Clinical, Kinematic and Muscle Assessment of Bilateral Coordinated Upper-Limb Movements Following Cervical Spinal Cord Injury.

Cervical spinal cord injury (cSCI) often results in bilateral impairment of the arms, leading to difficulties in performing daily activities. However, little is known about the neuromotor alterations that affect the ability of individuals with cSCI to perform coordinated movements with both arms. To address this issue, we developed and tested a functional assessment that integrates clinical, kinematic, and muscle activity measures, including the evaluation of bilateral arm movements. Twelve subjects with a C5-C7 spinal lesion and six unimpaired subjects underwent an evaluation that included three tests: the Manual Muscle Test, Range Of Motion test and Arm stabilisation test, a subsection of the "Van Lieshout arm/hand function test". During the latter, we recorded kinematic and muscle activity data from the upper-body during the execution of a set of movements that required participants to stabilize both arms against gravity at different configurations. Analytical methods, including muscle synergies, spinal maps, and Principal Component Analysis, were used to analyse the data. Clinical tests detected limitations in shoulder abduction-flexion of cSCI participants and alterations in elbows-wrists motor function. The instrumented assessment provided insight into how these limitations impacted the ability of cSCI participants to perform bilateral movements. They exhibited severe difficulty in performing movements involving over-the-shoulder motion and shoulder internal rotation due to altered patterns of activity of the scapular stabilizer muscles, latissimus dorsi, pectoralis, and triceps. Our findings shed light on the bilateral neuromotor changes that occur post-cSCI addressing not only motor deficits, but also the underlying abnormal, weak, or silent muscle activations.

The impact of cost-sharing on prescription drug demand: evidence from a double-difference regression kink design.

Pharmaceuticals represent the third-largest expenditure item in health care spending in the OECD countries, and cost growth is around 5% per year in many OECD countries. One possible way to contain the rise in pharmaceutical spending is the use of cost-sharing schemes that makes insured individuals directly bear parts of the cost of a drug. This study estimates the price sensitivity of demand for prescription drugs using data on all prescription drug purchases from a random sample of 400,000 Swedes followed from 2010 to 2013. We use a regression kink design (RKD) by exploiting the kinked Swedish cost-sharing scheme to assess the price elasticity. Further, since the cost-sharing scheme has changed over time, we also use a double-difference RKD to account for potential confounding nonlinearities around the kink. Our results indicate that the standard RKD results are biased and exaggerate the price sensitivity. Our preferred double-difference RKD specifications show no or minor price sensitivity (95% CI price elasticity from - 0.12 to 0.02). The results are similar in several sub-group analyses across age groups, sexes, and income quartiles.

R&D and market size: Who benefits from orphan drug legislation?

Since the early 80s, incentives have been introduced to stimulate R&D for rare diseases. We develop a theoretical model to study the impact of push and pull incentives on the intensive and extensive margin of optimal R&D investments. The model describes the mechanisms by which the type of incentives provided may favor R&D for orphan diseases with comparatively high prevalence. In our empirical analysis, we merge data on orphan drug designations by the Food and Drug Administration with Orphanet data on disease characteristics. In line with the theoretical results, we find evidence supporting the idea that the incentives adopted may have contributed substantially to widening the gap between more and less rare diseases classified as orphan. Our theoretical and empirical findings together suggest that, if providing some therapeutic option to patients with very rare diseases is a priority, a revision of the current system of incentives should be considered.

Recovery of Distal Arm Movements in Spinal Cord Injured Patients with a Body-Machine Interface: A Proof-of-Concept Study.

BACKGROUND: The recovery of upper limb mobility and functions is essential for people with cervical spinal cord injuries (cSCI) to maximize independence in daily activities and ensure a successful return to normality. The rehabilitative path should include a thorough neuromotor evaluation and personalized treatments aimed at recovering motor functions. Body-machine interfaces (BoMI) have been proven to be capable of harnessing residual joint motions to control objects like computer cursors and virtual or physical wheelchairs and to promote motor recovery. However, their therapeutic application has still been limited to shoulder movements. Here, we expanded the use of BoMI to promote the whole arm's mobility, with a special focus on elbow movements. We also developed an instrumented evaluation test and a set of kinematic indicators for assessing residual abilities and recovery. METHODS: Five inpatient cSCI subjects (four acute, one chronic) participated in a BoMI treatment complementary to their standard rehabilitative routine. The subjects wore a BoMI with sensors placed on both proximal and distal arm districts and practiced for 5 weeks. The BoMI was programmed to promote symmetry between right and left arms use and the forearms' mobility while playing games. To evaluate the effectiveness of the treatment, the subjects' kinematics were recorded while performing an evaluation test that involved functional bilateral arms movements, before, at the end, and three months after training. RESULTS: At the end of the training, all subjects learned to efficiently use the interface despite being compelled by it to engage their most impaired movements. The subjects completed the training with bilateral symmetry in body recruitment, already present at the end of the familiarization, and they increased the forearm activity. The instrumental evaluation confirmed this. The elbow motion's angular amplitude improved for all subjects, and other kinematic parameters showed a trend towards the normality range. CONCLUSION: The outcomes are preliminary evidence supporting the efficacy of the proposed BoMI as a rehabilitation tool to be considered for clinical practice. It also suggests an instrumental evaluation protocol and a set of indicators to assess and evaluate motor impairment and recovery in cSCI.

COVID-19: R0 is lower where outbreak is larger.

We use daily data from Lombardy, the Italian region most affected by the COVID-19 outbreak, to calibrate a SIR model on each municipality. Municipalities with a higher initial number of cases feature a lower rate of diffusion, not attributable to herd immunity: there is a robust and strongly significant negative correlation between the estimated basic reproduction number (R0) and the initial outbreak size. This represents novel evidence of the prevalence-response elasticity in a cross-sectional setting, characterized by a same health system and homogeneous social distancing regulations. By ruling out alternative explanations, we conclude that a higher number of cases causes changes of behavior, such as a more strict adoption of social distancing measures among the population, that reduce the spread. This finding calls for the distribution of detailed epidemiological data to populations affected by COVID-19 outbreaks.

The impact of managed entry agreements on pharmaceutical prices.

Managed entry agreements (MEAs) have been used for several years, with the aim of curbing the growth of pharmaceutical expenditure and enhancing patient access to innovation. Yet, much remains to be understood about their economic implications. This paper studies the impact of MEAs on list prices, that is, prices before the deduction of any discount. Using a theoretical model, we show that, under most price setting regimes, the introduction of an MEA leads to a higher list price. This is confirmed by our empirical analysis of a sample of 156 medicines in six countries, providing a conservative estimate of the increase in price due to the MEA of 5.9%. A relevant policy implication is that payers may overestimate the financial gains that can be achieved through this  tool.