Search

Introduction A potential precision medicine approach to smoking cessation is tailoring pharmacotherapy to a biomarker known as the nicotine metabolite ratio (NMR). Little is known about the potential impact and acceptability of this approach for American Indian (AI) persons. Aims and Methods Tribal-academic collaboration was formed and during 2019–2020 AI adults who smoke(N = 54) were recruited to (1) examine correlations between NMR, dependence, and smoking exposure; (2) assess the extent to which pharmacotherapy preference aligned with NMR-informed recommendations; (3) explore acceptability of NMR-informed pharmacotherapy selection. Participants provided samples for assessment of salivary NMR and urinary total nicotine equivalents (TNE) and completed a questionnaire that assessed cigarettes per day (CPD), Fagerstrom Test for Cigarette Dependence (FTCD), pharmacotherapy preference, and perceptions of NMR-informed pharmacotherapy selection. Results Significant positive correlations were observed between NMR and FTCD (r = 0.29;p = .0383) and its abbreviated version Heaviness of Smoking Index (HIS) (r = 0.28;p =.0426). Post-hoc analyses suggest that relationships between dependence and NMR were driven by time to first cigarette. Nonsignificant, but directionally consistent, relationships were observed between NMR and CPD (r = 0.21; p =0.1436) and TNE (r = 0.24;p = .2906). Most participants preferred nicotine replacement therapy (71%) over varenicline (29%) and preference for pharmacotherapy matched NMR-based recommendations in 54% of participants. NMR-informed pharmacotherapy selection was supported by 62% of participants. Conclusion In a sample of AI adults who smoke, NMR was related to cigarette dependence and about one-half of participants’ pharmacotherapy preference matched their NMR-informed recommendation. There was lower acceptability of NMR-informed approach in this sample of AI adults than prior studies among white or black/African American people who smoke. Implications Relationships between NMR, dependence, and self-preference for pharmacotherapy suggest that NMR-informed pharmacotherapy selection may have potential for enhancing smoking quitting success in this Tribe. Lower acceptability of NMR-informed pharmacotherapy in this Tribe suggests that this approach may not be equitably utilized. Future work could include identifying community-driven solutions to mitigate precision medicine concerns.

Increasing American Indian/Alaska Native (AI/AN) representation in genetic research is critical to ensuring that personalized medicine discoveries do not widen AI/AN health disparities by only benefiting well-represented populations. One reason for the under-representation of AIs/ANs in research is warranted research distrust due to abuse of some AI/AN communities in research. An approach to easing the tension between protecting AI/AN communities and increasing the representation of AI/AN persons in genetic research is community-based participatory research. This approach was used in a collaboration between a tribe and academic researchers in efforts to increase AI/AN participation in genetic research. From the lessons learned, the authors propose recommendations to researchers that may aid in conducting collaborative and respectful research with AI/AN tribes/communities and ultimately assist in increasing representation of AIs/ANs in personalized medicine discoveries.

As successes mount in reducing commercial tobacco use, an alarming disparity has taken shape in Minnesota. Recent studies revealed that overall smoking rates have dropped to 14%, whereas American Indians’ rates remain higher than 50%. With support from ClearWay Minnesota, the organization created from the state’s tobacco settlement, advocates working within sovereign tribal governments to create smoke-free policies came together to discuss effective strategies within tribal Nations. We discussed the history behind mainstream tobacco control’s failure to resonate with Native audiences and the need to reframe the movement to a goal of restoring traditional tobacco practices. We share our insights on this critical area for achieving health equity and provide recommendations for tribes, non-Indian advocates, and funders, with a plea for tribal inclusion in commercial tobacco “end-game” strategies.

Background Angiotensin-(1-9) is present in human and rat plasma and its circulating levels increased early after myocardial infarction or in animals treated with angiotensin-converting enzyme inhibitor. However, the cardiovascular effects of this peptide are unknown. Objective To determine whether angiotensin-(1-9) is a novel anti-cardiac hypertrophy factor in vitro and in vivo and whether this peptide is involved in the pharmacological effects of cardiovascular drugs acting on the renin-angiotensin system. Methods and results The administration of angiotensin-(1-9) to myocardial infarcted rats by osmotic minipumps (450 ng/kg per min, n = 6) vs. vehicle (n = 8) for 2 weeks decreased plasma angiotensin II levels, inhibited angiotensin-converting enzyme activity and also prevented cardiac myocyte hypertrophy. However, cardiac myocyte hypertrophy attenuation triggered by angiotensin-(1-9) was not modified with the simultaneous administration of the angiotensin-(1-7) receptor antagonist A779 (100 ng/kg per min, n = 6). In experiments in vitro with cultured cardiac myocytes incubated with norepinephrine (10 micromol/l) or with insulin-like growth factor-1 (10 nmol/l), angiotensin-(1-9) also prevented hypertrophy. In other experimental setting, myocardial infarcted rats (n = 37) were randomized to receive either vehicle (n = 12), enalapril (10 mg/kg per day, n = 12) or angiotensin II receptor blocker candesartan (10 mg/kg per day, n = 13) for 8 weeks. Both drugs prevented left ventricle hypertrophy and increased plasma angiotensin-(1-9) levels by several folds. Angiotensin-(1-9) levels correlated negatively with different left ventricular hypertrophy markers even after adjustment for blood pressure reduction. Conclusion Angiotensin-(1-9) is an effective and a novel anti-cardiac hypertrophy agent not acting via the Mas receptor.

Training the Trainers of Tomorrow Today (T4) is a new way to deliver “Training for Trainers”. Responding to local dissatisfaction with existing arrangements, T4 builds on 3 essential requirements for a future shape of training: 1. Clinical Leadership and a Collaborative Approach 2. Cross-Specialty Design and Participation 3. Local Delivery and Governance Networks Design principles also included: 3 levels of training to reflect differing needs of clinical supervisors, educational supervisors and medical education leader, mapping to GMC requirements and the London Deanery's Professional Development Framework; alignment of service, educational theory and research; recognition of challenges in delivering and ensuring attendance in busy acute and mental health settings, and the development of a faculty network. The delivery plan took into account census of professional development uptake and GMC Trainee Surveys. Strong engagement and uptake from the 11 Trusts in NW London has been achieved, with powerful penetration into all specialties. Attendance has exceeded expectations. Against an initial 12 month target of 350 attendances, 693 were achieved in the first 8 months. Evaluation of content demonstrates modules are pitched appropriately to attendees needs, with positive feedback from trainers new to the role. Delivery style has attracted high ratings of satisfaction: 87% attendees rating delivery as “good\excellent”. External evaluation of impact demonstrated improved training experiences through changes in supervision, the learning environment and understanding of learning styles. We have addressed sustainability of the programme by advertising and recruiting Local Faculty Development Trainers. Volunteer consultants and higher trainees are trained to deliver the programme on a cascade model, supported by the Specialty Tutors, individual coaching and educational bursaries. The Trainers are local champions for excellence in training, provide a communication between the programme and local providers, are a repository of expertise in their service, and trouble shoot local barriers to engagement.

We describe a patient who survived a peak serum magnesium level of 9.5 mmol/L (23.0 mg/dL) after an oral cathartic overdose. The patient presented in coma but regained full consciousness over the next six hours with supportive therapy. His serum magnesium had returned to near-normal levels by the following morning at the time of his hospital discharge. This case represents an unprecedented extent of ingestion-related hypermagnesemia in a surviving patient, given that serum levels of more than 8 mmol/L are frequently associated with death from cardiac arrest.