Comparative efectiveness of neutralising monoclonal antibodies in high risk COVID‑19 patients: a Bayesian network meta‑analysis

The purpose of this work was to review and synthesise the evidence on the comparative efectiveness  of neutralising monoclonal antibody (nMAB) therapies in individuals exposed to or infected with  SARS-CoV-2 and at high risk of developing severe COVID-19. Outcomes of interest were mortality,  healthcare utilisation, and safety. A rapid systematic review was undertaken to identify and synthesise relevant RCT evidence using a Bayesian Network Meta-Analysis. Relative treatment  efects for individual nMABs (compared with placebo and one another) were estimated. Pooled efects  for the nMAB class compared with placebo were estimated. Relative efects were combined with  baseline natural history models to predict the expected risk reductions per 1000 patients treated.  Eight articles investigating four nMABs (bamlanivimab, bamlanivimab/etesevimab, casirivimab/ imdevimab, sotrovimab) were identifed. All four therapies were associated with a statistically  signifcant reduction in hospitalisation (70–80% reduction in relative risk; absolute reduction of 35–40  hospitalisations per 1000 patients). For mortality, ICU admission, and invasive ventilation, the risk  was lower for all nMABs compared with placebo with moderate to high uncertainty due to small event  numbers. Rates of serious AEs and infusion reactions were comparable between nMABs and placebo.  Pairwise comparisons between nMABs were typically uncertain, with broadly comparable efcacy. In  conclusion, nMABs are efective at reducing hospitalisation among infected individuals at high-risk  of severe COVID-19, and are likely to reduce mortality, ICU admission, and invasive ventilation rates;  the efect on these latter outcomes is more uncertain. Widespread vaccination and the emergence  of nMAB-resistant variants make the generalisability of these results to current patient populations  difcult. </p

A comparison of relative-efficacy estimate(s) derived from both matching-adjusted indirect comparisons and standard anchored indirect treatment comparisons

ObjectivesWe present an empirical comparison of relative-efficacy estimate(s) from matching-adjusted indirect comparisons (MAICs) with estimates from corresponding standard anchored indirect treatment comparisons.MethodsA total of 80 comparisons were identified from 17 publications through a systematic rapid review. A standardized metric that used reported relative treatment efficacy estimates and their associated uncertainty was used to compare the methods across different treatment indications and outcome measures.ResultsOn aggregate, MAICs presented for connected networks tended to report a more favorable relative-efficacy estimate for the treatment for which individual-level patient data were available relative to the reported indirect treatment comparison estimate.ConclusionsAlthough we recognize the importance of MAIC and other population adjustment methods in certain situations, we recommend that results from these analyses are interpreted with caution. Researchers and analysts should carefully consider if MAICs are appropriate where presented and whether MAICs would have added value where omitted.</p

Walking naturally after spinal cord injury using a brain–spine interface

International audienceAbstract A spinal cord injury interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis 1,2 . Here, we restored this communication with a digital bridge between the brain and spinal cord that enabled an individual with chronic tetraplegia to stand and walk naturally in community settings. This brain–spine interface (BSI) consists of fully implanted recording and stimulation systems that establish a direct link between cortical signals 3 and the analogue modulation of epidural electrical stimulation targeting the spinal cord regions involved in the production of walking 4–6 . A highly reliable BSI is calibrated within a few minutes. This reliability has remained stable over one year, including during independent use at home. The participant reports that the BSI enables natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains. Moreover, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis

Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis

Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI

A spinal cord neuroprosthesis for locomotor deficits due to Parkinson’s disease

International audiencePeople with late-stage Parkinson’s disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD