Effects of posterior tibial nerve stimulation (PTNS) on lower urinary tract dysfunction: An umbrella review.

BACKGROUND: Lower urinary tract dysfunction (LUTD) is a common, troublesome condition that often negatively affects patients' quality of life. Current literature has long been interested in how posterior tibial nerve stimulation (PTNS) can affect this condition. AIM: To extensively and systematically explore how PTNS affects LUTD based on the most recent systematic reviews. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All the systematic reviews, with or without meta-analysis that assessed the effects of PTNS on LUTD were retrieved. The quality of the included studies was assessed using the Joanna Briggs Institute tool, and analysis was conducted using the Comprehensive Meta-Analysis version 3 tool. RESULTS: From a total of 3077 citations, 20 systematic reviews entered this study, and 13 of them included meta-analysis. The population of studies varied vastly, for instance, some studies included only children or women while other focused on a specific pathology like multiple sclerosis-induced neurogenic LUTD. The majority of included studies reported an overall improvement in LUTD following percutaneous PTNS, although admitting that these results were derived from moderate to low-quality evidence. CONCLUSION: The findings of this thorough umbrella review showed that the positive benefits of PTNS in treating LUTD are currently supported by low-quality evidence, and it is crucial to interpret them with great care.

Efficacy and safety of desmopressin in nocturia and nocturnal polyuria control of neurological patients: A systematic review and meta-analysis.

PURPOSE: Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to evaluate the efficacy and safety of desmopressin treatment on nocturia in patients with underlying neurological diseases. METHODS: Studies were identified by electronic search of PubMed, Embase, Cochrane, CINAHL, and Google Scholar databases. Studies were considered if they provided information on the effectiveness and safety of desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) in the treatment of nocturia and their participants had acquired neurological pathology. Two researchers independently extracted the articles using specified datasets, such as quality-of-study indicators. Statistical meta-analysis was carried out using Review Manager (RevMan) 5.4 statistical software (Cochrane Collaboration). RESULTS: Of a total of 1042 articles in the initial search, 14 studies were included. Most of the published papers were related to MS (n = 7), two were on spinal cord injury, and other conditions were neural tube defect, myelodysplasia, Parkinson's disease, stroke, and multiple system atrophy. Overall, a total of 200 patients (mostly females) were enrolled. Thirteen studies evaluated the intranasal formulation of desmopressin and one study evaluated oral desmopressin. A significant decrease in nocturia episodes was reported in seven studies evaluating this topic. An increase in the maximum hours of uninterrupted sleep was reported in the three studies in which this outcome was assessed. A significant reduction in the volume of nocturnal incontinence was found in one study. Three studies were eligible to include in the meta-analysis. The results showed that desmopressin compared to placebo, significantly reduced nighttime urination (mean difference: -0.75, 95% CI: -1.10 to -0.41; p < 0.00001). The rate of adverse events ranged from 0% to 68.42%. The critical appraisal results for all trials showed that most of the studies had low or moderate quality. CONCLUSIONS: Our results emphasized desmopressin's safety and efficacy in reducing nocturia episodes, with transient adverse effects on neurological patients. However, the data were achieved from low or medium-quality trials, and further well-designed randomized controlled trials are needed.

The effects of melatonin supplementation on neurobehavioral outcomes and clinical severity in rodent models of multiple sclerosis; a systematic review and meta-analysis.

BACKGROUND: Through the antioxidant and anti-inflammation pathways, melatonin is proposed as a safe and effective intervention in neurological diseases. This study aims to evaluate the effects of melatonin supplementation on the neurobehavioral and clinical outcomes in animal models of multiple sclerosis (MS). METHODS: This study was conducted following the PRISMA statement. Animal studies that reported the effects of melatonin in preclinical MS models, including the experimental autoimmune encephalomyelitis (EAE) and cuprizone model for demyelination are included in this study. A systematic search in PubMed, Web of Science, Embase, and Scopus up was conducted in April 2023. The collaborative Approach to Meta-Analysis and Review of Animal Experimental Studies (CAMARADES) critical appraisal tool was used for the quality assessment of the studies and the quantitative synthetizes were conducted using the comprehensive meta-analysis software. RESULTS: Out of 542 studies, finally 21 studies, including 14 studies in the EAE model and 7 studies of the toxic demyelination method with cuprizone were included. The route of administration was intraperitoneal in 18 studies, oral in 2 studies, and subcutaneous in 1 study. The quantitative synthesis of the EAE clinical severity scale was associated with significant differences (standardized mean difference [SDM]: - 2.52; - 3.61 to - 1.42; p value < 0.01). In subgroup analyses, the difference was statistically significant in the mouse subgroup (SMD: - 2.60; - 3.74 to - 1.46; p value < 0.01). DISCUSSION: This study encountered that melatonin may be associated with improved behavioral and cognitive outcomes of preclinical models of MS with acceptable safety profiles. FUNDING: The research was supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71005).

Ofatumumab regimens in chronic lymphocytic leukemia: a meta-analysis.

Ofatumumab's therapeutic impact on patients with chronic lymphocytic leukemia (CLL) has been the subject of increasing clinical research. However, in recent years, no studies have yet provided a pooled assessment of the treatment effect of ofatumumab vs. non-ofatumumab regimens. Therefore, we conducted a progression meta-analysis to evaluate the efficacy of ofatumumab-based treatment in CLL patients using data from clinical studies. Relevant publications from PubMed, Web of Science and ClinicalTrials.gov were searched. The efficacy outcomes were progression-free survival (PFS) and overall survival (OS). The articles reviewed in the mentioned databases and matching the specified keywords were searched until January 2023. The pooled efficacy analysis showed that there was a significant difference in PFS [hazard ratios (HR) = 0.62, 95% confidence interval (CI) = 0.52-0.74] and no significant difference in OS (HR = 0.86, 95% CI = 0.71-1.03) between ofatumumab-based therapy and non-ofatumumab therapy. Our analysis showed the pooled efficacy for PFS was statistically significantly improved with ofatumumab-based treatments for CLL compared with other groups. Also, ofatumumab had no statistically significant improvement in the OS of patients with CLL. Thus, ofatumumab-based therapies for CLL patients could be improved by other combinational-based regimens.

Cardiac hydatid disease; a systematic review.

BACKGROUND AND OBJECTIVES: Human cystic echinococcosis (CE), is a common health problem in low- and middle-income countries. Cardiac involvement is a relatively rare manifestation of Echinococcus infection. This study aims to summarize the evidence regarding the features of cardiac CE. METHODS: Case series of the patients with cardiac CE, were included in this study. Non-English papers, case reports, reviews, letters, , commentaries, and conference abstracts were not included. A systematic search was conducted in PubMed and EMBASE databases and the risk of bias in the included studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. RESULTS: Out of 3985 results of the searches, finally 37 studies were included in this systematic review. Based on available evidence, cardiac involvement is an uncommon but serious presentation of CE which presents with some non-specific signs and symptoms. Dyspnea, chest pain, and palpitation are the most common symptoms of the disease and normal sinus rhythm is the most common Electrocardiogram (ECG) feature. The disease is not associated with high mortality in case of timely diagnosis and appropriate management. DISCUSSION: Consecutive and complete inclusion of participants, statistical analysis, and appropriate reporting of the demographics were the sources of bias in the included studies. The exclusion of non-English papers was a limitation during the review process. FUNDING: The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 69380). REGISTRATION: This study was registered in the International prospective register of systematic reviews (PROSPERO ID: CRD42022381204).

The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials.

BACKGROUND: Tislelizumab is an anti-programmed death-1 (PD-1) monoclonal antibody with a construction that enables it to have a higher affinity to its target. We aimed to evaluate tislelizumab's safety and efficacy for treating non-small cell lung cancer (NSCLC). METHODS: Embase, Scopus, PubMed, Web of Science, and Google Scholar were searched up to December 20, 2022. The review only included randomized controlled trials (RCTs) that evaluated the safety or efficacy of tislelizumab for treating patients with lung cancer. The revised Cochrane risk-of-bias tool (RoB2) was utilized to evaluate study quality. RESULTS: There were four RCTs identified, which included 1565 patients with confirmed locally advanced or metastatic squamous and/or non-squamous types of NSCLC. Treatment with tislelizumab was associated with better progression-free survival (PFS) and objective response rate (ORR), particularly when used in combination with chemotherapy. Almost all patients in both arms reported at least one treatment-emergent adverse event (TEAE). Decreased hematologic indexes accounted for more than 20% of the grade ≥ 3 TEAEs in the tislelizumab plus chemotherapy group. The proportion of TEAE that led to death in the tislelizumab plus chemotherapy arms ranged from 3.2 to 4.2%. Hypothyroidism, pneumonitis, and hyperglycemia were the most frequently noted immune-mediated adverse events in the tislelizumab group. CONCLUSIONS: Tislelizumab, whether used alone or in combination with chemotherapy, seems to demonstrate both a safety and efficacy as a treatment for NSCLC.

Clinical efficacy and safety of melatonin supplementation in multiple sclerosis: a systematic review.

BACKGROUND: Melatonin is a neurohormone secreted predominantly by the pineal gland that is demonstrated to be associated with the pathogenesis of multiple sclerosis (MS). This research desires to evaluate the tolerability and beneficial effects of exogenous melatonin supplementations in patients with MS. METHODS: This study was executed following the PRISMA 2020 statement. Both observational and interventional studies which reported the clinical effectiveness and/or safety of melatonin supplementation in patients with MS were included in this systematic review. Ovid, PubMed, Scopus, Embase, and Web of Science databases were searched and the risk of bias in included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools based on study design. RESULTS: Out of 1304 results of database searches, finally, 14 articles, including 7 randomized controlled trials (RCTs), 6 case-control studies, and one quasi-experimental study, were included based on the full-text review. Included phenotypes of MS were mostly relapsing-remitting MS (RRMS) (in 11 studies); it was secondary progressive MS (SPMS) in only one study, and two other studies had a mixture of the different phenotypes. The course of treatment with melatonin supplementation was between 2 weeks and 12 months. There were no substantial safety issues. Although melatonin was associated with enhanced oxidative stress and inflammation status, concerning the clinical benefits, limited studies suggested improvements in sleep conditions, cognitive outcomes, and fatigue in MS. DISCUSSION: There are insufficient data to support the regular melatonin prescription in MS. Limitations such as the small number of included studies, the diversity of the dosage, route, and duration of melatonin administration, and the diversity of assessment tests lead to unconvincing findings in this study. There is a need for future studies to achieve a comprehensive judgment on this subject.

Radiological features of late-onset multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Late-onset multiple sclerosis (LOMS) is most commonly defined as the onset of the disease's presentations at age 50 or older. There is still much to discover about the radiological features of LOMS. The current study aims to assess the imaging features of LOMS, as well as the correlation between these findings and the clinical characteristics of these patients. METHOD: This study was conducted following the PRISMA statement. A systematic search was conducted through PubMed, Scopus, and EMBASE databases to identify the studies that have applied magnetic-resonance imaging (MRI) or other imaging methods to investigate the radiological findings, as well as the relationship between them and clinical findings of LOMS patients. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklists. Meta-analysis was conducted using the third version of the compressive meta-analysis software (CMA3). RESULTS: Our search identified 753 unique titles. Among them, 15 studies, including seven case-control, five case-series, and three cross-sectional studies, met the eligibility criteria. According to the quantitative synthesis, brain lesions were detected among 72.2% of LOMS patients (4 studies; 95% CI: 67.0% - 93.1%). In the context of spinal lesions, overall spinal cord involvement was 64.0% (8 studies; 95% CI: 42.5% - 81.1%). Based on the available evidence, supratentorial involvement was found in 82.7% of cases (3 studies; 95% CI: 17.4% - 99.1%), juxtacortical involvement in 34.1% (3 studies; 95% CI: 26.4% - 42.7%), infratentorial involvement in 51.3% (4 studies; 95% CI: 32.1% - 70.1%), and cerebellar involvement in 18.5% (3 studies; 95% CI: 13.9% - 24.1%). CONCLUSION: Based on the neuroimaging findings, we found that, given the heterogeneity of MS, LOMS patients have a high rate of spinal cord lesions and supratentorial involvement. The limited available evidence suggests that Barkhof criteria are the best compromise for the diagnosis of LOMS. There is still a need for future studies.

Efficacy of percutaneous and transcutaneous posterior tibial nerve stimulation on idiopathic overactive bladder and interstitial cystitis/painful bladder syndrome: A systematic review and meta-analysis.

OBJECTIVES: Percutaneous and transcutaneous posterior tibial nerve stimulation (PTNS and TTNS) showed a promising effect on overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome. We aimed to give a systematic review and meta-analysis on the efficacy and safety of these therapeutic methods as well. METHODS: We searched studies available on PubMed, Embase, Cochrane, Scopus, Web of Science, and ProQuest on March 31, 2021, to find both published and unpublished studies. The retrieved articles were screened by two independent researchers and then the selected studies were critically appraised by Cochrane risk-of-bias tool for randomized trials, and Joanna Briggs Institute's checklist for quasi-experimental studies. Finally, the results of studies were synthesized using Review Manager (RevMan) 5.4 statistical software when the data were homogenous. The meta-analysis was performed by calculating the effect size (mean difference) and their 95% confidence intervals (CIs). RESULTS: Of the total 3194 publications, 68 studies were included in our qualitative evaluation and 9 studies (11 trials) in the quantitative stage. When TTNS or PTNS were compared to sham, placebo, no treatment, or conservative management, a decrease in frequency of urination was observed in both TTNS (mean difference [MD]: -3.18, 95% CI: -4.42 to -1.94, and p < 0.00001), and PTNS (MD: -2.84, 95% CI: -4.22 to -1.45, and p < 0.00001), and overall TTNS or PTNS (MD: -2.95, 95% CI: -4.01 to -1.88, and p < 0.00001). Significant improvements in mean voiding volume (MVV) and decreasing nocturia were also observed. CONCLUSIONS: Nerve stimulations either PTNS or TTNS appear to be effective interventions in treating refractory idiopathic OAB in terms of daily voiding frequency, MVV, urgency episodes, and nighttime voiding frequency. However, our result did not show any improvement in terms of urinary incontinence, postvoid residual volume or urge incontinence, and maximum cystometric capacity which emphasized the efficacy of these modalities on dry-OAB rather than wet-OAB.

Pharmacotherapy of Alzheimer's disease: an overview of systematic reviews.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia. In this umbrella systematic review (SR), we summarized the efficacy of different pharmacological interventions in improving cognitive function in patients with AD. METHODS: A systematic search was performed through the PubMed, Scopus, Embase, and Cochrane databases for SRs of studies assessing the efficacy of pharmacological interventions versus placebo in improving cognitive function in AD or mild cognitive impairment due to AD. The risk of bias (RoB) was assessed using the Risk of Bias in SRs (ROBIS) tool. RESULTS: Out of 1748 articles found through the database survey, 33 SR articles were included. These studies assessed effects of immunotherapy, cholinesterase inhibitors (ChEIs), memantine, statins, lithium, nonsteroidal anti-inflammatory drugs (NSAIDs), antidiabetic agents, Cerebrolysin, RAS-targeting antihypertensive drugs (ARBs and ACEIs), psychostimulants, glycogen synthase kinase 3 (GSK-3) inhibitors, melatonin, and herbal medications on cognitive function in AD patients. There was no notable overall RoB in 18 studies (54.5%), the RoB in 14 studies (42.4%) was high, and in one study (3.0%) it was unclear. CONCLUSIONS: The use of ChEIs, including rivastigmine, galantamine, and donepezil, as well as memantine has demonstrated a positive impact on improving cognitive outcomes of AD patients, but no considerable effects were found for immunotherapies. Melatonin, statins, antihypertensive drugs, antidiabetic agents, Cerebrolysin, psychostimulants, and some herbal drugs such as Danggui-Shaoyao-San and Ginkgo biloba seem to be effective in improving cognitive function of AD patients, but the evidence in this regard is limited.

Clinical application of stem cell therapy in neurogenic bladder: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: This review aims to investigate the effect of stem cell (SC) therapy on the management of neurogenic bladder (NGB) in four neurological diseases, including spinal cord injury (SCI), Parkinson's disease (PD), multiple sclerosis (MS), and stroke, in the clinical setting. METHODS: An electronic database search was conducted in the Cochrane Library, EMBASE, Proquest, Clinicaltrial.gov , WHO, Google Scholar, MEDLINE via PubMed, Ovid, Web of Science, Scopus, ongoing trial registers, and conference proceedings in June 2019 and updated by hand searching on 1 February 2021. All randomized controlled trials (RCTs), quasi RCTs, phase I/II clinical trials, case-control, retrospective cohorts, and comprehensive case series that evaluated the regenerative potential of SCs on the management of NGB were included. Cochrane appraisal risk of bias checklist and the standardized critical appraisal instrument from the JBI Meta-Analysis of Statistics, Assessment, and Review Instrument (JBI-MAStARI) were used to appraise the studies. RESULTS: Twenty-six studies among 1282 relevant publications met our inclusion criteria. Only SC therapy was applied for SCI or MS patients. Phase I/II clinical trials (without control arm) were the most conducted studies, and only four were RCTs. Four studies with 153 participants were included in the meta-analysis. The main route of transplantation was via lumbar puncture. There were no serious adverse events. Only nine studies in SCI and one in MS have used urodynamics, and the others have reported improvement based on patient satisfaction. SC therapy did not significantly improve residual urine volume, detrusor pressure, and maximum bladder capacity. Also, the quality of these publications was low or unclear. CONCLUSION: Although most clinical trials provide evidence of the safety and effectiveness of MSCs on the management of NGB, the meta-analysis results did not show a significant improvement; however, the interpretation of study results is difficult because of the lack of placebo controls.

ApoE4-positive multiple sclerosis patients are more likely to have cognitive impairment: a cross-sectional study.

BACKGROUND: Multiple sclerosis (MS) presents with a wide variety of symptoms, including cognitive dysfunction. Previous studies in terms of the possible function of the ApoE4 allele as a risk factor for cognitive dysfunction in MS patients were associated with conflicting results. The role of the ε4 isoform of apolipoprotein (ApoE4) was investigated in this study as a risk factor for cognitive dysfunction in MS patients. METHODS: Mildly disabled relapsing-remitting MS (RRMS) patients were involved in this study. The neurocognitive assessment is conducted by the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery. After determining the genotype, patients were divided into two groups of ApoE4-positive and ApoE4-negative groups, and cognitive findings were compared. RESULTS: Seventy-one patients with a mean age of 31.43 ± 8.75 were involved in this study. Eleven out of 17 (64.70%) patients in the ApoE4-positive group had at least one impaired test, while this rate was 16 out of 54 (29.62%) in the ApoE4-negative group (p < 0.01). The rate of overall cognitive impairment (failure in ≥ 2 tests) was not statistically different between groups of the study (p = 0.75). Impairment in Paced Auditory Serial Addition Test (PASAT) task and also the mean score of Brief Visuospatial Memory Test-Revised (BVMT-R) tests were different between two groups (p = 0.01 and 0.02, respectively). CONCLUSION: MS ApoE4-positive patients are more likely to have at least one impaired cognitive test, but there is a need for more studies with larger sample sizes and based on MS-specific cognitive tests to confirm these findings.

Probiotics in Critically Ill Patients: An Umbrella Review.

Objectives: Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Because of the wide usage of antibiotics, acute changes in diet, and the stress of illness, critically ill patients' homeostasis of the gut microbiome can be disrupted during intensive care unit (ICU) confinement; probiotics are suggested as a beneficial intervention in critically ill patients. We tried to give an overview of the effects of probiotic supplements in critically ill patients based on published systematic reviews (SRs) and meta-analyses (MAs). Data sources: A systematic search was performed in four databases as well as hand searching. Study selection: The results were independently screened in two title/abstracts and full-text stages. Data extraction: Any reported outcomes in each study were extracted, using a data extraction table. Data synthesis: A wide range of outcomes of using probiotic supplements in critically ill patients have been reported in 20 included studies. Based on the current knowledge, we can say that probiotics may reduce the rate of ventilator-associated pneumonia, nosocomial pneumonia, the overall infection rate, duration of mechanical ventilation, and antibiotic use in critically ill patients, but there is not a significant association between using the probiotics and mortality, length of hospitalization, and incidence of diarrhea. Conclusion: Despite the various beneficial effects of probiotics in critically ill patients, there is not yet much evidence supporting the routine use of these supplements and further well-designed multicenter trials are needed to provide "evidence-based" recommendations. How to cite this article: Naseri A, Seyedi-Sahebari S, Mahmoodpoor A, Sanaie S. Probiotics in Critically Ill Patients: An Umbrella Review. Indian J Crit Care Med 2022;26(3):339-360.

The correlation between circulating inflammatory, oxidative stress, and neurotrophic factors level with the cognitive outcomes in multiple sclerosis patients.

INTRODUCTION: Changes in the levels of circulating markers of inflammation, oxidative stress, and neurotrophic factors might be a good candidate for the prediction of cognitive impairment in multiple sclerosis (MS). Here, the correlation between the mentioned circulating markers with the Cambridge neuropsychological test automated battery (CANTAB) task outcomes was determined in MS patients. METHODS: The CANTAB (paired-associate learning (PAL), reaction time (RTI), rapid visual information processing (RVP), and spatial working memory tasks (SWM)) was completed by the patients. Accordingly, the serum levels of interferon-γ (INF-γ), C-reactive protein (CRP), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), malondialdehyde (MDA), total antioxidant capacity (TAC), and the acetylcholine esterase (AChE) activity were measured. Cognitive impairment status and the correlation between the circulating factors with the CANTAB outcomes were determined. RESULTS: The cognitively impaired (CI) patients appropriately differentiated from not cognitively impaired (NCI) ones using the CANTAB tasks. The serum levels of MDA, TAC, CRP, INF-γ, and GDNF correlated with the cognitive scores in MS patients (p < 0.05). After adjusting for age, sex, disease duration, and disability levels (covariates in a regression model), the MDA, INF-γ, and GDNF factors levels were statistically different between CI and NCI groups (p < 0.05). DISCUSSION: The mentioned markers might predict the cognitive impairment progress and be used as an index of its detection, in addition to neuropsychological assessments, in MS patients.

Osteosarcoma: A comprehensive review of management and treatment strategies.

Osteosarcoma, a bone cancer usually seen in children and young adults, is generally a high-grade malignancy presented by extreme metastases to the lungs. Osteosarcoma has a tendency for appearing in bones with rapid growth rate. The etiology of osteosarcoma is multifaceted and poorly understood. A molecular consideration of this disease will lead to a directed tumor treatment. The present treatment for osteosarcoma comprises of an arrangement of systemic chemotherapy and wide surgical resection. Survival rate is increased by the progress of destructive systemic chemotherapies. So, the development of new treatment approaches for metastatic osteosarcoma is essential. Immunomodulation has been used in clinical settings. Through targeting surface antigens expressed on tumor cells, particular antibodies and exploitation of cellular immunotherapy against sarcomas have been confirmed to be effective as cancer therapeutics. In this article, we have reviewed epidemiology, etiology, pathogenesis, diagnosis, and treatment of osteosarcoma and we have focused on different methods of immunotherapy including vaccines, cell-based immunotherapy, cytokines, and monoclonal antibodies.

Implications of cognitive and daily living capabilities on early type 2 diabetes management: a preliminary case-control study.

BACKGROUND: Adherence to the transition from oral agents to insulin injections in Type 2 Diabetes Mellitus therapy varies among patients and is not uniformly successful, leading to suboptimal glycemic control in certain cases. This study aims to investigate the potential correlation between cognitive and daily functional capabilities and glycemic control in middle-aged to older adults (40-74 years old) diagnosed with Type 2 Diabetes Mellitus for less than 10 years, specifically those who have recently transitioned to insulin injections and have lower education levels within the context of a developing country. METHODS: A case-control study was conducted with 30 poorly controlled diabetes mellitus (PCDM) patients recognized by HbA1c levels > 8% compared to 30 fairly controlled diabetes mellitus (FCDM) patients with HbA1c levels ≤ 8%. Basic Montreal Cognitive Assessment (MoCA-B) score of less than 27 was investigated as the exposure among two groups. Additionally, intra- and inter-battery correlations were assessed among MoCA-B and Instrumental Activities of Daily Living (IADL) domains using Pearson's r. RESULTS: The primary outcomes showed no crude difference between MoCA-B scores in the two diabetic groups (p-value = 0.82). However, after adjusting for age, education, and IADL scores, cognitive decline in the less-educated younger elderly with high IADL scores demonstrated an unexpected protective effect against PCDM (p-value < 0.0001, OR 95% CI = 0-0.26). In linear regression analysis among MoCA-B and IADL scores, "delayed recall" and "orientation" domains from MoCA-B, and "managing medications" and "using the phone" from IADL were negatively associated with HbA1c levels (p-values of < 0.01, 0.043, 0.015, and 0.023, respectively). Intra- and inter-battery correlations further illustrated a strong association between MoCA-B's "orientation" with IADL's "using the phone" and "managing medications" (p-values < 0.0001). CONCLUSION: Superior performance in certain cognitive domains is linked to better glycemic control. Still, since assessing cognitive domains may be timely in clinical routine, a potential rapid approach might be taken by assessing patients' instrumental abilities to use cell phone or manage medications. Future studies including a larger sample size and a broader spectrum of psychosocial factors are needed to elaborate on our findings.

Serum lipids and cognitive outcomes in multiple sclerosis; a systematic review and meta-analysis.

BACKGROUND: Cognitive impairment is highly prevalent in multiple sclerosis (MS) with poorly understood underlying mechanisms. Lipids are considered to be associated with MS progression through the inflammatory and oxidative stress pathways, brain atrophy, cellular signaling, and tissue physiology. In addition, serum lipids are proposed as a modifiable factor affecting the neuropsychiatric condition; therefore, this study aims to assess the association between serum lipid levels and cognitive outcomes in MS. METHODS: This study was carried out following the PRISMA 2020 statement. A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase in March 2023, and the Joanna Briggs Institute (JBI)'s critical appraisal tools were utilized for risk of bias (RoB) assessments in the included studies. The quantitative synthesis was performed with the comprehensive meta-analysis (CMA3) software. RESULTS: Out of 508 screened records, 7 studies were eventually found to meet our inclusion criteria. In two studies, the course of MS in the sample of the study was only Relapsing-Remitting MS (RRMS), whereas the other five studies' sample was a combination of different phenotypes. Studies utilized different scales such as Minimal Assessment of Cognitive Function in MS (MACFIMS), Brief International Cognitive Assessment for MS (BICAMS), Montreal Cognitive Assessment (MoCA), Brief Repeatable Battery of Neuropsychological Tests (BRB-N) for cognitive evaluations. Dealing with possible confounders such as age, disease duration and level of disability was the most common possible source of bias in the included studies. One study revealed an inverse relationship between serum levels of apolipoproteins (including ApoA-I, ApoB, and ApoB/ApoA-I) and Symbol Digit Modalities Test (SDMT) scores. Also, a correlation between 24S-hydroxycholesterol (24OHC) serum concentrations and SDMT score was reported in one study. The association between serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) and different aspects of cognitive function was reported in the studies; however, serum levels of high-density lipoprotein cholesterol (HDL) were not found to be associated. The quantitative synthesis revealed a significant correlation between TC and the MoCA scores (r =-0.238; 95 %CI: -0.366 to -0.100; p-value = 0.001); however, the correlation between TG levels and MoCA were not statistically significant (r:-0.070; 95 %CI: -0.209 to 0.072; p-value: 0.334). In addition, the mata-analyses were not associated with significant findings regarding the correlation between lipid profiles (including HDL, LDL, TG, and TC) and other cognitive assessment scales including SDMT, Brief Visuospatial Memory Test (BVMT), and California Verbal Learning Test (CVLT) (p-values>0.05). DISCUSSION: Available evidence suggested a link between TC and LDL with cognitive outcomes of MS patients which was not evident in our quantitative synthesis. The limited number of studies, high RoB, different cognitive assessment scales and reporting methods, and the cross-sectional design of the included studies, were the main limitations that alleviate the clinical significance of the findings of this study and suggested further investigations on this topic. FUNDING AND REGISTRATION: The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71,909). This study is registered in the international prospective register of systematic reviews (PROSPERO ID: CRD42023441625).

Clinical and Epidemiological Findings of Pediatric Onset Multiple Sclerosis in East-Azerbaijan, Iran; A Population-based Study.

Objectives: Multiple sclerosis (MS) is among the most prevalent chronic immune-mediated inflammatory diseases. If MS onset is under 18, it is defined as pediatric-onset MS (POMS). This study aimed to determine the clinical and epidemiological aspects of POMS. Materials & Methods: This population-based study was conducted in East-Azerbaijan (EA) province and concerned POMS patients. The data concerning almost all of the POMS patients of the province was gathered from the only MS registry center in the university hospital of the Tabriz University of Medical Sciences by the end of 2017. The diagnosis of patients was based on McDonald's criteria. Results: Out of 2976 total cases of MS, eighty-five (2.85%) were POMS. The overall regional prevalence of POMS was 11.67 per 100,000 (95% CI:9.43-11.43). Sixty-seven cases were female (prevalence: 18.94 per 100,000 [95% CI:14.91-24.07], and eighteen were male (prevalence: 4.80 per 100,000 [95% CI:3.03-7.62]. The crude regional incidence in 2017 was 1.37/100,000 (95% CI:0.74-2.55). The mean age of onset was 15.81±1.33 years, with a minimum age of 12. 71.76% of the patients were diagnosed in the 16- or 17-years old age group. 7.05% had a positive family history, and 87.5% of the patients diagnosed the disease promptly. The most common first clinical presentations were blurred vision (43.75%), sensory (28.12%), cerebellar (15.62%), and brainstem (9.37%) symptoms. Conclusion: POMS is not a rare condition, and it mainly affects females. POMS prevalence increases significantly after age 15 years old, and the first manifestation of the disease is usually blurred vision.

Investigating the Association of Quantitative Gait Stability Metrics With User Perception of Gait Interruption Due to Control Faults During Human-Prosthesis Interaction.

This study aims to compare the association of different gait stability metrics with the prosthesis users' perception of their own gait stability. Lack of perceived confidence on the device functionality can influence the gait pattern, level of daily activities, and overall quality of life for individuals with lower limb motor deficits. However, the perception of gait stability is subjective and difficult to acquire online. The quantitative gait stability metrics can be objectively measured and monitored using wearable sensors; however, objective measurements of gait stability associated with human's perception of their own gait stability has rarely been reported. By identifying quantitative measurements that associate with users' perceptions, we can gain a more accurate and comprehensive understanding of an individual's perceived functional outcomes of assistive devices such as prostheses. To achieve our research goal, experiments were conducted to artificially apply internal disturbances in the powered prosthesis while the prosthetic users performed level ground walking. We monitored and compared multiple gait stability metrics and a local measurement to the users' reported perception of their own gait stability. The results showed that the center of pressure progression in the sagittal plane and knee momentum (i.e., residual thigh and prosthesis shank angular momentum about prosthetic knee joint) can potentially estimate the users' perceptions of gait stability when experiencing disturbances. The findings of this study can help improve the development and evaluation of gait stability control algorithms in robotic prosthetic devices.

A simplified model for whole-body angular momentum calculation.

The capability to monitor gait stability during everyday life could provide key information to guide clinical intervention to patients with lower limb disabilities. Whole body angular momentum (Lbody) is a convenient stability indicator for wearable motion capture systems. However, Lbody is costly to estimate, because it requires monitoring all major body segment using expensive sensor elements. In this study, we developed a simplified rigid body model by merging connected body segments to reduce the number of body segments, which need to be monitored. We demonstrated that the Lbody could be estimated by a seven-segment model accurately for both people with and without lower extremity amputation.