Efficacy of levamisole with standard care treatment vs. standard care in clinical presentations of non-hospitalized patients with COVID-19: a randomized clinical trial

Objective: The aim of this study was to evaluate the influence of adding a 10-day course of levamisole (LVM) to the standard care compared with standard care alone, on the clinical status of COVID-19 patients with mild to moderate disease. Methods:  In this randomized open-label trial, we enrolled non-hospitalized patients with mild to moderate COVID-19 at nine health centers in Tehran province, Iran, in 2021. Patients were randomly assigned to receive a 10-day course of LVM with standard care (n=185) or standard care alone (n=180) in a 1:1 ratio. On days 1 to 10, LVM was administered orally at a dosage of 50 mg. The participants were called and followed on days 1, 3, 5, 7, 9, and 14. The measured parameters were general health condition, hospitalization rate, signs and symptoms, and adverse events. The generalized estimating equations model was used for analysis. Results: Among 507 randomized patients, 473 patients started the experiment and received LVM plus standard care or received the standard care alone; 385 patients included in the analysis; 346 (98%) patients completed the trial. The median age of the patients was 40 years [IQR: 32-50.75]; and ‎201 (55.1%)‎ patiens were male. The mean age, sex ratio, and frequency of the underlying diseases of the patients in the two study groups had no ‎statistically significant differences (P>0.05). Compared to the control group, LVM improved the general health condition of the patients (B=-0.635; 95% CI: -0.041,-0.329; P<0.001). Patients receiving LVM compared with standard care group had significantly lower odds of developing fever (OR=0.260; 95% CI: 0.11‎‎3‎,0.59‎‎9‎; P=0.002), chills (OR=0.223; 95% CI:‎‎ 0.07‎‎6,‎0.64‎‎8‎; P= 0.006), fatigue (OR=0.576; 95% CI:‎ 0.34‎‎6,‎0.96‎‎0‎‎; P=0.034), and myalgia (OR=0.54‎‎4‎; 95% CI:‎ 0.31‎‎7‎,0.93‎‎2‎‎; P=0.027). No significant difference was observed in the rate of hospitalization. Although the intervention group had greater adverse effects than the control group, the difference was not statistically significant. Conclusion: Findings of this study suggest that LVM has clinical benefits in improving patients’ health condition with mild to moderate COVID-19

Diagnostic accuracy of circular RNA for diabetes Mellitus : a systematic review and diagnostic Meta-analysis

Acknowledgements: We thank all our staff at the Tehran University of medical sciences and at Kurdistan University of Medical sciences who helped us in this work. We also acknowledge the papers that we used and participants in those papers. Funding Information: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Publisher Copyright: © 2023, The Author(s).Peer reviewedPublisher PD

Correction: Protective effects of hydroalcoholic extracts from an ancient apple variety 'Mela Rosa dei Monti Sibillini' against renal ischemia/reperfusion injury in rats.

Correction for 'Protective effects of hydroalcoholic extracts from an ancient apple variety 'Mela Rosa dei Monti Sibillini' against renal ischemia/reperfusion injury in rats' by Hasan Yousefi-Manesh et al., Food Funct., 2019, 10, 7544–7552

Phenotype and Genotype Heterogeneity of PLA2G6-Associated Neurodegeneration in a Cohort of Pediatric and Adult Patients

BACKGROUND: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6. METHODS: An extensive review of the patients\u27 data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease\u27s underlying etiology followed by co-segregation analysis using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was used to assess the pathogenicity of genetic variants. We aimed to survey a genotype-genotype correlation in PLA2G6 considering all reported disease-causing variants in addition to our patients using the HGMD database and the chi-square statistical approach. RESULTS: Eighteen cases of INAD and 7 cases of late-onset PLAN were enrolled. Among 18 patients with INAD, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, the mean rate of progression was 0.58 points per month of symptoms (Standard error 0.22, lower 95% - 1.10, and upper 95% - 0.15). Sixty percent of the maximum potential loss in the INAD-RS had occurred within 60 months of symptom onset in INAD patients. Among seven adult cases of PLAN, hypokinesia, tremor, ataxic gate, and cognitive impairment were the most frequent clinical features. Various brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. Twenty unique variants in 25 patients with PLAN were detected including nine novel variants. Altogether, 107 distinct disease-causing variants from 87 patient were analyzed to establish a genotype-phenotype correlation. The P value of the chi-square test did not indicate a significant relationship between age of disease onset and the distribution of reported variants on PLA2G6. CONCLUSION: PLAN presents with a wide spectrum of clinical symptoms from infancy to adulthood. PLAN should be considered in adult patients with parkinsonism or cognition decline. Based on the current knowledge, it is not possible to foresee the age of disease onset based on the identified genotype

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

Enhancement of Thermoelectric Efficiency and Optical Properties of Hydrogen Absorption in SiC:Mn Nanotube

The effects of hydrogen absorption and manganese substitution on structural, electronic, optical, and thermoelectric properties of silicon-carbon nanotubes (SiCNT) are studied using the density functional theory and the GGA approximation. An examination of the PDOS curves and the electronic band structure showed that the Mn substitution leads to an increase in magnetic anisotropy and the occurrence of semi-metallic behavior and that the hydrogen absorption shifts the band gap toward the lower energies. A study of these nanostructures’ thermoelectric behavior reveals that the H absorption leads to a significant escalation in the figure of merit of the SiCNT to about 1.6 in the room temperature range. The effects of the H absorption on this nanotube’s optical properties, including the dielectric functions and its absorption spectra, are also investigated

Association of ADHD symptoms with type 2 diabetes and cardiovascular comorbidities in adults receiving outpatient diabetes care

Background: The relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and type 2 diabetes mellitus (T2D) and its cardiovascular outcomes have not been sufficiently studied. Methods: 2,986 adults with T2D from the Joslin Diabetes Center at Upstate Medical University were assessed for ADHD-like symptoms, executive dysfunction, and emotional control using the Adult Self-Report Scale V1.1 (ASRS) expanded version. Surveys were sent electronically, and clinical data were obtained from the electronic medical record. Pearson chi-square test was used for categorical variables association. When ASRS scores were the dependent variable, negative binomial regression correcting for demographic variables that were associated with the ASRS scores was used. Results: 155 (49.2%) of respondents met DSM-5 criteria for ADHD using the ASRS scores; Only ten (3.6%) of respondents had an ICD10 diagnosis of ADHD in their medical record; Forty-three (13.7%) had either a diagnosis of ADHD in the medical history or were taking medications used by people with ADHD. Higher levels of ADHD-like symptoms were found in patients with T2D compared with population norms. There was a modest association of the ASRS executive dysfunction subscale with overall cardiovascular comorbidities (p = 0.03). However, the p-value did not survive the multiple testing correction. Both ADHD-like symptoms and symptoms associated with emotional control, however, were not associated with specific cardiovascular diseases, hypertension, or with HbA1c, LDL-cholesterol, triglycerides, ALT, creatinine, or eGFR. Conclusion: Our results suggest that adults with T2D attending a tertiary care diabetes clinic are at risk for having ADHD-like symptoms, highlighting the importance of screening for ADHD symptoms in this specialty setting and referring undiagnosed adult patients for further assessment and treatment of ADHD. Larger studies are needed to clarify the relationship between ADHD-like symptoms, executive dysfunction, and emotional control with diabetic control and comorbidities

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case-control study

Background: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity.Methods: In a case-control study, we recruited patients with relapsing-remitting multiple sclerosis (RRMS). Patients were divided into two groups based on positive COVID-19 PCR at the end of the enroll-ment phase. Each patient was prospectively followed for 12 months. Demographical, clinical, and past medical history were collected during routine clinical practice. Assessments were performed every six months; MRI was performed at enrollment and 12 months later.Results: Three hundred and sixty-two patients participated in this study. MS patients with COVID-19 infection had significantly higher increases in the number of MRI lesions (p: 0.019, OR(CI): 6.37(1.54-26.34)) and EDSS scores (p: 0.017), but no difference was found in total annual relapses or relapse rates. COVID-19 infections were positively correlated with EDSS progression (p: 0.02) and the number of new MRI lesions (p: 0.004) and predicted the likelihood of the number of new MRI lesions by an odds of 5.92 (p: 0.018).Conclusion: COVID-19 may lead to higher disability scores in the RRMS population and is associated with developing new Gd-enhancing lesions in MRI imaging. However, no difference was observed between the groups regarding the number of relapses during follow-up.(c) 2022 Elsevier Espana, S.L.U. All rights reserved