The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disease that leads to progressive proximal muscle weakness and muscle atrophy. To assess the beneficial and adverse effects of nusinersen, a promising intervention for SMA, we conducted a systematic search and meta-analysis of the published randomized control trials (RCTs) of nusinersen for SMA. Materials and methods: Utilizing the Preferred Reporting for Systematic Review and Meta-Analysis (PRISMA), we searched PubMed, Scopus, Web of Science, Cochrane Central, and Clinicaltrials.gov from inception to 22 July 2021. Results: Three RCTs satisfying the inclusion and exclusion criteria covered 274 patients: 178 patients in the nusinersen group. Our results show a significant risk difference (RD) in the motor milestone response (RD: 0.51; 95% CI: 0.39, 0.62; p < 0.00001) and improvement in the HINE-2 score (RD: 0.26; 95% CI: 0.12, 0.40; p < 0.0003) in the nusinersen group compared to the control group. Moreover, a significant decrease in the risk ratio (RR) for severe adverse events (RR: 0.72; 95% CI: 0.57, 0.92; p = 0.007) and any adverse event leading to treatment discontinuation (RR: 0.40; 95% CI: 0.22, 0.74; p = 0.004) was observed. An insignificant result was found for any adverse effects (RR: 0.93; 95% CI: 0.97, 1.01; p = 0.14) and for serious adverse effects (RR: 0.81; 95% CI: 0.60, 1.07; p = 0.14). Conclusions: This review provides evidence that nusinersen treatment was effective in treatment for infants with SMA and was associated with fewer severe adverse events; however, more RCTs are needed to establish evidence.

The Incidence and Presentation Features of Glaucoma in Vogt-Koyanagi-Harada Syndrome: A Systematic Review and Meta-Analysis.

TOPIC: To determine the cumulative incidence and features of glaucoma in patients with Vogt-Koyanagi-Harada (VKH) syndrome compared with nonglaucoma patients. CLINICAL RELEVANCE: Knowing the exact burden of secondary glaucoma in VKH could guide its screening and management in clinical practice as a part of the regular follow-up for patients with VKH. METHODS: The review protocol was preregistered on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PROSPERO) [CRD42023462794]. PubMed, Scopus, Web of Science, EBSCOhost, and Google Scholar were searched for studies reporting the cumulative incidence and features of glaucoma presentation in VKH. A manual search was also conducted to supplement the primary search. Subgroup analyses based on glaucoma type, VKH stage, and patients' age were conducted. All analyses were conducted using STATA. Fixed- and random-effects models were selected according to the observed heterogeneity. Studies' methodological quality was determined using the National Institutes of Health tool. RESULTS: The analysis of 7084 eyes revealed a progressive increase in the cumulative incidence of secondary glaucoma over time. The cumulative incidence was lowest at VKH onset (7%) and highest at 15 years (26%). Open-angle (12%; 95% confidence interval [CI]: 9%-14%) is more common than angle-closure glaucoma (7%; 95% CI: 3%-13%). Glaucoma cumulative incidence is highest in the chronic recurrent stage of VKH (33%; 95% CI: 12%-59%) and among children < 18 years of age (26%; 95% CI: 16%-37%). Features associated with glaucoma occurrence in VKH showed comparable rates with nonglaucoma cases. However, a meta-analysis to determine risk factors of glaucoma development in VKH was not feasible secondary to the lack of adjusted risk measures in included studies. Studies' quality was questionable in 5 studies. The certainty of evidence was moderate-to-high. CONCLUSION: The cumulative incidence of glaucoma increases throughout VKH's course, with a higher tendency in children, chronic recurrent stages, and long-term follow-up. Future research should focus on examining risk factors of glaucoma development in VKH through adjusted multivariable regression models. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Corrigendum to "Feasibility of virtual low-cost quantitative continuous measurement of movements in the extremities of people with Parkinson's disease" [MethodsX 11 (2023) 102230].

[This corrects the article DOI: 10.1016/j.mex.2023.102230.].

Survival trends for patients with retinoblastoma between 2000 and 2018: What has changed?

INTRODUCTION: Retinoblastoma (RB) is the most common primary intraocular cancer of childhood. Over the last few decades, a variety of techniques and treatment modalities emerged that improved the survival and ocular salvage rate of patients with RB. We investigated the relative survival trends of patients with RB from 2000 to 2018 by using the Surveillance, Epidemiology, and End Results (SEER) database. DESIGN: Retrospective database review. METHODS: We extracted data from SEER 18 from 2000 to 2018. All patients with clinically diagnosed RB during the study period were included. We utilized SEER*Stat 8.3.9 and JPSurv software to estimate relative 5- and 10-year survival rates and trends and generated descriptive analyses with IBM SPSS. MAIN OUTCOME MEASURES: Patient survival rates at 5- and 10-year after RB diagnosis. RESULTS: RB was diagnosed in 1479 patients within the SEER 18 Program during our study period. The cohort comprised 776 (52.5%) males, 615 (41.6%) non-Hispanic whites, 487(32.9%) Hispanics, 1030 (69.6%) patients with unilateral disease, and 1087 (73.5%) patients with localized disease. Relative survival trends at 5- and 10-year significantly declined over the study periods (-0.42%, and -0.50% annually, respectively) but the decline was not significant in unilateral and bilateral RB cases separately. CONCLUSIONS: Five- and ten-year relative survival trends declined from 2000 to 2018 and were significantly decreasing. Further studies that include more patients are needed to identify the factors contributing to reduced survival of patients with RB over time.

The prevalence and presentation patterns of microcystic macular oedema: a systematic review and meta-analysis of 2128 glaucomatous eyes.

We conducted this research to determine the prevalence rate and presentation patterns with microcystic macular oedema (MMO) in glaucoma patients. The protocol was pre-registered on PROSPERO ( CRD42022316367 ). PubMed, Scopus, Web of Science, EMBASE, ProQuest, EBSCOHost, CENTRAL, clinicaltrials.gov, and Google Scholar were searched for articles reporting MMO in glaucoma patients. The primary outcome was the prevalence of MMO, while secondary outcomes included the comparison between MMO and non-MMO in terms of patients' characteristics (age, gender), glaucoma stage, and ocular parameters (axial length (AL), intraocular pressure, mean deviation, spherical equivalent). Data are reported as mean difference (MD) or log odds ratio (logOR) along with their corresponding 95% confidence intervals (CI) for continuous and dichotomous outcomes, respectively. The quality of included studies was assessed using the NIH tool, and the certainty of evidence was assessed using GRADE framework. Ten studies (2128 eyes) were included, revealing an overall prevalence rate of MMO of 8% (95%CI: 5-12%). When compared to non-MMO group, MMO was associated with lower age (MD = -5.91; 95%CI: -6.02: -5.20), greater risk of advanced glaucoma stage (LogOR=1.41; 95%CI: 0.72: 2.09), and lower mean deviation of the visual field (MD = -5.00; 95%CI: -7.01: -2.99). No significant difference was noted between both groups in terms of gender, axial length, or spherical equivalent. Three studies had good quality while seven had poor quality. MMO is a prevalent observation in glaucoma patients and is associated with patients' age and stage of the disease. However, the certainty of evidence remains very low.

Feasibility of virtual low-cost quantitative continuous measurement of movements in the extremities of people with Parkinson's disease.

A low-cost quantitative continuous measurement of movements in the extremities of people with Parkinson's disease, a structured motor assessment administered by a trained examiner to a patient physically present in the same room, utilizes sensors to generate output to facilitate the evaluation of the patient. However, motor assessments with the patient and the examiner in the same room may not be feasible due to distances between the patient and the examiner and the risk of transmission of infections between the patient and the examiner. Therefore, we propose a protocol for the remote assessment by examiners in different locations of both (A) videos of patients recorded during in-person motor assessments and (B) live virtual assessments of patients in different locations from examiners. The proposed procedure provides a framework for providers, investigators, and patients in vastly diverse locations to conduct optimal motor assessments required to develop treatment plans utilizing precision medicine tailored to the specific needs of each individual patient. The proposed protocol generates the foundation for providers to remotely perform structured motor assessments necessary for optimal diagnosis and treatment of people with Parkinson's disease and related conditions.

Non-invasive transcranial brain modulation for neurological disorders treatment: A narrative review.

Noninvasive brain stimulation/modulation is a rapidly emerging technique that has been implemented in different clinical applications. The commonly noninvasive techniques used in neurological manipulations include photobiomodulation (PBM), transcranial electrical stimulation (TES), transcranial magnetic stimulation (TMS), and ultrasound stimulation (USS). These techniques have the ability to excite, inhibit, or modulate neuronal activity in targeted brain areas to obtain the required therapeutic effects. However, each technique owns its unique mechanism of action that relies on specific parameters suitable for treating certain neurological disorders. Neurological disorders such as epilepsy, Parkinson's disease (PD), Alzheimer's disease (AD), and depression have been treated by one or more of these noninvasive techniques. The therapeutic outcomes of these techniques for neurological diseases are promising, yet with limitations. In the present review, the mechanisms of action of these different brain stimulation/modulation modalities were explored and a synopsis of their applications in the treatment of certain neurological disorders was provided. Moreover, methodological issues, limitations, and open questions were presented. Furthermore, some future directions were suggested.

Early centralized isolation strategy for all confirmed cases of COVID-19 remains a core intervention to disrupt the pandemic spreading significantly.

BACKGROUND: In response to the spread of the coronavirus disease 2019 (COVID-19), plenty of control measures were proposed. To assess the impact of current control measures on the number of new case indices 14 countries with the highest confirmed cases, highest mortality rate, and having a close relationship with the outbreak's origin; were selected and analyzed. METHODS: In the study, we analyzed the impact of five control measures, including centralized isolation of all confirmed cases, closure of schools, closure of public areas, closure of cities, and closure of borders of the 14 targeted countries according to their timing; by comparing its absolute effect average, its absolute effect cumulative, and its relative effect average. RESULTS: Our analysis determined that early centralized isolation of all confirmed cases was represented as a core intervention in significantly disrupting the pandemic's spread. This strategy helped in successfully controlling the early stage of the outbreak when the total number of cases were under 100, without the requirement of the closure of cities and public areas, which would impose a negative impact on the society and its economy. However, when the number of cases increased with the apparition of new clusters, coordination between centralized isolation and non-pharmaceutical interventions facilitated control of the crisis efficiently. CONCLUSION: Early centralized isolation of all confirmed cases should be implemented at the time of the first detected infectious case.