Publications by authors named "S E Ali"

8,734 Publications

Improving Clinical Trials for Anticomplement Therapies in Complement-Mediated Glomerulopathies: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Am J Kidney Dis 2021 Sep 24. Epub 2021 Sep 24.

University of Toronto, Toronto, Canada.

Blocking the complement system as a therapeutic strategy has been proposed for numerous glomerular diseases but presents a myriad of questions and challenges, not the least of which is demonstrating efficacy and safety. In light of these potential issues and because there are an increasing number of anti-complement therapy trials either planned or underway, the National Kidney Foundation (NKF) facilitated an all-virtual format scientific workshop entitled, "Improving Clinical Trials for Anti-complement Therapies in Complement-mediated Glomerulopathies." Attended by patient representatives and experts in glomerular diseases, complement physiology, and clinical trial design, the aim of this workshop was to develop standards applicable for designing and conducting clinical trials for anti-complement therapies across a wide spectrum of complement-mediated glomerulopathies. Discussions focused on study design, subject risk assessment and mitigation, laboratory measurements and biomarkers to support these studies, and identification of optimal outcome measures to detect benefit, specifically for trials in complement-mediated diseases. This report summarizes the discussions from this workshop and outlines consensus recommendations.
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http://dx.doi.org/10.1053/j.ajkd.2021.07.025DOI Listing
September 2021

Efficacy and safety of ivermectin for the treatment of COVID-19: A systematic review and meta-analysis.

QJM 2021 Sep 27. Epub 2021 Sep 27.

Faculty of Health Sciences, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.

Background And Aim: Ivermectin became a popular choice for COVID-19 treatment among clinicians and the public following encouraging results from preprint trials and in vitro studies. Early reviews recommended the use of ivermectin based largely on non-peer-reviewed evidence, which may not be robust. This systematic review and meta-analysis assessed the efficacy and safety of ivermectin for treating COVID-19 based on peer-reviewed randomized controlled trials (RCTs) and observational studies (OSs).

Methods: MEDLINE, EMBASE, and PubMed were searched from January 1st, 2020 to September 1st, 2021 for relevant studies. Outcomes included time to viral clearance, duration of hospitalization, mortality, incidence of mechanical ventilation, and incidence of adverse events. RoB2 and ROBINS-I were used to assess risk of bias. Random-effects meta-analyses were conducted. GRADE was used to evaluate quality of evidence.

Results: Three OSs and 14 RCTs were included in the review. Most RCTs were rated as having some concerns in regards to risk of bias, while observational studies were mainly rated as having a moderate risk of bias. Based on meta-analysis of RCTs, the use of ivermectin was not associated with reduction in time to viral clearance, duration of hospitalization, incidence of mortality and incidence of mechanical ventilation. Ivermectin did not significantly increase incidence of adverse events. Meta-analysis of OSs agrees with findings from RCT studies.

Conclusions: Based on very low to moderate quality of evidence, ivermectin was not efficacious at managing COVID-19. It's safety profile permits its use in trial settings to further clarify its role in COVID-19 treatment.

Protocol Registration: The review was prospectively registered in PROSPERO (CRD42021275302).
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http://dx.doi.org/10.1093/qjmed/hcab247DOI Listing
September 2021

Anti-HIV and anti-HCV small molecule protease inhibitors in-silico repurposing against SARS-CoV-2 M for the treatment of COVID-19.

J Biomol Struct Dyn 2021 Sep 27:1-15. Epub 2021 Sep 27.

Department of Life Sciences, Sharda University, Greater Noida, UP, India.

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is a global health emergency warranting development and implementation of targeted treatment. The enzyme main protease (M; also known as 3C-like protease) is emerging as an attractive drug target. This enzyme plays an indispensable role in processing the translated polyproteins of viral RNA. Inhibiting the activity of M would wedge viral replication. To facilitate the discovery of targeted therapy for COVID-19, we carried out the structure-assisted repurposing of existing protease inhibiting small molecules to target SARS-CoV-2 M. Based on the structure of SARS-CoV-2 M, here we report the small drug molecule namely saquinavir as its potent inhibitor. Findings support the premise that this promising antiviral protease inhibiting small drug molecule can be validated and implemented for the treatment and clinical management of COVID-19 pandemic disease.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1979097DOI Listing
September 2021

Nickel nanoparticles induce hepatotoxicity via oxidative and nitrative stress-mediated apoptosis and inflammation.

Toxicol Ind Health 2021 Sep 25:7482337211034711. Epub 2021 Sep 25.

Department of Analytical Chemistry and Instrumental Analysis, Institute of Sport- National Research Institute, Warsaw, Poland.

Nickel nanoparticles (Ni NPs) are utilized extensively in various industrial applications. However, there are increasing concerns about potential exposure to Ni NPs and consequent health effects. The aim of this study was to assess Ni NPs-induced liver toxicity in Sprague Dawley rats. Twenty-five rats were exposed to Ni NPs intraperitoneal injection at doses of 15, 30, and 45 mg/kg per body weight for 28 days. Results from ICP-MS analysis showed an increase in the concentration of Ni NPs in a dose-dependent manner. The liver dysfunction was indicated by considerable production of ALT, AST, ALP, LDH, and TB in Ni NPs-treated rats. Histological examination demonstrated liver injuries (inflammatory cells, congestion, necrosis, and pyknosis) in exposed rats with dose-dependent severity of pathologies by semi-quantitative histograding system. To explore the toxicological pathways, we examined oxidative stress biomarkers and detected Ni NPs significantly elevated the levels of MDA and LPO while decreasing the levels of CAT and GSH. All the changes in biomarkers were recorded in a dose-dependent relationship. In addition, we found upregulated NF-kβ indicating activation of inflammatory cytokines. ELISA results of serum revealed a remarkable increase of nitrative stress markers (iNOS and NO), ATPase activity, inflammatory cytokine (IL-6, IL-1β, and TNF-α), and apoptotic mediators (caspase-3 and caspase-9) in Ni NPs-treated groups than the control. In summary, the result of this study provided evidence of hepatotoxicity of Ni NPs and insightful information about the involved toxic pathways, which will help in health risk assessment and management, related preventive measures for the use of Ni-NPs materials.
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http://dx.doi.org/10.1177/07482337211034711DOI Listing
September 2021

Public health practitioners' perspective on the sustainability of the tuberculosis control programme at primary health care level in Pakistan.

East Mediterr Health J 2021 Sep 21;27(9):899-905. Epub 2021 Sep 21.

Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.

Background: In resource-limited settings, national tuberculosis (TB) control programmes are highly dependent on external funds, which may pose a challenge to programme sustainability. There is a recognized need for developing guidance around sustainable programming of current TB control initiatives.

Aims: The aim of this study was to explore public health practitioners' perspectives on the sustainability of TB control initiatives in Pakistan at the primary health care (PHC) level.

Methods: Guided by an interpretive epistemology, online in-depth interviews were conducted with 10 public health practitioners who had experience as resource planners in the TB control programme in Pakistan. Thematic content analysis was employed to the textual data as the analytical approach.

Results: Three themes were inductively derived from the thematic analysis: community involvement, stakeholder engagement and efficient use of the PHC system. Community involvement was a determinant in sustaining TB control initiatives. This was attributed to the nature of the disease and prevalent health seeking behaviour. Stakeholder engagement was associated with funding arrangements between public and private partners and considered important in how new initiatives can be made part of the routine structure. Overall, having an efficient PHC system was deemed critical in sustaining current TB control initiatives at the PHC level in Pakistan.

Conclusion: Fostering an enabling operational environment through regulations, supporting the utilization of existing resources, expanding the network of providers, inclusive planning, increasing spending on research and cost-effective testing are pivotal for sustaining the TB control initiatives.
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http://dx.doi.org/10.26719/emhj.21.044DOI Listing
September 2021
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