IntroductionNeuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory CNS demyelinating disease. Two groups of monoclonal antibodies (mAbs) are used to prevent disease relapse, i.e., Food and Drug Administration (FDA)-approved mAbs (e.g., eculizumab satralizumab, inebilizumab), and off-label mAb drugs (e.g., rituximab and tocilizumab). The FDA-approved mAbs have high efficacy but more expensive compared to the off-labels, and thus are less accessible. This systematic review and network meta-analysis (NMA) was to assess the efficacy and safety of both classes of mAbs compared to the current standard treatments.MethodsSystematically searches were conducted in MEDLINE and SCOPUS from inception until July 2021. Randomized-controlled trials (RCTs) were eligible if they compared any pair of treatments (mAbs, immunosuppressive drugs, or placebo) in adult patients with NMOSD. Studies with AQP4-IgG positive or negative were used in the analysis. Probability of relapse and time to event were extracted from the Kaplan-Meier curves using Digitizer. These data were then converted into individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate the median time to relapse and relative treatment effects using hazard ratios (HR). Two-stage NMA was used to determine post-treatment annualized relapse rate (ARR), expanded disability status score (EDSS) change, and serious adverse events (SAE). Risk of bias was assessed using the revised cochrane risk of bias tool.ResultsA total of 7 RCTs with 776 patients were eligible in the NMA. Five of the seven studies were rated low risk of bias. Both FDA-approved and off-label mAbs showed significantly lower risk of relapse than standard treatments, with HR (95% CI) of 0.13 (0.07, 0.24) and 0.16 (0.07, 0.37) respectively. In addition, the FDA-approved mAbs had 20% lower risk of relapse than the off-label mAbs, but this did not reach statistical significance. The ARRs were also lower in FDA-approved and off-label mAbs than the standard treatments with the mean-difference of−0.27 (-0.37,−0.16) and−0.31(-0.46,−0.16), respectively.ConclusionThe off-label mAbs may be used as the first-line treatment for improving clinical outcomes including disease relapse, ARR, and SAEs for NMOSD in countries where resources and accessibility of the FDA-approved mAbs are limited.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283424, identifier: CRD42021283424.
Objective: We aim to assess the accessibility to neurosurgical centers in Thailand for the management of traumatic brain injury (TBI) using a novel approach of geospatial mapping in low-middle income countries. Additionally, we seek to address issues of priority setting in hospital site selection accounting for national insurance schemes. Background: Road traffic injuries are among the leading causes of death in Thai youth. TBI accounts for 65% of all motorcycle-crash fatalities. In recent years, the proportion of TBI patients has more than doubled, resulting in excessive burden of disease currently unmet by epidemiological strategy. Design/Methods: Mapping neurosurgical accessibility in 77 provinces using population level data, spatial ancillary data, and reverse geocoding was conducted using ArcGIS. Mock-scenarios in which patients would have to be transferred to other hospital sites per the national insurance scheme were also assessed for the top-10 provinces with highest burden of disease. Results: The percentage of the population with access to a neurosurgical facility within the golden hour is 22.6%, with the greatest disparity occurring in the northern border regions, where access time averages 180 minutes and only 12.3% of the population has access to neurosurgical care. Mock-scenarios analysis revealed that the current allocation of provincial hospital care accessible to a patient injured in a region to which they do not have access results in 78.2% excess delayed care. Conclusions: With nearly 54 million people living too far away from a neurosurgical facility, that equates to 15,410 unnecessary deaths, given Thailand's high rate of mortality for TBI patients. The limitations of addressing this epidemiological gap include a lack of a national ambulance system with protocolized approaches to TBI management, brain-drain of neurosurgeons, and a lack of 24/7 neurosurgical care, which suggests that our findings may show an even larger disparity of care. Disclosure: Mr. Mahajan has nothing to disclose. Wuttipong Tirakotai has nothing to disclose.
Techataweewan, Nawaporn MD, PhD; Yaisarn, Naruedol MD; Iampreechakul, Prasert MD; Lertbutsayanukul, Punjama MD; Siriwimonmas, Somkiet MD; Techataweewan, Nathakan MD; Perumal, Vivek PhD Author Information
Abstract Purpose This study aimed to determine the effects of home-based dual-hemispheric transcranial direct current stimulation (dual-tDCS) combined with exercise on motor performance in patients with chronic stroke. Materials and methods We allocated 24 participants to the active or sham group. They completed 1-h home-based exercise after 20-min dual-tDCS at 2-mA, thrice a week for 4 weeks. The patients were assessed using the Fugl–Meyer Assessment (FMA), Wolf Motor Function Test, Timed Up and Go test, Five Times Sit-to-Stand Test, Six-meter Walk Test, and muscle strength assessment. Results Compared with the sham group, the active group showed improved FMA scores, which were sustained for at least 1 month. There was no between-group difference in the outcomes of the functional tasks. Conclusion Home-based dual-tDCS could facilitate motor recovery in patients with chronic stroke with its effect lasting for at least 1 month. However, its effects on functional tasks remain unclear. tDCS is safe and easy for home-based self-administration for patients who can use their paretic arms. This could benefit patients without access to health care centres or in situations requiring physical distancing. This home-based tDCS combined with exercise has the potential to be incorporated into telemedicine in stroke rehabilitation. IMPLICATIONS FOR REHABILITATION Twelve sessions of home-based dual-tDCS combined with exercises (3 days/week for 4 weeks) facilitated upper and lower limb motor recovery in patients with chronic stroke compared with exercise alone, with a post-effect for at least 1 month. Home-based tDCS could be safe and easily self-administrable by patients who can use their paretic arms. This intervention could be beneficial for patients living in the community without easy access to a health care centre or in situations where physical distancing is required.
Autoimmune encephalitis (AE) is a neurological disorder caused by autoimmune attack on cerebral proteins. Experts currently recommend staged immunotherapeutic management, with first-line immunotherapy followed by second-line immunotherapy if response to first-line therapy is inadequate. Meta-analysis of the evidence base may provide higher quality evidence to support this recommendation. We undertook a systematic review of observational cohort studies reporting AE patients treated with either second-line immunotherapy or first-line immunotherapy alone, and outcomes reported using the modified Rankin Scale (mRS; search date: April 22, 2020). We performed several one-stage multilevel individual patient data (IPD) meta-analyses to examine the association between second-line immunotherapy and final mRS scores (PROSPERO ID CRD42020181805). IPD were obtained for 356 patients from 25 studies. Most studies were rated as moderate to high risk of bias. Seventy-one patients (71/356, 19%) were treated with second-line immunotherapy. We did not find a statistically significant association between treatment with second-line immunotherapy and final mRS score for the cohort overall (odds ratio [OR] = 1.74, 95% confidence interval [CI] = .98-3.08, p = .057), or subgroups with anti-N-methyl-D-aspartate receptor encephalitis (OR = 1.03, 95% CI = .45-2.38, p = .944) or severe AE (maximum mRS score > 2; OR = 1.673, 95% CI = .93-3.00, p = .085). Treatment with second-line immunotherapy was associated with higher final mRS scores in subgroups with anti-leucine-rich glioma-inactivated 1 AE (OR = 6.70, 95% CI = 1.28-35.1, p = .024) and long-term (at least 12 months) follow-up (OR = 3.94, 95% CI = 1.67-9.27, p = .002). We did not observe an association between treatment with second-line immunotherapy and lower final mRS scores in patients with AE. This result should be interpreted with caution, given the risk of bias, limited adjustment for disease severity, and insensitivity of the mRS in estimating psychiatric and cognitive disability.
