Measures of outcome for stimulant trials: ACTTION recommendations and research agenda

BACKGROUND: The development and approval of an efficacious pharmacotherapy for stimulant use disorders has been limited by the lack of a meaningful indicator of treatment success, other than sustained abstinence. METHODS: In March, 2015, a meeting sponsored by Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) was convened to discuss the current state of the evidence regarding meaningful outcome measures in clinical trials for stimulant use disorders. Attendees included members of academia, funding and regulatory agencies, pharmaceutical companies, and healthcare organizations. The goal was to establish a research agenda for the development of a meaningful outcome measure that may be used as an endpoint in clinical trials for stimulant use disorders. RESULTS AND CONCLUSIONS: Based on guidelines for the selection of clinical trial endpoints, the lessons learned from prior addiction clinical trials, and the process that led to identification of a meaningful indicator of treatment success for alcohol use disorders, several recommendations for future research were generated. These include a focus on the validation of patient reported outcome measures of functioning, the exploration of patterns of stimulant abstinence that may be associated with physical and/or psychosocial benefits, the role of urine testing for validating self-reported measures of stimulant abstinence, and the operational definitions for reduction-based measures in terms of frequency rather than quantity of stimulant use. These recommendations may be useful for secondary analyses of clinical trial data, and in the design of future clinical trials that may help establish a meaningful indicator of treatment success

Bone Mineral Density in HIV-Negative Men Participating in a Tenofovir Pre-Exposure Prophylaxis Randomized Clinical Trial in San Francisco

Pre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco.We evaluated 1) the prevalence of low BMD using Dual Energy X-ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began study drug after a 9-month delay to evaluate changes in risk behavior associated with pill-use. At baseline, 20 participants (10%) had low BMD (Z score≤-2.0 at the L2-L4 spine, total hip, or femoral neck). Low BMD was associated with amphetamine (OR = 5.86, 95% CI 1.70-20.20) and inhalant (OR = 4.57, 95% CI 1.32-15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to have low BMD at baseline (OR = 0.26, 95% CI 0.10-0.71). In the longitudinal analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre-treatment/placebo group at the femoral neck (95% CI 0.4-1.9%), 0.8% net decline at the total hip (95% CI 0.3-1.3%), and 0.7% at the L2-L4 spine (95% CI -0.1-1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the femoral neck in the TDF vs. placebo groups (p = 0.13).Ten percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures.ClinicalTrials.gov: NCT00131677

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Paving a Two-Way Street: The Rewards and Challenges of Archival Projects with Community Partners

Academic libraries are increasingly engaged in establishing community-based archives programs, often with digital preservation, delivery, and exhibit components. Often these activities are in response to local communities\u27 needs to document valuable and vulnerable cultural heritage materials, fueled by the understanding that community partnerships create mutually beneficial opportunities for the academic institution, students, and staff. From a practical standpoint, institutions need to be able to identify potential points of synergy and challenge when working with both internal and external communities on collaborative digital projects; however, this can be difficult for institutions that are new to this kind of collaboration. Understanding the differing priorities of academic institutions and community archives and organizations, as well as their respective cultural contexts, is critical for successful collaboration. In this panel, representatives from three institutions (a small private college, a small private university, and a large public university) presented academic community-based digital projects as case studies to contextualize discussion of how to engage and develop community relationships and archives programs within an academic setting. Panelists explored the challenges of sustainability and management of expectations in community-based digital projects, including project process and management, digitization and technology needs, meeting research needs, and unexpected demands on both the community and the academic institution during and after the launch of community-based archives programs. In addition, panelists described tangible results of digital archival projects, including curriculum development, expanded partnerships, and increased “brand awareness” of the academic institution and community partners. The panelists demonstrated that size and resource base do not dictate the issues that are likely to emerge for institutions when they initiate a community-based project. By emphasizing a philosophy of strategic collaboration, as well as emerging theories of participatory community archives, the panelists offered attendees a chance to learn about the rewards and challenges of collaboration when creating novel approaches to expose unique collections. Panelists also emphasized ways to incorporate experiential learning for students and community members, including engagement in faculty/student collaborative research, work study/internship opportunities, and lifelong learning for community partners. Finally, the panelists provided insight into identifying potential partnerships at academic institutions and in local communities, including strategies for identifying and securing grants and other funding, both for launching and for sustaining community partnership projects

Therapy manuals for drug addiction.

"Contract number N-01DA-4-2205"--Manuals 1-2."Printed September 1999"--Manual 3, t.p. verso."Printed April 1998"--Manuals 1-2, t.p. verso.Shipping list no.: 98-0202-P (manuals 1-2).Includes bibliographical references.manual 1. A cognitive-behavioral approach : treating cocaine addiction / Kathleen M. Carroll -- manual 2. A community reinforcement plus voucher approach : treating cocaine addiction / Alan J. Budney, Stephen T. Higgins -- manual 3. An individual drug counseling approach to treat cocaine addiction : the collaborative cocaine treatment study model / Delinda E. Mercer, George E. Woody. -- manual 4. Drug conunseling for cocaine addiction: The collaborative cocaine treatment study modelMode of access: Internet