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Abstract
Probiotics may be an effective alternative to traditional drug therapy for constipation in the elderly.
To assess the efficacy and safety of probiotics in managing constipation among the elderly.
Eight databases were queried for randomized controlled trials (RCTs) investigating probiotics’ efficacy in addressing constipation among the elderly until January 2023. The meta-analysis was conducted employing R software version 4.2.2. The Cochrane risk of bias tool was utilized to evaluate the risk of bias, and the GRADE approach was employed to assess the credibility of the evidence concerning the efficacy of probiotics in treating constipation in older individuals.
A total of six RCTs involving 444 patients were included. Two studies were rated as low risk of bias. The meta-analysis findings revealed that probiotics, when compared to a placebo, led to an increase in stool frequency (MD = 1.02,95% CI [0.21, 2.07], p<0.05, very low quality), the probiotic group exhibited a notable impact on ameliorating symptoms associated with constipation (OR = 11.28, 95%CI [7.21, 17.64], p < 0.05, very low quality), no significant disparities were observed in terms of efforts to evacuate, manual maneuvers, and the incidence of adverse events (p>0.05).
The available evidence indicates a degree of uncertainty, ranging from low-to-very low, suggesting the efficacy of probiotics in augmenting bowel frequency and ameliorating constipation-related symptoms among elderly patients with constipation. Nevertheless, given the quality of the studies included, it is advisable to conduct further well-designed investigations with substantial sample sizes to substantiate the findings of this study.
To read the full-text of this research, you can request a copy directly from the authors.
... One of the main strengths of this systematic review and meta-analysis is the use of a rigorous and appropriate methodology, which is in line with the standards set by other recent reviews and meta-analyses [1, [25][26][27] using comparable methodological techniques. The strict standards for research selection, data extraction, and analysis process followed in this review guarantee the reliability and reproducibility of its findings, providing robust conclusions. ...
... The findings of the present review and the clinical trials analysed are in line with the evidence present in the literature [1, 4,5,31,33,35]. In summary, the potential mechanisms of probiotics' action on constipation, effectively reducing its incidence, include: (I) lowering the pH in the gut, stimulating digestive enzyme production, and facilitating food breakdown and absorption; (II) promoting gut motility, facilitating food's fast passage through the gut, and minimizing the incidence of constipation; (III) modulating the gut microbiota, increasing the abundance of beneficial bacteria, and inhibiting the growth of harmful bacteria; and (IV) promoting water absorption in the gut, making faeces soft and easy to pass, and minimizing the incidence of constipation [25,29,31,32]. ...
Aims: Research on probiotics for constipation management is still growing, and plays a crucial role in the definition of a management strategy for bowel wellbeing, constipation, and related outcomes. The present systematic review and meta-analysis of the beneficial effects of the SYNBIO® blend, to consolidate the data from various clinical trials, was conducted. Methods: A literature search using PubMed, Web of Science, and Google Scholar databases was conducted. The search was limited to clinical trials that used the SYNBIO® blend, either as dietary supplements or probiotic-enriched foods. Independently, two reviewers evaluated the trial’s quality and extracted all data. A 95% confidence interval (CI) of a weighted mean difference (MD) was used to pool continuous data. For the analysis, Review Manager version 5.4 was used. Results: Seven clinical trials involving a total of 1095 subjects were included in the analysis. Overall, the SYNBIO® blend significantly improved constipation relief by 0.75 (95% CI: 0.31 to 1.19; p = 0.0008) in 52% of the subjects, and significantly increased intestinal regularity by 1.90 compared to the placebo (95% CI: 1.02 to 2.78; p < 0.0001) in more than 60% of individuals. No adverse events were reported. Conclusions: The SYNBIO® blend was found to significantly improve overall constipation, intestinal regularity, abdominal pain, and intestinal cramping. This suggests that people with these specific symptoms could benefit from this probiotic combination.
Konstipasyon, bir kişinin "dışkılamada zorluk, bağırsak hareketlerinin azalması veya yavaşlama sorunları yaşaması" durumunu tanımlayan genel bir terimdir. Sağlık uzmanları konstipasyonu haftada üç defadan az dışkılama sıklığı olarak tanımlamaktadırlar. Görülme sıklığı yaş ilerledikçe artmakta ve yaşlı bireyler arasında en sık görülen kronik durumlardan birini oluşturmaktadır. Yapılan çalışmaların sonuçlarına göre huzurevi sakinlerinde konstipasyon daha da sık görülmektedir. Çeşitli tanımlayıcı çalışmalar, huzurevi sakinlerinin yaklaşık yarısının kronik konstipasyondan muzdarip olduğunu ve yüksek oranlarda düzenli olarak müshil kullandığını göstermiştir. Kronik hastalıkların sayısı ve çoklu ilaç kullanımının yaygın olması konstipasyon ile önemli ölçüde ilişkilidir. Ayrıca yaşlılarda hareketsizlik, yetersiz besin alımı ve dehidrasyonla ilişkili kırılganlık da konstipasyonun başlamasına katkıda bulunmaktadır. Kronik konstipasyonun sağlıkla ilgili yaşam kalitesi üzerinde olumsuz bir etkisi vardır ve hem zihinsel hem de fiziksel durumlarda önemli bir düşüşe neden olmakta, hastalara ve ulusal sağlık hizmetlerine ekonomik bir yük getirmektedir. Probiyotikler canlı mikroorganizmalardır. Bağırsak sağlığının yanı sıra konakçıya birçok yararlı etkileri nedeniyle güvenli ve yararlı bakteriler olarak kabul edilmekte ve birçok hastalığın tedavisinde etkili bir alternatif yaklaşım olarak kullanılmaktadır. Çeşitli çalışmalar probiyotiklerin konstipasyon üzerindeki yararlı etkilerini araştırmıştır. Bazı çalışmalar, probiyotiklerin yaşla ilişkili konstipasyon sorunlarını azaltmak için farmakolojik olmayan alternatif bir müdahale stratejisi olabileceğini göstermektedir. Bu bağlamda son yıllarda yaşlılarda konstipasyon tedavisinde probiyotiklerin etkinliğinin araştırılması konusunda yapılan çalışmalara ihtiyaç artmıştır.
The imbalance of microbial composition and diversity in favor of pathogenic microorganisms combined with a loss of beneficial gut microbiota taxa results from factors such as age, diet, antimicrobial administration for different infections, other underlying medical conditions, etc. Probiotics are known for their capacity to improve health by stimulating the indigenous gut microbiota, enhancing host immunity resistance to infection, helping digestion, and carrying out various other functions. Concurrently, the metabolites produced by these microorganisms, termed postbiotics, which include compounds like bacteriocins, lactic acid, and hydrogen peroxide, contribute to inhibiting a wide range of pathogenic bacteria. This review presents an update on using probiotics in managing and treating various human diseases, including complications that may emerge during or after a COVID-19 infection.
This integrative aimed to evaluate the effects and the potential mechanism of action of prebiotics, probiotics, and synbiotics on constipation-associated gastrointestinal symptoms and to identify issues that still need to be answered. A literature search was performed in the PubMed database. Animal models (n = 23) and clinical trials (n = 39) were included. In animal studies, prebiotic, probiotic, and synbiotic supplementation showed a decreased colonic transit time (CTT) and an increase in the number and water content of feces. In humans, inulin is shown to be the most promising prebiotic, while B. lactis and L. casei Shirota probiotics were shown to increase defecation frequency, the latter strain being more effective in improving stool consistency and constipation symptoms. Overall, synbiotics seem to reduce CTT, increase defecation frequency, and improve stool consistency with a controversial effect on the improvement of constipation symptoms. Moreover, some aspects of probiotic use in constipation-related outcomes remain unanswered, such as the best dose, duration, time of consumption (before, during, or after meals), and matrices, as well as their effect and mechanisms on the regulation of inflammation in patients with constipation, on polymorphisms associated with constipation, and on the management of constipation via 5-HT. Thus, more high-quality randomized control trials (RCTs) evaluating these lacking aspects are necessary to provide safe conclusions about their effectiveness in managing intestinal constipation.
Introduction:
Few reports exist regarding the therapeutic effects of probiotics on chronic constipation in elderly individuals. This study evaluated the effects of Bifidobacterium longum BB536 in elderly individuals with chronic constipation.
Methods:
This was a randomized, double-blind placebo-controlled, parallel-group superiority trial in Japan (UMIN 000033031). Eighty older adults diagnosed with chronic constipation were randomly assigned (1:1) to receive either probiotics (B. longum BB536, 5 × 1010 CFU, n=39) or placebo (n=41) once daily for up to 4 weeks. The severity of constipation was evaluated using the constipation scoring system (CSS). The primary endpoint was the difference in the changes from baseline in the CSS total score between the two groups at week 4.
Results:
A total of 79 patients (mean age of 77.9 years), including 38 patients in the BB536 group and 41 in the placebo group, completed the study. The primary endpoint was not significant (p=0.074), although there was significant improvement (P<0.01) in the BB536 group from baseline to week 4, but there were no significant changes in the placebo group. There was a significant difference and a tendency toward a difference in the changes from baseline on the "stool frequency" (P=0.008) and "failure of evacuation" (P=0.051) subscales, respectively, at week 4 between the two groups. Few adverse events related to the probiotics were observed.
Discussion:
The primary endpoints were not significant. However, probiotic supplementation significantly improved bowel movements. These results suggest that B. longum BB536 supplementation is safe and partially effective for improving chronic constipation in elderly individuals.
To perform a systematic review and meta-analysis to evaluate the effectiveness and safety of probiotics in the treatment of constipation-predominant irritable bowel syndrome (IBS-C), we searched for randomized controlled trials (RCTs) comparing probiotic care versus placebos for patients with IBS-C in five comprehensive databases (March 2022). The risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool. RevMan 5.3 was used to perform a meta-analysis on stool consistency, abdominal pain, bloating, quality of life (QoL), fecal Bifidobacterium and Lactobacillus counts, and adverse events. The GRADE approach was used to evaluate the certainty of the evidence. Ten RCTs involving 757 patients were included. Only three studies were rated as having a low risk of bias. The meta-analysis results show that, compared to the placebo, probiotics significantly improved stool consistency (MD = 0.72, 95% CI (0.18, 1.26), p < 0.05, low quality) and increased the number of fecal Bifidobacteria (MD = 1.75, 95% CI (1.51, 2.00), p < 0.05, low quality) and Lactobacillus (MD = 1.69, 95% CI (1.48, 1.89), p < 0.05, low quality), while no significant differences were found in abdominal pain scores, bloating scores, QoL scores, or the incidence of adverse events (p > 0.05). The low-to-very low certainty evidence suggests that probiotics might improve the stool consistency of patients with IBS-C and increase the number of Bifidobacteria and Lactobacilli in feces with good safety. However, more high-quality studies with large samples are needed to verify the findings.
The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
Background
Public or patient versions of guidelines (PVGs) are derivative documents that “translate” recommendations and their rationale from clinical guidelines for health professionals into a more easily understandable and usable format for patients and the public. PVGs from different groups and organizations vary considerably in terms of quality of their reporting. In order to address this issue, we aimed to develop a reporting checklist for developers of PVGs and other potential users.
Methods
First, we collected a list of potential items through reviewing a sample of PVGs, existing guidance for developing and reporting PVGs or other similar evidence-based patient tools, as well as qualitative studies on original studies of patients’ needs about the content and/or reporting of information in PVGs or similar evidence-based patient tools. Second, we conducted a two-round Delphi consultation to determine the level of consensus on the items to be included in the final reporting checklist. Third, we invited two external reviewers to provide comments on the checklist.
Results
We generated the initial list of 45 reporting items based on a review of a sample of 30 PVGs, four PVG guidance documents, and 46 relevant studies. After the two-round Delphi consultation, we formed a checklist of 17 items grouped under 12 topics for reporting PVGs.
Conclusion
The RIGHT-PVG reporting checklist provides an international consensus on the important criteria for reporting PVGs.
Background & Aims
Although functional gastrointestinal disorders (FGIDs), now called disorders of gut–brain interaction, have major economic effects on healthcare systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents.
Methods
Data were collected via the internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for internet and household groups, so data analyses were conducted and reported separately.
Results
Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.7% persons who completed the internet surveys (95% CI, 40.2–41.1) and 20.9% of persons who completed the household surveys. FGIDs were more prevalent among women than men, based on responses to the internet survey (odds ratio, 1.7; 95% CI, 1.6–1.7) and household survey (odds ratio, 1.4; 95% CI, 1.3–1.5). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%).
Conclusions
In a large-scale multi-national study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and healthcare use. Although the absolute prevalence was higher among internet respondents, similar trends and relative distributions were found in people who completed internet vs personal interviews.
Background & aims:
Clinical trials have reported controversial results regarding the effectiveness of probiotics in alleviating functional constipation in adults. We reviewed relevant randomized controlled trials to elucidate the effectiveness of probiotics on constipation symptoms in adults with functional constipation.
Methods:
We searched Medline, the Cochrane Library, Web of Science, and Google Scholar for relevant articles published up to April 2019. The primary outcomes of interest were stool frequency, gut transit time (GTT), stool consistency, and bloating. Two authors independently performed the study selection, risk-of-bias assessment, and data extraction. The outcome data were extracted from each included study and synthesized using weighted mean differences (WMDs) or standardized mean differences (SMDs). Pooled data synthesis was performed using a random-effects model.
Results:
In total, 2327 relevant studies were identified, 15 of which were found to be eligible randomized controlled trials and were included in the meta-analysis. Pooling of the extracted data demonstrated that probiotic consumption significantly reduced the whole GTT by 13.75 h [95% confidence interval (CI): -21.93 to -5.56 h] and increased the stool frequency by 0.98 (95% CI: 0.36 to 1.60) bowel movements per week. This increase was significant with the consumption of multispecies probiotics [at least two bacteria; WMD: 1.22 (95% CI: 0.50 to 1.94) bowel movements per week] but not with the consumption of Bifidobacterium lactis [WMD: 1.34 (95% CI: -0.27 to 2.94) bowel movements per week] or B. longum [WMD: -0.02 (95% CI: -0.56 to 0.53) bowel movements per week] alone. Multispecies probiotics (WMD: 1.37; 95% CI: 0.72 to 2.01), but not single-species probiotics (WMD: 1.18; 95% CI: -0.59 to 2.96), improved stool consistency (WMD: 1.30; 95% CI: 0.22 to 2.38). Similarly, multispecies probiotics (at least two bacteria; WMD: -0.49; 95% CI: -0.85 to -0.13), but not single-species probiotics (WMD: -0.24; 95% CI: -0.55 to 0.07), significantly decreased bloating. Performance bias were high, whereas detection bias was unclear because of inadequate reporting.
Conclusion:
Consumption of probiotics, in particular, multispecies probiotics, may substantially reduce the GTT, increase the stool frequency, and improve the stool consistency. Thus, probiotics can be regarded as safe and natural agents for alleviation of functional constipation in adults.
Chronic idiopathic constipation (CIC) has emerged as common problem for contemporary gastroenterology and is one of the most frequent complaints in primary care. Chronic idiopathic constipation significantly affects patients’ quality of life and has an impact on global health and economy. Functional gastrointestinal disorders and bowel disorders, according to Rome IV criteria, result from inappropriate gut-brain interactions. The pathophysiology is complex and poorly understood, with evidence accumulating that gut microbiota can be implicated in the development and function of the enteric nervous system. Gut bacteria modulate gut barrier function, short chain fatty acid synthesis, and bile acid metabolism, factors which play roles in the gut peristalsis regulation. The high prevalence of CIC, with poor treatment outcomes, warrants searches for new forms of therapy, including probiotic therapies. Probiotics are often recommended by medical practitioners, but evidence-based utility in adults with CIC is uncertain. Recommendations/guidelines are often based on results from individual studies, rather than meta-analyses or umbrella reviews. Additionally, meta-analyses often indicate a group of probiotics rather than individual strains, and they create difficulty for physicians in making therapeutic choices. More CIC patient randomised clinical studies utilising well-defined strains, or combinations, are necessary.
The aim of this narrative review is to assess and present evidence on the mechanisms of action of probiotics in constipation, their effectiveness and their utilisation by patients and healthcare professionals. Chronic constipation is a common bothersome disorder that has a considerable impact on patients' quality of life. Probiotics have been increasingly investigated for their effectiveness in various disorders, including chronic constipation. Probiotics may affect gut motility and constipation through their impact on the gut microbiota and fermentation, the central and enteric nervous system and the immune system. However, evidence for the effectiveness of probiotics in the management of constipation remains varied, with some strains demonstrating improvements, while others show no effect. Despite the uncertainty in evidence and the fact that the majority of healthcare professionals do not recommend probiotics for constipation, an increased prevalence of probiotic use by people with constipation has been shown. Therefore, there is a need for public health strategies to inform the public about where strong evidence of probiotic effectiveness exist, and where evidence is still weak. Education of healthcare professionals on the increased utilisation of probiotics for constipation by the public and on current evidence for the effectiveness of specific strains is also required.
Background
Recent systematic reviews and meta-analyses on the efficacy of probiotics in the treatment of functional constipation in children have yielded conflicting results.
Objectives
The aim of this study was to critically review and update the evidence in this field by mapping all the steps involved against those reported in previous reviews, in an attempt to understand the nature of their conflicting results.
Methods
Four literature databases, trial registries, and citations were searched through December 1, 2018. We included randomized controlled trials (RCTs) that assessed the effects of probiotics compared with placebo or treatment as usual on defecation frequency [bowel movements (BMs)/wk] or treatment success rates in children with functional constipation. Independent reviewers extracted the data and assessed risk of bias in each RCT. Data were pooled with (inverse variance) random-effects models.
Results
We identified 17 RCTs, of which 14 and 11 provided sufficient data to enable meta-analysis of the effects of probiotics compared with control on defecation frequency (n = 965) or treatment success (n = 835), respectively. When compared to (any) control intervention, probiotics did not significantly increase defecation frequency [weighted mean difference (WMD): 0.28 BMs/wk; 95% CI: −0.12, 0.69; P = 0.165] but were more efficacious in achieving treatment success (RR: 1.24; 95% CI: 1.03, 1.50; P = 0.024). These effects did not differ by type of control (i.e., active or inactive) intervention. However, in analyses confined to the RCTs that were free of high risk of bias (only 5), probiotics did not confer any beneficial effects on defecation frequency (WMD: −0.55 BMs/wk; 95% CI: −1.37, 0.26; P = 0.185) and achievement of treatment success (RR: 1.01; 95% CI: 0.90, 1.13; P = 0.873), compared with control interventions.
Conclusions
The current evidence thus does not support the use of probiotics as a single or coadjuvant therapy for treatment of functional constipation in children and refutes recently published reviews reporting favorable effects of probiotics. Conflicting findings of previous reviews resulted from methodologic errors, highlighting the susceptibility of evidence synthesis to oversights in study selection, quality assessments, and data extraction and collation. This review was registered at PROSPERO as CRD42019119109.
Background
Constipation is a prevalent gastrointestinal disorder. Patient dissatisfaction with prescribed medications is common, and there is need for alternative management strategies. Evidence shows that Bifidobacterium species may be beneficial in constipation.
Aim
To investigate changes in physiological and clinical measures of gut function in patients with chronic constipation following the consumption of Bifidobacterium lactis NCC2818, compared to placebo.
Methods
Participants were randomised to a 4‐week supplementation with B. lactis NCC2818 (1.5 x 10¹⁰ CFU/d) or placebo. Gut transit time was measured using a radio‐opaque marker, while symptoms and quality of life were assessed using validated questionnaires. Gut microbiota composition was assessed using quantitative polymerase chain reaction. Analysis of covariance was used for normally distributed variables, and Mann‐Whitney test for non‐normally distributed variables.
Results
Seventy‐five participants were randomised. There was no significant difference between the probiotic and placebo groups in gut transit time change from baseline to week 2 (−11.7 hours, SD 33.0 hours vs −12.9 hours, SD 33.6 hours; P = 0.863) or to week 4 (−20.4 hours, SD 32.5 h vs −8.7 hours, SD 33.8 hours; P = 0.103). There were also no improvements in stool output, symptoms, or quality of life. No differences were found in Bifidobacterium concentrations between the probiotic and placebo groups at week 4 (9.5 log10/g dry faeces, SD 0.3 vs 9.4 log10/g, SD 1.0; P = 0.509).
Conclusions
Bifidobacterium lactis NCC2818 was not effective in the management of mild chronic constipation. This study highlights the importance of further studies and their publication to better understand the strain‐specific effects of probiotics.
Background:
To evaluate the effect of probiotic supplementation on functional constipation in children.
Methods:
We performed electronic searches in PubMed, Embase, and Cochrane Library without language restriction to identify relevant studies from the time of inception of these databases to March 2018. The relative risk or weighted mean difference was calculated to evaluate the treatment effect of probiotics using random-effects model.
Results:
We included 4 trials reporting data on 382 children with functional constipation. Overall, there were no significant differences in treatment success (P = .697), spontaneous bowel movements per week (P = .571), fecal soiling episodes per week (P = .642), straining at defecation (P = .408), use of lactulose (P = .238), use of laxatives (P = .190), fecal incontinence (P = .139), pain during defecation (P = .410), flatulence (P = .109), and adverse events (P = .979) between probiotics and placebo. Further, the use of probiotics was associated with lower frequency of glycerin enema use (weighted mean difference -2.40, P = .004) and abdominal pain (weighted mean difference -4.80, P < .001).
Conclusion:
The findings of this study suggested that the use of probiotics was associated with significant improvement in glycerin enema use and abdominal pain but did not affect the treatment success and other function indices.
Context: Constipation in children is a prevalent, burdensome, and psychologically important pediatric issue, the treatment of which remains a global challenge. The use of probiotics has been reported for management of the gastrointestinal microbiota.
Objective: This study reviewed the existing literatures of 6 Randomized Control Trials (RCTs) to ascertain some baseline understanding and available information for the effects of probiotics on stool frequency and consistency in children with constipation.
Data Sources: PubMed, Springer, Elsevier Science, Cochrane Library, Scopus, Ovid (Medline, EMBASE, PsycINFO), Orbis, and Web of Science from the earliest record in each database to 15 September, 2016.
Study selection: Eligible studies were randomized controlled trials that compared the effect of probiotics interventions to any control intervention on stool frequency and consistency.
Data Extraction: Studies were identified by searching electronic databases. The meta-analysis was performed by Review Manager 5.3 software using a randomized model.
Results: Six studies were identified. The use of probiotics significantly increased the stool frequency [mean difference (MD), 0.73; 95% confidence interval (CI), 0.14–1.31; P = 0.02]. Subgroup assessment showed a significantly increased stool frequency in Asian patients (MD, 1.18; 95% CI, 0.33–2.02; P = 0.006), but no significant difference in stool consistency (MD, −0.07; 95% CI, −0.21–0.06; P = 0.27).
Limitations: Only six RCTs met the criteria and were included. Each RCT in this study was performed in a different country, and some of the included studies had a small sample size, which might have influenced the reliability and validity of the conclusions.
Conclusion: The present study shows that probiotics increase stool frequency and have beneficial effects in Asian children. However, caution is needed when interpreting these outcomes because of the existence of heterogeneity. Evidence from larger samples and more adequately powered RCTs with results obtained by standardized measurements are necessary to determine which species and dosage of probiotics and what length of treatment are most efficacious for constipation in children.
Functional constipation (FC) is a significant health problem in children and contrary to common belief, has serious ramifications on the lives of children and their families. It is defined by the Rome criteria which encourage the use of multiple clinical features for diagnosis. FC in children has a high prevalence (0.7%-29%) worldwide, both in developed and developing countries. Biopsychosocial risk factors such as psychological stress, poor dietary habits, obesity and child maltreatment are commonly identified predisposing factors for FC. FC poses a significant healthcare burden on the already overstretched health budgets of many countries in terms of out-patient care, in-patient care, expenditure for investigations and prescriptions. Complications are common and range from minor psychological disturbances, to lower health-related quality of life. FC in children also has a significant impact on families. Many paediatric clinical trials have poor methodological quality, and drugs proved to be useful in adults, are not effective in relieving symptoms in children. A significant proportion of inadequately treated children have similar symptoms as adults. These factors show that constipation is an increasing public health problem across the world with a significant medical, social and economic impact. This article highlights the potential public health impact of FC and the possibility of overcoming this problem by concentrating on modifiable risk factors rather than expending resources on high cost investigations and therapeutic modalities.
Objectives:
Constipation is often characterized by slow colonic transit, but the relationship between colonic transit time (CTT) and symptoms is unclear. The aims of this study were to investigate the effect of prucalopride, a 5-hydroxytryptamine receptor-4 agonist, on CTT and assess the relationship between CTT and symptoms.
Methods:
This was an integrated analysis of three randomized, placebo-controlled, phase 2 dose-finding trials of prucalopride in patients with chronic constipation (ClinicalTrials.gov identifiers: NCT00617513; NCT00631813; and NCT00596596). Measurements of CTT were analyzed using radio-opaque markers at the start and end (4 or 12 weeks) of treatment. At these visits, patients assessed the presence and severity of their symptoms.
Results:
In total, 280 patients had CTT measurements before and at the end of treatment and were included in the analysis. Their mean age was 43 years, 93% were women, and mean duration of constipation was 19 years. After a once daily treatment with prucalopride 2 mg (n=98) and 4 mg (n=70), CTT was reduced by 12.0 h (95% confidence interval (CI): –18.9, –5.1) and 13.9 h (95% CI: –20.5, –7.4), respectively; CTT increased by 0.5 h (95% CI: –4.5, 5.5) with placebo (n=112). At the end of the trial, symptoms including bloating/flatulence/distension and straining were rated as severe or very severe by a higher proportion of patients with slow or very slow CTT (>48 h) than by those with normal CTT.
Conclusions:
There was a clear relationship between increased CTT and increased symptom severity in patients with chronic constipation. Treatment with prucalopride accelerated CTT in these individuals.
Oral rehydration salts (ORS), zinc, and continued feeding are the recommended treatments for community-acquired acute diarrhea among young children. However, probiotics are becoming increasingly popular treatments for diarrhea in some countries. We sought to estimate the effect of probiotics on diarrhea morbidity and mortality in children < 5 years of age.
We conducted a systematic review of randomized controlled trials to estimate the effect of probiotic microorganisms for the treatment of community-acquired acute diarrhea in children. Data were abstracted into a standardized table and study quality was assessed using the Child Health Epidemiology Reference Group (CHERG) adaption of the GRADE technique. We measured the relative effect of probiotic treatment in addition to recommended rehydration on hospitalizations, duration and severity. We then calculated the average percent difference for all continuous outcomes and performed a meta-analysis for discrete outcomes.
We identified 8 studies for inclusion in the final database. No studies reported diarrhea mortality and overall the evidence was low to moderate quality. Probiotics reduced diarrhea duration by 14.0% (95% CI: 3.8-24.2%) and stool frequency on the second day of treatment by 13.1% (95% CI: 0.8 - 25.3%). There was no effect on the risk of diarrhea hospitalizations.
Probiotics may be efficacious in reducing diarrhea duration and stool frequency during a diarrhea episode. However, only few studies have been conducted in low-income countries and none used zinc (the current recommendation) thus additional research is needed to understand the effect of probiotics as adjunct therapy for diarrhea among children in developing countries.
Antibiotics and probiotics are widely used as growth promoters in agriculture. Most antibiotics prescribed in clinical practice are natural products that originate from Streptomyces spp, which were first used as agricultural probiotics. Antibiotics and probiotics both modify the gut microbiota. The effect of a probiotic species on the digestive flora depends on the strain and is largely determined by bacteriocin production. In human beings, as in animals, specific probiotics are associated with weight gain or loss. Improved understanding of the ability of specific probiotics to harvest energy from the host diet might lead to development of new treatments for obesity and malnutrition. In this Review, we present the effects of probiotics and antibiotics on the gut microbiota of human beings and animals and discuss their potential therapeutic use as interventions for weight gain and loss in human beings.
Chronic constipation is a very common symptom that is rarely associated with life-threatening diseases, but has a substantial impact on patient quality of life and consumption of healthcare resources. Despite the large number of affected patients and the social relevance of the condition, no cost-effectiveness analysis has been made of any diagnostic or therapeutic algorithm, and there are few data comparing different diagnostic and therapeutic approaches in the long term. In this scenario, increasing emphasis has been placed on demonstrating that a number of older and new therapeutic options are effective in treating chronic constipation in well-performed randomised controlled trials, but there is still debate as to when these therapeutic options should be included in diagnostic and therapeutic algorithms. The aim of this review is to perform a critical evaluation of the current diagnostic and therapeutic options available for adult patients with chronic constipation in order to identify a rational patient approach; furthermore we attempt to clarify some of the more controversial points to aid clinicians in managing this symptom in a more efficacious and cost-effective manner.
Aim:
To investigate the effects of the probiotic Bifidobacterium longum BB536 on the health management of elderly patients receiving enteral feeding.
Methods:
Two double-blind, placebo-controlled trials were performed with long-term inpatients receiving enteral tube feeding at Kitakyushu Hospital Group, Fukuoka, Japan. BB536 was administered as BB536-L and BB536-H powders that contained approximately 2.5 × 10¹⁰ and 5 × 10¹⁰ cfu of BB536, respectively. In the first trial, 83 patients (age range: 67-101 years) were randomized into 2 groups that received placebo (placebo group) or BB536-H (BB536 group) powders. In the second trial, 123 patients (age range: 65-102 years) were randomized into 3 groups, and each group received placebo (placebo group), BB536-L (BB536-L group), or BB536-H (BB536-H group) powders. Each patient received the study medication for 16 wk after 1 wk of pre-observation. Fecal samples were collected from each patient prior to and after the intervention during Trial 2. Clinical observations included body temperature, occurrence of infection, frequency of defecation, and fecal microbiota.
Results:
No significant changes were observed in the frequency of defecation for either treatment in Trial 1. However, a significant change was noted in the BB536-L group (P = 0.0439) in Trial 2 but not in the placebo or BB536-H groups. Subgroup analyses based on the frequency of defecation for each patient during the pre-observation period for both trials revealed significant increases in bowel movements in patients with a low frequency of defecation and significant decreases in the bowel movements of patients with a high frequency of defecation during the intervention period in the BB536 groups. The combination of Trials 1 and 2 data revealed a modulatory effect of BB536 ingestion on the changes in bowel movements. Significantly increased bowel movements were observed in patients in the low frequency subgroup with significant intergroup differences (P < 0.01). Significantly decreased bowel movements were observed in patients in the high subgroup, but no significant intergroup differences were observed compared with the placebo group. BB536 ingestion increased the prevalence of normally formed stools. BB536 intake also significantly (P < 0.01) increased the cell numbers of bifidobacteria in fecal microbiota, and significant intergroup differences were observed at week 16. No adverse events were reported in any group.
Conclusion:
Our results suggest that BB536 ingestion modulated the intestinal environment and may have improved the health care of elderly patients receiving enteral feeding.
To catalog what is known about the safety of interventions containing Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus strains used as probiotic agents in research to reduce the risk of, prevent, or treat disease.
We searched 12 electronic databases, references of included studies, and pertinent reviews for studies addressing the safety of probiotics from database inception to August 2010 without language restriction.
We identified intervention studies on probiotics that reported the presence or absence of adverse health outcomes in human participants, without restriction by study design, participant type, or clinical field. We investigated the quantity, quality, and nature of adverse events.
The search identified 11,977 publications, of which 622 studies were included in the review. In 235 studies, only nonspecific safety statements were made ("well tolerated"); the remaining 387 studies reported the presence or absence of specific adverse events. Interventions and adverse events were poorly documented. A number of case studies described fungemia and some bacteremia potentially associated with administered probiotic organisms. Controlled trials did not monitor routinely for such infections and primarily reported on gastrointestinal adverse events. Based on reported adverse events, randomized controlled trials (RCTs) showed no statistically significantly increased relative risk (RR) of the overall number of experienced adverse events (RR 1.00; 95% confidence interval [CI]: 0.93, 1.07, p=0.999); gastrointestinal; infections; or other adverse events, including serious adverse events (RR 1.06; 95% CI: 0.97, 1.16; p=0.201), associated with short-term probiotic use compared to control group participants; long-term effects are largely unknown. Existing studies primarily examined Lactobacillus alone or in combination with other genera, often Bifidobacterium. Few studies directly compared the safety among different intervention or participant characteristics. Indirect comparisons indicated that effects of delivery vehicles (e.g., yogurt, dairy) should be investigated further. Case studies suggested that participants with compromised health are most likely to experience adverse events associated with probiotics. However, RCTs in medium-risk and critically ill participants did not report a statistically significantly increased risk of adverse events compared to control group participants.
There is a lack of assessment and systematic reporting of adverse events in probiotic intervention studies, and interventions are poorly documented. The available evidence in RCTs does not indicate an increased risk; however, rare adverse events are difficult to assess, and despite the substantial number of publications, the current literature is not well equipped to answer questions on the safety of probiotic interventions with confidence.
To assess the impact of Bifidobacterium lactis HN019 supplementation on whole gut transit time (WGTT) and frequency of functional gastrointestinal (GI) symptoms in adults.
We randomized 100 subjects (mean age: 44 years; 64% female) with functional GI symptoms to consume a proprietary probiotic strain, B. lactis HN019 (Fonterra Research Centre, Palmerston North, New Zealand), at daily doses of 17.2 billion colony forming units (CFU) (high dose; n = 33), 1.8 billion CFU (low dose; n = 33), or placebo (n = 34) for 14 days. The primary endpoint of WGTT was assessed by X-ray on days 0 and 14 and was preceded by consumption of radiopaque markers once a day for 6 days. The secondary endpoint of functional GI symptom frequency was recorded with a subject-reported numeric (1-100) scale before and after supplementation.
Decreases in mean WGTT over the 14-day study period were statistically significant in the high dose group (49 ± 30 to 21 ± 32 h, p < 0.001) and the low dose group (60 ± 33 to 41 ± 39 h, p = 0.01), but not in the placebo group (43 ± 31 to 44 ± 33 h). Time to excretion of all ingested markers was significantly shorter in the treatment groups versus placebo. Of the nine functional GI symptoms investigated, eight significantly decreased in frequency in the high dose group and seven decreased with low dose, while two decreased in the placebo group. No adverse events were reported in any group.
Daily B. lactis HN019 supplementation is well tolerated, decreases WGTT in a dose-dependent manner, and reduces the frequency of functional GI symptoms in adults.
Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice?
Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.
Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4
Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?
A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …
Objective
To evaluate and map the reporting and methodological quality of network meta-analysis (NMA) on acupuncture.
Study Design and Setting
Published acupuncture NMAs were searched through eight databases from inception to Feb 2022. The reporting and methodological quality of included studies was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analysis (PRISMA-NMA) statement and the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist.
Results
A total of 113 NMAs were identified. Most (99, 87.61%) studies were performed in China. Most studies focused on multiple acupuncture techniques (82.30%), and the main studied ailments were pain and post-stroke sequelae (20.24%). The median (interquartile range (IQR)) score of the reporting quality was 26.5 (25-28.5). However, poor reporting rates in the protocol and registration (33.63%) and geometry of the network (35.40%), especially for China-based studies, were identified. The methodological quality of only 2 (1.77%) English studies was high. The reporting rate of Chinese studies was below 15% on each of items 4, 7, 10, and 12.
Conclusion
The reporting quality of the NMAs was moderate, but the methodological quality was very low. The reporting and methodological quality of future NMAs, especially for Chinese studies, need further improvement.
Background & Aims
Probiotics and synbiotics have been increasingly investigated for the management of chronic constipation. We aimed to investigate the effect of probiotics and synbiotics on stool output, gut transit time, symptoms and quality of life in adults with chronic constipation via a systematic review and meta-analysis of randomized controlled trials (RCTs).
Methods
Studies were identified using electronic databases, backward citation and hand-searching abstracts. The search date was 10 July 2022. RCTs reporting administration of probiotics or synbiotics in adults with chronic constipation were included. Risk of bias (RoB) was assessed with the Cochrane RoB 2.0 tool. Meta-analysis was conducted separately for probiotics and synbiotics. Results were synthesized using risk ratios (RR), mean differences or standardized mean differences (SMD) and 95% confidence intervals (CI) using a random-effects model.
Results
Thirty RCTs investigating probiotics and four RCTs investigating synbiotics were included. Overall, 369/647 (59%) responded to probiotic treatment and 252/567 (48%) to control (RR 1.28, 95% CI 1.07, 1.52, p=0.007). Probiotics increased stool frequency (SMD 0.71, 95% CI 0.37, 1.04, p<0.00001), with Bifidobacterium lactis having a significant effect, but not mixtures of probiotics, B. coagulans Unique IS2 or Lactobacillus casei Shirota. Probiotics did not impact stool consistency (SMD 0.26; 95% CI -0.03, 0.54, p=0.08). Probiotics improved integrative symptom scores compared to control (SMD -0.46, 95% CI -0.89, -0.04). Synbiotics did not impact stool output or integrative symptom scores compared to control.
Conclusions
Certain probiotics may improve response to treatment, stool frequency and integrative constipation symptoms, providing cautious optimism for their use as a dietary management option. There is currently insufficient evidence to recommend synbiotics in the management of chronic constipation. Caution is needed when interpreting these results due to high heterogeneity and risk of bias amongst the studies.
Background:
Functional constipation is defined as chronic constipation with no identifiable underlying cause. It is a significant cause of morbidity in children, accounting for up to 25% of visits to paediatric gastroenterologists. Probiotic preparations may sufficiently alter the gut microbiome and promote normal gut physiology in a way that helps relieve functional constipation. Several studies have sought to address this hypothesis, as well as the role of probiotics in other functional gut disorders. Therefore, it is important to have a focused review to assess the evidence to date.
Objectives:
To evaluate the efficacy and safety of probiotics for the management of chronic constipation without a physical explanation in children.
Search methods:
On 28 June 2021, we searched CENTRAL, MEDLINE, Embase, CINAHL, AMED, WHO ICTR, and ClinicalTrials.gov, with no language, date, publication status, or document type limitations.
Selection criteria:
We included randomised controlled trials (RCTs) that assessed probiotic preparations (including synbiotics) compared to placebo, no treatment or any other interventional preparation in people aged between 0 and 18 years old with a diagnosis of functional constipation according to consensus criteria (such as Rome IV).
Data collection and analysis:
We used standard methodological procedures expected by Cochrane.
Main results:
We included 14 studies (1127 randomised participants): 12 studies assessed probiotics in the treatment of functional constipation, whilst two studies investigated synbiotic preparations. Three studies compared probiotics to placebo in relation to the frequency of defecation at study end, but we did not pool them as there was very significant unexplained heterogeneity. Four studies compared probiotics to placebo in relation to treatment success. There may be no difference in global improvement/treatment success (RR 1.29, 95% CI 0.73 to 2.26; 313 participants; low-certainty evidence). Five studies compared probiotics to placebo in relation to withdrawals due to adverse events, with the pooled effect suggesting there may be no difference (RR 0.64, 95% CI 0.21 to 1.95; 357 participants; low-certainty evidence). The pooled estimate from three studies that compared probiotics plus an osmotic laxative to osmotic laxative alone found there may be no difference in frequency of defecation (MD -0.01, 95% CI -0.57 to 0.56; 268 participants; low-certainty evidence). Two studies compared probiotics plus an osmotic laxative to osmotic laxative alone in relation to global improvement/treatment success, and found there may be no difference between the treatments (RR 0.95, 95% CI 0.79 to 1.15; 139 participants; low-certainty evidence). Three studies compared probiotics plus osmotic laxative to osmotic laxative alone in relation to withdrawals due to adverse events, but it is unclear if there is a difference between them (RR 2.86, 95% CI 0.12 to 68.35; 268 participants; very low-certainty evidence). Two studies compared probiotics versus magnesium oxide. It is unclear if there is a difference in frequency of defecation (MD 0.28, 95% CI -0.58 to 1.14; 36 participants), treatment success (RR 1.08, 95% CI 0.74 to 1.57; 36 participants) or withdrawals due to adverse events (RR 0.50, 95% CI 0.05 to 5.04; 77 participants). The certainty of the evidence is very low for these outcomes. One study assessed the role of a synbiotic preparation in comparison to placebo. There may be higher treatment success in favour of synbiotics compared to placebo (RR 2.32, 95% CI 1.54 to 3.47; 155 participants; low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study assessed a synbiotic plus paraffin compared to paraffin alone. It is uncertain if there is a difference in frequency of defecation (MD 0.74, 95% CI -0.96, 2.44; 66 participants; very low-certainty evidence), or treatment success (RR 0.91, 95% CI 0.71 to 1.17; 66 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study compared a synbiotic preparation to paraffin. It is uncertain if there is a difference in frequency of defecation (MD -1.53, 95% CI -3.00, -0.06; 60 participants; very low-certainty evidence) or in treatment success (RR 0.86, 95% CI 0.65, 1.13; 60 participants; very low-certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. All secondary outcomes were either not reported or reported in a way that did not allow for analysis.
Authors' conclusions:
There is insufficient evidence to conclude whether probiotics are efficacious in successfully treating chronic constipation without a physical explanation in children or changing the frequency of defecation, or whether there is a difference in withdrawals due to adverse events when compared with placebo. There is limited evidence from one study to suggest a synbiotic preparation may be more likely than placebo to lead to treatment success, with no difference in withdrawals due to adverse events. There is insufficient evidence to draw efficacy or safety conclusions about the use of probiotics in combination with or in comparison to any of the other interventions reported. The majority of the studies that presented data on serious adverse events reported that no events occurred. Two studies did not report this outcome. Future studies are needed to confirm efficacy, but the research community requires guidance on the best context for probiotics in such studies, considering where they should be best considered in a potential treatment hierarchy and should align with core outcome sets to support future interpretation of findings.
Objective
This study collected randomized controlled trials (RCTs) published in the social sciences in China and assessed their risk of bias and reporting quality.
Study Design and Setting
Three databases were systematically searched for publications from January 2000 to June 2020 for RCTs in the social sciences published by Chinese researchers. The risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool (CCRBT), and reporting quality was assessed using the Consolidated Standards of Reporting Trials for Social and Psychological Interventions (CONSORT-SPI).
Results
A total of 316 RCTs were identified, including 204 articles in English and 112 articles in Chinese. The most frequently researched interventions focused on education (33.9%), and the most frequently studied population were students (32.9%). Eighty-seven percent of RCTs had intermediate reporting quality. Twenty-four of the 43 CONSORT-SPI sub-items had a compliance rate of less than 50%. Most RCTs had an unclear risk of bias for blinding outcome assessors (84.5%), blinding participants and personnel (82.9%), allocation concealment (73.1%), and random sequence generation (68.0%). A low proportion of CONSORT-SPI items were reported and, high proportion of the papers had unclear risk of bias.
Conclusion
The quality and reporting of RCTs in the social sciences needs improvement in China, especially for reporting methods and results. Most studies had an unclear risk of bias as they lacked important methodological information.
Objectives:
To assess the reporting and methodological quality of COVID-19 systematic reviews, and to analyze trends and gaps in the quality, clinical topics, author countries, and populations of the reviews using an evidence mapping approach.
Study design and setting:
A structured search for systematic reviews concerning COVID-19 was performed using PubMed, Embase, Cochrane Library, Campbell Library, Web of Science, CBM, WanFang Data, CNKI, and CQVIP from inception until June 2020. The quality of each review was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) checklist and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.
Results:
In total, 243 systematic reviews met the inclusion criteria, over 50% of which (128, 52.7%) were from 14 developing countries, with China contributing the most reviews (76, 31.3%). In terms of methodological quality of the studies, 30 (12.3%) were of moderate quality, 63 (25.9%) were of low quality, and 150 (61.7%) were of critically low quality. In terms of reporting quality, the median (interquartile range) PRISMA score was 14 (10-18). Regarding the topics of the reviews, 24 (9.9%) focused on the prevalence of COVID-19, 69 (28.4%) focused on the clinical manifestations, 30 (12.3%) focused on etiology, 43 (17.7%) focused on diagnosis, 65 (26.7%) focused on treatment, 104 (42.8%) focused on prognosis, and 25 (10.3%) focused on prevention. These studies mainly focused on general patients with COVID-19 (161, 66.3%), followed by children (22, 9.1%) and pregnant patients (18, 7.4%).
Conclusions:
This study systematically evaluated the methodological and reporting quality of systematic reviews of COVID-19, summarizing and analyzing trends in their clinical topics, author countries, and study populations. WHAT IS NEW?: Key findingsWhat this adds to what was known?What is the implication, what should change now?
Objectives
To evaluate the impact of a microbial cell preparation (MCP®) (Hexbio®; comprising MCP® BCMC® strains) on stool frequency, consistency, and constipation-related symptoms in elderly patients with multiple chronic medical conditions.DesignRandomised control trial.SettingMedical outpatient and medical/surgical in-patient unit in single tertiary center.ParticipantPatients aged ≥ 60 years who experience constipation and have multiple chronic medical conditions.Methods
Participants with constipation were blindly randomized into either a treatment (MCP® BCMC® strains) or a placebo group. The treatment was administered twice daily.MeasurementGastrointestinal symptoms and stool habits were assessed over a week during the intervention via the use of a questionnaire and stool diary.ResultsStool frequency was seen to be higher and the improvement in stool consistency was more significant in the treatment group than in the placebo group (p =<0.001). A significant improvement in symptoms was demonstrated in patients who received MCP® BCMC® strains,, specifically with respect to straining (p = < 0.001) and a sensation of incomplete evacuation (p = < 0.001). reduction in anorectal blockage symptoms and the need for manual stool evacuation was also demonstrated, but this finding was not statistically significant. Significant adverse events were not observed.Conclusions
An improvement in stool frequency and consistency was reported in elderly patients with chronic medical conditions following the administration of MCP® BCMC® strains.
Objective
Meta-analysis is of fundamental importance to obtain an unbiased assessment of the available evidence. In general, the use of meta-analysis has been increasing over the last three decades with mental health as a major research topic. It is then essential to well understand its methodology and interpret its results. In this publication, we describe how to perform a meta-analysis with the freely available statistical software environment R, using a working example taken from the field of mental health.
Methods
R package meta is used to conduct standard meta-analysis. Sensitivity analyses for missing binary outcome data and potential selection bias are conducted with R package metasens. All essential R commands are provided and clearly described to conduct and report analyses.
Results
The working example considers a binary outcome: we show how to conduct a fixed effect and random effects meta-analysis and subgroup analysis, produce a forest and funnel plot and to test and adjust for funnel plot asymmetry. All these steps work similar for other outcome types.
Conclusions
R represents a powerful and flexible tool to conduct meta-analyses. This publication gives a brief glimpse into the topic and provides directions to more advanced meta-analysis methods available in R.
The revised edition of the Handbook offers the only guide on how to conduct, report and maintain a Cochrane Review ? The second edition of The Cochrane Handbook for Systematic Reviews of Interventions contains essential guidance for preparing and maintaining Cochrane Reviews of the effects of health interventions. Designed to be an accessible resource, the Handbook will also be of interest to anyone undertaking systematic reviews of interventions outside Cochrane, and many of the principles and methods presented are appropriate for systematic reviews addressing research questions other than effects of interventions. This fully updated edition contains extensive new material on systematic review methods addressing a wide-range of topics including network meta-analysis, equity, complex interventions, narrative synthesis, and automation. Also new to this edition, integrated throughout the Handbook, is the set of standards Cochrane expects its reviews to meet. Written for review authors, editors, trainers and others with an interest in Cochrane Reviews, the second edition of The Cochrane Handbook for Systematic Reviews of Interventions continues to offer an invaluable resource for understanding the role of systematic reviews, critically appraising health research studies and conducting reviews.
Background:
Constipation is one of the most common diseases in children and it is also a significant healthcare burden, more than many other common childhood diseases. For some children, 1st-line treatment cannot relieve their constipation and their constipation symptoms maybe continue to adolescence. So, alternative treatment options such as lactobacilli are needed. However, the effectiveness and safety of lactobacilli is still unclear. To investigate this question, we conduct a systematic review and meta-analysis.
Methods:
The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Three main databases (PubMed, Embase, and the Cochrane Library) will be searched to December 20, 2018 for randomized controlled trials investigating the effects and safety of lactobacilli for constipation in children with no language restrictions. In addition, a manual search of the references of relevant published studies will also be considered.Two independent reviewers will conduct studies selection, data extraction, and risk of bias assessment. The primary outcome is defecation frequency, treatment success (bowl movement >3 times per week). The 2nd outcome is stool consistency, incidence of abdominal pain, patients using laxatives, and adverse events.
Results:
The results will provide useful information about the effect and safety of lactobacilli for constipation in children.
Conclusion:
The findings of this study will be published in a peer-reviewed journal.
Prospero registration number:
CRD42019125913.
Background
The Bristol Stool Form Scale (BSFS) is a 7-point scale used extensively in clinical practice and research for stool form measurement, which has undergone limited validity and reliability testing. AimTo determine the validity and reliability of the BSFS in measuring stool form in healthy adults and patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Methods
One hundred and sixty-nine healthy volunteers provided a stool sample and used the BSFS to classify stool form, which was compared with measured stool water content and with values from 19 patients with IBS-D. Eighty-six volunteers used the BSFS to classify 26 stool models to determine accuracy and reliability. ResultsVolunteers' classifications of stool type correlated with stool water (Spearman's rho = 0.491, P < 0.001), which increased in hard (Types 1-2), normal (Types 3-5) and loose stools (Types 6-7) (P < 0.001). The BSFS detected differences in stool form between healthy volunteers (mean 3.7, s.d. 1.5) and IBS-D patients (mean 5.0, s.d. 1.2) (P < 0.001). Overall, 977/1204 (81%) stool models were correctly classified (substantial accuracy, = 0.78), although <80% of Types 2, 3, 5 and 6 were classified correctly. On 852/1118 (76%) occasions, volunteers classified covert duplicate models to the same stool type (substantial reliability, = 0.72), but with only moderate reliability for Types 2 (63%, = 0.57) and 3 (62%, = 0.55). Conclusions
The BSFS demonstrated substantial validity and reliability, although difficulties arose around clinical decision points (Types 2, 3, 5, 6) that warrant investigation in larger clinical populations. Potential for improving validity and reliability through modifications to the BSFS or training in its use should be explored.
This paper provides recommendations, developed by the Working Group (WG) on Probiotics of the ESPGHAN, for the use of probiotics for the prevention of antibiotic-associated diarrhea (AAD) in children based on a systematic review of previously completed systematic reviews and of randomized controlled trials (RCTs) published subsequently to these reviews. The use of probiotics for the treatment of AAD is not covered. The recommendations were formulated only if at least 2 RCTs that used a given probiotic (with strain specification) were available. The quality of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. If the use of probiotics for preventing AAD is considered because of the existence of risk factors such as class of antibiotic(s), duration of antibiotic treatment, age, need for hospitalization, comorbidities, or previous episodes of AAD diarrhea, the WG recommends using Lactobacillus rhamnosus GG (moderate QoE, strong recommendation) or Saccharomyces boulardii (moderate QoE, strong recommendation). If the use of probiotics for preventing C. difficile-associated diarrhea is considered, the WG suggests using S. boulardii (low QoE, conditional recommendation). Other strains or combinations of strains have been tested, but sufficient evidence is still lacking.
Although probiotics have been used for many years by those who suffer from what would now be defined as irritable bowel syndrome (IBS), a scientific rationale for their use in this indication and clinical evidence to support their benefits have only emerged very recently. Evidence to support considering strategies, such as probiotics, that modulate the gut microbiome, in IBS, has been provided by laboratory studies implicating the microbiome and the host response to the enteric microenvironment in IBS, as well as in vitro and in vivo studies demonstrating the ability of various commensal bacteria to influence such relevant functions as motility, visceral sensation, gut barrier integrity, and brain-gut interactions. Clinical studies supporting a role for probiotics in the management of IBS predated such experimental data, and randomized controlled trials of probiotics in IBS continue to be reported. Their interpretation is hampered by the less than optimal quality of many studies; nevertheless, it is apparent that probiotics, as a category, do exert significant effects in IBS. Defining the optimal strain, dose, formulation, and duration of therapy is more challenging given the limitations of available data. There is also an urgent need for appropriately powered and rigorously designed clinical trials of appropriate duration of probiotics in IBS; such studies should also help to define those who are most likely to respond to probiotics. Future laboratory and translational research should attempt to define the mechanism(s) of action of probiotics in IBS and explore the response to bacterial components or products in this common and oftentimes troublesome disorder.
Background: Clinical management of constipation is complicated by the lack of a gold standard for evaluation of symptoms. A constipation symptom assessment instrument, the PAC-SYM, was developed to address the patient perspective on the disorder. Instrument content was based on literature review and results of focus groups. Methods: Two hundred and sixteen patients at nine sites participated in a 6-week psychometric evaluation of the PAC-SYM. The final instrument contained 12 items assigned to 3 subscales: stool symptoms, rectal symptoms, and abdominal symptoms. The psychometric properties of this final instrument were assessed. Results: Internal consistency and test-retest reliability of the final instrument was high (Cronbach's α = 0.89; intraclass correlation = 0.75). Concurrent validity was supported by the correlation with both subject and investigator constipation severity ratings (r= 0.68 and 0.72, respectively; P < 0.0001). Scores were moderately correlated with instruments measuring quality of life. Comparison of treatment responders with nonresponders showed the ability of the instrument to differentiate between groups on the basis of clinical severity (t = -6.12, P < 0.0001). Scores changed significantly over time among responders, indicating instrument responsiveness. Conclusions: The PAC-SYM is internally consistent, reproducible under stable conditions, valid, and responsive to change and provides a comprehensive means to assess the effectiveness of treatment for constipation.
A randomized, double blind, controlled study was conducted to evaluate a multi-species probiotic product, Duolac® Care, for the efficacy in functional constipation of elderly nursing home residents. Forty participants were randomly assigned to receive either one capsule containing six bacterial strains (2.5 × 108 viable cells/capsule) doubly coated with proteins and polysaccharides (DC group) or one capsule containing the same bacterial strains without the coating layers outside the cell (NC group) twice a day (5 × 108 viable cells/day). After consumption of 2 weeks, NC group showed a significant improvement in a symptom of Rome III criteria for constipation, ‘effort to evacuate’, but failed to show a significant improvement in weekly defecation frequency. By contrast, DC group showed significant improvements in symptoms of ‘effort to evacuate’ and ‘sensation of anorectal obstruction or blockage’ as well as being improved in ‘defecation frequency’. The quantitative analysis of the fecal bacteria revealed that the levels of all the bacterial species consumed were significantly increased after consumption in both groups. However DC group showed larger increases in the bacterial levels than NC group, and the overall bacterial levels in DC group were about 100-fold or greater than those in NC group. Therefore the improvements in the symptoms appeared to be closely associated with large increases of the bacterial species consumed. The double-coating layers of proteins and polysaccharides ensured increase in the levels of bacteria, indicating that the layers function to protect the bacteria from the digestive action in the GI tract. Therefore, Duolac® Care could be a treatment option in functional constipation.
Background:
Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Probiotics have been increasingly investigated in its management.
Objective:
The aim was to investigate the effect of probiotics on gut transit time, stool output, and constipation symptoms in adults with functional constipation via a systematic review and meta-analysis of randomized controlled trials (RCTs).
Design:
Studies were identified by searching 4 electronic databases, back-searching reference lists, contacting authors, and hand-searching abstracts. RCTs that reported administration of probiotics in adults with functional constipation were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Outcome data were synthesized by using weighted mean differences (WMDs) or standardized mean differences (SMDs) with the use of a random-effects model.
Results:
A total of 660 records were identified of which 14 were eligible (1182 patients). Overall, probiotics significantly reduced whole gut transit time by 12.4 h (95% CI: -22.3, -2.5 h) and increased stool frequency by 1.3 bowel movements/wk (95% CI: 0.7, 1.9 bowel movements/wk), and this was significant for Bifidobacterium lactis (WMD: 1.5 bowel movements/wk; 95% CI: 0.7, 2.3 bowel movements/wk) but not for Lactobacillus casei Shirota (WMD: -0.2 bowel movements/wk; 95% CI: -0.8, 0.9 bowel movements/wk). Probiotics improved stool consistency (SMD: +0.55; 95% CI: 0.27, 0.82), and this was significant for B. lactis (SMD: +0.46; 95% CI: 0.08, 0.85) but not for L. casei Shirota (SMD: +0.26; 95% CI: -0.30, 0.82). No serious adverse events were reported. Attrition and reporting bias were high, whereas selection bias was unclear due to inadequate reporting.
Conclusions:
Probiotics may improve whole gut transit time, stool frequency, and stool consistency, with subgroup analysis indicating beneficial effects of B. lactis in particular. However, caution is needed with the interpretation of these data due to their high heterogeneity and risk of bias. Adequately powered RCTs are required to better determine the species or strains, doses, and duration of use of probiotics that are most efficacious.
This article is the first of a series providing guidance for use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system of rating quality of evidence and grading strength of recommendations in systematic reviews, health technology assessments (HTAs), and clinical practice guidelines addressing alternative management options. The GRADE process begins with asking an explicit question, including specification of all important outcomes. After the evidence is collected and summarized, GRADE provides explicit criteria for rating the quality of evidence that include study design, risk of bias, imprecision, inconsistency, indirectness, and magnitude of effect. Recommendations are characterized as strong or weak (alternative terms conditional or discretionary) according to the quality of the supporting evidence and the balance between desirable and undesirable consequences of the alternative management options. GRADE suggests summarizing evidence in succinct, transparent, and informative summary of findings tables that show the quality of evidence and the magnitude of relative and absolute effects for each important outcome and/or as evidence profiles that provide, in addition, detailed information about the reason for the quality of evidence rating. Subsequent articles in this series will address GRADE's approach to formulating questions, assessing quality of evidence, and developing recommendations.
Comparison of quality of life (QoL) across disease areas requires the use of appropriate tools. Although many studies have investigated QoL in constipation, most used disease-specific tools that are inappropriate for cross-comparisons.
To identify studies of QoL in constipation and to compare these results with other chronic conditions.
A comprehensive literature search identified studies in constipation that used a generic QoL tool. Results were statistically pooled where possible and compared with published results using the same tools in other chronic conditions.
A total of 13 qualifying studies were identified, 10 in adults and three in children. Results from eight studies using the SF-36/12 tools were pooled; the remaining five were narratively reported. Mental and physical components of QoL scores were consistently impaired in both adult and child populations, with the greatest impact being seen in secondary care studies. Mental health effects predominated over physical domains. The magnitude of impact was comparable with that seen in patients with allergies, musculoskeletal conditions and inflammatory bowel disease.
The impact of constipation on QoL is significant and comparable with other common chronic conditions. Improving management may prove to be an effective way of improving QoL for a substantial number of patients.
To systematically evaluate and update evidence on the efficacy and safety of probiotic supplementation for the treatment of constipation.
The MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched in May 2009 for randomised controlled trials (RCTs) performed in paediatric or adult populations related to the study aim.
We included five RCTs with a total of 377 subjects (194 in the experimental group and 183 in the control group). The participants were adults (three RCTs, n = 266) and children (two RCTs, n = 111) with constipation. In adults, data suggests a favourable effect of treatment with Bifidobacterium lactis DN-173 010, Lactobacillus casei Shirota, and Escherichia coli Nissle 1917 on defecation frequency and stool consistency. In children, L. casei rhamnosus Lcr35, but not L. rhamnosus GG, showed a beneficial effect.
Until more data are available, we believe the use of probiotics for the treatment of constipation condition should be considered investigational.
About 35% of humans have methane-producing gut flora. Methane-producing irritable bowel syndrome (IBS) subjects are generally constipated. In animal models, methane infusion slows intestinal transit. Whether methanogenic flora alters colonic transit or stool characteristics and its relationship to constipation is unclear. The aim of this study was to examine the prevalence and association of methanogenic flora in patients with slow transit (ST) constipation and normal transit (NT) constipation and non-constipated controls.
Ninety-six consecutive subjects with chronic constipation (CC) (Rome III) were evaluated with radio-opaque marker (ROM) transit studies and were classified as ST (>20% ROM retention) or NT. All constipated subjects and 106 non-constipated controls underwent breath tests to assess methane production. Baseline CH4 of >or=3 p.p.m. was used to define presence of methanogenic flora. Stool frequency and consistency were assessed using a prospective stool diary. Correlation analyses were performed.
Forty-eight subjects had ST and 48 had NT. Prevalence of methanogenic flora was higher (P<0.05) in ST (75%) compared to NT (44%) or controls (28%). ST patients had higher methane production compared to NT and controls (P<0.05). NT patients also produced more methane compared to controls (P<0.05). There was moderate(P<0.05) correlation among baseline, peak, and area under the curve (AUC) of methane response with colonic transit but not with stool characteristics.
Presence of methanogenic flora is associated with CC. Methane production after carbohydrate challenge and its prevalence were higher in ST than NT, although stool characteristics were similar in both groups. Methane production correlated with colonic transit, suggesting an association with stool transport but not with stool characteristics.
Accurate information on harms of medical interventions is essential for evidence-based practice. Most newly introduced treatments usually have small, incremental benefits, if any, against already available interventions, and differences in the profile of harms should play a key role on treatment choice. Randomized trials offer an excellent opportunity to evaluate harms of interventions using the most robust experimental design available in clinical research. However, several empirical evaluations (Table) have shown that many trials do not report harms or report them in a fragmented or suboptimal way. In this issue, an excellent study by Pitrou et al1 adds more evidence on this issue.
Gastrointestinal transit time (GITT) and segmental colonic transit times were studied in 56 healthy subjects by repeated daily ingestion of 10 radiopaque markers followed by abdominal x-ray. A seven-day procedure including marker intake for 6 days and a single radiograph on day 7 was found to be a simple method to differentiate between rapid, normal and prolonged transit. Addition of 20 distinguishable markers on day 6 helped to describe transit profiles. Healthy women had longer GITT than men (median 2.4 and 1.9 days, respectively) measured as mean 50% excretion time for the ingested doses of markers. For comparisons with patients percentiles for transit were calculated. In constipated patients the 7-day method demonstrated prolonged GITT as well as transit dysfunction in separate colonic segments. The method seems convenient for clinical use in diagnostic as well as therapeutic studies of colonic transit.
Constipation is a common problem in elderly subjects, probiotics have been suggested to improve intestinal motility and reduce fecal enzyme activity.
Elderly subjects (n = 28) were enrolled in an open parallel study. The subjects were divided into 3 groups: 1 control group receiving juice; 1 group receiving juice supplemented with Lactobacillus reuteri, and 1 group receiving juice supplemented with Lactobacillus rhamnosus and Propionibacterium freudenreichii. During the first 3 weeks all subjects consumed unsupplemented juice. In the subsequent 4 weeks, the subjects received their designated juice. During the last 3 weeks, all subjects again received unsupplemented juice. From the subjects, defecation frequency, laxative use, fecal pH, mucin content and azoreductase activity were assessed during the last week of each period.
The subjects receiving the L. rhamnosus/P. freudenreichii-supplemented juice exhibited a 24% increase in defecation frequency. However, no reduction in laxative use was observed. The fecal azoreductase activity was also significantly reduced in this group. No changes in fecal pH or mucin excretion were observed.
Some relief from constipation may be observed with the combination of L. rhamnosus/P. freudenreichii. This probiotic combination also reduced fecal enzyme activity. The tested probiotics did not affect the mucosal barrier.
Employing a consensus approach, our working team critically considered the available evidence and multinational expert criticism, revised the Rome II diagnostic criteria for the functional bowel disorders, and updated diagnosis and treatment recommendations. Diagnosis of a functional bowel disorder (FBD) requires characteristic symptoms during the last 3 months and onset > or =6 months ago. Alarm symptoms suggest the possibility of structural disease, but do not necessarily negate a diagnosis of an FBD. Irritable bowel syndrome (IBS), functional bloating, functional constipation, and functional diarrhea are best identified by symptom-based approaches. Subtyping of IBS is controversial, and we suggest it be based on stool form, which can be aided by use of the Bristol Stool Form Scale. Diagnostic testing should be guided by the patient's age, primary symptom characteristics, and other clinical and laboratory features. Treatment of FBDs is based on an individualized evaluation, explanation, and reassurance. Alterations in diet, drug treatment aimed at predominant symptoms, and psychotherapy may be beneficial.
Constipation is a common, often chronic, gastrointestinal motility disorder characterized by such symptoms as straining, hard stool, and infrequent defecation. Published literature is limited regarding symptom prevalence, healthcare-seeking behaviour, and patient satisfaction with traditional therapies for chronic constipation.
To assess the prevalence of chronic constipation among a random sample of Americans, to identify the frequency, severity and bothersomeness of their symptoms, and to assess satisfaction levels with traditional treatments.
All members (N = 37,004) of the Knowledge Networks Panel, representative of the US population, participated in a web-based survey. Eligibility was established using a six-question screener.
Of the 24,090 panellists consenting to participate, 557 met eligibility requirements and took the 45-question survey. The most prevalent symptom was straining (79%). Hard stool and straining were the top two severe symptoms, and bloating, straining and hard stool were the top three bothersome symptoms. Symptoms affected quality of life of more than half (52%) the respondents. Among those who worked or went to school, 12% experienced reduced productivity and a mean of 2.4 days of absence in the month before the survey. Most respondents had used (96%) or were using (72%) constipation relief therapy; however, nearly half (47%) were not completely satisfied, mainly because of efficacy (82%) and safety (16%) concerns.
Chronic constipation is common. Individual symptoms are often severe and bothersome, and many patients are dissatisfied with traditional treatment options, primarily because of lack of efficacy.
Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study
Jan 2021
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A D Sperber
S I Bangdiwala
D A Drossman
AD Sperber
An evidence-based approach to the management of chronic constipation in North America