Anti-Cancer Effects of Lycopene in Animal Models of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

INTRODUCTION: Globally, hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer and the third important cause of cancer-related death. As there are only two targeted drugs for the treatment of advanced HCC-that merely extend survival by a few months-the need for alternative treatments is inevitable. Lycopene, a carotenoid that is known to be most abundant in red tomatoes and tomato-based products, has been investigated for its anticancer activity in various types of cancers including HCC. This review was conducted to evaluate the effects of lycopene on HCC from animal models to pave the way for further clinical studies. METHODS: Electronic databases and search engines including PubMed, EMBASE, and Google Scholar were searched for original records addressing the anticancer effect of lycopene in animal models of HCC. Data were extracted using a format prepared in Microsoft Excel and exported to Stata 15.0 for analyses. A meta-analysis was performed using a random-effects model at a 95% confidence level for the outcome measures: tumor incidence, number, and growth (tumor volume and size). The presence of publication bias between studies was evaluated using Egger's test and funnel plot. The study protocol was registered in the PROSPERO database with reference number: CRD42019159312. RESULTS: The initial database search yields 286 articles, of which 15 studies met the inclusion criteria. The characteristics of the included studies were a bit diversified. The studies involved a total of 644 animals (312 treatment and 332 control groups) and mice shared the majority (488) followed by rats (117) and ferrets (39). The meta-analysis showed that lycopene significantly reduced the incidence [RR 0.8; 95% CI 0.69, 0.92 (p=0.00); I2 = 30.4%, p=0.16; n=11], number [SMD-1.83; 95% CI -3.10, -0.57 (p=0.01); I2 = 95.9%, p=0.00; n=9], and growth [SMD -2.13; 95% CI -4.20, -0.04 (p=0.04); I2 = 94.6%, p=0.00; n=4] of HCC. CONCLUSIONS: Administration of lycopene appears to inhibit the initiation and progression of cancer in animal models of HCC. However, more controlled and thorough preclinical studies are needed to further evaluate its anti-HCC effects and associated molecular mechanisms.

Bacterial otitis media in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: Otitis media is inflammation of the middle ear, comprising a spectrum of diseases. It is the commonest episode of infection in children, which often occurs after an acute upper respiratory tract infection. Otitis media is ranked as the second most important cause of hearing loss and the fifth global burden of disease with a higher incidence in developing worlds like Sub-Saharan Africa and South Asia. Therefore, this systematic review is aimed to quantitatively estimate the current status of bacterial otitis media, bacterial etiology and their susceptibility profile in sub-Saharan Africa. METHODS: A literature search was conducted from major databases and indexing services including EMBASE (Ovid interface), PubMed/MEDLINE, Google Scholar, ScienceDirect, Cochrane Library, WHO African Index-Medicus and others. All studies (published and unpublished) addressing the prevalence of otitis media and clinical isolates conducted in sub-Saharan Africa were included. Format prepared in Microsoft Excel was used to extract the data and data was exported to Stata version 15 software for the analyses. Der-Simonian-Laird random-effects model at a 95% confidence level was used for pooled estimation of outcomes. The degree of heterogeneity was presented with I2 statistics. Publication bias was presented with funnel plots of standard error supplemented by Begg's and Egger's tests. The study protocol is registered on PROSPERO with reference number ID: CRD42018102485 and the published methodology is available from http://www.crd.york.ac.uk/CRD42018102485. RESULTS: A total of 33 studies with 6034 patients were included in this study. All studies have collected ear swab/discharge samples for bacterial isolation. The pooled isolation rate of bacterial agents from the CSOM subgroup was 98%, patients with otitis media subgroup 87% and pediatric otitis media 86%. A univariate meta-regression analysis indicated the type of otitis media was a possible source of heterogeneity (p-value = 0.001). The commonest isolates were P. aeruginosa (23-25%), S. aureus (18-27%), Proteus species (11-19%) and Klebsiella species. High level of resistance was observed against Ampicillin, Amoxicillin-clavulanate, Cotrimoxazole, Amoxicillin, and Cefuroxime. CONCLUSION: The analysis revealed that bacterial pathogens like P. aeruginosa and S. aureus are majorly responsible for otitis media in sub-Saharan Africa. The isolates have a high level of resistance to commonly used drugs for the management of otitis media.

Magnitude and causes of first-line antiretroviral therapy regimen changes among HIV patients in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Antiretroviral therapy (ART) has markedly decreased the morbidity and mortality due to HIV/AIDS. ART regimen change is a major challenge for the sustainability of human immunodeficiency virus (HIV) treatment program. This is found to be a major concern among HIV/AIDS patients in a resource-limited setting, where treatment options are limited. OBJECTIVES: The aim of this review is to generate the best available evidence regarding the magnitude of first-line antiretroviral therapy regimen change and the causes for regimen change among HIV patients on ART in Ethiopia. METHODS: The reviewed studies were accessed through electronic web-based search strategy from PubMed Medline, EMBASE, Hinari, Springer link and Google Scholar. Data were extracted using Microsoft Excel and exported to Stata software version 13 for analyses. The overall pooled estimation of outcomes was calculated using a random-effect model of DerSimonian-Laird method at 95% confidence level. Heterogeneity of studies was determined using I2 statistics. For the magnitude of regimen change, the presence of publication bias was evaluated using the Begg's and Egger's tests. The protocol of this systematic review and meta-analysis was registered in the Prospero database with reference number ID: CRD42018099742. The published methodology is available from: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=99742 . RESULTS: A total of 22 studies published between the years 2012 and 2018 were included. Out of 22 articles, 14 articles reported the magnitude of regimen change and consisted of 13,668 HIV patients. The estimated national pooled magnitude of regimen change was 37% (95% CI: 34, 44%; Range: 15.1-63.8%) with degree of heterogeneity (I2), 98.7%; p-value < 0.001. Seventeen articles were used to identify the causes for first-line antiretroviral therapy regimen change. The major causes identified were toxicity, 58% (95% CI: 46, 69%; Range: 14.4-88.5%); TB co-morbidity, 12% (95% CI: 8, 16%; Range: 0.8-31.7%); treatment failure, 7% (95% CI: 5, 9%; Range: 0.4-24.4%); and pregnancy, 5% (95% CI: 4, 7%; Range: 0.6-11.9%). CONCLUSIONS: The original first-line regimen was changed in one-third of HIV patients on ART in Ethiopia. Toxicity of the drugs, TB co-morbidity, treatment failure, and pregnancy were the main causes for the change of the first-line regimen among HIV patients on antiretroviral therapy.

Resistance profile of clinically relevant bacterial isolates against fluoroquinolone in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Fluoroquinolones are among the most frequently utilized antibacterial agents in developing countries like Ethiopia. Ciprofloxacin has become the most prescribed drug within this class and remains as one of the top three antibacterial agents prescribed in Ethiopia. However, several studies indicated that there is a gradual increase of antibacterial resistance. Therefore, this meta-analysis aimed to quantitatively estimate the prevalence of ciprofloxacin resistance bacterial isolates in Ethiopia. METHODS: Literature search was conducted from electronic databases and indexing services including EMBASE (Ovid interface), PubMed/MEDLINE, Google Scholar, Science Direct and WorldCat. Data were extracted with structured format prepared in Microsoft Excel and exported to STATA 15.0 software for the analyses. Pooled estimation of outcomes was performed with DerSimonian-Laird random-effects model at 95% confidence level. Degree of heterogeneity of studies was presented with I2 statistics. Publication bias was conducted with comprehensive meta-analysis version 3 software and presented with funnel plots of standard error supplemented by Begg's and Egger's tests. The study protocol has been registered on PROSPERO with reference number ID: CRD42018097047. RESULTS: A total of 37 studies were included for this study. The pooled prevalence of resistance in selected gram-positive bacterial isolates against ciprofloxacin was found to be 19.0% (95% confidence interval [CI]: 15.0, 23.0). The degree of resistance among Staphylococcus aureus, Coagulase negative Staphyloccoci (CoNS), Enterococcus faecalis and Group B Streptococci (GBS) was found to be 18.6, 21.6, 23.9, and 7.40%, respectively. The pooled prevalence of resistance in gram-negative bacteria was about 21.0% (95% CI: 17, 25). Higher estimates were observed in Neisseria gonorrhea (48.1%), Escherichia coli (24.3%) and Klebsiella pneumonia (23.2%). Subgroup analysis indicated that blood and urine were found to be a major source of resistant S. aureus isolates. Urine was also a major source of resistant strains for CoNS, Klebsiella and Proteus species. CONCLUSION: Among gram-positive bacteria, high prevalence of resistance was observed in E. faecalis and CoNS whereas relatively low estimate of resistance was observed among GBS isolates. Within gram-negative bacteria, nearly half of isolates in N. gonorrhoea were found ciprofloxacin resistant. From enterobacteriaceae isolates, K. pneumonia and E. coli showed higher estimates of ciprofloxacin resistance.