Comparative efficacy and safety of disease-modifying therapies in patients with relapsing multiple sclerosis: A systematic review and network meta-analysis.

BACKGROUND: Currently, 19 disease-modifying therapies (DMTs) have been approved for the treatment of patients with relapsing forms of multiple sclerosis (RMS). OBJECTIVE: The objective of this study was to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of DMTs in adults with RMS. METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the Food and Drug Administration, and European Medicines Agency websites for randomized controlled trials (RCTs) (from inception to July 2021). Eligible RCTs evaluated approved treatments for RMS as monotherapy and reported at least one of the primary outcome measures of interest. The primary outcome was efficacy (annualized relapse rate and 12-week confirmed disability progression) and safety (serious adverse events [AEs] and discontinuation due to AEs). We assessed the risk of bias (RoB) of included studies using the Cochrane RoB tool version 2.0 (https://www.bmj.com/content/343/bmj.d5928) for RCTs. Surface under the cumulative ranking (SUCRA) was used to rank therapies and to assess quality of general evidence, respectively. The Grading of Recommendations Assessment, Development and Evaluation framework was used to rank therapies and to assess quality of general evidence. RESULTS: A total of 43 records represent 45 RCTs selected for network meta-analysis. In total, 30,720 participants (median of 732; interquartile range: 248-931) were included, of which 67% were female. By SUCRA analysis, alemtuzumab (94.3%) presented the highest probability of being the best alternative for annualized relapse rate, whereas ofatumumab (93.5%) presented the highest probability of being the best alternative for 12-week confirmed disability progression. Interferon beta-1b subcutaneous (87.0%) presented the highest probability of the best safety among all DMTs for serious AEs, whereas alemtuzumab (92.4%) presented the highest probability of the best safety among all DMTs for discontinuation due to AEs. CONCLUSION: Network meta-analysis shows that alemtuzumab and ofatumumab present the highest efficacy among DMTs. Because there is little difference between these probabilities for many treatments, health professionals should use clinical shared decision making when formulating treatment plans with patients.

A global view of hypertensive disorders and diabetes mellitus during pregnancy.

Two important maternal cardiometabolic disorders (CMDs), hypertensive disorders in pregnancy (HDP) (including pre-eclampsia) and gestational diabetes mellitus (GDM), result in a large disease burden for pregnant individuals worldwide. A global consensus has not been reached about the diagnostic criteria for HDP and GDM, making it challenging to assess differences in their disease burden between countries and areas. However, both diseases show an unevenly distributed disease burden for regions with a low income or middle income, or low-income and middle-income countries (LMICs), or regions with lower sociodemographic and human development indexes. In addition to many common clinical, demographic and behavioural risk factors, the development and clinical consequences of maternal CMDs are substantially influenced by the social determinants of health, such as systemic marginalization. Although progress has been occurring in the early screening and management of HDP and GDM, the accuracy and long-term effects of such screening and management programmes are still under investigation. In addition to pharmacological therapies and lifestyle modifications at the individual level, a multilevel approach in conjunction with multisector partnership should be adopted to tackle the public health issues and health inequity resulting from maternal CMDs. The current COVID-19 pandemic has disrupted health service delivery, with women with maternal CMDs being particularly vulnerable to this public health crisis.

Epidemiology, Clinical Features, and Outcomes of Multisystem Inflammatory Syndrome in Children (MIS-C) and Adolescents-a Live Systematic Review and Meta-analysis.

Purpose of Review: A multisystem inflammatory condition occurring in children and adolescents with COVID-19 has become increasingly recognized and widely studied globally. This review aims to investigate and synthesize evolving evidence on its clinical characteristics, management, and outcomes in pediatric patients. Recent Findings: We retrieved data from PubMed, EMBASE, Cochrane Library, WHO COVID-19 Database, Google Scholar, and preprint databases, covering a timeline from December 1, 2019, to July 31, 2021. A total of 123 eligible studies were included in the final descriptive and risk factor analyses. We comprehensively reviewed reported multisystem inflammatory syndrome in children (MIS-C) cases from published and preprint studies of various designs to provide an updated evidence on epidemiology, clinical, laboratory and imaging findings, management, and short-term outcomes. Latest evidence suggests that African black and non-Hispanic white are the two most common ethnic groups, constituting 24.89% (95% CI 23.30-26.48%) and 25.18% (95% CI 23.51-26.85%) of the MIS-C population, respectively. Typical symptoms of MIS-C include fever (90.85%, 95% CI 89.86-91.84%), not-specified gastrointestinal symptoms (51.98%, 95% CI 50.13-53.83%), rash (49.63%, 95% CI 47.80-51.47%), abdominal pain (48.97%, 95% CI 47.09-50.85%), conjunctivitis (46.93%, 95% CI 45.17-48.69%), vomiting (43.79%, 95% CI 41.90-45.68%), respiratory symptoms (41.75%, 95% CI 40.01-43.49%), and diarrhea (40.10%, 95% CI 38.23-41.97%). MIS-C patients are less likely to develop conjunctivitis (OR 0.27, 95% CI 0.11-0.67), cervical adenopathy (OR 0.21, 95% CI 0.07-0.68), and rash (OR 0.44, 95% CI 0.26-0.77), in comparison with Kawasaki disease patients. Our review revealed that the majority of MIS-C cases (95.21%) to be full recovered while only 2.41% died from this syndrome. We found significant disparity between low- and middle-income countries and high-income countries in terms of clinical outcomes. Summary: MIS-C, which appears to be linked to COVID-19, may cause severe inflammation in organs and tissues. Although there is emerging new evidence about the characteristics of this syndrome, its risk factors, and clinical prognosis, much remains unknown about the causality, the optimal prevention and treatment interventions, and long-term outcomes of the MIS-C patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-022-00264-1.

Effect of different initial rituximab regimens on B cell depletion in children with autoimmune neurological diseases.

BACKGROUND: Rituximab (RTX) is a promising B-cell-depleting monoclonal antibody used to treat several autoimmune neurological diseases in children. The RTX administration regimen relies on the reconstitution of B cells in the peripheral blood. OBJECTIVE: The objective of this study was to investigate the effect of different initial RTX regimens on B cell depletion. METHODS: This single-center retrospective analysis included children with autoimmune neurological diseases who received RTX; Group 1 received two infusions of 375 mg/m2 RTX, while Group 2 received four infusions of the same dose. We examined the evolution of B cells at regular intervals in patients. The time required for B cell reconstitution, risk factors, and the effect on immunoglobulin (Ig) and T cells were studied. RESULTS: A total of 113 patients with the first course of rituximab were included. Median time required for B cell reconstitution was 147.7 [130.1-165.2] and 181.9 [165.2-198.6] days in Group 1 and 2 respectively (p = 0.008). Ig production was affected by RTX, which reduced IgG, IgA and IgM serum concentrations, yet within the normal level. There was significant difference in the decline of IgG between the two groups. Absolute cell counts for T cells did not change over time after treatment, and the variation trend was similar in the two groups. CONCLUSION: The initial regimen of RTX impacts time required for B cell reconstitution. There was an increased time to B cell reconstitution with four standard infusions of RTX when compared with two standard infusions. Furthermore, as the prolonged B cell depletion leads to decreased antibody production, regular measurements of serum Ig concentrations after RTX treatment and follow-up should be performed regularly.

Dalfampridine in the treatment of multiple sclerosis: a meta-analysis of randomised controlled trials.

BACKGROUND: Multiple sclerosis (MS) is a chronic illness involving the central nervous system (CNS) that is characterised by inflammation, demyelination, and degenerative changes. Dalfampridine is one of the available treatments for MS symptoms and comorbidities. This meta-analysis aimed to assess the safety and benefits of dalfampridine versus placebo in MS by summarising data deriving from previously published clinical randomised controlled studies (RCTs). RESULTS: A total of 9 RCTs were included in this meta-analysis, involving 1691 participants. There were significant differences between dalfampridine and placebo in terms of decreased 12-item Multiple Sclerosis Walking Scale score (weighted mean difference [WMD] = - 3.68, 95% confidence interval [CI] [- 5.55, - 1.80], p = 0.0001), improved response to the timed 25-foot walk test (relative risk [RR] = 2.57, 95% CI [1.04, 6.33], p = 0.04), increased 6-min walk test (WMD = 18.40, 95% CI [1.30, 35.51], p = 0.03), increased 9-Hole Peg Test score (WMD = 1.33, 95% CI [0.60, 2.05], p = 0.0004), and increased Symbol Digit Modalities Test score (WMD = 4.47, 95% CI [3.91, 5.02], p < 0.00001). Significant differences in the incidence of side effects were also observed (RR = 1.12, 95% CI [1.04, 1.21], p = 0.002). CONCLUSION: Dalfampridine exerts positive effects on walking ability, finger dexterity, and cognitive function. Treatment should be administered under the guidance of a physician or pharmacist given the higher incidence of adverse events.

Efficacy and safety of azathioprine for neuromyelitis optica spectrum disorders: A meta-analysis of real-world studies.

OBJECTIVE: This study aimed to perform a meta-analysis of the efficacy and safety of azathioprine (AZA) for neuromyelitis optica spectrum disorders (NMOSD), considering the potential predictive factors related to patient response to AZA in this disease. METHODS: We performed a systematic online query in PubMed, EMBASE, The Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, WANFANG DATA, and CQVIP DATA. The available studies on the use of AZA in NMOSD patients were included. RESULTS: We analyzed a total of 21 studies including 1016 patients. Results demonstrated that AZA significantly decreased annual relapse rate (ARR) by 1.164 (95% confidence intervals (CI), -1.396 to -0.932; p < 0.001). Subgroup analysis showed that AZA significantly decreased ARR in both low-dose group (effect size (ES): -1.545) and moderate-dose group (ES: -2.026). AZA therapy also resulted in a significant reduction of 1.117 (95% CI: -1.668 to -0.566; p < 0.001) in expanded disability status scale (EDSS) score. AZA did not affect EDSS score in the low-dose subgroup (ES: -0.535; p = 0.209) or the moderate-dose subgroup (ES: -0.709; p = 0.064). During AZA therapy, 47% of patients did not experience any relapses (95% CI, 39% to 54%). In addition, 13% of patients developed leukopenia, 11% had elevated liver enzyme levels, 8% experienced nausea or vomiting, 5% developed pancytopenia and 6% died during follow-up. CONCLUSION: AZA is effective in reducing relapse and improving patients' neurological function. However, liver function monitoring and routine blood monitoring remain necessary. Within the safe upper limit, a higher dose of AZA may be associated with a better efficacy for NMOSD.

Note: Differential amplified high-resolution tilt angle measurement system.

A high-resolution tilt angle measurement system is presented in this paper. In this system, the measurement signal is amplified by two steps: (1) amplified by operational amplifier and (2) differential amplified by two MEMS-based inclinometers. The novel application not only amplifies the signal but, more importantly, substantially reduces the electrical interference and common-mode noise among the same circuit design. Thus, both the extremely high resolution and great long-term stability are achieved in this system. Calibrated by an autocollimator, the system shows a resolution of 2 arc sec. The accuracy is better than ±1.5 arc sec. The zero-drift error is below ±1 arc sec and ±2 arc sec in the short and long term, respectively.

Depth selectivity for the assessment of microstructure by polarization studies.

A polarimetric imaging system capable of continuously selecting imaging depth in a turbid media is demonstrated. The proposed system is based on the orthogonal polarization spectral (OPS) technique, and is able to detect microstructure and microvessel. First, we compare the performance of four polarization imaging channels on a biological phantom, and find that there is a linear relation between the degrees of ellipticity and image contrast in co-linear/co-elliptical channels. In addition, the cross-linear channel has the best image contrast. We then prove the performance of depth selectivity of microvessel in a mouse ear.

[Depth selectivity by using polarization-controlled spectral technique].

A continuous depth selectivity is examined by changing the state of polarization of the signal light, based on the orthogonal polarization spectral (OPS) microcirculation imaging system. Unlike the traditional OPS system, which could only rend a two dimensional image of a certain cross-section, the elliptically polarized light controlled by the polarizer unit and the analyzer unit could do the microscopy refocusing without mechanically scanning the sample, as a result, the tissue information at different depths could be obtained. Because the proposed system matches the emission spectrum of the light source with the absorption spectrum of the erythrocyte, it has relatively high signal-to-noise ratio, and could be used to detect microcirculation. Imaging of a pork fat with a target is acquired, and the quantitative relationship between image contrast and the state of polarization is illustrated. The results show that from linearly to circularly polarized illumination, the image contrast gradually increases, and the maximum visible depth also increases. Finally, the auricle vessel of a nude mouse was detected by this polarization-controlled spectral imaging system. Through the experiment the feasibility of depth selectivity was proved. The proposed method provides new insights to microscopy refocusing of microcirculation.

An effective method for designing insensitive resonator of continuous-wave passively mode-locked laser.

An effective method for designing the insensitive resonator of a continuous-wave passively mode-locked laser is firstly presented in this paper. This method, using resonator transform circle graphic theory, is both intuitive and reliable. Theoretical results show that the resonator is suitable to obtain highly stable mode locking operation when the following two conditions are fulfilled. First, the transform circle of the terminal mirror opposite the semiconductor saturable absorber mirror (SESAM) propagates through a series of lens (including the thermal lens of the gain medium) and a small transform circle in the image space is obtained, which ensures the small spot size at the SESAM. Second, the resonator transform circles orthogonally (or nearly orthogonally) intersect at the SESAM, which ensures the spot size at the SESAM is insensitive to the external perturbation. The experimental results of the mode locking lasers show good agreement with the theoretical studies very well.

Compact optical roll-angle sensor with large measurement range and high sensitivity.

A simple and effective optical roll-angle sensor based on a magnetic garnet single crystal is demonstrated. The measurement is based on the principle that, when linearly polarized light whose polarization varies alternately in two orthogonal directions passes through a polarization analyzer, the transmitted optical intensity varies. The output voltage from an optical detector located after the analyzer can be used to determine the roll angle. The chief advantages of the sensor are that it is compact, flexible, low cost, and power effective and provides a fast response. Most importantly, the sensor is insensitive to various fluctuations such as optical intensity, photodiode responsivity, and temperature and to vibrations. This performance is most advantageous in long-distance or long-term measurements. Experimental results have shown that the angular resolution is 0.01 degree in a +/-30 degree range.