Abstract Introduction For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays.
Long-term abstinence is rarely achieved; many ...patients relapse and overdose after detoxification.
Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized.
This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies. Methods The National Institute on Drug Abuse
'
s Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24 weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients.
Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX. Results The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase.
Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms).
Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness. Conclusions XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance.
Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed. Clinical Trial Registration: NCT02032433.
Opioid use disorder continues to be a significant problem in the United States and worldwide. Three medications-methadone, buprenorphine, and extended-release injectable naltrexone,- are efficacious ...for treating opioid use disorder (OUD). However, the utility of these medications is limited, in part due to poor rates of retention in treatment. In addition, minimum recovery milestones and other factors that influence when and whether individuals can safely discontinue medications are unknown. The National Drug Abuse Treatment Clinical Trials Network (CTN) study "Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy" (RDD; CTN-0100) will be among the largest clinical trials on treatment of OUD yet conducted, consisting of two phases, the Retention phase, and the Duration-Discontinuation phase. The Retention phase, open to patients initiating treatment, will test different doses and formulations of buprenorphine (standard dose sublingual, high dose sublingual, or extended-release injection), and a digital therapeutic app delivering contingency management and cognitive behavioral counseling on the primary outcome of retention in treatment. The Discontinuation phase, open to patients in stable remission from OUD and choosing to discontinue medication (including participants from the Retention phase or from the population of patients treated at the clinical site, referred by an outside prescriber or self-referred) will study different tapering strategies for buprenorphine (sublingual taper vs taper with injection buprenorphine), and a digital therapeutic app which provides resources to promote recovery, on the primary outcome of relapse-free discontinuation of medication. This paper describes how the RDD trial derives from two decades of research in the CTN. Initial trials (CTN-0001; CTN-0002; CTN-0003) focused on opioid detoxification, showing buprenorphine-naloxone was effective for detoxification, but that acute detoxification did not appear to be an effective treatment strategy. Trials on comparative effectiveness of medications for opioid use disorder (MOUD) (CTN-0027; CTN-0030; and CTN-0051) highlighted the problem of dropout from treatment and few trials defined retention on MOUD as the primary outcome. Long-term follow-up studies on those patient samples demonstrated the importance of long-term continuation of medication for many patients to sustain remission. Overall, these trials highlight the potential of a stable research infrastructure such as CTN to advance treatment effectiveness through a programmatic succession of large clinical trials.
Background
Post-traumatic stress disorder (PTSD) is an established comorbidity in Bipolar Disorder (BD), but little is known about the characteristics of psychological trauma beyond a PTSD diagnosis ...and differences in trauma symptoms between BD-I and BD-II.
Objective
(1) To present characteristics of a trauma-exposed BD sample; (2) to investigate prevalence and trauma symptom profile across BD-I and BD-II; (3) to assess the impact of a lifetime PTSD diagnosis vs. a history of trauma on BD course; and (4) to research the impacts of sexual and physical abuse.
Methods
This multi-center study comprised 79 adult participants with BD with a history of psychological trauma and reports baseline data from a trial registered in Clinical Trials (
https://clinicaltrials.gov
; ref: NCT02634372). Clinical variables were gathered through clinical interview, validated scales and a review of case notes.
Results
The majority (80.8%) of our sample had experienced a relevant stressful life event prior to onset of BD, over half of our sample 51.9% had a lifetime diagnosis of PTSD according to the Clinician Administered PTSD scale. The mean Impact of Event Scale-Revised scores indicated high levels of trauma-related distress across the sample, including clinical symptoms in the PTSD group and subsyndromal symptoms in the non-PTSD group. Levels of dissociation were not higher than normative values for BD. A PTSD diagnosis (vs. a history of trauma) was associated with psychotic symptoms 2(1) = 5.404,
p
= 0.02 but not with other indicators of BD clinical severity. There was no significant difference between BD-I and BD-II in terms of lifetime PTSD diagnosis or trauma symptom profile. Sexual abuse significantly predicted rapid cycling 2(1) = 4.15,
p
= 0.042, while physical abuse was not significantly associated with any clinical indicator of severity.
Conclusion
Trauma load in BD is marked with a lack of difference in trauma profile between BD-I and BD-II. Although PTSD and sexual abuse may have a negative impact on BD course, in many indicators of BD severity there is no significant difference between PTSD and subsyndromal trauma symptoms. Our results support further research to clarify the role of subsyndromic PTSD symptoms, and highlight the importance of screening for trauma in BD patients.
Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. ...Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD.
This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale.
The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms.
The trial is registered at ClinicalTrials.gov, identifier: NCT02634372 . Registered on 3 December 2015.
•Counseling and 12-Step attendance were associated with later reduced opioid use.•Associations between psychosocial support and use grew over weeks of the trial.•12-Step had a larger association with ...reduced opioid use for those on naltrexone.•Group counseling had larger association with reduced use for buprenorphine-naloxone.•Relationship between psychosocial support and use are not causal; may be reciprocal.
Psychosocial support is recommended in conjunction with medication for opioid use disorder (MOUD), although optimal “dose,” modality, and timing of participation is not established. This study comprised a secondary analysis of counseling and 12-Step attendance and subsequent opioid use in a MOUD randomized clinical trial. Methods: The parent study randomly assigned 570 participants to receive buprenorphine-naloxone (BUP-NX, n=287) or extended-release injectable naltrexone (XR-NTX, n=283). Mixed-effects logistic regression models were fit with opioid use as the response variable, and a counseling/12-Step attendance predictor. Differences by treatment assignment were examined. Results: Any counseling or 12-Step attendance was associated with reduced odds of opioid use at the subsequent visit, whether considered individually or aggregated across type. A continuous relationship was observed for 12-Step attendance (F(1,5083)=5.01, p=.025); with each additional hour associated with 13% (95% CI: 0.83, 0.90) reduction in odds of opioid use. The strength of this association grew over time. In the BUP-NX arm, group counseling was associated with a greater reduction in odds of opioid use than for XR-NTX, (OR=0.32 (95% CI: .22, 0.48) vs. OR=0.69 (95% CI: 0.43, 1.08)). For XR-NTX, 12-Step was associated with a greater reduction in odds of opioid use (OR=0.35 (95% CI: 0.22, 0.54) vs. OR=0.65 (95% CI: 0.47, 0.89) for BUP-NX)). Conclusions: Psychosocial engagement has a proximal association with opioid use, the strength of that association may grow with dose and time. Alternatively, more motivated individuals may both attend more counseling/12-Step and have better treatment outcomes, or the relationship may be reciprocal.
For many reasons, the emergency department (ED) is a critical venue to initiate OUD interventions. The prevailing culture of the ED has been that substance use disorders are non-emergent conditions ...better addressed outside the ED where resources are less constrained. This study, its rapid funding mechanism, and accelerated timeline originated out of the urgent need to learn whether ED-initiated buprenorphine (BUP) with referral for treatment of OUD is generalizable, as well as to develop strategies to facilitate its adoption across a variety of ED settings and under real-world conditions. It both complements and uses methods adapted from Project ED Health (CTN-0069), a Hybrid Type 3 implementation-effectiveness study of using Implementation Facilitation (IF) to integrate ED-initiated BUP and referral programs.
ED-CONNECT (CTN 0079) was a three-site implementation study exploring the feasibility, acceptability, and impact of introducing ED-initiated BUP in rural and urban settings with high-need, limited resources, and different staffing structures. We used a multi-faceted approach to develop, introduce and iteratively refine site-specific ED clinical protocols and implementation plans for opioid use disorder (OUD) screening, ED-initiated BUP, and referral for treatment. We employed a participatory action research approach and use mixed methods incorporating data derived from abstraction of medical records and administrative data, assessments of recruited ED patient-participants, and both qualitative and quantitative inquiry involving staff from the ED and community, patients, and other stakeholders.
This study was designed to provide the necessary, time-sensitive understanding of how to identify OUD and initiate treatment with BUP in the EDs previously not providing ED-initiated BUP, in communities in which this intervention is most needed: high need, low resource settings.
The study was prospectively registered on ClinicalTrials.gov (NCT03544112) on June 01, 2018: https://clinicaltrials.gov/ct2/show/NCT03544112 .
Paspalum chaseanum Parodi (Poaceae) is a rare species seldom found in the vast phytogeographic Chaco region of South America. It occurs in some localities as a diploid with 20 somatic chromosomes, ...reproduces sexually and is self-incompatible. A tetraploid cytotype was recently collected in this geographic region. This accession was determined to reproduce of aposporous apomixis and was crossed, as pollen donor, onto a sexual autotetraploid plant of P. plicatulum Michx. The meiotic chromosome pairing behaviour of both parents and their hybrids was primarily as bivalents and quadrivalents, indicating that tetraploid P. chaseanum is likely to have an autoploid origin, and that both species share basically the same genome. Although some controversies exist regarding the subgeneric taxonomic classification of P. chaseanum, these results support its inclusion in the informal Plicatula group of Paspalum. The P. plicatulum×P. chaseanum hybrids segregated for apomixis. The amount of seed set in some hybrids (up to 17%) and the presence of sexual as well as facultative apomictic individuals in the progeny suggest that gene transfer through hybridisation is a feasible tool in genetic-improvement programs concerning these forage grass species.
Insect puparia were found adhered to the ribs and other tissues in the abdominal cavity of a natural male mummy found in Itacambira (State of Minas Gerais, Brazil) dating to the Colonial Period. They ...were collected for identification by scanning electron microscopy, and for comparison of several morphological features with those described in the literature. The puparia were found open and dorsoventrally flattened, making it difficult to visualize the dorsal projections. The tegument is covered by tapered spines and contains rows of small tubercles on the dorsal and lateral regions of the puparium. The posterior spiracle consists of four parallel openings arranged in pairs. These results are indicative that the specimens belong to the species Megaselia scalaris (Loew, 1866) (Diptera: Phoridae). Additionally, cuticular hydrocarbons of the puparia were analysed by gas chromatography coupled to mass spectrometry and compared with the profile of M. scalaris reared in the laboratory.
ABSTRACT Grama-tio-pedro (Paspalum oteroi Swallen) is a rare stoloniferous grass of the Plicatula group of Paspalum, well adapted to continuous grazing in areas subject to seasonal flooding in the ...Pantanal region, in central western Brazil. The species is a facultative apomictic (asexual reproduction by seed) tetraploid, sporadically cultivated on Pantanal farms, propagated either by cuttings or seed. Due to its potential for extensive cultivation and forage quality, Grama-tio-pedro appears as a candidate for genetic improvement within the Plicatula group through plant breeding. We used a colchicine-induced sexual autotetraploid genotype of P. plicatulum Michx. to obtain interspecific hybrids using the apomictic species, P. oteroi, as pollen donor. The very similar meiotic chromosome behavior observed in both parents, with main quadrivalent and bivalent associations, suggested that P. oteroi is a natural autotetraploid. The hybrids showed less irregular meiotic behavior with fewer quadrivalents and more bivalents than either parent. Fertility among interspecific hybrids varied from complete sterility in some of them to seed productions in others that were approximately twice as much as for either parent. The great variability of seed set performance may well be a drastic genetic consequence of joining two homologous chromosome sets of P. plicatulum together with two homologous sets of P. oteroi that, in turn, have some homeology between them. Most hybrids reproduce by sexual means, thus, they could be used as female parents in backcrosses and in crosses with other species of the Plicatula group for interspecific gene transferring in breeding programs.
La producción de carne en la Argentina representa una actividad económica importante para el país. El avance de la agricultura en la región pampeana trasladó la producción de carne a regiones ...marginales menos productivas. El norte argentino ocupa el 30% de la superficie destinada a la producción de carne y el 25% del stock ganadero a nivel nacional. La producción de carne se realiza principalmente sobre pastizales naturales de baja productividad. La baja adopción de tecnología limita el crecimiento de la producción de carne. La implantación de pasturas cultivadas aumenta la receptividad y los índices de producción pecuaria. Las especies forrajeras megatérmicas poseen ventajas para su crecimiento y adaptación a los ambientes desfavorables del trópico y subtrópico. Son especies de crecimiento primavera-estivo-otoñal adaptadas a temperaturas elevadas y altas concentraciones de dióxido de carbono atmosférico. También varias de ellas están adaptadas a condiciones de estrés salino y sequía. Este foro abordará sobre la importancia de las especies forrajeras megatérmicas para el norte de nuestro país, con énfasis en su biología reproductiva, genética, mejoramiento, ambientes de cultivo, manejo y producción de semillas.
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