Mohammed Ma'ARij Anwar

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Glaucoma forms the leading cause of irreversible blindness worldwide, with a disproportionately rising prevalence in Asian and African countries. Primary open angle glaucoma (POAG) accounts for the majority of cases. Medical therapies of POAG are not without side effects, meanwhile surgical treatments carry high complication rates. Ab-interno canaloplasty promises a safer, minimally invasive yet effective treatment option for mild-to-moderate POAG, as well as a cost-effective technique for low-resource countries. Despite this, no systematic review currently exists to verify this procedure's efficacy. Objective: To develop a protocol for a systematic review aimed at evaluating the efficacy canaloplasty against all other forms of POAG treatment. Methods: This systematic review and meta-analysis will include randomised controlled trials (RCTs) evaluating the short-term, medium-term and long-term efficacy and safety of ab-interno canaloplasty in treating POAG, in comparison to all other treatments. Mean change in intraocular pressure (IOP) will form the primary outcome measure. Secondary outcome measures include proportion of participants medication free after treatment and mean change in health-related quality of life (HRQoL). MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov databases will be searched for relevant RCTs. All studies will be subject to pre-specified inclusion and exclusion criteria. Quality of eligible RCTs will be assessed using the Cochrane risk of bias tool. Data will be extracted with a focus on raw data where possible and analysis will be performed using Revman 5.4 software to compare the mean changes in IOP (mmHg) between ab-interno canaloplasty and other comparator therapies. A funnel plot will be used to assess risk of publication bias if 10 or more trials are included in the review. I2 statistics will be used to assess heterogeneity. Sensitivity analysis will be conducted to exclude studies with high-risk of bias and, where possible, on the primary outcome. The GRADE approach will be used to summarise the main findings. Results: The results of this systematic review are not yet available as it is still at the protocol stage. This protocol was registered on the PROSPERO database for systematic reviews (CRD42024558671) on the 27th of June 2024. Data collection for this review began on the 14th of July 2024 with the anticipated completion date being early 2026. Conclusions: The findings will be important to patients, clinicians and policymakers worldwide in addressing the growing burden and health inequality of glaucoma. Clinical Trial: Prospero CRD42024558671

BACKGROUND Glaucoma forms the leading cause of irreversible blindness worldwide, with a disproportionately rising prevalence in Asian and African countries. Primary open angle glaucoma (POAG) accounts for the majority of cases. Medical therapies of POAG are not without side effects, meanwhile surgical treatments carry high complication rates. Ab-interno canaloplasty promises a safer, minimally invasive yet effective treatment option for mild-to-moderate POAG, as well as a cost-effective technique for low-resource countries. Despite this, no systematic review currently exists to verify this procedure's efficacy. OBJECTIVE To develop a protocol for a systematic review aimed at evaluating the efficacy canaloplasty against all other forms of POAG treatment. METHODS This systematic review and meta-analysis will include randomised controlled trials (RCTs) evaluating the short-term, medium-term and long-term efficacy and safety of ab-interno canaloplasty in treating POAG in comparison to all other treatments with the primary outcome measure of mean change in intraocular pressure (IOP). Secondary outcome measures include proportion of participants medication free after treatment and mean change in health-related quality of life. MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov databases will be searched for relevant RCTs. All studies will be subject to pre-specified inclusion and exclusion criteria. Quality of eligible RCTs will be assessed using the Cochrane risk of bias tool. Data will be extracted with a focus on raw data where possible and analysis will be performed using Revman 5.4 software to compare the mean changes in IOP (mmHg) between ab-interno canaloplasty and other comparator therapies. A funnel plot will be used to assess risk of publication bias if 10 or more trials are included in the review. I2 statistics will be used to assess heterogeneity. Sensitivity analysis will be conducted to exclude studies with high-risk of bias and, where possible, on the primary outcome. The GRADE approach will be used to summarise the main findings. RESULTS The results of this systematic review are not yet available as it is still at the protocol stage. This protocol was registered on the PROSPERO database for systematic reviews (CRD42024558671) on the 27th of June 2024. Data collection for this review began on the 14th of July 2024 with the anticipated completion date being within the following year. CONCLUSIONS The findings of this systematic review will be important to patients, clinicians and policymakers worldwide in addressing the growing burden and health inequality of glaucoma. CLINICALTRIAL Trial registration: PROSPERO CRD42024558671

Background: Streptococcus pneumoniae (Spn) has been a leading cause of bacterial meningitis in children. The most recent estimation of the global burden of Spn meningitis indicates a positive trajectory in eliminating Spn through the implementation of pneumococcal conjugate vaccines. However, continuous monitoring and assessment of the disease burden are necessary due to the evidence of serotype replacement, antibiotic resistance, and the impact of the recent COVID-19 pandemic. Objective: The aim of this systematic review is to provide an updated and focused assessment of the global and regional burden of Spn meningitis in children, which can guide policies and strategies to reduce the disease burden. Methods: Population-based studies published from January 1, 2000, to January 1, 2022, were preliminarily searched from the electronic databases PubMed, Embase, Global Health (CABI), and CINAHL Plus without any language restrictions. Studies were included if they reported the incidence, prevalence, mortality, or case-fatality ratio (CFR) for Spn meningitis in children aged 0-4 years; meningitis was confirmed by cerebrospinal fluid culture; the study period was a minimum of 1 year; the number of reported cases was at least 10; and the study had no methodological ambiguities. The article screening process follows the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Characteristics including study period, setting, World Health Organization region, income level, vaccination information, and participant data (age, number of cases, deaths, sequelae, and risk factors) will be extracted from the included studies. Search results will be updated and incorporated into our review prior to finalizing the extraction of data. Generalized linear mixed models meta-analysis will be performed to estimate the pooled incidence and CFR. We will further assess the risk of bias and heterogeneity, and will perform subgroup and sensitivity analyses to provide a meaningful interpretation of the current burden and literature for pneumococcal meningitis. Results: Our preliminary search in December 2021 yielded 9295 articles. Out of 275 studies that were assessed with our eligibility criteria, 117 articles were included. Data extraction and analysis are expected to be complete by January 2025. We plan to publish the results from the full study, including an updated search in 2024, by March 2025. Conclusions: Given that the major burden of Spn meningitis affects children under the age of 5 years, this systematic review will provide a thorough understanding of the global burden of Spn meningitis in this vulnerable population over a span of 2 decades. Insights into incidence trends, geospatial distribution, risk factors, and sequelae will be valuable for stakeholders, policy makers, and the academic community. This information will aid in the ongoing monitoring of the disease and in enhancing targeted vaccine programs to further mitigate the impact of the disease on children worldwide. Trial Registration: PROSPERO CRD42021293110; https://tinyurl.com/kc3j5k4m International Registered Report Identifier (IRRID): DERR1-10.2196/50678

Primitive myxoid mesenchymal tumour of infancy (PMMTI) is a rare mesenchymal tumour that typically appears in those under 6 months of age and preferentially affects the deep soft tissues of the trunk and paravertebral spinal regions. PMMTI has only recently been described, and there is scarce literature reporting cases regarding the management paradigm of the tumour. We report the case of an 11-week-old male who presented with bilaterally reduced movement and brisk reflexes in his lower limbs, and irritability. Despite numerous radiological investigations, including MRI, PMMTI was only diagnosed upon biopsy and histopathology. Although PMMTI is known to be relatively unresponsive to chemotherapy, we observed a notable decrease in tumour size after a series of chemotherapy sessions. After two-staged surgical resection of the tumour, the patient is currently stable and under close follow-up. In this article, we aim to report on the patient’s clinical presentation, investigations, diagnosis, and treatment, while also discussing the findings from a review of the literature pertaining to future approaches in managing PMMTI. Overall, this case highlights the importance of considering PMMTI in the differential diagnosis of deep soft tissue tumours in young infants and the potential for a combination of chemotherapy and surgical resection to be effective in treating this rare tumour.

BACKGROUND Streptococcus pneumoniae (Spn) has been a leading cause of bacterial meningitis in children. The most recent estimation of the global burden of Spn meningitis indicates a positive trajectory in eliminating Spn through the implementation of pneumococcal conjugate vaccines. However, continuous monitoring and assessment of the disease burden are necessary due to the evidence of serotype replacement, antibiotic resistance, and the impact of the recent COVID-19 pandemic. OBJECTIVE The aim of this systematic review is to provide an updated and focused assessment of the global and regional burden of Spn meningitis in children, which can guide policies and strategies to reduce the disease burden. METHODS Population-based studies published from January 1, 2000, to January 1, 2022, were preliminarily searched from the electronic databases PubMed, Embase, Global Health (CABI), and CINAHL Plus without any language restrictions. Studies were included if they reported the incidence, prevalence, mortality, or case-fatality ratio (CFR) for Spn meningitis in children aged 0-4 years; meningitis was confirmed by cerebrospinal fluid culture; the study period was a minimum of 1 year; the number of reported cases was at least 10; and the study had no methodological ambiguities. The article screening process follows the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Characteristics including study period, setting, World Health Organization region, income level, vaccination information, and participant data (age, number of cases, deaths, sequelae, and risk factors) will be extracted from the included studies. Search results will be updated and incorporated into our review prior to finalizing the extraction of data. Generalized linear mixed models meta-analysis will be performed to estimate the pooled incidence and CFR. We will further assess the risk of bias and heterogeneity, and will perform subgroup and sensitivity analyses to provide a meaningful interpretation of the current burden and literature for pneumococcal meningitis. RESULTS Our preliminary search in December 2021 yielded 9295 articles. Out of 275 studies that were assessed with our eligibility criteria, 117 articles were included. Data extraction and analysis are expected to be complete by January 2025. We plan to publish the results from the full study, including an updated search in 2024, by March 2025. CONCLUSIONS Given that the major burden of Spn meningitis affects children under the age of 5 years, this systematic review will provide a thorough understanding of the global burden of Spn meningitis in this vulnerable population over a span of 2 decades. Insights into incidence trends, geospatial distribution, risk factors, and sequelae will be valuable for stakeholders, policy makers, and the academic community. This information will aid in the ongoing monitoring of the disease and in enhancing targeted vaccine programs to further mitigate the impact of the disease on children worldwide. CLINICALTRIAL PROSPERO CRD42021293110; https://tinyurl.com/kc3j5k4m INTERNATIONAL REGISTERED REPORT DERR1-10.2196/50678

Objectives Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial. We aim to identify and prioritise candidate drugs which have the best available evidence for efficacy, acceptable safety profiles and are feasible for evaluation within the trial protocol. Methods We conducted a two-stage systematic review to identify potential neuroprotective interventions. First, we reviewed clinical studies in MND, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and multiple sclerosis, identifying drugs described in at least one MND publication or publications in two or more other diseases. We scored and ranked drugs using a metric evaluating safety, efficacy, study size and study quality. In stage two, we reviewed efficacy of drugs in MND animal models, multicellular eukaryotic models and human induced pluripotent stem cell (iPSC) studies. An expert panel reviewed candidate drugs over two shortlisting rounds and a final selection round, considering the systematic review findings, late breaking evidence, mechanistic plausibility, safety, tolerability and feasibility of evaluation in MND-SMART. Results From the clinical review, we identified 595 interventions. 66 drugs met our drug/disease logic. Of these, 22 drugs with supportive clinical and preclinical evidence were shortlisted at round 1. Seven drugs proceeded to round 2. The panel reached a consensus to evaluate memantine and trazodone as the first two arms of MND-SMART. Discussion For future drug selection, we will incorporate automation tools, text-mining and machine learning techniques to the systematic reviews and consider data generated from other domains, including high-throughput phenotypic screening of human iPSCs.