Cross-sectional analysis of the Parkinson's disease Non-motor International Longitudinal Study baseline non-motor characteristics, geographical distribution and impact on quality of life.

Growing evidence suggests that non-motor symptoms (NMS) in Parkinson's disease (PD) have differential progression patterns that have a different natural history from motor progression and may be geographically influenced. We conducted a cross-sectional analysis of 1607 PD patients of whom 1327 were from Europe, 208 from the Americas, and 72 from Asia. The primary objective was to assess baseline non-motor burden, defined by Non-Motor Symptoms Scale (NMSS) total scores. Other aims included identifying the factors predicting quality of life, differences in non-motor burden between drug-naïve and non-drug-naïve treated patients, and non-motor phenotypes across different geographical locations. Mean age was 65.9 ± 10.8 years, mean disease duration 6.3 ± 5.6 years, median Hoehn and Yahr stage was 2 (2-3), and 64.2% were male. In this cohort, mean NMSS scores were 46.7 ± 37.2. Differences in non-motor burden and patterns differed significantly between drug-naïve participants, those with a disease duration of less than five years, and those with a duration of five years or over (p ≤ 0.018). Significant differences were observed in geographical distribution (NMSS Europe: 46.4 ± 36.3; Americas: 55.3 ± 42.8; Asia: 26.6 ± 25.1; p < 0.001), with differences in sleep/fatigue, urinary, sexual, and miscellaneous domains (p ≤ 0.020). The best predictor of quality of life was the mood/apathy domain (ß = 0.308, p < 0.001). This global study reveals that while non-motor symptoms are globally present with severe NMS burden impacting quality of life in PD, there appear to be differences depending on disease duration and geographical distribution.

RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Self-directed video versus instructor-based neonatal resuscitation training: a randomized controlled blinded non-inferiority multicenter international study.

OBJECTIVE: To compare the efficacy of video-assisted self-directed neonatal resuscitation skills course with video-assisted facilitator-led course. METHODS: This multicenter, randomized, blinded, non-inferiority-controlled trial compared two methods of teaching basic neonatal resuscitation skills using mask ventilation. Groups of novice providers watched an instructional video. One group received instructor facilitation (Ins-Video). The other group did not (Self-Video). An Objective Structured Clinical Exam (OSCE) measured skills performance, and a written test gauged knowledge. RESULTS: One hundred and thirty-four students completed the study. Sixty-three of 68 in the Self-Video Group (92.6%) and 59 of 66 in the Ins-Video Group (89.4%) achieved post-training competency in positive pressure ventilation (primary outcome). OSCE passing rates were low in both groups. Knowledge survey scores were comparable between groups and non-inferior. CONCLUSIONS: Video self-instruction taught novice providers positive pressure ventilation skills and theoretical knowledge, but it was insufficient for mastery of basic neonatal resuscitation in simulation environment.

Cardiac autonomic activity predicts dominance in verbal over spatial reasoning tasks: results from a preliminary study.

The present study sought to determine whether autonomic activity is associated with dominance in verbal over spatial reasoning tasks. A group of 19 healthy adults who performed a verbal and spatial aptitude test was evaluated. Autonomic function was assessed by means of heart rate variability analysis, before and during the tasks. The results showed that a better relative performance in verbal over spatial reasoning tasks was associated with vagal prevalence in normal subjects.

A double-blind, placebo-controlled, randomized, crossover pilot study of the safety and efficacy of multiple doses of intra-oral tropicamide films for the short-term relief of sialorrhea symptoms in Parkinson's disease patients.

OBJECTIVE: This proof-of-concept, pilot study aimed to explore the safety and anti-sialorrhea efficacy of single doses of intra-oral slow dissolving thin films containing tropicamide (NH004) or placebo. METHODS: Nineteen non-demented, idiopathic stable or fluctuating PD patients who complained of sialorrhea received 3 doses (0.3, 1, 3mg) of tropicamide and placebo in random order, separated by 7 days. A 10-cm visual analog scale (VAS) was used to measure the patient's subjective feelings of saliva levels at baseline and at 15, 30, 45, 90 and 120 min after treatment administration. For the last 7 patients, saliva volume was measured at baseline and 75 min after treatment. Fluctuating patients were evaluated in the ON-condition. RESULTS: The mean age of included patients was 67±12 years, 78% were male. Median disease duration was 8 years. The mean decrease in VAS score from baseline to 120 min were -0.55±0.54, -1.08±0.54, -1.53±0.52 and -0.81±0.51 for placebo and 0.3, 1 and 3mg tropicamide, respectively (F=0.6 p=0.6, ANOVA). Tropicamide 1mg resulted in a significant VAS score decrease (95%CI: -2.57 to -0.48). Saliva volume was reduced by 27%, 33% or 20% after tropicamide 0.3, 1 or 3mg vs 5% with placebo (p=0.5, Friedman). No adverse events were detected in any of the treatment sequences. DISCUSSION: Results of this pilot, proof-of-concept study show that NH004 was safe and exerted antisialorrhea effects worthy of further exploration.

Sleep habits, alertness, cortisol levels, and cardiac autonomic activity in short-distance bus drivers: differences between morning and afternoon shifts.

OBJECTIVE: To evaluate sleep, alertness, salivary cortisol levels, and autonomic activity in the afternoon and morning shifts of a sample of short-distance bus drivers. METHODS: A sample of 47 bus drivers was evaluated. Data regarding subjects and working characteristics, alertness (psychomotor vigilance task), sleep habits (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Actigraphy), endocrine stress response (salivary cortisol), and autonomic activity (heart-rate variability) were collected. RESULTS: Sleep restriction was highly prevalent. Drivers in the morning shift slept 1 hour less than those in the afternoon shift, showed lower reaction time performance, a flattening of cortisol morning-evening difference, and higher overweight prevalence. CONCLUSIONS: The differences found between morning and afternoon shifts point out to the need of the implementation of educational strategies to compensate the sleep loss associated with an early work schedule.