Fixed-Dose Combination (Polypill) for Cardiovascular Disease Prevention: A Meta-Analysis.

INTRODUCTION: This meta-analysis was performed to assess the efficacy of fixed-dose combination (polypill) in reducing the risk of mortality and cardiovascular events. METHODS: Medline, Scopus, Web of Science, and Cochrane Central were searched during May 2021. All randomized trials investigating the efficacy of antihypertensive and lipid-lowering ± antiplatelet drug combinations in patients at cardiovascular risk were included. Outcomes were presented as risk ratios or standardized mean differences with 95% CIs. RESULTS: A total of 16 trials (N = 26,567 participants) were included. The risk reduction for all-cause mortality (risk ratio = 0.90; 95% CI = 0.79, 1.01; I2 = 0%; moderate certainty) and major adverse cardiac events (risk ratio=0.84; 95% CI=0.68, 1.04; I2=51%; very low certainty) did not reach statistical significance in comparison with those of the control group. Subgroup analysis of studies that used an active control yielded similar results. However, significant reductions in major adverse cardiac event risk were observed in studies that exclusively targeted primary prevention, followed patients for ≥4 years, and had a low risk of bias. The polypill group had significantly higher adherence (risk ratio=1.18; 95% CI=1.06, 1.32; I2=96%; very low certainty) and comprable rates of adverse side effects (risk ratio=1.10; 95% CI=0.98, 1.23; I2=58%; moderate certainty) with those of the control group. Patients randomized to the polypill had significant reductions in systolic and diastolic blood pressure as well as in total and low-density lipoprotein cholesterol. DISCUSSION: Despite reductions in cardiovascular risk factors, the observed mortality benefit for the polypill did not reach statistical significance. Further studies are needed to validate its clinical benefits and determine the patient populations likely to achieve such benefits.

Break the Silence: Knowledge and Attitude Towards Sexual and Reproductive Health Among Egyptian Youth.

Sexual health and education are rarely investigated in the Middle East countries, including Egypt. We performed the current study to investigate the knowledge, attitudes and behaviors towards sexual health practices among Egyptian youth. A self-administered questionnaire was translated from English to Arabic. After pilot-testing, the eligible population was invited to fill it online. Nine-hundred and fifty-five participants filled the questionnaire (53% males and 88.5% single). Around 61% of the participants were of the opinion that sexual education is necessary and rejected the notion that sexual education is religiously prohibited. Only 26% discussed sex-related matters with a parent. Although over 80% think that masturbation is either prohibited, wrong or medically harmful, 62% have masturbated before. Living with parents was not associated with less masturbation (p = 0.23). Moreover, although 85% of the participants think that watching pornography is either wrong or prohibited, 74% have watched porn clips before (significantly more frequent among males: p < 0.0001). A quarter of the responders indicated that they have been touched by a stranger/relative against their will. In conclusion, the majority of surveyed Egyptian youth expressed unfavorable attitudes towards masturbation and watching pornography -despite being quite common- and supported the importance of sexual education.

Carnosic acid alleviates chlorpyrifos-induced oxidative stress and inflammation in mice cerebral and ocular tissues.

Chlorpyrifos is an organophosphate pesticide whose exposure leads to inhibition of acetylcholinesterase (AChE) enzyme and induces oxidative stress, inflammation, and neurotoxicity. The current study was designed to evaluate the efficacy of carnosic acid (CA) in ameliorating CPF-induced cytotoxicity in mice brain and eye tissues. We allocated 40 male Swiss albino mice to receive DMSO 1% solution, oral CA 60 mg/kg/day bw, CPF 12 mg/kg/day bw via gastric gavage, or CPF plus CA at 30 and 60 mg/kg/day bw. Carnosic acid was administered once/day for 14 days, while CPF was administered in the last 7 days of the experiment. Biochemical analysis showed that CPF administration was associated with significant increases in the serum concentrations of interleukin-1ß, IL-6, and tumor necrosis factor-α, while it was associated with significant reductions in serum AChE levels in mice. Moreover, CPF-intoxicated mice exhibited significantly higher levels of malondialdehyde and nitric oxide in the brain and eye tissues. However, they had significantly lower levels of reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase in comparison with normal controls. Pretreatment with CA at 30 and 60 mg/kg/day bw for 14 days significantly alleviated all the aforementioned CPF-induced alterations in a dose-dependent manner; more frequent restorations of the normal control ranges were observed in the higher dose group. In conclusion, CA offers a neuroprotective effect against CPF-induced oxidative stress and inflammation and should be further studied in upcoming experimental and clinical research.

Early versus delayed removal of indwelling urinary catheter after elective cesarean delivery: systematic review and meta-analysis of randomized controlled trials.

Background: Timing of removal of the indwelling urinary catheter after elective cesarean delivery (CD) is controversial. Early removal could be associated with fewer urinary symptoms.Objective: This review aims to evaluate the evidence from published randomized clinical trials (RCTs) about the outcomes of early versus delayed removal of indwelling urinary catheter after elective cesarean delivery (CD).Data sources: Electronic databases were searched using the following MeSH terms (early Or Late Or immediate OR delayed removal) AND (Urinary catheter) AND (cesarean section OR cesarean delivery OR CS)Methods of study selection: All RCTs assessing the timing of removal of urinary catheter were considered for this meta-analysis. One hundred seventy-two studies were identified of which three studies deemed eligible for this review. Quality and risk of bias assessment were performed for all studies.Data extraction: Two researchers independently extracted the data from the individual articles and entered into RevMan software. The relative risk (RR), the weighted mean difference (WMD) and 95% confidence interval (CI) were calculated. The extracted outcomes were significant bacteriuria, urinary symptoms (urinary retention necessitating re-catheterization, dysuria, urinary frequency, urgency) postoperative oral rehydration and length of hospital stay.Results: Three RCTs (early removal: n = 298 and delayed removal: n = 311) were included. The pooled estimate showed that early removal significantly reduced dysuria (RR = 0.60, 95% CI [0.38, 0.95], p=.03), urinary frequency (RR = 0.32, 95% CI [0.16, 0.66], p=.002) and significant bacteriuria (RR = 0.49, 95% CI [0.30, 0.83], p=.007) than delayed removal.Conclusions: This meta-analysis suggests that early removal of the indwelling urinary catheter in patients who underwent elective CD showed significant less dysuria, less urinary frequency and a decrease in the incidence of significant bacteriuria.

Mesenchymal Stem Cell Therapy for Doxorubicin-Induced Cardiomyopathy: Potential Mechanisms, Governing Factors, and Implications of the Heart Stem Cell Debate.

Over the past decades, researchers have reported several mechanisms for doxorubicin (DOX)-induced cardiomyopathy, including oxidative stress, inflammation, and apoptosis. Another mechanism that has been suggested is that DOX interferes with the cell cycle and induces oxidative stress in C-kit+ cells (commonly known as cardiac progenitor cells), reducing their regenerative capacity. Cardiac regeneration through enhancing the regenerative capacity of these cells or administration of other stem cells types has been the axis of several studies over the past 20 years. Several experiments revealed that local or systemic injections with mesenchymal stem cells (MSCs) were associated with significantly improved cardiac function, ameliorated inflammatory response, and reduced myocardial fibrosis. They also showed that several factors can affect the outcome of MSC treatment for DOX cardiomyopathy, including the MSC type, dose, route, and timing of administration. However, there is growing evidence that the C-kit+ cells do not have a cardiac regenerative potential in the adult mammalian heart. Similarly, the protective mechanisms of MSCs against DOX-induced cardiomyopathy are not likely to include direct differentiation into cardiomyocytes and probably occur through paracrine secretion, antioxidant and anti-inflammatory effects. Better understanding of the involved mechanisms and the factors governing the outcomes of MSCs therapy are essential before moving to clinical application in patients with DOX-induced cardiomyopathy.

Health Benefits of Polyphenols and Carotenoids in Age-Related Eye Diseases.

Oxidative stress and inflammation play a critical role in the initiation and progression of age-related ocular abnormalities as cataract, glaucoma, diabetic retinopathy, and macular degeneration. Therefore, phytochemicals with proven antioxidant and anti-inflammatory activities, such as carotenoids and polyphenols, could be of benefit in these diseases. We searched PubMed and Web of Science databases for original studies investigating the benefits of different carotenoids and polyphenols in age-related ophthalmic diseases. Our results showed that several polyphenols (such as anthocyanins, Ginkgo biloba, quercetin, and resveratrol) and carotenoids (such as lutein, zeaxanthin, and mezoxanthin) have shown significant preventive and therapeutic benefits against the aforementioned conditions. The involved mechanisms in these findings include mitigating the production of reactive oxygen species, inhibiting the tumor necrosis factor-α and vascular endothelial growth factor pathways, suppressing p53-dependent apoptosis, and suppressing the production of inflammatory markers, such as interleukin- (IL-) 8, IL-6, IL-1a, and endothelial leucocyte adhesion molecule-1. Consumption of products containing these phytochemicals may be protective against these diseases; however, adequate human data are lacking. This review discusses the role and mechanisms of polyphenols and carotenoids and their possible synergistic effects on the prevention and treatment of age-related eye diseases that are induced or augmented by oxidative stress and inflammation.

Adipose-derived stem cells: Effectiveness and advances in delivery in diabetic wound healing.

With the increasing global prevalence of diabetes mellitus, a significant rise in the number of patients suffering from non-healing wounds is expected. However, available treatments, such as revascularization surgery and foot care education are often insufficient to ensure satisfactory wound healing. One therapeutic strategy that has been identified as particularly promising utilizes adipose-derived stem cells (ADSCs). Through a comprehensive literature search of published and ongoing studies, we aimed to provide an overview of the experimental basis, the scientific background, and advances in the delivery of ADSCs for treating non-healing diabetic wounds. ADSCs have the capacity to differentiate into multiple cell lineages and are considered an alternative to bone marrow-derived mesenchymal stem cells. They can be easily extracted from the adipose tissue and are capable of in-vitro expansion. The reviewed experimental studies showed that ADSCs can enhance diabetic wound healing through increasing epithelialization and granulation tissue formation, anti-inflammatory and anti-apoptotic effects, and release of angiogenic cytokines. Moreover, few small clinical trials showed that ADSCs treatment in patients with diabetic ulcers caused enhanced ulcer evolution, lower pain scores, and improved claudication walking distances with no reported complications. In conclusion, ADSCs have a promising potential in the regenerative therapy of chronic diabetic wounds. However, larger studies should confirm their efficacy and long-term safety in diabetic patients.

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.

Intranasal sumatriptan for acute migraine attacks: a systematic review and meta-analysis.

We performed this systematic review and meta-analysis to evaluate the tolerability and efficacy of intranasal sumatriptan, a selective serotonin agonist, compared to placebo or other migraine therapeutics for the treatment of acute migraine attacks. We searched PubMed, SCOPUS, Embase, and Cochrane CENTRAL for relevant randomized controlled trials (RCTs). Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. We performed subgroup and meta-regression analyses for different doses and treatment endpoints. Sixteen RCTs (n = 5925 patients) matched our inclusion criteria. The overall effect-estimate showed that intranasal sumatriptan was superior to placebo in terms of pain relief (RR = 1.70, 95% CI [1.31, 2.21], p < 0.0001) and headache relief (RR = 1.58, 95% CI [1.35, 1.84], p < 0.00001) at 2 h. Although sumatriptan was superior to placebo in terms of headache relief at 30 min (RR = 1.31, 95% CI [1.08, 1.59], p = 0.005), no significant difference was found between both groups in terms of the frequency of pain-free participants at 30 min (RR = 1.18, 95% CI [0.49, 2.88], p = 0.71). Subgroup analysis and meta-regression models showed that increasing the dose of sumatriptan reduced the time needed for headache relief; however, this clinical improvement with higher doses was associated with more frequent adverse events in comparison to smaller doses. In conclusion, intranasal sumatriptan is effective for the treatment of acute migraine attacks. However, it was associated with a six-fold increase in the risk of taste disturbance, compared to the placebo. Future RCTs are recommended to provide head-to-head comparison of different administration routes and drug formulations of sumatriptan.

Cutting electrocautery versus scalpel for surgical incisions: a systematic review and meta-analysis.

BACKGROUND: Although cutting electrocautery can be superior to the scalpel in reducing blood loss and incisional time, several reports associated electrocautery with higher rates of wound infection, impaired healing, and worse cosmesis. We performed this systematic review and meta-analysis to compare cutting electrocautery versus scalpel for surgical incisions. MATERIALS AND METHODS: We conducted a computerized literature search of five electronic databases and included all published original studies comparing cutting electrocautery and scalpel surgical incisions. Relevant data were extracted from eligible studies and pooled as odds ratios (ORs) or standardized mean difference (SMD) values in a meta-analysis model, using RevMan and Comprehensive Meta-analysis software. RESULTS: Forty-one studies (36 randomized trials, four observational, and one quasirandom study) were included in the pooled analysis (6422 participants). Compared with the scalpel incision, cutting electrocautery resulted in significantly less blood loss (SMD = -1.16, 95% CI [-1.60 to -0.72]), shorter incisional (SMD = -0.63, 95% CI [-0.96 to -0.29]) and operative times (SMD = -0.59, 95% CI [-1.12 to -0.05]), and lower pain scores (SMD = -0.91, 95% CI [-1.27 to -0.55]) with no significant differences in terms of wound infection rates (OR = 0.92, 95% CI [0.74-1.15]) or overall subjective scar score (SMD = -0.49, 95% CI [-1.72 to 0.75]). CONCLUSIONS: Surgical incision using electrocautery can be quicker with less blood loss and postoperative pain scores than the scalpel incision. No statistically significant difference was found between both techniques in terms of postoperative wound complications, hospital stay duration, and wound cosmetic characteristics. Therefore, we recommend routine use of cutting electrocautery for surgical incisions.

Meta-Analysis of Creatine for Neuroprotection Against Parkinson's Disease.

BACKGROUND: Creatine is an antioxidant agent that showed neuroprotective effects in animal models of Parkinson's disease (PD). Creatine was selected by the National Institute of Neurological Disorders and Stroke as a possible disease modifying agent for Parkinson's disease. Therefore, many clinical trials evaluated the efficacy of creatine for patients with PD. The aim of this systematic review and meta-analysis is to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of Creatine for patients with PD. METHODS: We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search for PubMed, EBSCO, web of science and Ovid Midline was carried out. We included RCTs comparing creatine with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, and UPDRS III were pooled as mean difference (MD) between two groups from baseline to the endpoint. Statistical heterogeneity was assessed by visual inspection of the forest plot and measured by chi-square and I square tests. RESULTS: Three RCTs (n=1935) were included in this study. The overall effect did not favor either of the two groups in terms of: UPDRS total score (MD 1.07, 95% CI [3.38 to 1.25], UPDRS III (MD 0.62, 95% CI [2.27 to 1.02]), UPDRS II (MD 0.03, 95% CI [0.81 to 0.86], or UPDRS I (MD 0.03, 95% CI [0.33 to 0.28]). CONCLUSION: Current evidence does not support the use of creatine for neuroprotection against PD. Future well-designed, randomized controlled trials are needed.

Sunitinib alone or in combination with chemotherapy for the treatment of advanced breast cancer: A systematic review and meta-analysis.

INTRODUCTION: Sunitinib is an orally delivered tyrosine kinase inhibitor that exhibits antiangiogenic effects. FDA has approved sunitinib for the treatment of metastatic renal cell carcinoma. However, its efficacy for the treatment of advanced breast cancer (ABC) remains controversial. Therefore, we performed this systematic review and meta-analysis to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of sunitinib alone and in combination with chemotherapy for the treatment of ABC. METHODS: We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search of PubMed, SCOPUS, web of knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL) has been conducted using relevant keywords. Studies were screened for eligibility and data were extracted to an online data extraction form. Progression free survival (PFS) and overall survival (OS) were pooled as Hazard ratio (HR) in a meta-analysis model using generic inverse variance method. Objective response rate (ORR) and complications were pooled as relative risk (RR) in a random effect model meta-analysis using Mantel-Haenzel method. RESULTS: Six RCTs, with a total sample size of 2273 patients, met our eligibility criteria and were included in this meta-analysis. Sunitinib monotherapy was not superior to chemotherapy in terms of PFS (HR = 1.00, 95% CI [0.86 to 1.16], P = 0.99), OS (HR = 1.07; 95% CI [0.87 to 1.32], P = 0.5), or ORR (RR = 0.70, 95% CI [0.74 to 1.03], P = 0.07). Sunitinib in combination with chemotherapy did not show superiority to chemotherapy in terms of PFS (HR = 0.99, 95% CI [0.86 to 1.14], P = 0.89) and OS (HR = 1.04, 95% CI [0.85 to 1.28], P = 0.69). However, the ORR favored sunitinib in combination with chemotherapy group (RR = 1.15, 95% CI [1.01 to 1.31]) with a statistically significant P value (P = 0.03). CONCLUSIONS: Current evidence shows that sunitinib, either alone or in combination with chemotherapy, has no clinical benefit for patients with advanced breast cancer. However, previous studies did not considered patient stratification and outcome assessment based on molecular markers. In terms of safety, toxicity was common with sunitinib treatment.