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The Cochrane Database of Systematic... Jul 2013Patients undergoing vascular surgery are a high-risk population with widespread atherosclerosis, an adverse cardiovascular risk profile and often multiple... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients undergoing vascular surgery are a high-risk population with widespread atherosclerosis, an adverse cardiovascular risk profile and often multiple co-morbidities. Postoperative cardiovascular complications, including myocardial infarct (MI), are common. Statins are the medical treatment of choice to reduce high cholesterol levels. Evidence is accumulating that patients taking statins at the time of surgery are protected against a range of perioperative complications, but the specific benefits for patients undergoing noncardiac vascular surgery are not clear.
OBJECTIVES
We examined whether short-term statin therapy, commenced before or on the day of noncardiac vascular surgery and continuing for at least 48 hours afterwards, improves patient outcomes including the risk of complications, pain, quality of life and length of hospital stay. We also examined whether the effect of statin therapy on these outcomes changes depending on the dose of statin received.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE via Ovid SP (1966 to August 2012), EMBASE via Ovid SP (1966 to August 2012), CINAHL via EBSCO host (1966 to August 2012) and ISI Web of Science (1946 to July 2012) without any language restriction. We used a combination of free text search and controlled vocabulary search. The results were limited to randomized controlled clinical trials (RCTs). We conducted forwards and backwards citation of key articles and searched two clinical trial Websites for ongoing trials (www.clinicaltrials.gov and http://www.controlled-trials.com).
SELECTION CRITERIA
We included RCTs that had compared short-term statin therapy, either commenced de novo or with existing users randomly assigned to different dosages, in adult participants undergoing elective and emergency noncardiac arterial surgery, including both open and endovascular procedures. We defined short-term as commencing before or on the day of surgery and continuing for at least 48 hours afterwards.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data, including information on adverse events. We contacted study authors for additional information. We performed separate analyses for the comparisons of statin with placebo/no treatment and between different doses of statin. We presented results as pooled risk ratios (RRs) with 95% confidence intervals (CIs) based on random-effects models (inverse variance method). We employed the Chi(2) test and calculated the I(2) statistic to investigate study heterogeneity.
MAIN RESULTS
We identified six eligible studies in total. The six Included studies were generally of high quality, but the largest eligible study was excluded because of concerns about its validity. Study populations were statin naive, which led to a considerable loss of eligible participants.Five RCTs compared statin use with placebo or standard care. We pooled results from three studies, with a total of 178 participants, for mortality and non-fatal event outcomes. In the statin group, 7/105 (6.7%) participants died within 30 days of surgery, as did 10/73 (13.7%) participants in the control group. Only one death in each group was from cardiovascular causes, with an incidence of 0.95% in statin participants and 1.4% in control participants, respectively. All deaths occurred in a single study population, and so effect estimates were derived from one study only. The risk ratio (RR) of all-cause mortality in statin users showed a non-significant decrease in risk (RR 0.73, 95% CI 0.31 to 1.75). For cardiovascular death, the risk ratio was 1.05 (95% CI 0.07 to 16.20). Non-fatal MI within 30 days of surgery was reported in three studies and occurred in 4/105 (3.8%) participants in the statin group and 8/73 (11.0%) participants receiving placebo, for a non-significant decrease in risk (RR 0.47, 95% CI 0.15 to 1.52). Several studies reported muscle enzyme levels as safety measures, but only three (with a total of 188 participants) reported explicitly on clinical muscle syndromes, with seven events reported and no significant difference found between statin users and controls (RR 0.94, 95% CI 0.24 to 3.63). The only participant-reported outcome was nausea in one small study,with no significant difference in risk between groups.Two studies compared different doses of atorvastatin, with a total of 145 participants, but reported data were not sufficient to allow us to determine the effect of higher doses on any outcome.
AUTHORS' CONCLUSIONS
Evidence was insufficient to allow review authors to conclude that statin use resulted in either a reduction or an increase in any of the outcomes examined. The existing body of evidence leaves questions about the benefits of perioperative use of statins for vascular surgery unanswered. Widespread use of statins in the target population means that it may now be difficult for researchers to undertake the large RCTs needed to demonstrate any effect on the incidence of postoperative cardiovascular events. However, participant-reported outcomes have been neglected and warrant further study.
Topics: Adult; Angioplasty; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Cause of Death; Cholestyramine Resin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Perioperative Care; Postoperative Complications; Pyrroles; Randomized Controlled Trials as Topic; Sitosterols; Vascular Surgical Procedures
PubMed: 23824754
DOI: 10.1002/14651858.CD009971.pub2 -
The Cochrane Database of Systematic... Jun 2013Obstetric cholestasis has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been empiric. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obstetric cholestasis has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been empiric. The first version of this review, published in 2001, and including nine randomised controlled trials involving 227 women, concluded that there was insufficient evidence to recommend any of the interventions alone or in combination. This is the first update.
OBJECTIVES
To evaluate the effectiveness and safety of therapeutic and delivery interventions in women with cholestasis of pregnancy.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 February 2013) and reference lists of identified studies.
SELECTION CRITERIA
Randomised controlled trials that compared two intervention strategies for women with a clinical diagnosis of obstetric cholestasis.
DATA COLLECTION AND ANALYSIS
The review authors independently assessed trials for eligibility and risk of bias. We independently extracted data and checked these for accuracy.
MAIN RESULTS
We included 21 trials with a total of 1197 women. They were mostly at moderate to high risk of bias. They assessed 11 different interventions resulting in 15 different comparisons.Compared with placebo, ursodeoxycholic acid (UDCA) showed improvement in pruritus in five (228 women) out of seven trials. There were no significant differences in instances of fetal distress in the UDCA groups compared with placebo (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.22 to 2.02; five trials, 304 women; random-effects analysis: T² = 0.74; I² = 48%). There were significantly fewer total preterm births with UDCA (RR 0.46; 95% CI 0.28 to 0.73; two trials, 179 women). The difference for spontaneous preterm births was not significant (RR 0.99; 95% CI 0.41 to 2.36, two trials, 109 women).Two trials (48 women) reported lower (better) pruritus scores for S-adenosylmethionine (SAMe) compared with placebo, while two other trials of 34 women reported no significant differences between groups.UDCA was more effective in improving pruritus than either SAMe (four trials; 133 women) or cholestyramine (one trial; 84 women), as was combined UDCA+SAMe when compared with placebo (one trial; 16 women) and SAMe alone (two trials; 68 women). However, combined UDCA+SAMe was no more effective than UDCA alone in regard to pruritus improvement (one trial; 53 women) and two trials (80 women) reported data were insufficient to draw any conclusions from. In one trial comparing UDCA and dexamethasone (83 women), a significant improvement with UDCA was seen only in a subgroup of women with severe obstetric cholestasis (23 women).Danxiaoling significantly improved pruritus in comparison to Yiganling. No significant differences were seen in pruritus improvement with other interventions.Eight trials reported fetal or neonatal deaths, with two deaths reported overall (both in the placebo groups).Women receiving UDCA and cholestyramine experienced nausea, vomiting and diarrhoea. Guar gum caused mild abdominal distress, diarrhoea and flatulence during the first days of treatment. Women found charcoal suspension unpleasant to swallow. Dexamethasone caused nausea, dizziness and stomach pain in one woman.One trial (62 women) looked at the timing of delivery intervention. There were no stillbirths or neonatal deaths in 'early delivery' or the 'await spontaneous labour' group. There were no significant differences in the rates of caesarean section, meconium passage or admission to neonatal intensive care unit between the two groups.
AUTHORS' CONCLUSIONS
Different approaches to assessing and reporting pruritus precluded pooling of trials comparing the effects of UDCA versus placebo on pruritus, but examination of individual trials suggests that UDCA significantly improves pruritus, albeit by a small amount. Fewer instances of fetal distress/asphyxial events were seen in the UDCA groups when compared with placebo but the difference was not statistically significant. Large trials of UDCA to determine fetal benefits or risks are needed.A single trial was too small to rule in or out a clinically important effect of early term delivery on caesarean section.There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction (YCHD), Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy.
Topics: Charcoal; Cholagogues and Choleretics; Cholestasis; Cholestyramine Resin; Drugs, Chinese Herbal; Female; Galactans; Humans; Mannans; Plant Gums; Pregnancy; Pregnancy Complications; Pruritus; Randomized Controlled Trials as Topic; S-Adenosylmethionine; Ursodeoxycholic Acid
PubMed: 23794285
DOI: 10.1002/14651858.CD000493.pub2 -
The American Journal of Medicine Mar 2013Sodium polystyrene sulfonate (Kayexalate; Sanofi-Aventis, Paris, France) is a cation-exchange resin routinely used in the management of hyperkalemia. However, its use... (Review)
Review
BACKGROUND
Sodium polystyrene sulfonate (Kayexalate; Sanofi-Aventis, Paris, France) is a cation-exchange resin routinely used in the management of hyperkalemia. However, its use has been associated with colonic necrosis and other fatal gastrointestinal adverse events. Although the addition of sorbitol to sodium polystyrene sulfonate preparations was previously believed to be the cause of gastrointestinal injury, recent reports have suggested that sodium polystyrene sulfonate itself may be toxic. Our objective was to systematically review case reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use.
METHODS
MEDLINE (1948 to July 2011), EMBASE (1980 to July 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (1993 to July 27, 2011), bibliographies of identified articles, and websites of relevant drug agencies and professional associations in the United States and Canada were reviewed to identify eligible reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. Causality criteria of the World Health Organization causality assessment system were applied to each report.
RESULTS
Thirty reports describing 58 cases (41 preparations containing sorbitol and 17 preparations without sorbitol) of adverse events were identified. The colon was the most common site of injury (n=44; 76%), and transmural necrosis (n=36; 62%) was the most common histopathologic lesion reported. Mortality was reported in 33% of these cases due to gastrointestinal injury.
CONCLUSIONS
Sodium polystyrene sulfonate use, both with and without sorbitol, may be associated with fatal gastrointestinal injury. Physicians must be cognizant of the risk of these adverse events when prescribing this therapy for the management of hyperkalemia.
Topics: Cation Exchange Resins; Colonic Diseases; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; Male; Middle Aged; Necrosis; Polystyrenes; Sorbitol
PubMed: 23321430
DOI: 10.1016/j.amjmed.2012.08.016 -
The Cochrane Database of Systematic... May 2012Non-oliguric hyperkalaemia of the newborn is defined as a plasma potassium level > 6.5 mmol/L in the absence of acute renal failure. Hyperkalaemia is a common... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-oliguric hyperkalaemia of the newborn is defined as a plasma potassium level > 6.5 mmol/L in the absence of acute renal failure. Hyperkalaemia is a common complication in the first 48 hours of life in very low birth weight (VLBW) (birth weight < 1500 g) and/or very preterm newborns (≤32 weeks gestational age).
OBJECTIVES
To determine the effectiveness and safety of interventions for non-oliguric hyperkalaemia [for the purpose of this review defined as serum potassium > 6.0 mmol/L (the clinical setting in which interventions would likely be introduced prior to reaching a grossly abnormal level) and urine output > 0.5 ml/kg/hour] in preterm or VLBW infants during their first 72 hours of life.
SEARCH METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2006) was searched to identify relevant randomised and quasi-randomised controlled trials. The following data bases were searched in June 2006; MEDLINE from 1966, EMBASE from 1980, CINAHL from 1982. Search updated in June 2011.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials conducted in preterm and/or VLBW neonates with a diagnosis of non-oliguric hyperkalaemia. Interventions included were those aimed at redistributing serum potassium (sodium bicarbonate or insulin and glucose) or increasing the elimination of potassium from the body [diuretics (any type) or ion exchange resins (any type), or exchange transfusion, or peritoneal dialysis, or salbutamol, or albuterol] or counteracting potential arrhythmias from hyperkalaemia (calcium) versus placebo or no intervention; or comparing any two of these interventions. Primary outcome measure was 'All cause mortality during initial hospital stay'. Secondary outcomes included common adverse outcomes seen in preterm infants.
DATA COLLECTION AND ANALYSIS
We used the standard review methods of the Cochrane Neonatal Review Group. Two authors assessed all studies identified as potentially relevant by the literature search for inclusion in the review. Statistical methods included relative risk (RR), risk difference (RD), number needed to treat to benefit (NNTB) or number needed to treat to harm (NNTH) for dichotomous and weighted mean difference (WMD) for continuous outcomes reported with 95% confidence intervals (CI). We used a fixed effect model for meta-analysis. Heterogeneity was assessed using the I squared (I(2) ) statistic.
MAIN RESULTS
Three randomised trials, enrolling 74 preterm infants (outcome data available on 71 infants) evaluated interventions for hyperkalaemia. Urine output was ascertained in only one study (Hu 1999). In none of the trials could we ascertain that allocation to the comparison groups was concealed. The sample sizes of the three trials were very small with 12 (Malone 1991), 19 (Singh 2002) and 40 infants enrolled (Hu 1999). The intervention and the outcome assessments could not be blinded to the clinical staff in two trials (Malone 1991; Hu 1999).One study (Malone 1991), glucose and insulin, compared to cation-exchange resin, caused a reduction in all cause mortality that was of borderline statistical significance: RR 0.18 (95% CI 0.03 to 1.15); RD -0.66 (95% CI -1.09 to -0.22); NNTB 2 (95% CI 1 to 5)]. In the study of Hu (Hu 1999), the incidence of intraventricular haemorrhage ≥ grade 2 was significantly reduced [RR 0.30 (95% CI 0.10 to 0.93); RD -0.35 (95% CI -0.62 to -0.08); NNTB 3 (95% CI 2 to 13).Albuterol inhalation versus saline inhalation changed serum K+ from baseline at four hours [WMD -0.69 mmol/L (95% CI -0.87 to -0.51)] and at eight hours [WMD -0.59 mmol/L (95% CI -0.78 to -0.40)] after initiation of treatment. No differences noted in mortality or other clinical outcomes (Singh 2002).No serious side effects were noted with either the combination of insulin and glucose or albuterol inhalation. Other interventions listed in our objectives have not been studied to date.
AUTHORS' CONCLUSIONS
In view of the limited information from small studies of uncertain quality, no firm recommendations for clinical practice can be made. It appears that the combination of insulin and glucose is preferred over treatment with rectal cation-resin for hyperkalaemia in preterm infants. Both the combination of insulin and glucose and albuterol inhalation deserve further study. The two interventions could possibly be tested against each other. The effectiveness of other potentially effective interventions for non-oliguric hyperkalaemia (diuretics, exchange transfusion, peritoneal dialysis and calcium) have not been tested in randomised controlled trials.
Topics: Albuterol; Glucose; Humans; Hyperkalemia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Insulin; Polystyrenes; Potassium; Randomized Controlled Trials as Topic; Reference Values
PubMed: 22592703
DOI: 10.1002/14651858.CD005257.pub3 -
Shock (Augusta, Ga.) Oct 2011Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin adsorption therapy by polymyxin... (Review)
Review
Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column hemoperfusion (PMX) has been used for the treatment of septic shock patients in Japan since 1994. The covalent binding of polymyxin B onto the surface of the polystyrene-based carrier fiber in PMX inactivates the endotoxin in the blood without exerting toxicity. This study was performed as a systematic review to evaluate the efficacy and mechanism of PMX treatment in patients with septic shock. The PubMed database and references from identified articles were used to search and review the literature relating to the efficacy and mechanism of PMX treatment in patients with septic shock. Polymyxin B-immobilized fiber column hemoperfusion adsorbed monocytes, activated neutrophils, and anandamide, as well as endotoxin through direct covalent bond, hydrophobic and ionic interactions, and hydrodynamics, and reduced the blood concentrations of inflammatory cytokines, plasminogen activator inhibitor 1 and adhesion molecules. Polymyxin B-immobilized fiber column hemoperfusion increased blood pressure and reduced the dosage requirements for vasopressive/inotropic agents. The meta-analysis showed that PMX treatment had beneficial effects on the hemodynamics, pulmonary oxygenation, and mortality. These beneficial effects may be attributable to the direct adsorption of endotoxin, monocytes, activated neutrophils, and anandamide, as well as indirect decrease in inflammatory cytokines and other mediators. Polymyxin B-immobilized fiber column hemoperfusion treatment has additional effects on reducing endothelial damage, proapoptotic activity, and immunosuppression. Further studies will be needed to confirm the efficacy and mechanism of PMX treatment in septic shock.
Topics: Anti-Bacterial Agents; Endotoxins; Hemodynamics; Hemoperfusion; Humans; Polymyxin B; Shock, Septic
PubMed: 21654557
DOI: 10.1097/SHK.0b013e318225f839 -
Advances in Therapy Jun 2010Coronary heart disease (CHD) is the leading cause of mortality worldwide. With increasingly urbanized lifestyles in developing countries and the aging populations, the... (Review)
Review
INTRODUCTION
Coronary heart disease (CHD) is the leading cause of mortality worldwide. With increasingly urbanized lifestyles in developing countries and the aging populations, the major risk factors for CHD such as obesity, diabetes mellitus, and hypercholesterolemia are likely to increase in the future. In the current report, we reviewed the evidence on the effect of cholesterol lowering using pharmacological agents.
METHODS
A PubMed/Medline systematic search was performed over the past 12 years (1998-2009 inclusive) and relevant papers written in the English language were selected. We used key phrases including, "risk factors for hypercholesterolemia," "management of hypercholesterolemia," "guidelines for management of hypercholesterolemia," and "pharmacological management of hypercholesterolemia."
RESULTS
There were a total of over 3500 reports. We selected key publications on the effect of cholesterol lowering using different pharmacological agents.
CONCLUSION
Several options exist with regards to pharmacological management of hypercholesterolemia. There is a substantial body of evidence to support the effect of a population shift towards a favorable risk profile, which has huge potential in reducing the burden of CHD globally.
Topics: Anticholesteremic Agents; Azetidines; Cholestyramine Resin; Coronary Disease; Drug Therapy, Combination; Evidence-Based Practice; Ezetimibe; Fatty Acids, Omega-3; Gemfibrozil; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Niacin; Patient Selection; Phytosterols; Practice Guidelines as Topic; Primary Prevention; Risk Assessment; Risk Factors; Risk Reduction Behavior; Secondary Prevention; Treatment Outcome
PubMed: 20533012
DOI: 10.1007/s12325-010-0033-6 -
Alimentary Pharmacology & Therapeutics Oct 2009Recurrent, watery diarrhoea affects one-third of patients diagnosed with irritable bowel syndrome ('IBS-D'). Idiopathic bile acid malabsorption ('I-BAM') may be the... (Review)
Review
BACKGROUND
Recurrent, watery diarrhoea affects one-third of patients diagnosed with irritable bowel syndrome ('IBS-D'). Idiopathic bile acid malabsorption ('I-BAM') may be the cause.
AIM
To determine the prevalence of I-BAM in patients suffering from IBS-D.
METHODS
A systematic search was performed of publications reporting patients presenting with IBS-D type symptoms, who were subsequently confirmed as having I-BAM by SeHCAT scanning.
RESULTS
Eighteen relevant studies, 15 prospective, comprising 1223 patients were identified. Five studies (429 patients) indicated that 10% (CI: 7-13) patients had severe bile acid malabsorption (SeHCAT 7 day retention <5% of baseline value). 17 studies (1073 patients) indicated that 32% (CI: 29-35) patients had moderate bile acid malabsorption (SeHCAT <10%). 7 studies (618 patients) indicated that 26% (CI: 23-30) patients had mild (SeHCAT <15%) bile acid malabsorption. Pooled data from 15 studies showed a dose-response relationship according to severity of malabsorption to treatment with a bile acid binder: response to colestyramine occurred in 96% of patients with <5% retention, 80% at <10% retention and 70% at <15% retention.
CONCLUSIONS
Idiopathic adult-onset bile acid malabsorption is not rare. International guidelines for the management of irritable bowel syndrome need to be revised so that clinicians become more aware of this possibility.
Topics: Adult; Anion Exchange Resins; Bile Acids and Salts; Cholestyramine Resin; Diarrhea; Dose-Response Relationship, Drug; Humans; Irritable Bowel Syndrome; Malabsorption Syndromes; Prevalence; Prospective Studies; Retrospective Studies; Severity of Illness Index
PubMed: 19570102
DOI: 10.1111/j.1365-2036.2009.04081.x -
The American Journal of Gastroenterology Jan 2009To conduct a systematic review to determine effective treatments for patients with collagenous colitis or lymphocytic colitis, the two subtypes of microscopic colitis. (Review)
Review
OBJECTIVES
To conduct a systematic review to determine effective treatments for patients with collagenous colitis or lymphocytic colitis, the two subtypes of microscopic colitis.
METHODS
Relevant papers were identified via the MEDLINE, PUBMED, and Cochrane Collaboration databases, manual searches of the references of identified papers and review papers on microscopic colitis, as well as searches of abstracts from major gastroenterological meetings.
RESULTS
All studies assessing treatment of microscopic colitis had relatively small sample sizes. A total of 10 randomized trials included patients with collagenous colitis. Budesonide was studied for induction of response in three trials and for maintenance of response in two trials. The pooled odds ratio for inducing clinical response with budesonide was 12.32 (95% confidence interval, CI 5.53-27.46), and for maintaining clinical response was 8.82 (95% CI 3.19-24.37), with a number needed to treat (NNT) of 2 patients for each outcome. Budesonide also induced and maintained histological response and was well tolerated. Bismuth subsalicylate, prednisolone, and mesalamine with or without cholestyramine may be effective, whereas Boswellia serrata extract and probiotics were ineffective for treating collagenous colitis. Three randomized trials included patients with lymphocytic colitis. Budesonide was shown in one study to be effective for inducing clinical response (OR 9.00; 95% CI 1.98-40.93), with an NNT of three patients. Budesonide also induced histological response and was well tolerated. Bismuth subsalicylate and mesalamine with or without cholestyramine may be effective for treating lymphocytic colitis. No trials assessed maintenance of response in patients with lymphocytic colitis.
CONCLUSIONS
Budesonide is effective and well tolerated for inducing and maintaining clinical and histological responses in patients with collagenous colitis, and for inducing clinical and histological responses in patients with lymphocytic colitis. Determining the magnitude of benefit is limited by the small sample sizes of the studies. The evidence for other agents, including bismuth subsalicylate, prednisolone, B. serrata extract, probiotics, and mesalamine with or without cholestyramine is weaker. It is not clear that any of these agents induce or maintain actual remission of collagenous or lymphocytic colitis, as opposed to clinical or histological response.
Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Cholestyramine Resin; Colitis, Microscopic; Humans; Mesalamine; Probiotics; Randomized Controlled Trials as Topic; Salicylates
PubMed: 19098875
DOI: 10.1038/ajg.2008.16 -
The Cochrane Database of Systematic... Apr 2008Lymphocytic colitis is a cause of chronic diarrhea. Therapy is based mainly on case series and uncontrolled trials, or by extrapolation of data for treating collagenous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lymphocytic colitis is a cause of chronic diarrhea. Therapy is based mainly on case series and uncontrolled trials, or by extrapolation of data for treating collagenous colitis, a related disorder. This review was performed to identify therapies for lymphocytic colitis that have been proven in randomized controlled trials.
OBJECTIVES
To determine effective treatments for patients with clinically active lymphocytic colitis.
SEARCH STRATEGY
The MEDLINE, PUBMED and EMBASE databases were searched using the search criteria "microscopic colitis" or "lymphocytic colitis" and "treatment" or "therapy" or "management" to identify relevant papers published between 1970 and December 2007. Manual searches from the references of identified papers and relevant review papers were performed. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. The trial registry website www.ClinicalTrials.gov was searched to identify registered but unpublished trials. Finally, the Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies.
SELECTION CRITERIA
Five randomized controlled trials were identified. Three of these studies, which assessed bismuth subsalicylate vs. placebo, budesonide vs. placebo, and mesalazine vs. mesalazine vs. cholestyramine in treating active disease, are included in this review.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by each author onto 2x2 tables (treatment versus placebo or active comparator and response versus no response). For therapies assessed in one trial only, P values were derived using the chi-square test.
MAIN RESULTS
Forty-one patients were enrolled in the trial studying budesonide (9 mg/day for 6 weeks versus placebo). Budesonide was more effective than placebo at inducing both clinical (P = 0.004; NNT = 3) and histological responses (P = 0.04; NNT = 3). Forty-one patients were enrolled in the study assessing mesalazine versus mesalazine plus cholestyramine. A high proportion of patients in each group responded to treatment. However, no statistically significant difference in clinical response was found between the two treatment groups (P = 0.95). Five patients were enrolled in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks vs. placebo). There were no differences in clinical (P=0.10) or histological responses (P=0.71) in patients treated with bismuth subsalicylate compared with placebo.
AUTHORS' CONCLUSIONS
A single trial studying budesonide suggests that it may be effective for the treatment of active lymphocytic colitis. An ongoing placebo-controlled trial may confirm the benefit of budesonide. There is weaker evidence that mesalazine with or without cholestyramine may be effective for the treatment of lymphocytic colitis, but this benefit needs to be confirmed in a placebo-controlled study. No conclusions can be made regarding bismuth subsalicylate. These agents require further study before they can be recommended as treatment options for lymphocytic colitis. Further trials studying interventions for lymphocytic colitis are warranted.
Topics: Antidiarrheals; Bismuth; Budesonide; Cholestyramine Resin; Colitis, Lymphocytic; Humans; Mesalamine; Organometallic Compounds; Randomized Controlled Trials as Topic; Salicylates
PubMed: 18425936
DOI: 10.1002/14651858.CD006096.pub3 -
Critical Care (London, England) 2007Severe sepsis and septic shock are common problems in the intensive care unit and carry a high mortality. Endotoxin, one of the principal components on the outer... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Severe sepsis and septic shock are common problems in the intensive care unit and carry a high mortality. Endotoxin, one of the principal components on the outer membrane of gram-negative bacteria, is considered important to their pathogenesis. Polymyxin B bound and immobilized to polystyrene fibers (PMX-F) is a medical device that aims to remove circulating endotoxin by adsorption, theoretically preventing the progression of the biological cascade of sepsis. We performed a systematic review to describe the effect in septic patients of direct hemoperfusion with PMX-F on outcomes of blood pressure, use of vasoactive drugs, oxygenation, and mortality reported in published studies.
METHODS
We searched PubMed, the Cochrane Collaboration Database, and bibliographies of retrieved articles and consulted with experts to identify relevant studies. Prospective and retrospective observational studies, pre- and post-intervention design, and randomized controlled trials were included. Three authors reviewed all citations. We identified a total of 28 publications - 9 randomized controlled trials, 7 non-randomized parallel studies, and 12 pre-post design studies - that reported at least one of the specified outcome measures (pooled sample size, 1,425 patients: 978 PMX-F and 447 conventional medical therapy).
RESULTS
Overall, mean arterial pressure (MAP) increased by 19 mm Hg (95% confidence interval [CI], 15 to 22 mm Hg; p < 0.001), representing a 26% mean increase in MAP (range, 14% to 42%), whereas dopamine/dobutamine dose decreased by 1.8 microg/kg per minute (95% CI, 0.4 to 3.3 microg/kg per minute; p = 0.01) after PMX-F. There was significant intertrial heterogeneity for these outcomes (p < 0.001), which became non-significant when analysis was stratified for baseline MAP. The mean arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio increased by 32 units (95% CI, 23 to 41 units; p < 0.001). PMX-F therapy was associated with significantly lower mortality risk (risk ratio, 0.53; 95% CI, 0.43 to 0.65). The trials assessed had suboptimal method quality.
CONCLUSION
Based on this critical review of the published literature, direct hemoperfusion with PMX-F appears to have favorable effects on MAP, dopamine use, PaO2/FiO2 ratio, and mortality. However, publication bias and lack of blinding need to be considered. These findings support the need for further rigorous study of this therapy.
Topics: Adult; Aged; Cardiotonic Agents; Dobutamine; Dopamine; Endotoxins; Hemoperfusion; Humans; Middle Aged; Polymyxin B; Sepsis; Survival Rate; Treatment Outcome
PubMed: 17448226
DOI: 10.1186/cc5780