-
Atherosclerosis Sep 2013Several lines of evidence have indicated the insulin-sensitizing, anti-diabetic and anti-atherosclerotic properties of adiponectin, as well as the inverse association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several lines of evidence have indicated the insulin-sensitizing, anti-diabetic and anti-atherosclerotic properties of adiponectin, as well as the inverse association between circulating levels of this adipokine and development of cardiovascular outcomes. Improvement of adiponectin status has been reported as a pleiotropic effect of fibrate therapy, but the findings have not been conclusive.
OBJECTIVE
To systematically review and meta-analyze available evidence from randomized placebo-controlled trials (RCTs) on the impact of fibrate therapy on circulating levels of adiponectin.
METHODS
A comprehensive literature search in Medline was carried out to identify RCTs comparing the effect of fibrate therapy vs. placebo on circulating concentrations of adiponectin. A meta-analysis of eligible studies was performed using a random-effects model. Quality assessment, sensitivity analysis and publication bias evaluations were conducted using standard methods.
RESULTS
Twelve RCTs comprising 443 cases and 437 controls met the selection criteria for systematic review, out of which 9 RCTs (399 cases and 401 controls) were included in the meta-analysis. Quantitative data synthesis revealed a significant effect for fibrate therapy in increasing circulating adiponectin levels (weighed mean difference: 0.38 μg/mL; 95% confidence interval: 0.13-0.63 μg/mL; p = 0.003). The effect size remained statistically significant when restricting the analysis to fenofibrate trials [0.31 (0.21-0.42) μg/mL; p < 0.00001). The observed effect was robust in sensitivity analyses and independent of fibrate dose. Imputation for potential missing studies led to the estimation of a greater effect size for fibrate therapy [0.53 (0.24-0.82) μg/mL].
CONCLUSION
The present meta-analysis suggests that fibrate therapy increases circulating levels of adiponectin. Whether increase in adiponectin levels contributes to reduction of cardiovascular effects in subjects with dyslipidemia treated with fibrates merits further investigation.
Topics: Adiponectin; Dyslipidemias; Fenofibrate; Gene Expression Regulation; Humans; Hypolipidemic Agents; Insulin; Randomized Controlled Trials as Topic; Regression Analysis; Research Design; Risk; Triglycerides
PubMed: 23958262
DOI: 10.1016/j.atherosclerosis.2013.06.026 -
The Lancet. Psychiatry Jun 2021Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is... (Comparative Study)
Comparative Study Meta-Analysis
Standard versus reduced dose of antipsychotics for relapse prevention in multi-episode schizophrenia: a systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is unclear. We aimed to compare risks and benefits of reduced versus standard doses of antipsychotics.
METHODS
We searched Embase, Medline, PsycINFO, and the Cochrane Library from database inception until June 17, 2020, for randomised trials in adults with schizophrenia or schizoaffective disorder lasting at least 24 weeks, including individuals clinically stable at baseline, and comparing at least two doses of the same antipsychotic, excluding trials in first-episode psychosis or treatment-resistant schizophrenia. We compared low-dose (within 50-99% of the lower limit of the standard dose) and very-low dose (less than 50% of the lower limit) with standard dose, defined as doses higher than the lower limit of the treatment dose recommended by the International Consensus Study. Data from published reports on number of participants, treatment, sex, age, number of events, and changes in psychopathology scores were extracted independently by at least two authors. Investigators or sponsors were contacted by email to obtain missing information regarding outcomes. Co-primary outcomes were relapse and all-cause discontinuation. Study-level data were meta-analysed using random-effects models, calculating risk ratios (RRs) for dichotomous data, and Hedges' g for continuous data. The protocol was registered with OSF registries.
FINDINGS
7853 references were identified in the database search and one additional reference from a manual review of relevant studies. 5744 abstracts were assessed for eligibility, and 101 references were assessed for full-text review. Of these, 79 were excluded for a variety of reasons, resulting in 22 studies being included in the meta-analysis, reporting on 24 trials and 3282 individuals. Study participants had a median age of 38 years (IQR 36-40) with 2166 (65·9%) males and 1116 (34·0%) females. Compared with standard dose, low dose increased the risk of relapse by 44% (16 trials, 1920 participants; RR 1·44, 95% CI 1·10-1·87; p=0·0076; I=46%) and the risk of all-cause discontinuation by 12% (16 trials, 1932 participants; RR 1·12, 1·03-1·22; p=0·0085; I=0%). Very low dose increased the risk of relapse by 72% (13 trials, 2058 participants; RR 1·72, 95% CI 1·29-2·29; p=0·0002; I=70%) and all-cause discontinuation by 31% (11 trials, 1866 participants; RR 1·31, 1·11-1·54; p=0·0011; I=63%). Compared with low dose, very low dose did not significantly increase the risk of relapse (five trials, 686 participants; RR 1·31, 95% CI 0·96-1·79; p=0·092; I=51%) or all-cause discontinuation (five trials 686 participants; RR 1·11, 95% CI 0·95-1·30; p=0·18; I=43%). Subgroup analyses comparing double-blind versus open-label studies, first-generation versus second-generation antipsychotics, and oral versus long-acting injectable antipsychotics were consistent with the overall results. Most studies were classified as having some concerns in the risk of bias assessment, which was mainly caused by absence of publicly available study registrations.
INTERPRETATION
During maintenance treatment in multi-episode schizophrenia, antipsychotic doses should probably not be reduced below the standard dose range recommended for acute stabilisation, because reducing the dose further is associated with an increased risk of both relapse and all-cause discontinuation.
FUNDING
None.
Topics: Adult; Antipsychotic Agents; Dose-Response Relationship, Drug; Humans; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia; Secondary Prevention; Treatment Outcome
PubMed: 34023019
DOI: 10.1016/S2215-0366(21)00078-X -
European Journal of Clinical... Feb 2021Medicines regulatory authorities advise that patient information leaflets (PILs) should provide specific advice on what actions to take if one or more doses are missed....
PURPOSE
Medicines regulatory authorities advise that patient information leaflets (PILs) should provide specific advice on what actions to take if one or more doses are missed. We aimed to assess the content in this regard, of PILs and Summaries of Product Characteristics (SmPCs) of prescription only medicines (POMs) marketed in the UK.
METHODS
PILs and SmPCs were accessed via the electronic Medicines Compendium. The following terms were used in the advanced search facility: miss(ed), omit(ted), adhere(d), delay(ed), forgot, forget, lapse. Identified documents were screened for instructions on missed doses which were categorised according to level of specificity, and cross-referenced to the National Patient Safety Agency (NPSA) grading of risk of harm from omitted and delayed medicines. Any supporting clinical or pharmacological evidence was identified from SmPCs.
RESULTS
Two thousand two hundred eighty-four documents were identified from 7248 PILs and SmPCs relating to 1501 POMs. Seven hundred eighty-three (52%) POMs had SmPCs or PILs with no instructions on missed doses; 487 POMs (32%) included non-specific advice (e.g. "take as soon as possible"); 138 (9%) provided specific instructions; and 93 (6%) referred patients to seek medical advice. SmPCs for only 13/138 (9%) of those which included specific instructions provided any supporting clinical or pharmacological evidence. Instructions were absent for several medicines where the NPSA assessed that dose omissions may result in significant risk of harm.
CONCLUSIONS
Advice on missed doses is generally inadequate. Pharmaceutical companies and regulatory authorities should produce clear and concise instructions on what patients should do if they miss doses, with supporting evidence where necessary.
Topics: Drug Administration Schedule; Drug Labeling; Humans; Medication Adherence; Prescription Drugs; United Kingdom
PubMed: 32989529
DOI: 10.1007/s00228-020-03003-x -
The Cochrane Database of Systematic... Aug 2010Spironolactone is an aldosterone antagonist, considered fourth line therapy for hypertension in patients already treated with multiple medications. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Spironolactone is an aldosterone antagonist, considered fourth line therapy for hypertension in patients already treated with multiple medications.
OBJECTIVES
Primary: to determine the effect of spironolactone on patient mortality, morbidity, and to quantify the magnitude of blood pressure lowering effect of spironolactone monotherapy.Secondary: to determine the prevalence of adverse reactions observed with spironolactone monotherapy and to determine if there is a blood-pressure lowering dose response with spironolactone.
SEARCH STRATEGY
We searched the following databases: Cochrane Central Register of Controlled Trials (3rd Quarter 2009), MEDLINE (2005 - Sept. 2009), and EMBASE (2007 - Sept. 2009). References from retrieved studies were reviewed to identify any studies missed in the initial search. No language restrictions were applied.
SELECTION CRITERIA
We selected RCTs studying patients with primary hypertension. We excluded studies of patients with secondary or gestational hypertension, and studies where patients were receiving multiple antihypertensives.
DATA COLLECTION AND ANALYSIS
Two reviewers independently reviewed the search results for studies meeting our criteria. Three reviewers extracted data and assessed trial quality using a standardized data extraction form. Data synthesis and analysis was performed using RevMan 5.
MAIN RESULTS
Meta-analysis of the 5 cross-over studies found a reduction in SBP of 20.09 mmHg (95%CI:16.58-23.06,p<0.00001) and a 6.75 mmHg (95%CI:4.8-8.69,p<0.00001) reduction in DBP. These results were statistically significant and there was no evidence of heterogeneity between the studies. There may be a dose response effect with spironolactone up to 50 mg/day, but the confidence intervals around the mean end-of-study blood pressure for doses ranging 25-500 mg/day all overlapped. In other words, it appears that doses >50mg/day do not produce further reductions in either SBP or DBP. One cross-over study found that spironolactone 25 mg/day did not statistically significantly change SBP or DBP compared to placebo, SBP: -9.9 (95%CI:-21.15,1.35); DBP -2.34 (95%CI:-7.92,3.06).
AUTHORS' CONCLUSIONS
From the limited available evidence, spironolactone appears to lower blood pressure compared to placebo to a similar degree in patients with primary (essential) hypertension when doses of 100-500 mg/day are given. A dose of 25 mg/day did not statistically significantly reduce systolic or diastolic blood pressure, compared to placebo. Given the lack of a dose-response, coupled with a possible increased risk in adverse events with higher doses, doses of 25 to 100 mg/day are reasonable. There is no evidence of the effect of spironolactone on clinical outcomes in hypertensive patients.
Topics: Antihypertensive Agents; Blood Pressure; Cross-Over Studies; Humans; Hypertension; Randomized Controlled Trials as Topic; Spironolactone
PubMed: 20687095
DOI: 10.1002/14651858.CD008169.pub2 -
The Cochrane Database of Systematic... Feb 2014Trabeculectomy is performed as a treatment for many types of glaucoma in an attempt to lower the intraocular pressure. The surgery involves creating a channel through... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Trabeculectomy is performed as a treatment for many types of glaucoma in an attempt to lower the intraocular pressure. The surgery involves creating a channel through the sclera, through which intraocular fluid can leave the eye. If scar tissue blocks the exit of the surgically created channel, intraocular pressure rises and the operation fails. Antimetabolites such as 5-Fluorouracil (5-FU) are used to inhibit wound healing to prevent the conjunctiva scarring down on to the sclera. This is an update of a Cochrane review first published in 2000, and previously updated in 2009.
OBJECTIVES
To assess the effects of both intraoperative application and postoperative injections of 5-FU in eyes of people undergoing surgery for glaucoma at one year.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2013), EMBASE (January 1980 to July 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 25 July 2013. We also searched the reference lists of relevant articles and the Science Citation Index and contacted investigators and experts for details of additional relevant trials.
SELECTION CRITERIA
We included randomised trials of intraoperative application and postoperative 5-FU injections compared with placebo or no treatment in trabeculectomy for glaucoma.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. We used standard methodological procedures expected by The Cochrane Collaboration. We contacted trial investigators for missing information. Data were summarised using risk ratio (RR), Peto odds ratio and mean difference, as appropriate.The participants were divided into three separate subgroup populations (high risk of failure, combined surgery and primary trabeculectomy) and the interventions were divided into three subgroups of 5-FU injections (intraoperative, regular dose postoperative and low dose postoperative). The low dose was defined as a total dose less than 19 mg.
MAIN RESULTS
Twelve trials, which randomised 1319 participants, were included in the review. As far as can be determined from the trial reports, the methodological quality of the trials was not high, including a high risk of detection bias in many. Of note, only one study reported low-dose postoperative 5-FU and this paper was at high risk of reporting bias.Not all studies reported population characteristics, of those that did mean age ranged from 61 to 75 years. 83% of participants were white and 40% were male. All studies were a minimum of one year long.A significant reduction in surgical failure in the first year after trabeculectomy was detected in eyes at high risk of failure and those undergoing surgery for the first time receiving regular-dose 5-FU postoperative injections (RR 0.44, 95% confidence interval (CI) 0.29 to 0.68 and 0.21, 0.06 to 0.68, respectively). No surgical failures were detected in studies assessing combined surgery. No difference was detected in the low-dose postoperative 5-FU injection group in patients undergoing primary trabeculectomy (RR 0.93, 95% CI 0.70 to 1.24). Peroperative 5-FU in patients undergoing primary trabeculectomy significantly reduced risk of failure (RR 0.67, 95% CI 0.51 to 0.88). This translates to a number needed to treat for an additional beneficial outcome of 4.1 for the high risk of failure patients, and 5.0 for primary trabeculectomy patients receiving postoperative 5-FU.Intraocular pressure was also reduced in the primary trabeculectomy group receiving intraoperative 5-FU (mean difference (MD) -1.04, 95% CI -1.65 to -0.43) and regular-dose postoperative 5-FU (MD -4.67, 95% CI -6.60 to -2.73). No significant change occurred in the primary trabeculectomy group receiving low-dose postoperative 5-FU (MD -0.50, 95% CI -2.96 to 1.96). Intraocular pressure was particularly reduced in the high risk of failure population receiving regular-dose postoperative 5-FU (MD -16.30, 95% CI -18.63 to -13.97). No difference was detected in the combined surgery population receiving regular-dose postoperative 5-FU (MD -1.02, 95% CI -2.40 to 0.37).Whilst no evidence was found of an increased risk of serious sight-threatening complications, other complications are more common after 5-FU injections. None of the trials reported on the participants' perspective of care.The quality of evidence varied between subgroups and outcomes, most notably the evidence for combined surgery and low-dose postoperative 5-FU was found to be very low using GRADE. The combined surgery postoperative 5-FU subgroup because no surgical failures have been reported and the sample size is small (n = 118), and the low-dose postoperative 5-FU group because of the small sample size (n = 76) and high risk of bias of the only contributing study.
AUTHORS' CONCLUSIONS
Postoperative injections of 5-FU are now rarely used as part of routine packages of postoperative care but are increasingly used on an ad hoc basis. This presumably reflects an aspect of the treatment that is unacceptable to both patients and doctors. None of the trials reported on the participants' perspective of care, which constitutes a serious omission for an invasive treatment such as this.The small but statistically significant reduction in surgical failures and intraocular pressure at one year in the primary trabeculectomy group and high-risk group must be weighed against the increased risk of complications and patient preference.
Topics: Antimetabolites; Cicatrix; Fluorouracil; Glaucoma; Humans; Randomized Controlled Trials as Topic; Trabeculectomy; Wound Healing
PubMed: 24554410
DOI: 10.1002/14651858.CD001132.pub2 -
The Cochrane Database of Systematic... Jul 2016Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with cystic fibrosis and appropriate antibiotic therapy is vital.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with cystic fibrosis and appropriate antibiotic therapy is vital. Antibiotics for pulmonary exacerbations are usually given intravenously, and for long-term treatment, via a nebuliser. Oral anti-pseudomonal antibiotics with the same efficacy and safety as intravenous or nebulised antibiotics would benefit people with cystic fibrosis due to ease of treatment and avoidance of hospitalisation. This is an update of a previous review.
OBJECTIVES
To determine the benefit or harm of oral anti-pseudomonal antibiotic therapy for people with cystic fibrosis, colonised with Pseudomonas aeruginosa, in the:1. treatment of a pulmonary exacerbation; and2. long-term treatment of chronic infection.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We contacted pharmaceutical companies and checked reference lists of identified trials.Date of last search: 08 July 2016.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials comparing any dose of oral anti-pseudomonal antibiotics, to other combinations of inhaled, oral or intravenous antibiotics, or to placebo or usual treatment for pulmonary exacerbations and long-term treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently selected the trials, extracted data and assessed quality. We contacted trial authors to obtain missing information.
MAIN RESULTS
We included three trials examining pulmonary exacerbations (171 participants) and two trials examining long-term therapy (85 participants). We regarded the most important outcomes as quality of life and lung function. The analysis did not identify any statistically significant difference between oral anti-pseudomonal antibiotics and other treatments for these outcome measures for either pulmonary exacerbations or long-term treatment. One of the included trials reported significantly better lung function when treating a pulmonary exacerbation with ciprofloxacin when compared with intravenous treatment; however, our analysis did not confirm this finding. We found no evidence of difference between oral anti-pseudomonal antibiotics and other treatments regarding adverse events or development of antibiotic resistance, but trials were not adequately powered to detect this. None of the studies had a low risk of bias from blinding which may have an impact particularly on subjective outcomes such as quality of life. The risk of bias for other criteria could not be clearly stated across the studies.
AUTHORS' CONCLUSIONS
We found no conclusive evidence that an oral anti-pseudomonal antibiotic regimen is more or less effective than an alternative treatment for either pulmonary exacerbations or long-term treatment of chronic infection with P. aeruginosa. Until results of adequately-powered future trials are available, treatment needs to be selected on a pragmatic basis, based upon any available non-randomised evidence, the clinical circumstances of the individual, the known effectiveness of drugs against local strains and upon individual preference.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Child; Chronic Disease; Cystic Fibrosis; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Outcome
PubMed: 27412131
DOI: 10.1002/14651858.CD005405.pub4 -
The Cochrane Database of Systematic... Mar 2017Functional dyspepsia (FD or non-ulcer dyspepsia) is defined as continuous or frequently recurring epigastric pain or discomfort for which no organic cause can be found.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional dyspepsia (FD or non-ulcer dyspepsia) is defined as continuous or frequently recurring epigastric pain or discomfort for which no organic cause can be found. Acid suppressive therapy, including proton pump inhibitors (PPIs), has been proposed as a therapeutic option in FD, but its efficacy remains controversial. While PPIs are generally considered safe and well tolerated, they have been associated with adverse events, especially in the long term. For this reason, decisions on whether to initiate or continue PPI therapy should be made based on an appropriate clinical indication. Therefore, we conducted a systematic review to evaluate whether PPI therapy provides symptomatic relief in FD.
OBJECTIVES
To determine the efficacy of proton pump inhibitors in the improvement of global symptoms of dyspepsia and quality of life compared to placebo, H2 receptor antagonists or prokinetics, in people with functional dyspepsia.
SEARCH METHODS
We searched in the following electronic databases: the Cochrane Library (to January 2016), MEDLINE (OvidSP; to February 2016), Embase (OvidSP; to February 2016), and SIGLE grey literature (up to February 2016) and clinical trial registries; we handsearched abstracts from conferences up to February 2016. We screened non-systematic reviews, systematic reviews and guidelines to identify any additional trials. We contacted trialists to obtain missing information.
SELECTION CRITERIA
All randomized controlled trials (RCTs) comparing any PPI with placebo, H2 receptor antagonists (H2RAs) or prokinetics for the treatment of FD. Participants were adults (aged 16 years or greater) with an adequate diagnosis of FD (any validated criteria such as Rome I, II, III or Lancet Working Group).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility, trial quality and extracted data. We collected data on dyspeptic symptoms, quality of life and number of overall adverse events. Specific adverse events were beyond the scope of this review.
MAIN RESULTS
We identified 23 RCTs from 22 papers (with 8759 participants) studying the effect of PPIs versus placebo, H2RAs or prokinetics for improvement of global symptoms of dyspepsia and quality of life in people with FD. Low-dose PPIs had similar efficacy as standard-dose PPIs, therefore we combined these subgroups for the analysis. Two to eight weeks of therapy with PPI was slightly more effective than placebo at relieving overall dyspepsia symptoms in people with FD (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.94; participants = 5968; studies = 16; number needed to treat for an additional beneficial outcome (NNTB) 13; moderate quality evidence). PPIs may be slightly more effective than H2RAs (RR 0.88, 95% CI 0.74 to 1.04; participants = 740; studies = 2, NNTB 13; low quality evidence), and slightly more effective than prokinetics (RR 0.90, 95% CI 0.81 to 1.00; participants = 892; studies = 4; NNTB 20; low quality evidence) at relieving overall dyspepsia symptoms in people with FD. PPIs plus prokinetics were possibly slightly more effective than PPIs alone at relieving overall dyspepsia symptoms (RR 0.85, 95% CI 0.68 to 1.08; participants = 407; studies = 2; NNTB 18; moderate quality evidence).The was no difference when subgrouped by Helicobacter pylori status, country of origin, or presence of reflux or Rome III subtypes. There were no differences in the number of adverse events observed between PPIs and any of the other treatments.
AUTHORS' CONCLUSIONS
There is evidence that PPIs are effective for the treatment of FD, independent of the dose and duration of treatment compared with placebo. PPIs may be slightly more effective than H2RAs for the treatment of FD; however, the evidence is scarce. The trials evaluating PPIs versus prokinetics are difficult to interpret as they are at risk of bias. Although the effect of these drugs seems to be small, the drugs are well tolerated.
Topics: Dyspepsia; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28271513
DOI: 10.1002/14651858.CD011194.pub2 -
Vascular Jun 2023Exercise therapy is an important treatment option for people with intermittent claudication (IC). Appropriate reporting of exercise interventions in populations with IC...
BACKGROUND
Exercise therapy is an important treatment option for people with intermittent claudication (IC). Appropriate reporting of exercise interventions in populations with IC within randomised controlled trials (RCTs) is important to ensure that research can be translated into clinical practice. Therefore, the purpose of our review is to evaluate the reporting of exercise interventions in RCTs of exercise therapy in patients with IC.
METHODS
A systematic search was performed to identify relevant trials in patients with IC published until May 2020. Studies including only participants with critical limb ischaemia or asymptomatic peripheral artery disease were excluded. Each trial was scored using the recently developed 'Consensus on Exercise Reporting Template' (CERT) which has a maximum obtainable score of 19.
RESULTS
Of 1489 unique records identified from the search, 73 trials were included, reporting 107 exercise interventions. Overall, the average CERT score was 10/19. The exercise equipment used, the use of supervision and a description of whether the exercise prescription was tailored or generic were the most frequently reported intervention components. The motivational strategies used, intervention adherence and intervention fidelity were the most underreported CERT components. There was no trend indicating that CERT scores were higher in more recent publications.
CONCLUSIONS
We have identified that important details about exercise interventions are frequently missing from the published literature. These missing data hinder replication of research findings and limit the translation of evidence into clinical practice.
Topics: Humans; Intermittent Claudication; Exercise Therapy; Exercise; Peripheral Arterial Disease
PubMed: 35130092
DOI: 10.1177/17085381211070700 -
The Cochrane Database of Systematic... Nov 2017Functional dyspepsia (FD or non-ulcer dyspepsia) is defined as continuous or frequently recurring epigastric pain or discomfort for which no organic cause can be found.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional dyspepsia (FD or non-ulcer dyspepsia) is defined as continuous or frequently recurring epigastric pain or discomfort for which no organic cause can be found. Acid suppressive therapy, including proton pump inhibitors (PPIs), has been proposed as a therapeutic option in FD, but its efficacy remains controversial. While PPIs are generally considered safe and well tolerated, they have been associated with adverse events, especially in the long term. For this reason, decisions on whether to initiate or continue PPI therapy should be made based on an appropriate clinical indication. Therefore, we conducted a systematic review to evaluate whether PPI therapy provides symptomatic relief in FD.
OBJECTIVES
To determine the efficacy of proton pump inhibitors in the improvement of global symptoms of dyspepsia and quality of life compared to placebo, H2 receptor antagonists or prokinetics, in people with functional dyspepsia.
SEARCH METHODS
We searched in the following electronic databases: the Cochrane Library (to May 2017), MEDLINE (OvidSP; to May 2017), Embase (OvidSP; to May 2017), and SIGLE grey literature (up to May 2017) and clinical trial registries; we handsearched abstracts from conferences up to May 2017. We screened non-systematic reviews, systematic reviews and guidelines to identify any additional trials. We contacted trialists to obtain missing information.
SELECTION CRITERIA
All randomized controlled trials (RCTs) comparing any PPI with placebo, H2 receptor antagonists (H2RAs) or prokinetics for the treatment of FD of at least two weeks' duration. Participants were adults (aged 16 years or greater) with an adequate diagnosis of FD (any validated criteria such as Rome I, II, III or Lancet Working Group).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility and trial quality, and extracted data. We collected data on dyspeptic symptoms, quality of life and number of overall adverse events. Specific adverse events were beyond the scope of this review.
MAIN RESULTS
We identified 25 RCTs from 27 papers (with 8453 participants) studying the effect of PPIs versus placebo, H2RAs or prokinetics for improvement of global symptoms of dyspepsia and quality of life in people with FD. Low-dose PPIs had similar efficacy as standard-dose PPIs, therefore we combined these subgroups for the analysis. PPI was more effective than placebo at relieving overall dyspepsia symptoms in people with FD (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.94; participants = 6172; studies = 18; number needed to treat for an additional beneficial outcome (NNTB) 11; moderate quality evidence). PPIs may have little or no effect compared with H2RAs (RR 0.88, 95% CI 0.74 to 1.04; participants = 740; studies = 2; low quality evidence), and may be slightly more effective than prokinetics (RR 0.89, 95% CI 0.81 to 0.99; participants = 1033; studies = 5; NNTB 16; low quality evidence) at relieving overall dyspepsia symptoms in people with FD. PPIs plus prokinetics have probably little or no effect compared with PPIs alone at relieving overall dyspepsia symptoms (RR 0.85, 95% CI 0.68 to 1.08; participants = 407; studies = 2; moderate quality evidence).There was no difference when subgrouped by Helicobacter pylori status, country of origin, or presence of reflux or Rome III subtypes. There were no differences in the number of adverse events observed between PPIs and any of the other treatments. There were fewer adverse events in the combination of PPI plus prokinetics compared to prokinetics alone (RR 0.60, 95% CI 0.39 to 0.93; participants = 407; studies = 2; moderate quality evidence).
AUTHORS' CONCLUSIONS
There is evidence that PPIs are effective for the treatment of FD, independent of the dose and duration of treatment compared with placebo. PPIs may be slightly more effective than prokinetics for the treatment of FD; however, the evidence is scarce. The trials evaluating PPIs versus prokinetics are difficult to interpret as they are at risk of bias. Although the effect of these drugs seems to be small, the drugs are well tolerated.
Topics: Dyspepsia; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 29161458
DOI: 10.1002/14651858.CD011194.pub3 -
The Cochrane Database of Systematic... Dec 2015Sepsis occurs when an infection is complicated by organ failures as defined by a sequential organ failure assessment (SOFA) score of two or higher. Sepsis may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sepsis occurs when an infection is complicated by organ failures as defined by a sequential organ failure assessment (SOFA) score of two or higher. Sepsis may be complicated by impaired corticosteroid metabolism. Giving corticosteroids may benefit patients. The original review was published in 2004 and was updated in 2010 and again in 2015.
OBJECTIVES
To examine the effects of corticosteroids on death at one month in patients with sepsis, and to examine whether dose and duration of corticosteroids influence patient response to this treatment.
SEARCH METHODS
We searched the Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (October 2014), EMBASE (October 2014), Latin American Caribbean Health Sciences Literature (LILACS; October 2014) and reference lists of articles, and we contacted trial authors. The original searches were performed in August 2003 and in October 2009.
SELECTION CRITERIA
We included randomized controlled trials of corticosteroids versus placebo or supportive treatment in patients with sepsis.
DATA COLLECTION AND ANALYSIS
All review authors agreed on the eligibility of trials. One review author extracted data, which were checked by the other review authors, and by the primary author of the paper when possible. We obtained some missing data from trial authors. We assessed the methodological quality of trials.
MAIN RESULTS
We identified nine additional studies since the last update, for a total of 33 eligible trials (n = 4268 participants). Twenty-three of these 33 trials were at low risk of selection bias, 22 were at low risk of performance and detection bias, 27 were at low risk of attrition bias and 14 were at low risk of selective reporting.Corticosteroids reduced 28-day mortality (27 trials; n = 3176; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.76 to 1.00; P value = 0.05, random-effects model). The quality of evidence for this outcome was downgraded from high to low for imprecision (upper limit of 95% CI = 1) and for inconsistency (significant heterogeneity across trial results). Heterogeneity was related in part to the dosing strategy. Treatment with a long course of low-dose corticosteroids significantly reduced 28-day mortality (22 trials; RR 0.87, 95% CI 0.78 to 0.97; P value = 0.01, fixed-effect model). The quality of evidence was downgraded from high to moderate for inconsistency (owing to non-significant effects shown by one large trial). Corticosteroids also reduced mortality rate in the intensive care unit (13 trials; RR 0.82, 95% CI 0.68 to 1.00; P value = 0.04, random-effects model) and at the hospital (17 trials; RR 0.85, 95% CI 0.73 to 0.98; P value = 0.03, random-effects model). Quality of the evidence for in-hospital mortality was downgraded from high to moderate for inconsistency and imprecision (upper limit of 95% CI for RR approaching 1). Corticosteroids increased the proportion of shock reversal by day seven (12 trials; RR 1.31, 95% CI 1.14 to 1.51; P value = 0.0001) and by day 28 (seven trials; n = 1013; RR 1.11, 95% CI 1.02 to 1.21; P value = 0.01) and reduced the SOFA score by day seven (eight trials; mean difference (MD) -1.53, 95% CI -2.04 to -1.03; P value < 0.00001, random-effects model) and survivors' length of stay in the intensive care unit (10 trials; MD -2.19, 95% CI -3.93 to -0.46; P value = 0.01, fixed-effect model) without inducing gastroduodenal bleeding (19 trials; RR 1.24, 95% CI 0. 92 to 1.67; P value = 0.15, fixed-effect model), superinfection (19 trials; RR 1.02, 95% CI 0.87 to 1.20; P value = 0.81, fixed-effect model) or neuromuscular weakness (three trials; RR 0.62, 95% CI 0.21 to 1.88; P value = 0.40, fixed-effect model). Corticosteroid increased the risk of hyperglycaemia (13 trials; RR 1.26, 95% CI 1.16 to 1.37; P value < 0.00001, fixed-effect model) and hypernatraemia (three trials; RR 1.64, 95% CI 1.28 to 2.09; P value < 0.0001, fixed-effect model).
AUTHORS' CONCLUSIONS
Overall, low-quality evidence indicates that corticosteroids reduce mortality among patients with sepsis. Moderate-quality evidence suggests that a long course of low-dose corticosteroids reduced 28-day mortality without inducing major complications and led to an increase in metabolic disorders.
Topics: Adrenal Cortex Hormones; Adult; Child; Critical Care; Dexamethasone; Fludrocortisone; Humans; Hydrocortisone; Methylprednisolone; Organ Dysfunction Scores; Prednisolone; Randomized Controlled Trials as Topic; Sepsis; Shock, Septic; Time Factors
PubMed: 26633262
DOI: 10.1002/14651858.CD002243.pub3