IMPORTANCE Despite the legalization and widespread use of cannabis products for a variety of medical concerns in the US, there is not yet a strong clinical literature to support such use. The risks and benefits of obtaining a medical marijuana card for common clinical outcomes are largely unknown. OBJECTIVETo evaluate the effect of obtaining a medical marijuana card on target clinical and cannabis use disorder (CUD) symptoms in adults with a chief concern of chronic pain, insomnia, or anxiety or depressive symptoms. DESIGN, SETTING, AND PARTICIPANTSThis pragmatic, single-site, single-blind randomized clinical trial was conducted in the Greater Boston area from July 1, 2017, to July 31, 2020. Participants were adults aged 18 to 65 years with a chief concern of pain, insomnia, or anxiety or depressive symptoms. Participants were randomized 2:1 to either the immediate card acquisition group (n = 105) or the delayed card acquisition group (n = 81). Randomization was stratified by chief concern, age, and sex. The statistical analysis followed an evaluable population approach. INTERVENTIONSThe immediate card acquisition group was allowed to obtain a medical marijuana card immediately after randomization. The delayed card acquisition group was asked to wait 12 weeks before obtaining a medical marijuana card. All participants could choose cannabis products from a dispensary, the dose, and the frequency of use. Participants could continue their usual medical or psychiatric care. MAIN OUTCOMES AND MEASURESPrimary outcomes were changes in CUD symptoms, anxiety and depressive symptoms, pain severity, and insomnia symptoms during the trial. A logistic regression model was used to estimate the odds ratio (OR) for CUD diagnosis, and linear models were used for continuous outcomes to estimate the mean difference (MD) in symptom scores. RESULTSA total of 186 participants (mean [SD] age 37.2 [14.4] years; 122 women [65.6%]) were randomized and included in the analyses. Compared with the delayed card acquisition group, the immediate card acquisition group had more CUD symptoms (MD, 0.28; 95% CI, 0.15-0.40; P < .001); fewer self-rated insomnia symptoms (MD, -2.90; 95% CI, -4.31 to -1.51; P < .001); and reported no significant changes in pain severity or anxiety or depressive symptoms. Participants in the immediate card acquisition group also had a higher incidence of CUD during the intervention (17.1% [n = 18] in the immediate card acquisition group vs 8.6% [n = 7] in the delayed card acquisition group; adjusted odds ratio, 2.88; 95% CI, 1.17-7.07; P = .02), particularly those with a chief concern of anxiety or depressive symptoms. (continued) Key Points Question What are the risks and benefits of obtaining a medical marijuana card for adults who seek medical marijuana for pain, insomnia, and anxiety or depressive symptoms? Findings In this randomized clinical trial involving 186 participants, immediate acquisition of a medical marijuana card increased the incidence and severity of cannabis use disorder (CUD) and resulted in no sign...

The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy 1,2 . However, measuring tumour infiltrating lymphocytes (TILs) is restricted by lack of appropriate data. Whole exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations.Here we develop a method for T cell fraction estimation from WES samples, utilising a signal from T cell receptor excision circle (TRECs) loss during VDJ recombination of the T cell receptor alpha (TCRA) gene. This score significantly correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma and using a meta-analysis of immunotherapy-treated tumours, we show that this score predicts immunotherapy response, providing value beyond tumour mutational burden. Applying this score to a multi-sample pancancer cohort revealed high diversity in immune infiltration within tumours. Subclonal loss of 12q24.31-32, encompassing SPPL3, was associated with reduced TCRA T cell fraction. Our method, T cell ExTRECT (T cell Exome TREC Tool), quantifies the T cell infiltrate of WES samples.Here we propose a method for the estimation of the T cell fraction present in a WES sample. This method utilises a somatic copy number-based signal from VDJ recombination and the loss of TRECs. We explore the underlying features which predict T cell infiltrate in tumours and blood and evaluate determinants of immune heterogeneity within tumours. Finally, we demonstrate that our estimated T cell fraction can be used as a predictor of clinical response to CPI therapy. Results Inferring T cell fraction from WES dataT cell diversity, which is required for immune system recognition of foreign antigens, is a product of VDJ recombination, where segments within the T cell receptor genes recombine.The alpha chain of the T cell receptor is encoded by the TCRA gene (also known as TRA) and the result of VDJ recombination is the excision of unselected gene segments from TCRA as TRECs, with the T cell undergoing a deletion event within TCRA.Tools to infer cancer somatic copy number alteration (SCNA) [6][7][8][9] rely on the read depth ratio (RDR), reflecting the log of the ratio of reads between the tumour sample and its matched control (e.g. buffy coat in a centrifuged blood sample). Deviation in the RDR from zero is assumed to reflect a tumour SCNA. However, within TCRA this assumption does not hold; a deviance in the RDR may reflect T cell specific deletion events and SCNA tools may thus erroneously infer tumour SCNA. Indeed, in the TRACERx100 cohort multiple SCNA within TCRA were inferred in 165/327 tumour regions (Extended Data Fig. 1a). The RDR deviated the most within segments frequently included within TRECs (Extended Data Fig. 1b-c). This suggests that most detected SCNAs within TCRA...

Low diet quality is a significant public health problem in the United States, especially among low-income populations. The food environment influences dietary choices. When applied to eating behavior, behavioral economics (BE) recognizes that decision biases instigated by a food environment saturated with unhealthy foods may lead people to purchase such foods, even when they possess the necessary information and skills to make healthy dietary choices. Choice architecture, a BE concept that involves modifying the appeal or availability of choices to “nudge” people toward a certain choice, retains freedom of choice but makes unhealthy options less convenient or visible. Choice architecture has been demonstrated to influence food choices in various settings, including supermarkets, convenience stores, and food pantries. These modifications are low-cost and feasible to implement, making them a viable strategy to help “nudge” patrons toward healthier choices in food establishments serving low-income populations, including food pantries and retailers accepting the Supplemental Nutrition Assistance Program. This narrative review searched, appraised, and underscored the strengths and limitations of extant research studies that used choice architecture adaptations to influence food choices among low-income populations in the United States. Findings from studies in food pantry settings suggest the potential of BE strategies to improve the healthfulness of food choices and dietary intake in low-income populations. In food retail settings, research suggests that BE strategies increase sales of healthy foods, like fruits and vegetables. We identify new areas of research needed to determine if BE-based modifications in low-income settings have sustained impacts on diet quality.

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