Palomar Health

Total ankle replacement (TAR) has become an effective treatment for end‐stage ankle osteoarthritis. Multiple factors, including patient characteristics, surgical technique, alignment, and bearing surfaces, influence TAR survivorship. Polyethylene (PE) fatigue is a key consideration in improving outcomes. This study establishes a novel, clinically relevant testing protocol incorporating varus‐valgus rotation to simulate polyethylene fatigue failures observed in mobile‐bearing total ankle replacements. Using this robust methodology, we evaluated the impact of oxidation and antioxidant stabilization on ultrahigh‐molecular‐weight polyethylene (UHMWPE) performance in a mobile bearing implant application. A six‐degree‐of‐freedom simulator was used to iteratively adjust loading parameters (1500–3000 N, −4° to +8° flexion‐extension, ±5° axial rotation, and ±3° or ±8° varus‐valgus rotation at 37 ± 3°C in 20 g/L bovine serum) until clinically observed midline fractures were replicated. Oxidation levels were measured by Fourier‐transform infrared spectroscopy per ASTM F2102. This validated loading protocol was then applied to conventional (25 kGy GUR 1020) and vitamin E‐stabilized (75 kGy GUR 1020‐E) UHMWPE inserts and tested to visible fracture or a 3‐million‐cycle runout. Post‐test fractographic analysis identified crack initiation sites. Conventional aged UHMWPE demonstrated fatigue failure under varus‐valgus rotation (OI = 2.59 ± 1.11) but no failure without rotation. Vitamin E‐stabilized UHMWPE showed no fatigue failure after 3 million cycles, even under varus‐valgus rotation (OI = 0.23 ± 0.02). Fractography revealed fractures originating at the trough and propagating with cyclic loading. Oxidation significantly reduces polyethylene fatigue life, and varus‐valgus rotation exacerbates this effect in mobile bearing TAR implants. Antioxidant‐stabilized UHMWPE showed promising resistance to fatigue and oxidation. These findings support the role of antioxidant stabilization in improving TAR performance, and the protocols developed here provide a framework for assessing the safety of alternative materials.

DNA-encoded chemical library (DEL) technology provides a time- and cost-efficient method to simultaneously screen billions of compounds for their affinity to a protein target of interest. Here we report its use to identify a novel chemical series of inhibitors of the thioesterase activity of polyketide synthase 13 (Pks13) from Mycobacterium tuberculosis (Mtb). We present three chemically distinct series of inhibitors along with their enzymatic and Mtb whole cell potency, the measure of on-target activity in cells, and the crystal structures of inhibitor-enzyme complexes illuminating their interactions with the active site of the enzyme. One of these inhibitors showed a favorable pharmacokinetic profile and demonstrated efficacy in an acute mouse model of tuberculosis (TB) infection. These findings and assay developments will aid in the advancement of TB drug discovery.

Within the past decade tremendous advances have occurred in our understanding of dyslexia. Reliable data now validate the definition of dyslexia as an unexpected difficulty in reading in an individual who has the ability to be a much better reader. That dyslexia is unexpected is now codified in US federal law (PL 115-391). Replicated studies using functional brain imaging have documented a neural signature for dyslexia. Epidemiologic, longitudinal data now demonstrate that dyslexia is highly prevalent, affecting 20% of the population, affecting boys and girls equally. These data further demonstrate that the achievement gap between dyslexic and typical readers is now evident as early as first grade and persists. Evidence-based, efficient, inexpensive screening tools now offer the possibility of universal screening to identify children at risk for dyslexia as early as first grade. Specialized schools which focus on dyslexic students provide welcoming communities, ensuring that dyslexic children will not only survive but thrive. Taken together, these findings indicate that we must act and act now to ensure that this 21st century knowledge of dyslexia is disseminated to educators, policy makers, and most of all to parents of dyslexic children.

IntroductionTo investigate the impact of the digital Livongo Diabetes Prevention Program (DPP) on weight at 12 months, understand participants’ self-monitoring behaviors associated with greater weight loss, and evaluate the impact of coaching interactions on more frequent self-monitoring behaviors.Research design and methodsA retrospective analysis was performed using data from 2037 participants enrolled in the Livongo DPP who completed lesson 1 and recorded a starting weight during 2016–2017. Self-monitoring behaviors, including weigh-ins, food logging, activity, and coach–participant interactions, were analyzed at 6 and 12 months. Subgroup analysis was conducted based on those who were highly engaged versus those minimally engaged. Multiple regression analysis was performed using demographic, self-monitoring, and lesson attendance data to determine predictors of weight loss at 12 months and coaching impact on self-monitoring.ResultsParticipants had a mean age of 50 years (SD ±12), with a starting weight of 94 kg (SD ±21), were college-educated (78%), and were female (74%). Overall, participants lost on average 5.1% of their starting weight. Highly engaged participants lost 6.6% of starting body weight, with 25% losing ≥10% at 12 months. Logistic regression analysis showed each submitted food log was associated with 0.23 kg (p<0.05) weight loss, each lesson completed was associated with 0.14 kg (p<0.05) weight loss, and a week of 150 active minutes was associated with 0.1 kg (p<0.01) weight loss. One additional coach–participant message each week was associated with 1.4 more food logs per week, 1.6% increase in weeks with four or more weigh-ins, and a 2.7% increase in weeks with 150 min of activity.ConclusionsFood logging had the largest impact on weight loss, followed by lesson engagement and physical activity. Future studies should examine further opportunities to deliver nutrition-based content to increase and sustain weight loss for DPP.

BackgroundApproximately half of hospitalized patients suffer functional decline due to spending the vast majority of their time in bed. Previous studies of early mobilization have demonstrated improvement in outcomes, but the interventions studied have been resource-intensive. We aimed to decrease the time hospital inpatients spend in bed through a pragmatic mobilization protocol.MethodsThis prospective, non-blinded, controlled clinical trial assigned inpatients to the study wards per routine clinical care in an urban teaching hospital. All subjects on intervention wards were provided with a behavioral intervention, consisting of educational handouts, by the nursing staff. Half of the intervention wards were supplied with recliner chairs in which subjects could sit. The primary outcome was hospital length of stay. The secondary outcome was the ‘6-Clicks’ functional score.ResultsDuring a 6-month study period, 6082 patient encounters were included. The median length of stay was 84 hours (IQR 44–175 hours) in the control group, 80 hours (IQR 44–155 hours) in the group who received the behavioral intervention alone, and 88 hours (IQR 44–185 hours) in the group that received both the behavioral intervention and the recliner chair. In the multivariate analysis, neither the behavioral intervention nor the provision of a recliner chair was associated with a significant decrease in length of stay or increase in functional status as measured by the ‘6-Clicks’ functional score.ConclusionThe program of educational handouts and provision of recliner chairs to discourage bed rest did not increase functional status or decrease length of stay for inpatients in a major urban academic center. Education and physical resources must be supplemented by other active interventions to reduce time spent in bed, functional decline, and length of stay.Trial registrationClinicalTrials.gov, HS-16-00804.

There is variability in physician practice regarding delivery method and timeliness of test results to cancer patients. Our aim was to survey patients to determine if there was a difference between actual and preferred care for disclosure of test results. A de-identified survey was distributed to online cancer support groups to query patients about their experience regarding communication of cancer testing and timeliness. Analyses of the differences between actual and preferred communication and wait times were performed. Overall, 1000 patients completed the survey. The analysis herein was restricted to 784 breast cancer survivors. Survey responders were predominately White (non-Hispanic; 89%), college educated (78%), and media 'savvy' (online medical media usage; 97%). Differences between actual and preferred care were identified for the domains of mode of communication and wait times for initial breast cancer diagnostic biopsies and other tests. A total of 309 (39%) of 784 patients received face-to-face communication for a new cancer diagnosis, with 394 (50%) patients preferring this option (p<0.0001). In addition, 315 (40%) of 784 patients received their cancer biopsy result within 2days, with 646 (82%) patients preferring this option (p<0.0001). Differences were also identified between actual and preferred care for multiple other test types. Actual care for timeliness and modes of communication did not reflect patient-desired care. National and local initiatives to improve performance are needed. As a first step, we recommend that each patient be queried about their preference for mode of communication and timeliness, and efforts made to comply.

Abstract Date Presented 4/16/2015 This poster presentation details the results of a longitudinal study on recovery from traumatic brain injury (TBI) both during and after interdisciplinary functional rehabilitation. Outcome variables include client functioning and self-reported life satisfaction as well as postdischarge caregiver burden.