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Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis.The Lancet. Gastroenterology &... Nov 2019There are several drugs available for the treatment of chronic idiopathic constipation, but their relative efficacy is unclear because there have been no head-to-head... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are several drugs available for the treatment of chronic idiopathic constipation, but their relative efficacy is unclear because there have been no head-to-head randomised controlled trials. We did a network meta-analysis to compare the efficacy of these therapies in patients with chronic idiopathic constipation.
METHODS
We searched Medline, Embase, Embase Classic, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published from inception to week 3 June, 2019, to identify randomised controlled trials assessing the efficacy of drugs (osmotic or stimulant laxatives, elobixibat, linaclotide, lubiprostone, mizagliflozin, naronapride, plecanatide, prucalopride, tegaserod, tenapanor, or velusetrag) in adults with chronic idiopathic constipation. Participants had to be treated for a minimum of 4 weeks, and we extracted data for all endpoints preferentially at 4 weeks, 12 weeks, or both. Trials included in the analysis reported a dichotomous assessment of overall response to therapy (response or no response to therapy). We pooled the data using a random effects model, and reported efficacy and safety of all treatments as a pooled relative risk (RR) with 95% CIs to summarise the effect of each comparison tested. To rank treatments, we used P-scores, which measure the extent of certainty that a treatment is better than another treatment, averaged over all competing treatments.
FINDINGS
We identified 33 eligible randomised controlled trials of drugs, comprising 17 214 patients. Based on an endpoint of failure to achieve three or more complete spontaneous bowel movements (CSBMs) per week, the stimulant diphenyl methane laxatives bisacodyl and sodium picosulfate, at a dose of 10 mg once daily, were ranked first at 4 weeks (RR 0·55, 95% CI 0·48-0·63, P-score 0·99), and prucalopride 2 mg once daily ranked first at 12 weeks (0·82, 0·78-0·86, P-score 0·96). When response to therapy was defined as falilure to achieve an increase of one or more CSBM per week from baseline, diphenyl methane laxatives at a dose of 10 mg once daily ranked first at 4 weeks (0·44, 0·37-0·54, P-score 0·99), with prucalopride 4 mg once daily ranked first at 12 weeks (0·74, 0·66-0·83, P-score 0·79), although linaclotide 290 μg once daily and prucalopride 2 mg once daily had similar efficacy (P-scores of 0·76 and 0·71, respectively). Bisacodyl ranked last in terms of safety for total number of adverse events and abdominal pain (P-score 0·08).
INTERPRETATION
Almost all drugs studied were superior to placebo, according to either failure to achieve three or more CSBMs per week or or failure to achieve an increase of one or more CSBM per week over baseline. Although diphenyl methane laxatives ranked first at 4 weeks, patients with milder symptoms might have been included in these trials. Prucalopride ranked first at 12 weeks, and many of the included trials recruited patients who previously did not respond to laxatives, suggesting that this drug is likely to be the most efficacious for patients with chronic idiopathic constipation. However, because treatment duration in most trials was 4-12 weeks, the long-term relative efficacy of these drugs is unknown.
FUNDING
None.
Topics: Constipation; Humans; Laxatives; Randomized Controlled Trials as Topic
PubMed: 31474542
DOI: 10.1016/S2468-1253(19)30246-8 -
Gut Microbes 2021Several studies reported a potential role of methane producing archaea in the pathophysiology of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We... (Meta-Analysis)
Meta-Analysis
Several studies reported a potential role of methane producing archaea in the pathophysiology of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the prevalence of methane positive small intestinal bacterial overgrowth (SIBO) in IBS and IBD compared with controls. MEDLINE (PubMed) and Embase electronic databases were searched from inception until March 2021 for case-control and prevalence studies reporting SIBO in IBS and IBD. We extracted data from published studies and calculated pooled prevalence of SIBO in IBS or IBD, odds ratios (OR), and 95% CIs, utilizing a random effects model. The final dataset included 17 independent studies assessing the prevalence of methane positive SIBO in 1,653 IBS-patients and 713 controls, and 7 studies assessing the prevalence of methane positive SIBO in 626 IBD-patients and 497 controls, all utilizing breath test for SIBO diagnosis. Prevalence of methane positive SIBO in IBS and IBD was 25.0% (95% CI 18.8-32.4) and 5.6% (95% CI 2.6-11.8), respectively. Methane positive SIBO in IBS was not increased compared to controls (OR = 1.2, 95% CI 0.8-1.7, = .37) but was significantly more prevalent in IBS-C as compared to IBS-D (OR = 3.1, 95% CI 1.7-5.6, = .0001). The prevalence of methane-positive SIBO in patients with IBD was 3-fold lower at 7.4% (95% CI 5.4-9.8) compared to 23.5% (95% CI 19.8-27.5) in controls. The prevalence of methane positive SIBO was significantly lower in Crohn's disease as compared to ulcerative colitis, (5.3%, 95% CI 3.0-8.5 vs. 20.2%, 95% CI 12.8-29.4). This systematic review and meta-analysis suggests methane positivity on breath testing is positively associated with IBS-C and inversely with IBD. However, the quality of evidence is low largely due to clinical heterogeneity of the studies. Thus, causality is uncertain and further studies are required.
Topics: Bacteria; Breath Tests; Case-Control Studies; Female; Humans; Inflammatory Bowel Diseases; Intestine, Small; Irritable Bowel Syndrome; Male; Methane
PubMed: 34190027
DOI: 10.1080/19490976.2021.1933313 -
Vaccines Aug 2020Ruminants produce considerable amounts of methane during their digestive process, which makes the livestock industry as one of the largest sources of anthropogenic... (Review)
Review
Ruminants produce considerable amounts of methane during their digestive process, which makes the livestock industry as one of the largest sources of anthropogenic greenhouse gases. To tackle this situation, several solutions have been proposed, including vaccination of ruminants against microorganisms responsible for methane synthesis in the rumen. In this review, we summarize the research done on this topic and describe the state of the art of this strategy. The different steps implied in this approach are described: experimental design, animal model (species, age), antigen (whole cells, cell parts, recombinant proteins, peptides), adjuvant (Freund's, Montanide, saponin, among others), vaccination schedule (booster intervals and numbers) and measurements of treatment success (immunoglobulin titers and/or effects on methanogens and methane production). Highlighting both the advances made and knowledge gaps in the use of vaccines to inhibit ruminant methanogen activity, this research review opens the door to future studies. This will enable improvements in the methodology and systemic approaches so as to ensure the success of this proposal for the sustainable mitigation of methane emission.
PubMed: 32825375
DOI: 10.3390/vaccines8030460 -
Muscles, Ligaments and Tendons Journal 2016nutraceuticals are common support therapy for management of tendinopathies. Even if they are widely diffused, our knowledge is still poor. The aim of this systematic... (Review)
Review
BACKGROUND
nutraceuticals are common support therapy for management of tendinopathies. Even if they are widely diffused, our knowledge is still poor. The aim of this systematic review is to analyze the most commonly used nutraceuticals and their effects on tendons.
METHODS
glucosamine and chondroitin sulphate, vitamin C, hydrolazed type 1 collagen, arginine alpha-keto-glutarate, bromelain, curcumin, boswellic acid, and methil-sulfonil-methane were considered. During the last week of Dicember 2015 a comprehensive research of main databases for each substance was made in relation with tendinopathy. Repeated articles, articles not in English nor in Italian, not common nutraceuticals, and articles not related with tendons or tenocytes were excluded. Clinical article quality was assessed independently by two reviewers using the modified Coleman methodology score.
RESULTS
preclinical and clinical data from 46 articles from all databases were analyzed. All these nutraceuticals demonstrated several effects on normal and pathological tendons. Preclinical and clinical studies showed a possible role on collagen synthesis, inflammation, mechanical properties, and maturation of collagen bundles, antioxidant effect, edema, and analgesia. The majority clinical studies had some methodological limitations with an average Modified Coleman Methodology Score of 51.3 points and SD of 20.5 points. In particular, there were very low values in power, error, outcome assessment, and clinical effect.
CONCLUSION
preclinical results are very encouraging, however they are not fully confirmed by clinical studies. There are few clinical papers on the use of nutraceuticals in tendon disorders, and their methodological quality is poor. Furthermore, in most of the studies more than one supplement was administered at the same time. This may bias the results, and the effect of each single component cannot be determined. Furthermore, the interactions between nutraceuticals and drugs, or other dietary supplements (especially at high doses) has not been evaluated, neither their effects on chronic diseases. For these reasons, it is not possible to draw any definitive raccomendations on the use of nutraceutical supplementation in tendinopathies.
PubMed: 27331031
DOI: 10.11138/mltj/2016.6.1.048 -
The ISME Journal Jan 2024Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing... (Review)
Review
Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing microbial ecology. Since their first application for aerobic gammaproteobacterial methane oxidizers less than a decade ago, GEMs have substantially increased our understanding of the metabolism of methanotrophs, a microbial guild of high relevance for the natural and biotechnological mitigation of methane efflux to the atmosphere. Particularly, GEMs helped to elucidate critical metabolic and regulatory pathways of several methanotrophic strains, predicted microbial responses to environmental perturbations, and were used to model metabolic interactions in cocultures. Here, we conducted a systematic review of GEMs exploring aerobic methanotrophy, summarizing recent advances, pointing out weaknesses, and drawing out probable future uses of GEMs to improve our understanding of the ecology of methane oxidizers. We also focus on their potential to unravel causes and consequences when studying interactions of methane-oxidizing bacteria with other methanotrophs or members of microbial communities in general. This review aims to bridge the gap between applied sciences and microbial ecology research on methane oxidizers as model organisms and to provide an outlook for future studies.
Topics: Methane; Oxidation-Reduction; Aerobiosis; Metabolic Networks and Pathways; Models, Biological
PubMed: 38861460
DOI: 10.1093/ismejo/wrae102 -
Heliyon Nov 2023Combined application of biochar and nitrogen (N) fertilizer could offer opportunities to increase rice yield and reduce methane emissions from paddy fields. However,... (Review)
Review
Combined application of biochar and nitrogen (N) fertilizer could offer opportunities to increase rice yield and reduce methane emissions from paddy fields. However, this strategy may increase nitrous oxide (NO) emissions, hence its interactive effects on GHG emissions, global warming potential (GWP) and GHG intensity (GHGI) remained poorly understood. We conducted a systematic review to i) evaluate the overall effects of combined application of biochar and N fertilizer rates on GHGs emissions, GWP, rice yield, and GHGI, ii) determine the quantities of biochar and N-fertilizer application that increase rice yield and reduce GHGs emissions and GHGI, and iii) examine the effects of biochar and different types of nitrogen fertilizers on rice yield, GHGs, GWP, and GHGI using data from 45 research articles and 183 paired observations. The extracted data were grouped based on biochar and N rates used by researchers as well as N fertiliser types. Accordingly, biochar rates were grouped into low (≤9 tons/ha), medium (>9 and ≤ 20 ton/ha) and high (>20 tons/ha), while N rates were grouped into three categories: low (≤140 kg N/ha), medium (>140 and ≤ 240 kg N/ha), and high (>240 kg N/ha). For fertiliser types, N rates were grouped as: low (≤150 kg N/ha), medium (>150 and ≤250 kg N/ha), and high (>250 kg N/ha) and N types into: urea, NPK, NPK plus urea (NPK_urea) and NPK plus (NH)SO (NPK_(NH)SO). Results showed that biochar and N fertiliser significantly affected GHGs emissions, GWP, GHGI and rice yield. Compared to control (i.e., sole N application), co-application of high biochar and medium N rates significantly decreased CH emission (82 %) while low biochar with low N rates enhanced CH emission (114 %). In contrast, high biochar combined with low N decreased NO emission by 91 % whereas medium biochar and high N rates resulted in 82 % increase in NO emission relative to control. The highest GWP and GHGI were observed under co-application of medium biochar and low N rates. Highest rice yield was observed under low biochar rate and high N rate. Regardless of N fertiliser type and biochar rates, increasing N rates increased rice yield and NO emissions. The highest GWP and GHGI were recorded under sole NPK application. Combination of low biochar and medium N produced low GHGs emissions, high grain yield, and the lowest GHGI, and could be recommended to smallholder farmers to increase rice yield and reduce greenhouse gas emissions from paddy rice field. Further studies should be conducted to evaluate the effects of biochar properties on soil characteristics and greenhouse gas emissions.
PubMed: 38045115
DOI: 10.1016/j.heliyon.2023.e22132 -
International Journal of Environmental... Feb 2023Constructed wetlands (CWs) are an eco-technology for wastewater treatment and are applied worldwide. Due to the regular influx of pollutants, CWs can release... (Meta-Analysis)
Meta-Analysis Review
Constructed wetlands (CWs) are an eco-technology for wastewater treatment and are applied worldwide. Due to the regular influx of pollutants, CWs can release considerable quantities of greenhouse gases (GHGs), ammonia (NH), and other atmospheric pollutants, such as volatile organic compounds (VOCs) and hydrogen sulfide (HS), etc., which will aggravate global warming, degrade air quality and even threaten human health. However, there is a lack of systematic understanding of factors affecting the emission of these gases in CWs. In this study, we applied meta-analysis to quantitatively review the main influencing factors of GHG emission from CWs; meanwhile, the emissions of NH, VOCs, and HS were qualitatively assessed. Meta-analysis indicates that horizontal subsurface flow (HSSF) CWs emit less CH and NO than free water surface flow (FWS) CWs. The addition of biochar can mitigate NO emission compared to gravel-based CWs but has the risk of increasing CH emission. Polyculture CWs stimulate CH emission but pose no influence on NO emission compared to monoculture CWs. The influent wastewater characteristics (e.g., C/N ratio, salinity) and environmental conditions (e.g., temperature) can also impact GHG emission. The NH volatilization from CWs is positively related to the influent nitrogen concentration and pH value. High plant species richness tends to reduce NH volatilization and plant composition showed greater effects than species richness. Though VOCs and HS emissions from CWs do not always occur, it should be a concern when using CWs to treat wastewater containing hydrocarbon and acid. This study provides solid references for simultaneously achieving pollutant removal and reducing gaseous emission from CWs, which avoids the transformation of water pollution into air contamination.
Topics: Humans; Gases; Greenhouse Gases; Methane; Nitrous Oxide; Wastewater; Wetlands
PubMed: 36900888
DOI: 10.3390/ijerph20053876 -
Global Change Biology Mar 2015The establishment of sustainable soil waste management practices implies minimizing their environmental losses associated with climate change (greenhouse gases: GHGs)... (Review)
Review
The establishment of sustainable soil waste management practices implies minimizing their environmental losses associated with climate change (greenhouse gases: GHGs) and ecosystems acidification (ammonia: NH3 ). Although a number of management strategies for solid waste management have been investigated to quantify nitrogen (N) and carbon (C) losses in relation to varied environmental and operational conditions, their overall effect is still uncertain. In this context, we have analyzed the current scientific information through a systematic review. We quantified the response of GHG emissions, NH3 emissions, and total N losses to different solid waste management strategies (conventional solid storage, turned composting, forced aerated composting, covering, compaction, addition/substitution of bulking agents and the use of additives). Our study is based on a meta-analysis of 50 research articles involving 304 observations. Our results indicated that improving the structure of the pile (waste or manure heap) via addition or substitution of certain bulking agents significantly reduced nitrous oxide (N2 O) and methane (CH4 ) emissions by 53% and 71%, respectively. Turned composting systems, unlike forced aerated composted systems, showed potential for reducing GHGs (N2 O: 50% and CH4 : 71%). Bulking agents and both composting systems involved a certain degree of pollution swapping as they significantly promoted NH3 emissions by 35%, 54%, and 121% for bulking agents, turned and forced aerated composting, respectively. Strategies based on the restriction of O2 supply, such as covering or compaction, did not show significant effects on reducing GHGs but substantially decreased NH3 emissions by 61% and 54% for covering and compaction, respectively. The use of specific additives significantly reduced NH3 losses by 69%. Our meta-analysis suggested that there is enough evidence to refine future Intergovernmental Panel on Climate Change (IPCC) methodologies from solid waste, especially for solid waste composting practices. More holistic and integrated approaches are therefore required to develop more sustainable solid waste management systems.
Topics: Air Pollutants; Air Pollution; Gases; Greenhouse Effect; Nitrogen; Solid Waste; Waste Management
PubMed: 25393229
DOI: 10.1111/gcb.12806 -
Journal of Dairy Science Jan 2024To investigate the effects of supplemental monensin administration on the metabolic responses of dairy cows, a systematic review and dose-response meta-analysis were... (Meta-Analysis)
Meta-Analysis
Effects of monensin supplementation on rumen fermentation, methane emissions, nitrogen balance, and metabolic responses of dairy cows: A systematic review and dose-response meta-analysis.
To investigate the effects of supplemental monensin administration on the metabolic responses of dairy cows, a systematic review and dose-response meta-analysis were conducted. Initially, 604 studies were identified through comprehensive database searches, including Google Scholar, Scopus, Science Direct, and PubMed, using key words related to dairy cows, monensin, and metabolic outcomes. After a 2-stage screening process, 51 articles with a total of 60 experiments were selected for meta-analysis based on criteria such as study implementation date between 2001 and 2022, presence of a control group that did not receive monensin supplementation, reporting of at least 1 outcome variable, and presentation of means and corresponding errors. The meta-analysis used the 1-stage random-effects method, and sensitivity analyses were performed to assess the robustness of the results. The results showed that the administration of monensin at a dosage of 19 to 26 mg/kg was inversely related to methane emissions and that the administration of monensin at a dosage of 18 to 50 mg/kg resulted in a significant decrease in dry matter intake. Administration of monensin at doses of 13 to 28 and 15 to 24 mg/kg also resulted in a significant decrease in ruminal acetate proportion and an increase in propionate proportion, respectively, with no effects on ruminal butyrate, NH, or pH levels. We found no effects on blood parameters or nitrogen retention, but a significant negative correlation was observed between monensin supplementation and fecal nitrogen excretion. Based on the analysis of all variables evaluated, the optimal dose range of monensin was estimated to be 19 to 24 mg/kg.
Topics: Female; Cattle; Animals; Monensin; Milk; Fermentation; Methane; Rumen; Nitrogen; Dietary Supplements; Diet; Lactation
PubMed: 37709041
DOI: 10.3168/jds.2023-23441 -
Nutrients Dec 2022Bacterial overgrowth in the small intestine (SIBO) is a pathological growth of the intestinal microbiota in the small intestine that causes clinical symptoms and can... (Meta-Analysis)
Meta-Analysis Review
The Prevalence of Small Intestinal Bacterial Overgrowth in Patients with Non-Alcoholic Liver Diseases: NAFLD, NASH, Fibrosis, Cirrhosis-A Systematic Review, Meta-Analysis and Meta-Regression.
Bacterial overgrowth in the small intestine (SIBO) is a pathological growth of the intestinal microbiota in the small intestine that causes clinical symptoms and can lead to digestive and absorption disorders. There is increasing evidence that people with NAFLD have a distinct gut microflora profile as well metabolome changes compared to people without NAFLD. Thorough analysis of observational and RCT studies in the current databases (EMBASE, Web of Science, PubMed, Cinahl, Clinical Trials) was conducted from 3 November 2021 to 21 June 2022. The following inclusion criteria were applied: confirmed NAFLD, NASH, LIVER FIBROSIS, CIRRHOSIS due to steatosis; diagnostic methods of liver diseases—biopsy, elastography, transabdominal ultrasound; nonalcoholic fatty liver disease activity score; confirmed SIBO; diagnostic methods of SIBO−breath tests (hydrogen test; methane test and mix test; duodenal and jejunal aspiration before any type of intervention; adults above 18yo; number of participants ≥20; full articles. We excluded review articles, populations with HBV/HCV infection and alcohol etiology and interventions that may affect NAFLD or SIBO treatment. The quality of each study methodology was classified by means of the Cochrane Collaboration’s tool (RCT) and Newcastle—Ottawa Quality Assessment Scale adapted for cross-sectional, cohort and case-control studies. The random effects meta-analysis of outcomes for which ≥2 studies contributed data was conducted. The I2 index to measure heterogeneity and the χ2 test of homogeneity (statistically significant heterogeneity p < 0.05) were applied. For categorical outcome, the pooled event rate (effect size) was calculated. This systematic review was reported according to PRISMA reporting guidelines. We initially identified 6643 studies, from which 18 studies were included in final meta-analysis. The total number of patients was 1263. Accepted SIBO diagnostic methods were both available breath tests (n-total = 15) and aspirate culture (n-total = 3). We found that among patients with non-alcoholic liver diseases, the random overall event rate of SIBO was 0.350 (95% CI, 0.244−0.472), p = 0.017. The subgroup analysis regarding a type of diagnosis revealed that the lowest ER was among patients who developed simultaneously NAFLD, NASH and fibrosis: 0.197 (95% CI, 0.054−0.510) as compared to other annotated subgroups. The highest prevalence of SIBO was observed in the NASH subgroup: 0.411 (95% CI, 0.219−0.634). There were no statistically significant differences in the prevalence of SIBO in different subgroups (p = 0.854). Statistically significant heterogeneity between studies was estimated (I2 = 86.17%, p = 0.00). Egger’s test did not indicate a publication bias (df = 16, p = 0.885). A meta-regression using a random-effects model revealed that higher percentage of males in the population with liver diseases is a predisposing factor toward SIBO (Q = 4.11, df = 1, p = 0.0426 with coefficient = 0.0195, SE = 0.0096, Z = 2.03). We showed that the prevalence of SIBO in patients with chronic non-alcoholic liver diseases can be as high as 35%, and it increases with the percentage of men in the population. The prevalence of SIBO does not differ significantly depending on the type of chronic liver disease. Despite the high heterogeneity and moderate and low quality of included studies, our meta-analysis suggests the existence of a problem of SIBO in the population of patients with non-alcoholic liver diseases, and the presence of SIBO, in turn, determines the therapeutic treatment of such type of patients, which indicates the need for further research in this area. The study protocol was registered with the international Prospective Register of Systematic Reviews (PROSPERO ID: CRD42022341473).
Topics: Male; Adult; Humans; Non-alcoholic Fatty Liver Disease; Prevalence; Cross-Sectional Studies; Liver Cirrhosis; Intestine, Small
PubMed: 36558421
DOI: 10.3390/nu14245261