Current clinical assessments of people with multiple sclerosis are episodic and may miss critical features of functional fluctuations between visits.
The goal of the research was to assess the ...feasibility of remote active testing and passive monitoring using smartphones and smartwatch technology in people with multiple sclerosis with respect to adherence and satisfaction with the FLOODLIGHT test battery.
People with multiple sclerosis (aged 20 to 57 years; Expanded Disability Status Scale 0-5.5; n=76) and healthy controls (n=25) performed the FLOODLIGHT test battery, comprising active tests (daily, weekly, every two weeks, or on demand) and passive monitoring (sensor-based gait and mobility) for 24 weeks using a smartphone and smartwatch. The primary analysis assessed adherence (proportion of weeks with at least 3 days of completed testing and 4 hours per day passive monitoring) and questionnaire-based satisfaction. In-clinic assessments (clinical and magnetic resonance imaging) were performed.
People with multiple sclerosis showed 70% (16.68/24 weeks) adherence to active tests and 79% (18.89/24 weeks) to passive monitoring; satisfaction score was on average 73.7 out of 100. Neither adherence nor satisfaction was associated with specific population characteristics. Test-battery assessments had an at least acceptable impact on daily activities in over 80% (61/72) of people with multiple sclerosis.
People with multiple sclerosis were engaged and satisfied with the FLOODLIGHT test battery. FLOODLIGHT sensor-based measures may enable continuous assessment of multiple sclerosis disease in clinical trials and real-world settings.
ClinicalTrials.gov: NCT02952911; https://clinicaltrials.gov/ct2/show/NCT02952911.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
BACKGROUND AND PURPOSE—Five randomized controlled trials have consistently shown that mechanical thrombectomy (MT) in addition to best medical treatment (±intravenous tissue-type plasminogen ...activator) improves outcome after acute ischemic stroke in patients with large artery anterior circulation stroke. Whether direct MT is equally effective as combined intravenous thrombolysis with MT (ie, bridging thrombolysis) remains unclear.
METHODS—We retrospectively compared clinical and radiological outcomes in 167 bridging patients with 255 patients receiving direct MT because of large artery anterior circulation stroke. We matched all patients from the direct MT group who would have qualified for intravenous tissue-type plasminogen activator with controls from the bridging group, using multivariate and propensity score analyses. Functional independence was defined as modified Rankin Scale score of 0 to 2.
RESULTS—From February 2009 to August 2014, 40 patients from the direct MT group would have qualified for bridging thrombolysis but were treated with MT only. Clinical and radiological characteristics did not differ from the bridging cohort, except for higher rates of hypercholesterolemia (P=0.019), coronary heart disease (P=0.039), and shorter intervals from symptom onset to endovascular intervention (P=0.01) in the direct MT group. Functional independence, mortality, and intracerebral hemorrhage rates did not differ (P>0.1). After multivariate matching analysis outcome in both groups did not differ, except for lower rates of asymptomatic intracerebral hemorrhage (P=0.023) and lower mortality (P=0.007) in the direct MT group.
CONCLUSIONS—In patients with large anterior circulation stroke, direct mechanical intervention seems to be equally effective as bridging thrombolysis. A randomized trial comparing direct MT with bridging therapy is warranted.
Objective
Intravenous thrombolysis and endovascular therapy (IVT/EVT) are evidence‐based treatments for adults with arterial ischemic stroke (AIS). However, randomized controlled trials in pediatric ...patients are lacking. This study aimed to describe feasibility, safety, and outcome of IVT/EVT in children with AIS.
Methods
This retrospective study (01/2000–12/2015) included a multicenter, population‐based consecutive cohort of patients aged 1 month to 16 years, diagnosed with AIS and presenting with pediatric National Institutes of Health Stroke Scale (pedNIHSS) ≥ 4. Clinical and radiological data of patients receiving IVT/EVT were compared to those receiving standard care (SC) using linear regression to adjust for potential confounders. EVT included intra‐arterial thrombolysis and/or mechanical thrombectomy. Outcome was assessed 6 months after stroke using the pediatric stroke outcome measure (PSOM).
Results
Overall, 150 patients (age 7.1 ± 4.9 years, 55 37% females) presented with pedNIHSS ≥ 4. Recanalization treatment was performed in 16 (11%), of whom 5 (3%) were treated with IVT and 11 (7%) with EVT. Patients receiving recanalization treatment were older (mean age = 11.0 vs 6.9 years, p = 0.01) and more severely affected (median pedNIHSS = 13.5 vs 8.0, p < 0.001). Death and bleeding complications did not differ between the 2 groups. Median (interquartile range) PSOM 6 months after AIS was 2.5 (1–4.3) and 1 (0–2) in the IVT/EVT and SC groups, respectively (p = 0.014). However, after multiple linear regression analysis, only higher baseline pedNIHSS remained associated with an unfavorable outcome (p < 0.001).
Interpretation
Recanalization treatment is feasible and seems to be safe in severely affected pediatric AIS patients. The assessment of efficacy of IVT/EVT in pediatric stroke patients requires larger studies. Ann Neurol 2018;83:1125–1132
In patients with active rheumatoid arthritis (RA) despite methotrexate, to compare the efficacy of adding tocilizumab to that of switching to tocilizumab monotherapy.
Double-blind, 2-year study in ...which adults with active RA (DAS28 >4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO). The primary endpoint was the DAS28-erythrocyte sedimentation rate (ESR) remission rate at week 24. Secondary objectives included other symptomatic outcomes, quality of life and progression of structural damage.
Of 556 randomly assigned patients, 512 (92%) completed 24 weeks. DAS28-ESR remission rates were 40.4% for TCZ+MTX and 34.8% for TCZ+PBO (p=0.19); American College of Rheumatology 20/50/70/90 rates were 71.5%/45.5%/24.5%/5.8% (TCZ+MTX) and 70.3%/40.2%/25.4%/5.1% (TCZ+PBO; differences not significant). A significant difference between groups was seen for low DAS28 (61.7% vs 51.4%). Radiographic progression was small and not different between groups (Genant-Sharp score progression ≤ smallest detectable change in 91% (TCZ+MTX) and 87% (TCZ+PBO)). Rates per 100 patient-years of serious adverse events and serious infections were 21 and six, respectively, for TCZ+MTX and 18 and six, respectively, for TCZ+PBO. Alanine aminotransferase elevations greater than threefold the upper limit of normal occurred in 7.8% and 1.2% of TCZ+MTX and TCZ+PBO patients, respectively.
No clinically relevant superiority of the TCZ+MTX add-on strategy over the switch to tocilizumab monotherapy strategy was observed. The combination was more commonly associated with transaminase increases. Meaningful clinical and radiographic responses were achieved with both strategies, suggesting that tocilizumab monotherapy might be a valuable treatment strategy in suitable RA patients.
Objective To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus. Design Systematic review and meta-analysis of individual patient ...data. Data sources Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013. Eligibility Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival. Results The search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a 56% reduction in the risk of non-melanoma skin cancer (0.44, 0.30 to 0.63) compared with controls. The most pronounced effect was seen in patients who converted to sirolimus from an established immunosuppressive regimen, resulting in a reduction in risk of malignancy (0.34, 0.28 to 0.41), non-melanoma skin cancer (0.32, 0.24 to 0.42), and other cancers (0.52, 0.38 to 0.69). Sirolimus was associated with an increased risk of death (1.43, 1.21 to 1.71) compared with controls. Conclusions Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients. The benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus. Given the risk of mortality, however, the use of this drug does not seem warranted for most patients with kidney transplant. Further research is needed to determine if different populations, such as those at high risk of cancer, might benefit from sirolimus.
Randomized controlled trials have shown that mechanical thrombectomy (MT) plus best medical treatment improves outcome in stroke patients with large-vessel occlusion in the anterior circulation. ...Whether direct MT is equally effective as bridging thrombolysis (intravenous thrombolysis plus MT) in intravenous thrombolysis eligible patients remains unclear.
We compared clinical and radiological outcomes at 3 months in 249 bridging patients with 111 patients receiving direct MT for large-vessel occlusion anterior circulation stroke from 2 prospective registries (study period Essen: June 2012 to August 2013, Bern February 2009 to August 2014). We matched all patients from the direct MT group who would have qualified for intravenous thrombolysis with controls from the bridging group, using multivariate and propensity score methods. Subgroup analyses for internal carotid artery occlusions were performed.
Baseline characteristics did not differ between the direct MT group and bridging cohort, except for higher rates of coronary heart disease (
=0.029) and shorter intervals from onset to endovascular therapy (
<0.001) in the MT group. Functional outcome, mortality, and intracerebral hemorrhage did not differ, neither in univariate nor after multivariate and propensity score matching. However, in patients with internal carotid artery occlusion, mortality in the direct cohort was significantly lower.
In this matched-pair analysis, there was no difference in outcome in patients with large-vessel occlusion anterior circulation stroke treated with direct MT compared with those treated with bridging thrombolysis; however, mortality in patients with internal carotid artery occlusion treated with direct MT was significantly lower than after bridging thrombolysis. Randomized trials comparing direct MT with bridging therapy are needed.
Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide ...tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis.
The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5–15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints–erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4–6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012.
Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 77% women and 59 23% men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35–0·73) with tapered prednisone and −0·08 (–0·27 to 0·12) with continued prednisone (difference 0·61 0·35–0·88; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71–0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency.
In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose.
F Hoffmann-La Roche.
Leveraging consumer technology such as smartphone and smartwatch devices to objectively assess people with multiple sclerosis (PwMS) remotely could capture unique aspects of disease progression. This ...study explores the feasibility of assessing PwMS and Healthy Control's (HC) physical function by characterising gait-related features, which can be modelled using machine learning (ML) techniques to correctly distinguish subgroups of PwMS from healthy controls. A total of 97 subjects (24 HC subjects, 52 mildly disabled (PwMSmild, EDSS 0-3) and 21 moderately disabled (PwMSmod, EDSS 3.5-5.5) contributed data which was recorded from a Two-Minute Walk Test (2MWT) performed out-of-clinic and daily over a 24-week period. Signal-based features relating to movement were extracted from sensors in smartphone and smartwatch devices. A large number of features ( n = 156) showed fair-to-strong (R <inline-formula><tex-math notation="LaTeX">></tex-math></inline-formula> 0.3) correlations with clinical outcomes. LASSO feature selection was applied to select and rank subsets of features used for dichotomous classification between subject groups, which were compared using Logistic Regression (LR), Support Vector Machines (SVM) and Random Forest (RF) models. Classifications of subject types were compared using data obtained from smartphone, smartwatch and the fusion of features from both devices. Models built on smartphone features alone achieved the highest classification performance, indicating that accurate and remote measurement of the ambulatory characteristics of HC and PwMS can be achieved with only one device. It was observed however that smartphone-based performance was affected by inconsistent placement location (running belt versus pocket). Results show that PwMSmod could be distinguished from HC subjects (Acc. 82.2 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 2.9%, Sen. 80.1 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 3.9%, Spec. 87.2 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 4.2%, F<inline-formula><tex-math notation="LaTeX">_{1}</tex-math></inline-formula> 84.3 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 3.8), and PwMSmild (Acc. 82.3 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 1.9%, Sen. 71.6 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 4.2%, Spec. 87.0 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 3.2%, F<inline-formula><tex-math notation="LaTeX">{1}</tex-math></inline-formula> 75.1 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 2.2) using an SVM classifier with a Radial Basis Function (RBF). PwMSmild were shown to exhibit HC-like behaviour and were thus less distinguishable from HC (Acc. 66.4 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 4.5%, Sen. 67.5 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 5.7%, Spec. 60.3 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 6.7%, F<inline-formula><tex-math notation="LaTeX">_{1}</tex-math></inline-formula> 58.6 <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula> 5.8). Finally, it was observed that subjects in this study demonstrated low intra- and high inter-subject variability which was representative of subject-specific gait characteristics.
Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact ...of comorbid SDB and AF on long-term outcomes after stroke.
In this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed. Patients were screened for SDB by respiratory polygraphy during acute hospitalization. Screening for AF was performed using a 7-day ECG up to 3× in the first 6 months. Follow-up visits were scheduled at 1, 3, 12, 24, and 36 months poststroke. Cox regression models adjusted for various factors (age, sex, body mass index, hypertension, diabetes, dyslipidemia, and heart failure) were used to assess the impact of comorbid SDB and AF on subsequent death or cerebro-cardiovascular events.
Among 353 patients (299 ischemic stroke and 54 transient ischemic attacks), median age, 67 (interquartile range, 57-74) years with 63% males. Moderate-to-severe SDB (apnea-hypopnea index score, ≥15/h) was present in 118 (33.4%) patients. Among the 56 (15.9%) patients with AF, 28 had comorbid moderate-to-severe SDB and AF. Over 36 months, there were 12 deaths and 67 recurrent cerebro-cardiovascular events. Patients with comorbid moderate-to-severe SDB and AF had a higher risk of subsequent death or cerebro-cardiovascular events compared with those with only moderate-to-severe SDB without AF (hazard ratio, 2.49 95% CI, 1.18-5.24) and to those without moderate-to-severe SDB or AF (hazard ratio, 2.25 95% CI, 1.12-4.50). However, no significant difference was found between the comorbid moderate-to-severe SDB and AF group and the group with only AF without moderate-to-severe SDB (hazard ratio, 1.64 95% CI, 0.62-4.36).
Comorbid moderate-to-severe SDB and AF significantly increase the risk of long-term mortality or recurrent cerebro-cardiovascular events after acute ischemic stroke. Considering both conditions as cumulative and modifiable cerebro-cardiovascular risk factors is of interest for the management of acute stroke.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT02559739.
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