Measures of Impairment and Activity Limitation Associated with Falls In Ambulatory Nursing Home Residents

Background: The majority of fall risk data is collected from the community-dwelling population, which is not representative of geriatric sub-populations. Few publications are available exclusively studying falls and risk factors within specific sub-populations. The purpose of this study is to assess which measures of impairment and activity limitation are associated with increased number of past falls within nursing home residents. Methods: In this retrospective correlational study, ambulatory nursing home residents (N=17; 83.7 ± 11.71 years) were recruited from local nursing home facilities. Mini-Mental Status Examination (MMSE), gait speed (GS), lower extremity manual muscle testing (MMT), ankle plantar flexion/dorsiflexion (DF) active range of motion (AROM), hand grip strength, Timed Up and Go (TUG), 5 Times Sit-to-Stand (5TSTS), and assistive device (AD) assessment were recorded in a single visit along with gender, marital status, ethnicity, age, and number of oral medications and active diagnoses. Results: Pearson’s r correlations were calculated with the measures of impairment and fall history in the past 6 months. A moderate correlation existed between increased number of falls and the following measures: 5TSTS (0.585, p=0.007), TUG (0.475, p=0.027), and GS (0.457, p=0.032), right DF AROM (-0.436, p=0.040), and right DF strength (-0.504, p=0.023). The 5TSTS was significantly correlated to past falls at p<0.01 (99%CI). Conclusion: TUG, 5TSTS, gait speed, right ankle DF AROM, and right ankle DF strength were all correlated with increased number of falls, indicating that these measures as possible useful tools in determining fall risk within the ambulatory nursing home resident population

Sulfonamides as Selective Na_V1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement

Human genetic evidence has identified the voltage-gated sodium channel Na_V1.7 as an attractive target for the treatment of pain. We initially identified naphthalene sulfonamide <b>3</b> as a potent and selective inhibitor of Na_V1.7. Optimization to reduce biliary clearance by balancing hydrophilicity and hydrophobicity (Log <i>D</i>) while maintaining Na_V1.7 potency led to the identification of quinazoline <b>16</b> (AM-2099). Compound <b>16</b> demonstrated a favorable pharmacokinetic profile in rat and dog and demonstrated dose-dependent reduction of histamine-induced scratching bouts in a mouse behavioral model following oral dosing