Effect of an interdisciplinary inpatient program for patients with CRPS in reducing disease activity -a single center prospective cohort study.

OBJECTIVE The aim of this study was to evaluate the benefit of inpatient treatment in reducing disease activity in patients with CRPS who have exhausted outpatient options. Furthermore, the study sought to identify patient-related outcome variables that predict a reduction in disease activity. METHODS The primary outcome was disease severity (CRPS Severity Score, range 0-16 points)). Secondary outcomes included depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities, all of which were assessed using the Promis-29. Furthermore, pain catastrophizing, neuropathic pain, quality of life, pain self-efficacy, medication intake, and the patient's global impression of change were examined in accordance with current international agreed recommendations, assessed at discharge, three-month and six-month post-discharge. Mixed-effects models were conducted to identify baseline variables associated with CRPS severity. RESULTS Twenty-five patients completed the program (mean age 49.28 (SD 11.23) years, 92% females, mean symptom duration 8.5 (SD 6.5) months). Results showed a significant reduction between baseline and discharge of disease activity (CSS -2.36, p < 0.0001), pain (PROMIS-29 pain -0.88, p = 0.005) and emotional function (PROMIS-29 depression -5.05, p < 0.001; fatigue -4.63, p = 0.002). Moderate evidence for a reduction between baseline and discharge could be observed for pain interference (+2.27, p = 0.05), social participation (PROMIS-29 +1.93, p = 0.05), anxiety (PROMIS-29 -3.32, p = 0.02) and physical function (PROMIS-29 +1.3, p = 0.03). On discharge, 92% of patients (23 of 25) reported improvement in their overall condition. In the follow-up period, medication intake could be reduced after 3 (MQS -8.22, p = 0.002) and 6 months (MQS -8.69, p = 0.001), and there was further improvement in social participation after 3 months (PROMIS-29 +1.72, 0.03) and sleep after 6 months (PROMIS-29 +2.38, 0.008). In the mixed models, it was demonstrated that patients experiencing less pain at baseline also exhibited lower disease activity. CONCLUSION The results of this study confirm that inpatient interdisciplinary treatment of CRPS patients improves disease activity, pain, physical function, emotional function, and social participation. Most improvements were maintained for up six months after discharge. The majority of patients reported that their overall condition had improved during the study period

Genetic Influences on Response to Novel Objects and Dimensions of Personality in Papio Baboons

Behavioral variation within and between populations and species of the genus Papio has been studied extensively, but little is known about the genetic causes of individual- or population-level differences. This study investigates the influence of genetic variation on personality (sometimes referred to as temperament) in baboons and identifies a candidate gene partially responsible for the variation in that phenotype. To accomplish these goals, we examined individual variation in response to both novel objects and an apparent novel social partner (using a mirror test) among pedigreed baboons (n = 578) from the Southwest National Primate Research Center. We investigated the frequency and duration of individual behaviors in response to novel objects and used multivariate factor analysis to identify trait-like dimensions of personality. Exploratory factor analysis identified two distinct dimensions of personality within this population. Factor 1 accounts for 46.8 % of the variance within the behavioral matrix, and consists primarily of behaviors related to the boldness of the subject. Factor 2 accounts for 18.8 % of the variation, and contains several anxiety like behaviors. Several specific behaviors, and the two personality factors, were significantly heritable, with the factors showing higher heritability than most individual behaviors. Subsequent analyses show that the behavioral reactions observed in the test protocol are associated with animals\u27 social behavior observed later in their home social groups. Finally we used linkage analysis to map quantitative trait loci for the measured phenotypes. Single nucleotide polymorphisms in a positional candidate gene (SNAP25) are associated with variation in one of the personality factors, and CSF levels of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. This study documents heritable variation in personality among baboons and suggests that sequence variation in SNAP25 may influence differences in behavior and neurochemistry in these nonhuman primates

Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study

Introduction: Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types&nbsp;1–3 SMA. Here, an analysis was performed after all patients had received at least 1&nbsp;year of treatment with risdiplam. Methods: Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6&nbsp;months and 60&nbsp;years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2&nbsp;years of treatment. Results: A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0&nbsp;years (1–60&nbsp;years) and 39.1&nbsp;kg (9.2–108.9&nbsp;kg), respectively. About 63% of patients aged 2–60&nbsp;years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions: The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients