Polysubstance use patterns among high dose benzodiazepine users: a latent class analysis and differences between male and female use

Benzodiazepines (BZDs) represent one of the most widely used groups of pharmaceuticals, but if used for long periods of time they are associated with dependence and an increased risk of harmful effects. High-dose (HD) BZD dependence is a specific substance use disorder associated with a poor quality of life. It is especially important to pinpoint differences in HD BZD addict subgroups in order to tailor treatment to the individual's specific needs, also considering possible comorbidities with other substance use disorders. We conducted a study to evaluate HD BZD dependence (converted doses to diazepam equivalents, mg) in an Italian sample of 1,354 participants. We also investigated if and to which extent participants co-used other substances (alcohol, tobacco, cannabis/cannabinoids, cocaine, and heroin). We then performed latent class analysis (LCA) to identify the use patterns of these substances, finding three classes: participants in Class 1 (4.3% of the sample) had the highest probability of also using cocaine and alcohol (Polysubstance BZD users); Class 2 comprised subjects with the highest probability of being former heroin, cocaine, THC, and alcohol users (Former polysubstance BZD users); Class 3 represented mono-dependence BZD users (78.5% of the sample) and was the most prevalent among women, while young men were most prevalent in Class 1. The present study underlines different characteristics in HD BZD users both concerning other addictions and sex, and also highlights the need for a stricter control of BZD use, ranging from prescriptions to sales

Transcranial direct current stimulation (tDCS) over the left prefrontal cortex does not affect time-trial self-paced cycling performance: Evidence from oscillatory brain activity and power output

To test the hypothesis that transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) influences performance in a 20-min time-trial self-paced exercise and electroencephalographic (EEG) oscillatory brain activity in a group of trained male cyclists. There were no differences (F = 0.31, p > 0.05) in power output between the stimulation conditions: anodal (235W[95%CI 222–249 W]; cathodal (235W[95%CI 222–248 W] and sham (234W[95%CI 220–248 W]. Neither heart rate, sRPE nor EEG activity were affected by tDCS (all Ps > 0.05). tDCS over the left DLFC did not affect self-paced exercise performance in trained cyclists. Moreover, tDCS did not elicit any change on oscillatory brain activity either at baseline or during exercise. Our data suggest that the effects of tDCS on endurance performance should be taken with caution.This project was supported by grants from from the Spanish Ministerio de Economía, Industria y Competitividad-PSI2016-75956-P to D. S. and M.Z., a predoctoral grant from the Spanish Ministerio de Economía, Industria y Competitividad (BES-2014-069050) to L.F.C., and a Spanish “Ministerio de Educación, Cultura y Deporte” predoctoral grant (FPU14/06229) to D.H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Therapeutic alliance impact on analgesic outcomes in a real-world clinical setting: An observational study

A good therapeutic alliance is relevant for healthcare providers exposed to patients\u27 suffering, especially since patients and physicians may understand the painful experience differently. Our aim was to explore the impact of therapeutic alliance on analgesic outcomes in a real-world interdisciplinary pain unit (PU). A cross-sectional observational study was conducted on outpatients (n = 69) using opioids on a long-term basis for the treatment of chronic non-cancer pain, where clinical pharmacologists and pharmacists advised patients about their opioid treatment. Responses to the patient-doctor relationship questionnaire (PDRQ), sociodemographic and clinical information (pain level, quality of life and hospital use) were collected, whereas pharmacology data (analgesic prescription, adverse events, and compliance) were obtained from electronic health records. Patients were predominantly middle-aged (75 % women, 72 % retired), experiencing moderate pain (VAS 40–70 mm) on average, and under a high morphine equianalgesic dosage (95 ± 88 mg per day, mainly tapentadol or fentanyl). Patients with better PDRQ outcomes, and therefore better therapeutic alliance, showed lower pain intensity than patients with worse PDRQ outcomes (pain intensity: high scores 60 ± 47 mm and medium scores 60 ± 45 mm vs. low scores 80±75 mm, p < 0.01). Along with this, pain intensity was lower when patients affirmed that, thanks to the healthcare providers, they “gained new insight”, “felt better”, or “felt content with their doctor’s treatment”. What´s more, patients who affirmed “I benefit from the treatment” experienced increased pain relief (benefit 40 ± 30 vs. non-benefit 19 ± 26 mm, p = 0.010) and improved quality of life (benefit 33 ± 25 vs. non-benefit 18 ± 16 mm, p = 0.031). However, there was a percentage of patients who did not fully understand the provided information, which is something to be taken into account to improve in clinical routine. Therapeutic alliance supported by pharmacist experts on pain management can be an effective strategy to improve analgesic outcomes. Further efforts are needed to improve communication strategies for pain management. Future directions of research should include the analysis of the role of the pharmacist in poly-professional consultations as related to the advice of patients about their medication, and the mutual trust with the patients

A virtual reality study on postretrieval extinction of smoking memory reconsolidation in smokers

Exposure to smoking-related stimuli may induce the reconsolidation of smoking-related memories in smokers. Research has proposed that extinction applied after the retrieval of a smoking memory may inhibit reconsolidation and prevent craving. The aim of this study was to test the effect of postretrieval extinction (PRE) on the reconsolidation of smoking memory by using a virtual reality (VR) simulation in smokers. On the day 1 session, the study exposed 46 smokers to a neutral and then to a smoking VR scenario under a fixed-block protocol. On day 2, the study randomized participants into three groups (G) and exposed them to a 15-s VR immersion in smoking (G1, G3) or neutral (G2) scenario for memory retrieval. After 15 min, the study exposed G1 and G2 to a VR PRE during the temporal window of memory vulnerability, whereas the study exposed G3 to extinction immediately after retrieval. On day 3, the study exposed all groups to neutral and smoking scenarios similar to day 1. All groups significantly increased craving for cigarettes after exposure to the smoking scenario on day 1 (p 0.01). On day 3, VR PRE after a 15-second VR smoking memory retrieval was able to inhibit reconsolidation in G1, but not in G3 exposed to PRE before the window of vulnerability, or in G2 not exposed to the smoking memory retrieval. These findings show the superiority of VR PRE after smoking memory retrieval compared to a standard extinction procedure

High-dose benzodiazepine use and QTc interval prolongation, a latent class analysis study

Benzodiazepine (BDZ) addiction is a widespread and multifaceted phenomenon. For many patients, especially females, the concomitant use of other drugs also increases their risk of QTc prolongation, possibly leading to complications such as seizures and even sudden death. However, the relationship between BDZ use and QTc prolongation is currently unclear. The present study aims to examine patterns of polysubstance use among a sample of Italian adults with BDZ dependence in relation with their QTc prolongation risk. We used Latent Class Analysis (LCA) on data collected from 251 inpatients of the Addiction Medicine Unit in Verona to group patients into three classes according to their substance use and their QTc prolongation risk. Results showed no significant relationship between QTc prolongation and BDZ use in any of the classes considered. We conclude that BDZs, even if used long-term and at high dosages, can be considered safe in terms of cardiovascular complications for patients

Novel evidence on the effect of tramadol on self-pace high-intensity cycling

The use of tramadol is a controversial topic in cycling. In order to provide novel evidence on this issue, we tested 29 participants in a pre-loaded cycling time trial (TT; a 20-min TT preceded by 40-min of constant work-rate at 60% of the VO2max) after ingesting 100 mg of tramadol (vs placebo and paracetamol (1.5 g)). Participants performed the Psychomotor Vigilance Task (PVT) at rest and a Sustained Attention to Response Task (SART) during the 60 min of exercise. Oscillatory electroencephalography (EEG) activity was measured throughout the exercise. The results showed higher mean power output during the 20-min TT in the tramadol vs. paracetamol condition, but no reliable difference was reported between tramadol and placebo (nor paracetamol vs. placebo). Tramadol resulted in faster responses in the PVT and higher heart rate during exercise. The main effect of substance was reliable in the SART during the 40-min constant workload (no during the 20-min TT), with slower reaction time, but better accuracy for tramadol and paracetamol than for placebo. This study supports the increased behavioural and neural efficiency at rest for tramadol but not the proposed ergogenic or cognitive (harmful) effect of tramadol (vs. placebo) during self-paced high-intensity cycling

Transcranial direct current stimulation (tDCS) over the left prefrontal cortex does not affect time-trial self-paced cycling performance: Evidence from oscillatory brain activity and power output

Objectives: To test the hypothesis that transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) influences performance in a 20-min time-trial self-paced exercise and electroencephalographic (EEG) oscillatory brain activity in a group of trained male cyclists. Design: The study consisted of a pre-registered (https://osf.io/rf95j/), randomised, sham-controlled, single-blind, within-subject design experiment. Methods: 36 trained male cyclists, age 27 (6.8) years, weight 70.1 (9.5) Kg; VO2max: 54 (6.13) ml.min-1.kg-1, Maximal Power output: 4.77 (0.6) W/kg completed a 20-min time-trial self-paced exercise in three separate sessions, corresponding to three stimulation conditions: anodal, cathodal and sham. tDCS was administered before each test during 20-min at a current intensity of 2.0 mA. The anode electrode was placed over the DLPFC and the cathode in the contralateral shoulder. In each session, power output, heart rate, sRPE and EEG (at baseline and during exercise) was measured. Results: There were no differences (F = 0.31, p > 0.05) in power output between the stimulation conditions: anodal (235 W [95%CI 222–249 W]; cathodal (235 W [95%CI 222–248 W] and sham (234 W [95%CI 220–248 W]. Neither heart rate, sRPE nor EEG activity were affected by tDCS (all Ps > 0.05). Conclusion: tDCS over the left DLFC did not affect self-paced exercise performance in trained cyclists. Moreover, tDCS did not elicit any change on oscillatory brain activity either at baseline or during exercise. Our data suggest that the effects of tDCS on endurance performance should be taken with caution

Tramadol effects on physical performance and sustained attention during a 20-min indoor cycling time-trial: A randomised controlled trial

Objectives: To investigate the effect of tramadol on performance during a 20-min cycling time-trial (Experiment 1), and to test whether sustained attention would be impaired during cycling after tramadol intake (Experiment 2). Design: randomized, double-blind, placebo controlled trial. Methods: In Experiment 1, participants completed a cycling time-trial, 120-min after they ingested either tramadol or placebo. In Experiment 2, participants performed a visual Oddball task during the time-trial. Electroencephalography measures (EEG) were recorded throughout the session. Results: In Experiment 1, average time-trial power output was higher in the tramadol vs. placebo condition (tramadol: 220 watts vs. placebo: 209 watts; p 0.05). No behavioural differences were found between conditions in the Oddball task. Crucially, the time frequency analysis in Experiment 2 revealed an overall lower target-locked power in the beta-band (p < 0.01), and higher alpha suppression (p < 0.01) in the tramadol vs. placebo condition. At baseline, EEG power spectrum was higher under tramadol than under placebo in Experiment 1 while the reverse was true for Experiment 2. Conclusions: Tramadol improved cycling power output in Experiment 1, but not in Experiment 2, which may be due to the simultaneous performance of a cognitive task. Interestingly enough, the EEG data in Experiment 2 pointed to an impact of tramadol on stimulus processing related to sustained attention. Trial registration: EudraCT number: 2015-005056-96