Buprenorphine treatment of opioid dependence: analysis of individual patient data

AbstractBackgroundThe efficacy and safety of buprenorphine alone and in combination with naloxone for treatment of opioid dependence were evaluated in Federally-sponsored randomized clinical trials. Meta-analysis of pooled individual participant data provides an opportunity to identify multiple predictors of buprenorphine treatment outcome.MethodsWe selected six buprenorphine efficacy and safety trials from NIDA’s Data Share database for analysis. Treatment, sociodemographic, and drug use history variable domains were systematically harmonized and included in analysis. After exclusions, 3,022 participants randomized or enrolled in buprenorphine treatment for opioid dependence (mean (SD) age 36.1 (9.8) years, 33% female, 66% White, 16% Hispanic, 14% Black), were analyzed using a generalized linear mixed model with time-weighted treatment variables and participant covariates. We defined positive urinalysis or self-reported lapse as the primary outcome.ResultsFour treatment variables were significantly associated (p < 0.001) with lapse. Time-weighted dose and time-weighted adaptive dose had greater estimated effects than time-in-trial and time-weighted clinic visit. All treatment variables were novel predictors of lapse.ConclusionsIn a large cohort of trial participants treated with buprenorphine and behavioral counseling for opioid dependence, we identified and ranked four novel treatment factors reflecting components of buprenorphine dose, clinical provider engagement and patient engagement. Additional research to explore the effects of pharmacologic and non- pharmacologic treatment factors, and to explore relations with provider and patient factors will help our understanding of buprenorphine treatment outcomes. Continued analyses of publicly available data will extend discovery and support development of personalized opioid use disorder treatments.Highlights (3 to 5 bullet point max 85 characters each including spaces)Treatment and participant variables were harmonized in six buprenorphine trialsTime-weighted treatment variables were used in a random effects mixed model of lapseBuprenorphine dose and three clinical interactions were protective against lapseSupport of protective treatment factors may improve buprenorphine treatment success

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Effect of acupuncture for methadone maintenance treatment patients: study protocol of a randomized clinical trial

Trials ◽

10.1186/s13063-020-04930-x ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Hao Wen ◽

Shichao Xu ◽

Jingchun Zeng ◽

Shuqi Ge ◽

Yuan Liao ◽

...

Keyword(s):

Clinical Trial ◽

Adjunctive Therapy ◽

Opioid Dependence ◽

Methadone Maintenance ◽

Controlled Trial ◽

Urine Test ◽

Efficacy And Safety ◽

Opioid Use ◽

Randomized Controlled ◽

Sf 36

Abstract Background Opioid dependence is an increasing public health problem all over the world. Patients with opioid dependence have to receive methadone maintenance therapy (MMT) as replacement therapy for years or even for their entire life. Acupuncture as a kind of therapy has been used to treat substance dependence for many years. Jin’s three-needle acupuncture (JTN), a type of acupuncture technique, has been applied to treat various diseases for several decades. However, JTN as an acupuncture technique has not been used to treat patients receiving MMT. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of acupuncture as adjunctive therapy for patients receiving MMT. Methods/design This study is a parallel-arm, randomized controlled trial that aims to evaluate the efficacy and safety of acupuncture as adjunctive therapy for patients receiving MMT. A total of 140 eligible participants who range in age from 18 to 60 years and fulfil the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V), for opiate dependence will be enrolled into this study. All eligible participants will be randomly assigned to the acupuncture group or routine group in a 1:1 allocation ratio. Participants who are enrolled in the acupuncture group will receive MMT and JTN treatment for 30 min per session. Meanwhile, those who are assigned to the routine arm will receive MMT only. All 18 sessions of JTN treatment will be delivered over 6 weeks (3 per week) and followed by a 4-week follow-up period. The primary outcome measure will be the visual analogue scale (VAS) for drug craving and the daily consumption of methadone (DCOM). Secondary outcome measures will include the urine test for opioid use, the 36-item Short Form Survey (SF-36), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory II (BDI-II) and Pittsburgh sleep quality index (PSQI). VAS, DCOM, BAI, BDI-II and the urine test for opioid use will be evaluated at baseline, the second week, the fourth week, the sixth week and the tenth week. SF-36 and PSQI will be assessed at baseline, the fourth week, the sixth week and the tenth week. Discussion The results of this trial will provide evidence on the efficacy and safety of acupuncture as adjunctive therapy for patients receiving MMT. Trial registration Chinese Clinical Trial Registry ChiCTR1900026357. Registered on 2 October 2019.

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Clinical Evaluation of Three Surgical Modalities in the Treatment of Peri-Implantitis: A Randomized Controlled Clinical Trial

Journal of Clinical Medicine ◽

10.3390/jcm8070966 ◽

2019 ◽

Vol 8 (7) ◽

pp. 966 ◽

Cited By ~ 6

Author(s):

Selena Toma ◽

Michel C. Brecx ◽

Jerome F. Lasserre

Keyword(s):

Bone Loss ◽

Mixed Model ◽

Linear Mixed Model ◽

Treatment Success ◽

The Other ◽

Successful Outcome ◽

Controlled Clinical Trial ◽

Gingival Index ◽

Bleeding On Probing ◽

Attachment Level

Objectives: To compare the efficacy of three mechanical procedures for surgically treating peri-implantitis. Materials and Methods: In a randomized, prospective, parallel-group study, 47 patients with peri-implantitis were treated with (a) plastic curettes (n = 15 patients, 25 implants), (b) an air-abrasive device (Perio-Flow®, n = 16 patients,22 implants), or (c) a titanium brush (Ti-Brush®, n = 16 patients, 23 implants). Patients were assessed for the following measures at three timepoints (baseline, and three and six months after surgery): plaque index, bleeding on probing, gingival index, probing pocket depth (PPD), relative attachment level, and bone loss. Treatment outcome was considered successful when the implant was still present with PPD ≤ 5 mm, no bleeding on probing, and no further mean bone loss ≥ 0.5 mm. Results: A greater reduction of gingival index and PPD was observed in the titanium brush group than in the other groups at six months (P < 0.001). Relative attachment level decreased from baseline in each group at three months but was more marked in the titanium brush group (P < 0.001). At six months, there was less bone loss in the titanium brush group than in the plastic curette group (P < 0.001; linear mixed model and Kruskal–Wallis). A successful outcome was observed in 22% of implants in the plastic curette group, 27% in the Perio-Flow® group, and 33% in the Ti-Brush® group. Conclusions: The titanium brush and glycine air-polishing device were more effective than the other methods, but treatment success remained low. Combining mechanical procedures with antimicrobials and/or antibiotics might be a more effective strategy and warrants careful investigation.

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Widespread associations between grey matter structure and the human phenome

10.1101/696864 ◽

2019 ◽

Cited By ~ 1

Author(s):

Baptiste Couvy-Duchesne ◽

Lachlan T. Strike ◽

Futao Zhang ◽

Yan Holtz ◽

Zhili Zheng ◽

...

Keyword(s):

Substance Use ◽

Body Size ◽

Grey Matter ◽

Mixed Model ◽

Linear Mixed Model ◽

Income Level ◽

List Type ◽

Hip Circumference ◽

Blood Assay ◽

The Brain

AbstractThe recent availability of large-scale neuroimaging cohorts (here the UK Biobank [UKB] and the Human Connectome Project [HCP]) facilitates deeper characterisation of the relationship between phenotypic and brain architecture variation in humans. We tested the association between 654,386 vertex-wise measures of cortical and subcortical morphology (from T1w and T2w MRI images) and behavioural, cognitive, psychiatric and lifestyle data. We found a significant association of grey-matter structure with 58 out of 167 UKB phenotypes spanning substance use, blood assay results, education or income level, diet, depression, being a twin as well as cognition domains (UKB discovery sample: N=9,888). Twenty-three of the 58 associations replicated (UKB replication sample: N=4,561; HCP, N=1,110). In addition, differences in body size (height, weight, BMI, waist and hip circumference, body fat percentage) could account for a substantial proportion of the association, providing possible insight into previous MRI case-control studies for psychiatric disorders where case status is associated with body mass index. Using the same linear mixed model, we showed that most of the associated characteristics (e.g. age, sex, body size, diabetes, being a twin, maternal smoking, body size) could be significantly predicted using all the brain measurements in out-of-sample prediction. Finally, we demonstrated other applications of our approach including a Region Of Interest (ROI) analysis that retain the vertex-wise complexity and ranking of the information contained across MRI processing options.HighlightsOur linear mixed model approach unifies association and prediction analyses for highly dimensional vertex-wise MRI dataGrey-matter structure is associated with measures of substance use, blood assay results, education or income level, diet, depression, being a twin as well as cognition domainsBody size (height, weight, BMI, waist and hip circumference) is an important source of covariation between the phenome and grey-matter structureGrey-matter scores quantify grey-matter based risk for the associated traits and allow to study phenotypes not collectedThe most general cortical processing (“fsaverage” mesh with no smoothing) maximises the brain-morphometricity for all UKB phenotypes

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Evaluation of Functional Status Among Patients Undergoing Maintenance Treatments for Opioid use Disorders

10.21203/rs.3.rs-47994/v1 ◽

2020 ◽

Author(s):

Juan Jesús Ruíz Ruíz ◽

José María Martínez Delgado ◽

Nuria García ◽

Bartolomé Baena

Keyword(s):

Sexual Dysfunction ◽

Opioid Dependence ◽

Functional Disability ◽

Methadone Treatment ◽

Sexual Problems ◽

Opioid Use ◽

Whodas 2.0 ◽

Maintenance Program ◽

Methadone Group ◽

Buprenorphine Treatment

Abstract Objective Methadone and buprenorphine are the most prevalent types of opioid maintenance programs in Andalusia. The main objective is comparing the functional and health status of patients with pharmacological opioid maintenance treatments according to different socio-demographic characteristic, disabilities and sexual functioning difficulties. Methods A total of 593 patients from the Andalusia community, 329 were undergoing methadone treatment and 264 were undergoing buprenorphine treatment. The patients were interviewed by socio-demographic and opioid-related variables, assessed by functional disability and health variables ( WHODAS 2.0. ) and for sexual dysfunction ( PRSexDQ-SALSEX ). Results We found significant differences in the socio-demographic and the opioid-related variables as the onset of opioid use, being on previous maintenance programs, opioid intravenous use, the length of previous maintenance programs, polydrug use and elevated seroprevalence rates (HCV and HIV) between the methadone group and the buprenorphine group. There were differences in the Understanding and communication domain, Getting around domain, Participation in society domain and in the WHODAS 2.0. simple and complex score, favoring buprenorphine-treated patients. The methadone group had elevated sexual dysfunction than the buprenorphine group. Opioid-related variables as seroprevalence rates, other previous lifetime maintenance program, the daily opioid dosage and the daily alcohol use are the most discriminative variables between both groups. Participation in society variables and sexual problems were the most important clinical variables in distinguishing the methadone group from the buprenorphine group. Conclusions The methadone group showed higher prevalence in opioid dependence-related variables, elevated disabilities in participation in society activities and sexual problems compared with the buprenorphine group.

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A Retrospective Longitudinal Study in a Cohort of Children With Dyskinetic Cerebral Palsy Treated With Tetrabenazine

Frontiers in Neurology ◽

10.3389/fneur.2021.612429 ◽

2021 ◽

Vol 12 ◽

Author(s):

Roberta Scalise ◽

Giuseppina Sgandurra ◽

Valentina Menici ◽

Nicola Capodagli ◽

Roberta Di Pietro ◽

...

Keyword(s):

Cerebral Palsy ◽

Longitudinal Study ◽

Movement Disorders ◽

Mixed Model ◽

Randomized Clinical Trials ◽

Linear Mixed Model ◽

Rating Scale ◽

Random Effect ◽

Empirical Literature ◽

Significant Clinical Improvement

Tetrabenazine has been studied with a variety of hyperkinetic movement disorders, but there is limited and empirical literature on the potential efficacy of tetrabenazine in children with dyskinetic cerebral palsy (DCP). The purpose of this study was to evaluate the efficacy of tetrabenazine in a sample of children with DCP using the Movement Disorders—Childhood Rating Scale 4–18 Revised (MD-CRS 4–18 R). The study is a multicenter retrospective longitudinal study in which the participants were selected from the databases of each Center involved, according to detailed inclusion criteria. The study was performed on 23 children and adolescents (19 male and 4 females; mean age 8.28 years, SD 3.59) with DCP having been evaluated before starting the treatment (baseline), after 6 and 12 months of treatment and in a sub-cohort after >2 years follow-up. A linear mixed model was used to evaluate the effects of the different timings on each MD-CRS 4–18 R Index (Index I, Index II, and Global Index) adding age and type of movement disorder as random effect. A significant clinical improvement related to a reduction of MD-CRS 4-18 R Indexes was detected between the baseline and after 6 and 12 months of treatment. Findings support the efficacy of tetrabenazine in children with DCP through a standardized outcome measure (MD-CRS 4–18 R) and confirm the use of this scale as a suitable tool to detect changes in further randomized clinical trials.

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Predictors of buprenorphine treatment success of opioid dependence in two Baltimore City grassroots recovery programs

Addictive Behaviors ◽

10.1016/j.addbeh.2017.05.010 ◽

2017 ◽

Vol 73 ◽

pp. 129-132 ◽

Cited By ~ 10

Author(s):

April Joy Damian ◽

Tamar Mendelson ◽

Deborah Agus

Keyword(s):

Opioid Dependence ◽

Treatment Success ◽

Baltimore City ◽

Recovery Programs ◽

Buprenorphine Treatment

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The relationships of reduction in pain with other symptoms for cancer patients treated with stereotactic body radiation therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e17588 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e17588-e17588

Author(s):

Tito R. Mendoza ◽

Xin Shelley Wang ◽

Laurence D Rhines ◽

Ugur Selek ◽

Hadley J. Sharp ◽

...

Keyword(s):

Cancer Patients ◽

Mixed Model ◽

Linear Mixed Model ◽

Spinal Metastases ◽

Symptom Burden ◽

Quantitative Relationship ◽

High Dose ◽

Opioid Use ◽

Point Reduction ◽

Disturbed Sleep

e17588 Background: Radiotherapy attenuates pain in patients with spinal metastases. A newer technology is stereotactic body radiotherapy (SBRT) that allows for high dose radiation to be accurately given to a target while sparing nearby tissues. Although a previous study reported improvement in pain, fatigue, disturbed sleep, drowsiness, sadness, fatigue, distress, lack of appetite, nausea, and difficulty remembering after SBRT, it did not examined the quantitative relationship of pain reduction with improvement in symptom burden. Methods: Cancer patients (n=149) with mechanically stable, non–cord-compressing, spinal metastases (n=166) were treated by SBRT in a phase I/II study. Patients received a total dose of 27–30 Gy, typically in three fractions. Symptoms were measured repeatedly using the M. D. Anderson Symptom Inventory (MDASI). Linear mixed model was fitted with pain as the dependent variable and other symptoms as predictor variables to determine the effect of other symptoms on pain throughout the treatment trajectory. Opioid use was a covariate in the analysis. Results: As reported previously, there were significant reduction in pain (p=0·00003) disturbed sleep, drowsiness, sadness (all p<0·0001), fatigue, distress, lack of appetite, nausea, and difficulty remembering (all p<0·05) during the six months post-SBR. Based on our linear mixed models, a 1-point reduction in fatigue (p<.001) is associated with 0.26 reduction in pain. Similarly, a 1-point reduction in in sleep disturbance (p<.001), numbness (p<.001), distress (p<.005), lack of appetite (p<.01) and dry mouth (p<.03) were associated with reductions of 0.25, 0.22, 0.16, 0.15, and 0.14 in pain, respectively. Opioid use was significantly reduced after SBRT. Conclusions: Significant reduction in pain from SBRT is associated with improvement in symptom burden. These findings may provide insights into how symptoms are interrelated during cancer treatment.

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Is OR “portable” in meta-analysis? Time to consider bivariate generalized linear mixed model

10.1101/2020.11.05.20226811 ◽

2020 ◽

Author(s):

Mengli Xiao ◽

Yong Chen ◽

Stephen Cole ◽

Richard MacLehose ◽

David Richardson ◽

...

Keyword(s):

Clinical Trials ◽

Mixed Model ◽

Linear Mixed Model ◽

Meta Analysis ◽

Generalized Linear Mixed Model ◽

Baseline Risk ◽

Marginal Effect ◽

List Type ◽

Effect Measure ◽

Meta Analyses

AbstractObjectivesA recent paper by Doi et al. advocated completely replacing the relative risk (RR) with the odds ratio (OR) as the effect measure used to report the association between a treatment and a binary outcome in clinical trials and meta-analyses. Besides some practical advantages of RR over OR and the well-known issue of the OR being non-collapsible, Doi et al.’s key assumption that the OR is “portable” in the meta-analysis, i.e., study-specific ORs are likely not correlated with baseline risks, was not well justified.Study designs and settingsWe summarized the Spearman’s rank correlation coefficient between study-specific OR and the baseline risk in 40,243 meta-analyses from the Cochrane Database of Systematic Reviews (CDSR).ResultsStudy-specific ORs are negatively correlated with baseline risk of disease (i.e., higher ORs tend to be observed in studies with lower baseline risks of disease) for most meta-analyses in CDSR. Using a meta-analysis comparing the effect of oral sumatriptan (100 mg) versus placebo on mitigating the acute headache at 2 hours after drug administration, we demonstrate that there is a strong negative correlation between OR (RR or RD) with the baseline risk and the conditional effects notably vary with baseline risks.ConclusionsReplacing RR or RD with OR is currently unadvisable in clinical trials and meta-analyses. It is possible that no effect measure is “portable” in a meta-analysis. In cases where portability of the effect measure is challenging to satisfy, we suggest presenting the conditional effect based on the baseline risk using a bivariate generalized linear mixed model. The bivariate generalized linear mixed model can be used to account for correlation between the effect measure and baseline disease risk. Furthermore, in addition to the overall (or marginal) effect, we recommend that investigators also report the effects conditioning on the baseline risk.What is New?Key findingsIn most meta-analyses in Cochrane Database of Systematic Reviews, there is notable negative correlation between ORs and baseline risks.When such a correlation is not negligible, the OR is not “portable” across studies with different baseline risks.When an effect measure is not “portable”, one may derive the effects conditioning on the baseline risk from a bivariate generalized linear mixed model.What this study adds to what was knownThe recommendation to replace the RR with the OR in clinical trials and meta-analyses is misguided.The OR is not a better effect summary than RR and RD in a single study or in meta-analyses; the noncollapsibility of OR can lead to misleading results in a single study and the OR is generally not portable in the meta-analysis.In addition to reporting effect measures such as the OR, RR or RD, it is also important to present the baseline risk.What is the implication and what should change now?When none of the effects are “portable” in a meta-analysis, in addition to report the overall (or marginal) effect, one should also report the effects conditioning on the baseline risk, regardless of the measure of choice.

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