Assessing alcohol and other drug prevention needs among Indigenous youth ages 13-17: Developing a culturally grounded Indigenous youth harm reduction intervention.

Perceptions of alcohol and other drug (AOD) use, harm reduction, and culture were examined among 10 U.S. Indigenous youth 13-17 years of age. Key findings were contextualized within the four constructs of Indigenous relationality: (a) youth understand the harms of AOD use (people); (b) youth appreciate non-abstinence-based education (ideas); (c) youth need safe spaces to talk about the impacts of AOD use (place); and (d) youth desire to help prevent AOD harms for themselves and others (cosmos). Findings from this community-based participatory study serve as the theoretical foundation to support the development of an Indigenous youth harm reduction intervention to prevent AOD use and related harms among urban Indigenous youth in the Pacific Northwest.

Bortezomib-based therapy for relapsed/refractory multiple myeloma in real-world medical practice.

OBJECTIVE: The efficacy and safety of bortezomib-based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE® OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real-world medical practice. METHOD: Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment-free interval, progression-free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. RESULTS: In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (≥partial response) was 69%, including 37% complete response/near-complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment-free interval was 7.9 months. After 22.6 months' median follow-up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new-onset any-grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. CONCLUSION: These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population.

A systematic review of noninferiority margins in oncology clinical trials.

Aim: A systematic literature review was conducted to identify and characterize noninferiority margins for relevant end points in oncology clinical trials. Materials & methods: Randomized, controlled, noninferiority trials of patients with cancer were identified in PubMed and Embase. Results: Of 2284 publications identified, 285 oncology noninferiority clinical trials were analyzed. The median noninferiority margin was a hazard ratio of 1.29 (mean: 1.32; range: 1.05-2.05) for studies that reported time-to-event end points (n = 192). The median noninferiority margin was 13.0% (mean: 12.7%; range: 5.0-20.0%) for studies that reported response end points as absolute rate differences (n = 31). Conclusion: Although there was consistency in the noninferiority margins' scale, variability was evident in noninferiority margins across trials. Increased transparency may improve consistency in noninferiority margin application in oncology clinical trials.

Racial and Ethnic Approaches to Community Health (REACH) Detroit partnership: improving diabetes-related outcomes among African American and Latino adults.

OBJECTIVES: We sought to determine the effects of a community-based, culturally tailored diabetes lifestyle intervention on risk factors for diabetes complications among African Americans and Latinos with type 2 diabetes. METHODS: One hundred fifty-one African American and Latino adults with diabetes were recruited from 3 health care systems in Detroit, Michigan, to participate in the Racial and Ethnic Approaches to Community Health (REACH) Detroit Partnership diabetes lifestyle intervention. The curriculum, delivered by trained community residents, was aimed at improving dietary, physical activity, and diabetes self-care behaviors. Baseline and postintervention levels of diabetes-specific quality-of-life, diet, physical activity, self-care knowledge and behaviors, and hemoglobin A1C were assessed. RESULTS: There were statistically significant improvements in postintervention dietary knowledge and behaviors and physical activity knowledge. A statistically significant improvement in A1C level was achieved among REACH Detroit program participants (P<.0001) compared with a group of patients with diabetes in the same health care system in which no significant changes were observed (P=.160). CONCLUSIONS: A culturally tailored diabetes lifestyle intervention delivered by trained community residents produced significant improvement in dietary and diabetes self-care related knowledge and behaviors as well as important metabolic improvements.

Rit promotes MEK-independent neurite branching in human neuroblastoma cells.

Rit, by sequence homology, is a member of the Ras subfamily of small guanine triphosphatases (GTPases). In PC6 cells, Rit signals through pathways both common to and different from those activated by Ras to promote cell survival and neurite outgrowth. However, the specific morphological changes induced by Rit in human cells are not known. Here, we show in a human neuronal model that Rit increases neurite outgrowth and branching through MEK-dependent and MEK-independent signaling mechanisms, respectively. Adenoviral expression of wild-type or constitutively active Rit increased neurite initiation, elongation and branching on endogenous matrix or a purified laminin-1 substratum of SH-SY5Y cells as assessed using image analysis. This outgrowth was morphologically distinct from that promoted by constitutively active Ras or Raf (evidenced by increased branching and elongation). Constitutively active Rit increased phosphorylation of ERK 1/2, but not Akt, and the MEK inhibitor PD 098059 blocked constitutively active Rit-induced neurite initiation but not elongation or branching. These results suggest that Rit plays a key role in human neuronal development and regeneration through activating both known and as yet undefined signaling pathways.