A systematic review of integrative medicine for opioid withdrawal

Introduction: The United States has been battling an opioid epidemic for decades. As substance use disorders have grown, so too has investigation into treatment options, including integrative medicine approaches, for managing opioid withdrawal symptoms (OWS). Objectives: This systematic review sought to assess the use of integrative medicine approaches for the alleviation of OWS in patients dependent on opioids and to summarize the available data. Methods: The authors searched using synonyms for opioids, substance use disorder, and integrative medicine and standardized searches in Embase, PubMed, and Cochrane Library. We also hand searched references for systematic reviews. This review did not include articles that could not be obtained as full-text publications via interlibrary loan. The review also excluded studies with interventions involving acupuncture because multiple systematic reviews on this approach already exist. In addition, we also excluded studies of therapy for opioid maintenance. We evaluated studies for inclusion based on the Jadad criteria. We compared opioid withdrawal outcomes of the studies to determine the efficacy of integrative medicine approaches. Results: The authors identified a total of 382 unique publications initially for possible inclusion through systematic searches. After applying inclusion and exclusion criteria, five studies met Jadad criteria. The authors identified an additional two studies for inclusion via hand searching. A total of seven studies included interventions consisting of passionflower, weinicom, fu-yuan pellet, jinniu capsules, tai-kang-ning, dynorphin, and l-tetrahydropalmatine. Analyzing the articles was difficult given the varied scoring methods they used to quantify opioid withdrawal symptoms and the small sample sizes in the trials. Most showed evidence that supported integrative medicine approaches for OWS, although the strength of evidence was limited because of sample sizes. Conclusions: This review found evidence of multiple integrative medicine approaches for opioid withdrawal symptoms. Well-designed randomized controlled trials should assess the efficacy of integrative medicine for improvement in OWS

Interventions to increase uptake of the human papillomavirus vaccine in unvaccinated college students: A systematic literature review

© 2019, American Association of Colleges of Pharmacy. All rights reserved. The Committee was charged with the responsibility for examining the need for change in pharmacy education and the models of leadership that would enable that change to occur across the academy. They also examined the question of faculty wellbeing in a time of change and made several recommendations and suggestions regarding both charges. Building upon the work of the previous Academic Affairs Committee, the 2018-19 AAC encourages the academy to implement new curricular models supporting personalized learning that creates engaged and lifelong learners. This will require transformational leadership and substantial investments in faculty development and new assessment strategies and resources. Recognizing that the magnitude of the recommended change will produce new stress on faculty, the committee identified the need for much additional work on student, faculty and leaders’ wellbeing, noting the limited amount of empirical evidence on pharmacy related to stress and resilience. That said, if faculty and administrators are not able to address personal and community wellbeing, their ability to support their students’ wellbeing will be compromised

Ocular Hypotensive Effect of ONO-9054, an EP3/FP Receptor Agonist: Results of a Randomized, Placebo-controlled, Dose Escalation Study

Purpose: To assess pharmacodynamic and safety profiles of ONO-9054 following single and multiple day dosing in subjects with ocular hypertension or open-angle glaucoma. Materials and Methods: This was a phase I, single-center, randomized, double-masked, placebo-controlled dose-escalation study. Nine subjects were randomized to each of ONO-9054 3, 10, 20, 30 μg/mL and 12 to placebo. Subjects received a single drop to each eye at 07:00±30 minutes (single dose). Following a 4-day no-treatment period, subjects were dosed once daily for 14 consecutive days (multiple day dosing). Intraocular pressure (IOP) was measured regularly and compared with baseline measurements. Ocular examinations assessed safety and tolerability. Results: Mean IOP decreased dose dependently. Following single dosing, IOP decreased from 22.9±4.0 to 15.9±2.3 mm Hg (ONO-9054, 30 μg/mL) at peak effect 9 hours postdose; the reduction in placebo-treated subjects was from 22.3±2.4 to 21.5±3.3 mm Hg. Following multiple day dosing, the greatest reduction in IOP occurred 1 hour postdose on day 18, from 23.3±0.6 to 15.1±2.4 mm Hg (ONO-9054, 10 μg/mL); the smallest reduction at this time was from 23.9±0.8 to 18.6±2.0 mm Hg (ONO-9054, 3 μg/mL). Pressures remained reduced on day 19, 25 hours after the last dose, when the lowest measurement was 15.8±2.1 mm Hg (ONO-9054, 10 μg/mL). Anterior uveitis and vitreous detachment were each reported in 2 subjects and considered moderate by the Investigator. Ocular hyperemia and tolerability symptoms were generally mild and transient. Conclusions: ONO-9054 was well-tolerated and elicited dose-dependent reductions in IOP, which were sustained for at least 24 hours following 2 weeks of consecutive daily dosing

Ocular hypotensive effect of the novel EP3/FP agonist ONO-9054 versus Xalatan: results of a 28-day, double-masked, randomised study

Background/aims ONO-9054 is being developed for the reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) and open-angle glaucoma (OAG). This study compared the novel dual EP3/FP agonist ONO-9054 with the FP agonist Xalatan. Methods Adults (n=123) with bilateral mild/moderate OAG or OHT, with unmedicated IOP of ≥24 mm Hg at 8:00 hours, ≥21 mm Hg at 10:00 hours and ≤36 mm Hg, were randomised 1:1 to receive ONO-9054 (0.003%, 30 μg/mL) or Xalatan (0.005%, 50 μg/mL) once daily for 28 days. Results Day 29 mean diurnal IOP was −7.2 mm Hg for ONO-9054 vs −6.6 mm Hg for Xalatan. At 08:00 hours, the IOPs were comparable, and at all later time points the decrease in IOP was greater for ONO-9054. On day 29, the odds of a mean IOP reduction of ≤−25%, ≤−30% and ≤−35% for ONO-9054 were 2.39, 2.37 and 4.85 times more, respectively, than the odds for Xalatan (p<0.05, post hoc analyses). The percentage of subjects achieving target IOPs on day 29 (≤17, ≤16 and ≤15 mm Hg) was greater for ONO-9054 than for Xalatan; the odds of achieving an IOP ≤15 mm Hg for ONO-9054 were 2.4 times more than the odds for Xalatan (p<0.01, post hoc analysis). Conclusions Subjects randomised to receive ONO-9054 were more likely to achieve a greater per cent reduction in IOP and were more likely to achieve target IOPs than those receiving Xalatan. The effects of ONO-9054 in reducing IOP appear to persist longer than those of Xalatan

DNA methylation and body mass index:investigating identified methylation sites at HIF3A in a causal framework

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation.Rebecca C. Richmond, Gemma C. Sharp, Mary E. Ward, Abigail Fraser, Oliver Lyttleton, Wendy L. McArdle, Susan M. Ring, Tom R. Gaunt, Debbie A. Lawlor, George Davey Smith, and Caroline L. Relto

Clinical Trials A Novel Dual Agonist of EP3 and FP Receptors for OAG and OHT: Safety, Pharmacokinetics, and Pharmacodynamics of ONO-9054 in Healthy Volunteers

PURPOSE. The use of a dual prostaglandin E3 (EP3) and prostaglandin F (FP) receptor agonist is a novel approach for the reduction of intraocular pressure (IOP) in open angle glaucoma and ocular hypertension and, as such, ONO-9054 may have benefits over existing therapies. The objectives of this phase I study were to assess the safety, tolerability, systemic pharmacokinetics (PK), and pharmacodynamics (PD) profiles of , the prodrug of ONO-AG-367, in healthy, normotensive adults. METHODS. In this randomized, double-masked, placebo-controlled, single-dose escalating study, 48 male and female healthy volunteers each received a single drop of ONO-9054 0.3, 1.0, 3.0, 10.0, 20.0, or 30.0 lg/mL, or matching placebo in each eye. Blood samples of PK were taken up to 24 hours post dose; ocular and systemic safety, tolerability, and PD assessments were conducted up to approximately 72 hours post dose, and on day 7 at the follow-up visit. RESULTS. We found ONO-9054 was safe and well tolerated and ONO-AG-367 exhibited dosedependent systemic PK with rapid elimination. The effect of PD was assessed by reduction in IOP, with the maximum change from baseline in IOP in these normotensive individuals of À28.23% achieved at the 30.0 lg/mL dose at 9 hours post administration. CONCLUSIONS. A single dose of the novel EP3 and FP receptor agonist ONO-9054 was safe and well tolerated in healthy volunteers at doses between 0.3 and 30.0 lg/mL and resulted in a significant reduction in intraocular IOP with maximum reduction at 9 hours post dose. This supports further evaluation of ONO-9054 for the treatment of ocular hypertension and open angle glaucoma. (ClinicalTrials.gov number, NCT01508988.

Tyrosine Phosphorylation of Tau by the Src Family Kinases Lck and Fyn

<p>Abstract</p> <p>Background</p> <p>Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease, where it is hyperphosphorylated on serine and threonine residues, and recently phosphotyrosine has been demonstrated. The Src-family kinase Fyn has been linked circumstantially to the pathology of Alzheimer's disease, and shown to phosphorylate Tyr18. Recently another Src-family kinase, Lck, has been identified as a genetic risk factor for this disease.</p> <p>Results</p> <p>In this study we show that Lck is a tau kinase. <it>In vitro</it>, comparison of Lck and Fyn showed that while both kinases phosphorylated Tyr18 preferentially, Lck phosphorylated other tyrosines somewhat better than Fyn. In co-transfected COS-7 cells, mutating any one of the five tyrosines in tau to phenylalanine reduced the apparent level of tau tyrosine phosphorylation to 25-40% of that given by wild-type tau. Consistent with this, tau mutants with only one remaining tyrosine gave poor phosphorylation; however, Tyr18 was phosphorylated better than the others.</p> <p>Conclusions</p> <p>Fyn and Lck have subtle differences in their properties as tau kinases, and the phosphorylation of tau is one mechanism by which the genetic risk associated with Lck might be expressed pathogenically.</p

Wading through the swamp: what does tropical peatland restoration mean to national-level stakeholders in Indonesia?

Ecological restoration is considered to play an important role in mitigating climate change, protecting biodiversity and preventing environmental degradation. Yet, there are often multiple perspectives on what outcomes restoration should be aiming to achieve, and how we should get to that point. In this paper we interview a range of policy makers, academics and NGO representatives to explore the range of perspectives on the restoration of Indonesia's tropical peatlands – key global ecosystems that have undergone large‐scale degradation. Thematic analysis suggests that participants agreed about the importance of restoration, but had differing opinions on how effective restoration activities to date have been and what a restored peatland landscape should look like. These results exemplify how ecological restoration can mean different things to different people, but also highlight important areas of consensus for moving forward with peatland restoration strategies

How Can I Drink Safely?; Perception Versus the Reality of Alcohol Consumption

This article investigates differences between perception and actual consumption of alcohol in young adults within the UK, suggesting that inaccurate information in the public domain may hamper those seeking to drink safely plus the development of moderate drinking cultures. Results confirm that inaccurate information may be preventing the development of safe drinking behaviours among certain groups. In addition, they indicate that some groups choose to ignore safe consumption limits in particular circumstances. Results indicate that many government strategies aimed at reducing unsafe drinking behaviour are inaccurately targeted; changing male public consumption behaviour may trigger changes in female behaviour