinocytes can be grown in culture and placed on a dermal substitute, but this results in delay and requires two operations. We developed an organotypic skin substitute, which achieves cover in one procedure, and

J. Nanchahal; R. Dover; W. R. Otto

2002-01-01

337

Educators Take Another Look at Substitutes  

ERIC Educational Resources Information Center

The mythology surrounding the substitute teacher is not a pretty one: Paper airplanes, lost learning, bullying. But as schools collect more information about teacher absenteeism and its consequences, districts and schools are exploring ways to professionalize substitute teaching--or experiment with alternative ways of coping with teacher absences.…

Zubrzycki, Jaclyn

2012-01-01

338

Aromatic nucleophilic substitutions under microwave irradiation  

Microsoft Academic Search

In order to study the effect of microwave irradiation over aromatic nucleophilic substitutions at atmospheric pressure and in a homogeneous medium, experiments with disubstituted-benzenes and the nucleophiles piperidine and potassium t-butoxide, in refluxing DMSO or DMF, were carried out. The aromatic nucleophilic substitutions under microwave irradiation were 2.7 to 12 times faster than under conventional reflux.

Gean V. Salmoria; Evandro Dall'Oglio; César Zucco

1998-01-01

339

Substitute Teachers: Making Lost Days Count  

ERIC Educational Resources Information Center

As K-12 teachers and administrators grow increasingly concerned with issues of accountability, research-based methods, and intervention strategies, little discussion exists on the impact of substitute teachers in the classroom. In the rush to analyze test scores, are the days covered by substitute teachers even considered? Though districts are…

True, Charlene; Butler, Kyle; Sefton, Rachel

2011-01-01

340

Efficient Cryptanalysis of Homophonic Substitution Amrapali Dhavare  

E-print Network

technique to the "Zodiac 340" cipher, which is an unsolved message created by the infamous Zodiac killer was created by the infamous Zodiac killer in 1969 [5]. Another Zodiac cipher, the "Zodiac 408. Keywords: homophonic substitution cipher, simple substitution cipher, hill climb, heuristic search, Zodiac

Stamp, Mark

341

Electrical passivation by hydrogen of substitutional cobalt in monocrystalline germanium  

NASA Astrophysics Data System (ADS)

Co has been implanted at 90 keV in n- and p-type germanium wafers and in-diffused using a 5 min thermal anneal at 500C. Deep level transient spectroscopy reveals three levels which are considered to be due to substitutional Co impurities. To passivate the electrical levels of substitutional Co, samples were hydrogenated using a DC-plasma for 4 h at 200C. For both the n- and p-type material the Co levels have disappeared up to at least 5 ?m beyond the surface. Directly after the plasma treatment different levels due to irradiation damage have been observed, one of which was assigned to the di-vacancy. The irradiation damage related defects disappeared due to a rapid thermal anneal of 1 min at 400C. Two electron traps E230 and E270 which were only present in Co-implanted samples after a hydrogenation have been tentatively assigned to cobalt related defect levels.

Lauwaert, J.; Van Gheluwe, J.; Clauws, P.

2007-12-01

342

Some comments on the substituted judgement standard.  

PubMed

On a traditional interpretation of the substituted judgement standard (SJS) a person who makes treatment decisions on behalf of a non-competent patient (e.g. concerning euthanasia) ought to decide as the patient would have decided had she been competent. I propose an alternative interpretation of SJS in which the surrogate is required to infer what the patient actually thought about these end-of-life decisions. In clarifying SJS it is also important to differentiate the patient's consent and preference. If SJS is part of an autonomy ideal of the sort found in Kantian ethics, consent seems more important than preference. From a utilitarian perspective a preference-based reading of SJS seems natural. I argue that the justification of SJS within a utilitarian framework will boil down to the question whether a non-competent patient can be said to have any surviving preferences. If we give a virtue-ethical justification of SJS the relative importance of consent and preferences depends on which virtue one stresses--respect or care. I argue that SJS might be an independent normative method for extending the patient's autonomy, both from a Kantian and a virtue ethical perspective. PMID:19234760

Egonsson, Dan

2010-02-01

343

A Novel Approach for the Synthesis of N-substituted Pyrroles Starting Directly From Nitro Compounds in Water  

Microsoft Academic Search

A distinct novel approach for a facile high-yielding synthesis of N-substituted pyrroles has been discovered by the treatment of nitroarenes with 2, 5-dimethoxytetrahydrofuran using indium in dilute aqueous HCl at room temperature.

Biswanath Das; Digambar Balaji Shinde; Boddu Shashi Kanth; Jayprakash Narayan Kumar

2011-01-01

344

Novel Approach for the Synthesis of N-Substituted Pyrroles Starting Directly from Nitro Compounds in Water  

Microsoft Academic Search

A novel approach for a facile high-yielding synthesis of N-substituted pyrroles has been discovered by the treatment of nitroarenes with 2,5-dimethoxytetrahydrofuran using indium in dilute aqueous HCl at room temperature.

Biswanath Das; Digambar Balaji Shinde; Boddu Shashi Kanth; Jayprakash Narayan Kumar

2012-01-01

345

tert-butyl-substituted cyclooctatetraenes  

SciTech Connect

Reaction of cyclooctatetraene (COT) with tert-butyllithium provides a convenient synthesis of tert-butylcyclooctatetraene, 4. As a byproduct of the reaction mixture, 1,4-di-tert-butylcyclooctatriene has been isolated and converted to 1,4-di-tert-butylcyclooctatetraene, 5, by deprotonation with potassium amide and oxidation with iodine. An independent synthesis of 5 was developed from 9-oxabicyclo(6.1.0)octa-2,4,6-triene (cyclooctatetraene oxide), 9. The highly substituted compound 1,3,5,7-tetra-tert-butylcyclooctatetraene (6) has been prepared in 24% overall yield in four steps. The acetylenic ketone 27, prepared from (tert-butylethynyl)copper and pivaloyl chloride, undergoes condensation with dimethyl malonate to give the pyrone ester 28. This ester undergoes facile hydrolysis and decarboxylation in hot concentrated sulfuric acid to yield 4,6-di-tert-butyl-2H-pyran-2-one (22) which is converted to 6 in one step by photolysis in dilute solution.

Miller, M.J. (Univ. of California, Berkeley); Lyttle, M.H.; Streitwieser, A. Jr.

1981-05-08

346

Uproar over Milk Substitutes Act.  

PubMed

Health policy activists lobbied 7 years for the Infant Milk Substitutes, Feeding Bottles and Infant Food Bill. Proponents of the bill say that it basically curtails unethical marketing practices, not the sales of baby foods, and argue that it was conceived to reduce the trend of mothers over-diluting commercial milk in order to reduce household expenses as well as stem the potential erosion of knowledge on locally available weaning foods. Even though the bill will become an Act only after its rules and regulations have been finalized, the government has already banned baby food advertisements on television and in other electronic media under its control. Women's groups now argue that the bill tends to focus almost exclusively upon the welfare of children and compromises the position of women who can not lactate adequately. Moreover, they hold that the bill may be used to compel wives to stay out of the formal workforce so that they may feed their babies. The intention of the bill may be meaningless without complementary legislation addressing the problems of working mothers. Specifically, amendments to the Maternity Benefits Act of 1961 would extend maternity leave to 4 months after delivery and lengthen the duration of nursing breaks. It is, however, feared that these changes may reduce employment prospects for women. PMID:12179211

1993-11-15

347

40 CFR 721.640 - Amine substituted metal salts.  

Code of Federal Regulations, 2013 CFR

...false Amine substituted metal salts. 721.640 Section 721...640 Amine substituted metal salts. (a) Chemical substance...generically as amine substituted metal salts (PMNs P-96-1337/1338...uses are: (i) Release to water. Requirements as...

2013-07-01

348

40 CFR 721.562 - Substituted alkylamine salt.  

Code of Federal Regulations, 2011 CFR

...false Substituted alkylamine salt. 721.562 Section 721...562 Substituted alkylamine salt. (a) Chemical substance...as a substituted alkylamine salt (PMN P-85-941) is subject...uses are: (i) Release to water. Requirements as...

2011-07-01

349

40 CFR 721.640 - Amine substituted metal salts.  

Code of Federal Regulations, 2012 CFR

...false Amine substituted metal salts. 721.640 Section 721...640 Amine substituted metal salts. (a) Chemical substance...generically as amine substituted metal salts (PMNs P-96-1337/1338...uses are: (i) Release to water. Requirements as...

2012-07-01

350

40 CFR 721.640 - Amine substituted metal salts.  

Code of Federal Regulations, 2010 CFR

...false Amine substituted metal salts. 721.640 Section 721...640 Amine substituted metal salts. (a) Chemical substance...generically as amine substituted metal salts (PMNs P-96-1337/1338...uses are: (i) Release to water. Requirements as...

2010-07-01

351

40 CFR 721.640 - Amine substituted metal salts.  

Code of Federal Regulations, 2011 CFR

...false Amine substituted metal salts. 721.640 Section 721...640 Amine substituted metal salts. (a) Chemical substance...generically as amine substituted metal salts (PMNs P-96-1337/1338...uses are: (i) Release to water. Requirements as...

2011-07-01

352

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.  

Code of Federal Regulations, 2010 CFR

... Substituted phenylimino carbamate derivative. 721.2025 Section 721.2025... Substituted phenylimino carbamate derivative. (a) Chemical substance and significant...as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject...

2010-07-01

353

40 CFR 721.1760 - Substituted benzotriazole derivatives.  

Code of Federal Regulations, 2013 CFR

... false Substituted benzotriazole derivatives. 721.1760 Section 721.1760...721.1760 Substituted benzotriazole derivatives. (a) Chemical substances and significant...generically as substituted benzotriazole derivatives (PMNs P-93-374 and...

2013-07-01

354

40 CFR 721.1760 - Substituted benzotriazole derivatives.  

Code of Federal Regulations, 2012 CFR

... false Substituted benzotriazole derivatives. 721.1760 Section 721.1760...721.1760 Substituted benzotriazole derivatives. (a) Chemical substances and significant...generically as substituted benzotriazole derivatives (PMNs P-93-374 and...

2012-07-01

355

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.  

Code of Federal Regulations, 2011 CFR

... Substituted phenylimino carbamate derivative. 721.2025 Section 721.2025... Substituted phenylimino carbamate derivative. (a) Chemical substance and significant...as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject...

2011-07-01

356

40 CFR 721.1760 - Substituted benzotriazole derivatives.  

Code of Federal Regulations, 2010 CFR

... false Substituted benzotriazole derivatives. 721.1760 Section 721.1760...721.1760 Substituted benzotriazole derivatives. (a) Chemical substances and significant...generically as substituted benzotriazole derivatives (PMNs P-93-374 and...

2010-07-01

357

40 CFR 721.1760 - Substituted benzotriazole derivatives.  

Code of Federal Regulations, 2011 CFR

... false Substituted benzotriazole derivatives. 721.1760 Section 721.1760...721.1760 Substituted benzotriazole derivatives. (a) Chemical substances and significant...generically as substituted benzotriazole derivatives (PMNs P-93-374 and...

2011-07-01

358

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.  

Code of Federal Regulations, 2012 CFR

... Substituted phenylimino carbamate derivative. 721.2025 Section 721.2025... Substituted phenylimino carbamate derivative. (a) Chemical substance and significant...as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject...

2012-07-01

359

40 CFR 721.2025 - Substituted phenylimino carbamate derivative.  

Code of Federal Regulations, 2013 CFR

... Substituted phenylimino carbamate derivative. 721.2025 Section 721.2025... Substituted phenylimino carbamate derivative. (a) Chemical substance and significant...as a substituted phenylimino carbamate derivative (PMN P-91-487) is subject...

2013-07-01

360

40 CFR 721.6060 - Alkylaryl substituted phosphite.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Alkylaryl substituted phosphite. 721.6060 Section 721.6060... § 721.6060 Alkylaryl substituted phosphite. (a) Chemical substance and significant...identified generically as alkylaryl substituted phosphite (PMN P-91-899) is subject...

2010-07-01

361

40 CFR 721.8140 - Substituted propane (generic).  

Code of Federal Regulations, 2010 CFR

... 2010-07-01 false Substituted propane (generic). 721.8140 Section 721...Substances § 721.8140 Substituted propane (generic). (a) Chemical substance...identified generically as a substituted propane (PMN P-01-298) is subject to...

2010-07-01

362

40 CFR 721.8140 - Substituted propane (generic).  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false Substituted propane (generic). 721.8140 Section 721...Substances § 721.8140 Substituted propane (generic). (a) Chemical substance...identified generically as a substituted propane (PMN P-01-298) is subject to...

2013-07-01

363

40 CFR 721.8140 - Substituted propane (generic).  

Code of Federal Regulations, 2011 CFR

... 2011-07-01 false Substituted propane (generic). 721.8140 Section 721...Substances § 721.8140 Substituted propane (generic). (a) Chemical substance...identified generically as a substituted propane (PMN P-01-298) is subject to...

2011-07-01

364

40 CFR 721.8140 - Substituted propane (generic).  

Code of Federal Regulations, 2012 CFR

... 2012-07-01 false Substituted propane (generic). 721.8140 Section 721...Substances § 721.8140 Substituted propane (generic). (a) Chemical substance...identified generically as a substituted propane (PMN P-01-298) is subject to...

2012-07-01

365

40 CFR 721.2532 - Substituted diphenylmethane (generic).  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Substituted diphenylmethane (generic). 721.2532 Section...Substances § 721.2532 Substituted diphenylmethane (generic). (a) Chemical substance...identified generically as a substituted diphenylmethane (PMN P-97-4) is subject...

2010-07-01

366

Toxicity of N-substituted aromatics to acetoclastic methanogenic activity in granular sludge.  

PubMed Central

N-substituted aromatics are important priority pollutants entering the environment primarily through anthropogenic activities associated with the industrial production of dyes, explosives, pesticides, and pharmaceuticals. Anaerobic treatment of wastewaters discharged by these industries could potentially be problematical as a result of the high toxicity of N-substituted aromatics. The objective of this study was to examine the structure-toxicity relationships of N-substituted aromatic compounds to acetoclastic methanogenic bacteria. The toxicity was assayed in serum flasks by measuring methane production in granular sludge. Unacclimated cultures were used to minimize the biotransformation of the toxic organic chemicals during the test. The nature and the degree of the aromatic substitution were observed to have a profound effect on the toxicity of the test compound. Nitroaromatic compounds were, on the average, over 500-fold more toxic than their corresponding aromatic amines. Considering the facile reduction of nitro groups by anaerobic microorganisms, a dramatic detoxification of nitroaromatics towards methanogens can be expected to occur during anaerobic wastewater treatment. While the toxicity exerted by the N-substituted aromatic compounds was closely correlated with compound apolarity (log P), it was observed that at any given log P, N-substituted phenols had a toxicity that was 2 orders of magnitude higher than that of chlorophenols and alkylphenols. This indicates that toxicity due to the chemical reactivity of nitroaromatics is much more important than partitioning effects in bacterial membranes. PMID:8526501

Donlon, B A; Razo-Flores, E; Field, J A; Lettinga, G

1995-01-01

367

Mössbauer Study of Multiple Substitutions in YBCO  

NASA Astrophysics Data System (ADS)

Mössbauer studies of multiple substitutions in YBCO with general formula (Y1-Z Ca Z )Ba2(Cu1-X-Y Fe Y M X )3O7-? are reported. XRD has been used to find out the lattice parameters. All the samples show a single tetragonal phase formation. Iodometric titration is done to estimate the oxygen content. The present study discusses the effect of multiple substitutions of 3d-ions like Ni, Zn, Co, Mn, Cr in YBCO and the effect of various substitutions on charge balancing, oxygen content and site occupancy.

Sarkar, M.; Patel, N. V.; Mehta, P. K.; Somayajulu, D. R. S.

2001-11-01

368

A users' guide to understanding therapeutic substitutions.  

PubMed

Therapeutic substitutions are common at the level of ministries of health, clinicians, and pharmacy dispensaries. Guidance in determining whether drugs offer similar risk-benefit profiles is limited. Those making decisions on therapeutic substitutions should be aware of potential biases that make differentiating therapeutic agents difficult. Readers should consider whether the biological mechanisms and doses are similar across agents, whether the evidence is sufficiently valid across agents, and whether the safety and therapeutic effects of each drug are similar. This article uses a problem-based format to address the biological mechanism, validity, and results of a scenario in which therapeutic substitutions may be considered. PMID:24291506

Mills, Edward J; Gardner, David; Thorlund, Kristian; Briel, Matthias; Bryan, Stirling; Hutton, Brian; Guyatt, Gordon H

2014-03-01

369

40 CFR 721.7255 - Polyethyleneamine crosslinked with substituted polyethylene glycol (generic).  

Code of Federal Regulations, 2010 CFR

...Polyethyleneamine crosslinked with substituted polyethylene glycol (generic). 721.7255...Polyethyleneamine crosslinked with substituted polyethylene glycol (generic). (a) Chemical...polyethyleneamine crosslinked with substituted polyethylene glycol with substituted...

2010-07-01

370

40 CFR 721.7255 - Polyethyleneamine crosslinked with substituted polyethylene glycol (generic).  

Code of Federal Regulations, 2011 CFR

...Polyethyleneamine crosslinked with substituted polyethylene glycol (generic). 721.7255...Polyethyleneamine crosslinked with substituted polyethylene glycol (generic). (a) Chemical...polyethyleneamine crosslinked with substituted polyethylene glycol with substituted...

2011-07-01

371

Anticancer Activity of Methyl-Substituted Oxaliplatin Analogs†  

PubMed Central

Oxaliplatin is successfully used in systemic cancer therapy. However, resistance development and severe adverse effects are limiting factors for curative cancer treatment with oxaliplatin. The purpose of this study was to comparatively investigate in vitro and in vivo anticancer properties as well as the adverse effects of two methyl-substituted enantiomerically pure oxaliplatin analogs [[(1R,2R,4R)-4-methyl-1,2-cyclohexanediamine] oxalatoplatinum(II) (KP1537), and [(1R,2R,4S)-4-methyl-1,2-cyclohexanediamine]oxalatoplatinum(II) (KP1691)] and to evaluate the impact of stereoisomerism. Although the novel oxaliplatin analogs demonstrated in multiple aspects activities comparable with those of the parental compound, several key differences were discovered. The analogs were characterized by reduced vulnerability to resistance mechanisms such as p53 mutations, reduced dependence on immunogenic cell death induction, and distinctly attenuated adverse effects including weight loss and cold hyperalgesia. Stereoisomerism of the substituted methyl group had a complex and in some aspects even contradictory impact on drug accumulation and anticancer activity both in vitro and in vivo. To summarize, methyl-substituted oxaliplatin analogs harbor improved therapeutic characteristics including significantly reduced adverse effects. Hence, they might be promising metal-based anticancer drug candidates for further (pre)clinical evaluation. PMID:22331606

Jungwirth, Ute; Xanthos, Dimitris N.; Gojo, Johannes; Bytzek, Anna K.; Korner, Wilfried; Heffeter, Petra; Abramkin, Sergey A.; Jakupec, Michael A.; Hartinger, Christian G.; Windberger, Ursula; Galanski, Markus; Keppler, Bernhard K.; Berger, Walter

2012-01-01

372

Electrophoretic deposition of zinc-substituted hydroxyapatite coatings.  

PubMed

Zinc-substituted hydroxyapatite nanoparticles synthesized by the co-precipitation method were used to coat stainless steel plates by electrophoretic deposition in n-butanol with triethanolamine as a dispersant. The effect of zinc concentration in the synthesis on the morphology and microstructure of coatings was investigated. It is found that the deposition current densities significantly increase with the increasing zinc concentration. The zinc-substituted hydroxyapatite coatings were analyzed by X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy. It is inferred that hydroxyapatite and triethanolamine predominate in the chemical composition of coatings. With the increasing Zn/Ca ratios, the contents of triethanolamine decrease in the final products. The triethanolamine can be burnt out by heat treatment. The tests of adhesive strength have confirmed good adhesion between the coatings and substrates. The formation of new apatite layer on the coatings has been observed after 7days of immersion in a simulated body fluid. In summary, the results show that dense, uniform zinc-substituted hydroxyapatite coatings are obtained by electrophoretic deposition when the Zn/Ca ratio reaches 5%. PMID:24863199

Sun, Guangfei; Ma, Jun; Zhang, Shengmin

2014-06-01

373

40 CFR 721.267 - N-[2-[(substituted dinitrophenyl)azo]diallylamino-4- substituted phenyl] acetamide (generic name).  

Code of Federal Regulations, 2010 CFR

...azo]diallylamino-4- substituted phenyl] acetamide (generic name). 721...azo]diallylamino-4- substituted phenyl] acetamide (generic name). (a...azo]diallylamino-4-substituted phenyl] acetamide (PMN P-95-513)...

2010-07-01

374

The crystal chemistry and thermal stability of sol-gel prepared fluoride-substituted talc  

NASA Astrophysics Data System (ADS)

Stable, colloidal sols were prepared from the addition of methanolic (Mg(OCH3)2) to one equivalent of H2O2 in methanol. Fluoride was quantitatively incorporated by treatment of these sols with HF. Stable sols were obtained when sols, prepared from the acid catalyzed hydrolysis of tetramethylorthosilicate (TMOS), were combined with these fluoridated magnesium sols. Solvent removal gave xerogels, which were calcined, and treated with stoichiometric quantities of water at 750 °C and 1.6 kbar. The resulting products were high-purity, single-phase talcs with fluoride substitution as high as 75 mole percent; the fluoride substitution is higher than any previously reported. Powder XRD analysis showed a non-linear decrease in d(060) spacing with increasing fluoride substitution, which is attributed to a decrease in the b-dimension of talc when fluoride replaced hydroxide. FTIR spectroscopy showed a non-linear decrease in vO-H in talc with increasing fluoride substitution, which was attributed to an increase in hydrogen bonding of the OH groups and an increase in the electronegativity of the octahedral layer in talc with increasing fluoride substitution. The thermal stability of the talcs was studied using DT and TG, powder XRD, FTIR, and fluoride ion-selective electrode analyses. Synthetic talc without fluoride decomposed at 860 °C, whereas talc with 68% fluoride substitution showed essentially no decomposition when heated to 1060 °C. When heated to 1200 °C, 68% fluoride substituted talc formed amorphous material, enstatite, protoenstatite, norbergite, and chondrodite. The upper stability temperature of talc, taken as the maximum rate of the first endothermic event in its DTA profile, was dependent on the extent of fluoride substitution. Talc with 100% fluoride substitution is predicted to be stable up to ˜1100°C.

Rywak, A. A.; Burlitch, J. M.

1996-10-01

375

Acid Strengths of Some Substituted Picric Acids.  

National Technical Information Service (NTIS)

The aqueous dissociation constants for a number of substituted picric acids and related compounds were determined spectrophotometrically, and the values obtained correlated with the mid-equivalence potentials obtained by half-neutralization in acetone sol...

P. J. Pearce, R. J. J. Simkins

1968-01-01

376

Substituted Phenserines as Specific Inhibitors of Acetylcholinesterase.  

National Technical Information Service (NTIS)

The invention relates to substituted phenylcarbamate or naphthylcarbamate tricyclic compounds which provide highly potent and selective cholinergic agonist and blocking activity and their use as pharmaceutical agents. The invention further relates to impr...

A. Brossi, M. Brzostowska, S. I. Rapoport, N. Greig, X. S. He

1991-01-01

377

Questioning nuclear waste substitution: a case study.  

PubMed

This article looks at the ethical quandaries, and their social and political context, which emerge as a result of international nuclear waste substitution. In particular it addresses the dilemmas inherent within the proposed return of nuclear waste owned by Japanese nuclear companies and currently stored in the United Kingdom. The UK company responsible for this waste, British Nuclear Fuels Limited (BNFL), wish to substitute this high volume intermediate-level Japanese-owned radioactive waste for a much lower volume of much more highly radioactive waste. Special focus is given to ethical problems that they, and the UK government, have not wished to address as they move forward with waste substitution. The conclusion is that waste substitution can only be considered an ethical practice if a set of moderating conditions are observed by all parties. These conditions are listed and, as of yet, they are not being observed. PMID:17703611

Marshall, Alan

2007-03-01

378

Emerging drugs of abuse: current perspectives on substituted cathinones  

PubMed Central

Substituted cathinones are synthetic analogs of cathinone that can be considered as derivatives of phenethylamines with a beta-keto group on the side chain. They appeared in the recreational drug market in the mid-2000s and now represent a large class of new popular drugs of abuse. Initially considered as legal highs, their legal status is variable by country and is rapidly changing, with government institutions encouraging their control. Some cathinones (such as diethylpropion or pyrovalerone) have been used in a medical setting and bupropion is actually indicated for smoking cessation. Substituted cathinones are widely available from internet websites, retail shops, and street dealers. They can be sold under chemical, evocative or generic names, making their identification difficult. Fortunately, analytical methods have been developed in recent years to solve this problem. Available as powders, substituted cathinones are self-administered by snorting, oral injestion, or intravenous injection. They act as central nervous system stimulants by causing the release of catecholamines (dopamine, noradrenaline, and serotonin) and blocking their reuptake in the central and peripheral nervous system. They may also decrease dopamine and serotonin transporter function as nonselective substrates or potent blockers and may inhibit monoamine oxidase effects. Nevertheless, considerable differences have been found in the potencies of the different substituted cathinones in vitro. Desired effects reported by users include increased energy, empathy, and improved libido. Cardiovascular (tachycardia, hypertension) and psychiatric/neurological signs/symptoms (agitation, seizures, paranoia, and hallucinations) are the most common adverse effects reported. Severe toxicity signs compatible with excessive serotonin activity, such as hyperthermia, metabolic acidosis, and prolonged rhabdomyolysis, have also been observed. Reinforcing potential observed in animals predicts a high potential for addiction and abuse in users. In case of overdose, no specific antidote exists and no curative treatment has been approved by health authorities. Therefore, management of acute toxic effects is mainly extrapolated from experience with cocaine/amphetamines. PMID:24966713

Paillet-Loilier, Magalie; Cesbron, Alexandre; Le Boisselier, Reynald; Bourgine, Joanna; Debruyne, Daniele

2014-01-01

379

Nutrient-substituted hydroxyapatites: synthesis and characterization  

NASA Technical Reports Server (NTRS)

Incorporation of Mg, S, and plant-essential micronutrients into the structure of synthetic hydroxyapatite (HA) may be advantageous for closed-loop systems, such as will be required on Lunar and Martian outposts, because these apatites can be used as slow-release fertilizers. Our objective was to synthesize HA with Ca, P, Mg, S, Fe, Cu, Mn, Zn, Mo, B, and Cl incorporated into the structure, i.e., nutrient-substituted apatites. Hydroxyapatite, carbonate hydroxyapatite (CHA), nutrient-substituted hydroxyapatite (NHA), and nutrient-substituted carbonate hydroxyapatite (NCHA) were synthesized by precipitating from solution. Chemical and mineralogical analysis of precipitated samples indicated a considerable fraction of the added cations were incorporated into HA, without mineral impurities. Particle size of the HA was in the 1 to 40 nm range, and decreased with increased substitution of nutrient elements. The particle shape of HA was elongated in the c-direction in unsubstituted HA and NHA but more spherical in CHA and NCHA. The substitution of cations and anions in the HA structure was confirmed by the decrease of the d[002] spacing of HA with substitution of ions with an ionic radius less than that of Ca or P. The DTPA-extractable Cu ranged from 8 to 8429 mg kg-1, Zn ranged from 57 to 1279 mg kg-1, Fe from 211 to 2573 mg kg-1, and Mn from 190 to 1719 mg kg-1, depending on the substitution level of each element in HA. Nutrient-substituted HA has the potential to be used as a slow-release fertilizer to supply micronutrients, S, and Mg in addition to Ca and P.

Golden, D. C.; Ming, D. W.

1999-01-01

380

Chemical characterization of silicon-substituted hydroxyapatite.  

PubMed

Bioceramic specimens have been prepared by incorporating a small amount of silicon (0.4 wt %) into the structure of hydroxyapatite [Ca10(PO4)6(OH)2, HA] via an aqueous precipitation reaction to produce a silicon-substituted hydroxyapatite (Si-HA). The results of chemical analysis confirmed the proposed substitution of the silicon (or silicate) ion for the phosphorus (or phosphate) ion in hydroxyapatite. The Si-HA was produced by first preparing a silicon-substituted apatite (Si-Ap) by a precipitation process. A single-phase Si-HA was obtained by heating/calcining the as-prepared Si-Ap to temperatures above 700 degrees C; no secondary phases, such as tricalcium phosphate (TCP), tetracalcium phosphate (TeCP), or calcium oxide (CaO), were observed by X-ray diffraction analysis. Although the X-ray diffraction patterns of Si-HA and stoichiometric HA appeared to be identical, refinement of the diffraction data revealed some small structural differences between the two materials. The silicon substitution in the HA lattice resulted in a small decrease in the a axis and an increase in the c axis of the unit cell. This substitution also caused a decrease in the number of hydroxyl (OH) groups in the unit cell, which was expected from the proposed substitution mechanism. The incorporation of silicon in the HA lattice resulted in an increase in the distortion of the PO4 tetrahedra, indicated by an increase in the distortion index. Analysis of the Si-HA by Fourier transform infrared (FTIR) spectroscopy indicated that although the amount of silicon incorporated into the HA lattice was small, silicon substitution appeared to affect the FTIR spectra of HA, in particular the P-O vibrational bands. The results demonstrate that phase-pure silicon-substituted hydroxyapatite may be prepared using a simple precipitation technique. PMID:10397946

Gibson, I R; Best, S M; Bonfield, W

1999-03-15

381

Beta-substituted terthiophene [2]rotaxanes.  

PubMed

Two kinds of beta-substituted terthiophene [2]rotaxanes were synthesized using the host-guest pairs of the electron-deficient cyclophane cyclobis(paraquat-p-phenylene) (CBPQT(4+)) and the electron-rich terthiophenes with diethyleneglycol chains at the beta-position. One is made from the alpha-position non-substituted terthiophene (3 T-beta-Rx) and the other is made from the alpha-dibromo-substituted terthiophene (3 TBr-beta-Rx). The binding constants of the beta-substituted terthiophene threads were confirmed to be smaller than that of the alpha-substituted terthiophene analogue. By UV/Vis absorption measurements, we confirmed the charge-transfer (CT) band in the visible region with an extinction coefficient of approximately 10(2) (M(-1) cm(-1)). Strong, but not quantitative, quenching of the terthiophene fluorescence was confirmed for the [2]rotaxanes. Although the beta-substituted terthiophene thread was electrochemically polymerizable, the [2]rotaxane 3 T-beta-Rx was not polymerizable. This result indicates that the interlocked CBPQT(4+) macrocycle effectively suppresses the electrochemical polymerization of the terthiophene unit because electrostatic repulsive and steric effects of CBPQT(4+) hinder the dimerization of the terthiophene radical cations. In the electrochemical measurement, we confirmed the shift of the first reduction peak towards less negative potential compared to free CBPQT(4+) and the splitting of the second reduction peak. These electrochemical behaviors are similar to those observed for the highly-constrained [2]rotaxanes. The beta-substituted terthiophene [2]rotaxanes reported herein are important key compounds to prepare polythiophene polyrotaxanes. PMID:19308975

Ikeda, Taichi; Higuchi, Masayoshi; Kurth, Dirk G

2009-01-01

382

Telecommunications\\/ transportation substitution and energy conservation Part 2  

Microsoft Academic Search

Part 1 of this article reviewed existing research both on attitudes toward telecommunications substitution for travel and on operational experiments with teleconferencing and telecommuting. Part 2 examines major factors influencing substitution, including government policy. It concludes that government policy can significantly facilitate telecommunications substitution for travel and, indeed, the achievement of any real measure of substitution may depend upon proactive

Kenneth L. Kraemer; John Leslie King

1982-01-01

383

Comparison of Dermal Substitutes in Wound Healing Utilizing a Nude Mouse Model  

PubMed Central

Background: Dermal skin substitutes have become a standard of care in burn treatment. Objective: To compare and assess wound contracture reduction and histologic incorporation into the wound, dermal substitutes were implanted into full-thickness skin wounds in nude mice. Materials and Methods: Thirty-seven mice received a full-thickness 2 × 2 cm dorsal skin wound, and were either implanted with an acellular dermal matrix, Alloderm, Dermagraft-TC, Dermalogen, or Integra or assigned to the control group (with no dermal substitute). At 28 days postsurgery, the wounds were assessed for contraction, epithelialization, and other histological characteristics. Results: Each dermal substitute decreased wound contracture, but Alloderm and the acellular dermal matrix did so significantly compared to the control (P < .01 and P < .03, respectively). Within-group and control comparisons showed no significant differences with respect to the presence of dystrophic calcification, squamous hyperplasia, infiltration of neutrophils, fibroblasts, and macrophages, epidermal keratinocyte stratification, or collagen fiber configuration. Conclusions: Integra elicited the greatest foreign body response. Although the Dermalogen group had the thickest elastin fiber fragments, Dermagraft may have initiated the earliest elastin fiber formation in the wounds. While all dermal substitutes were incorporated into the wound bed and wound contracture was decreased, acellular dermal matrix and Alloderm, both human skin–derived products, produced less contraction and the thickest new “dermis” in the healed wounds compared to the control or synthetic dermal substitutes. PMID:16921409

Truong, Anh-Tuan N.; Kowal-Vern, Areta; Latenser, Barbara A.; Wiley, Dorion E.; Walter, Robert J.

2005-01-01

384

Rapid hydrothermal flow synthesis and characterisation of carbonate- and silicate-substituted calcium phosphates.  

PubMed

A range of crystalline and nano-sized carbonate- and silicate-substituted hydroxyapatite has been successfully produced by using continuous hydrothermal flow synthesis technology. Ion-substituted calcium phosphates are better candidates for bone replacement applications (due to improved bioactivity) as compared to phase-pure hydroxyapatite. Urea was used as a carbonate source for synthesising phase pure carbonated hydroxyapatite (CO?-HA) with ?5?wt% substituted carbonate content (sample 7.5CO?-HA) and it was found that a further increase in urea concentration in solution resulted in biphasic mixtures of carbonate-substituted hydroxyapatite and calcium carbonate. Transmission electron microscopy images revealed that the particle size of hydroxyapatite decreased with increasing urea concentration. Energy-dispersive X-ray spectroscopy result revealed a calcium deficient apatite with Ca:P molar ratio of 1.45 (±0.04) in sample 7.5CO?-HA. For silicate-substituted hydroxyapatite (SiO?-HA) silicon acetate was used as a silicate ion source. It was observed that a substitution threshold of ?1.1?wt% exists for synthesis of SiO?-HA in the continuous hydrothermal flow synthesis system, which could be due to the decreasing yields with progressive increase in silicon acetate concentration. All the as-precipitated powders (without any additional heat treatments) were analysed using techniques including Transmission electron microscopy, X-ray powder diffraction, Differential scanning calorimetry, Thermogravimetric analysis, Raman spectroscopy and Fourier transform infrared spectroscopy. PMID:22983020

Chaudhry, Aqif A; Knowles, Jonathan C; Rehman, Ihtesham; Darr, Jawwad A

2013-09-01

385

Azo Group-Assisted Nucleophilic Aromatic Substitutions in Haloarene Derivatives: Preparation of Substituted  

E-print Network

Azo Group-Assisted Nucleophilic Aromatic Substitutions in Haloarene Derivatives: Preparation piotr@ctrvax.vanderbilt.edu Received July 25, 2003 Aryldiazo substituents were used in nucleophilic aromatic substitution reactions of halogens. The Ph-NdN- group activates ortho fluorine atoms toward

Kaszynski, Piotr

386

Regioselective nucleophilic substitution reaction of meso-hexakis(pentafluorophenyl) substituted [26]hexaphyrin  

Microsoft Academic Search

Reaction of various alkoxides led to the selective replacement of the p-fluorine substituents of meso-hexakis(pentafluorophenyl) substituted [26]hexaphyrin. Reaction with isopropyl amine gave meso-hexakis(4-isopropylamino-2,3,5,6-tetrafluorophenyl) substituted [28]hexaphyrin.

Masaaki Suzuki; Soji Shimizu; Ji-Young Shin; Atsuhiro Osuka

2003-01-01

387

The effect of particle size on the osteointegration of injectable silicate-substituted calcium phosphate bone substitute materials  

PubMed Central

Calcium phosphate (CaP) particles as a carrier in an injectable bone filler allows less invasive treatment of bony defects. The effect of changing granule size within a poloxamer filler on the osteointegration of silicate-substituted calcium phosphate (SiCaP) bone substitute materials was investigated in an ovine critical-sized femoral condyle defect model. Treatment group (TG) 1 consisted of SiCaP granules sized 1000–2000 ?m in diameter (100 vol %). TG2 investigated a granule size of 250–500 ?m (75 vol %), TG3 a granule size of 90–125 ?m (75 vol %) and TG4 a granule size of 90–125 ?m (50 vol %). Following a 4 and 8 week in vivo period, bone area, bone-implant contact, and remaining implant area were quantified within each defect. At 4 weeks, significantly increased bone formation was measured in TG2 (13.32% ± 1.38%) when compared with all other groups (p = 0.021 in all cases). Bone in contact with the bone substitute surface was also significantly higher in TG2. At 8 weeks most new bone was associated within defects containing the smallest granule size investigated (at the lower volume) (TG4) (42.78 ± 3.36%) however this group was also associated with higher amounts of fragmented SiCaP. These smaller particles were phagocytosed by macrophages and did not appear to have a negative influence on healing. In conclusion, SiCaP granules of 250–500 ?m in size may be a more suitable scaffold when used as an injectable bone filler and may be a convenient method for treating bony defects. © 2013 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 902–910, 2013 PMID:23362131

Coathup, Melanie J; Cai, Qian; Campion, Charlie; Buckland, Thomas; Blunn, Gordon W

2013-01-01

388

Substituting telecommunications for travel - Feasible or desirable  

NASA Technical Reports Server (NTRS)

This paper reviews recent advances in telecommunications and examines the detailed structure of travel to estimate the feasibility of substituting telecommunications for various travel objectives. The impact of travel is analyzed from a social, economic, energy, and pollution standpoint to assess the desirability of substitution. Perhaps 35-50% of the nation's travel could, in theory, be replaced by very advanced telecommunications (such as a much improved large-screen teleconferencing network), but public resistance would be massive. Much economic dislocation would result since, for example, over 25% of retail sales are travel-related. The energy savings would be modest since only 25% of the nation's energy is consumed by transportation. However, all pollution would be reduced substantially since transportation accounts for 75% of the carbon monoxide, 60% of the hydrocarbon, and 55% of the nitrogen oxide pollution in the nation. Problems related to the implementation of large-scale substitution are discussed.

Van Vleck, E. M.

1974-01-01

389

Nonlinear self-adjointness through differential substitutions  

NASA Astrophysics Data System (ADS)

It is known (Ibragimov, 2011; Galiakberova and Ibragimov, 2013) [14,18] that the property of nonlinear self-adjointness allows to associate conservation laws of the equations under study, with their symmetries. In this paper we show that, even when the equation is nonlinearly self-adjoint with a non differential substitution, finding the explicit form of the differential substitution can provide new conservation laws associated to its symmetries. By using the general theorem on conservation laws (Ibragimov, 2007) [11] and the property of nonlinear self-adjointness we find some new conservation laws for the modified Harry-Dym equation. By using a differential substitution we construct a conservation law for the Harry-Dym equation, which has not been derived before using Ibragimov method.

Gandarias, M. L.

2014-10-01

390

Poly-substance use and antisocial personality traits at admission predict cumulative retention in a buprenorphine programme with mandatory work and high compliance profile  

Microsoft Academic Search

Background  Continuous abstinence and retention in treatment for alcohol and drug use disorders are central challenges for the treatment\\u000a providers. The literature has failed to show consistent, strong predictors of retention. Predictors and treatment structure\\u000a may differ across treatment modalities. In this study the structure was reinforced by the addition of supervised urine samples\\u000a three times a week and mandatory daily

Leif Öhlin; Morten Hesse; Mats Fridell; Per Tätting

2011-01-01

391

Soluble N-Substituted Organosilane Polybenzimidazoles  

SciTech Connect

Six organosilane derivatives were synthesized, and are more soluble in common organic solvents (tetrahydrofuran and chloroform) than the parent polybenzimidazole. Our polymer modification pathway provides a straightforward synthesis that can be carried out at room temperature and give reasonable yields. Solution 1H NMR spectra of both the parent and deprotonated polybenzimidazoles are reported. Based upon the NMR analysis in CDCl3, nearly all of the benzimidazole N-H positions are substituted by the organosilane moieties. Some of the modified polymers have similar thermal properties compared to the parent polymer, and the average molecular weights are higher for the substituted polybenzimidazoles than the parent PBI.

Klaehn, J. R.; Luther, T. A.; Orme, C. J.; Jones, M. G.; Wertsching, A. K.; Peterson, E. S.

2007-10-01

392

Characterization of mutagenic activity in grain-based coffee-substitute blends and instant coffees  

SciTech Connect

Several grain-based coffee-substitute blends and instant coffees showed a mutagenic response in the Ames/Salmonella test using TA98, YG1024 and YG1O29 with metabolic activation. The beverage powders contained 150 to 500 TA98 and 1150 to 4050 YG1024 revertant colonies/gram, respectively. The mutagenic activity in the beverage powders was shown to be stable to heat and the products varied in resistance to acid nitrite treatment. Characterization of the mutagenic activity, using HPLC-and the Ames test of the collected fractions, showed the coffee-substitutes and instant coffees contain several mutagenic compounds, which are most likely aromatic amines.

Johansson, M.A.E.; Knize, M.G.; Felton, J.S.; Jagerstad, M.

1994-06-01

393

Preparation and characterization of cobalt-substituted anthrax lethal factor  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Cobalt-substituted anthrax lethal factor (CoLF) is highly active. Black-Right-Pointing-Pointer CoLF can be prepared by bio-assimilation and direct exchange. Black-Right-Pointing-Pointer Lethal factor binds cobalt tightly. Black-Right-Pointing-Pointer The electronic spectrum of CoLF reveals penta-coordination. Black-Right-Pointing-Pointer Interaction of CoLF with thioglycolic acid follows a 2-step mechanism. -- Abstract: Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of mitogen-activated protein kinase kinases near their N-termini. The current report concerns the preparation of cobalt-substituted LF (CoLF) and its characterization by electronic spectroscopy. Two strategies to produce CoLF were explored, including (i) a bio-assimilation approach involving the cultivation of LF-expressing Bacillus megaterium cells in the presence of CoCl{sub 2}, and (ii) direct exchange by treatment of zinc-LF with CoCl{sub 2}. Independent of the method employed, the protein was found to contain one Co{sup 2+} per LF molecule, and was shown to be twice as active as its native zinc counterpart. The electronic spectrum of CoLF suggests the Co{sup 2+} ion to be five-coordinate, an observation similar to that reported for other Co{sup 2+}-substituted gluzincins, but distinct from that documented for the crystal structure of native LF. Furthermore, spectroscopic studies following the exposure of CoLF to thioglycolic acid (TGA) revealed a sequential mechanism of metal removal from LF, which likely involves the formation of an enzyme: Co{sup 2+}:TGA ternary complex prior to demetallation of the active site. CoLF reported herein constitutes the first spectroscopic probe of LF's active site, which may be utilized in future studies to gain further insight into the enzyme's mechanism and inhibitor interactions.

Saebel, Crystal E.; Carbone, Ryan; Dabous, John R.; Lo, Suet Y. [Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Rd., Sudbury, Ontario, Canada P3E 2C6 (Canada)] [Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Rd., Sudbury, Ontario, Canada P3E 2C6 (Canada); Siemann, Stefan, E-mail: ssiemann@laurentian.ca [Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Rd., Sudbury, Ontario, Canada P3E 2C6 (Canada)] [Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Rd., Sudbury, Ontario, Canada P3E 2C6 (Canada)

2011-12-09

394

Sol-gel preparation and characterization of non-substituted and Sr-substituted lanthanum cobaltates  

Microsoft Academic Search

This paper reports on the results concerning the sol-gel preparation and characterization of Sr-substituted perovskite lanthanum\\u000a cobaltates La1?xSrxCoO3?? (x = 0.0, 0.25, 0.5 and 0.75). The metal ions, generated by dissolving starting materials in diluted acetic acid were complexed\\u000a by 1,2-ethanediol to obtain the precursors for the non-substituted and Sr-substituted LaCoO3. The influence of the synthesis temperature, heating time and

Sigute Cizauskaite; Aivaras Kareiva

2008-01-01

395

Sol–gel preparation and characterization of non-substituted and Sr-substituted gadolinium cobaltates  

Microsoft Academic Search

An aqueous sol–gel chemistry approach for the preparation of Sr-substituted perovskite gadolinium cobaltates Gd1?xSrxCoO3?? (x=0.0, 0.25, 0.5 and 0.75) has been applied. The metal ions, generated by dissolving starting materials in diluted acetic acid were complexed by EDTA to obtain the precursors for non-substituted and Sr-substituted GdCoO3. However, only two single-phase cobaltate samples with x=0.0 and 0.25 have been obtained

S. Cizauskaite; S. Johnsen; J.-E. Jørgensen; A. Kareiva

2011-01-01

396

Coal as a Substitute for Carbon Black  

NASA Technical Reports Server (NTRS)

New proposal shows sprayed coal powder formed by extrusion of coal heated to plastic state may be inexpensive substitute for carbon black. Carbon black is used extensively in rubber industry as reinforcing agent in such articles as tires and hoses. It is made from natural gas and petroleum, both of which are in short supply.

Kushida, R. O.

1982-01-01

397

Multisensory perceptual learning and sensory substitution.  

PubMed

One of the most exciting recent findings in neuroscience has been the capacity for neural plasticity in adult humans and animals. Studies of perceptual learning have provided key insights into the mechanisms of neural plasticity and the changes in functional neuroanatomy that it affords. Key questions in this field of research concern how practice of a task leads to specific or general improvement. Although much of this work has been carried out with a focus on a single sensory modality, primarily visual, there is increasing interest in multisensory perceptual learning. Here we will examine how advances in perceptual learning research both inform and can be informed by the development and advancement of sensory substitution devices for blind persons. To allow 'sight' to occur in the absence of visual input through the eyes, visual information can be transformed by a sensory substitution device into a representation that can be processed as sound or touch, and thus give one the potential to 'see' through the ears or tongue. Investigations of auditory, visual and multisensory perceptual learning can have key benefits for the advancement of sensory substitution, and the study of sensory deprivation and sensory substitution likewise will further the understanding of perceptual learning in general and the reverse hierarchy theory in particular. It also has significant importance for the developing understanding of the brain in metamodal terms, where functional brain areas might be best defined by the computations they carry out rather than by their sensory-specific processing role. PMID:23220697

Proulx, Michael J; Brown, David J; Pasqualotto, Achille; Meijer, Peter

2014-04-01

398

Formalizations Of Substitution Of Equals For Equals  

E-print Network

-half of Leibniz's characterization of equality holds in pure predicate calculus F1: Definition 1. Substitution the relation between these three formalizations. In Sect. 2, we present Church's first-order logic F1 [2. In Sect. 3, we introduce introduce logic LF, which includes Leibniz as an inference rule, and prove that F

Schneider, Fred B.

399

Formalizations Of Substitution Of Equals For Equals  

E-print Network

­half of Leibniz's characterization of equality holds in pure predicate calculus F1: Definition 1. Substitution]. This article explores the relation between these three formalizations. In Sect. 2, we present Church's first), called Leibniz. In Sect. 3, we introduce introduce logic LF, which includes Leibniz as an inference rule

Schneider, Fred B.

400

A Partial Taxonomy of Substitutability and Interchangeability  

E-print Network

Substitutability, interchangeability and related concepts in Constraint Programming were introduced approximately twenty years ago and have given rise to considerable subsequent research. We survey this work, classify, and relate the different concepts, and indicate directions for future work, in particular with respect to making connections with research into symmetry breaking. This paper is a condensed version of a larger work in progress.

Karakashian, Shant; Choueiry, Berthe Y; Prestwhich, Steven; Freuder, Eugene C

2010-01-01

401

Syntheses of novel substituted-boranophosphate nucleosides.  

PubMed

A number of substituted (borano) nucleic acids, 3'-[diethylphosphite(cyano, carboxy, or carbamoyl) borano] deoxynucleosides (3a-4c) and 5'-[diethylphosphite(cyano or carboxy) borano] deoxynucleosides (6a-7d) were prepared by a variety of synthetic procedures. The syntheses of the pyrophosphates (2a-2c), as precursors for 3a-4c, are also described. PMID:12484452

Vyakaranam, Kamesh; Rana, Geeta; Spielvogel, Bernard F; Maguire, John A; Hosmane, Narayan S

2002-01-01

402

Implicit Semantic Perception in Object Substitution Masking  

ERIC Educational Resources Information Center

Decades of research on visual perception has uncovered many phenomena, such as binocular rivalry, backward masking, and the attentional blink, that reflect "failures of consciousness". Although stimuli do not reach awareness in these paradigms, there is evidence that they nevertheless undergo semantic processing. Object substitution masking (OSM),…

Goodhew, Stephanie C.; Visser, Troy A. W.; Lipp, Ottmar V.; Dux, Paul E.

2011-01-01

403

Substituting transistor for diode improves rectifying means  

NASA Technical Reports Server (NTRS)

Unusual transistor connection that substitutes for a silicon diode and allows significantly higher repetition rates without increasing power loss rectifies an alternating current. Operation speed is improved by a factor of 10 or more when a given diode is replaced by this transistor circuit.

Muller, R. M.

1966-01-01

404

The Approval Plan: Selection Aid, Selection Substitute  

ERIC Educational Resources Information Center

Approval plans are used by many libraries as an adjunct to title-by-title selection, and sometimes as a substitute for it. The author examines this approach to purchasing library materials, considering positive and negative effects approval plans may have on collection balance as well as on acquisitions budgets and workflow. The article also…

Fenner, Audrey

2004-01-01

405

Tissue substitutes in experimental radiation physics  

Microsoft Academic Search

In this review of tissue substitute materials, the historical development of the important systems is traced from the early 1900's. Tabulations of the constituents, elemental compositions, specific gravities, and the photon and electron interaction characteristics of 64 materials are given together with recommendations of systems having useful simulation properties. Formulation and manufacturing procedures are described and possible future developments in

D. R. White

1978-01-01

406

Substitution Criteria and Policy for Major Items.  

National Technical Information Service (NTIS)

The lack of adequate guidance and policy and, in some cases, conflicting guidance in the processing of major items that are used as substitutes for authorized items have created problems in the management of these items. This report investigates the exist...

U. R. Poskus

1979-01-01

407

Law of substitution for mixed arrays  

SciTech Connect

The nuclear safety justification of a mixed array of dissimilar fissile units of metal units and dilute solution units, according to Clayton, has been a persistent and nagging problem. Dissimilar uranium metal or dissimilar uranium solution units in a mixed array can also create a modeling nightmare for the nuclear criticality safety engineer. Now, a calculational method known as the Law of Substitution has been developed to ensure that the k/sub eff/ of an array of uranium metal and uranium solution units will satisfy any k/sub eff/ limit set by the nuclear safety engineer. The nuclear criticality safety engineer can utilize the Law of Substitution to safely mix or substitute different uranium metal units, different uranium solution units, and more importantly, uranium metal and dilute UO/sub 2/ solution units in an array. The Law of Substitution is as follows: (1) calculate the k/sub eff/ of each unit type in its own infinite planar array. (2) Determine the edge-to-edge spacing of the infinite planar array of each type of unit to satisfy a desired k/sub eff/. (3) Select the largest edge-to-edge spacing from among the similar units in their infinite planar arrays and use that spacing for the finite or infinite planar array of mixed units.

Koudelka, A.J.

1987-01-01

408

Substitution effects in magnetic and superconducting materials  

Microsoft Academic Search

Chemical substitutions at very low level have been proved to be a very effective tool to change important physical parameters in many kinds of materials. These modifications may be the result of, for instance, subtle variations of the position of the Fermi level with respect to the density of states, presence of additional electrons which may change the hole carrier

O. PEÑA

409

Catalytic Asymmetric Synthesis of Highly Substituted Pyrrolizidines  

PubMed Central

A catalytic asymmetric double (1,3)-dipolar cycloaddition reaction has been developed. Using a chiral silver catalyst, enantioenriched pyrrolizidines can be prepared in one flask from inexpensive, commercially available starting materials. The pyrrolizidine products contain a variety of substitution patterns and as many as six stereogenic centers. PMID:23565328

Lim, Andrew D.; Codelli, Julian A.

2012-01-01

410

Allogeneic skin substitutes applied to burns patients.  

PubMed

Early re-surfacing of burn wounds remains the ideal but is limited by the availability of skin graft donor sites. Cultured grafts overcome these problems and autologous keratinocytes can be grown in culture and placed on a dermal substitute, but this results in delay and requires two operations. We developed an organotypic skin substitute, which achieves cover in one procedure, and have previously found allogeneic cell survival up to 2.5 years after grafting onto clean elective wounds (tattoo removal). Here, we report a short series using the same model applied to burns patients with less than 20% total body surface area affected. The skin substitutes consisted of allogeneic dermal fibroblasts embedded in a collagen gel overlain with allogeneic epidermal keratinocytes, and were grafted to patients with tangentially excised burns. A side-by-side comparison with meshed split-thickness autografts was performed. No grafts became infected. The allogeneic skin substitute showed little effective take at 1 week, and by 2 weeks only small islands of keratinocytes survived. These sites were subsequently covered with meshed split-thickness autograft, which took well. It is concluded that further development of this model is needed to overcome the hostile wound bed seen in burns patients. PMID:11996857

Nanchahal, J; Dover, R; Otto, W R

2002-05-01

411

Are substitution rates and RNA editing correlated?  

PubMed Central

Background RNA editing is a post-transcriptional process that, in seed plants, involves a cytosine to uracil change in messenger RNA, causing the translated protein to differ from that predicted by the DNA sequence. RNA editing occurs extensively in plant mitochondria, but large differences in editing frequencies are found in some groups. The underlying processes responsible for the distribution of edited sites are largely unknown, but gene function, substitution rate, and gene conversion have been proposed to influence editing frequencies. Results We studied five mitochondrial genes in the monocot order Alismatales, all showing marked differences in editing frequencies among taxa. A general tendency to lose edited sites was observed in all taxa, but this tendency was particularly strong in two clades, with most of the edited sites lost in parallel in two different areas of the phylogeny. This pattern is observed in at least four of the five genes analyzed. Except in the groups that show an unusually low editing frequency, the rate of C-to-T changes in edited sites was not significantly higher that in non-edited 3rd codon positions. This may indicate that selection is not actively removing edited sites in nine of the 12 families of the core Alismatales. In all genes but ccmB, a significant correlation was found between frequency of change in edited sites and synonymous substitution rate. In general, taxa with higher substitution rates tend to have fewer edited sites, as indicated by the phylogenetically independent correlation analyses. The elimination of edited sites in groups that lack or have reduced levels of editing could be a result of gene conversion involving a cDNA copy (retroprocessing). If so, this phenomenon could be relatively common in the Alismatales, and may have affected some groups recurrently. Indirect evidence of retroprocessing without a necessary correlation with substitution rate was found mostly in families Alismataceae and Hydrocharitaceae (e.g., groups that suffered a rapid elimination of all their edited sites, without a change in substitution rate). Conclusions The effects of substitution rate, selection, and/or gene conversion on the dynamics of edited sites in plant mitochondria remain poorly understood. Although we found an inverse correlation between substitution rate and editing frequency, this correlation is partially obscured by gene retroprocessing in lineages that have lost most of their edited sites. The presence of processed paralogs in plant mitochondria deserves further study, since most evidence of their occurrence is circumstantial. PMID:21070620

2010-01-01

412

Element-substituted polyaromatic mesophases: II a comparison of various synthesis routes for boron substitution  

Microsoft Academic Search

The synthesis of boron-substituted polyaromatic mesophase was studied by (1) co-pyrolysis of a filtered coal tar pitch with three different borane complexes, (2) pyrolysis of a boron-containing polymer produced by co-polymerisation of divinylbenzene with borane, and (3) pyrolysis of boron-substituted\\/crosslinked acenaphthylene, produced by hydroboronation of acenaphthylene. The pyrolyses were performed at an argon gas pressure of 1 MPa to suppress

J. Gremmels; G. Geiger; M. Braun; K. J. Hüttinger

1998-01-01

413

Water/Wastewater Treatment Plant Operator Qualifications.  

ERIC Educational Resources Information Center

This article summarizes in tabular form the U.S. and Canadian programs for classification of water and wastewater treatment plant personnel. Included are main characteristics of the programs, educational and experience requirements, and indications of requirement substitutions. (CS)

Water and Sewage Works, 1979

1979-01-01

414

An in vitro study into the effect of zinc substituted hydroxyapatite on osteoclast number and activity.  

PubMed

Zinc ions have been shown to inhibit osteoclast development and proliferation both in vitro and in vivo. The same inhibiting effect has been observed in vitro when zinc was substituted into tri-calcium phosphate (TCP). Because of the solubility of TCP it is not an ideal candidate for a material to inhibit osteoclast activity in the long term. Hydroxyapatite (HA) is less soluble and so potentially offers a more long-term, sustainable effect. Previous work has shown that zinc can successfully be substituted into HA and still retain phase purity after heat treatment. The study reported here presents the effects of zinc substituted HA on the development and activity of osteoclast-like cells. It was found that increasing zinc substitution levels led to a decrease in the number of these cells present after 21 days. When resorption activity was investigated it was found that an increase in the amount of zinc present in the discs led to a significant decrease in the amount of resorption taking place on the discs. These results provide evidence for the potential of zinc substituted HA as a material to reduce resorptive activity to provide long-term bonding of implant to bone. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4136-4141, 2014. PMID:24443251

Shepherd, David V; Kauppinen, Kyösti; Brooks, Roger A; Best, Serena M

2014-11-01

415

40 CFR 721.6181 - Fatty acid, reaction product with substituted oxirane, formaldehyde-phenol polymer glycidyl ether...  

Code of Federal Regulations, 2011 CFR

...substituted oxirane, formaldehyde-phenol polymer glycidyl ether, substituted proplyamine...substituted oxirane, formaldehyde-phenol polymer glycidyl ether, substituted proplyamine...substituted oxirane, formaldehyde-phenol polymer glycidyl ether, substituted...

2011-07-01

416

40 CFR 721.6181 - Fatty acid, reaction product with substituted oxirane, formaldehyde-phenol polymer glycidyl ether...  

Code of Federal Regulations, 2010 CFR

...substituted oxirane, formaldehyde-phenol polymer glycidyl ether, substituted proplyamine...substituted oxirane, formaldehyde-phenol polymer glycidyl ether, substituted proplyamine...substituted oxirane, formaldehyde-phenol polymer glycidyl ether, substituted...

2010-07-01

417

Practical Linguistic Steganography using Contextual Synonym Substitution and a  

E-print Network

Practical Linguistic Steganography using Contextual Synonym Substitution and a Novel Vertex Coding steganography is concerned with hiding information in natural language text. One of the major transformations used in linguistic steganography is synonym substitution. However, few existing studies have studied

418

Representations of Substitute Teachers and the Paradoxes of Professionalism.  

ERIC Educational Resources Information Center

Explores narratives about teacher work articulated through representations of substitute teachers, using this representation to render visible assumptions governing boundaries of professionalism. The article discusses professional teachers as constructed in educational reform; images of substitute teachers (incompetent, unqualified, deviant…

Weems, Lisa

2003-01-01

419

48 CFR 1328.106-2 - Substitution of surety bonds.  

Code of Federal Regulations, 2013 CFR

...Bonds and Other Financial Protections 1328.106-2 Substitution of surety bonds. The designee authorized to approve substituting a new surety bond for the previously approved original bond is set forth in CAM...

2013-10-01

420

48 CFR 1328.106-2 - Substitution of surety bonds.  

Code of Federal Regulations, 2011 CFR

...Bonds and Other Financial Protections 1328.106-2 Substitution of surety bonds. The designee authorized to approve substituting a new surety bond for the previously approved original bond is set forth in CAM...

2011-10-01

421

48 CFR 1328.106-2 - Substitution of surety bonds.  

Code of Federal Regulations, 2010 CFR

...Bonds and Other Financial Protections 1328.106-2 Substitution of surety bonds. The designee authorized to approve substituting a new surety bond for the previously approved original bond is set forth in CAM...

2010-10-01

422

48 CFR 1328.106-2 - Substitution of surety bonds.  

Code of Federal Regulations, 2012 CFR

...Bonds and Other Financial Protections 1328.106-2 Substitution of surety bonds. The designee authorized to approve substituting a new surety bond for the previously approved original bond is set forth in CAM...

2012-10-01

423

Hollow fiber liquid-phase microextraction combined with ultra-high performance liquid chromatography-tandem mass spectrometry for the simultaneous determination of naloxone, buprenorphine and norbuprenorphine in human plasma.  

PubMed

A hollow fiber liquid phase microextraction (HF-LPME) combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the extraction and determination of naloxone (NLX), buprenorphine (BP) and its major metabolite norbuprenorphine (NBP) in human plasma. The optimum extraction conditions of HF-LPME were: the porous of polyvinylidene fluoride (PVDF) hollow fiber was full of component solvent (1-octanol/chloroform/toluene, 2/4/4), the pH of donor phase was 8.7, the extraction time was 30min and stirring speed was 1000 revolutions per minute (rpm). The UHPLC-MS/MS method was performed with Waters ACQUITY UPLCTM BEH C18, 50mm×2.1mm, 1.7?m, using methanol-0.2%formic acid as mobile phase with a gradient elution at a flow rate of 0.25mL/min. The target compounds were detected under a tandem quadrupole mass spectrometer in positive electrospray ionization (ESI) mode, then analyzed in multiple reaction monitoring (MRM) mode and the isotope internal standard method was used for quantification. The results showed that linearities were in the range of 0.1-25ng/mL (R>0.996). The limits of detection (LOD) of BP/NBP/NLX were 0.05/0.05/0.025ng/mL and the limits of quantitation (LOQ) of BP/NBP/NLX were 0.1/0.1/0.05ng/mL, respectively. The spiked recoveries were in the range of 92.1-106.0% with relative standard deviation (RSD) values were less than 15%. This method was simple, inexpensive, sensitive and has been successfully used to quantify plasma samples from patients included in a clinical pharmacogenetic study. PMID:24566267

Sun, Wenjun; Qu, Shuping; Du, Zhenxia

2014-03-01