Systematic reviews and meta-analysis combine results and analysis of data from different primary studies (e.g. cross-sectional studies, case-control studies, cohort studies) conducted on similar or related research topics. They are secondary studies that guide clinical decision-making, delivery of care and policy development. This article aims to discuss how to conduct a systematic review and meta-analysis. The steps in conducting a systematic review and meta-analysis include: 1) Identify the purpose including formulating the research question and validating the purpose of the literature scan, 2) Formulate the objectives, 3) Literature search including selection of studies based on population, intervention, comparison and outcome, 4) Retrieval of full text articles, 5) Critical appraisal of articles, 6) Data extraction, 7) Data analysis and 8) Writing the final report. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) is a useful guide in conducting and write systematic review and meta-analysis. While ethics approval is not usually required for systematic review and meta-analysis, authors of such study should still observe good practices including avoiding plagiarism, maintaining transparency and ensuring data accuracy.

BACKGROUND AND PURPOSE: This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37). METHODS: Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. RESULTS: The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. CONCLUSIONS: Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders.
Amyotrophic Lateral Sclerosis* ; Brain Stem ; Cerebellum ; Dementia ; Diagnosis ; Diffusion Tensor Imaging ; Frontotemporal Dementia* ; Humans ; Motor Cortex ; Motor Neurons ; Transcranial Magnetic Stimulation

OBJECTIVE: Both constitutive and inducible forms of nitric oxide synthase exist in endothelial cells. Disorders that produce acute lung injury frequently release endotoxin and cytoknes, such as interferon(IFNgamma) and tumor necrosis factor (TNFalpha). Endotoxin and these cytokines likely act as important mediators of cell injury. Because nitric oxide (NO) avidly reacts with iron, it may affect the activity of key enzymes, such as mitochondrial aconitase, which contain an iron-sulfur structure as a prosthetic group. METHOD: We studied the effect of IFNgamma, TNFalpha and E. coli lipopolysaccharide(LPS) on NO production and mitochondrial aconitase activity in cultured rat lung microvascular endothelial cells(RLMVC). RESULT: Exposing RLMVC for 24 hours to IFNgamma(500 U/mL), TNFalpha(300 U/mL) and LPS(5 microgram/mL) significantly increases nitrite production to 20+/-1 micrometer compared to 0.07 micrometer in control cells(P<0.05, n=4). Cytokine treatment also reduced mitochondrial aconitase activity from 196+/-8 to 102+/-34 nmole/min/mg of cell protein(P<0.05, n=4). Treatment with the inhibitor of nitric oxide synthase N-monomethyl-L-arginine(NMMA) (0.5 mM) not only significantly blunted the cytokine-mediated increase in nitrite formation (3+/-0.5 micrometer vs 20+/-1 micrometer with cytokines, P<0.05, n=4), but also prevented the cytokine-mediated drop in aconitase activity (161+/- 24 vs. 196+/-8 nmole/min/mg of cell protein, NS). CONCLUSION: Exposing RLMVC to IFNgamma, TNFalpha and E. coli LPS substantially decreases mitochondrial aconitase activity. Nitric oxide appears to mediate this effect. Our results suggest that the excessive production of NO by endothelial cells, in response to cytokines and endotoxin, may inhibit the function of the endothelial cell itself.
Aconitate Hydratase* ; Acute Lung Injury ; Animals ; Cytokines* ; Endothelial Cells* ; Iron ; Lung* ; Nitric Oxide Synthase ; Nitric Oxide* ; Rats* ; Tumor Necrosis Factor-alpha

Objective: Although evidence implicates striatal cholinergic impairment as a mechanism underlying tardive dyskinesia, trials of nonspecific cholinergic agents have been inconclusive. As a partial agonist at specific nicotinic receptor subtypes, varenicline reduces drug-induced dyskinesias in animal models suggesting promise as a treatment for tardive dyskinesia. Methods: Three schizophrenia patients with tardive dyskinesia who were smokers underwent an open trial of varenicline. After a 2-week baseline, subjects received varenicline 1 mg twice daily. Changes from baseline on the Abnormal Involuntary Movement Scale were measured after a 4-week varenicline stabilization period, and 6 weeks after the smoking quit date in one patient. Results: Varenicline had no effect on mean Abnormal Involuntary Movement Scale scores after 4 weeks. Although smoking decreased after 4 weeks on varenicline and diminished further in one patient after 10 weeks, this also appeared to have no effect on ratings of tardive dyskinesia. Conclusion In contrast to animal models, no significant change in tardive dyskinesia occurred in response to varenicline replacement in three schizophrenia patients. Further investigations of cholinergic mechanisms in tardive dyskinesia are worthwhile as agents for specific cholinergic targets become available for treatment. In addition, treatment trials of tardive dyskinesia should control for smoking status, while patients on antipsychotics receiving nicotine replacement therapies for smoking should be studied further for changes in movement.

Objective: Although evidence implicates striatal cholinergic impairment as a mechanism underlying tardive dyskinesia, trials of nonspecific cholinergic agents have been inconclusive. As a partial agonist at specific nicotinic receptor subtypes, varenicline reduces drug-induced dyskinesias in animal models suggesting promise as a treatment for tardive dyskinesia. Methods: Three schizophrenia patients with tardive dyskinesia who were smokers underwent an open trial of varenicline. After a 2-week baseline, subjects received varenicline 1 mg twice daily. Changes from baseline on the Abnormal Involuntary Movement Scale were measured after a 4-week varenicline stabilization period, and 6 weeks after the smoking quit date in one patient. Results: Varenicline had no effect on mean Abnormal Involuntary Movement Scale scores after 4 weeks. Although smoking decreased after 4 weeks on varenicline and diminished further in one patient after 10 weeks, this also appeared to have no effect on ratings of tardive dyskinesia. Conclusion In contrast to animal models, no significant change in tardive dyskinesia occurred in response to varenicline replacement in three schizophrenia patients. Further investigations of cholinergic mechanisms in tardive dyskinesia are worthwhile as agents for specific cholinergic targets become available for treatment. In addition, treatment trials of tardive dyskinesia should control for smoking status, while patients on antipsychotics receiving nicotine replacement therapies for smoking should be studied further for changes in movement.

Methods: All adult patients diagnosed with spinal spondylosis and migraine treated with CGRP inhibitors at a single academic institution between 2017 and 2020 were retrospectively identified. Patient demographic and medical data, follow-up duration, migraine severity and frequency, spinal pain, functional status, and mobility before and after the administration of CGRP inhibitors were collected. Paired univariate analysis was conducted to determine significant changes in spinal pain, headache severity, and headache frequency before and after the administration of CGRP inhibitors. The correlation between changes in the spinal pain score and functional or mobility improvement was assessed with Spearman’s rho. Results: In total, 56 patients were included. The mean follow-up time after the administration of CGRP inhibitors was 123 days for spinal pain visits and 129 days for migraine visits. Backeck pain decreased significantly (p <0.001) from 6.30 to 4.36 after starting CGRP inhibitor therapy for migraine control. As recorded in the spine follow-up notes, 25% of patients experienced a functional improvement in the activities of daily living, and 17.5% experienced mobility improvement while taking CGRP inhibitors. Change in back/ neck pain moderately correlated (ρ=−0.430) with functional improvement but was not correlated with mobility improvement (ρ=−0.052). Conclusions Patients taking CGRP inhibitors for chronic migraines with comorbid degenerative spinal conditions experienced significant off-target reduction of backeck pain.

INTRODUCTION: This study aimed to compare the effectiveness of immature Magnifera indica L. (mango) fruit with albendazole in reducing Ascaris lumbricoides infection among children. METHODS: Children aged 2 to 14 years were enrolled in a randomized, controlled, non-inferiority trial. Participants were randomly allocated to receive 250 mL immature mango fruit puree daily for 3 days or one dose of albendazole 400 mg tablet. Egg reduction rates and cure rates were computed and compared. Adverse effects were monitored during and after administration of treatment. RESULTS: There was a statistically significant decrease between the pre- and post-treatment EPG of those who took immature mango fruit (p < 0.001) and those who took albendazole (p < 0.001). There was a higher ERR and CR for the albendazole group, but the difference was not significant (p = 0.472, p = 785, respectively). Risk analysis of reduction in intensity showed mango is non-inferior to albendazole (RR = 0.80, 95% CI 0.67, 0.97; p = 0.026). Risk analysis of cure showed mango is noninferior to albendazole in both PP (RR = 0.92, 95% CI 0.68, 1.25; p = 0.607) and ITT (RR=0.79, 95% CI 0.58, 1.08; p = 0.139). CONCLUSION Immature Mangifera indica Linn is non-inferior to albendazole in terms of effectiveness in the reduction of ascariasis infection.
Ascariasis

Objective: The present study investigated, whether computer-aided therapy in patients with Parkinson’s disease is equivalent/non-inferior to conventional Lee Silvermann Voice Treatment (LSVT)-BIGtherapy in respect to motor outcome as measured by the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III) and quality of life as measured by the Parkinson’s Disease Questionnaire (PDQ-39). Methods: In this controlled, rater-blinded study, 34 patients were included and 24 patients randomized to train seven standard exercises of the BIG-therapy either by a computer (BeBIG-group) or by a certified LSVT-BIG therapist (ThBIG-group) over four weeks. Equivalence was assessed by comparing the confidence interval of the BeBIG-group to the equivalence margin of the ThBIG-group. Results: There were no significant group differences in respect to age, disease duration, L-dopa equivalent daily dose or clinical stage of the disease. Both groups profited significantly from the therapy as demonstrated by an improvement in the MDS-UPDRS-III of 9.17 point in the BeBIG-group and of 8.92 points in the ThBIG-group. There was a non-significant decrease in the PDQ-39 of 9.23 points in the BeBIG-group and 4.23 points in the ThBIG-group. However, equivalence could not be demonstrated as the improvement of the BeBIG-group exceeded the confidence interval of the ThBIG-group. Conclusion: Physical training by a computer as well as by a therapist improves motor symptoms and quality of life in Parkinson’s disease. Both therapies are not equivalent, superiority of the computerized training can however not be concluded, as the study was only designed to test for non-inferiority. Therefore, computerized training can be considered as an add-on-therapy

Background: Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors. Objectives: This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease. Methods: This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner. Results: Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups. There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status. Conclusion The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.
COVID-19 ; Interleukin-6