IMPORTANCE Convergent biological, epidemiological, and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease (PD).OBJECTIVE To determine the safety, tolerability, and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial. DESIGN, SETTING, AND PARTICIPANTSThe Safety of Urate Elevation in PD (SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging trial of inosine, enrolled participants from 2009 to 2011 and followed them for up to 25 months at outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States. Seventy-five consenting adults (mean age, 62 years; 55% women) with early PD not yet requiring symptomatic treatment and a serum urate concentration less than 6 mg/dL (the approximate population median) were enrolled.INTERVENTIONS Participants were randomized to 1 of 3 treatment arms: placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation using 500-mg capsules taken orally up to 2 capsules 3 times per day. They were followed for up to 24 months (median, 18 months) while receiving the study drug plus 1 washout month. MAIN OUTCOMES AND MEASURESThe prespecified primary outcomes were absence of unacceptable serious adverse events (safety), continued treatment without adverse event requiring dose reduction (tolerability), and elevation of urate assessed serially in serum and once (at 3 months) in cerebrospinal fluid.RESULTS Serious adverse events (17), including infrequent cardiovascular events, occurred at the same or lower rates in the inosine groups relative to placebo. No participant developed gout and 3 receiving inosine developed symptomatic urolithiasis. Treatment was tolerated by 95% of participants at 6 months, and no participant withdrew because of an adverse event. Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups (P < .001 for each) vs placebo, and cerebrospinal fluid urate level was greater in both inosine groups (P = .006 and <.001, respectively). Secondary analyses demonstrated nonfutility of inosine treatment for slowing disability.CONCLUSIONS AND RELEVANCE Inosine was generally safe, tolerable, and effective in raising serum and cerebrospinal fluid urate levels in early PD. The findings support advancing to more definitive development of inosine as a potential disease-modifying therapy for PD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00833690

During development and homeostasis, precise control of Wnt/β-catenin signaling is in part achieved by secreted and membrane proteins that negatively control activity of the Wnt co-receptors Lrp5 and Lrp6. Lrp4 is related to Lrp5/6 and is implicated in modulation of Wnt/β-catenin signaling, presumably through its ability to bind to the Wise (Sostdc1)/sclerostin (Sost) family of Wnt antagonists. To gain insights into the molecular mechanisms of Lrp4 function in modulating Wnt signaling, we performed an array of genetic analyses in murine tooth development, where Lrp4 and Wise play important roles. We provide genetic evidence that Lrp4 mediates the Wnt inhibitory function of Wise and also modulates Wnt/β-catenin signaling independently of Wise. Chimeric receptor analyses raise the possibility that the Lrp4 extracellular domain interacts with Wnt ligands, as well as the Wnt antagonists. Diverse modes of Lrp4 function are supported by severe tooth phenotypes of mice carrying a human mutation known to abolish Lrp4 binding to Sost. Our data suggest a model whereby Lrp4 modulates Wnt/β-catenin signaling via interaction with Wnt ligands and antagonists in a context-dependent manner.

BackgroundA quarter of acute hospital beds are occupied by persons living with dementia, many of whom have communication problems. Healthcare professionals lack confidence in dementia communication skills, but there are no evidence-based communication skills training approaches appropriate for professionals working in this context. We aimed to develop and pilot a dementia communication skills training course that was acceptable and useful to healthcare professionals, hospital patients and their relatives.MethodsThe course was developed using conversation analytic findings from video recordings of healthcare professionals talking to patients living with dementia in the acute hospital, together with systematic review evidence of dementia communication skills training and taking account of expert and service-user opinion. The two-day course was based on experiential learning theory, and included simulation and video workshops, reflective diaries and didactic teaching. Actors were trained to portray patients living with dementia for the simulation exercises. Six courses were run between January and May 2017. 44/45 healthcare professionals attended both days of the course. Evaluation entailed: questionnaires on confidence in dementia communication; a dementia communication knowledge test; and participants’ satisfaction. Video-recorded, simulated assessments were used to measure changes in communication behaviour.ResultsHealthcare professionals increased their knowledge of dementia communication (mean improvement 1.5/10; 95% confidence interval 1.0–2.0; p<0.001). Confidence in dementia communication also increased (mean improvement 5.5/45; 95% confidence interval 4.1–6.9; p<0.001) and the course was well-received. One month later participants reported using the skills learned in clinical practice. Blind-ratings of simulated patient encounters demonstrated behaviour change in taught communication behaviours to close an encounter, consistent with the training, but not in requesting behaviours.ConclusionWe have developed an innovative, evidence-based dementia communication skills training course which healthcare professionals found useful and after which they demonstrated improved dementia communication knowledge, confidence and behaviour.

Children in rural areas are disproportionately affected by pediatric obesity. Poor access to healthcare providers, lack of nutrition education, lower socioeconomic status, and fewer

Background The purpose of this study is to describe and assess a remote height and weight protocol that was developed for an ongoing trial conducted during the SARS COV-2 pandemic. Methods Thirty-eight rural families (children 8.3 ± 0.7 years; 68% female; and caregivers 38.2 ± 6.1 years) were provided detailed instructions on how to measure height and weight. Families obtained measures via remote data collection (caregiver weight, child height and weight) and also by trained staff. Differences between data collection methods were examined. Results Per absolute mean difference analyses, slightly larger differences were found for child weight (0.21 ± 0.21 kg), child height (1.53 ± 1.29 cm), and caregiver weight (0.48 ± 0.42 kg) between school and home measurements. Both analyses indicate differences had only minor impact on child BMI percentile (− 0.12, 0.68) and parent BMI (0.05, 0.13). Intraclass coefficients ranged from 0.98 to 1.00 indicating that almost all of the variance was due to between person differences and not measurement differences within a person. Conclusion Results suggest that remote height and weight collection is feasible for caregivers and children and that there are minimal differences in the various measurement methods studied here when assessing group differences. These differences did not have clinically meaningful impacts on BMI. This is promising for the use of remote height and weight measurement in clinical trials, especially for hard-to reach-populations. Trial registration Clinical. Registered in clinicaltrials.gov (NCT03304249) on 06/10/2017.