•We analyzed posts to a cannabis-specific forum on the Reddit platform.•Posts about emerging cannabis forms of use are common and increasing.•Users report greater average effects with dabs, edibles, ...and concentrates.•Many posts are regarding first-time use or asking for advice.•Few posts mention adverse health effects.
Legalization of medical and recreational cannabis has coincided with an increase in novel forms of cannabis use and a burgeoning cannabis product industry. This research seeks to understand the occurrence of discussions about these emerging and traditional forms of use in an online social media discussion forum.
We analyzed posts to a cannabis-specific forum on the Reddit social media platform posted from January 2010–December 2016. For each of various keywords describing smoking, vaping, edibles, dabbing, and butane hash oil (BHO) concentrate use, we analyzed (1) relative prevalence of posts mentioning these cannabis forms of use; (2) user-reported subjective ratings of “highness” on a scale of 1–10; (3) the ten most common words mentioned in posts; and (4) the frequency of adverse health effect terms.
Form of use was mentioned in approximately 17.7% of 2.26 million posts; smoking was the most commonly mentioned form of cannabis use. From 2010–2016, relative post volume increased significantly for posts mentioning dabbing (3.63/1000 additional posts per year, p < .001), butane hash oil terms (3.16/1000, p < .001), and edible terms (2.84/1000, p = .002). Mean subjective highness was significantly greater for posts mentioning dabbing (mean = 7.8, p < .001), butane hash oil terms (mean = 7.5, p < .001), and edible terms (mean = 7.2, p < .001) but not significantly different for vaping (mean = 6.7, p = .19), when compared to smoking (mean = 6.8).
Despite limitations in representativeness, findings indicate a significant increase in online discussion of emerging cannabis forms of use over time and greater subjective effects of dabbing, butane hash oil, and edible use.
Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory ...and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerability, and activity of autologous MSCs derived from bone marrow and infused intravenously in patients with active multiple sclerosis.
MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18–50 years) with active relapsing-remitting or progressive multiple sclerosis were included if they had a disease duration of 2–15 years since onset of multiple sclerosis and an Expanded Disability Status Scale score of 2·5–6·5. Patients were randomly assigned (1:1), according to a crossover design, to receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at week 24, with a follow-up visit at week 48. Primary objectives were to test safety and activity of MSC treatment. The primary safety endpoint was to assess the number and severity of adverse events within each treatment arm. The primary efficacy endpoint was the number of gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after all participants completed the week 24 visit. Efficacy endpoints were evaluated using a predefined statistical testing procedure. Safety was monitored throughout the study by recording vital signs and adverse events at each visit.
From July 16, 2012, until July 31, 2019, 144 patients were randomly assigned to first receive early intravenous infusion of autologous bone marrow-derived MSCs (n=69) or placebo (n=75). MSC treatment did not meet the primary endpoint of efficacy on the total number of GELs accumulated from baseline to week 24 (rate ratio RR 0·94, 95% CI 0·58–1·50; p=0·78). 213 adverse events were recorded, similarly distributed between groups (93 cases recorded in 35 51% of 69 patients treated first with MSCs vs 120 cases in 42 56% of 75 patients infused first with placebo). The most frequent adverse events reported were infection and infestations, with a total of 54 (25%) of 213 adverse events (18 19% of 93 in the early-MSC group and 36 30% of 120 in the delayed-MSC group). Nine serious adverse events were reported in seven patients treated with placebo versus none in the MSC group. All serious adverse events were considered to be unrelated to the treatment infusion. No deaths were reported during the study.
Bone marrow-derived MSC treatment was safe and well tolerated but did not show an effect on GELs, an MRI surrogate marker of acute inflammation, in patients with active forms of multiple sclerosis, at week 24. Thus, this study does not support the use of bone marrow-derived MSCs to treat active multiple sclerosis. Further studies should address the effect of MSCs on parameters related to tissue repair.
Fondazione Italiana Sclerosi Multipla (FISM), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and the Multiple Sclerosis International Federation (MSIF) for centralised activities. Individual trials participating in the MESEMS network are funded by the following agencies: FISM and Compagnia di San Paolo (Italy); The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors’ Research Foundation (Denmark); the Spanish Health Research Institute Carlos 3 and the Andalusian Public Foundation Progreso y Salud (Spain); the Royan Institute for Stem Cell Biology and Technology (Iran); the Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, and Salzburg (Austria); the Fondation pour l’aide à la recherche sur la sclérose en plaques (ARSEP), French Muscular Dystrophy Association (AFM)-Telethon (France); the UK Multiple Sclerosis Society and the UK Stem Cell Foundation (UK); and the Multiple Sclerosis Society of Canada and The Multiple Sclerosis Scientific Research Foundation and Research Manitoba (Canada).
Abstract Background We aimed to examine prevalence and correlates of past-month electronic cigarette (“e-cigarette”) use and use of e-cigarettes to aid a cessation attempt in three samples of young ...adult smokers recruited online in 2009–2010 (Study 1), 2010–2011 (Study 2), and 2013 (Study 3). Methods Participants were young adults aged 18 to 25 who smoked at least one cigarette in the previous month (Study 1, N = 1987 and Study 2, N = 570) or smoked 3 or more days each week and used Facebook 4 or more days per week (Study 3, N = 79). We examined both past-month e-cigarette use and ever use of e-cigarettes to quit conventional cigarettes. Results Prevalence of past-month use of e-cigarettes was higher in each subsequent study: Study 1 (6%), Study 2 (19%), and Study 3 (41%). In multivariate analyses, significant correlates of past-month e-cigarette use were identified for Study 1 (male sex OR = 2.1, p = .03; past-year quit attempt OR = 1.6, p = .03) and Study 2 (male sex, OR = 1.7, p = .03; younger age OR = 0.88, p = .05), but not Study 3. In multivariate analyses, significant correlates of ever use of e-cigarette to quit conventional cigarettes were identified for Study 1 (education, OR = 1.2, p = .02; smoking within 30 min of waking, OR = 2.8, p = .02; past year quit attempt OR = 4.1, p = .02), and Study 3 (desire to quit smoking, OR = 1.3, p = .02), but not Study 2. Conclusions E-cigarette use is increasingly common among young adults, particularly men. E-cigarette use for quitting conventional cigarettes appears more common among those more nicotine dependent and interested in quitting.
This study assesses the ecological risks (ERA) of pesticides to aquatic organisms in the River Madre de Dios (RMD), which receives surface runoff water from banana, pineapple, and rice plantations on ...the Caribbean coast of Costa Rica. Water samples collected over 2 years at five sites in the RMD revealed a total of 26 pesticides. Their toxicity risk to aquatic organisms was assessed using three recent ERA models. (1) The PERPEST model showed a high probability (>50 %) of clear toxic effects of pesticide mixtures on algae, macrophytes, zooplankton, macroinvertebrates, and community metabolism and a low probability (<50 %) of clear effects on fish. (2) Species sensitivity distributions (SSD) showed a moderate to high risk of three herbicides: ametryn, bromacil, diuron and four insecticides: carbaryl, diazinon, ethoprophos, terbufos. (3) The multi-substance potentially affected fraction (msPAF) model showed results consistent with PERPEST: high risk to algae (maximum msPAF: 73 %), aquatic plants (61 %), and arthropods (25 %) and low risk to fish (0.2 %) from pesticide mixtures. The pesticides posing the highest risks according to msPAF and that should be substituted with less toxic substances were the herbicides ametryn, diuron, the insecticides carbaryl, chlorpyrifos, diazinon, ethoprophos, and the fungicide difenoconazole. Ecological risks were highest near the plantations and decreased progressively further downstream. The risk to fish was found to be relatively low in these models, but water samples were not collected during fish kill events and some highly toxic pesticides known to be used were not analyzed for in this study. Further sampling and analysis of water samples is needed to determine toxicity risks to fish during peaks of pesticide mixture concentrations. The msPAF model, which estimates the ecological risks of mixtures based on their toxic modes of action, was found to be the most suitable model to assess toxicity risks to aquatic organisms in the RMD. The PERPEST model was found to be a strong tool for screening risk assessments. The SSD approach is useful in deriving water quality criteria for specific pesticides. This study, through the application of three ERA models, clearly shows that pesticides used in plantations within the RMD watershed are expected to have severe adverse effects on most groups of aquatic organisms and that actions are urgently needed to reduce pesticide pollution in this high biodiversity ecosystem.
Background and purpose
Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti‐inflammatory agents have failed to show efficacy in ...ameliorating disability progression. The aim of this study was to investigate a potential effect of anti‐inflammatory disease‐modifying treatment on disability outcomes in PPMS.
Methods
Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease‐modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention‐to‐treat and an as‐treated approach in paired, pairwise‐censored analyses.
Results
Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on‐study pairwise‐censored follow‐up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3‐month confirmed EDSS progression events was observed between the groups hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6–1.7, P = 0.87. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6–1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7–1.6, P = 0.69).
Conclusion
Our pooled analysis of disease‐modifying agents suggests that these therapies have no substantial effect on short‐ to medium‐term disability outcomes in PPMS.
Abstract
Introduction
Engagement with online content and online social network integration are associated with smoking behavior change, but less is known about social dynamics of shared engagement ...between participants in group-based social media interventions.
Methods
Participants were 251 young adult smokers aged 18 to 25 assigned to one of 29 secret Facebook groups tailored to their readiness to quit smoking (“pre-contemplation,” “contemplation,” and “preparation”). Groups varied in size and were randomly assigned to receive monetary incentives for engagement. All groups received daily posts for 90 days and were assessed for remote biochemically verified smoking abstinence at the end of the intervention. Across 29 groups, we examined associations between group features (group size, incentive condition, readiness to quit) with how connected members were within the group based on shared engagement with the same content (measured by density). At the individual level, we examined associations between 7-day biochemically verified smoking abstinence and how connected an individual was within the group (measured by degree centrality).
Results
After adjusting for comment volume, being in a contemplation group (vs. pre-contemplation group) was associated with a decrease in comment-based density. Individual degree centrality was significantly associated with biochemically verified smoking abstinence for both comments and likes.
Conclusions
Future group-based social media interventions for smoking cessation may want to focus on promoting connected engagement between participants, rather than simply quantity of engagement.
Implications
Participants in a smoking cessation intervention delivered through Facebook groups were more likely to have biochemically verified smoking abstinence if they were more connected to the rest of the group via shared engagement. Promoting shared engagement between participants may be more likely to promote behavior change than volume of engagement alone.
Background and purpose
Oral or intravenous methylprednisolone (≥500 mg/day for 5 days) is recommended for multiple sclerosis (MS) relapses. Nonetheless, the optimal dose remains uncertain. We ...compared clinical and radiological effectiveness, safety and quality of life (QoL) of oral methylprednisolone 1250 mg/day (standard high dose) versus 625 mg/day (lesser high dose), both for 3 days in MS relapses.
Methods
A total of 49 patients with moderate to severe MS relapse within the previous 15 days were randomized in a pilot, double‐blind, multicentre, non‐inferiority trial (ClinicalTrial.gov, NCT01986998). The primary endpoint was non‐inferiority of the lesser high dose by Expanded Disability Status Scale (EDSS) score improvement on day 30 (non‐inferiority margin, 1 point). The secondary endpoints were EDSS score change on days 7 and 90, changes in T1 gadolinium‐enhanced and new/enlarged T2 lesions on days 7 and 30, and safety and QoL results.
Results
The primary outcome was achieved mean (95% confidence interval) EDSS score difference, −0.26 (−0.7 to 0.18) at 30 days (P = 0.246). The standard high dose yielded a superior EDSS score improvement on day 7 (P = 0.028). No differences were observed in EDSS score on day 90 (P = 0.352) or in the number of T1 gadolinium‐enhanced or new/enlarged T2 lesions on day 7 (P = 0.401, 0.347) or day 30 (P = 0.349, 0.529). Safety and QoL were good at both doses.
Conclusions
A lesser high‐dose oral methylprednisolone regimen may not be inferior to the standard high dose in terms of clinical and radiological response.
Abstract
Introduction
This trial investigated whether a Facebook smoking cessation intervention culturally tailored to young sexual and gender minority (SGM) smokers (versus non-tailored) would ...increase smoking abstinence.
Methods
Participants were 165 SGM young adult US smokers (age 18–25) recruited from Facebook in April 2018 and randomized to an SGM-tailored (POP; N = 84) or non-tailored (TSP-SGM; N = 81) intervention. Interventions delivered weekly live counseling sessions and 90 daily Facebook posts to participants in Facebook groups. Primary analyses compared POP and TSP-SGM on biochemically verified smoking abstinence (yes/no; primary outcome), self-reported 7-day point prevalence abstinence (yes/no), reduction in cigarettes per week by 50+% from baseline (yes/no), making a quit attempt during treatment (yes/no), and stage of change (precontemplation/contemplation vs. preparation/action). Supplemental analyses compared POP to two historical control groups.
Results
POP participants were more likely than TSP-SGM participants to report smoking abstinence at 3 (23.8% vs. 12.3%; OR = 2.50; p = .03) and 6 months (34.5% vs. 12.3%; OR = 4.06; p < .001) and reduction in smoking at 3 months (52.4% vs. 39.5%; OR = 2.11; p = .03). Biochemically verified smoking abstinence did not significantly differ between POP and TSP-SGM at 3 (OR = 2.00; p = .33) or 6 months (OR = 3.12; p = .08), potentially due to challenges with remote biochemical verification. In supplemental analyses, POP participants were more likely to report abstinence at 3 (OR = 6.82, p = .01) and 6 (OR = 2.75, p = .03) months and reduced smoking at 3 months (OR = 2.72, p = .01) than participants who received a referral to Smokefree.gov.
Conclusions
This pilot study provides preliminary support for the effectiveness of a Facebook smoking cessation intervention tailored to SGM young adults.
Implications
SGM individuals have disproportionately high smoking prevalence. It is unclear whether smoking cessation interventions culturally tailored to the SGM community are more effective than non-tailored interventions. This pilot trial found preliminary evidence that an SGM-tailored Facebook smoking cessation intervention increased reported abstinence from smoking, compared to a non-tailored intervention.
Trial Registration
NCT03259360.
Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of ...individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (>80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement.
Biochemical verification of smoking abstinence remains an important validity check of cessation trial outcomes. Digital health trials rarely establish in-person contacts between participants and ...intervention providers, requiring novel strategies to biochemically verify outcomes. We describe remote verification of smoking abstinence via saliva cotinine and individual predictors of compliance in a digital intervention.
Data came from a feasibility trial and randomized controlled trial of a Facebook smoking cessation intervention for young adults. In both trials, participants completed baseline and follow-up surveys at 3, 6 and 12 months. Participants indicating past 7-day point prevalence smoking abstinence were mailed a saliva cotinine kit. Participants were instructed to electronically send two photos - one of them giving a saliva sample and the other with the test results. We investigated predictors of compliance with these procedures, independent of verification results, among participants that were mailed a kit at any follow-up point (N=130; mean age = 21.3; 59.2% female) using logistic and multinomial regression.
A total of 189 kits were sent out, of which 97 were completed (51.3% compliance). We did not identify significant predictors of completing any vs no kits using logistic regression. We also found no significant predictors of extent of kit completion (none vs some; none vs all) using multinomial regression and controlling for number of kits sent.
Findings demonstrate the feasibility of this biochemical verification method and suggest low risk for bias of results. Future studies should replicate findings in larger samples and improve compliance with verification procedures.
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