A systematic review and meta-analysis of the diagnostic accuracy of nucleic acid amplification tests in cerebrospinal fluid for tuberculous meningitis

Introduction: Diagnosis of tuberculous meningitis (TBM) is difficult and poses a significant challenge to physicians worldwide. Recently, nucleic acid amplification (NAA) tests have shown promise for diagnosis of TBM, although performance has been variable. We undertook a systematic review and meta-analysis to evaluate the diagnostic accuracy of NAA tests in cerebrospinal fluid (CSF) samples against culture as the reference standard or a combined reference standard (CRS) for TBM.Methods: We searched Embase, PubMed, Web of Science and the Cochrane library for the relevant records. QUADS-2 tool was used to assess the quality assessment of the studies. Diagnostic accuracy measures (i.e. sensitivity and specificity) were pooled with a random effects model. All Statistical analyses were performed with STATA version 14 (Stata Corporation, College Station, TX, USA), Meta-DiSc version 1.4 (Cochrane Colloquium, Barcelona, Spain) and RveMan version 5.3 (Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration).Results: Sixty-three studies were included in final analysis, comprising 1381cases of confirmed TBM and 5712 non-TBM controls. These 63 studies were divided into two groups comprising 71 datasets (43 in-house tests and 28 commercial tests) that used culture as the reference standard and 24 datasets (21 in-house tests and 3 commercial tests) that used a CRS. Studies which used a culture reference standard had better pooled summary estimates compared to studies which used CRS. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of NAA tests against culture were 82% (95% CI: 75-87), 99% (95% CI: 98-99), 58.6 (35.3-97.3) and 0.19 (0.14-0.25), respectively. The pooled sensitivity, specificity, PLR and NLR of NAA tests against CRS were 68% (95% CI: 41-87), 98% (95% CI: 95-99), 36.5 (15.6-85.3) and 0.32 (0.15-0.70), respectively.Conclusion: The analysis has demonstrated that the diagnostic accuracy of NAA tests is currently insufficient to replace culture as a lone diagnostic test. NAA tests may be used in combination with culture due to the advantage of time to result and in scenarios where culture tests are not feasible. Further work to improve NAA tests would benefit from standardized reference standards and the methodology

Methicillin-resistant staphylococcus epidermidis in Iran: A systematic review and meta-analysis

Objective: Methicillin-resistant Staphylococcus epidermidis (MRSE) remains one of the most prevalent drug-resistant bacteria causing health care infections. Limited data are available about how the frequency of MRSE changed in Iran over the past years. The current study aimed at determining the frequency of MRSE in different cities of Iran. Methods: Databases including Web of Sciences, Scopus, Embase, Medline, and Iranian databases were searched to find studies addressing the frequency of MRSE in Iran published from Mar 2006 to Jan 2016. The data were analyzed using comprehensive meta-analysis version 2.2 (Biostat). Of the 139 records identified in the databases, 15 studies met the inclusion criteria. Results: The analyses showed that the frequency of MRSE infections was 73.9 95% confidence interval (95% CI) 61.4-83.4 among culture-positive cases of S. epidermidis in different parts of Iran. The frequency of MRSE was higher in the studies conducted from 2011 to 2015, based on further stratified analyses. Conclusions: The regular surveillance on antimicrobial susceptibility pattern and formulation of definite antibiotic policy may control high rate of MRSE associated infections in Iran. Moreover, rapid and reliable diagnosis of MRSE isolates and regular screening of the personnel and surfaces of hospitals in terms of MRSE are indispensable. © 2018, Archives of Clinical Infectious Diseases

Comparison of influenza type A and B with COVID-19: A global systematic review and meta-analysis on clinical, laboratory and radiographic findings

We compared clinical symptoms, laboratory findings, radiographic signs and outcomes of COVID-19 and influenza to identify unique features. Depending on the heterogeneity test, we used either random or fixed-effect models to analyse the appropriateness of the pooled results. Overall, 540 articles included in this study; 75,164 cases of COVID-19 (157 studies), 113,818 influenza type A (251 studies) and 9266 influenza type B patients (47 studies) were included. Runny nose, dyspnoea, sore throat and rhinorrhoea were less frequent symptoms in COVID-19 cases (14, 15, 11.5 and 9.5, respectively) in comparison to influenza type A (70, 45.5, 49 and 44.5, respectively) and type B (74, 33, 38 and 49, respectively). Most of the patients with COVID-19 had abnormal chest radiology (84, p < 0.001) in comparison to influenza type A (57, p < 0.001) and B (33, p < 0.001). The incubation period in COVID-19 (6.4 days estimated) was longer than influenza type A (3.4 days). Likewise, the duration of hospitalization in COVID-19 patients (14 days) was longer than influenza type A (6.5 days) and influenza type B (6.7 days). Case fatality rate of hospitalized patients in COVID-19 (6.5, p < 0.001), influenza type A (6, p < 0.001) and influenza type B was 3(p < 0.001). The results showed that COVID-19 and influenza had many differences in clinical manifestations and radiographic findings. Due to the lack of effective medication or vaccine for COVID-19, timely detection of this viral infection and distinguishing from influenza are very important. © 2020 John Wiley & Sons Ltd

Bovine Leukemia virus (BLV) and risk of breast cancer: A systematic review and meta-analysis of case-control studies

Background: Breast cancer is reported as one of the most common cancers among females worldwide. Infectious agents especially viruses have been considered as role players in the development of breast cancer. Although some investigations suggest an association between bovine leukemia virus (BLV) and breast cancer, the involvement of this virus as a risk factor remains controversial. The present study aimed to find out any possible association between BLV and breast cancer through conducting a systematic review and meta-analysis. Methods: Systematic literature search was performed by finding related case-control articles from the PubMed, Google Scholar, Web of Science, Scopus, and EMBASE databases. The heterogeneity and the multivariable-adjusted OR and corresponding 95 CI were applied by meta-analysis and forest plot across studies. All statistical analyses were performed using Stata 14.1. Result: Based on a comprehensive literature search, 9 case-control studies were included for meta-analysis. The combination of all included studies showed that BLV infection is associated with an increased risk of breast cancer summary OR (95% CI) 2.57 (1.45, 4.56). Conclusion: This is the first meta-analysis to analyze a potential association between BLV infection and the risk of breast cancer. Control of the infection in cattle herds and screening of the milk and dairy products may help to reduce the transmission of the virus to humans. © 2020 The Author(s)

Efficacy and safety of covid-19 vaccines: A systematic review and meta-analysis of randomized clinical trials

The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6 (95 CI 0.936�0.954) and 80.2 (95 CI 0.96.4�0.92.7) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6; 95 CI 0.939�0.997) and second (98.2; 95 CI 0.980�0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines� adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Comparison of confirmed COVID-19 with SARS and MERS cases - Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta-analysis

Introduction: Within this large-scale study, we compared clinical symptoms, laboratory findings, radiographic signs, and outcomes of COVID-19, SARS, and MERS to find unique features. Method: We searched all relevant literature published up to February 28, 2020. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Study has been registered in the PROSPERO database (ID 176106). Result: Overall 114 articles included in this study; 52 251 COVID-19 confirmed patients (20 studies), 10 037 SARS (51 studies), and 8139 MERS patients (43 studies) were included. The most common symptom was fever; COVID-19 (85.6, P <.001), SARS (96, P <.001), and MERS (74, P <.001), respectively. Analysis showed that 84 of Covid-19 patients, 86 of SARS patients, and 74.7 of MERS patients had an abnormal chest X-ray. The mortality rate in COVID-19 (5.6, P <.001) was lower than SARS (13, P <.001) and MERS (35, P <.001) between all confirmed patients. Conclusions: At the time of submission, the mortality rate in COVID-19 confirmed cases is lower than in SARS- and MERS-infected patients. Clinical outcomes and findings would be biased by reporting only confirmed cases, and this should be considered when interpreting the data. © 2020 John Wiley & Sons, Lt

Clinical characteristics, laboratory findings, radiographic signs and outcomes of 61,742 patients with confirmed COVID-19 infection: A systematic review and meta-analysis

Introduction: In the current time where we face a COVID-19 pandemic, there is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. Method: We searched all relevant literature published up to February 28, 2020. We used Random-effect models to analyze the appropriateness of the pooled results. Result: Eighty studies were included in the meta-analysis, including 61,742 patients with confirmed COVID-19 infection. 62.5 (95 CI 54.5�79, p 50 years old was 39.5, and in all range group was 6. Conclusions: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases. © 202

Clinical characteristics and outcomes of pregnant women with COVID-19 and comparison with control patients: A systematic review and meta-analysis

In a large-scale study, 128176 non-pregnant patients (228 studies) and 10000 pregnant patients (121 studies) confirmed COVID-19 cases included in this Meta-Analysis. The mean (confidence interval CI) of age and gestational age of admission (GA) in pregnant women was 33 (28�37) years old and 36 (34�37) weeks, respectively. Pregnant women show the same manifestations of COVID-19 as non-pregnant adult patients. Fever (pregnant: 75.5%; non-pregnant: 74%) and cough (pregnant: 48.5%; non-pregnant: 53.5%) are the most common symptoms in both groups followed by myalgia (26.5%) and chill (25%) in pregnant and dysgeusia (27%) and fatigue (26.5%) in non-pregnant patients. Pregnant women are less probable to show cough (odds ratio OR 0.7; 95% CI 0.67�0.75), fatigue (OR: 0.58; CI: 0.54�0.61), sore throat (OR: 0.66; CI: 0.61�0.7), headache (OR: 0.55; CI: 0.55�0.58) and diarrhea (OR: 0.46; CI: 0.4�0.51) than non-pregnant adult patients. The most common imaging found in pregnant women is ground-glass opacity (57%) and in non-pregnant patients is consolidation (76%). Pregnant women have higher proportion of leukocytosis (27% vs. 14%), thrombocytopenia (18% vs. 12.5%) and have lower proportion of raised C-reactive protein (52% vs. 81%) compared with non-pregnant patients. Leucopenia and lymphopenia are almost the same in both groups. The most common comorbidity in pregnant patients is diabetes (18%) and in non-pregnant patients is hypertension (21%). Case fatality rate (CFR) of non-pregnant hospitalized patients is 6.4% (4.4�8.5), and mortality due to all-cause for pregnant patients is 11.3% (9.6�13.3). Regarding the complications of pregnancy, postpartum hemorrhage (54.5% 7�94), caesarean delivery (48% 42�54), preterm labor (25% 4�74) and preterm birth (21% 12�34) are in turn the most prevalent complications. Comparing the pregnancy outcomes show that caesarean delivery (OR: 3; CI: 2�5), low birth weight (LBW) (OR: 9; CI: 2.4�30) and preterm birth (OR: 2.5; CI: 1.5�3.5) are more probable in pregnant woman with COVID-19 than pregnant women without COVID-19. The most prevalent neonatal complications are neonatal intensive care unit admission (43% 2�96), fetal distress (30% 12�58) and LBW (25% 16�37). The rate of vertical transmission is 5.3% (1.3�16), and the rate of positive SARS-CoV-2 test for neonates born to mothers with COVID-19 is 8% (4�16). Overall, pregnant patients present with the similar clinical characteristics of COVID-19 when compared with the general population, but they may be more asymptomatic. Higher odds of caesarean delivery, LBW and preterm birth among pregnant patients with COVID-19 suggest a possible association between COVID-19 infection and pregnancy complications. Low risk of vertical transmission is present, and SARS-CoV-2 can be detected in all conception products, particularly placenta and breast milk. Interpretations of these results should be done cautiously due to the heterogeneity between studies; however, we believe our findings can guide the prenatal and postnatal considerations for COVID-19 pregnant patients. © 2020 John Wiley & Sons Ltd

Prevalence of antibiotic resistance in Escherichia coli strains simultaneously isolated from humans, animals, food, and the environment: a systematic review and meta-analysis

Ali Pormohammad,1 Mohammad Javad Nasiri,2 Taher Azimi2,31Student Research Committee, Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, IranBackground: Antimicrobial resistance is a serious public health problem worldwide. We aimed to investigate the prevalence of antibiotic resistance in Escherichia coli strains simultaneously isolated from humans, animals, food, and the environment.Methods: Studies on PubMed, Embase, and the Cochrane Library published from January 1, 2000 to January 1, 2018 were searched. The quality of the included studies was assessed by the modified critical appraisal checklist recommended by the Joanna Briggs Institute. All analyses were conducted using Biostat&rsquo;s Comprehensive Meta-Analysis version 2.0. Depending on the heterogeneity test for each antibiotic, we used a random- or fixed-effect model for pooled prevalence of drug resistance. Studies were eligible if they had investigated and reported resistance in two or more isolation sources (human, animal, food, or environment). To decrease heterogeneity and bias, we excluded studies that had reported E. coli drug resistance isolated from one source only. We included publications that reported drug resistance with minimum inhibitory concentration or disk diffusion method (DDM) as antibiotic-susceptibility tests.Results: Of the 39 included studies, 20 used the DDM and 19 minimum inhibitory concentration for their antibiotic-susceptibility testing. Colistin had the lowest prevalence, with 0.8% (95% CI 0.2%&ndash;3.8%) and amoxicillin the highest, with 70.5% (95% CI 57.5%&ndash;81%) in isolated human E. coli strains tested with the DDM. To assess historical changes in antimicrobial drug resistance, subgroup analysis from 2000 to 2018 showed a significant increase in ciprofloxacin resistance.Conclusion: Monitoring and evaluating antibiotic-sensitivity patterns and preparation of reliable antibiotic strategies may lead to better outcomes for inhibition and control of E. coli infections in different regions of the world.Keywords: antibiotic, drug resistance, Escherichia col

Technetium-99 m-PEGylated dendrimer-G2-(Dabcyle-Lys6,Phe7)-pHBSP: A novel Nano-Radiotracer for molecular and early detecting of cardiac ischemic region

In cardiac ischemic disorder, pyroglutamate helix B surface peptide (pHBSP) which derived from erythropoietin causes to increase cell stability. To improve the serum stability of pHBSP, two lipophilic amino acids Arg6, Ala7 were replaced with Fmoc-(Dabcyle)-Lys-OH and Fmoc-Phe-OH during the peptide synthesis. This peptide was subsequently conjugated to PEGylated dendrimer-G2 and labeled with 99mTcO4 � to detect cardiac ischemic region. Radiochemical purity (RCP) of 99mTc-PEGylated dendrimer-G2-(Dabcyle-Lys6,Phe7)-pHBSP was evaluated by ITLC method. In addition, the radiopeptide was investigated for stability in human serum and binding affinity to hypoxic cells in myocardium H9c2 cell lines. Biodistribution and SPECT/CT scintigraphy were assessed in cardiac ischemic rats. Radiochemical yield indicated that the anionic dendrimer has a very high potential to complex formation with 99mTcO� 4 (RCP &gt; 94) which was stable in human serum with RCP 89 up to 6 h. The binding of 99mTc- nanoconjugate to hypoxic cells was significantly more than normoxic cells (3-fold higher compared to normoxic cells at 1 h). In biodistribution studies, erythropoietin receptor-Beta common receptor (EPO-BcR)-positive uptake in the cardiac ischemic region was 3.62 ± 0.44 ID/g 30 min post injection. SPECT imaging showed a prominent uptake of 99mTc-nanoconjugate in EPO-BcR expressing ischemic heart. © 202