Trial protocol of an open label pilot study of lisdexamfetamine for the treatment of acute methamphetamine withdrawal

Introduction Methamphetamine (MA) use disorder is an important public health concern. MA withdrawal is often the first step in ceasing or reducing use. There are no evidence-based withdrawal treatments, and no medication is approved for the treatment of MA withdrawal. Lisdexamfetamine (LDX) dimesilate, used in the treatment of attention deficit hyperactivity disorder and binge eating disorder has the potential as an agonist therapy to ameliorate withdrawal symptoms, and improve outcomes for patients. Methods A single arm, open-label pilot study to test the safety and feasibility of LDX for the treatment of MA withdrawal. Participants will be inpatients in a drug and alcohol withdrawal unit, and will receive a tapering dose of LDX over five days: 250mg LDX on Day 1, reducing by 50mg per day to 50mg on Day 5. Optional inpatient Days 6 and 7 will allow for participants to transition to ongoing treatment. Participants will be followed-up on Days 14, 21 and 28. All participants will also receive standard inpatient withdrawal care. The primary outcomes are safety (measured by adverse events, changes in vital signs, changes in suicidality and psychosis) and feasibility (the time taken to enrol the sample, proportion of screen / pre-screen failures). Secondary outcomes are acceptability (treatment satisfaction questionnaire, medication adherence, concomitant medications, qualitative interviews), retention to protocol (proportion retained to primary and secondary endpoints), changes in withdrawal symptoms (Amphetamine Withdrawal Questionnaire) and craving for MA (visual analogue scale), and sleep outcomes (continuous actigraphy and daily sleep diary). Discussion This is the first study to assess lisdexamfetamine for the treatment of acute MA withdrawal. If safe and feasible results will go to informing the development of multi-centre randomised controlled trials to determine the efficacy of the intervention

The Backspin Backhand Drive In Tennis To Balls Of Varying Height

Modern tactics dictate that while the forehand drive is seldom hit with backspin, the backhand must be able to be hit with topspin or backspin depending on the height of bounce of the ball and/or tactical requirement of a particular rally. No studies have clearly identified the mechanical characteristics of the backspin stroke, although data are available on topspin (Elliott et al., 1989), flat (Pecore, 1979; Young, 1970) and one versus twohanded (Groppel and Ward, 1979) backhand drives. Three-dimensional (3D) high speed cinematography was used to compare backspin backhand techniques of 13 high performance players hitting low (hip height) and high (shoulder height) bouncing balls. The Direct Linear Transformation method was used for 3D space reconstruction from 2D images recorded from laterally placed phaselocked cameras operating at 200 fps. Players modified their technique for a low backspin backhand to hit a high bouncing ball by: 1. adopting a more upright trunk (67°) and larger front knee angle (175°) than was recorded for the lower stroke (61 ° and 156°) respectively. 2. adopting a more closed shoulder alignment in the transverse plane (line joining the two acromion processes was 20° beyond a perpendicular to the net) than was recorded for the lower stroke, where the shoulder alignment at impact was perpendicular to the net. 3. hitting the ball with a larger 3D shoulder joint angle (60°) than was .recorded for the lower stroke (54°). 4. impacting the ball with a less inclined approach trajectory of the racket (16 °) and more vertical racket-free (83°) than was recorded for the lower impact (-25° and 78° respectively). 5. reducing the racket velocity at impact from 20.6m s-l for the lower stroke to 19.5 m s-l for the high stroke. 6. modifying the role of rotation of the upper arm (outward rotation) and forearm (supination). Although not quantitatively measured in this study, it was evident when reviewing the film that outward rotation of the upper arm and forearm supination both would seem to play an integral role in the generation of racket-head velocity for the higher backhand. A comprehensive anaiysis of the mechanics of these strokes will be presented in this paper

A clinical research priority setting study for issues related to the use of methamphetamine and emerging drugs of concern in Australia

Introduction: This study aimed to gather a range of opinions, including those of affected people (consumers, concerned others) to identify clinical research priorities for methamphetamine and emerging drugs of concern in Australia, to guide the work of the National Centre for Clinical Research on Emerging Drugs (NCCRED). Methods: A priority setting study was conducted (February–March 2019) in four phases: online stakeholder survey, thematic analysis of responses, rapid literature review, expert panel ranking of priorities against predetermined criteria. Results: Forty-seven respondents completed the survey, including people identifying as one or more of: researcher (53%, n = 25), clinician (45%; n = 21), family/friend/caregiver of someone who uses methamphetamine/emerging drugs (15%, n = 7) and consumer of methamphetamine/emerging drugs (13%, n = 6). Expert panel, evidence-informed top-ranked clinical research priorities for methamphetamine were: strategies to overcome barriers to intervention uptake, pilot medication trials for adults seeking treatment, and communication strategies regarding evidence-based treatments. For emerging drugs of concern, top-ranked priorities were: piloting community-located drug checking, feasibility of social media/other opportunities to alert consumers of emerging risks, GHB overdose and withdrawal management, and impacts of an early warning information system on reducing harms. Discussion and Conclusions: We demonstrate feasibility of a structured, collaborative clinical research priority setting process. Results have informed the establishment of NCCRED; using the identified priorities to guide seed funding, fellowships/scholarships and research programs. Broader uptake of this methodology by policymakers/research funders would assist to embed areas of concern identified by affected communities and other stakeholders in research prioritisation

Supplementary Material for: Measuring objective and subjective sleep during lisdexamfetamine treatment of acute methamphetamine withdrawal: A feasibility study

Background: Sleep disturbance is common during methamphetamine (MA) use and withdrawal, however the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. Objective: To investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal. Method: We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7-days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3-5. Results: 10 participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n=8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 minutes, sleep onset latency 22.4 minutes, wake after sleep onset (WASO) 75.2 minutes and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 minutes (p=0.008) and WASO 47 minutes (p<0.001) less). Overall sleep quality was 4.4 on a nine-point Likert-scale within the diary. Conclusions: Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which needs to be explored in more detail