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The Cochrane Database of Systematic... Jan 2021Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence of up to 90%, which can significantly affect quality of life, both during periods of active disease or in remission. It is important that iron deficiency anaemia is treated effectively and not be assumed to be a normal finding of inflammatory bowel disease. The various routes of iron administration, doses and preparations present varying advantages and disadvantages, and a significant proportion of people experience adverse effects with current therapies. Currently, no consensus has been reached amongst physicians as to which treatment path is most beneficial.
OBJECTIVES
The primary objective was to evaluate the efficacy and safety of the interventions for the treatment of iron deficiency anaemia in people with inflammatory bowel disease.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and two other databases on 21st November 2019. We also contacted experts in the field and searched references of trials for any additional trials.
SELECTION CRITERIA
Randomised controlled trials investigating the effectiveness and safety of iron administration interventions compared to other iron administration interventions or placebo in the treatment of iron deficiency anaemia in inflammatory bowel disease. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology.
MAIN RESULTS
We included 11 studies (1670 randomised participants) that met the inclusion criteria. The studies compared intravenous iron sucrose vs oral iron sulphate (2 studies); oral iron sulphate vs oral iron hydroxide polymaltose complex (1 study); oral iron fumarate vs intravenous iron sucrose (1 study); intravenous ferric carboxymaltose vs intravenous iron sucrose (1 study); erythropoietin injection + intravenous iron sucrose vs intravenous iron sucrose + injection placebo (1 study); oral ferric maltol vs oral placebo (1 study); oral ferric maltol vs intravenous ferric carboxymaltose (1 study); intravenous ferric carboxymaltose vs oral iron sulphate (1 study); intravenous iron isomaltoside vs oral iron sulphate (1 study); erythropoietin injection vs oral placebo (1 study). All studies compared participants with CD and UC together, as well as considering a range of disease activity states. The primary outcome of number of responders, when defined, was stated to be an increase in haemoglobin of 20 g/L in all but two studies in which an increase in 10g/L was used. In one study comparing intravenous ferric carboxymaltose and intravenous iron sucrose, moderate-certainty evidence was found that intravenous ferric carboxymaltose was probably superior to intravenous iron sucrose, although there were responders in both groups (150/244 versus 118/239, RR 1.25, 95% CI 1.06 to 1.46, number needed to treat for an additional beneficial outcome (NNTB) = 9). In one study comparing oral ferric maltol to placebo, there was low-certainty evidence of superiority of the iron (36/64 versus 0/64, RR 73.00, 95% CI 4.58 to 1164.36). There were no other direct comparisons that found any difference in the primary outcomes, although certainty was low and very low for all outcomes, due to imprecision from sparse data and risk of bias varying between moderate and high risk. The reporting of secondary outcomes was inconsistent. The most common was the occurrence of serious adverse events or those requiring withdrawal of therapy. In no comparisons was there a difference seen between any of the intervention agents being studied, although the certainty was very low for all comparisons made, due to risk of bias and significant imprecision due to the low numbers of events. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes were reported in any of the studies. An analysis of all intravenous iron preparations to all oral iron preparations showed that intravenous administration may lead to more responders (368/554 versus 205/373, RR 1.17, 95% CI 1.05 to 1.31, NNTB = 11, low-certainty due to risk of bias and inconsistency). Withdrawals due to adverse events may be greater in oral iron preparations vs intravenous (15/554 versus 31/373, RR 0.39, 95% CI 0.20 to 0.74, low-certainty due to risk of bias, inconsistency and imprecision).
AUTHORS' CONCLUSIONS
Intravenous ferric carboxymaltose probably leads to more people having resolution of IDA (iron deficiency anaemia) than intravenous iron sucrose. Oral ferric maltol may lead to more people having resolution of IDA than placebo. We are unable to draw conclusions on which of the other treatments is most effective in IDA with IBD (inflammatory bowel disease) due to low numbers of studies in each comparison area and clinical heterogeneity within the studies. Therefore, there are no other conclusions regarding the treatments that can be made and certainty of all findings are low or very low. Overall, intravenous iron delivery probably leads to greater response in patients compared with oral iron, with a NNTB (number needed to treat) of 11. Whilst no serious adverse events were specifically elicited with any of the treatments studied, the numbers of reported events were low and the certainty of these findings very low for all comparisons, so no conclusions can be drawn. There may be more withdrawals due to such events when oral is compared with intravenous iron delivery. Other outcomes were poorly reported and once again no conclusions can be made as to the impact of IDA on any of these outcomes. Given the widespread use of many of these treatments in practice and the only guideline that exists recommending the use of intravenous iron in favour of oral iron, research to investigate this key issue is clearly needed. Considering the current ongoing trials identified in this review, these are more focussed on the impact in specific patient groups (young people) or on other symptoms (such as fatigue). Therefore, there is a need for studies to be performed to fill this evidence gap.
Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Bias; Colitis, Ulcerative; Crohn Disease; Disaccharides; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Fumarates; Hematinics; Humans; Iron Compounds; Maltose; Middle Aged; Placebos; Pyrones; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33471939
DOI: 10.1002/14651858.CD013529.pub2 -
BMJ Open Feb 2022Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for clinical outcomes in high cardiovascular (CV) risk patients.
DATA SOURCES
MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Embase, ClinicalTrials.gov, Clinical Trial Results and the American College of Cardiology web site were searched.
STUDY SELECTION
Randomised controlled trials (RCTs) of BA versus placebo in high CV risk patients reporting clinical outcomes were included.
MAIN OUTCOMES AND MEASURES
Primary efficacy outcomes were major adverse cardiovascular events (MACE), all-cause mortality, CV mortality and non-fatal myocardial infarction (MI). Safety outcomes included new onset or worsening of diabetes mellitus (DM), muscular disorders, gout and worsening of renal function.
RESULTS
Six RCTs with a total of 3956 patients and follow-ups of four to 52 weeks were identified. Heterogeneity mainly derived from differing follow-up duration and baseline CV risk. No difference in MACE (OR 0.84; 95% CI 0.61 to 1.15), all-cause mortality (OR 2.37; CI 0.80 to 6.99) and CV mortality (OR 1.66; CI 0.45 to 6.04) for BA versus placebo was observed. BA showed beneficial trends for non-fatal MI (OR 0.57; CI 0.32 to 1.00) and was associated with a lower risk of new-onset or worsening of DM (OR 0.68; CI 0.49 to 0.94), but higher risk of gout (OR 3.29; CI 1.28 to 8.46) and a trend for muscular disorders (OR 2.60; CI 1.15 to 5.91) and worsening of renal function (OR 4.24; CI 0.98 to 18.39).
CONCLUSION
BA in high CV risk patients showed no significant effects on major CV outcomes in short-term follow-up. Unfavourable effects on muscular disorders, renal function and gout sound a note of caution. Hence, further studies with longer term follow-up in carefully selected populations are needed to clarify the risk/benefit ratio of this novel therapy.
Topics: Cholesterol, LDL; Dicarboxylic Acids; Fatty Acids; Humans; Treatment Outcome
PubMed: 35210334
DOI: 10.1136/bmjopen-2021-048893 -
Cardiovascular Diabetology Aug 2020Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the prevention of cardiovascular events and diabetes is lacking. Thus, we aim to evaluate the benefit and safety of bempedoic acid use for the prevention of cardiovascular events and diabetes.
METHODS
We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials with no language restriction from inception until March 3, 2020. Pairs of reviewers independently identified randomized controlled trials comparing the use of bempedoic acid with placebo or no treatment for primary prevention of cardiovascular events in statin-intolerant patients with hypercholesterolemia. The primary outcomes were major adverse cardiac events, and percent change in LDL-C.
RESULTS
We identified 11 trials including a total of 4391 participants. Bempedoic acid use was associated with a reduction in composite cardiovascular outcome (RR 0.75, 95% CI 0.56-0.99; I = 0%). Bempedoic acid reduced LDL-C levels (MD - 22.91, 95% CI - 27.35 to - 18.47; I = 99%), and similarly reduced CRP levels (MD -24.70, 95% CI - 32.10 to - 17.30; I = 53%). Bempedoic acid was associated with a reduction in rates of new-onset or worsening diabetes (RR 0.65, 95% CI 0.44-0.96; I = 23%).
CONCLUSIONS
Bempedoic acid in patients with hypercholesterolemia was associated with a lower risk of cardiovascular events and diabetes.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus; Dicarboxylic Acids; Down-Regulation; Fatty Acids; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Male; Middle Aged; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32787939
DOI: 10.1186/s12933-020-01101-9 -
Archivio Italiano Di Urologia,... Mar 2016To analyze the clinical evidence on the efficacy of phytotherapy in the treatment of calculi in the urinary tract. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To analyze the clinical evidence on the efficacy of phytotherapy in the treatment of calculi in the urinary tract.
METHODS
To be eligible, full-length articles should include the results of randomized controlled trials enrolling patients affected by urolithiasis, reporting any comparison between an experimental herbal agent versus placebo or any active comparator, aimed at preventing the formation or facilitating the dissolution of calculi in any portion of the urinary tract. Fifteen databases were searched for relevant references. The primary outcomes investigated were (i) the reduction of stone size and/or number and (ii) the urinary excretion rates of calcium, urate, or oxalate. The secondary outcome of the review was the adverse effects (AE) of treatment. Risk of bias (ROB) and quality of the evidence were assessed according to Cochrane and GRADE guidelines. We performed a random-effect meta-analysis.
RESULTS
541 articles were retrieved and 16 studies were finally confirmed as eligible. Multiple Cochrane ROB tool items were rated as having high risk of bias in each analyzed trial report. Pooled analysis of continuous data could be performed for three different comparisons: (i) phytotherapy versus citrate as single agent (ii) phytotherapy versus placebo, (iii) preparation of Didymocarpus pedicellata (DP)--combined with other herbal agents--versus placebo. Results showed that citrate is superior to phytotherapy in significantly decreasing both the size of urinary stones (mean difference: phytotherapy, 0.42 mm higher; 95% CI: 0.23 to 0.6; Z = 4.42, P < 0.0001; I2 = 30%) and the urinary excretion rate of urate (mean difference: 42.32 mg/24h higher, 95% CI: 19.44 to 65.19; Z = 3.63, P = 0.0003; I2 = 96%), assessed after 3 months on-therapy. No significant differences in the excretion rates of urinary calcium or oxalate were found. The DP preparation was superior to placebo in inducing total clearance (risk ratio: 6.19, 95% CI: 2.60 to 14.74; Z = 4.12, P < 0.0001; I2 = 0%) and size reduction (mean difference: DP preparation, 4.93 mm lower; 95% CI: -9.18 to -0.67; Z = 2.27, P = 0.02; I2 = 99%) of renal and ureteral stones after 3 months of therapy. No significant differences in the inter-arm variation of excretion rates of urinary calcium or urate were found as result of the pooled phytotherapy-placebo comparison. Herbal remedies were in general devoid of side effects and in few cases citrate appeared to induce GI disturbances in a higher fraction of patients. Most reports did not provide inferential data concerning AE, and meta-analysis was not feasible.
CONCLUSIONS
Citrate is more effective than phytotherapy in decreasing the size of existing calculi in the urinary tract and in decreasing the urinary excretion rate of uric acid. A preparation containing Didymocarpus pedicellata combined with other herbal agents induces stone size reduction and clearance significantly better than placebo. Mayor limitations in the applicability of these results are the low quality of the evidence and the multiple sources of bias assessed in the studies included in the present review.
Topics: Calcium; Citric Acid; Humans; Oxalic Acid; Phytotherapy; Plant Preparations; Plants, Medicinal; Randomized Controlled Trials as Topic; Uric Acid; Urinary Calculi
PubMed: 27072174
DOI: 10.4081/aiua.2016.1.38 -
The Cochrane Database of Systematic... Aug 2015Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including oral fumaric acid esters (FAE). These contain dimethyl fumarate (DMF), the main active ingredient, and monoethyl fumarate. FAE are licensed for psoriasis in Germany but used off-licence in many countries.
OBJECTIVES
To assess the effects and safety of oral fumaric acid esters for psoriasis.
SEARCH METHODS
We searched the following databases up to 7 May 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials. We handsearched six conference proceedings that were not already included in the Cochrane Skin Group Specialised Register.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of FAE, including DMF monotherapy, in individuals of any age and sex with a clinical diagnosis of psoriasis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. Primary outcomes were improvement in Psoriasis Area and Severity Index (PASI) score and the proportion of participants discontinuing treatment due to adverse effects.
MAIN RESULTS
We included 6 studies (2 full reports, 2 abstracts, 1 brief communication, and 1 letter), with a total of 544 participants. Risk of bias was unclear in several studies because of insufficient reporting. Five studies compared FAE with placebo, and one study compared FAE with methotrexate. All studies reported data at 12 to 16 weeks, and we identified no longer-term studies. When FAE were compared with placebo, we could not perform meta-analysis for the primary outcome of PASI score because the three studies that assessed this outcome reported the data differently, although all studies reported a significant reduction in PASI scores with FAE. Only 1 small study designed for psoriatic arthritis reported on the other primary outcome of participants discontinuing treatment due to adverse effects (2 of 13 participants on FAE compared with none of the 14 participants on placebo; risk ratio (RR) 5.36, 95% confidence interval (CI) 0.28 to 102.1; 27 participants; very low-quality evidence). However, these findings are uncertain due to indirectness and a very wide confidence interval. Two studies, containing 247 participants and both only reported as abstracts, allowed meta-analysis for PASI 50, which showed superiority of FAE over placebo (RR 4.55, 95% CI 2.80 to 7.40; low-quality evidence), with a combined PASI 50 of 64% in those given FAE compared with a PASI 50 of 14% for those on placebo, representing a number needed to treat to benefit of 2. The same studies reported more participants achieving PASI 75 with FAE, but we did not pool the data because of significant heterogeneity; none of the studies measured PASI 90. One study reported significant improvement in participants' quality of life (QoL) with FAE, measured with Skindex-29. However, we could not compute the mean difference because of insufficient reporting in the abstract. More participants experienced adverse effects, mainly gastrointestinal disturbance and flushing, on FAE (RR 4.72, 95% CI 2.45 to 9.08; 1 study, 99 participants; moderate-quality evidence), affecting 76% of participants given FAE and 16% of the placebo group (representing a number needed to treat to harm of 2). The other studies reported similar findings or did not report adverse effects fully.One study of 54 participants compared methotrexate (MTX) with FAE. PASI score at follow-up showed superiority of MTX (mean Difference (MD) 3.80, 95% CI 0.68 to 6.92; 51 participants; very low-quality evidence), but the difference was not significant after adjustment for baseline disease severity. The difference between groups for the proportion of participants who discontinued treatment due to adverse effects was uncertain because of imprecision (RR 0.19, 95% CI 0.02 to 1.53; 1 study, 51 participants; very low-quality evidence). Overall, the number of participants experiencing common nuisance adverse effects was not significantly different between the 2 groups, with 89% of the FAE group affected compared with 100% of the MTX group (RR 0.89, 95% CI 0.77 to 1.03; 54 participants; very low-quality evidence). Flushing was more frequent in those on FAE, with 13 out of 27 participants affected compared with 2 out of 27 given MTX. There was no significant difference in the number of participants who attained PASI 50, 75, and 90 in the 2 groups (very low-quality evidence) whereas this study did not measure the effect of treatments on QoL. The included studies reported no serious adverse effects of FAE and were too small and of limited duration to provide evidence about rare or delayed effects.
AUTHORS' CONCLUSIONS
Evidence suggests that FAE are superior to placebo and possibly similar in efficacy to MTX for psoriasis; however, the evidence provided in this review was limited, and it must be noted that four out of six included studies were abstracts or brief reports, restricting study reporting. FAE are associated with nuisance adverse effects, including flushing and gastrointestinal disturbance, but short-term studies reported no serious adverse effects.
Topics: Administration, Oral; Arthritis, Psoriatic; Dermatologic Agents; Fumarates; Humans; Methotrexate; Psoriasis; Randomized Controlled Trials as Topic; Severity of Illness Index
PubMed: 26258748
DOI: 10.1002/14651858.CD010497.pub2 -
Diabetes & Vascular Disease Research Sep 2017Aliskiren was shown to increase adverse events in patients with diabetes and concomitant renin-angiotensin blockade. We aim to investigate the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
Effects of aliskiren on mortality, cardiovascular outcomes and adverse events in patients with diabetes and cardiovascular disease or risk: A systematic review and meta-analysis of 13,395 patients.
BACKGROUND
Aliskiren was shown to increase adverse events in patients with diabetes and concomitant renin-angiotensin blockade. We aim to investigate the efficacy and safety of aliskiren in patients with diabetes and increased cardiovascular risk or established cardiovascular disease.
METHODS
MEDLINE and Embase were searched for prospective studies comparing addition of aliskiren to standard medical therapy in patients with diabetes and cardiovascular disease, or ⩾1 additional cardiovascular risk factor (hypertension, abnormal lipid profile, microalbuminuria/proteinuria, chronic kidney disease). Relative risk for efficacy (all-cause mortality, combined cardiovascular mortality and hospitalisation) and safety (hyperkalaemia, hypotension, renal impairment) outcomes was calculated.
RESULTS
Of 2151 studies identified in the search, seven studies enrolling 13,395 patients were included. Aliskiren had no effect on all-cause mortality (relative risk: 1.05, 95% confidence interval: 0.90 to 1.24, p = 0.53), or combined cardiovascular mortality or heart failure hospitalisation (relative risk: 1.07, 95% confidence interval: 0.81 to 1.40, p = 0.64). Patients receiving aliskiren had a greater risk of developing hyperkalaemia (relative risk: 1.32, 95% confidence interval: 1.14 to 1.53, p = 0.0003) and renal impairment (relative risk: 1.15, 95% confidence interval: 1.02 to 1.30, p = 0.03), but not hypotension.
CONCLUSION
Patients with diabetes and cardiovascular disease or cardiovascular risk do not benefit from the addition of aliskiren to standard medical therapy. Detrimental safety profile in pooled analysis supports current warnings.
Topics: Amides; Cardiovascular Agents; Cardiovascular Diseases; Chi-Square Distribution; Diabetes Mellitus; Fumarates; Humans; Odds Ratio; Renin-Angiotensin System; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 28844155
DOI: 10.1177/1479164117715854 -
Canadian Journal of Gastroenterology &... Nov 2014Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided... (Review)
Review
BACKGROUND
Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition.
OBJECTIVE
To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation.
SEARCH METHODS
PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation.
RESULTS
A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.
Topics: Bisacodyl; Canada; Citrates; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives; Magnesium Oxide; Organometallic Compounds; Paraffin; Picolines; Polyethylene Glycols; Psyllium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25390617
DOI: 10.1155/2014/631740 -
Journal of Sport and Health Science Dec 2020Citrulline is one of the non-essential amino acids that is thought to improve exercise performance and reduce post-exercise muscle soreness. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Citrulline is one of the non-essential amino acids that is thought to improve exercise performance and reduce post-exercise muscle soreness. We conducted a systematic review and meta-analysis to determine the effect of citrulline supplements on the post-exercise rating of perceived exertion (RPE), muscle soreness, and blood lactate levels.
METHODS
A random effects model was used to calculate the effect sizes due to the high variability in the study design and study populations of the articles included. A systematic search of PubMed, Web of Science, and ClinicalTrials.gov was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving healthy individuals and that investigated the acute effect of citrulline supplements on RPE, muscle soreness, and blood lactate levels. The supplementation time frame was limited to 2 h before exercise. The types and number of participants, types of exercise tests performed, supplementation protocols for L-citrulline or citrulline malate, and primary (RPE and muscle soreness) and secondary (blood lactate level) study outcomes were extracted from the identified studies.
RESULTS
The analysis included 13 eligible articles including a total of 206 participants. The most frequent dosage used in the studies was 8 g of citrulline malate. Citrulline supplementation significantly reduced RPE (n = 7, p = 0.03) and muscle soreness 24-h and 48-h after post-exercise (n = 7, p = 0.04; n = 6, p = 0.25, respectively). However, citrulline supplementation did not significantly reduce muscle soreness 72-h post-exercise (n = 4, p = 0.62) or lower blood lactate levels (n = 8, p = 0.17).
CONCLUSION
Citrulline supplements significantly reduced post-exercise RPE and muscle soreness without affecting blood lactate levels.
Topics: Citrulline; Dietary Supplements; Fruit and Vegetable Juices; Humans; Lactic Acid; Malates; Myalgia; Perception; Physical Exertion; Resistance Training
PubMed: 33308806
DOI: 10.1016/j.jshs.2020.02.003 -
The Cochrane Database of Systematic... Oct 2015Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate levels. These people have a higher incidence of calcium phosphate and calcium oxalate stones. Oral citrate therapy increases the urinary citrate levels, which in turn binds with calcium and inhibits the crystallisation thus reduces stone formation. Despite the widespread use of oral citrate therapy for prevention and treatment of calcium oxalate stones, the evidence to support its clinical efficacy remains uncertain.
OBJECTIVES
The objective of this review was to determine the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 29 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that assessed the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones in adults treated for a minimum of six months.
DATA COLLECTION AND ANALYSIS
Two authors assessed studies for inclusion in this review. Data were extracted according to predetermined criteria. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes.
MAIN RESULTS
We included seven studies that included a total of 477 participants, most of whom had oxalate stones. Of these, three studies (247 participants) compared potassium citrate with placebo or no intervention; three (166 participants) compared potassium-sodium citrate with no intervention; and one (64 participants) compared potassium-magnesium citrate with placebo. Overall, quality of the reporting of the included studies was considered moderate to poor, and there was a high risk of attrition bias in two studies.Compared with placebo or no intervention, citrate therapy significantly reduced the stone size (4 studies, 160 participants: RR 2.35, 95% CI 1.36 to 4.05). New stone formation was significantly lower with citrate therapy compared to control (7 studies, 324 participants: RR 0.26, 95% CI 0.10 to 0.68). The beneficial effect on stone size stability was also evident (4 studies, 160 participants: RR 1.97, 95% CI 1.19 to 3.26). Adverse events were reported in four studies, with the main side effects being upper gastrointestinal disturbance and one patient reported a rash. There were more gastrointestinal adverse events in the citrate group; however this was not significant (4 studies, 271 participants: RR 2.55, 95% CI 0.71 to 9.16). There were significantly more dropouts due to adverse events with citrate therapy compared to control (4 studies, 271 participants: RR 4.45, 95% CI 1.28 to 15.50). The need for retreatment was significantly less with citrate therapy compared to control (2 studies, 157 participants: RR 0.22, 95% CI 0.06 to 0.89).
AUTHORS' CONCLUSIONS
Citrate salts prevent new stone formation and reduce further stone growth in patients with residual stones that predominantly contain oxalate. The quality of reported literature remains moderate to poor; hence a well-designed statistically powered multi-centre RCT is needed in order to answer relevant questions concerning the efficacy of citrate salts.
Topics: Adult; Calcium Oxalate; Calcium Phosphates; Citrates; Drug Combinations; Humans; Kidney Calculi; Magnesium Compounds; Potassium Compounds; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 26439475
DOI: 10.1002/14651858.CD010057.pub2 -
BMC Pharmacology & Toxicology Dec 2020Bempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of bempedoic acid alone or combining with other lipid-lowering therapies in hypercholesterolemic patients: a meta-analysis of randomized controlled trials.
BACKGROUND
Bempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other lipid-lowering drugs is better than these drugs alone. This study systematically reviewed the efficacy and safety of bempedoic acid monotherapy or combination togethers in hypercholesterolemic patients.
METHODS
Randomized controlled trials were searched across Medline, Embase, Cochrane library, web of science, etc. The net change scores [least squares mean (LSM) percentage change] in LDL-C level were meta-analyzed using weighted mean difference. The reductions in other lipids including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein (ApoB) and high sensitivity C reactive protein (hsCRP) were also assessed. Odds ratio (OR) of the incidence of adverse events (AEs) were calculated to evaluate the safety of bempedoic acid.
RESULTS
A total of 13 trials (4858 participates) were included. Pooled data showed that the combination togethers resulted in greater reductions in LDL-C level than monotherapies (bempedoic acid + statin vs. statin: LSM difference (%), - 18.37, 95% CI, - 20.16 to - 16.57, I = 0; bempedoic acid + ezetimibe vs. ezetimibe: LSM difference (%), - 18.89, 95% CI, - 29.66 to - 8.13, I = 87%). But the difference in efficacy between bempedoic acid and ezetimibe was not obvious. Meta-regression analysis showed the treatment duration was a source of heterogeneity (adj R = 16.92, 95% CI, 0.04 to 0.72). Furthermore, the background therapy of statin before screening decreased the efficacy of bempedoic acid. In addition, bempedoic acid also resulted in a significant reduction in TC, non-HDL-C, ApoB and hsCRP level. The OR of muscle-related AEs by the combination of bempedoic acid and statin was 1.29 (95% CI, 1.00 to 1.67, I = 0) when compared with statin alone.
CONCLUSION
This study showed the efficacy of combination togethers were similar but stronger than these drugs alone. Of note, a trend of high risk of muscle-related AEs by the combination of bempedoic acid and statin was observed, though it is not statistically significant, such risk is needed to be confirmed by more trials, because it is important for us to determine which is the better combinative administration for statin-intolerant patients.
Topics: Anticholesteremic Agents; Dicarboxylic Acids; Drug Therapy, Combination; Fatty Acids; Humans; Hypercholesterolemia; Hypolipidemic Agents; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33276805
DOI: 10.1186/s40360-020-00463-w