Esketamine combined with a mindfulness-based intervention for individuals with alcohol problems.

BACKGROUND: Alcohol use disorder (AUD) is a major public health issue, posing harmful consequences for individuals and society. Recent advances in addiction research have highlighted the therapeutic potential of ketamine-assisted therapy for AUD. However, the exact mechanisms underlying its effectiveness remain unknown. AIMS: This double-blind, pilot study aimed to investigate esketamine combined with mindfulness-based intervention (MBI) to examine whether esketamine enhances engagement in MBI for individuals with alcohol misuse problems and whether enhanced engagement has any impact on alcohol-related outcomes. METHODS: In all, 28 individuals with alcohol problems were randomly assigned to receive sublingual esketamine hydrochloride (AWKN002: 115.1 mg) or vitamin C (placebo) in an oral thin film and took part in 2 weeks of daily MBI. Participants were assessed on various self-report measures, including mindfulness, engagement in MBI (physical and psychological), alcohol cravings and consumption. RESULTS: Esketamine enhanced psychological engagement with a daily MBI, compared to placebo, and led to transient decreases in alcohol cravings. Esketamine also resulted in significantly greater mystical experiences and dissociative states compared to placebo. CONCLUSIONS: The findings suggest that esketamine may improve treatment outcomes when combined with mindfulness-based therapies through its ability to increase engagement with meditative practice.

Challenges and practical recommendations for successfully recruiting inactive, statin-free older adults to clinical trials.

OBJECTIVES: To outline the challenges and provide practical recommendations for recruiting inactive, statin-free older adults to facilitate feasible study designs. Data was obtained from a double-blind randomised-controlled clinical trial investigating the effects of acipimox versus placebo on muscle function and metabolism in older (65-75 years), inactive, statin-free males. The initial recruitment target was 20 volunteers within 12 months (November 2016-November 2017). RESULTS: Recruitment occurred via the Exeter 10,000 database containing 236 'eligible' males, a Facebook campaign reaching > 8000 ≥ 65 years old males, 400 directly-addressed letters to ≥ 66 year old males, > 1500 flyers distributed within the community, > 40 emails to local community groups, 4 recruitment talks, 2 magazine adverts and 1 radio advert. Widespread recruitment efforts reaching > 120,000 people led to the recruitment of 20 volunteers (18 completed the clinical trial) within a 25-month timeframe, highlighting the challenge of the timely recruitment of inactive, statin-free older adults for clinical trials. We recommend recruitment for future clinical trials should take a multi-pronged approach from the outset, prioritising the use of volunteer databases, Facebook campaigns and delivering recruitment talks.

Professional learning needs in using video calls identified through workshops.

BACKGROUND: Most people want to die at home but only half do. Supporting patients in rural locations is challenging. Video calls such as Skype, might help but are not routinely used; we should consider learning needs to increase uptake and ensure effective use. We aimed to identify learning needs of healthcare professionals (HCPs) in using video calls to support patients (and their carers) to die at home. METHODS: Face-to-face workshops were held in five Southwest England locations. Participants discussed advantages, disadvantages, scenarios for use, and the learning needs of video call users. Ideas were documented on flipcharts and discussions audio-recorded. The 116 participants included nurses, allied HCPs, doctors and previously bereaved volunteers. Lists of advantages, disadvantages, scenarios and learning needs were compiled and circulated to participants. In a subsequent online workshop, 21 participants ranked seven groups of learning needs in priority order. RESULTS: Most participants thought video calls could be used to advantage in many end-of-life scenarios, especially in rural areas. Seven themes, covering 59 learning needs for HCPs, were identified (in priority order): (i) confidence and technical ability in using video calls; (ii) being aware of how video calls fit into clinical practice; (iii) managing video calls; (iv) communication skills on 'camera'; (v) understanding how patients and families may be affected by video call use; (vi) presenting video calls as an option to patients and families to assess their readiness; (vii) normal professional skills that become essential for effective video calls. CONCLUSIONS: Although almost ubiquitous, video call software is not routinely and effectively used in British clinical practice. Supporting patients and families at end-of-life is one example where it could be used to advantage, but clinicians need to plan and practise before using it in real situations. Learning needs were identified that could be developed into learning modules and/or courses.

Clinically available iron chelators induce neuroprotection in the 6-OHDA model of Parkinson's disease after peripheral administration.

The iron content of the substantia nigra pars compacta increases in the brains of Parkinson's disease patients. Hence, its removal by iron chelators may retard the progression of the disease. However, information on the ability of clinically available iron chelators to cross the blood brain barrier and be neuroprotective is limited. In this present study three iron chelators, which are currently approved for clinical use, namely the hexadendate, deferrioxamine, the bidentate deferiprone and the tridendate chelator deferasirox have been investigated for their efficacy to induce neuroprotection. Previous studies have shown that both deferiprone and deferrioxamine exert neuroprotection in the 6-hydroxy dopamine (6-OHDA) model but no such studies have investigated deferasirox. Focal administration of deferasirox (0.5, 2 and 10 µg) into the substantia nigra pars compacta of rats significantly attenuated the loss of dopaminergic neurons and striatal dopamine content resulting from 6-OHDA toxicity. Systemic administration of deferasirox (20 mg/kg), deferiprone (10 mg/kg) or deferrioxamine (30 mg/kg), to the 6-OHDA rat model of Parkinson's disease, significantly attenuated the loss of dopaminergic neurons and striatal dopamine content. Further studies to comprehend the action of these chelators showed that local application of either 0.4 mM deferrioxamine, or 1 mM deferasirox, via a microdialysis probe into the striatum, prior to that of 200 µM 6-OHDA, prevented the generation of hydroxyl radicals. Our results confirm that the administration of these chelators show therapeutic efficacy and should be considered as therapeutic agents for the treatment of Parkinson's disease.