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

Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis

Introduction: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. Methods: We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P 0.05). Conclusions: In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events

Canagliflozin attenuates the progression of atherosclerosis and inflammation process in APOE knockout mice

Background: Sodium glucose co-transporter2 inhibitors reduce the incidence of cardiovascular events in patients with type 2 diabetes mellitus based on the results of recent cardiovascular outcome studies. Herein, we investigated the efects of long-term treatment with canaglifozin on biochemical and immunohistochemical markers related to atherosclerosis and atherosclerosis development in the aorta of apolipoprotein E knockout (Apo-E(−/−) ) mice. Methods: At the age of 5 weeks, mice were switched from normal to a high-fat diet. After 5 weeks, Apo-E(−/−) mice were divided into control-group (6 mice) treated with 0.5% hydroxypropyl methylcellulose and Cana-group (7 mice) treated with canaglifozin (10 mg/kg per day) per os. After 5 weeks of intervention, animals were sacrifced, and heart and aorta were removed. Sections stained with hematoxylin–eosin (H&E) were used for histomorphometry whereas Masson’s stained tissues were used to quantify the collagen content. Immunohistochemistry to assess MCP-1, CD68, a-smooth muscle actin, MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out and q-PCR experiments were performed to quantify mRNA expression. Results: Canaglifozin-group mice had lower total-cholesterol, triglycerides and glucose levels (P<0.01), while heart rate was signifcantly lower (P<0.05). Histomorphometry revealed that one in seven Cana-group mice versus four in six control mice developed atheromatosis, while aortic root plaque was signifcantly less, and collagen was 1.6 times more intense in canaglifozin-group suggesting increased plaque stability. Immunohistochemistry revealed that MCP-1 was signifcantly less expressed (P<0.05) in the aortic root of canaglifozin-group while reduced expression of a-actin and CD68 was not reaching signifcance (P=0.15). VCAM-1 and MCP-1 mRNA levels were lower (P=0.02 and P=0.07, respectively), while TIMP-1/MMP-2 ratio expression was higher in canaglifozin-group approaching statistical signifcance (P=0.07). Conclusions: Canaglifozin attenuates the progression of atherosclerosis, reducing (1) hyperlipidemia and hyper‑ glycemia, and (2) infammatory process, by lowering the expression of infammatory molecules such as MCP-1 and VCAM-1. Moreover, canaglifozin was found to increase the atherosclerotic plaque stability via increasing TIMP-1/ MMP-2 ratio expression

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

Trend der multiresistenten Tuberkulose im Iran: Eine Analyse veröffentlichter Daten

Introduction: Multidrug-resistant tuberculosis (MDR-TB) is one of the major public health threats especially in developing countries. In Iran, the emergence and spread of MDR-TB are likely to pose a significant problem for the National Tubeculosis Control Program (NTP). In this study, to determine the trend of MDR-TB in Tehran, the results of published studies were analyzed.Methods: Several databases were searched, including Medline, Embase, Web of Science and Iranian databases. Studies which report the prevalence of MDR-TB by World Health Organization (WHO)-endorsed drug susceptibility testing (DST) methods were included in the study. Data were analyzed with SPSS 20 (SPSS, Chicago, Illinois, USA).Results: Analysis of the MDR-TB trend did not show any increase among new TB cases, but the trend of MDR-TB was significantly increased among previously treated cases. The prevalence of MDR-TB from 48.0% in 1996 reached 58.0% in 2004 (P<0.05). Conclusions: Our analysis shows an increasing trend in MDR-TB, particularly in retreatment cases. This study strongly highlights the need to develop further strategies for surveillance, monitoring, and management of MDR-TB cases.Einleitung: Die multiresistente Tuberkulose (MDR-TB) ist insbesondere in Entwicklungsländern eine der größten Bedrohungen für die öffentliche Gesundheit. Im Iran stellt die Verbreitung von MDR-TB ein erhebliches Problem für das nationale Tuberkulose-Kontrollprogramm (NTP) dar. Daher sollte der Trend der MDR-TB durch das Nationale Tubekulose-Referenzzentrum im Iran ermittelt werden. Methode: Systematisch wurden in Medline, Embase, Web of Science und iranischen Datenbanken ermittelte Veröffentlichungen des Zeitraums 1996 bis 2017 ausgewertet. Dabei wurden nur Berichte zur Prävalenz von MDR-TB eingeschlossen, sofern die klinische Diagnose durch eine valide Labordiagnose bestätigt worden war. Die Daten wurden mittels SPSS 20 analysiert; eine Irrtumswahrscheinlichkeit von p<0,05 wurde im der Chi-Quadrat-Test als Signifikanzniveau definiert.Ergebnisse: Die Analyse ergab keinen signifikanten Anstieg neuer Fälle von MDR-TB. Dagegen war die Häufigkeit einer Wiederbehandlung von MDR-TB von 1996 mit 48,0% auf 58,0% im Jahr 2004 signifikant angestiegen (p<0,05).Schlussfolgerung: Basierend auf der Analyse ist bei MDR-TB ein zunehmender Trend zu verzeichnen, insbesondere für die Notwendigkeit der Wiederbehandlung. Die Studie unterstreicht die Notwendigkeit der Surveillance und Entwicklung neuer Behandlungsstrategien von MDR-TB