Optimizing Screening for Intrastriatal Interventions in Huntington's Disease Using Predictive Models.

BACKGROUND: Intrastriatal delivery of potential therapeutics in Huntington's disease (HD) requires sufficient caudate and putamen volumes. Currently, volumetric magnetic resonance imaging is rarely done in clinical practice, and these data are not available in large research cohorts such as Enroll-HD. OBJECTIVE: The objective of this study was to investigate whether predictive models can accurately classify HD patients who exceed caudate and putamen volume thresholds required for intrastriatal therapeutic interventions. METHODS: We obtained and merged data for 1374 individuals across three HD cohorts: IMAGE-HD, PREDICT-HD, and TRACK-HD/TRACK-ON. We imputed missing data for clinical variables with >72% non-missing values and used the model-building algorithm BORUTA to identify the 10 most important variables. A random forest algorithm was applied to build a predictive model for putamen volume >2500 mm3 and caudate volume >2000 mm3 bilaterally. Using the same 10 predictors, we constructed a logistic regression model with predictors significant at P < 0.05. RESULTS: The random forest model with 1000 trees and minimal terminal node size of 5 resulted in 83% area under the curve (AUC). The logistic regression model retaining age, CAG repeat size, and symbol digit modalities test-correct had 85.1% AUC. A probability cutoff of 0.8 resulted in 5.4% false positive and 66.7% false negative rates. CONCLUSIONS: Using easily obtainable clinical data and machine learning-identified initial predictor variables, random forest, and logistic regression models can successfully identify people with sufficient striatal volumes for inclusion cutoffs. Adopting these models in prescreening could accelerate clinical trial enrollment in HD and other neurodegenerative disorders when volume cutoffs are necessary enrollment criteria. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Efficacy of therapeutic plasma exchange in patients with severe COVID-19: A systematic review and meta-analysis.

We conducted this systematic review and meta-analysis to evaluate the existing evidence and to quantitatively synthesise evidence on the impact of therapeutic plasma exchange (TPE) on severe COVID-19 patients. This systematic review and meta-analysis protocol was prospectively registered on PROSPERO (CRD42022316331). We systemically searched six electronic databases (PubMed, Scopus, Web of Science, ScienceDirect, clinicaltrial.gov, and Cochrane Central Register of Controlled Trials) from inception until 1 June 2022. We included studies comparing patients who received TPE versus those who received the standard treatment. For risk of bias assessment, we used the Cochrane risk of bias assessment tool, the ROBINS1 tool, and the Newcastle Ottawa scale for RCTs, non-RCTs, and observational studies, respectively. Continuous data were pooled as standardized mean difference (SMD), and dichotomous data were pooled as risk ratio in the random effect model with the corresponding 95% confidence intervals (CI). Thirteen studies (one randomized controlled trials (RCT) and 12 non-RCTs) were included in the meta-analysis, with a total of 829 patients. There is a moderate-quality evidence from one RCT that TPE reduces the lactic dehydrogenase (LDH) levels (SMD -1.09, 95% CI [-1.59 to -0.60]), D-dimer (SMD -0.86, 95% CI [-1.34 to -0.37]), and ferritin (SMD -0.70, 95% CI [-1.18 to -0.23]), and increases the absolute lymphocyte count (SMD 0.54, 95% CI [0.07-1.01]), There is low-quality evidence from mixed-design studies that TPE was associated with lower mortality (relative risk 0.51, 95% CI [0.35-0.74]), lower IL-6 (SMD -0.91, 95% CI [-1.19 to -0.63]), and lower ferritin (SMD -0.51, 95% CI [-0.80 to -0.22]) compared to the standard control. Among severely affected COVID-19 patients, TPE might provide benefits such as decreasing the mortality rate, LDH, D-dimer, IL-6, and ferritin, in addition to increasing the higher absolute lymphocyte count. Further well-designed RCTs are needed.

Physical therapy interventions for the management of hand tremors in patients with Parkinson's disease: a systematic review.

BACKGROUND: Several physical therapy modalities have been used to improve hand tremors in patients with Parkinson's disease (PD). However, little is known about the efficacy of these techniques. Therefore, we conducted this study to synthesize evidence from published studies on the efficacy of physical therapy techniques for hand tremors in PD patients. METHODS: We followed the PRISMA statement and Cochrane handbook guidelines when conducting this study. We conducted an electronic literature search of PubMed, Cochrane Central Register of Clinical Trials, Web of Science, Ovid, and Embase, and then we selected clinical trials assessing the efficacy of any physical therapy intervention for hand tremors in patients with PD. Study outcomes were extracted, and evidence was synthesized narratively. RESULTS: A total of six modalities described in six studies were included in this systematic review. Out of the six interventions, the tremor's glove and electrical stimulation showed significant improvements in root mean square angular velocity (59% and 43.8%, respectively) and UPDRS tremor score (P < 0.05 for both). Also, eccentric exercises were associated with significant reductions in the mean resting tremor amplitude (P < 0.05). These data were dependent on single studies; therefore, a meta-analysis was not feasible. CONCLUSION: Several physical therapy interventions, such as electrical stimulation, exercises, transcranial low voltage pulsed electromagnetic fields, weights, and virtual reality showed promising results in reducing hand tremors. However, this evidence was based on a limited number of included studies, and more RCTs with larger sample sizes are required to confirm the efficacy of these interventions.

Efficacy of Hibiscus sabdariffa on Reducing Blood Pressure in Patients With Mild-to-Moderate Hypertension: A Systematic Review and Meta-Analysis of Published Randomized Controlled Trials.

We aimed to assess the efficacy of Hibiscus sabdariffa in patients with mild-to-moderate hypertension or metabolic syndrome (MetS) by comparing it against placebo, antihypertensive drugs, or other herbal products. Four databases were searched for randomized clinical trials (RCTs) examining the efficacy of H. sabdariffa in patients with mild-to-moderate hypertension or hypertension associated with MetS. Data on the change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were extracted and analyzed using Review Manager Version 5.3. A total of 13 RCTs (1205 participants) were analyzed. Hibiscus sabdariffa significantly reduced both SBP and DBP compared with placebo (mean difference -6.67, P = 0.004 and -4.35 mm Hg, P = 0.02). Subgroup analysis showed that change in SBP and DBP was statistically significant in patients with only hypertension, whereas not significant in patients with hypertension associated with MetS. When H. sabdariffa was compared with active controls (antihypertensive drugs or other herbals), the change in SBP and DBP was not statistically significant (all P > 0.05). Hibiscus sabdariffa is effective in reducing the SBP and DBP in patients with mild-to-moderate hypertension, but was neither effective in those with MetS nor superior to antihypertensive drugs. Further RCTs are required to determine the long-term efficacy of H. sabdariffa and to describe patients who would benefit most from this treatment.

A systematic review of vaccine-induced thrombotic thrombocytopenia in individuals who received COVID-19 adenoviral-vector-based vaccines.

Reports of thrombotic response after receiving COVID-19 Adenoviral-Vector Based Vaccines raise concerns about vaccine-induced thrombotic thrombocytopenia (VITT); therefore, we conduct this systematic review to report susceptible demographics outcomes, commonalities, and prognosis of reporting cases. We identified published articles by searching PubMed, SCOPUS, and Web of Science from December 2020 till May 2021, with an updated search in September 2021. All case reports and case series reporting thrombotic response after receiving COVID-19 Adenoviral-Vector Based Vaccines were eligible for including. In addition, two authors independently extracted data and assessed the quality of the included studies. A total of 157 patients with thrombotic events after the ChAdOx1 nCoV-19 vaccine and 16 patients with thrombotic events after Ad26.COV2. S vaccine was included in our study. 72% of the ChAdOx1 nCoV-19 cases were females, while in Ad26.COV2.S subgroup, all reported patients were females. The commonest presentations were deep vein thrombosis 20 (12.7%) and cerebral venous sinus thrombosis 18 (11.5%) in the ChAdOx1 nCoV-19 subgroup while cerebral venous sinus thrombosis 14 (87.5%) and pulmonary embolism 2 (12.5%) in the Ad26.COV2. S subgroup. In this study, we described the certain demographics associated with VITT and the clinical presentations of those cases in the ChAdOx1 nCoV-19 and Ad26.COV2. S vaccines. Young individuals, particularly females, may be more susceptible to VITT, and future studies should seek to confirm this association. In addition, the clinical presentation of VITT commonly includes cerebral thrombi, pulmonary embolism, and deep venous thrombosis, but other presentations are also possible, highlighting the importance of clinical vigilance in recent vaccine recipients.

Intravenous thrombolysis before mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion; should we cross that bridge? A systematic review and meta-analysis of 36,123 patients.

BACKGROUND: The use of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) is a debatable subject in the field of neuro-interventional surgery. We conducted this systematic review and meta-analysis to synthesize evidence from published studies on the outcomes of IVT + MT compared with MT alone in AIS-LVO patients. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to January 2022 for relevant clinical trials and observational studies. Eligible studies were identified, and all relevant outcomes were pooled in the meta-analysis DerSimonian-Liard random-effects model. RESULTS: Forty-nine studies, with a total of 36,123 patients, were included in this meta-analysis. IVT + MT was significantly superior to MT alone in terms of successful recanalization (RR 1.06, 95% CI 1.03 to 1.09), mortality (RR 0.75, 95% CI 0.68-0.82), favorable functional outcome (RR 1.21, 95% CI 1.13 to 1.29), and complete recanalization (RR 1.06, 95% CI 1.00 to 1.11). There were no significant differences between the two groups in terms of improvement of the National Institute of Health Stroke Scale (NIHSS) score at 24 h or at discharge (p > 0.05). Complications including symptomatic intracranial hemorrhage, symptomatic intracerebral hemorrhage (sICH), procedure-related complications, and parenchymal hematoma were comparable between the two groups (p > 0.05). CONCLUSION: For AIS-LVO, IVT + MT is associated with slightly better rates of survival, successful and complete recanalization, and favorable functional outcome as compared with MT alone. Further clinical trials are needed to corroborate such benefits of bridging IVT.

Tranexamic acid for patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of 2991 patients.

OBJECTIVE: We aimed to synthesize evidence from published clinical trials on the efficacy and safety of tranexamic acid (TXA) administration in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We followed the standard methods of the Cochrane Handbook of Systematic Reviews for interventions and the PRISMA statement guidelines 2020 when conducting and reporting this study. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until 1 January 2022. We selected observational studies and clinical trials comparing TXA versus no TXA in aSAH patients. Data of all outcomes were pooled as the risk ratio (RR) with the corresponding 95% confidence intervals in the meta-analysis models. RESULTS: Thirteen studies with a total of 2991 patients were included in the analysis. TXA could significantly cut the risk of rebleeding (RR 0.56, 95% CI 0.44 to 0.72) and mortality from rebleeding (RR 0.60, 95% CI 0.39 to 0.92, p = 0.02). However, TXA did not significantly improve the overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus (all p > 0.05). In terms of safety, no significant adverse events were reported. No statistical heterogeneity or publication bias was found in all outcomes. CONCLUSION: In patients with aSAH, TXA significantly reduces the incidence of rebleeding and mortality from rebleeding. However, current evidence does not support any benefits in overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus.

Comment on Abbas et al. The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Medicina 2022, 58, 213.

We read with interest the article by Abbas et al. [...].

Mavoglurant (AFQ056) for the treatment of levodopa-induced dyskinesia in patients with Parkinson's disease: a meta-analysis.

BACKGROUND: Mavoglurant (AFQ056), a selective metabotropic glutamate receptor 5 (mGluR5) inhibitor, was tested for t levodopa-induced dyskinesia (LID) in patients with Parkinson's Disease (PD). However, clinical trials showed inconsistent results regarding the efficacy of mavoglurant in treating LID in patients with Parkinson's disease (PD). METHODS: A computer literature search of PubMed, Scopus, Web of science, and Cochrane CENTRAL was conducted until March 2021. We selected relevant randomized controlled trials comparing mavoglurant to placebo. Study data were extracted and pooled as mean difference (MD) in the meta-analysis model. RESULTS: Six RCTs were included in this meta-analysis with a total of 485 patients. Mavoglurant was not significantly superior to placebo in terms of the "off-time" (MD -0.27 h, 95% CI -0.65 to 0.11), "on time" (MD 0.29 h, 95% CI -0.09 to 0.66), Lang-Fahn activities of daily living dyskinesia scale (MD -0.95, 95% CI -1.98 to 0.07), UPDRS-III (MD -0.51, 95% CI -1.66 to 0.65), or UPDRS-IV (MD -0.41, 95% CI -0.85 to 0.03). However, the pooled modified abnormal involuntary movement scale favored the mavoglurant group than the placebo group (MD -2.53, 95% CI -4.23 to -0.82). CONCLUSIONS: This meta-analysis provides level one evidence that mavoglurant is not effective in treating the LID in patients with PD.

Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent.

Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders and possible effective therapeutics have not yet been precisely identified. This necessitates developing multi-target treatments, which would simultaneously modulate neuroinflammation, apoptosis, and oxidative stress. The present review aims to explore the potential therapeutic use of astaxanthin (ASX) in neurological and neuroinflammatory diseases. ASX, a member of the xanthophyll group, was found to be a promising therapeutic anti-inflammatory agent for many neurological disorders, including cerebral ischemia, Parkinson's disease, Alzheimer's disease, autism, and neuropathic pain. An effective drug delivery system of ASX should be developed and further tested by appropriate clinical trials.

An updated review of mesoporous carbon as a novel drug delivery system.

The nanotechnology approach has been recently adopted to provide more reliable, effective, controlled, and safe drug delivery systems. Nanostructured materials have gained great interest, including siliceous and carbonaceous nanoparticles. The effectiveness of mesoporous carbon nanoparticles (MCNs) in tumor imaging, targeting, and treatment is urging for more future studies. MCNs possess superior properties such as their biocompatibility, large surface area, large pore volume, tunability, and more responsive behavior to internal and external release triggers. These outstanding features make MCNs more applicable for stimuli-responsive drug delivery than the conventional forms of mesoporous silica nanoparticles (MSNs) and other carbon nanoparticles. In this review, we outlined the latest updates regarding the safety, benefits, and potential applications of MCNs.

Neural Stem Cell-Based Therapies and Glioblastoma Management: Current Evidence and Clinical Challenges.

Gliomas, which account for nearly a quarter of all primary CNS tumors, present significant contemporary therapeutic challenges, particularly the highest-grade variant (glioblastoma multiforme), which has an especially poor prognosis. These difficulties are due to the tumor's aggressiveness and the adverse effects of radio/chemotherapy on the brain. Stem cell therapy is an exciting area of research being explored for several medical issues. Neural stem cells, normally present in the subventricular zone and the hippocampus, preferentially migrate to tumor masses. Thus, they have two main advantages: They can minimize the side effects associated with systemic radio/chemotherapy while simultaneously maximizing drug delivery to the tumor site. Another feature of stem cell therapy is the variety of treatment approaches it allows. Stem cells can be genetically engineered into expressing a wide variety of immunomodulatory substances that can inhibit tumor growth. They can also be used as delivery vehicles for oncolytic viral vectors, which can then be used to combat the tumorous mass. An alternative approach would be to combine stem cells with prodrugs, which can subsequently convert them into the active form upon migration to the tumor mass. As with any therapeutic modality still in its infancy, much of the research regarding their use is primarily based upon knowledge gained from animal studies, and a number of ongoing clinical trials are currently investigating their effectiveness in humans. The aim of this review is to highlight the current state of stem cell therapy in the treatment of gliomas, exploring the different mechanistic approaches, clinical applicability, and the existing limitations.

Diagnostic Accuracy of Dual-Energy CT in Detection of Acute Pulmonary Embolism: A Systematic Review and Meta-Analysis.

PURPOSE: In this systematic review and meta-analysis, we aimed to investigate the accuracy of dual-energy computed tomography (DECT) in the detection of acute pulmonary embolism (PE). METHODS: We searched Medline (via PubMed), EBSCO, Web of Science, Scopus, and the Cochrane Library for relevant published studies. We selected studies assessing the accuracy of DECT in the detection of PE. Quality assessment of bias and applicability was conducted using the Quality of Diagnostic Accuracy Studies-2 tool. Meta-analysis was performed to calculate mean estimates of sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). The summary receiver operating characteristic (sROC) curve was drawn to get the Cochran Q-index and the area under the curve (AUC). RESULTS: Seven studies were included in our systematic review. Of the 182 patients included, 108 patients had PEs. The pooled analysis showed an overall sensitivity and specificity of 88.9% (95% confidence interval [CI]: 81.4%-94.1%) and 94.6% (95% CI: 86.7%-98.5%), respectively. The pooled PLR was 8.186 (95% CI: 3.726-17.986), while the pooled NLR was 0.159 (95% CI: 0.093-0.270). Cochran-Q was 0.8712, and AUC was 0.935 in the sROC curve. CONCLUSION: Dual-energy computed tomography shows high sensitivity, specificity, and diagnostic accuracy in the detection of acute PE. The high PLR highlights the high clinical importance of DECT as a prevalence-independent, rule-in test. Studies with a larger sample size with standardized reference tests are still needed to increase the statistical power of the study and support these findings.

Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson's disease: a systematic review and metaanalysis.

BACKGROUND: Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson's disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS. METHODS: A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows). RESULTS: Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=-0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=-0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=-0.05, p=0.65; WAIS-R digit symbol: SMD=-0.16, p=0.29; Trail Making Test Part B: SMD=-0.14, p=0.23; Stroop color-word interference: SMD=-0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=-0.04, p=0.73, and unilateral DBS SMD=-0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=-0.09, p=0.37, and unilateral DBS SMD=-0.29, p=0.22; Boston Naming Test: SMD=-0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11). CONCLUSIONS: There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.

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.

Meta-Analysis of Grazoprevir plus Elbasvir for Treatment of Hepatitis C Virus Genotype 1 Infection.

BACKGROUND AND AIM: Grazoprevir is an NS3/4A protease inhibitor (PI), while elbasvir is an NS5A inhibitor. We performed this meta-analysis to directly compare grazoprevir plus elbasvir and ribavirin regimen vs. grazoprevir and elbasvir without ribavirin in the treatment of hepatitis C virus genotype 1 infection and to precisely evaluate the efficacy of the latter regimen in cirrhotic, IL28 CC genotype patients and those coinfected with human immunodeficiency virus. MATERIAL AND METHODS: A computer literature search of PubMed, Scopus, EBSCO, Embase, and Cochrane central was conducted. Studies were screened for eligibility. Sustained virologic response (SVR) rates were pooled using OpenMeta[Analyst] software for windows. A subgroup analysis was performed to stratify the treatment efficacy according to the different baseline characteristics of HCV patients. RESULTS: Eight randomized controlled trials (n = 1,297 patients) were pooled in the final analysis. The overall SVR rate was 96.6% with 95% CI [95.5% to 98%]. For cirrhotic patients, the SVR rate was 95.7% with 95% CI [93.9% to 97.5%] and for non-cirrhotic patients, the SVR rate was 97% with 95% CI [95.9% to 98.4%]. Furthermore, the addition of ribavirin (RBV) to the treatment regimen did not significantly improve the SVR (RR 1.003, 95% CI [0.944 to 1.065]). The dual regimen was effective in patient populations with NS3 resistance-associated (RAS). However, this regimen achieved lower SVR rates (< 90%) in patients with NS5A RAS. CONCLUSIONS: We conclude that the 12-week treatment regimen of the fixed dose combination of grazoprevir plus elbasvir achieved high SVR rates in patients with HCV genotype 1 infection. The addition of ribavirin to this regimen did not add a significant benefit.

Tobacco smoking in Egypt: a scoping literature review of its epidemiology and control measures.

BACKGROUND: According to World Health Organization (WHO) reports, the prevalence of smoking is increasing in many developing countries, including Egypt. The aim of this study is to summarize the published data in the literature about tobacco smoking in Egypt. METHODS: A computerized literature search of PubMed and relevant Egyptian journals was conducted using the relevant keywords. The findings of retrieved studies were extracted and discussed in a narrative approach. RESULTS: Our search retrieved 44 relevant studies. The most updated prevalence of tobacco smoking in Egypt is 22% in 2010 and is increasing. Highly significant odds ratios were reported for sibling, parent, and peer smoking as risk factors for smoking. Cardiovascular disorders, malignant tumors, and erectile dysfunction are common complications of smoking in the Egyptian population. Efforts to control tobacco smoking are available, but inadequate. CONCLUSIONS: Tobacco smoking is a prevalent health problem in Egypt, associated with cardiovascular disorders and malignant tumors. Health education programmes should be delivered through mass media and school-based programmes to reach a large section of the Egyptian population.

Efficacy and safety of atazanavir/ritonavir-based antiretroviral therapy for HIV-1 infected subjects: a systematic review and meta-analysis.

Atazanavir (ATZ) is a well-tolerated protease inhibitor that can be boosted with ritonavir (r) to treat infection with resistant strains of human immunodeficiency virus 1 (HIV-1). The aim of this meta-analysis was to compare the efficacy, safety, and metabolic effects of ATZ/r regimen versus commonly used antiretroviral drugs such as lopinavir (LPV) and darunavir (DRV) in HIV-1-infected patients. We searched PubMed, Scopus, Embase and Cochrane CENTRAL, using relevant keywords. Data were extracted from eligible randomized trials and pooled as risk ratios (RR) or standardized mean differences (SMD) in a meta-analysis model using RevMan software. Nine randomized controlled trials (RCTs) (3292 patients) were eligible for the final analysis. After 96 weeks of treatment, the pooled effect estimate did not favor either ATZ/r or LPV/r in terms of virological failure rate (RR 1.11, 95% CI [0.74, 1.66]). However, ATZ/r was marginally superior to LPV/r in terms of increasing the proportion of patients with HIV RNA <50 copies/ml (RR 1.09, 95% CI [1.01, 1.17]). The pooled effect estimate did not favor ATZ/r over DRV/r regarding the change in plasma levels of total cholesterol, triglycerides, or high-density lipoprotein at 24, 48, and 96 weeks. Moreover, no significant difference was found between the two regimens (ATZ/r and DRV/r) in terms of change in visceral (SMD -0.06, 95%CI [-0.33, 0.21]) or subcutaneous adipose tissue (SMD 0.12, 95% CI [-0.15, 0.39]). The ATZ/r regimen was generally as effective and well-tolerated as the LPV/r regimen for the treatment of HIV-1 patients. Compared to the DRV/r regimen, ATZ/r has no favorable effect on the plasma lipid profile or adipose tissue distribution.

Efficacy and safety of transcatheter aortic valve replacement in aortic stenosis patients at low to moderate surgical risk: a comprehensive meta-analysis.

BACKGROUND: Recently, transcatheter aortic valve replacement (TAVR) has become the procedure of choice in high surgical risk patients with aortic stenosis (AS). However, its value is still debated in operable AS cases. We performed this meta-analysis to compare the safety and efficacy of TAVR to surgical aortic valve replacement (SAVR) in low-to-moderate surgical risk patients with AS. METHODS: A systematic search of five authentic databases retrieved 11 eligible studies (20,056 patients). Relevant Data were pooled as risk ratios (RRs) or standardized mean differences (SMD), with their 95% confidence interval, using Comprehensive Meta-Analysis and RevMan software for windows. RESULTS: At one-year of follow-up, the pooled effect-estimates showed no significant difference between TAVR and SAVR groups in terms of all-cause mortality (RR 1.02, 95% CI [0.83, 1.26], stroke (RR 0.83, 95%CI [0.56, 1.21]), myocardial infarction (RR 0.82, 95% CI [0.57, 1.19]), and length of hospital stay (SMD -0.04, 95% CI [-0.34, 0.26]). The incidence of major bleeding (RR 0.45, 95% CI [0.24, 0.86]) and acute kidney injury (RR 0.52, 95% CI [0.30, 0.88]) was significantly lower in the TAVR group, compared to the SAVR group. However, TAVR was associated with a higher risk of permanent pacemaker implantation (RR 2.57, 95% CI [1.36, 4.86]), vascular-access complications at 1 year (RR 1.99, 95%CI [1.04, 3.80]), and paravalvular aortic regurgitation at 30 days (RR 3.90, 95% CI [1.25, 12.12]), compared to SAVR. CONCLUSIONS: Due to the comparable mortality rates in SAVR and TAVR groups and the lower risk of life-threatening complications in the TAVR group, TAVR can be an acceptable alternative to SAVR in low-to-moderate risk patients with AS. However, larger trials with longer follow-up periods are required to compare the long-term outcomes of both techniques.

Evidence for association between hepatitis C virus and Parkinson's disease.

Parkinson's disease (PD) is a globally prevalent neurodegenerative disorder, characterized by progressive neuronal loss in the substantia nigra and formation of Lewy bodies. These pathological characteristics are clinically translated into motor symptoms, such as bradykinesia, rigidity, resting tremors, and postural instability. Emerging data from epidemiological studies suggest a possible association between PD and hepatitis C virus (HCV) infection, which affects up to 71 million individuals worldwide. Preclinical studies have shown that HCV can penetrate and replicate within the brain macrophages and microglial cells, increasing their production of pro-inflammatory cytokines that can directly cause neuronal toxicity. Other studies reported that interferon, previously used to treat HCV infection, can increase the risk of PD through inhibition of the nigrostriatal dopaminergic transmission or induction of neuroinflammation. In this article, we provide a comprehensive review on the possible association between HCV infection and PD and highlight recommendations for further research and practice in this regard.