Sarah J. Nelson

Opioid misuse is at a crisis level. In response to this epidemic, the National Institutes of Health has funded $945 million in research through the Helping to End Addiction Long-term (HEAL) Pain Management Initiative, including funding to the Vanderbilt Recruitment Innovation Center (RIC) to strategize methods to catalyze participant recruitment. The RIC, recognizing the challenges presented to clinical researchers in recruiting individuals experiencing pain, conducted a review of evidence in the literature on successful participant recruitment methods for chronic pain trials, in preparation for supporting the HEAL Pain trials. Study design as it affects recruitment was reviewed, with issues such as sufficient sample size, impact of placebo, pain symptom instability, and cohort characterization being identified as problems. Potential solutions found in the literature include targeted electronic health record phenotyping, use of alternative study designs, and greater clinician education and involvement. For retention, the literature reports successful strategies that include maintaining a supportive staff, allowing virtual study visits, and providing treatment flexibility within the trial. Community input on study design to identify potential obstacles to recruitment and retention was found to help investigators avoid pitfalls and enhance trust, especially when recruiting underrepresented minority populations. Our report concludes with a description of generalizable resources the RIC has developed or adapted to enhance recruitment and retention in the HEAL Pain studies. These resources include, among others, a Recruitment and Retention Plan Template, a Competing Trials Tool, and MyCap, a mobile research application that interfaces with Research Electronic Data Capture (REDCap).

Purpose: To investigate the potential value of pre‐external‐beam radiation therapy (XRT) choline‐to‐NAA (N‐acetylaspartate) index (CNI), apparent diffusion coefficient (ADC), and relative cerebral blood volume (rCBV) for predicting survival in newly diagnosed patients with glioblastoma multiforme (GBM).Materials and Methods: Twenty‐eight patients with GBM were studied using in vivo proton magnetic resonance spectroscopic imaging (¹H MRSI) and diffusion‐ and perfusion‐weighted imaging after surgery but prior to XRT. Patients were categorized on the basis of their volumes of morphologic and metabolic abnormalities (volume of CNI ≥ 2 and CNI values), normalized ADC (nADC), or rCBV values within the T1 contrast‐enhancing and T2 regions. The median survival time was compared.Results: A significantly shorter median survival time was observed for patients with a large volume of metabolic abnormality than for those with a small abnormality (12.0 and 17.1 months, respectively, P = 0.002). A similar pattern was observed for patients with a low mean nADC value compared to those with high mean nADC value within the T2 region (11.2 and 21.7 months, respectively, P = 0.004). A shorter median survival time was also observed for patients with contrast‐enhancing residual disease than for those without the presence of contrast enhancement with marginal significance.Conclusion: The pre‐XRT volume of the metabolic abnormality and the nADC value within the T2 region may be valuable in predicting outcome for patients with GBM. J. Magn. Reson. Imaging 2004;19:546–554.

This study examined the effects of brain lesions and neuropsychological impairment on the efficacy of treatment for depression in patients with comorbid diagnoses of multiple sclerosis (MS) and major depressive disorder (MDD). Thirty patients meeting criteria for MS and MDD received 1 of 3 16-week treatments for depression and were followed for 6 months following treatment cessation. T2-weighted magnetic resonance imaging and neuropsychological evaluations were also obtained. End-of-treatment Beck Depression Inventory (BDI; A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) results residualized for baseline BDI were related to right temporal periventricular lesion volume (R2=.32, p=.002) and left temporal grey-white junction lesion volume (R2=.19, p=.02) but were not statistically related to lesion volume in any other brain region or to neuropsychological function. BDI results at 6-month follow-up, residualized for end-of-treatment BDI, were predicted by total lesion volume (R2=.22, p=.005), lesion volume in many discrete areas, and neuropsychological functioning (R2=.29, p=.0009). The effect of total lesion volume on 6-month follow-up BDI results was fully mediated by neuropsychological function.

A highly enriched plasma membrane fraction has been isolated from dark-grown cotyledons ofRicinus communis by phase partitioning. This is demonstrated by the properties of the associated ATPase: high vanadate sensitivity, azide and nitrate insensitivity, sharp pH optimum around 6.5, and high specificity for ATP as substrate. The upper plasma membrane fraction also contained a pyrophosphatase activity, normally considered to be located on the tonoplast or Golgi membranes, which showed a specific activity higher than that in the lower phase. Sucrose gradient centrifugation of both microsomal and upper phase fractions showed a comigration of some pyrophosphatase activity with the plasma membrane fraction. Sucrose uptake changes with development inRicinus cotyledons. The ATPase activity in the upper (plasma membrane) phase also varied in a similar way with development, whereas activity in the lower phase showed little change. Pyrophosphatase activity in the upper phase also increased with development but did not show a peak and fall as seen for sucrose uptake and ATPase. The possibility that changes in plasma membrane ATPase may contribute to changes in sucrose uptake capacity and the possible cellular origin and physiological significance of the pyrophosphatase activity are discussed.