•The COVID-19 pandemic stands to exacerbate the ongoing opioid overdose epidemic.•Emergency authorities to expand access to buprenorphine have been implemented.•One-third of clinicians reported ...remote buprenorphine initiation to new patients.•Permanent adoption of authorities may enable expanded access to buprenorphine.
To determine how clinicians with a DATA waiver to prescribe buprenorphine for opioid use disorder (OUD) adapted during the COVID-19 pandemic to emergency authorities, including use of telehealth to prescribe buprenorphine, the challenges faced by clinicians, and strategies employed by them to manage patients with OUD.
From June 23, 2020 to August 19, 2020, we conducted an electronic survey of U.S. DATA-waivered clinicians. Descriptive statistics and multivariable logistic regression were used for analysis.
Among 10,238 respondents, 68 % were physicians, 25 % nursing-related providers, and 6% physician assistants; 28 % reported never prescribing or not prescribing in the 12 months prior to the survey. Among the 72 % of clinicians who reported past 12-month buprenorphine prescribing (i.e. active practitioners during the pandemic) 30 % reported their practice setting closed to in-person visits during COVID-19; 33 % reported remote prescribing to new patients without an in-person examination. The strongest predictors of remote buprenorphine prescribing to new patients were prescribing buprenorphine to larger numbers of patients in an average month in the past year and closure of the practice setting during the pandemic; previous experience with remote prescribing to established patients prior to COVID-19 also was a significant predictor. Among clinicians prescribing to new patients without an in-person examination, 5.5 % reported difficulties with buprenorphine induction, most commonly withdrawal symptoms.
Telehealth practices and prescribing to new patients without an in-person examination were adopted by DATA-waivered clinicians during the first six months of COVID-19. Permanent adoption of these authorities may enable expanded access to buprenorphine treatment.
Benzodiazepines (BZDs) are indicated for the short-term treatment of chronic insomnia disorder, since real-world use of them in large doses for a long time could cause serious side effects. Patients ...with long-term use of BZDs are prone to BZDs tolerance and dependence, but sudden withdrawal from BZDs can lead to rebound and withdrawal symptoms, resulting in difficulty in withdrawal. We reviewed recent studies about the withdrawal from long-term use of BZDs in chronic insomnia disorder patients, focusing on the overview of BZDs, timing and strategy of withdrawal, and treatment of withdrawal symptoms. Our review will contribute to enriching the ideas of appropriately discontinuing BZDs in chronic insomnia disorder patients with long-term use of BZDs.
Background and Aims
A total of 2.4 million adults in England were dispensed a benzodiazepine or Z‐drug (BZRA) in 2017/18, and more than 250 000 patients in the UK take BZRAs beyond the recommended ...duration. Deprescribing is a clinician‐guided process of withdrawing inappropriate drugs. This review aimed to evaluate the evidence base supporting the feasibility and clinical effectiveness of all forms of deprescribing initiatives used to discontinue long‐term (≥ 4 weeks) BZRAs.
Method
Systematic review of randomized controlled trials evaluating BZRAs deprescribing among adults in community, primary or outpatient settings. MEDLINE, Embase and PsycINFO were searched from inception to February 2021. Primary outcomes were successful discontinuation in the short (< 4 weeks) or long term (≥ 4 weeks) and the occurrence of withdrawal symptoms, behavioural or psychological symptoms. Studies were categorized as pharmacological or non‐pharmacological supported interventions. Study quality was assessed using the Cochrane risk‐of‐bias tool. Where appropriate, risk ratios (RRs), mean differences and 95% confidence intervals (CIs) were calculated, and Mantel–Haenszel methods using the random‐effect meta‐analysis was undertaken to calculate summary effect estimates.
Results
Ten studies were included (n = 1431 participants). Heterogeneity in study design and effect was observed. Benzodiazepines were successfully deprescribed when gradually tapered with non‐pharmacological support compared with gradual tapering alone in the short term (n = 124; RR = 2.02; 95% CI = 1.41, 2.89) and long term (n = 123; RR = 2.45; 95% CI = 1.56, 3.85). Benzodiazepine deprescribing was more successful when supported by non‐pharmacological methods versus routine care (n = 189; RR = 3.26; 95% CI = 2.36, 4.51). Quality of evidence reporting effectiveness was very low to low.
Conclusions
It may be feasible to deprescribe benzodiazepines depending on the process and support mechanisms employed.
The effects of Brexit on British foreign, security and defence policy have been complex. Initial efforts to agree structured cooperation failed, with later governments refusing to negotiate on this ...area, followed by unstructured re-engagement after Russia's invasion of Ukraine. This article argues that these changes can be explained by reference to the factional politics during the Brexit negotiations within the Conservative Party, with the defeat of May's Withdrawal Agreement bringing to power a pro-Brexit faction with a distinct foreign policy worldview and incentives to demonstrate a cleaner break from the European Union. Empirically, the article draws on a series of interviews conducted with UK and EU policymakers. The findings demonstrate the significance of ideology and party factions in a policy domain where the UK is powerful enough to treat EU institutions as useful rather than necessary, and shows the direct and indirect ways factional politics brings about external change.
Aims
To compare the effects of (i) high versus low nicotine concentration e‐liquid, (ii) fixed versus adjustable power and (iii) the interaction between the two on: (a) vaping behaviour, (b) ...subjective effects, (c) nicotine intake and (d) exposure to acrolein and formaldehyde in e‐cigarette users vaping in their everyday setting.
Design
Counterbalanced, repeated measures with four conditions: (i) low nicotine (6 mg/ml)/fixed power; (ii) low nicotine/adjustable power; (iii) high nicotine (18 mg/ml)/fixed power; and (iv) high nicotine/adjustable power.
Setting
London and the South East, England.
Participants
Twenty experienced e‐cigarette users (recruited between September 2016 and February 2017) vaped ad libitum using an eVic Supreme™ with a ‘Nautilus Aspire’ tank over 4 weeks (1 week per condition).
Measurements
Puffing patterns daily puff number (PN), puff duration (PD), interpuff interval (IPI), ml of e‐liquid consumed, changes to power (where permitted) and subjective effects (urge to vape, nicotine withdrawal symptoms) were measured in each condition. Nicotine intake was measured via salivary cotinine. 3‐Hydroxypropylmercapturic acid (3‐HPMA), a metabolite of the toxicant acrolein, and formate, a metabolite of the carcinogen formaldehyde, were measured in urine.
Findings
There was a significant nicotine concentration × power interaction for PD (P < 0.01). PD was longer with low nicotine/fixed power compared with (i) high nicotine/fixed power (P < 0.001) and (ii) low nicotine/adjustable power (P < 0.01). PN and liquid consumed were higher in the low versus high nicotine condition (main effect of nicotine, P < 0.05). Urge to vape and withdrawal symptoms were lower, and nicotine intake was higher, in the high nicotine condition (main effects of nicotine: P < 0.01). While acrolein levels did not differ, there was a significant nicotine × power interaction for formaldehyde (P < 0.05).
Conclusions
Use of a lower nicotine concentration e‐liquid may be associated with compensatory behaviour (e.g. higher number and duration of puffs) and increases in negative affect, urge to vape and formaldehyde exposure.
Opiates are essential for treating pain, but termination of opiate therapy can cause a debilitating withdrawal syndrome in chronic users. To alleviate or avoid the aversive symptoms of withdrawal, ...many of these individuals continue to use opiates. Withdrawal is therefore a key determinant of opiate use in dependent individuals, yet its underlying mechanisms are poorly understood and effective therapies are lacking. Here, we identify the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal. We show that withdrawal from morphine induces long-term synaptic facilitation in lamina I and II neurons within the rodent spinal dorsal horn, a principal site of action for opiate analgesia. Genetic ablation of Panx1 in microglia abolished the spinal synaptic facilitation and ameliorated the sequelae of morphine withdrawal. Panx1 is unique in its permeability to molecules up to 1 kDa in size and its release of ATP. We show that Panx1 activation drives ATP release from microglia during morphine withdrawal and that degrading endogenous spinal ATP by administering apyrase produces a reduction in withdrawal behaviors. Conversely, we found that pharmacological inhibition of ATP breakdown exacerbates withdrawal. Treatment with a Panx1-blocking peptide (
panx) or the clinically used broad-spectrum Panx1 blockers, mefloquine or probenecid, suppressed ATP release and reduced withdrawal severity. Our results demonstrate that Panx1-mediated ATP release from microglia is required for morphine withdrawal in rodents and that blocking Panx1 alleviates the severity of withdrawal without affecting opiate analgesia.
Rationale
It is well established that nicotine improves, and deprivation impairs, cognitive performance and mood in smokers. Prospective memory (PM), remembering to execute a delayed intention at a ...given time point, is under-explored in smokers. Whilst a handful of studies have shown improved PM with nicotine, the effects of nicotine delivered via the electronic cigarette (e-cigarette) have not been investigated.
Objective
This study explores whether, by comparison with placebo, nicotine delivered via the e-cigarette can improve PM, tobacco withdrawal symptoms and desire to smoke in abstinent smokers.
Methods
Twenty smokers, abstinent for 8–10 h, each completed two experimental sessions under nicotine (18 mg) and placebo (0 mg) e-cigarette conditions. Participants completed a single-item desire-to-smoke scale and the Mood and Physical Symptoms Scale. PM was measured using the Cambridge Prospective Memory Test.
Results
Compared with placebo, the nicotine e-cigarette reduced the desire to smoke and tobacco withdrawal symptoms, and improved time-based but not event-based PM. There was a moderate, marginally significant negative correlation between PM performance during abstinence and nicotine dependence.
Conclusions
This is the first study to show that nicotine derived via e-cigarette can improve PM in abstinent smokers, suggesting efficient nicotine delivery. The finding that the effect of nicotine was restricted to time-based rather than event-based PM is consistent with the view that nicotine acts to improve performance on strategic (effortful) rather than automatic processing. These findings add to the growing body of evidence that the e-cigarette can replace some of the effects of nicotine derived from tobacco smoking, thus highlighting its potential for smoking cessation.
Background: Anxiety is a negative emotion that contributes to craving and relapse during drug withdrawal. Sirtuins 1 (SIRT1) has been reported to be critical in both negative emotions and drug ...addiction. However, it remains incompletely elucidated whether SIRT1 is involved in morphine withdrawal-associated anxiety. Methods: We established a mouse model of anxiety-like behaviors induced by morphine withdrawal and then detected neuronal activity with immunofluorescence and mitochondrial morphology with electron microscopy, mitochondrial DNA contents with quantitative real-time PCR, and mitochondrial function with the ATP content detection kit and the Mitochondrial Complex IV Activity Kit in the basolateral amygdala (BLA). The mitochondrial molecules were detected by western blot. Then we used virus-mediated downregulation and overexpression of SIRT1 in BLA to investigate the effect of SIRT1 on anxiety and mitochondrial function. Finally, we examined the effects of pharmacological inhibition of SIRT1 on anxiety and mitochondrial function. Results: We found that BLA neuronal activity, mitochondrial function, and mtDNA content were significantly higher in morphine withdrawal mice. Furthermore, the expression levels of mitochondrial molecules increased in BLA cells. Virus-mediated downregulation of SIRT1 in BLA prevented anxiety-like behaviors in morphine withdrawal mice, whereas overexpression of SIRT1 in BLA facilitated anxiety-like behaviors in untreated mice through the SIRT1/ peroxisome proliferator activated receptor gamma coactivator 1-alpha pathway. Intra-BLA infusion of selective SIRT1 antagonist EX527 effectively ameliorated anxiety-like behaviors and mitochondrial dysfunction in mice with morphine withdrawal. Conclusion: Our results implicate a causal role for SIRT1 in the regulation of anxiety through actions on mitochondrial biogenesis. Inhibitors targeting SIRT1 may have therapeutic potential for the treatment of opioid withdrawal-associated anxiety. Keywords: Anxiety, morphine withdrawal, basolateral amygdala, mitochondria, SIRT1
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