Perceived stigma of patients undergoing treatment with cannabis-based medicinal products

Cannabis-based medicinal products (CBMPs) are prescribed with increasing frequency. This study aimed to investigate the perceived stigma attached to patients prescribed CBMPs in the UK to establish its prevalence. A qualitative survey was developed by an expert multidisciplinary group and data were collected via Qualtrics. In total, 2319 patients on CBMP therapy were invited to take part in this study. 450 (19.4%) participants completed the questionnaire. In total, 81.3% (n = 366), 76.9% (n = 346), and 61.3% (n = 276) of participants reported feeling very comfortable or comfortable telling friends, family, and medical professionals, respectively, about their treatment. Participants thought that friends (n = 372; 82.7%) and family (n = 339; 75.3%) were very approving or somewhat approving of their CBMP prescription. However, participants thought that only 37.8% (n = 170) of healthcare professionals and 32.9% (n = 148) of society in general were very approving or somewhat approving of their CBMP prescription. 57.1% (n = 257), 55.3% (n = 249), and 40.2% (n = 181) of participants were afraid of what the police or criminal justice system, other government agencies, and healthcare professionals might think about their treatment. This study highlights those patients treated with CBMPs experience a high prevalence of perceived stigma from many corners of society. Future work should be undertaken to explore strategies to reduce perceived stigma at an individual and community level to avoid discrimination of patients, likely increasing appropriate access

Cannabis use in the UK:a quantitative comparison of individual differences in medical and recreational cannabis users

There is a paucity of research, especially in the UK, that investigates individual differences in both medical and recreational cannabis users. A cross-sectional survey study design was used to assess recreational cannabis users and medical cannabis users currently living in the UK. Recreational cannabis users were invited to take part via social media. Medical cannabis users were recruited from Sapphire Medical Clinics, London, UK, which provides treatment with prescribed cannabis-based medicinal products. Demographic data and cannabis use frequency, as well as post-traumatic stress disorder symptoms (PCL-5), depression symptoms (Centre for Epidemiological Studies Depression Scale), trait and state anxiety (State-Trait Anxiety Inventory), and cannabis use motives [Comprehensive Marijuana Motives Questionnaire (CMMQ)] were collected. The Chi-square and independent-sample t-tests were used for the comparison of categorical variables and normally distributed continuous variables. Data were analyzed using analyses of variance (ANOVAs) and t-tests. Statistical significance was considered where the value of p was <0.05. The survey was completed by 161 participants. Medical cannabis users were older, consumed cannabis more often, had a higher “Sleep” motive on the CMMQ, and had a higher prevalence in self-reporting current diagnoses of neurological problems, mood disorders, and anxiety disorders (p < 0.05). Recreational cannabis users had higher scores on several motives for use (e.g., “Enjoyment,” “Coping,” “Experimentation,” “Boredom,” and “Celebration”) and higher state anxiety scores (p < 0.05). The most common motives for cannabis use in both groups were “Enjoyment,” “Low Risk,” and “Sleep.” There were no differences between groups in gender, “Low-Risk” motive, post-traumatic stress disorder symptoms, depression scores, trait anxiety scores, self-reported prevalence of substance use-related disorders, and past consumption of alcohol, tobacco, or caffeine (p > 0.05). The current study not only demonstrates a difference in age and motivations for cannabis consumption between recreational and medical cannabis users but also shows areas of potential overlap, including mental health outcomes, past substance use, and gender. These UK-specific findings indicate that recreational cannabis users experience higher state anxiety, highlighting the need for further evaluation of potential anxiogenic/anxiolytic properties of cannabis. These findings demonstrate the importance of researching individual differences in cannabis users and hold significant implications for future research, clinical practice, and legislation

Disinfection of the Access Orifice in NOTES: Evaluation of the Evidence Base

Introduction. Appropriate prevention of infection is a key area of research in natural orifice translumenal endoscopic surgery (NOTES), as identified by the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR). Methods. A review of the literature was conducted evaluating the evidence base for access orifice preparation/treatment in NOTES procedures in the context of infectious complications. Recommendations based on the Oxford Centre for Evidence-Based Medicine guidelines were made. Results. The most robust evidence includes several experimental randomised controlled trials assessing infectious complications in the transgastric approach to NOTES. Transvaginal procedures are long established for accessing the peritoneal cavity following disinfection with antiseptic. Only experimental case series for transcolonic and transvesical approaches are described. Conclusion. Grade C recommendation requiring no preoperative preparation can be made for the transgastric approach. Antiseptic irrigation is recommended for transvaginal (grade C) NOTES access, as is current practice. Further human trials need to be conducted to corroborate the current evidence base for transgastric closure. It is important that future trials are conducted in a methodologically robust fashion, with emphasis on clinical outcomes and standardisation of enterotomy closure and postoperative therapy

MTL-CEBPA, a small activating RNA therapeutic upregulating C/EBP-α, in patients with advanced liver cancer: a first-in-human, multicenter, open-label, phase I trial

Purpose: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug which up-regulates C/EBP-α. Experimental Design: We conducted a phase I, open label, dose escalation trial of MTL-CEBPA in adults with advanced HCC with cirrhosis, or resulting from non-alcoholic steatohepatitis (NASH) or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose escalation phase (3+3 design). Results: 38 participants have been treated across 6 dose levels (28-160 mg/m2) and 3 dosing schedules. 34 patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose and no maximum dose was reached across the 3 schedules evaluated. Grade 3 treatment related adverse events occurred in 9 (24%) patients. In 24 HCC patients evaluable for efficacy, an objective tumour response was achieved in 1 patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKI); 3 patients had a complete response with one further PR and two with SD. Conclusions: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging Phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC

UK Medical Cannabis Registry palliative care patients cohort: initial experience and outcomes

Introduction: Palliative care aims to improve quality of life through optimal symptom control and pain management. Cannabis-based medicinal products (CBMPs) have a proven role in the treatment of chemotherapy-induced nausea and vomiting. However, there is a paucity of high-quality evidence with regards to the optimal therapeutic regimen, safety, and effectiveness of CBMPs in palliative care, as existing clinical trials are limited by methodological heterogeneity. The aim of this study is to summarise the outcomes of the initial subgroup of patients from the UK Medical Cannabis Registry who were prescribed CBMPs for a primary indication of palliative care, cancer pain and chemotherapy-induced nausea and vomiting, including effects on health-related quality of life and clinical safety. Methods: A case series from the UK Medical Cannabis Registry of patients, who were receiving CBMPs for the indication of palliative care was undertaken. The primary outcome consisted of changes in patient-reported outcome measures including EQ-5D-5L, General Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), Pain Visual Analog Scale (VAS) and the Australia-Modified Karnofsky Performance Scale at 1 and 3 months compared to baseline. Secondary outcomes included the incidence and characteristics of adverse events. Statistical significance was defined by p-value< 0.050. Results: Sixteen patients were included in the analysis, with a mean age of 63.25 years. Patients were predominantly prescribed CBMPs for cancer-related palliative care (n = 15, 94%). The median initial CBD and THC daily doses were 32.0 mg (Range: 20.0–384.0 mg) and 1.3 mg (Range: 1.0–16.0 mg) respectively. Improvements in patient reported health outcomes were observed according to SQS, EQ-5D-5L mobility, pain and discomfort, and anxiety and depression subdomains, EQ-5D-5L index, EQ-VAS and Pain VAS validated scales at both 1-month and 3-months, however, the changes were not statistically significant. Three adverse events (18.75%) were reported, all of which were either mild or moderate in severity. Conclusion: This small study provides an exploratory analysis of the role of CBMPs in palliative care in the first cohort of patients since CBMPs legalisation in the UK. CBMPs were tolerated with few adverse events, all of which were mild or moderate and resolved spontaneously. Further long-term safety and efficacy studies involving larger cohorts are needed to establish CBMPs role in palliative care, including comparisons with standard treatments

MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-α, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial.

PURPOSE: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULTS: Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSIONS: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC