[Integrative medicine: what's new in 2022]. / Médecine intégrative : ce qui a changé en 2022.

To illustrate the news of 2022, we present first a scientific article on mindfulness: a meta-analysis shows both preventive and therapeutic effects for the pediatric population. A second scientific article is summarized: it investigated acupuncture in an obstetrical context, demonstrating its effectiveness on post-caesarean pain and on functional capacity, by improving early mobilization. Hence, these approaches have an increasing level of scientific evidence in these given fields, calling for a clinical implementation. Finally, we offer a practical summary concerning the prescription of cannabis, especially useful following the abolishment of the obligatory FOPH authorization as of August 1, 2022. Nevertheless, we underline that the evidence for cannabinoids being effective remains weak in most indications.

En termes de nouveautés 2022, nous présentons en premier lieu un article scientifique traitant de la pleine conscience : une méta-analyse montre des effets tant préventifs que thérapeutiques pour la population pédiatrique. Le deuxième article scientifique présenté traite de l'acupuncture dans un contexte obstétrical, démontrant son efficacité sur la douleur postcésarienne et sur la capacité fonctionnelle, en améliorant la mobilisation précoce. Ces deux approches bénéficient donc d'un niveau de preuve scientifique croissant appelant à une implantation clinique. Finalement, nous offrons un résumé pratique concernant la prescription de cannabis, tout particulièrement utile suite à la levée de l'obligation d'autorisation de l'OFSP dès le 1er août 2022. Néanmoins, nous soulignons que les preuves restent faibles concernant l'efficacité des cannabinoïdes dans la plupart des indications.

Toward individualized medicine in stroke-The TiMeS project: Protocol of longitudinal, multi-modal, multi-domain study in stroke.

Despite recent improvements, complete motor recovery occurs in <15% of stroke patients. To improve the therapeutic outcomes, there is a strong need to tailor treatments to each individual patient. However, there is a lack of knowledge concerning the precise neuronal mechanisms underlying the degree and course of motor recovery and its individual differences, especially in the view of brain network properties despite the fact that it became more and more clear that stroke is a network disorder. The TiMeS project is a longitudinal exploratory study aiming at characterizing stroke phenotypes of a large, representative stroke cohort through an extensive, multi-modal and multi-domain evaluation. The ultimate goal of the study is to identify prognostic biomarkers allowing to predict the individual degree and course of motor recovery and its underlying neuronal mechanisms paving the way for novel interventions and treatment stratification for the individual patients. A total of up to 100 patients will be assessed at 4 timepoints over the first year after the stroke: during the first (T1) and third (T2) week, then three (T3) and twelve (T4) months after stroke onset. To assess underlying mechanisms of recovery with a focus on network analyses and brain connectivity, we will apply synergistic state-of-the-art systems neuroscience methods including functional, diffusion, and structural magnetic resonance imaging (MRI), and electrophysiological evaluation based on transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG) and electromyography (EMG). In addition, an extensive, multi-domain neuropsychological evaluation will be performed at each timepoint, covering all sensorimotor and cognitive domains. This project will significantly add to the understanding of underlying mechanisms of motor recovery with a strong focus on the interactions between the motor and other cognitive domains and multimodal network analyses. The population-based, multi-dimensional dataset will serve as a basis to develop biomarkers to predict outcome and promote personalized stratification toward individually tailored treatment concepts using neuro-technologies, thus paving the way toward personalized precision medicine approaches in stroke rehabilitation.

Systematic reviews of randomized controlled trials of cannabinoid products in chronic pain conditions and for symptoms associated with multiple sclerosis: what do they tell us?

INTRODUCTION: To investigate whether published systematic reviews of randomized controlled trials provide sufficient clarity to inform prescribing of medicinal cannabinoid products, we examined their features and findings in two well-researched areas: chronic cancer/noncancer pain and multiple sclerosis (MS)-related symptoms. AREAS COVERED: Structured searches from January 2011 to 2 February 2021 identified 31 systematic reviews (with/without meta-analyses) that met the inclusion criteria. Support for the efficacy of cannabinoids was minimal in cancer pain, and somewhat stronger in noncancer (especially neuropathic) pain and MS spasticity. All systematic reviews and most meta-analyses grouped cannabinoid products together without appropriate consideration of their differential attributes (active constituent(s), concentration/strength, dosage forms, administration route), dosing regimens or treatment durations. Patient populations and efficacy outcome measures were inhomogeneous, particularly for studies in noncancer pain and MS. Separate results for specific cannabinoid formulations were rarely provided. EXPERT OPINION: The therapeutic effect of cannabinoids, as already demonstrated for some products, is not reflected clearly in the current range of systematic reviews and meta-analyses in chronic pain and MS. To truly inform evidence-based practice, future publications should aim to present results by individual product from well-conducted clinical trials using appropriate and homogeneous outcome measures in well-defined patient populations.

Long-term worsening of different body functions in persons with progressive multiple sclerosis.

BACKGROUND: It is unclear whether EDSS is responsive to disability worsening in advanced MS. OBJECTIVE: To explore the dynamics of disability worsening in persons with advanced-stage MS (EDSS ≥5.5) using three disability worsening definitions (EDSS, Rivermead Mobility Index (RMI), 9-Hole Peg Test (9-HPT)). METHODS: EDSS-, RMI- and 9-HPT-based disability worsening were assessed over a minimum of two years in a cohort of 286 persons with advanced MS attending inpatient rehabilitation using Kaplan-Meier Curves and multivariable Cox regression. Furthermore, the correspondence between EDSS-, RMI- and 9-HPT-based disability worsening was analyzed. RESULTS: Disability progression was observed in 49% (9-HPT), 52% (EDSS) and 53% (RMI), with 9-HPT-based worsening slightly lagging behind. The Multiple Sclerosis Severity Score (MSSS) was the only consistent factor predicting disability worsening based on all three definitions (EDSS: hazard ratio 1.48 [1.30;1.68]; RMI: 1.12 [0.99;1.27]; 9-HPT: 1.36 [1.18;1.57]). Correspondence between EDSS and the other definitions (9-HPT and RMI) was 44.3% and 55.7% at time of EDSS progression and 65.1% and 72.5% overall, respectively. CONCLUSION: In persons with advanced-stage MS, half still developed disability worsening in different functional systems over a median of 6 years. MSSS seems a valid predictor for disability worsening in all three outcome measures in advanced MS.

Recommended outcome measures for inpatient rehabilitation of multiple sclerosis are not appropriate for the patients with substantially impaired mobility.

BACKGROUND: In multiple sclerosis (MS) rehabilitation, most currently used outcome measures were validated in patients with a relapsing remitting MS and mild to moderate impairments. We aimed to assess whether these measures were also adequate in more impaired patients, frequently encountered in those with progressive MS (PMS). METHODS: Outcome measurements were extracted from medical records of 229 patients with PMS undergoing 3 weeks of routine inpatient rehabilitation between 2011 and 2015. We assessed the acceptability of Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk (T25FW), 2-Minute Walk Test (2MWT), Rivermead Mobility Index (RMI) and the Functional Independence Measure (FIM) by analysing their statistical distributions, concurrent validity by comparing Spearman correlations with pre-specified hypotheses, and responsiveness across impairment status by calculating standardized response means. RESULTS: Our concurrent validity hypotheses were mainly satisfied. However, all outcome measures had skewed distributions, showed low variability, and thus were inadequately discriminative. Moreover, 9HPT was never responsive across the impairment states, whereas the T25FW was responsive for mildly impaired patients, and the 2MWT for mild to moderate MS, respectively. Generic multi-items measures such as RMI and FIM-motor were adequately responsive for all severity levels. CONCLUSIONS: Currently used outcome measures are inadequate for patients with impaired mobility, and there is a dire need of specifically designed outcome measures for routine care that are less burdensome and short-term responsive.

Within-day variability on short and long walking tests in persons with multiple sclerosis.

OBJECTIVE: To compare within-day variability of short (10 m walking test at usual and fastest speed; 10MWT) and long (2 and 6-minute walking test; 2MWT/6MWT) tests in persons with multiple sclerosis. DESIGN: Observational study. SETTING: MS rehabilitation and research centers in Europe and US within RIMS (European network for best practice and research in MS rehabilitation). SUBJECTS: Ambulatory persons with MS (Expanded Disability Status Scale 0-6.5). INTERVENTION: Subjects of different centers performed walking tests at 3 time points during a single day. MAIN MEASURES: 10MWT, 2MWT and 6MWT at fastest speed and 10MWT at usual speed. Ninety-five percent limits of agreement were computed using a random effects model with individual pwMS as random effect. Following this model, retest scores are with 95% certainty within these limits of baseline scores. RESULTS: In 102 subjects, within-day variability was constant in absolute units for the 10MWT, 2MWT and 6MWT at fastest speed (+/-0.26, 0.16 and 0.15m/s respectively, corresponding to +/-19.2m and +/-54 m for the 2MWT and 6MWT) independent on the severity of ambulatory dysfunction. This implies a greater relative variability with increasing disability level, often above 20% depending on the applied test. The relative within-day variability of the 10MWT at usual speed was +/-31% independent of ambulatory function. CONCLUSIONS: Absolute values of within-day variability on walking tests at fastest speed were independent of disability level and greater with short compared to long walking tests. Relative within-day variability remained overall constant when measured at usual speed.

Local dynamic stability as a responsive index for the evaluation of rehabilitation effect on fall risk in patients with multiple sclerosis: a longitudinal study.

BACKGROUND: Gait and balance problems are common in patients with multiple sclerosis, leading to high risk for falls. Local Dynamic Stability (LDS), a non-linear gait stability index, has been advocated as an early indicator of risk for falls. With this longitudinal study over three weeks, we aimed to assess the responsiveness of Local Dynamic Stability to a rehabilitation program and to compare it to other measures. METHODS: Eighteen patients (mean 54 years, median EDSS score: 5) participated. They were admitted to inpatient rehabilitation and received a three weeks individually tailored program. They performed a 3-minute walking test at the beginning and at the end of the stay, as well as pain, wellbeing, fatigue, and balance assessment. The Local Dynamic Stability was computed from the acceleration signals measured with a 3D-accelerometer. RESULTS: At the end of the rehabilitation process, patients reported reduced pain (Effect Size: -0.7), fatigue (ES:-0.6), and increased wellbeing (ES: 1.1). A small positive effect on static balance was observed (ES: 0.3). LDS was improved (ES: 0.6), and the effect was higher than walking speed improvement (ES: 0.4). CONCLUSIONS: The Local Dynamic Stability seemed responsive to assess rehabilitation effects in patients with multiple sclerosis. It could constitute a valuable gait quality index, which could evaluate potential effects of rehabilitation on fall risk. TRIAL REGISTRATION: Current Controlled Trials ISRCTN69803702.

Which walking capacity tests to use in multiple sclerosis? A multicentre study providing the basis for a core set.

BACKGROUND: Many different walking capacity test formats are being used. It is unclear whether walking speed, obtained from short tests, and walking distance, obtained from long tests, provide different clinical information. OBJECTIVES: To determine the differential effect of various short and long walk test formats on gait velocity, and the actual relationship between walking speed and walking distance in multiple sclerosis (MS) patients with diverse ambulation status. METHODS: A cross-sectional multicentre study design was applied. Ambulatory MS patients (Expanded Disability Status Scale (EDSS) 0-6.5; n = 189) were tested at 11 sites. Short tests consisted of the Timed 25-Foot Walk (static start, fastest speed) and 10-Metre Walk Test (dynamic start, usual and fastest speed). Long tests consisted of the 2- and 6-Minute Walk Tests (fastest speed). Subjects were divided into mild (EDSS 0-4; n = 99) or moderate (EDSS 4.5-6.5; n = 79) disability subgroups. RESULTS: In both subgroups, the start protocol, instructed pace and length of test led to significantly different gait velocities. Fastest walking speed and 6-Minute walking distance showed the strongest correlation (R (2) = 0.78 in mild and R (2) = 0.81 in moderate MS; p < 0.01). Short tests' relative estimation errors for 6-Minute walking distance were 8-12% in mildly and 15-16% in moderately affected subjects. Based on the 2-Minute Walk Test, estimation errors significantly reduced to approximately 5% in both subgroups. CONCLUSIONS: A single short test format at fastest speed accurately describes an MS patient's general walking capacity. For intervention studies, a long test is to be considered. We propose the Timed 25-Foot Walk and 2-Minute Walk Test as standards. Further research on responsiveness is needed.

Robotic-assisted step training (lokomat) not superior to equal intensity of over-ground rehabilitation in patients with multiple sclerosis.

BACKGROUND: Robot-assisted gait training (RAGT) has been suggested as an intervention to improve walking capacity in patients with multiple sclerosis (MS). OBJECTIVE: This study aimed to evaluate whether RAGT (Lokomat) is superior to over-ground walking training in terms of quality of life, activity level, and gait. METHODS: A total of 67 patients with MS with the Expanded Disability Status Scale (EDSS) 3.0 to 6.5 were randomized to walking or RAGT, in addition to multimodal rehabilitation. Primary outcomes were walking speed, activity level (estimated metabolic equivalent, metabolic equivalents [METs], using an accelerometer), and quality of life (Well-Being Visual Analogue Scale (VAS) and EQ-5D European VAS. RESULTS: In all, 49 patients finished the interventions. Mean age was 56 years (range 36-74 years), mean EDSS was 5.8 (3.0-6.5), and the preferred walking speed at baseline was 0.56 m/s (0.06-1.43 m/s). Before rehabilitation, participants spent on average 68 min/d at an MET ≥ 3. The walking group improved gait speed nonsignificantly more than the RAGT; the upper bound of the confidence interval (CI) did not exclude a clinically relevant benefit (defined as a difference of 0.05 m/s) in favor of the walking group; the lower bound of the CI did exclude a clinically important benefit in favor of the Lokomat. Quality of life improved in both groups, with a nonsignificant between-group difference in favor of the walking group. Both groups had reduced their activity by 8 weeks after the rehabilitation. CONCLUSION: It is unlikely that RAGT is better than over-ground walking training in patients with an EDSS between 3.0 and 6.5.