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Contains fulltext : 297079.pdf (Publisher’s version ) (Open Access), Effisayil 1 was a multicentre, randomized, double-blind, placebo-controlled study of the anti-interleukin (IL)-36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre-specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline.

Background: Walkway and treadmill induced trips have contrasting advantages, for instance walkway trips have high-ecological validity whereas belt accelerations on a treadmill have high-clinical feasibility for perturbation-based balance training (PBT). This study aimed to (i) compare adaptations to repeated overground trips with repeated treadmill belt accelerations in older adults and (ii) determine if adaptations to repeated treadmill belt accelerations can transfer to an actual trip on the walkway. Method: Thirty-eight healthy community-dwelling older adults underwent one session each of walkway and treadmill PBT in a randomised crossover design on a single day. For both conditions, 11 trips were induced to either leg in pseudo-random locations interspersed with 20 normal walking trials. Dynamic balance (e.g., margin of stability) and gait (e.g., step length) parameters from 3D motion capture were used to examine adaptations in the walkway and treadmill PBT and transfer of adaptation from treadmill PBT to a walkway trip. Results: No changes were observed in normal (no-trip) gait parameters in both training conditions, except for a small (0.9 cm) increase in minimum toe elevation during walkway walks (P < 0.01). An increase in the margin of stability and recovery step length was observed during walkway PBT (P < 0.05). During treadmill PBT, an increased MoS, step length and decreased trunk sway range were observed (P < 0.05). These adaptations to treadmill PBT did not transfer to a walkway trip. Conclusions: This study demonstrated that older adults could learn to improve dynamic stability by repeated exposure to walkway trips as well as treadmill belt accelerations. However, the adaptations to treadmill belt accelerations did not transfer to an actual trip. To enhance the utility of treadmill PBT for overground trip recovery performance, further development of treadmill PBT protocols is recommended to improve ecological authenticity.

Background: People with Parkinson’s disease (PD) have difficulties generating quick and accurate steps in anticipation of and/or in response to environmental hazards. However, neural mechanisms underlying performance in cognitively demanding stepping tasks are unclear. Objective: This study compared activation patterns in cognitive and motor cortical regions using functional near-infrared spectroscopy (fNIRS) between people with PD and age-matched healthy older adults (HOA) during stepping tasks. Methods: Fifty-two people with PD and 95 HOA performed a simple choice stepping reaction time test (CSRT) and 2 cognitively demanding stepping tests (inhibitory CSRT [iCSRT] and Stroop stepping test [SST]) on a computerized step mat. Cortical activation in the dorsolateral prefrontal cortex (DLPFC), Broca’s area, supplementary motor area (SMA), and premotor cortex (PMC) were recorded using fNIRS. Stepping performance and cortical activity were contrasted between groups and between the CSRT and the iCSRT and SST. Results: The PD group performed worse than the HOA in all 3 stepping tests. A consistent pattern of interactions indicated differential hemodynamic responses between the groups. Compared with the CSRT, the PD group exhibited reduced DLPFC activity in the iCSRT and reduced SMA and PMC activity in the SST. The HOA exhibited increased DLPFC, SMA, and PMC activity when performing the SST in comparison with the CSRT task. Conclusions: In contrast to the HOA, the PD group demonstrated reduced cortical activity in the DLPFC, SMA, and PMC during the more complex stepping tasks requiring inhibitory control. This may reflect subcortical and/or multiple pathway damage with subsequent deficient use of cognitive and motor resources.

Impaired mobility often co-occurs with depression. However, there is no systematic review evidence as to whether mobility impairments precede the onset of depression. The objective of this systematic review and meta-analysis was to evaluate whether mobility impairment could predict incident depression. A systematic search of cohort studies were performed in MEDLINE, EMBASE, CINAHL and PsycINFO. The target population was people with no depressive symptoms at baseline and follow-up for depression or depressive symptoms of at least three months. Of 1061 identified abstracts, 13 studies met the review eligibility criteria. The majority of included studies (8 out of 13) were of high methodological quality. Follow-up periods ranged from 12 months to 16 years. Gait speed was the most consistently reported mobility measure. Participants with slow gait speed were at higher risk of developing depressive symptoms (pooled OR = 1.93, 95%CI: 1.54 to 2.42, 11 studies). This review shows that slow gait speed is predictive of the onset of depressive symptoms. Systematic review registration number: CRD42020153791

Objectives: Pain is a risk factor for falls in older adults, but the mechanisms are not well understood, limiting our ability to implement effective preventive strategies. The aim of this study was to systematically review and synthesize the literature that has examined the impact of pain on static, dynamic, multicomponent, and reactive balance in community-dwelling older adults. Design: Systematic review and meta-analysis. Setting and Participants: Studies from inception to March 2019 were identified from electronic databases (MEDLINE, EMBASE, PsycINFO, CINAHL), contact with the primary authors, and reference lists of included articles. Methods: Cross-sectional and case-control studies that compared objective balance measures between older (minimum age 60 years) adults with and without pain were included. Results: Thirty-nine eligible studies (n = 17,626) were identified. All balance modalities (static, dynamic, multicomponent, and reactive) were significantly poorer in participants with pain compared to those without pain. Subgroup analyses revealed that chronic pain (pain persisting ≥3 months) impaired balance more than pain of unspecified duration. The effects of pain at specific sites (neck, lower back, hip, knee, and foot) on balance were not significantly different. Conclusions and Implications: Pain is associated with poor static, dynamic, multicomponent, and reactive balance in community-dwelling older adults. Pain in the neck, lower back, hip, knee, and foot all contribute to poor balance, and this is even more pronounced for chronic pain. Comprehensive balance and pain characteristic assessments may reveal mechanisms underlying the contribution of pain to instability and increased fall risk in older people.

Aim. To compare reactive balance in people with multiple sclerosis (MS) with healthy controls and to examine the ability of people with MS to adapt their reactive balance and retain training effects. Data Sources. Electronic databases (PubMed, EMBASE, PsychINFO) and reference lists of included articles from inception to February 25, 2019. Study Selection. Case-control and intervention studies that assessed reactive balance using mechanical perturbations in people with a confirmed diagnosis of MS. Results. Meta-analyses of 9 studies (n = 342) showed that people with MS have significantly worse reactive balance than healthy controls (standardized mean difference [SMD] 0.78, 95% CI 0.44-1.11, P <.0001, I2 = 47%). Specifically, people with MS have greater center of mass displacements (SMD 0.41, 95% CI 0.05-0.77, P =.02, I2 = 9%) and longer response times (MD (ms) 31.45, 95% CI 19.91-42.98, P <.0001, I2 = 75%) in response to standing perturbations than healthy controls. Subsequent meta-analyses revealed training comprising repeated exposure to perturbations improved response times (P <.001) and training effects on response times could be retained for 24 hours (P <.001) in people with MS. Conclusions. Reactive balance assessments can highlight functional impairments related to falls in people with MS, and perturbation training can acutely improve reactive balance control and such improvements can be retained for 24 hours in this population. Systematic review registration number: CRD42019126130.

Background: pain is associated with increased postural sway and falls in older adults. However, the impact of pain on reactive balance induced by postural perturbations and how this might predispose older adults to falls is not known. Objective: to investigate whether any pain, back/neck pain and lower limb pain are associated with poor reactive balance and prospective fall outcomes in older adults. Design: 12-month prospective cohort study. Setting: community. Subjects: 242 community-dwelling older adults aged 70+ years. Methods: participants completed a questionnaire on the presence of pain and underwent force-controlled waist-pull postural perturbations while standing. Force thresholds for stepping, step initiation time, step velocity and step length were quantified. Falls were monitored with monthly falls calendars for 12-months. Results: participants with lower limb pain had significantly lower force thresholds for stepping. Those with any pain or pain in the back/neck had longer step initiation time, slower step velocity and shorter step length. The three pain measures (any pain, back/neck pain, lower limb pain) were significantly associated with multiple falls when adjusted for age, sex, body mass index, use of polypharmacy, strength and walking speed. In mediation analyses, there was a significant indirect effect of reactive balance for the relationship between back/neck pain and falls with fractures. Conclusions: older people with pain have impaired reactive balance and an increased risk of falls. Reactive balance partially mediated the association between pain and fall-related fractures. Further research is required to confirm the findings of this study.

(1) Background: The present study aimed to examine physical, cognitive and emotional factors affecting falls in community-dwelling older adults with and without pain; (2) Methods: Data from 789 older adults who participated in a community-based health survey were analyzed. Participants completed questionnaires on the presence of pain and previous falls. Muscle weakness (handgrip strength < 26.0 kg for men and < 18.0 kg for women) and low skeletal muscle mass (appendicular skeletal muscle mass index < 7.0 kg/m2 for men and < 5.7 kg/m2 for women) were determined. Mild cognitive impairment (MCI) and depressive symptoms were assessed using the National Center for Geriatrics and Gerontology-Functional Assessment Tool and 15-item geriatric depression scale (GDS-15), respectively; (3) Results: In participants with pain, MCI and GDS-15 were associated with previous falls after adjusting for age, sex, education and medication use. In participants without pain, muscle weakness and low skeletal muscle mass were associated with previous falls when adjusting for the above covariates; (4) Conclusions: Falls in participants with pain were associated with cognitive and emotional factors, whereas falls in those without pain were associated with physical factors. Fall prevention interventions for older adults with pain may require tailored strategies to address cognitive and emotional factors.