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The Cochrane Database of Systematic... Jun 2017Peripheral artery disease (PAD) is associated with a high clinical and socioeconomic burden. Treatments to alleviate the symptoms of PAD and decrease the risks of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral artery disease (PAD) is associated with a high clinical and socioeconomic burden. Treatments to alleviate the symptoms of PAD and decrease the risks of amputation and death are a high societal priority. A number of growth factors have shown a potential to stimulate angiogenesis. Growth factors delivered directly (as recombinant proteins), or indirectly (e.g. by viral vectors or DNA plasmids encoding these factors), have emerged as a promising strategy to treat patients with PAD.
OBJECTIVES
To assess the effects of growth factors that promote angiogenesis for treating people with PAD of the lower extremities.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Specialised Register (June 2016) and CENTRAL (2016, Issue 5). We searched trial registries for details of ongoing or unpublished studies. We also checked the reference lists of relevant publications and, if necessary, tried to contact the trialists for details of the studies.
SELECTION CRITERIA
We included randomised controlled trials comparing growth factors (delivered directly or indirectly) with no intervention, placebo or any other intervention not based on the growth factor's action in patients with PAD of the lower extremities. The primary outcomes were limb amputation, death and adverse events. The secondary outcomes comprised walking ability, haemodynamic measures, ulceration and rest pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials and assessed the risk of bias. We used outcomes of the studies at low risk of bias for the main analysis and of all studies in the sensitivity analyses. We calculated odds ratios (OR) for dichotomous outcomes and mean differences for continuous outcomes with 95% confidence intervals (CI). We evaluated statistical heterogeneity using the I statistic and Cochrane's Q test. We conducted meta-analysis for the overall effect and for each growth factor as a subgroup analysis using OR in a fixed-effect model. We evaluated the robustness of the results in a sensitivity analysis using risk ratio (RR) and/or a random-effects model. We also assessed the quality of the evidence for each outcome.
MAIN RESULTS
We included 20 trials in the review and used 14 studies (on approximately 1400 participants) with published results in the analyses. Six published studies compared fibroblast growth factors (FGF), four studies hepatocyte growth factors (HGF) and another four studies vascular endothelial growth factors (VEGF), versus placebo or no therapy. Six of these studies exclusively or mainly investigated participants with intermittent claudication and eight studies exclusively participants with critical limb ischaemia. Follow-up generally ranged from three months to one year. Two small studies provided some data at 2 years and one of them also at 10 years.The direction and size of effects for growth factors on major limb amputations (OR 0.99, 95% CI 0.71 to 1.38; 10 studies, N = 1075) and death (OR 0.99, 95% CI 0.69 to 1.41; 12 studies, N = 1371) at up to two years are uncertain. The quality of the evidence is low due to risk of bias and imprecision (at one year, moderate-quality evidence due to imprecision). However, growth factors may decrease the rate of any limb amputations (OR 0.56, 95% CI 0.31 to 0.99; 6 studies, N = 415). The quality of the evidence is low due to risk of bias and selective reporting.The direction and size of effects for growth factors on serious adverse events (OR 1.09, 95% CI 0.79 to 1.50; 13 studies, N = 1411) and on any adverse events (OR 1.10, 95% CI 0.73 to 1.64; 4 studies, N = 709) at up to two years are also uncertain. The quality of the evidence is low due to risk of bias and imprecision (for serious adverse events at one year, moderate-quality evidence due to imprecision).Growth factors may improve haemodynamic measures (low-quality evidence), ulceration (very low-quality evidence) and rest pain (very low-quality evidence) up to one year, but they have little or no effect on walking ability (low-quality evidence). We did not identify any relevant differences in effects between growth factors (FGF, HGF and VEGF).
AUTHORS' CONCLUSIONS
The results of this review do not support the use of therapy with the growth factors FGF, HGF or VEGF in people with PAD of the lower extremities to prevent death or major limb amputation or to improve walking ability. However, the use of these growth factors may improve haemodynamic measures and decrease the rate of any limb amputations (probably due to preventing minor amputations) with an uncertain effect on adverse events; an improvement of ulceration and rest pain is very uncertain. New trials at low risk of bias are needed to generate evidence with more certainty.
Topics: Amputation, Surgical; Fibroblast Growth Factors; Hepatocyte Growth Factor; Humans; Intermittent Claudication; Leg; Leg Ulcer; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A
PubMed: 28594443
DOI: 10.1002/14651858.CD011741.pub2 -
Access Microbiology 2023In Central Africa, it is difficult to tackle antibiotic resistance, because of a lack of data and information on bacterial resistance, due to the low number of studies... (Review)
Review
BACKGROUND
In Central Africa, it is difficult to tackle antibiotic resistance, because of a lack of data and information on bacterial resistance, due to the low number of studies carried out in the field. To fill this gap, we carried out a systematic review of the various studies, and devised a molecular epidemiology of antimicrobial resistance from humans, animals and the environmental samples.
METHOD
A systematic search of all publications from 2005 to 2020 on bacterial resistance in Central Africa (Gabon, Cameroon, Democratic Republic of Congo, Central African Republic, Chad, Republic of Congo, Equatorial Guinea, São Tomé and Príncipe, Angola) was performed on Pubmed, Google scholar and African Journals Online (AJOL). All circulating resistance genes, prevalence and genetic carriers of these resistances were collected. The study area was limited to the nine countries of Central Africa.
RESULTS
A total of 517 studies were identified through a literature search, and 60 studies carried out in eight countries were included. Among all articles included, 43 articles were from humans. Our study revealed not only the circulation of beta-lactamase and carbapenemase genes, but also several other types of resistance genes. To finish, we noticed that some studies reported mobile genetic elements such as integrons, transposons, and plasmids.
CONCLUSION
The scarcity of data poses difficulties in the implementation of effective strategies against antibiotic resistance, which requires a health policy in a 'One Health' approach.
PubMed: 37691840
DOI: 10.1099/acmi.0.000556.v5 -
Microbial Drug Resistance (Larchmont,... Jan 2021We have conducted a systematic review to update available information on plasmid-mediated colistin resistance (mobilized colistin resistance []) genes in North African...
We have conducted a systematic review to update available information on plasmid-mediated colistin resistance (mobilized colistin resistance []) genes in North African countries. We have searched the articles of PubMed, Scopus, and Web of Science databases reporting plasmid-mediated colistin resistance bacteria isolated in North African countries. After searching and selection, 30 studies that included 208 positive isolates were included. Different positive strains frequencies were recorded and ranged from 2% in clinical isolates to 12.3% in environmental samples. was the predominant species recorded and these microorganisms showed high resistance to ciprofloxacin and cotrimoxazole. IncHI2 plasmids are probably the key vectors responsible for the dissemination of genes in these countries. This review highlighted that the -positive isolates are circulating in different ecological niches with different frequencies. Therefore, actions should be implemented to prevent the dissemination of the genes within and outside of these countries, such as microbiological and molecular surveillance programs and restriction use of colistin in farming.
Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Humans; Plasmids
PubMed: 32522081
DOI: 10.1089/mdr.2019.0471 -
European Journal of Medical Research Jul 2023Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Vitro experiments have shown that adding... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Vitro experiments have shown that adding cytokines can help DPSCs to be transformed from multipotent stem cells to osteoblasts. TGF-β has been proved to have an effect on the proliferation and mineralization of bone tissue, but its effect on the osteogenesis and proliferation of dental pulp stem cells is still uncertain. We aim to determine the effect of TGF-β on the osteogenesis and proliferation of dental pulp stem cells.
METHODS
We have identified studies from the Cochrane Central Register of Controlled Trials, PubMed, Embase, and China national knowledge infrastructure (CNKI) for studies interested in TGF-β and proliferation and differentiation of dental pulp stem cells in the following indicators: A490 (an index for evaluating cell proliferation), bone sialoprotein (BSP), Col plasmid-1 (Col-1), osteocalcin (OCN), runt-related transcription factor 2 (Runx-2); and the number of mineralized nodules. Any language restrictions were rejected. Furthermore, we drew a forest plot for each outcome. We conducted a sensitivity analysis, data analysis, heterogeneity, and publication bias test. We evaluate the quality of each study under the guidance of Cochrane's tool for quality assessment.
RESULTS
The pooled data showed that TGF-β could promote the proliferation and ossification of dental pulp stem cells. All the included results support this conclusion except for the number of mineralized nodules: TGF-β increases the A490 index (SMD 3.11, 95% CI [0.54-5.69]), promotes the production of BSP (SMD 3.11, 95% CI [0.81-6.77]), promotes the expression of Col-1 (SMD 4.71, 95% CI [1.25-8.16]) and Runx-2 (SMD 3.37, 95% CI [- 0.63 to 7.36]), increases the content of OCN (SMD 4.32, 95% CI [1.20-7.44]) in dental pulp, and has no significant effect on the number of mineralized nodules (SMD 3.87, 95% CI [- 1.76 to 9.51]) in dental pulp stem cells.
CONCLUSIONS
TGF-β promotes the proliferation and osteogenesis of dental pulp stem cells.
Topics: Humans; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Pulp; Osteogenesis; Stem Cells; Transforming Growth Factor beta
PubMed: 37501191
DOI: 10.1186/s40001-023-01227-y -
Scientific Reports Apr 2022The comprehensive effect size of several commercial vaccines and vaccine candidates against edema disease (ED) has not been evaluated to date. To integrate the... (Meta-Analysis)
Meta-Analysis
The comprehensive effect size of several commercial vaccines and vaccine candidates against edema disease (ED) has not been evaluated to date. To integrate the effectiveness of ED vaccines reported so far and to compare and evaluate the posterior-effect estimates of each vaccine type with network models, we identified eligible studies (n = 12) from the electronic databases using specified search strings. Data for dichotomous outcomes (i.e., mortality and clinical symptoms) and continuous outcomes (i.e., fecal shedding and average daily gain) were extracted and analyzed. Conventional meta-analysis shows that, compared with that in non-vaccinated pigs, vaccinated animals are likely to show reduced mortality (OR = 0.07) and clinical signs of ED (OR = 0.11), and increased productivity (SMD = 0.73). Although reduced fecal shedding (SMD = - 1.29) was observed in vaccinated pigs, this could not be fully determined on insufficient grounds. In contrast to mortality and clinical symptoms, fecal shedding (I = 88%) and average daily gain (I = 85%) showed immense heterogeneity, which was attributed to the small sample size and vaccination route, respectively. According to the Bayesian network meta-analysis, the plasmid-based DNA vaccine demonstrated a better effect for all outcomes compared to other types of vaccines. However, these findings should be carefully interpreted with consideration to potential mediators, insufficient data, and inconsistent network models.
Topics: Animals; Bayes Theorem; Edema; Edema Disease of Swine; Escherichia coli Infections; Network Meta-Analysis; Shiga-Toxigenic Escherichia coli; Swine; Vaccine Efficacy
PubMed: 35440612
DOI: 10.1038/s41598-022-10439-x -
Annals of the New York Academy of... Oct 2021In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating... (Meta-Analysis)
Meta-Analysis
Risk factors for, and molecular epidemiology and clinical outcomes of, carbapenem- and polymyxin-resistant Gram-negative bacterial infections in pregnant women, infants, and toddlers: a systematic review and meta-analyses.
In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating multidrug-resistant bacterial infections among pregnant women and infants. Resistance to carbapenems and polymyxins is increasing, even in otherwise vulnerable groups such as pregnant women, toddlers, and infants, for whom therapeutic options are limited. In almost all countries, carbapenem-/polymyxin-resistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii infect and/or colonize neonates and pregnant women, causing periodic outbreaks with very high infant mortalities. Downregulation of plasmid-borne bla , bla , bla , bla bla , bla , and ompK35/36 in clonal strains accelerates the horizontal and vertical transmissions of carbapenem resistance among these pathogens. New Delhi metallo-β-lactamase (NDM)-positive isolates in infants/neonates have been mainly detected in China and India, while OXA-48-positive isolates in infants/neonates have been mainly detected in Africa. NDM-positive isolates in pregnant women have been found only in Madagascar. Antibiotic therapy, prolonged hospitalization, invasive procedures, mechanical ventilation, low birth weight, and preterm delivery have been common risk factors associated with carbapenem/polymyxin resistance. The use of polymyxins to treat carbapenem-resistant infections may be selecting for resistance to both agents, restricting therapeutic options for infected infants and pregnant women. Currently, low- and middle-income countries have the highest burden of these pathogens. Antibiotic stewardship, periodic rectal and vaginal screening, and strict infection control practices in neonatal ICUs are necessary to forestall future outbreaks and deaths.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Carbapenems; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Infant; Infant, Newborn; Middle Aged; Molecular Epidemiology; Mortality; Polymyxins; Pregnancy; Pregnancy Complications, Infectious; Risk Assessment; Risk Factors; Young Adult
PubMed: 34212401
DOI: 10.1111/nyas.14650 -
Vaccine Jan 2021Recent deadly outbreaks of Marburg virus underscore the need for an effective vaccine. A summary of the latest research is needed for this WHO priority pathogen. This... (Review)
Review
BACKGROUND
Recent deadly outbreaks of Marburg virus underscore the need for an effective vaccine. A summary of the latest research is needed for this WHO priority pathogen. This systematic review aimed to determine progress towards a vaccine for Marburg virus.
METHODS
Article search criteria were developed to query PubMed for peer-reviewed articles from 1990 through 2019 on Marburg virus vaccine clinical trials in humans and pre-clinical studies in non-human primates (NHP). Abstracts were reviewed by two authors. Relevant articles were reviewed in full. Discrepancies were resolved by a third author. Data abstracted included year, author, title, vaccine construct, number of subjects, efficacy, and demographics. Assessment for risk of bias was performed using the Syrcle tool for animal studies, and the Cochrane Collaboration risk of bias tool for human studies.
RESULTS
101 articles were identified; 27 were related to Marburg vaccines. After full text review, 21 articles were selected. 215 human subjects were in three phase 1 clinical trials, and 203 NHP in 18 studies. Vaccine constructs were DNA plasmids, recombinant vesicular stomatitis virus (VSV) vectors, adenovirus vectors, virus-like particles (VLP), among others. Two human phase 1 studies of DNA vaccines had 4 adverse effects requiring vaccine discontinuation among 128 participants and 31-80% immunogenicity. In NHP challenge studies, 100% survival was seen in 6 VSV vectored vaccines, 2 DNA vaccines, 2 VLP vaccines, and in 1 adenoviral vectored vaccine.
CONCLUSION
In human trials, two Marburg DNA vaccines provided either low immunogenicity or a failure to elicit durable immunity. A variety of NHP candidate Marburg vaccines demonstrated favorable survival and immunogenicity parameters, to include VSV, VLP, and adenoviral vectored vaccines. Elevated binding antibodies appeared to be consistently associated with protection across the NHP challenge studies. Further human trials are needed to advance vaccines to limit the spread of this highly lethal virus.
Topics: Animals; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Marburgvirus; Primates; Viral Vaccines
PubMed: 33309082
DOI: 10.1016/j.vaccine.2020.11.042 -
International Journal of Antimicrobial... Jan 2021Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) are widespread. Here we used the 'One Health'...
Epidemiology and prevalence of extended-spectrum β-lactamase- and carbapenemase-producing Enterobacteriaceae in humans, animals and the environment in West and Central Africa.
Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) are widespread. Here we used the 'One Health' approach to determine knowledge gaps on ESBL-E and CPE in West and Central Africa. We searched all articles on ESBL-E and CPE in these African regions published in PubMed, African Journals Online and Google Scholar from 2000 onwards. Among the 1201 articles retrieved, we selected 165 studies (West Africa, 118; Central Africa, 47) with data from 22 of the 26 West and Central Africa countries. Regarding the settings, 136 articles focused only on humans (carriage and/or infection), 6 articles on humans and animals, 13 on animals, 1 on humans and the environment, 8 on the environment and 1 on humans, animals and environments. ESBL-E prevalence ranged from 11-72% in humans and 7-79% in aquatic environments (wastewater). In animals, ESBL-E prevalence hugely varied: 0% in cattle, 11-36% in chickens, 20% in rats, 21-71% in pigs and 32-75% in dogs. The bla gene was the predominant ESBL-encoding gene and was associated with plasmids of incompatibility groups F, H, K, Y, N, I1 and R. CPE were studied only in humans. Class B metallo-β-lactamases (NDM) and class D oxacillinases (OXA-48 and OXA-181) were the most common carbapenemases. Our results show major knowledge gaps, particularly on ESBL and CPE in animals and the environment, that might limit antimicrobial resistance management in these regions. The results also emphasise the urgent need to improve active surveillance programmes in each country and to support antimicrobial stewardship.
Topics: Africa, Central; Africa, Western; Animals; Anti-Bacterial Agents; Bacterial Proteins; Cattle; Chickens; Dogs; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Environmental Microbiology; Humans; Plasmids; Prevalence; Rats; Swine; beta-Lactamases
PubMed: 33075511
DOI: 10.1016/j.ijantimicag.2020.106203 -
Annals of the New York Academy of... Mar 2022Antimicrobial resistance (AMR) is a public health threat globally. Carbapenems are β-lactam antibiotics used as last-resort agents for treating antibiotic-resistant... (Meta-Analysis)
Meta-Analysis
Antimicrobial resistance (AMR) is a public health threat globally. Carbapenems are β-lactam antibiotics used as last-resort agents for treating antibiotic-resistant infections. Mobile genetic elements (MGEs) play an important role in the dissemination and expression of antimicrobial resistance genes (ARGs), including the mobilization of ARGs within and between species. The presence of MGEs around carbapenem-hydrolyzing enzymes, called carbapenemases, in bacterial isolates in Africa is concerning. The association between MGEs and carbapenemases is described herein. Specific plasmid replicons, integrons, transposons, and insertion sequences were found flanking specific and different carbapenemases across the same and different clones and species isolated from humans, animals, and the environment. Notably, similar genetic contexts have been reported in non-African countries, supporting the importance of MGEs in driving the intra- and interclonal and species transmission of carbapenemases in Africa and globally. Technical and budgetary limitations remain challenges for epidemiological analysis of carbapenemases in Africa, as studies undertaken with whole-genome sequencing remained relatively few. Characterization of MGEs in antibiotic-resistant infections can deepen our understanding of carbapenemase epidemiology and facilitate the control of AMR in Africa. Investment in genomic epidemiology will facilitate faster clinical interventions and containment of outbreaks.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Humans; One Health; Plasmids; beta-Lactamases
PubMed: 34753206
DOI: 10.1111/nyas.14703 -
Infection and Drug Resistance 2022Carbapenemases are β-lactamase enzymes that hydrolyze a variety of β-lactams including carbapenem and belong to different Ambler classes (A, B, D). These enzymes can... (Review)
Review
Carbapenemases are β-lactamase enzymes that hydrolyze a variety of β-lactams including carbapenem and belong to different Ambler classes (A, B, D). These enzymes can be encoded by plasmid or chromosomal-mediated genes. The major issues associated with carbapenemases-producing organisms are compromising the activity and increasing the resistance to carbapenems which are the last resort antibiotics used in treating serious infections. The global increase of pathogen, carbapenem-resistant has significantly threatened public health. Thus, there is a pressing need for a better understanding of this pathogen, to know the various carbapenem resistance encoding genes and dissemination of resistance genes from which help in developing strategies to overcome this problem. The horizontal transfer of resistant determinants through mobile genetic elements increases the incidence of multidrug, extensive drug, and Pan-drug resistant . Therefore, the current review aims to know the various mechanisms of carbapenem resistance, categorize and discuss carbapenemases encoding genes and various mobile genetic elements, and the prevalence of carbapenemase genes in recent years in from various geographical regions.
PubMed: 36579124
DOI: 10.2147/IDR.S386641