Evolution of Fagan's Nomogram; a Commentary

I read with interest your paper entitled "Pre and post-test probabilities and Fagan’s nomogram. I would like to add a note concerning an update on Fagan’s Nomogram. In 2011, a group of researchers published a modern version of the nomogram that they named "Bayes’ theorem nomogram"

Pregnancy Screening before Diagnostic Radiography in Emergency Department; an Educational Review

Radiation exposure during pregnancy may have serious teratogenic effects to the fetus. In modern medical practice, there is an increasing dependence on imaging techniques in most medical specialties. Therefore, checking the pregnancy status before imaging women of child bearing age is essential. Lack of international regulations and standard protocols exposes the patient to unexpected fetal radiation effects and the health professionals to medicolegal suits. Recently, the American Academy of Radiology and the European community of Medical Ionizing Radiation Protection released national guidelines regarding pregnancy screening before imaging potentially pregnant females. However, different methods of pregnancy screening exist among different radiology centers. This review aims to discuss the most recent guidelines for imaging females of childbearing age and highlight the need for an international regulation to guide pregnancy screening before radiological exposure

Association of antioxidant nutraceuticals and acetaminophen (paracetamol): Friend or foe?

Acetaminophen (paracetamol or APAP) is an analgesic and antipyretic drug that can induce oxidative stress-mediated hepatotoxicity at high doses. Several studies reported that antioxidant nutraceuticals, in particular phenolic phytochemicals from dietary food, spices, herbs and algae have hepatoprotective effects. Others, however, suggested that they may negatively impact the metabolism, efficacy and toxicity of APAP. The aim of this review is to discuss the pros and cons of the association of antioxidant nutraceuticals and APAP by reviewing the in vivo evidence, with particular reference to APAP pharmacokinetics and hepatotoxicity. Results from the murine models of APAP-induced hepatotoxicity showed amelioration of liver damage with nutraceuticals coadministration, as well as reductions in tissue markers of oxidative stress, and serum levels of hepatic enzymes, bilirubin, cholesterol, triglycerides and inflammatory cytokines. On the other hand, both increased and decreased APAP plasma levels have been reported, depending on the nutraceutical type and route of administration. For example, studies showed that repeated administration of flavonoids causes down-regulation of cytochrome P450 enzymes and up-regulation of uridine diphosphate glucuronosyltransferases (UGT). Moreover, nutraceuticals can alter the levels of APAP metabolites, such as mercapturate glucuronide, sulfate and cysteine conjugates. Overall, the reviewed in vivo studies indicate that interactions between APAP and nutraceuticals or plant foods exist. However, the majority of data come from animal models with doses of phytochemicals far from dietary ones. Human studies should investigate gene-diet interactions, as well as ethnic variability in order to clarify the pros and cons of co-administering antioxidant nutraceuticals and APAP. Keywords: Acetaminophen, Antioxidants, Food-drug interaction, Nutraceuticals, Paracetamo

Awareness of Basic Life Support among Egyptian Medical Students; a Cross-Sectional Study

Introduction: It is important for all medical and paramedical staff to be aware of basic life support (BLS) maneuvers. In this study, we aimed to evaluate the level of BLS awareness among Egyptian medical students.Methods: The level of BLS knowledge was assessed using a validated questionnaire and the results were analyzed using an answer key, prepared from the Advanced Cardiac Life Support (ACLS) manual. We used the Student's t-test to analyze the association between awareness level and year of study, previous BLS training and practical experience.Results: A total of 823 medical students with the mean age of 20.3 ± 2.7 years, from Al-Azhar medical schools completed the questionnaire (463 and 360 in academic and clinical years, respectively). About 72% and 84% of students failed to recognize the proper point of chest compression in adults and infants, respectively. Moreover, the majority (80%) did not know how to give rescue breathing in infants. Only 18% of students correctly identified early signs of shock and only 22% knew how to help patients with myocardial infarction. Being in clinical years, previous BLS training or practical experience were significantly associated with higher BLS knowledge scores (p < 0.001).Conclusion: The level of BLS awareness among Egyptian medical students is generally poor. Introduction of regular BLS courses into the undergraduate curriculum is a must to increase the level of BLS knowledge among Egyptian future physicians

C-Abl inhibition; a novel therapeutic target for Parkinson’s disease

Parkinson’s disease (PD) is the most prevalent movement disorder in the world. The major pathological hallmarks of PD are death of dopaminergic neurons and the formation of Lewy bodies. At the moment, there is no cure for PD; current treatments are symptomatic. Investigators are searching for neuroprotective agents and disease modifying strategies to slow the progress of PD. However, recently, due to the ignorance of the main pathological sequence of PD, many drug targets failed to provide neuroprotective effects in human trials. Currently, a huge amount of evidence suggests the involvement of C-Abelson (c-Abl) tyrosine kinase enzyme in the pathology of PD. C-abl plays a role in PD pathology on the levels of parkin activation, alpha synuclein aggregation, and impaired autophagy of toxic elements. Experimental studies showed that (1) c-abl activation is involved in neuronal death and (2) c-abl inhibition shows neuroprotective effects and prevents dopaminergic neurons’ death. Current evidence from experimental studies and the first in-human trial shows that c-abl inhibition holds the promise for neuroprotection against PD and therefore, justifies the movement towards larger clinical trials. In this review article, we discussed the role of c-abl in PD pathology and the findings of preclinical experiments and the first in-human trial. In addition, based on the lessons of the last decade and current preclinical evidence, we provide recommendations for future research in this area

Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases

Effects of Antioxidant Supplements on the Survival and Differentiation of Stem Cells

Although physiological levels of reactive oxygen species (ROS) are required to maintain the self-renewal capacity of stem cells, elevated ROS levels can induce chromosomal aberrations, mitochondrial DNA damage, and defective stem cell differentiation. Over the past decade, several studies have shown that antioxidants can not only mitigate oxidative stress and improve stem cell survival but also affect the potency and differentiation of these cells. Further beneficial effects of antioxidants include increasing genomic stability, improving the adhesion of stem cells to culture media, and enabling researchers to manipulate stem cell proliferation by using different doses of antioxidants. These findings can have several clinical implications, such as improving neurogenesis in patients with stroke and neurodegenerative diseases, as well as improving the regeneration of infarcted myocardial tissue and the banking of spermatogonial stem cells. This article reviews the cellular and molecular effects of antioxidant supplementation to cultured or transplanted stem cells and draws up recommendations for further research in this area

Quality Assessment of Published Systematic Reviews in High Impact Cardiology Journals: Revisiting the Evidence Pyramid

Objective: Systematic reviews are increasingly used as sources of evidence in clinical cardiology guidelines. In the present study, we aimed to assess the quality of published systematic reviews in high impact cardiology journals. Methods: We searched PubMed for systematic reviews published between 2010 and 2019 in five general cardiology journals with the highest impact factor (according to Clarivate Analytics 2019). We extracted data on eligibility criteria, methodological characteristics, bias assessments, and sources of funding. Further, we assessed the quality of retrieved reviews using the AMSTAR tool. Results: A total of 352 systematic reviews were assessed. The AMSTAR quality score was low or critically low in 71% (95% CI: 65.7–75.4) of the assessed reviews. Sixty-four reviews (18.2%, 95% CI: 14.5–22.6) registered/published their protocol. Only 221 reviews (62.8%, 95% CI: 57.6–67.7) reported adherence to the EQUATOR checklists, 208 reviews (58.4%, 95% CI: 53.9–64.1) assessed the risk of bias in the included studies, and 177 reviews (52.3%, 95% CI: 45.1–55.5) assessed the risk of publication bias in their primary outcome analysis. The primary outcome was statistically significant in 274 (79.6%, 95% CI: 75.1–83.6) and had statistical heterogeneity in 167 (48.5%, 95% CI: 43.3–53.8) reviews. The use and sources of external funding was not disclosed in 87 reviews (24.7%, 95% CI: 20.5–29.5). Data analysis showed that the existence of publication bias was significantly associated with statistical heterogeneity of the primary outcome and that complex design, larger sample size, and higher AMSTAR quality score were associated with higher citation metrics. Conclusion: Our analysis uncovered widespread gaps in conducting and reporting systematic reviews in cardiology. These findings highlight the importance of rigorous editorial and peer review policies in systematic review publishing, as well as education of the investigators and clinicians on the synthesis and interpretation of evidence

Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies

BackgroundCurrent evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality.MethodsPubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach.ResultsTen observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria. The overall combined estimate suggested that statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79 to 0.93]), CVD death (HR: 0.80 [95% CI 0.78 to 0.81]), and stroke (HR: 0.85 [95% CI 0.76 to 0.94]) and a non-significant association with risk of MI (HR 0.74 [95% CI 0.53 to 1.02]). The beneficial association of statins with the risk of all-cause mortality remained significant even at higher ages (> 75 years old; HR 0.88 [95% CI 0.81 to 0.96]) and in both men (HR: 0.75 [95% CI: 0.74 to 0.76]) and women (HR 0.85 [95% CI 0.72 to 0.99]). However, this association with the risk of all-cause mortality remained significant only in those with diabetes mellitus (DM) (HR 0.82 [95% CI 0.68 to 0.98]) but not in those without DM. The level of evidence of all the primary outcomes was rated as "very low."ConclusionsStatin therapy in older people (aged ≥ 65 years) without CVD was associated with a 14%, 20%, and 15% lower risk of all-cause mortality, CVD death, and stroke, respectively. The beneficial association with the risk of all-cause mortality remained significant even at higher ages (> 75 years old), in both men and women, and in individuals with DM, but not in those without DM. These observational findings support the need for trials to test the benefits of statins in those above 75 years of age

Quality Assessment of Published Systematic Reviews in High Impact Cardiology Journals: Revisiting the Evidence Pyramid

Objective: Systematic reviews are increasingly used as sources of evidence in clinical cardiology guidelines. In the present study, we aimed to assess the quality of published systematic reviews in high impact cardiology journals.Methods: We searched PubMed for systematic reviews published between 2010 and 2019 in five general cardiology journals with the highest impact factor (according to Clarivate Analytics 2019). We extracted data on eligibility criteria, methodological characteristics, bias assessments, and sources of funding. Further, we assessed the quality of retrieved reviews using the AMSTAR tool.Results: A total of 352 systematic reviews were assessed. The AMSTAR quality score was low or critically low in 71% (95% CI: 65.7–75.4) of the assessed reviews. Sixty-four reviews (18.2%, 95% CI: 14.5–22.6) registered/published their protocol. Only 221 reviews (62.8%, 95% CI: 57.6–67.7) reported adherence to the EQUATOR checklists, 208 reviews (58.4%, 95% CI: 53.9–64.1) assessed the risk of bias in the included studies, and 177 reviews (52.3%, 95% CI: 45.1–55.5) assessed the risk of publication bias in their primary outcome analysis. The primary outcome was statistically significant in 274 (79.6%, 95% CI: 75.1–83.6) and had statistical heterogeneity in 167 (48.5%, 95% CI: 43.3–53.8) reviews. The use and sources of external funding was not disclosed in 87 reviews (24.7%, 95% CI: 20.5–29.5). Data analysis showed that the existence of publication bias was significantly associated with statistical heterogeneity of the primary outcome and that complex design, larger sample size, and higher AMSTAR quality score were associated with higher citation metrics.Conclusion: Our analysis uncovered widespread gaps in conducting and reporting systematic reviews in cardiology. These findings highlight the importance of rigorous editorial and peer review policies in systematic review publishing, as well as education of the investigators and clinicians on the synthesis and interpretation of evidence