Exploring the suitability of cannabis use with next-day responsibilities: A behavioral-economic and qualitative study.

Cannabis demand is sensitive to next-day responsibilities, such as job interviews; however, it is unclear how demand is affected by non-work-related responsibilities and how reported compatibility of cannabis use (i.e., how suitable one perceives cannabis use to be in a situation) influences demand. This study examined the effects of a range of responsibilities on cannabis demand in a crowdsourced sample of adults who smoked cannabis at least monthly (n = 177; 78% White; 47% women; mean age = 36.52). Participants completed hypothetical marijuana purchase tasks asking how much cannabis they would consume at escalating prices in the context of no responsibilities and next-day responsibilities spanning work, leisure, and caregiving. Cannabis demand was significantly reduced in all responsibility conditions (ps < .008; ds .28-.94), with the largest reductions for the job interview and caring-for-kids conditions. Higher ratings of suitability of cannabis use in each situation were correlated with higher demand. Finally, a qualitative thematic analysis characterized why cannabis use was considered suitable or unsuitable with each responsibility. These results suggest that demand is sensitive to next-day responsibilities. However, these effects are not uniform, and future research is needed to examine these individual differences and the timing of upcoming responsibilities.

Insights from home parenteral nutrition infusion data.

OBJECTIVE: Patients with chronic intestinal failure use home parenteral nutrition infusion support. Non-compliance of home parenteral nutrition treatment is well documented, especially if clinical resources are remote. Objective delivery data from Infusion Pump reports have the potential to support treatment progress and planning. The aim of this study was to report the efficacy and accuracy of the Eitan Insights digital health platform for home parenteral nutrition use (a platform providing data-driven insights from the pump-recorded data). METHODS: A prospective, single-center observational study of 20 patients treated with home parenteral nutrition ≥3 d/wk was conducted over 2022. The patients recorded the pre- and postinfusion home parenteral nutrition bag weight, duration of infusion, and alarms. We compared manual records to the pump data. Repeated measures analysis of variance was used for statistical analysis. RESULTS: A total of 45 data sets were collected, with no adverse events noted. In multiple comparisons between patient factors and descriptive statistics, there was no significant difference between manually recorded and pump-recorded data for volume infused (mean values of manual versus pump were 1707 ± 362 mL and 1708 ± 405 mL; P = 0.939) and infusion duration (mean values of manual versus pump iwere 9h 43 min ± 2.48 SD versus 9h 45 min ± 2.41 SD; P = 0.858). CONCLUSION: The data collected by the digital platform accurately reflect patients' infusion data. This connected device has the potential to allow clinicians to be more informed and assess treatment trends and proactive resource planning through the Infusion Pump data insights.

Computational Exploration of Potential CFTR Binding Sites for Type I Corrector Drugs.

Cystic fibrosis (CF) is a recessive genetic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The recent development of a class of drugs called "correctors", which repair the structure and function of mutant CFTR, has greatly enhanced the life expectancy of CF patients. These correctors target the most common disease causing CFTR mutant F508del and are exemplified by the FDA-approved VX-809. While one binding site of VX-809 to CFTR was recently elucidated by cryo-electron microscopy, four additional binding sites have been proposed in the literature and it has been theorized that VX-809 and structurally similar correctors may engage multiple CFTR binding sites. To explore these five binding sites, ensemble docking was performed on wild-type CFTR and the F508del mutant using a large library of structurally similar corrector drugs, including VX-809 (lumacaftor), VX-661 (tezacaftor), ABBV-2222 (galicaftor), and a host of other structurally related molecules. For wild-type CFTR, we find that only one site, located in membrane spanning domain 1 (MSD1), binds favorably to our ligand library. While this MSD1 site also binds our ligand library for F508del-CFTR, the F508del mutation also opens a binding site in nucleotide binding domain 1 (NBD1), which enables strong binding of our ligand library to this site. This NBD1 site in F508del-CFTR exhibits the strongest overall binding affinity for our library of corrector drugs. This data may serve to better understand the structural changes induced by mutation of CFTR and how correctors bind to the protein. Additionally, it may aid in the design of new, more effective CFTR corrector drugs.