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The Cochrane Database of Systematic... Jul 2016Chagas disease-related cardiomyopathy is a major cause of morbidity and mortality in Latin America. Despite the substantial burden to the healthcare system, there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chagas disease-related cardiomyopathy is a major cause of morbidity and mortality in Latin America. Despite the substantial burden to the healthcare system, there is uncertainty regarding the efficacy and safety of pharmacological interventions for treating heart failure in people with Chagas disease. This is an update of a Cochrane review published in 2012.
OBJECTIVES
To assess the clinical benefits and harms of current pharmacological interventions for treating heart failure in people with Chagas cardiomyopathy.
SEARCH METHODS
We updated the searches in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 1), MEDLINE (Ovid; 1946 to to February Week 1 2016), EMBASE (Ovid; 1947 to 2016 Week 07), LILACS (1982 to 15 February 2016), and Web of Science (Thomson Reuters; 1970 to 15 February 2016). We checked the reference lists of included papers. We applied no language restrictions.
SELECTION CRITERIA
We included randomised clinical trials (RCTs) that assessed the effects of pharmacological interventions to treat heart failure in adult patients (18 years or older) with symptomatic heart failure (New York Heart Association classes II to IV), regardless of the left ventricular ejection fraction stage (reduced or preserved), with Chagas cardiomyopathy. We did not apply limits to the length of follow-up. Primary outcomes were all-cause mortality, cardiovascular mortality at 30 days, time-to-heart decompensation, disease-free period (at 30, 60, and 90 days), and adverse events.
DATA COLLECTION AND ANALYSIS
Two authors independently performed study selection, 'Risk of bias' assessment and data extraction. We estimated relative risk (RR) and 95% confidence intervals (CIs) for dichotomous outcomes. We measured statistical heterogeneity using the I² statistic. We used a fixed-effect model to synthesize the findings. We contacted authors for additional data. We developed 'Summary of findings' (SoF) tables and used GRADE methodology to assess the quality of the evidence.
MAIN RESULTS
In this update, we identified one new trial. Therefore, this version includes three trials (108 participants). Two trials compared carvedilol against placebo and another assessed rosuvastatin versus placebo. All trials had a high risk of bias.Meta-analysis of two trials showed a lower proportion of all-cause mortality in the carvedilol groups compared with the placebo groups (RR 0.69; 95% CI 0.12 to 3.88, I² = 0%; 69 participants; very low-quality evidence). Neither of the trials reported on cardiovascular mortality, time-to-heart decompensation, or disease-free periods.One trial (30 participants) found no difference in hospital readmissions (RR 1.00; 95% CI 0.31 to 3.28; very low-quality of evidence) or reported adverse events (RR 0.92; 95% CI 0.67 to 1.27; very low-quality of evidence) between the carvedilol and placebo groups.There was very low-quality evidence from two trials of inconclusive effects on quality of life (QoL) between the carvedilol and placebo groups. One trial (30 participants) assessed QoL with the Minnesota Living With Heart Failure Questionnaire (21 items; item scores range from 0 to 5; a lower MLHFQ score is better). The MD was -14.74; 95% CI -24.75 to -4.73. The other trial (39 participants) measured QoL with the Medical Outcomes Study 36-item short-form health survey (SF-36; item scores range from 0 to 100; higher SF-36 score is better). Data were not provided.One trial (39 participants) assessed the effect of rosuvastatin versus placebo. The trial did not report on any primary outcomes or adverse events. There was very low-quality evidence of uncertain effects on QoL (no data were provided).
AUTHORS' CONCLUSIONS
This first update of our review found very low-quality evidence for the effects of either carvedilol or rosuvastatin, compared with placebo, for treating heart failure in people with Chagas disease. The three included trials were underpowered and had a high risk of bias. There were no conclusive data to support or reject the use of either carvedilol or rosuvastatin for treating Chagas cardiomyopathy. Unless randomised clinical trials provide evidence of a treatment effect, and the trade-off between potential benefits and harms is established, policy-makers, clinicians, and academics should be cautious when recommending or administering either carvedilol or rosuvastatin to treat heart failure in people with Chagas disease. The efficacy and safety of other pharmacological interventions for treating heart failure in people with Chagas disease remains unknown.
Topics: Adult; Carbazoles; Cardiotonic Agents; Carvedilol; Chagas Cardiomyopathy; Heart Failure; Humans; Middle Aged; Propanolamines; Quality of Life; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Survival Analysis
PubMed: 27388039
DOI: 10.1002/14651858.CD009077.pub3 -
BMJ Open May 2016To assess the clinical and haemodynamic effects of carvedilol for patients with cirrhosis and portal hypertension. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the clinical and haemodynamic effects of carvedilol for patients with cirrhosis and portal hypertension.
DESIGN
A systematic review and meta-analysis.
DATA SOURCES
We searched PubMed, Cochrane library databases, EMBASE and the Science Citation Index Expanded through December 2015. Only randomised controlled trials (RCTs) were included.
OUTCOME MEASURE
We calculated clinical outcomes (all-cause mortality, bleeding-related mortality, upper gastrointestinal bleeding) as well as haemodynamic outcomes (hepatic venous pressure (HVPG) reduction, haemodynamic response rate, post-treatment arterial blood pressure (mean arterial pressure; MAP) and adverse events).
RESULTS
12 RCTs were included. In 7 trials that looked at haemodynamic outcomes compared carvedilol versus propranolol, showing that carvedilol was associated with a greater reduction (%) of HVPG within 6 months (mean difference -8.49, 95% CI -12.36 to -4.63) without a greater reduction in MAP than propranolol. In 3 trials investigating differences in clinical outcomes between carvedilol versus endoscopic variceal band ligation (EVL), no significant differences in mortality or variceal bleeding were demonstrated. 1 trial compared clinical outcomes between carvedilol versus nadolol plus isosorbide-5-mononitrate (ISMN), and showed that no significant difference in mortality or bleeding had been found. 1 trial comparing carvedilol versus nebivolol showed a greater reduction in HVPG after 14 days follow-up in the carvedilol group.
CONCLUSIONS
Carvedilol may be more effective in decreasing HVPG than propranolol or nebivolol and it may be as effective as EVL or nadolol plus ISMN in preventing variceal bleeding. However, the overall quality of evidence is low. Further large-scale randomised studies are required before we can make firm conclusions.
TRIAL REGISTRATION NUMBER
CRD42015020542.
Topics: Antihypertensive Agents; Carbazoles; Carvedilol; Dose-Response Relationship, Drug; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemodynamics; Humans; Hypertension, Portal; Liver Cirrhosis; Propanolamines; Propranolol; Treatment Outcome
PubMed: 27147389
DOI: 10.1136/bmjopen-2015-010902 -
Critical Care Medicine Jun 2016ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary... (Review)
Review
OBJECTIVES
ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary work to inform the design of a randomized trial of a complex intervention to improve recovery from critical illness, we sought to identify pharmacological interventions that may play a role in this area.
DATA SOURCES
We systematically reviewed the published literature relating to pharmacological intervention for the treatment and prevention of ICU-acquired weakness.
STUDY SELECTION
We searched MEDLINE, EMBASE, CINAHL+, Web of Science, and both U.S. and European trial registries up to July 2014 alongside reviews and reference lists from populations with no age or language restrictions. We included studies that reported a measure of muscle structure or physical function as an outcome measure.
DATA EXTRACTION
We estimated pooled odds ratios and 95% CI using data extracted from published articles or where available, original data provided by the authors. Assessment of bias was performed using the Cochrane Collaboration's risk of bias tool.
DATA SYNTHESIS
Ten studies met the inclusion criteria. The current body of evidence does not support the use of any pharmacological agent in this setting, although maintaining euglycemia may reduce the prevalence of critical illness polyneuropathy.
CONCLUSIONS
At present, no pharmacological intervention can be recommended to prevent or treat ICU-acquired weakness. Further research is required into this field to include more novel agents such as myostatin inhibitors. Challenges in the conduct of research in this area are highlighted.
Topics: Adrenergic beta-Antagonists; Anabolic Agents; Critical Illness; Glutamine; Growth Hormone; Humans; Hyperglycemia; Hypoglycemic Agents; Immunoglobulins, Intravenous; Immunologic Factors; Insulin; Muscle Weakness; Oxandrolone; Polyneuropathies; Propranolol
PubMed: 26958749
DOI: 10.1097/CCM.0000000000001652 -
The Cochrane Database of Systematic... Dec 2015Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy.
OBJECTIVES
To compare the relative effectiveness of interventions for central serous chorioretinopathy.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (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 5 October 2015.
SELECTION CRITERIA
Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data. We pooled data from all studies using a fixed-effect model. For interventions applied to the eye (i.e. not systemic interventions), we synthesized direct and indirect evidence in a network meta-analysis model.
MAIN RESULTS
We included 25 studies with 1098 participants (1098 eyes) and follow-up from 16 weeks to 12 years. Studies were conducted in Europe, North and South America, Middle East, and Asia. The trials were small (most trials enrolled fewer than 50 participants) and poorly reported; often it was unclear whether key aspects of the trial, such as allocation concealment, had been done. A substantial proportion of the trials were not masked.The studies considered a variety of treatments: anti-VEGF (ranibizumab, bevacizumab), PDT (full-dose, half-dose, 30%, low-fluence), laser treatment (argon, krypton and micropulse laser), beta-blockers, carbonic anhydrase inhibitors, Helicobactor pylori treatment, and nutritional supplements (Icaps, lutein); there were only one or two trials contributing data for each comparison. We downgraded for risk of bias and imprecision for most analyses, reflecting study limitations and imprecise estimates. Network meta-analysis (as planned in our protocol) did not help to resolve this uncertainty due to a lack of trials, and problems with intransitivity, particularly with respect to acute or chronic CSC.Low quality evidence from two trials suggested little difference in the effect of anti-VEGF (ranibizumab or bevacizumab) or observation on change in visual acuity at six months in acute CSC (mean difference (MD) 0.01 LogMAR (logarithm of the minimal angle of resolution), 95% confidence interval (CI) -0.02 to 0.03; 64 participants). CSC had resolved in all participants by six months. There were no significant adverse effects noted.Low quality evidence from one study (58 participants) suggested that half-dose PDT treatment of acute CSC probably results in a small improvement in vision (MD -0.10 logMAR, 95% CI -0.18 to -0.02), less recurrence (risk ratio (RR) 0.10, 95% CI 0.01 to 0.81) and less persistent CSC (RR 0.12, 95% CI 0.01 to 1.02) at 12 months compared to sham treatment. There were no significant adverse events noted.Low quality evidence from two trials (56 participants) comparing anti-VEGF to low-fluence PDT in chronic CSC found little evidence for any difference in visual acuity at 12 months (MD 0.03 logMAR, 95% CI -0.08 to 0.15). There was some evidence that more people in the anti-VEGF group had recurrent CSC compared to people treated with PDT but, due to inconsistency between trials, it was difficult to estimate an effect. More people in the anti-VEGF group had persistent CSC at 12 months (RR 6.19, 95% CI 1.61 to 23.81; 34 participants).Two small trials of micropulse laser, one in people with acute CSC and one in people with chronic CSC, provided low quality evidence that laser treatment may lead to better visual acuity (MD -0.20 logMAR, 95% CI -0.30 to -0.11; 45 participants). There were no significant adverse effects noted.Other comparisons were largely inconclusive.We identified 12 ongoing trials covering the following interventions: aflibercept and eplerenone in acute CSC; spironolactone, eplerenone, lutein, PDT, and micropulse laser in chronic CSC; and micropulse laser and oral mifepristone in two trials where type of CSC not clearly specified.
AUTHORS' CONCLUSIONS
CSC remains an enigmatic condition in large part due to a natural history of spontaneous improvement in a high proportion of people and also because no single treatment has provided overwhelming evidence of efficacy in published RCTs. While a number of interventions have been proposed as potentially efficacious, the quality of study design, execution of the study and the relatively small number of participants enrolled and followed to revealing endpoints limits the utility of existing data. It is not clear whether there is a clinically important benefit to treating acute CSC which often resolves spontaneously as part of its natural history. RCTs comparing individual treatments to the natural history would be valuable in identifying potential treatment groups for head-to-head comparison. Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials.
Topics: Carbonic Anhydrase Inhibitors; Central Serous Chorioretinopathy; Helicobacter Infections; Helicobacter pylori; Humans; Laser Therapy; Photochemotherapy; Propranolol; Randomized Controlled Trials as Topic; Remission, Spontaneous; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity; Watchful Waiting
PubMed: 26691378
DOI: 10.1002/14651858.CD011841.pub2 -
The Cochrane Database of Systematic... Dec 2015Twin pregnancies are associated with a high risk of neonatal mortality and morbidity due to an increased rate of preterm birth. Betamimetics can decrease contraction... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Twin pregnancies are associated with a high risk of neonatal mortality and morbidity due to an increased rate of preterm birth. Betamimetics can decrease contraction frequency or delay preterm birth in singleton pregnancies by 24 to 48 hours. The efficacy of oral betamimetics in women with a twin pregnancy is unproven.
OBJECTIVES
To assess the effectiveness of prophylactic oral betamimetics for the prevention of preterm labour and birth for women with twin pregnancies.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group Trials Register (21 September 2015), MEDLINE (January 1966 to 31 July 2015), EMBASE (January 1985 to 31 July 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials in twin pregnancies comparing oral betamimetics with placebo or any intervention with the specific aim of preventing preterm birth. Quasi-randomised controlled trials, cluster-randomised trials and cross-over trials were not eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two authors assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS
Overall, the quality of evidence is low for the primary outcomes. All of the included trials had small numbers of participants and few events. Preterm birth, the most important primary outcome, had wide confidence intervals crossing the line of no effect.Six trials (374 twin pregnancies) were included, but only five trials (344 twin pregnancies) contributed data. All trials compared oral betamimetics with placebo.Betamimetics reduced the incidence of preterm labour (two trials, 194 twin pregnancies, risk ratio (RR) 0.37; 95% confidence interval (CI) 0.17 to 0.78; low quality evidence). However, betamimetics did not reduce prelabour rupture of membranes (one trial, 144 twin pregnancies, RR 1.42; 95% CI 0.42 to 4.82; low quality evidence), preterm birth less than 37 weeks' gestation (four trials, 276 twin pregnancies, RR 0.85; 95% CI 0.65 to 1.10; low quality evidence), or less than 34 weeks' gestation (one trial, 144 twin pregnancies, RR 0.47; 95% CI 0.15 to 1.50; low quality evidence). Mean neonatal birthweight in the betamimetic group was significantly higher than in the placebo group (three trials, 478 neonates, mean difference 111.22 g; 95% CI 22.21 to 200.24). Nevertheless, there was no evidence of an effect of betamimetics in reduction of low birthweight (two trials, 366 neonates, average RR 1.19; 95% CI 0.77 to 1.85, random-effects), or small-for-gestational age neonates (two trials, 178 neonates, average RR 0.90; 95% CI 0.41 to 1.99, random-effects). Two trials showed that betamimetics significantly reduced the incidence of respiratory distress syndrome (388 neonates, RR 0.30; 95% CI 0.12 to 0.77), but the difference was not significant when the analysis was adjusted to account for the non-independence of twins (194 twins, RR 0.35; 95% CI 0.11 to 1.16). Three trials showed no evidence of an effect of betamimetics in reducing neonatal mortality, either with the unadjusted analysis, assuming twins are completely independent of each other (452 neonates, average RR 0.90; 95% CI 0.15 to 5.37, random-effects), or in the adjusted analysis, assuming non-independence of twins (226 twins, average RR 0.74; 95% CI 0.23 to 2.38, random-effects). A maternal death was reported in one trial without a significant difference between the groups (144 women, RR 2.84; 95% CI 0.12 to 68.57).
AUTHORS' CONCLUSIONS
There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women with a twin pregnancy.
Topics: Administration, Oral; Adrenergic beta-Agonists; Adult; Albuterol; Female; Fenoterol; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Isoxsuprine; Pregnancy; Pregnancy, Twin; Premature Birth; Randomized Controlled Trials as Topic; Ritodrine; Terbutaline; Tocolytic Agents
PubMed: 26645888
DOI: 10.1002/14651858.CD004733.pub4 -
Journal of Psychopharmacology (Oxford,... Feb 2016The effects of propranolol in the treatment of anxiety disorders have not been systematically evaluated previously. The aim was to conduct a systematic review and... (Comparative Study)
Comparative Study Meta-Analysis Review
The effects of propranolol in the treatment of anxiety disorders have not been systematically evaluated previously. The aim was to conduct a systematic review and meta-analysis of randomised controlled trials, addressing the efficacy of oral propranolol versus placebo or other medication as a treatment for alleviating either state or trait anxiety in patients suffering from anxiety disorders. Eight studies met the inclusion criteria. These studies concerned panic disorder with or without agoraphobia (four studies, total n = 130), specific phobia (two studies, total n = 37), social phobia (one study, n = 16), and posttraumatic stress disorder (PTSD) (one study, n = 19). Three out of four panic disorder trials qualified for pooled analyses. These meta-analyses found no statistically significant differences between the efficacy of propranolol and benzodiazepines regarding the short-term treatment of panic disorder with or without agoraphobia. Also, no evidence was found for effects of propranolol on PTSD symptom severity through inhibition of memory reconsolidation. In conclusion, the quality of evidence for the efficacy of propranolol at present is insufficient to support the routine use of propranolol in the treatment of any of the anxiety disorders.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Anti-Anxiety Agents; Anxiety Disorders; Humans; Propranolol; Randomized Controlled Trials as Topic; Severity of Illness Index
PubMed: 26487439
DOI: 10.1177/0269881115612236 -
The Cochrane Database of Systematic... Aug 2015Drugs with combined alpha and beta blocking activity are commonly prescribed to treat hypertension. However, the blood pressure (BP) lowering efficacy of this class of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Drugs with combined alpha and beta blocking activity are commonly prescribed to treat hypertension. However, the blood pressure (BP) lowering efficacy of this class of beta blockers has not been systematically reviewed and quantified.
OBJECTIVES
To quantify the dose-related effects of various types of dual alpha and beta adrenergic receptor blockers (dual receptor blockers) on systolic and diastolic blood pressure versus placebo in patients with primary hypertension.
SEARCH METHODS
We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for randomized controlled trials up to October 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Group's Specialised Register.
SELECTION CRITERIA
Randomized double blind placebo controlled parallel or cross-over trials. Studies contained a beta blocker monotherapy arm with a fixed dose. Patients enrolled in the studies had primary hypertension at baseline. Duration of the studies was from three to 12 weeks. Drugs in this class of beta blockers are carvedilol, dilevalol and labetalol.
DATA COLLECTION AND ANALYSIS
Two review authors (GW and AL) confirmed the inclusion of studies and extracted the data independently. RevMan 5.3 was used to synthesize data.
MAIN RESULTS
We included eight studies examining the blood pressure lowering efficacy of carvedilol and labetalol in 1493 hypertensive patients. Five of the included studies were parallel design; three were cross-over design. The two largest included studies were unpublished carvedilol studies. The estimates of BP lowering effect (systolic BP/diastolic BP millimeters of mercury; SPB/DBP mm Hg) were -4 mm Hg (95% confidence intervals (CI) -6 to -2)/-3 mm Hg (95% CI -4 to -2) for carvedilol (>1000 subjects) and -10 mm Hg (95% CI -14 to -7)/-7 mm Hg (95% CI -9 to -5) for labetalol (110 subjects). The effect of labetalol is likely to be exaggerated due to high risk of bias. Carvedilol, within the recommended dose range, did not show a significant dose response effect for SBP or DBP. Carvedilol had little or no effect on pulse pressure (-1 mm Hg) and did not change BP variability. Overall, once and twice the starting dose of carvedilol and labetalol lowered BP by -6 mm Hg (95% CI -7 to -4) /-4 mm Hg (95% CI -4 to -3) (low quality evidence) and lowered heart rate by five beats per minute (95% CI -6 to -4) (low quality evidence). Five studies (N = 1412) reported withdrawal due to adverse effects; the risk ratio was 0.88 (95% CI 0.54 to 1.42) (moderate quality evidence).
AUTHORS' CONCLUSIONS
This review provides low quality evidence that in patients with mild to moderate hypertension, dual receptor blockers lowered trough BP by an average of -6/-4 mm Hg and reduced heart rate by five beats per minute. Due to the larger sample size from the two unpublished studies, carvedilol provided a better estimate of BP lowering effect than labetalol. The BP lowering estimate from combining carvedilol once and twice the starting doses is -4/-3 mm Hg. Doses higher than the recommended starting dose did not provide additional BP reduction. Higher doses of dual receptor blockers caused more bradycardia than lower doses. Based on indirect comparison with other classes of drugs, the blood pressure lowering effect of dual alpha- and beta-receptor blockers is less than non-selective, beta1 selective and partial agonist beta blockers, as well as thiazides and drugs inhibiting the renin angiotensin system. Dual blockers also had little or no effect on reducing pulse pressure, which is similar to the other beta-blocker classes, but less than the average reduction of pulse pressure seen with thiazides and drugs inhibiting the renin angiotensin system. Patients taking dual receptor blockers were not more likely to withdraw from the study compared to patients taking placebo.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-Antagonists; Antihypertensive Agents; Blood Pressure; Carbazoles; Carvedilol; Essential Hypertension; Heart Rate; Humans; Hypertension; Labetalol; Propanolamines; Randomized Controlled Trials as Topic; Withholding Treatment
PubMed: 26306578
DOI: 10.1002/14651858.CD007449.pub2 -
The Cochrane Database of Systematic... Jan 2015People undergoing major vascular surgery have an increased risk of postoperative cardiac complications. Beta-adrenergic blockers represent an important and established... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People undergoing major vascular surgery have an increased risk of postoperative cardiac complications. Beta-adrenergic blockers represent an important and established pharmacological intervention in the prevention of cardiac complications in people with coronary artery disease. It has been proposed that this class of drugs may reduce the risk of perioperative cardiac complications in people undergoing major non-cardiac vascular surgery.
OBJECTIVES
To review the efficacy and safety of perioperative beta-adrenergic blockade in reducing cardiac or all-cause mortality, myocardial infarction, and other cardiovascular safety outcomes in people undergoing major non-cardiac vascular surgery.
SEARCH METHODS
The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (January 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 12). We searched trials databases and checked reference lists of relevant articles.
SELECTION CRITERIA
We included prospective, randomised controlled trials of perioperative beta-adrenergic blockade of people over 18 years of age undergoing non-cardiac vascular surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection and data extraction. We resolved disagreements through discussion. We performed meta-analysis using a fixed-effect model with odds ratios (ORs) and 95% confidence intervals (CIs).
MAIN RESULTS
We included two studies in this review, both of which were double-blind, randomised controlled trials comparing perioperative beta-adrenergic blockade (metoprolol) with placebo, on cardiovascular outcomes in people undergoing major non-cardiac vascular surgery. We included 599 participants receiving beta-adrenergic blockers (301 participants) or placebo (298 participants). The overall quality of studies was good. However, one study did not report random sequence generation or allocation concealment techniques, indicating possible selection bias, and the other study did not report outcome assessor blinding and was possibly underpowered. It should be noted that several of the outcomes were only reported in a single study and neither of the studies reported on vascular patency/graft occlusion, which reduces the quality of evidence to moderate. There was no evidence that perioperative beta-adrenergic blockade reduced all-cause mortality (OR 0.62, 95% CI 0.03 to 15.02), cardiovascular mortality (OR 0.34, 95% CI 0.01 to 8.32), non-fatal myocardial infarction (OR 0.83, 95% CI 0.46 to 1.49; P value = 0.53), arrhythmia (OR 0.70, 95% CI 0.26 to 1.88), heart failure (OR 1.71, 95% CI 0.40 to 7.23), stroke (OR 2.67, 95% CI 0.11 to 67.08), composite cardiovascular events (OR 0.87, 95% CI 0.55 to 1.39; P value = 0.57) or re-hospitalisation at 30 days (OR 0.86, 95% CI 0.48 to 1.52). However, there was strong evidence that beta-adrenergic blockers increased the odds of intra-operative bradycardia (OR 4.97, 95% CI 3.22 to 7.65; P value < 0.00001) and intra-operative hypotension (OR 1.84, 95% CI 1.31 to 2.59; P value = 0.0005).
AUTHORS' CONCLUSIONS
This meta-analysis currently offers no clear evidence that perioperative beta-adrenergic blockade reduces postoperative cardiac morbidity and mortality in people undergoing major non-cardiac vascular surgery. There is evidence that intra-operative bradycardia and hypotension are more likely in people taking perioperative beta-adrenergic blockers, which should be weighed with any benefit.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Adult; Cardiovascular Diseases; Cause of Death; Humans; Injections, Intravenous; Metoprolol; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Vascular Surgical Procedures
PubMed: 25879091
DOI: 10.1002/14651858.CD006342.pub2 -
BMJ Clinical Evidence Jan 2015Changes in air pressure during flying can cause ear-drum pain and perforation, vertigo, and hearing loss. It has been estimated that 10% of adults and 22% of children... (Review)
Review
INTRODUCTION
Changes in air pressure during flying can cause ear-drum pain and perforation, vertigo, and hearing loss. It has been estimated that 10% of adults and 22% of children might have changes to the ear drum after a flight, although perforation is rare. Symptoms usually resolve spontaneously.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to prevent middle-ear pain during air travel? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found three studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: nasal balloon inflation, nasal decongestants (topical), and oral pseudoephedrine.
Topics: Air Travel; Earache; Humans; Nasal Decongestants; Pseudoephedrine
PubMed: 25599243
DOI: No ID Found -
The Cochrane Database of Systematic... Dec 2014Myasthenia is a condition in which neuromuscular transmission is affected by antibodies against neuromuscular junction components (autoimmune myasthenia gravis, MG; and... (Review)
Review
BACKGROUND
Myasthenia is a condition in which neuromuscular transmission is affected by antibodies against neuromuscular junction components (autoimmune myasthenia gravis, MG; and neonatal myasthenia gravis, NMG) or by defects in genes for neuromuscular junction proteins (congenital myasthenic syndromes, CMSs). Clinically, some individuals seem to benefit from treatment with ephedrine, but its effects and adverse effects have not been systematically evaluated.
OBJECTIVES
To assess the effects and adverse effects of ephedrine in people with autoimmune MG, transient neonatal MG, and the congenital myasthenic syndromes.
SEARCH METHODS
On 17 November 2014, we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. We also searched reference lists of articles, conference proceedings of relevant conferences, and prospective trial registers. In addition, we contacted manufacturers and researchers in the field.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) and quasi-RCTs comparing ephedrine as a single or add-on treatment with any other active treatment, placebo, or no treatment in adults or children with autoimmune MG, NMG, or CMSs.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study design and quality, and extracted data. We contacted study authors for additional information. We collected information on adverse effects from included articles, and contacted authors.
MAIN RESULTS
We found no RCTs or quasi-RCTs, and therefore could not establish the effect of ephedrine on MG, NMG and CMSs. We describe the results of 53 non-randomised studies narratively in the Discussion section, including observations of endurance, muscle strength and quality of life. Effects may differ depending on the type of myasthenia. Thirty-seven studies were in participants with CMS, five in participants with MG, and in 11 the precise form of myasthenia was unknown. We found no studies for NMG. Reported adverse effects included tachycardia, sleep disturbances, nervousness, and withdrawal symptoms.
AUTHORS' CONCLUSIONS
There was no evidence available from RCTs or quasi-RCTs, but some observations from non-randomised studies are available. There is a need for more evidence from suitable forms of prospective RCTs, such as series of n-of-one RCTs, that use appropriate and validated outcome measures.
Topics: Adrenergic Agents; Adult; Child; Cholinesterase Inhibitors; Ephedrine; Humans; Infant, Newborn; Myasthenia Gravis; Myasthenia Gravis, Neonatal; Myasthenic Syndromes, Congenital
PubMed: 25515947
DOI: 10.1002/14651858.CD010028.pub2