Efficacy of Cerebellar Transcranial Magnetic Stimulation in Treating Essential Tremor: A Randomized, Sham-Controlled Trial.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) of the cerebellar hemisphere represents a new option in treating essential tremor (ET) patients. We aimed to determine the efficacy of cerebellar rTMS in treating ET using different protocols regarding the number of sessions, exposure duration, and follow-up duration. METHODS: A randomized sham-controlled trial was conducted, in which 45 recruit patients were randomly allocated to 2 groups. The first (active group) comprised 23 patients who were exposed to 12 sessions of active rTMS with 900 pulses of 1-Hz rTMS at 90% of the resting motor threshold daily on each side of the cerebellar hemispheres over 4 weeks. The second group (sham group) comprised 22 patients who were exposed to 12 sessions of sham rTMS. Both groups were reassessed at baseline and after 1 day, 1 month, 2 months, and 3 months using the Fahn-Tolosa-Marin tremor-rating scale (FTM). RESULTS: Demographic characteristics did no differ between the two groups. There were significant reductions both in FTM subscores A and B and in the FTM total score in the active-rTMS group during the period of assessment and after 3 months (p=0.031 and 0.011, respectively). However, subscore C did not change significantly from baseline when assessed at 2 and 3 months (p=0.073 and 0.236, respectively). Furthermore, the global assessment score was significantly higher in the active-rTMS group (p>0.001). CONCLUSIONS: Low-frequency rTMS over the cerebellar cortex for 1 month showed relative safety and long-lasting efficacy in patients with ET. Further large-sample clinical trials are needed that include different sites of stimulation and longer follow-ups.

Etiology of Pediatric Uveitis in a Tertiary Pediatric Eye Hospital in Egypt.

PURPOSE: To report the causes of childhood-onset uveitis in a tertiary pediatric ophthalmology hospital in Egypt. METHODS: Retrospective study of the medical records of all uveitis patients following up at a tertiary pediatric ophthalmology hospital in Egypt from January 2017 to December 2020. RESULTS: The present study included 388 patients. The most common anatomical category was intermediate uveitis (30.4%), and around half of these children had pars planitis. This was followed by panuveitis (25.5%), posterior uveitis (23.5%), and anterior uveitis (20.6%), in decreasing frequency. Juvenile idiopathic arthritis, toxoplasmosis, and Vogt-Koyanagi-Harada syndrome were the most common causes of anterior uveitis, posterior uveitis, and panuveitis respectively. Cataract (40.5%), glaucoma (33.8%), and cystoid macular edema (31.6%) were the most frequent ocular complications. CONCLUSION: The present report provides the relative prevalence of the different anatomical types of uveitis, as well as their main causes in a cohort of Egyptian patients with childhood-onset uveitis.

Association of Allergic Symptoms with Dengue Infection and Severity: A Systematic Review and Meta-analysis.

The relationship between the severity of dengue infection and allergy is still obscure. We conducted an electronic search across 12 databases for relevant articles reporting allergic symptoms, dengue infection, and dengue classification. These studies were categorized according to dengue severity and allergy symptoms, and a meta-analysis was performed by pooling the studies in each category. Among the included 57 articles, pruritus was the most common allergic sign followed by non-specified allergy and asthma (28.6%, 13%, and 6.5%, respectively). Despite the reported significant association of dengue with pruritus and total IgE level (P < 0.05), in comparison with non-dengue cases and healthy controls, there was no association between the different severe dengue group with pruritus, skin allergy, food allergy or asthma. However, removing the largest study revealed a significant association between asthma with dengue hemorrhagic fever (DHF) rather than dengue fever (DF). In comparison with DF, DHF was associated with IgE positivity. Furthermore, specific-IgE level was higher in secondary DF rather than primary DF. There was a possible association between allergy symptoms and dengue severity progression. Further studies are needed to clarify this association.

Correction to: Association of Allergic Symptoms with Dengue Infection and Severity: A Systematic Review and Meta-analysis.

The spelling of the fifth author's name was misspelled. The byline should appear as shown above.

Prevalence and burden of dengue infection in Europe: A systematic review and meta-analysis.

Imported dengue cases are thought to be important source for transmission of autochthonous dengue in Europe. We aimed to investigate the prevalence of dengue in Europe, its severity, and factors associated with it. Out of 5287 reports resulting from the search of nine electronic search engines, we included 174 reports. Meta-analysis was performed by pooling the event rate and 95% confidence interval (CI). Subgroup meta-analyses were performed to test the effect of the covariates. Among 20 284 reported cases, 130 autochthonous dengue cases were reported in eight countries with the highest number of cases reported in Israel (n = 41). The highest number of imported dengue cases was in Germany (n = 6638) then France (n = 6610). Most cases were imported from Southeast Asia (n = 2533) especially Thailand. Dengue infection cases increased with time, with 4157 cases reported in 2010. Second dengue infection and dengue serotype 2 were positively associated with dengue severity. The proportion of autochthonous dengue infection increased with time to reach 14.8% (95% CI, 7.6-26.9) in 2015. The pooled proportion of severe dengue was 6.18% (95% CI, 2.7-13.3). The United Kingdom and France had the highest rate of severe dengue (25%; 95% CI, 6.3-62.3, and 21.4%; 95% CI, 24.5-18.7, respectively). This change may be due to the surveillance efforts instead of true biological phenomenon; thus, the lack of surveillance is an obvious limitation. In conclusion, imported and autochthonous dengue has been increasing in Europe. Severe dengue began to increase recently in Europe. European health authorities should pay more attention for the diagnosis and control of dengue infection among returning travelers, especially the travelers with fever of unknown origin.

Serum Biomarkers for the Early Detection of the Early-Onset Neonatal Sepsis: A Single-Center Prospective Study.

BACKGROUND: Reducing the hazards of the early-onset neonatal sepsis (EONS) is a priority justifying the further investigation for potential biomarkers for its early diagnosis. PURPOSE: We aimed to investigate the diagnostic value of presepsin, procalcitonin, lactoferrin, interleukin (IL)-6, and IL-8 for the early diagnosis of EONS. METHODS: A prospective comparative study, including 30 cases with highly suspected EONS and 30 matched controls, was conducted. Besides the complete blood count and blood culture, C-reactive protein, procalcitonin, presepsin, IL-6, IL-8, and lactoferrin were measured at the admission and after 72 hours. RESULTS: At the time of the admission, presepsin, procalcitonin, C-reactive protein, and IL-8 were significantly higher in the sepsis group. The levels of presepsin, procalcitonin, and IL-8 significantly decreased after 72 hours of the admission. Presepsin, procalcitonin, IL-8, and IL-6 showed a high diagnostic ability for sepsis at admission with area under the curve of 0.934, 0.798, 0.775, and 0.751, respectively. The cutoff values of presepsin, procalcitonin, IL-8, and IL-6 were 821 pg/mL, 2.3 ng/mL, 54 pg/mL, and 24 pg/mL, with a sensitivity of 88.9%, 72.2%, 83.3%, and 94.4% and specificity of 85.7%, 80.9%, 71.4%, and 52.4%, respectively. Lactoferrin had the lowest diagnostic ability with area under the curve of 0.558. IMPLICATIONS FOR PRACTICE: Presepsin was the most accurate biomarker followed by procalcitonin, IL-8, and IL-6 regarding the early diagnosis and management of EONS. The combination between these biomarkers is highly recommended. IMPLICATIONS FOR RESEARCH: Further studies are needed to investigate the diagnostic ability of the combination of these biomarkers.

A step by step guide for conducting a systematic review and meta-analysis with simulation data.

BACKGROUND: The massive abundance of studies relating to tropical medicine and health has increased strikingly over the last few decades. In the field of tropical medicine and health, a well-conducted systematic review and meta-analysis (SR/MA) is considered a feasible solution for keeping clinicians abreast of current evidence-based medicine. Understanding of SR/MA steps is of paramount importance for its conduction. It is not easy to be done as there are obstacles that could face the researcher. To solve those hindrances, this methodology study aimed to provide a step-by-step approach mainly for beginners and junior researchers, in the field of tropical medicine and other health care fields, on how to properly conduct a SR/MA, in which all the steps here depicts our experience and expertise combined with the already well-known and accepted international guidance.We suggest that all steps of SR/MA should be done independently by 2-3 reviewers' discussion, to ensure data quality and accuracy. CONCLUSION: SR/MA steps include the development of research question, forming criteria, search strategy, searching databases, protocol registration, title, abstract, full-text screening, manual searching, extracting data, quality assessment, data checking, statistical analysis, double data checking, and manuscript writing.

Methodological steps used by authors of systematic reviews and meta-analyses of clinical trials: a cross-sectional study.

BACKGROUND: The quality of systematic reviews and meta-analyses (SR/MAs) depends on the extent of the methods used. We investigated the methodological steps used by authors of SR/MAs of clinical trials via an author survey. METHODS: We conducted an email-based cross-sectional study by contacting corresponding authors of SR/MAs that were published in 2015 and 2016 and retrieved through the PubMed database. The 27-item questionnaire was developed to study the methodological steps used by authors when conducting a SR/MA and the demographic characteristics of the respondent. Besides the demographic characteristics, methodological questions regarding the source, extraction and synthesis of data were included. RESULTS: From 10,292 emails sent, 384 authors responded and were included in the final analysis. Manual searches were carried out by 69.2% of authors, while 87.3% do updated searches, 49.2% search grey literature, 74.9% use the Cochrane tool for risk of bias assessment, 69.8% assign more than two reviewers for data extraction, 20.5% use digital software to extract data from graphs, 57.9% use raw data in the meta-analysis, and 43.8% meta-analyze both adjusted and non-adjusted data. There was a positive correlation of years of experience in conducting of SR/MAs with both searching grey literature (P = 0.0003) and use of adjusted and non-adjusted data (P = 0.006). CONCLUSIONS: Many authors still do not carry out many of the vital methodological steps to be taken when performing any SR/MA. The experience of the authors in SR/MAs is highly correlated with use of the recommended tips for SR/MA conduct. The optimal methodological approach for researchers conducting a SR/MA should be standardized.

Introduction of Novel Surgical Techniques: A Survey on Knowledge, Attitude, and Practice of Surgeons.

Purpose. To investigate the knowledge, attitude, and practice of surgeons toward introducing novel surgical techniques in Egypt, Palestine, and Vietnam. Summary Background Data. Despite the recent advances in modern surgical care and its role in advancing the quality and the length of lives, surgery in the developing world has stagnated or even regressed. Methods. A survey was undertaken among the surgeons in 9 hospitals belonging to the 3 countries. Questions were categorized into knowledge, attitude, and practice questions. Meta-analyses were performed to estimate the event rate and compare between knowledge and practice, senior and junior surgeons. Results. A total of 244 responses, with a response rate of 79.7%, were included in the analysis. Regarding knowledge and attitude, the results were satisfactory except that only 55.8% of surgeons appraised their level of education and 43.3% wanted to earn money from the novel procedure. There was a significant difference between knowledge and practice regarding getting informed consent from the patients (P = .024), discussing the novelty of the procedure (P < .001), discussing the alternative procedures (P < .001), discussing the surgeons' experience and level of skills (P < .001), discussing the risk of the new procedure (P < .001), and monitoring the outcomes after the new procedure (P < .001). Conclusions. Most surgeons have sufficient knowledge and are motivated regarding adopting novel surgical techniques in order to provide the best care for the patients. However, there was a gap between knowledge and practice. Training programs and evidence-based guidelines regarding the introduction of novel surgical techniques are needed to overcome these challenges.

Surgical treatment of diverticulitis and its complications: A systematic review and meta-analysis of randomized control trials.

PURPOSE: The surgical interventions of diverticulitis vary according to its grade and severity. There is a controversy about the best of these different surgical procedures. We aimed to systematically review and meta-analyze randomized controlled trials (RCTs) comparing outcomes and complications between different surgical approaches for acute diverticulitis and its complications. METHODS: Nine electronic databases including PubMed, Scopus, and Web of Science were searched for RCTs comparing different surgical procedures for different grades of diverticulitis. The risk of bias was assessed using the Cochrane Collaboration tool. The protocol was registered in PROSPERO (CRD42015032290). RESULTS: Outcome data were analyzed from five RCTs comparing laparoscopic sigmoid resection (LSR) (n = 247) versus open sigmoid resection (OSR) (n = 237) for treatment of acute complicated diverticulitis with minimal heterogeneity. There was no significant difference in short-term postoperative overall morbidity (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.61-1.31; P = 0.56) and long-term postoperative major morbidity (RR 0.78, 95% CI 0.46-1.31, P = 0.34). In other six RCTs compared laparoscopic lavage with resection for treatment of perforated diverticulitis with peritonitis, the postoperative mortality rate was non-significant in both short-term (RR 1.55, 95% CI 0.79-3.04; P = 0.21) and long-term (RR 0.67, 95% CI 0.29-1.58; P = 0.36) follow up. CONCLUSIONS: LSR is not superior over OSR regarding postoperative morbidity and mortality for acute symptomatic diverticulitis. Furthermore, laparoscopic lavage was proved to be as safe as resection for perforated diverticulitis with peritonitis. Further RCTs are still needed to make an accurate decision regarding these and other procedures.

Prediction Model for Antimalarial Activities of Hemozoin Inhibitors by Using Physicochemical Properties.

The rapid spread of strains of malaria parasites that are resistant to several drugs has threatened global malaria control. Hence, the aim of this study was to predict the antimalarial activity of chemical compounds that possess anti-hemozoin-formation activity as a new means of antimalarial drug discovery. After the initial in vitro anti-hemozoin-formation high-throughput screening (HTS) of 9,600 compounds, a total of 224 hit compounds were identified as hemozoin inhibitors. These 224 compounds were tested for in vitro erythrocytic antimalarial activity at 10 µM by using chloroquine-mefloquine-sensitive Plasmodium falciparum strain 3D7A. Two independent experiments were conducted. The physicochemical properties of the active compounds were extracted from the ChemSpider and SciFinder databases. We analyzed the extracted data by using Bayesian model averaging (BMA). Our findings revealed that lower numbers of S atoms; lower distribution coefficient (log D) values at pH 3, 4, and 5; and higher predicted distribution coefficient (ACD log D) values at pH 7.4 had significant associations with antimalarial activity among compounds that possess anti-hemozoin-formation activity. The BMA model revealed an accuracy of 91.23%. We report new prediction models containing physicochemical properties that shed light on effective chemical groups for synthetic antimalarial compounds and help with in silico screening for novel antimalarial drugs.

Beclabuvir in combination with asunaprevir and daclatasvir for hepatitis C virus genotype 1 infection: A systematic review and meta-analysis.

Daclatasvir, asunaprevir (ASV), and beclabuvir (BCV) are direct-acting antivirals (DAAs) for patients with hepatitis C virus genotype 1 infection. This systematic review and meta-analysis investigating the efficacy and safety of this three-drug combination in HCV genotype 1 infection. Eleven electronic search engines were searched for relevant publications. Studies were screened for eligibility and data was extracted. The outcomes were pooled as event rate and risk ratio (RR). The protocol was registered in PROSPERO (CRD42017054391). Among the included six studies, five studies were included for the meta-analysis (n = 1261). The three-drug combination showed a high response rate in naïve patients with sustained virologic response at week-12 posttreatment (SVR12 ) rate = 95.7% (95%CI [93.8-97.1]) and no difference detected by adding ribavirin (RBV) (the pooled RR = 0.98, 95%CI [0.90-1.08], P = 0.70) or comparing with interferon-experienced patients (RR = 1.02, 95%CI [0.98-1.07], P = 0.31) regardless the genotype 1 subtypes or IL28B genotype. Treatment failure was minimal and showed no difference regarding the previous comparisons. Increasing the dose or the duration did not show a significant increase in the efficacy. In conclusion, this analysis showed high response rates in HCV genotype 1-infected patients treated with daclatasvir, ASV, and BCV irrespective of RBV use, prior interferon-based therapy, or restriction on non-cirrhotic patients, IL28B genotype, or baseline resistance-associated variants.

The therapeutic effect of probiotics on rheumatoid arthritis: a systematic review and meta-analysis of randomized control trials.

Rheumatoid arthritis is an autoimmune disease in which probiotics appears to have an immune modulating action along with decreased inflammatory process. Therefore, we aim to investigate the efficacy of probiotics as an adjuvant therapy for rheumatoid arthritis. A comprehensive literature search was performed using nine databases including PubMed and Web of Science. Interesting data was extracted and meta-analyzed. We assessed the risk of bias using Cochrane Collaboration's tool. The protocol was registered in PROSPERO (CRD 42016036769). We found nine studies involving 361 patients who met our eligibility criteria. Our meta-analysis indicated that pro-inflammatory cytokine IL-6 was significantly lower in the probiotics compared with the placebo group (standardized mean difference = - 0.708; 95% confidence interval (CI) - 1.370 to 0.047, P = 0.036). However, there was no difference between probiotics and placebo in disease activity score (mean difference 0.023; 95% CI - 0.584 to 0.631, P = 0.940). Probiotics lowered pro-inflammatory cytokines IL-6 in RA; however, its clinical effect is still unclear. Hence, many high-quality randomized controlled trials (RCTs) are still needed to prove this effect.

Medicinal plants for in vitro antiplasmodial activities: A systematic review of literature.

The increasing resistance of malaria to drugs raise the need to new antimalarial agents. Antiplasmodial herbs and their active compounds are the most promising source the new antimalarial agents. This study aimed to identify the medicinal plants with very good in vitro antiplasmodial activities, with half-maximal inhibitory concentration (IC50)≤1µg/ml, and to determine trends in the process of screening their antiplasmodial activities. A total of 58 reports published in the English language were retrieved from the bibliographical databases. Screening and data extraction were performed by two independent reviewers. The herbs were categorized as very good, good, moderate and inactive if the IC50 values were <0.1µg/ml, 0.1-1µg/ml, >1-5µg/ml and >5µg/ml respectively. We documented 752 medicinal plants belonging to 254 genera. The majority of the plants were reported from Africa followed by Asia. The traditional use for malaria treatment was the most common reason for the selection of the plants for investigation. About 80% of the plants experimented were reported to be inactive. Among plants identified as having very good to good antiplasmodial crude extracts are Harungana madagascariensis, Quassia africana, and Brucea javanica, while Picrolemma spruce, Aspidosperma vargasi, Aspidosperma desmanthum, and Artemisia annua were reported to have individual compound isolates with very good antiplasmodial activities. In conclusion, the number of plant species assessed so far is still small compared with the stock in nature's plant library. A mechanism of systematically approaching and exploring the untouched plant genera needs to be designed.

Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis.

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59-1.02; p = 0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40-0.86; p = 0.007) but not in Asia (OR, 1.24; 95% CI, 0.96-1.61; p = 0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57-0.87; p = 0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46-1.07; p = 0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61-1.11; p = 0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender.

High-Throughput Screening and Prediction Model Building for Novel Hemozoin Inhibitors Using Physicochemical Properties.

It is essential to continue the search for novel antimalarial drugs due to the current spread of resistance against artemisinin by Plasmodium falciparum parasites. In this study, we developed in silico models to predict hemozoin inhibitors as a potential first-step screening for novel antimalarials. An in vitro colorimetric high-throughput screening assay of hemozoin formation was used to identify hemozoin inhibitors from 9,600 structurally diverse compounds. The physicochemical properties of positive hits and randomly selected compounds were extracted from the ChemSpider database; they were used for developing prediction models to predict hemozoin inhibitors using two different approaches, i.e., traditional multivariate logistic regression and Bayesian model averaging. Our results showed that a total of 224 positive-hit compounds exhibited the ability to inhibit hemozoin formation, with 50% inhibitory concentrations (IC50s) ranging from 3.1 µM to 199.5 µM. The best model according to traditional multivariate logistic regression included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and number of atoms of hydrogen, while the best model according to Bayesian model averaging included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and index of refraction. Both models had a good discriminatory power, with area under the curve values of 0.736 and 0.781 for the traditional multivariate model and Bayesian model averaging, respectively. In conclusion, the prediction models can be a new, useful, and cost-effective approach for the first screen of hemozoin inhibition-based antimalarial drug discovery.