Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to ...prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX.
We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433.
Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 72% of 283) than BUP-NX (270 94% of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 65% of 283) than for BUP-NX (163 57% of 287; hazard ratio HR 1·36, 95% CI 1·10–1·68), most or all of this difference accounted for by early relapse in nearly all (70 89% of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group).
In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications.
NIDA Clinical Trials Network.
To compare the acromegaly mortality rates with those expected for the general population from studies published before and after 2008.
We performed a systematic review and included observational ...studies in which the number of deaths observed in acromegaly was compared with the expected mortality for the general population mortality observed/expected (O/E). The following electronic databases were used as our data sources: EMBASE, MEDLINE and LILACS. From the observed and expected deaths, we recalculated all standardized mortality ratios (SMR) and their respective confidence intervals (95% CI), which were plotted in a meta-analysis using the software RevMan 5.3.
We identified 2303 references, and 26 studies fulfilled our eligibility criteria. From the 17 studies published before 2008, the mortality in acromegaly was increased, while from the nine studies published after 2008, the mortality was not different from the general population (SMR: 1.35, CI: 0.99-1.85). In six studies where somatostatin analogs (SAs) were used as adjuvant treatment, acromegaly mortality was not increased (SMR: 0.98, CI: 0.83-1.15), whereas in series including only patients treated with surgery and/or radiotherapy, mortality was significantly higher (SMR: 2.11; CI: 1.54-2.91). In studies published before and after 2008, the mortality was not increased in patients who achieved biochemical control, while it was higher in those with active disease. Cancer has become a leader cause of deaths in acromegaly patients in the last decade, period in which life expectancy improved.
Mortality in acromegaly is normalized with biochemical control and decreased in the last decade with the more frequent use of SAs as adjuvant therapy. Increased life expectancy has been associated with more deaths due to cancer.
Background: In clinical trials of behavioral health interventions, outcome variables often take the form of counts, such as days using substances or episodes of unprotected sex. Classically, count ...data follow a Poisson distribution; however, in practice such data often display greater heterogeneity in the form of excess zeros (zero-inflation) or greater spread in the values (overdispersion) or both. Greater sample heterogeneity may be especially common in community-based effectiveness trials, where broad eligibility criteria are implemented to achieve a generalizable sample. Objectives: This article reviews the characteristics of Poisson model and the related models that have been developed to handle overdispersion (negative binomial (NB) model) or zero-inflation (zero-inflated Poisson (ZIP) and Poisson hurdle (PH) models) or both (zero-inflated negative binomial (ZINB) and negative binomial hurdle (NBH) models). Methods: All six models were used to model the effect of an HIV-risk reduction intervention on the count of unprotected sexual occasions (USOs), using data from a previously completed clinical trial among female patients (N = 515) participating in community-based substance abuse treatment (Tross et al. Effectiveness of HIV/AIDS sexual risk reduction groups for women in substance abuse treatment programs: Results of NIDA Clinical Trials Network Trial. J Acquir Immune Defic Syndr 2008; 48(5):581-589). Goodness of fit and the estimates of treatment effect derived from each model were compared. Results: The ZINB model provided the best fit, yielding a medium-sized effect of intervention. Conclusions and Scientific Significance: This article illustrates the consequences of applying models with different distribution assumptions on the data. If a model used does not closely fit the shape of the data distribution, the estimate of the effect of the intervention may be biased, either over- or underestimating the intervention effect.
In this review, we provide an overview of the current understanding of the main mechanisms of pharmacological action of essential oils and their components in various biological systems. A brief ...introduction on essential oil chemistry is presented to better understand the relationship of chemical aspects with the bioactivity of these products. Next, the antioxidant, anti-inflammatory, antitumor, and antimicrobial activities are discussed. The mechanisms of action against various types of viruses are also addressed. The data show that the multiplicity of pharmacological properties of essential oils occurs due to the chemical diversity in their composition and their ability to interfere with biological processes at cellular and multicellular levels via interaction with various biological targets. Therefore, these natural products can be a promising source for the development of new drugs.
Amid worsening opioid overdose death rates, the nation continues to face a persistent addiction treatment gap limiting access to quality care for opioid use disorder (OUD). Three FDA-approved ...medications (methadone, buprenorphine, and extended-release naltrexone) have high quality evidence demonstrating reductions in drug use and overdose events, but most individuals with OUD do not receive them. The development of a unified public health framework, such as a Cascade of Care, could improve system level practice and treatment outcomes. In response to feedback from many stakeholders over the past year, we have expanded upon the OUD treatment cascade, first published in 2017, with additional attention to prevention stages and both individual-level and population-based services to better inform efforts at the state and federal level. The proposed cascade framework has attracted considerable interest from federal agencies including the Centers for Disease Control and Prevention (CDC) and National Institute on Drug Abuse (NIDA) along with policy-makers nationwide. We have reviewed recent literature and evidence-based interventions related to prevention, identification, and treatment of individuals with OUD and modeled updated figures from the 2016 National Survey on Drug Use and Health. Many currently employed interventions (prescriber guidelines, prescription monitoring programs, naloxone rescue) address prevention of OUD or downstream complications but not treatment of the underlying disorder itself. An OUD Cascade of Care framework could help structure local and national efforts to combat the opioid epidemic by identifying key targets, interventions, and quality indicators across populations and settings to achieve these ends. Improved data collection and reporting methodology will be imperative.
Overdose risk during a course of treatment with medication for opioid use disorder (MOUD) has not been clearly delineated. The authors sought to address this gap by leveraging a new data set from ...three large pragmatic clinical trials of MOUD.
Adverse event logs, including overdose events, from the three trials (N=2,199) were harmonized, and the overall risk of having an overdose event in the 24 weeks after randomization was compared for each study arm (one methadone, one naltrexone, and three buprenorphine groups), using survival analysis with time-dependent Cox proportional hazard models.
By week 24, 39 participants had ≥1 overdose event. The observed frequency of having an overdose event was 15 (5.30%) among 283 patients assigned to naltrexone, eight (1.51%) among 529 patients assigned to methadone, and 16 (1.15%) among 1,387 patients assigned to buprenorphine. Notably, 27.9% of patients assigned to extended-release naltrexone never initiated the medication, and their overdose rate was 8.9% (7/79), compared with 3.9% (8/204) among those who initiated naltrexone. Controlling for sociodemographic and time-varying medication adherence variables and baseline substance use, a proportional hazard model did not show a significant effect of naltrexone assignment. Significantly higher probabilities of experiencing an overdose event were observed among patients with baseline benzodiazepine use (hazard ratio=3.36, 95% CI=1.76, 6.42) and those who either were never inducted on their assigned study medication (hazard ratio=6.64, 95% CI=2.12, 19.54) or stopped their medication after initial induction (hazard ratio=4.04, 95% CI=1.54, 10.65).
Among patients with opioid use disorder seeking medication treatment, the risk of overdose events over the next 24 weeks is elevated among those who fail to initiate or discontinue medication and those who report benzodiazepine use at baseline.
Background
Mesh surgery for stress urinary incontinence or pelvic organ prolapse can result in complications such as mesh exposure, mesh extrusion, voiding dysfunction, dyspareunia, and pain. There ...is limited knowledge or guidance on the effective management for mesh‐related complications.
Objective
To determine the best management of mesh complications; a systematic review was conducted as part of the national clinical guideline ‘Urinary incontinence (update) and pelvic organ prolapse in women: management’.
Search strategy
Search strategies were developed for each indication for referral.
Selection criteria
Relevant interventions included complete or partial mesh removal, mesh division, and non‐surgical treatments such as vaginal estrogen.
Data collection and analysis
Characteristics and outcome data were extracted, and as a result of the heterogeneous nature of the data a narrative synthesis was conducted.
Main results
Twenty‐four studies were included; five provided comparative data and four studies stated the indication for referral. Reported outcomes (including pain, dyspareunia, satisfaction, quality of life, incontinence, mesh exposure, and recurrence) and the reported incidences of these varied widely.
Conclusions
The current evidence base is limited in quantity and quality and does not permit firm recommendations to be made on the most effective management for mesh‐related complications. Robust data are needed so that mesh complications can be managed effectively in the future.
Tweetable
Systematic review demonstrates that the outcomes following mesh revision surgery are highly variable.
Tweetable
Systematic review demonstrates that the outcomes following mesh revision surgery are highly variable.
The concept of "deaths of despair" (suicide, overdose, and alcohol-related liver disease) highlights the importance of detecting and understanding the course of co-occurring depression in patients ...with opioid use disorder (OUD).
In a 24-week trial of 570 patients with
-defined OUD randomized to buprenorphine-naloxone (BUP-NX) or extended-release naltrexone (XR-NTX) from January 2014 to January 2017, the prevalence of depression (assessed with Hamilton Depression Rating Scale HDRS) was examined at baseline and after 4 weeks of treatment, and the association between depression and relapse to opioid use was explored using logistic regression.
Among 473 patients who initiated medication, 14.2% (67/473) had moderate/severe depression (HDRS ≥ 17) and 34.9% (165/473) had mild depression (8 ≤ HDRS ≤ 16) at baseline. Patients with moderate/severe depression had more frequent histories of anxiety disorders and suicidal ideation. After 4 weeks of treatment, approximately two-thirds of participants with depression either responded (HDRS reduced ≥ 50% from baseline) or remitted (HDRS ≤ 7), with no significant differences between medication treatment groups. Those with moderate/severe depression were less likely to remit (52.8%; 28/53) compared to those with mild depression (76%; 98/129) at week 4 (OR = 0.43, 95% CI = 0.21-0.89,
= .02). Further, those who remitted at week 4 had lower, but not significantly different, risk of relapse to opioids compared to those who did not remit (OR = 0.55, 95% CI = 0.28-1.08,
= .08).
Depression is common among patients with OUD and often remits after initiation of BUP-NX or XR-NTX, although when it does not remit it may be associated with worse opioid use outcome. Depression should be screened and followed during initiation of treatment and, when it does not remit, specific depression treatment should be considered.
ClinicalTrials.gov identifier: NCT02032433.
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