SUMMARYIn June 2019, the Purine and Pyrimidine Society (PPS) organized the 18th biennial symposium on Purine and Pyrimidine Metabolism at the International Agency for Research on Cancer in Lyon, France. This meeting went over 3 days and gathered students and researchers working in various specialties such as inborn errors, hyper- and hypouricemia and gout, cancer, enzymology, and cardiovascular diseases to exchange and discuss recent advances in the field of purine and pyrimidine metabolism. Here, we give an overview of oral presentations given during the symposium.PURPOSE Lifirafenib is an investigational, reversible inhibitor of B-RAFV600E, wild-type A-RAF, B-RAF, C-RAF, and EGFR. This first-in-human, phase I, dose-escalation/dose-expansion study evaluated the safety, tolerability, and efficacy of lifirafenib in patients with B-RAF- or K-RAS/N-RAS-mutated solid tumors. METHODS During dose escalation, adult patients with histologically/cytologically confirmed advanced solid tumors received escalating doses of lifirafenib. Primary end points were safety/tolerability during dose escalation and objective response rate in preselected patients with B-RAF and K-RAS/N-RAS mutations during dose expansion. RESULTS The maximum tolerated dose was established as 40 mg/d; dose-limiting toxicities included reversible thrombocytopenia and nonhematologic toxicity. Across the entire study, the most common grade ≥ 3 treatment-emergent adverse events were hypertension (n = 23; 17.6%) and fatigue (n = 13; 9.9%). One patient with B-RAF-mutated melanoma achieved complete response, and 8 pat RAS mutations who are resistant/refractory to first-generation B-RAF inhibitors are warranted.Background/Objectives Older homeless-experienced adults have low rates of advance care planning (ACP) engagement despite high rates of morbidity and mortality. To inform intervention development, we examined potential barriers and solutions to ACP engagement. Design Cross-sectional qualitative study. Setting We recruited adults who were homeless in the prior three years and ≥50 years of age in the San Francisco Bay Area, and recruited clinical stakeholders from a national meeting of homeless providers. We analyzed qualitative data using thematic analysis. selleck products Measurements We conducted semistructured interviews with homeless-experienced older adults (n = 20) and focus groups with clinical stakeholders (n = 24) about perceived barriers and solutions to ACP engagement. Results Participants considered ACP important, reflecting on deaths of people in their networks who had died. Participant-identified barriers to ACP included poor ACP knowledge, lack of familial ties and social isolation, competing priorities, avoidance and lack of readiness, fatalism and mistrust, and lack of ACP training for clinical and nonclinical staff. They identified solutions that included framing ACP as a way to provide meaning and assert choice, providing easy-to-read written documents focused on the populations' unique needs, tailoring content and delivery, initiating ACP in nonclinical settings, such as permanent supportive housing, and providing incentives. Conclusions Both older homeless-experienced adults and clinical stakeholders believe that ACP is important, but acknowledge multiple barriers that impede engagement. By focusing on potential solutions, including capitalizing on opportunities outside of health care settings, focusing on the period after housing, and tailoring content, there are opportunities to improve ACP uptake.Background Communication between clinicians and families of dying children in the pediatric intensive care unit (PICU) is critically important for optimal care of the child and the family. Objective We examined the current state of clinician perspective on communication with families of dying children in the PICU. Design Prospective case series over a 15-month study period. Setting/Subjects We surveyed nurses, psychosocial staff, and physicians who cared for dying children in PICUs at five U.S. academic hospitals. Measurements Clinicians reported on the location of communication, perceived barriers to end-of-life care, and rated the quality of communication (QOC). Results We collected 565 surveys from 287 clinicians who cared for 169 dying children. Clinicians reported that the majority of communication occurred at the bedside, and less commonly family conferences and rounds. Ten barriers to care were examined and were reported with frequencies of 2%-32%. QOC was rated higher when the majority of conversations occurred during family conferences (p = 0.01) and lower for patients of non-white race (p = 0.03). QOC decreased when 8 of the 10 barriers to care were reported. Conclusions When a child is dying, clinicians report that communication with the family occurs most frequently at the child's bedside. This has important implications for future ICU communication research as the majority of previous research and education has focused on family care conferences. In addition, findings that QOC is perceived as lower for non-white patients and when clinicians perceive that barriers hindering care are present can help direct future efforts to improve communication in the PICU.Background To address the alarming rise in opioid overdose deaths, states have increased public access to the overdose reversal medication, naloxone. While some studies suggest that increased naloxone accessibility reduces opioid overdose deaths, others raise concerns about unintended consequences, such as increases in risky drug use and opioid re-use post-overdose to counter naloxone-induced withdrawal symptoms. Few studies have examined the impact of expanded naloxone access on the attitudes and behaviors of opioid users. Methods In this qualitative study, we conducted in-depth, semi-structured interviews with 36 English-speaking opioid users 18+ years of age. Informants were recruited from an urban methadone clinic, a needle exchange program and a residential treatment program. The approximately hour-long interviews focused on users' attitudes and behaviors surrounding naloxone, opioid use and overdose. Transcribed audio-recordings of interviews were analyzed using NVivo. Results Informants were ambivalent about naloxone, widely acknowledging its life-saving benefits while reporting such negative effects as severe withdrawal symptoms and the promotion of riskier drug use.